ID   ENV_HV190               Reviewed;         845 AA.
AC   O70902;
DT   27-JUN-2006, integrated into UniProtKB/Swiss-Prot.
DT   01-AUG-1998, sequence version 1.
DT   27-MAR-2024, entry version 130.
DE   RecName: Full=Envelope glycoprotein gp160 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   AltName: Full=Env polyprotein {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Contains:
DE     RecName: Full=Surface protein gp120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=SU {ECO:0000255|HAMAP-Rule:MF_04083};
DE     AltName: Full=Glycoprotein 120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=gp120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Contains:
DE     RecName: Full=Transmembrane protein gp41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=TM {ECO:0000255|HAMAP-Rule:MF_04083};
DE     AltName: Full=Glycoprotein 41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=gp41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Flags: Precursor;
GN   Name=env {ECO:0000255|HAMAP-Rule:MF_04083};
OS   Human immunodeficiency virus type 1 group M subtype H (isolate 90CF056)
OS   (HIV-1).
OC   Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC   Ortervirales; Retroviridae; Orthoretrovirinae; Lentivirus;
OC   Human immunodeficiency virus 1.
OX   NCBI_TaxID=388826;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=9621027; DOI=10.1128/jvi.72.7.5680-5698.1998;
RA   Gao F., Robertson D.L., Carruthers C.D., Morrison S.G., Jian B., Chen Y.,
RA   Barre-Sinoussi F., Girard M., Srinivasan A., Abimiku A.G., Shaw G.M.,
RA   Sharp P.M., Hahn B.H.;
RT   "A comprehensive panel of near-full-length clones and reference sequences
RT   for non-subtype B isolates of human immunodeficiency virus type 1.";
RL   J. Virol. 72:5680-5698(1998).
RN   [2]
RP   REVIEW.
RX   PubMed=12974773; DOI=10.1034/j.1600-0463.2003.11107803.x;
RA   Geijtenbeek T.B., van Kooyk Y.;
RT   "Pathogens target DC-SIGN to influence their fate DC-SIGN functions as a
RT   pathogen receptor with broad specificity.";
RL   APMIS 111:698-714(2003).
RN   [3]
RP   REVIEW.
RX   PubMed=12873764; DOI=10.1016/s0005-2736(03)00161-5;
RA   Gallo S.A., Finnegan C.M., Viard M., Raviv Y., Dimitrov A., Rawat S.S.,
RA   Puri A., Durell S., Blumenthal R.;
RT   "The HIV Env-mediated fusion reaction.";
RL   Biochim. Biophys. Acta 1614:36-50(2003).
RN   [4]
RP   REVIEW.
RX   PubMed=15719026; DOI=10.1038/sj.cdd.4401584;
RA   Perfettini J.-L., Castedo M., Roumier T., Andreau K., Nardacci R.,
RA   Piacentini M., Kroemer G.;
RT   "Mechanisms of apoptosis induction by the HIV-1 envelope.";
RL   Cell Death Differ. 12:916-923(2005).
RN   [5]
RP   REVIEW.
RX   PubMed=15725757; DOI=10.1089/aid.2005.21.171;
RA   Hartley O., Klasse P.J., Sattentau Q.J., Moore J.P.;
RT   "V3: HIV's switch-hitter.";
RL   AIDS Res. Hum. Retroviruses 21:171-189(2005).
RN   [6]
RP   REVIEW.
RX   PubMed=16114975; DOI=10.2165/00003495-200565130-00002;
RA   Reeves J.D., Piefer A.J.;
RT   "Emerging drug targets for antiretroviral therapy.";
RL   Drugs 65:1747-1766(2005).
RN   [7]
RP   REVIEW.
RX   PubMed=16437164; DOI=10.1038/sj.emboj.7600947;
RA   Lusso P.;
RT   "HIV and the chemokine system: 10 years later.";
RL   EMBO J. 25:447-456(2006).
CC   -!- FUNCTION: [Envelope glycoprotein gp160]: Oligomerizes in the host
CC       endoplasmic reticulum into predominantly trimers. In a second time,
CC       gp160 transits in the host Golgi, where glycosylation is completed. The
CC       precursor is then proteolytically cleaved in the trans-Golgi and
CC       thereby activated by cellular furin or furin-like proteases to produce
CC       gp120 and gp41. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- FUNCTION: [Surface protein gp120]: Attaches the virus to the host
CC       lymphoid cell by binding to the primary receptor CD4. This interaction
CC       induces a structural rearrangement creating a high affinity binding
CC       site for a chemokine coreceptor like CXCR4 and/or CCR5. Acts as a
CC       ligand for CD209/DC-SIGN and CLEC4M/DC-SIGNR, which are respectively
CC       found on dendritic cells (DCs), and on endothelial cells of liver
CC       sinusoids and lymph node sinuses. These interactions allow capture of
CC       viral particles at mucosal surfaces by these cells and subsequent
CC       transmission to permissive cells. HIV subverts the migration properties
CC       of dendritic cells to gain access to CD4+ T-cells in lymph nodes. Virus
CC       transmission to permissive T-cells occurs either in trans (without DCs
CC       infection, through viral capture and transmission), or in cis
CC       (following DCs productive infection, through the usual CD4-gp120
CC       interaction), thereby inducing a robust infection. In trans infection,
CC       bound virions remain infectious over days and it is proposed that they
CC       are not degraded, but protected in non-lysosomal acidic organelles
CC       within the DCs close to the cell membrane thus contributing to the
CC       viral infectious potential during DCs' migration from the periphery to
CC       the lymphoid tissues. On arrival at lymphoid tissues, intact virions
CC       recycle back to DCs' cell surface allowing virus transmission to CD4+
CC       T-cells. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- FUNCTION: [Transmembrane protein gp41]: Acts as a class I viral fusion
CC       protein. Under the current model, the protein has at least 3
CC       conformational states: pre-fusion native state, pre-hairpin
CC       intermediate state, and post-fusion hairpin state. During fusion of
CC       viral and target intracellular membranes, the coiled coil regions
CC       (heptad repeats) assume a trimer-of-hairpins structure, positioning the
CC       fusion peptide in close proximity to the C-terminal region of the
CC       ectodomain. The formation of this structure appears to drive apposition
CC       and subsequent fusion of viral and target cell membranes. Complete
CC       fusion occurs in host cell endosomes and is dynamin-dependent, however
CC       some lipid transfer might occur at the plasma membrane. The virus
CC       undergoes clathrin-dependent internalization long before endosomal
CC       fusion, thus minimizing the surface exposure of conserved viral
CC       epitopes during fusion and reducing the efficacy of inhibitors
CC       targeting these epitopes. Membranes fusion leads to delivery of the
CC       nucleocapsid into the cytoplasm. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBUNIT: [Surface protein gp120]: The mature envelope protein (Env)
CC       consists of a homotrimer of non-covalently associated gp120-gp41
CC       heterodimers. The resulting complex protrudes from the virus surface as
CC       a spike. There seems to be as few as 10 spikes on the average virion.
CC       Interacts with host CD4, CCR5 and CXCR4. Gp120 also interacts with the
CC       C-type lectins CD209/DC-SIGN and CLEC4M/DC-SIGNR (collectively referred
CC       to as DC-SIGN(R)). Gp120 and gp41 interact with GalCer. Gp120 interacts
CC       with host ITGA4/ITGB7 complex; on CD4+ T-cells, this interaction
CC       results in rapid activation of integrin ITGAL/LFA-1, which facilitates
CC       efficient cell-to-cell spreading of HIV-1. Gp120 interacts with cell-
CC       associated heparan sulfate; this interaction increases virus
CC       infectivity on permissive cells and may be involved in infection of
CC       CD4- cells. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBUNIT: [Transmembrane protein gp41]: The mature envelope protein
CC       (Env) consists of a homotrimer of non-covalently associated gp120-gp41
CC       heterodimers. The resulting complex protrudes from the virus surface as
CC       a spike. There seems to be as few as 10 spikes on the average virion.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBCELLULAR LOCATION: [Surface protein gp120]: Virion membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Peripheral membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host cell membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Peripheral membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host endosome membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Note=The surface protein is not
CC       anchored to the viral envelope, but associates with the extravirion
CC       surface through its binding to TM. It is probably concentrated at the
CC       site of budding and incorporated into the virions possibly by contacts
CC       between the cytoplasmic tail of Env and the N-terminus of Gag.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBCELLULAR LOCATION: [Transmembrane protein gp41]: Virion membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host cell membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host endosome membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Note=It is probably concentrated at
CC       the site of budding and incorporated into the virions possibly by
CC       contacts between the cytoplasmic tail of Env and the N-terminus of Gag.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: Some of the most genetically diverse regions of the viral
CC       genome are present in Env. They are called variable regions 1 through 5
CC       (V1 through V5). Coreceptor usage of gp120 is determined mainly by the
CC       primary structure of the third variable region (V3) in the outer domain
CC       of gp120. The sequence of V3 determines which coreceptor, CCR5 and/or
CC       CXCR4 (corresponding to R5/macrophage, X4/T cell and R5X4/T cell and
CC       macrophage tropism), is used to trigger the fusion potential of the Env
CC       complex, and hence which cells the virus can infect. Binding to CCR5
CC       involves a region adjacent in addition to V3. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- DOMAIN: The membrane proximal external region (MPER) present in gp41 is
CC       a tryptophan-rich region recognized by the antibodies 2F5, Z13, and
CC       4E10. MPER seems to play a role in fusion. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- DOMAIN: The 17 amino acids long immunosuppressive region is present in
CC       many retroviral envelope proteins. Synthetic peptides derived from this
CC       relatively conserved sequence inhibit immune function in vitro and in
CC       vivo. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: The YXXL motif is involved in determining the exact site of
CC       viral release at the surface of infected mononuclear cells and promotes
CC       endocytosis. YXXL and di-leucine endocytosis motifs interact directly
CC       or indirectly with the clathrin adapter complexes, opperate
CC       independently, and their activities are not additive.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: The CD4-binding region is targeted by the antibody b12.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- PTM: Highly glycosylated by host. The high number of glycan on the
CC       protein is reffered to as 'glycan shield' because it contributes to
CC       hide protein sequence from adaptive immune system. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- PTM: Palmitoylation of the transmembrane protein and of Env polyprotein
CC       (prior to its proteolytic cleavage) is essential for their association
CC       with host cell membrane lipid rafts. Palmitoylation is therefore
CC       required for envelope trafficking to classical lipid rafts, but not for
CC       viral replication. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- PTM: Specific enzymatic cleavages in vivo yield mature proteins.
CC       Envelope glycoproteins are synthesized as an inactive precursor that is
CC       heavily N-glycosylated and processed likely by host cell furin in the
CC       Golgi to yield the mature SU and TM proteins. The cleavage site between
CC       SU and TM requires the minimal sequence [KR]-X-[KR]-R. About 2 of the 9
CC       disulfide bonds of gp41 are reduced by P4HB/PDI, following binding to
CC       CD4 receptor. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- MISCELLANEOUS: Inhibitors targeting HIV-1 viral envelope proteins are
CC       used as antiretroviral drugs. Attachment of virions to the cell surface
CC       via non-specific interactions and CD4 binding can be blocked by
CC       inhibitors that include cyanovirin-N, cyclotriazadisulfonamide analogs,
CC       PRO 2000, TNX 355 and PRO 542. In addition, BMS 806 can block CD4-
CC       induced conformational changes. Env interactions with the coreceptor
CC       molecules can be targeted by CCR5 antagonists including SCH-D,
CC       maraviroc (UK 427857) and aplaviroc (GW 873140), and the CXCR4
CC       antagonist AMD 070. Fusion of viral and cellular membranes can be
CC       inhibited by peptides such as enfuvirtide and tifuvirtide (T 1249).
CC       Resistance to inhibitors associated with mutations in Env are observed.
CC       Most of the time, single mutations confer only a modest reduction in
CC       drug susceptibility. Combination of several mutations is usually
CC       required to develop a high-level drug resistance. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- MISCELLANEOUS: HIV-1 lineages are divided in three main groups, M (for
CC       Major), O (for Outlier), and N (for New, or Non-M, Non-O). The vast
CC       majority of strains found worldwide belong to the group M. Group O
CC       seems to be endemic to and largely confined to Cameroon and neighboring
CC       countries in West Central Africa, where these viruses represent a small
CC       minority of HIV-1 strains. The group N is represented by a limited
CC       number of isolates from Cameroonian persons. The group M is further
CC       subdivided in 9 clades or subtypes (A to D, F to H, J and K).
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SIMILARITY: Belongs to the HIV-1 env protein family.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- WEB RESOURCE: Name=hivdb; Note=HIV drug resistance database;
CC       URL="https://hivdb.stanford.edu";
CC   -!- WEB RESOURCE: Name=HIV drug resistance mutations;
CC       URL="https://www.iasusa.org/content/hiv-drug-resistance-mutations";
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DR   EMBL; AF005496; AAD03181.1; -; Genomic_DNA.
DR   SMR; O70902; -.
DR   GlyCosmos; O70902; 32 sites, No reported glycans.
DR   ABCD; O70902; 1 sequenced antibody.
DR   Proteomes; UP000007685; Segment.
DR   GO; GO:0044175; C:host cell endosome membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0016020; C:membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:0019031; C:viral envelope; IEA:UniProtKB-KW.
DR   GO; GO:0055036; C:virion membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005198; F:structural molecule activity; IEA:UniProtKB-UniRule.
DR   GO; GO:0075512; P:clathrin-dependent endocytosis of virus by host cell; IEA:UniProtKB-UniRule.
DR   GO; GO:0039654; P:fusion of virus membrane with host endosome membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:0019064; P:fusion of virus membrane with host plasma membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:1903905; P:positive regulation of establishment of T cell polarity; IEA:UniProtKB-UniRule.
DR   GO; GO:1903908; P:positive regulation of plasma membrane raft polarization; IEA:UniProtKB-UniRule.
DR   GO; GO:1903911; P:positive regulation of receptor clustering; IEA:UniProtKB-UniRule.
DR   GO; GO:0019082; P:viral protein processing; IEA:UniProtKB-UniRule.
DR   GO; GO:0019062; P:virion attachment to host cell; IEA:UniProtKB-UniRule.
DR   GO; GO:0019049; P:virus-mediated perturbation of host defense response; IEA:UniProtKB-UniRule.
DR   CDD; cd09909; HIV-1-like_HR1-HR2; 1.
DR   Gene3D; 1.10.287.210; -; 1.
DR   Gene3D; 2.170.40.20; Human immunodeficiency virus 1, Gp160, envelope glycoprotein; 2.
DR   Gene3D; 1.20.5.490; Single helix bin; 1.
DR   HAMAP; MF_04083; HIV_ENV; 1.
DR   InterPro; IPR036377; Gp120_core_sf.
DR   InterPro; IPR037527; Gp160.
DR   InterPro; IPR000328; GP41-like.
DR   InterPro; IPR000777; HIV1_Gp120.
DR   Pfam; PF00516; GP120; 1.
DR   Pfam; PF00517; GP41; 1.
DR   SUPFAM; SSF56502; gp120 core; 2.
DR   SUPFAM; SSF58069; Virus ectodomain; 1.
PE   3: Inferred from homology;
KW   AIDS; Apoptosis; Clathrin-mediated endocytosis of virus by host;
KW   Cleavage on pair of basic residues; Coiled coil; Disulfide bond;
KW   Fusion of virus membrane with host endosomal membrane;
KW   Fusion of virus membrane with host membrane; Glycoprotein;
KW   Host cell membrane; Host endosome; Host membrane; Host-virus interaction;
KW   Lipoprotein; Membrane; Palmitate; Reference proteome; Signal;
KW   Transmembrane; Transmembrane helix; Viral attachment to host cell;
KW   Viral envelope protein; Viral immunoevasion;
KW   Viral penetration into host cytoplasm; Virion; Virus endocytosis by host;
KW   Virus entry into host cell.
FT   SIGNAL          1..28
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CHAIN           29..845
FT                   /note="Envelope glycoprotein gp160"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000244651"
FT   CHAIN           29..500
FT                   /note="Surface protein gp120"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000244652"
FT   CHAIN           501..845
FT                   /note="Transmembrane protein gp41"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000244653"
FT   TOPO_DOM        29..673
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   TRANSMEM        674..694
FT                   /note="Helical"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   TOPO_DOM        695..845
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          127..149
FT                   /note="V1"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          150..189
FT                   /note="V2"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          289..322
FT                   /note="V3"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          355..365
FT                   /note="CD4-binding loop"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          376..407
FT                   /note="V4"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          450..460
FT                   /note="V5"
FT   REGION          452..460
FT                   /note="V5"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          501..521
FT                   /note="Fusion peptide"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          563..581
FT                   /note="Immunosuppression"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          651..672
FT                   /note="MPER; binding to GalCer"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          708..731
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COILED          622..656
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   MOTIF           701..704
FT                   /note="YXXL motif; contains endocytosis signal"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   MOTIF           844..845
FT                   /note="Di-leucine internalization motif"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   COMPBIAS        717..731
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   SITE            500..501
FT                   /note="Cleavage; by host furin"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        84
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        126
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        132
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        133
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        136
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        149
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        153
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        179
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        180
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        190
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        223
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        227
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        234
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        255
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        269
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        286
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        294
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        324
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        331
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        347
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        377
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        383
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        391
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        395
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        402
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        437
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        449
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        454
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        600
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        605
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        614
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        626
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        50..70
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        115..198
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        122..189
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        127..150
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        211..240
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        221..232
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        289..323
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        369..434
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        376..407
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        587..593
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
SQ   SEQUENCE   845 AA;  95827 MW;  3B0ADABC0343C310 CRC64;
     METQRNYPSL WRWGTLILGM LLICSAAQNL WVTVYYGVPV WKEAKTTLFC ASDAKAYETE
     KHNVWATHAC VPTDPNPQEM VMENVTESFN MWENNMVEQM HTDIISLWDQ SLKPCVKLTP
     LCVTLNCTNV RNNTSNSTSS MEAGGELTNC SFNVTTVLRD KQQKVHALFY RLDVVPIDNN
     STQYRLINCN TSVITQACPK VSFEPIPIHY CAPAGFAILK CNNKTFNGTG LCTNVSTVQC
     THGIRPVVST QLLLNGSLAE EQIIIRTKNI SDNTKNIIVQ LKTPVNITCT RPNNNTRTSI
     HLGPGRAFYA TGDIIGDIRQ AHCNISRTDW NKTLHQVVTQ LGIHLNNRTI SFKPNSGGDM
     EVRTHSFNCR GEFFYCNTSG LFNSSWEMHT NYTSNDTKGN ENITLPCRIK QIVNMWQRVG
     RAMYAPPIQG NIMCVSNITG LILTIDEGNA SAENYTFRPG GGDMRDNWRS ELYKYKVVKI
     EPLGIAPTKT RRRVVEREKR AVGMGASFLG FLGAAGSTMG AASITLTVQA RQLLSGIVQQ
     QSNLLRAIQA RQHMLQLTVW GIKQLQARVL AVERYLRDQQ LLGIWGCSGK LICTTNVPWN
     SSWSNKSQSE IWDNMTWMEW DKQISNYTEE IYRLLEVSQT QQEKNEQDLL ALDKWASLWT
     WFDISHWLWY IKIFIMIVGG LIGLRIIFAV LSIVNRVRQG YSPLSFQTLV PNPRGPDRPE
     GTEEGGGEQD RDRSVRLVNG FLPVVWDDLR SLSLFSYRLL RDLLLIVVRT VELLGRRGRE
     ALKYLWNLLQ YWGQELKNSA IDLLNTTAIA VAEGTDGIIV IVQRAWRAIL HIPRRIRQGF
     ERSLL
//
ID   ENV_HV192               Reviewed;         856 AA.
AC   O12164;
DT   27-JUN-2006, integrated into UniProtKB/Swiss-Prot.
DT   01-JUL-1997, sequence version 1.
DT   27-MAR-2024, entry version 133.
DE   RecName: Full=Envelope glycoprotein gp160 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   AltName: Full=Env polyprotein {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Contains:
DE     RecName: Full=Surface protein gp120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=SU {ECO:0000255|HAMAP-Rule:MF_04083};
DE     AltName: Full=Glycoprotein 120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=gp120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Contains:
DE     RecName: Full=Transmembrane protein gp41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=TM {ECO:0000255|HAMAP-Rule:MF_04083};
DE     AltName: Full=Glycoprotein 41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=gp41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Flags: Precursor;
GN   Name=env {ECO:0000255|HAMAP-Rule:MF_04083};
OS   Human immunodeficiency virus type 1 group M subtype C (isolate 92BR025)
OS   (HIV-1).
OC   Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC   Ortervirales; Retroviridae; Orthoretrovirinae; Lentivirus;
OC   Human immunodeficiency virus 1.
OX   NCBI_TaxID=388812;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=8627686; DOI=10.1128/jvi.70.3.1651-1667.1996;
RA   Gao F., Morrison S.G., Robertson D.L., Thornton C.L., Craig S.,
RA   Karlsson G., Sodroski J., Morgado M., Galvao-Castro B., von Briesen H.,
RA   Beddows S., Weber J., Sharp P.M., Shaw G.M., Hahn B.H.;
RT   "Molecular cloning and analysis of functional envelope genes from human
RT   immunodeficiency virus type 1 sequence subtypes A through G. The WHO and
RT   NIAID Networks for HIV Isolation and Characterization.";
RL   J. Virol. 70:1651-1667(1996).
RN   [2]
RP   REVIEW.
RX   PubMed=12974773; DOI=10.1034/j.1600-0463.2003.11107803.x;
RA   Geijtenbeek T.B., van Kooyk Y.;
RT   "Pathogens target DC-SIGN to influence their fate DC-SIGN functions as a
RT   pathogen receptor with broad specificity.";
RL   APMIS 111:698-714(2003).
RN   [3]
RP   REVIEW.
RX   PubMed=12873764; DOI=10.1016/s0005-2736(03)00161-5;
RA   Gallo S.A., Finnegan C.M., Viard M., Raviv Y., Dimitrov A., Rawat S.S.,
RA   Puri A., Durell S., Blumenthal R.;
RT   "The HIV Env-mediated fusion reaction.";
RL   Biochim. Biophys. Acta 1614:36-50(2003).
RN   [4]
RP   REVIEW.
RX   PubMed=15719026; DOI=10.1038/sj.cdd.4401584;
RA   Perfettini J.-L., Castedo M., Roumier T., Andreau K., Nardacci R.,
RA   Piacentini M., Kroemer G.;
RT   "Mechanisms of apoptosis induction by the HIV-1 envelope.";
RL   Cell Death Differ. 12:916-923(2005).
RN   [5]
RP   REVIEW.
RX   PubMed=15725757; DOI=10.1089/aid.2005.21.171;
RA   Hartley O., Klasse P.J., Sattentau Q.J., Moore J.P.;
RT   "V3: HIV's switch-hitter.";
RL   AIDS Res. Hum. Retroviruses 21:171-189(2005).
RN   [6]
RP   REVIEW.
RX   PubMed=16114975; DOI=10.2165/00003495-200565130-00002;
RA   Reeves J.D., Piefer A.J.;
RT   "Emerging drug targets for antiretroviral therapy.";
RL   Drugs 65:1747-1766(2005).
RN   [7]
RP   REVIEW.
RX   PubMed=16437164; DOI=10.1038/sj.emboj.7600947;
RA   Lusso P.;
RT   "HIV and the chemokine system: 10 years later.";
RL   EMBO J. 25:447-456(2006).
CC   -!- FUNCTION: [Envelope glycoprotein gp160]: Oligomerizes in the host
CC       endoplasmic reticulum into predominantly trimers. In a second time,
CC       gp160 transits in the host Golgi, where glycosylation is completed. The
CC       precursor is then proteolytically cleaved in the trans-Golgi and
CC       thereby activated by cellular furin or furin-like proteases to produce
CC       gp120 and gp41. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- FUNCTION: [Surface protein gp120]: Attaches the virus to the host
CC       lymphoid cell by binding to the primary receptor CD4. This interaction
CC       induces a structural rearrangement creating a high affinity binding
CC       site for a chemokine coreceptor like CXCR4 and/or CCR5. Acts as a
CC       ligand for CD209/DC-SIGN and CLEC4M/DC-SIGNR, which are respectively
CC       found on dendritic cells (DCs), and on endothelial cells of liver
CC       sinusoids and lymph node sinuses. These interactions allow capture of
CC       viral particles at mucosal surfaces by these cells and subsequent
CC       transmission to permissive cells. HIV subverts the migration properties
CC       of dendritic cells to gain access to CD4+ T-cells in lymph nodes. Virus
CC       transmission to permissive T-cells occurs either in trans (without DCs
CC       infection, through viral capture and transmission), or in cis
CC       (following DCs productive infection, through the usual CD4-gp120
CC       interaction), thereby inducing a robust infection. In trans infection,
CC       bound virions remain infectious over days and it is proposed that they
CC       are not degraded, but protected in non-lysosomal acidic organelles
CC       within the DCs close to the cell membrane thus contributing to the
CC       viral infectious potential during DCs' migration from the periphery to
CC       the lymphoid tissues. On arrival at lymphoid tissues, intact virions
CC       recycle back to DCs' cell surface allowing virus transmission to CD4+
CC       T-cells. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- FUNCTION: [Transmembrane protein gp41]: Acts as a class I viral fusion
CC       protein. Under the current model, the protein has at least 3
CC       conformational states: pre-fusion native state, pre-hairpin
CC       intermediate state, and post-fusion hairpin state. During fusion of
CC       viral and target intracellular membranes, the coiled coil regions
CC       (heptad repeats) assume a trimer-of-hairpins structure, positioning the
CC       fusion peptide in close proximity to the C-terminal region of the
CC       ectodomain. The formation of this structure appears to drive apposition
CC       and subsequent fusion of viral and target cell membranes. Complete
CC       fusion occurs in host cell endosomes and is dynamin-dependent, however
CC       some lipid transfer might occur at the plasma membrane. The virus
CC       undergoes clathrin-dependent internalization long before endosomal
CC       fusion, thus minimizing the surface exposure of conserved viral
CC       epitopes during fusion and reducing the efficacy of inhibitors
CC       targeting these epitopes. Membranes fusion leads to delivery of the
CC       nucleocapsid into the cytoplasm. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBUNIT: [Surface protein gp120]: The mature envelope protein (Env)
CC       consists of a homotrimer of non-covalently associated gp120-gp41
CC       heterodimers. The resulting complex protrudes from the virus surface as
CC       a spike. There seems to be as few as 10 spikes on the average virion.
CC       Interacts with host CD4, CCR5 and CXCR4. Gp120 also interacts with the
CC       C-type lectins CD209/DC-SIGN and CLEC4M/DC-SIGNR (collectively referred
CC       to as DC-SIGN(R)). Gp120 and gp41 interact with GalCer. Gp120 interacts
CC       with host ITGA4/ITGB7 complex; on CD4+ T-cells, this interaction
CC       results in rapid activation of integrin ITGAL/LFA-1, which facilitates
CC       efficient cell-to-cell spreading of HIV-1. Gp120 interacts with cell-
CC       associated heparan sulfate; this interaction increases virus
CC       infectivity on permissive cells and may be involved in infection of
CC       CD4- cells. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBUNIT: [Transmembrane protein gp41]: The mature envelope protein
CC       (Env) consists of a homotrimer of non-covalently associated gp120-gp41
CC       heterodimers. The resulting complex protrudes from the virus surface as
CC       a spike. There seems to be as few as 10 spikes on the average virion.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBCELLULAR LOCATION: [Surface protein gp120]: Virion membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Peripheral membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host cell membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Peripheral membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host endosome membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Note=The surface protein is not
CC       anchored to the viral envelope, but associates with the extravirion
CC       surface through its binding to TM. It is probably concentrated at the
CC       site of budding and incorporated into the virions possibly by contacts
CC       between the cytoplasmic tail of Env and the N-terminus of Gag.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBCELLULAR LOCATION: [Transmembrane protein gp41]: Virion membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host cell membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host endosome membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Note=It is probably concentrated at
CC       the site of budding and incorporated into the virions possibly by
CC       contacts between the cytoplasmic tail of Env and the N-terminus of Gag.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: Some of the most genetically diverse regions of the viral
CC       genome are present in Env. They are called variable regions 1 through 5
CC       (V1 through V5). Coreceptor usage of gp120 is determined mainly by the
CC       primary structure of the third variable region (V3) in the outer domain
CC       of gp120. The sequence of V3 determines which coreceptor, CCR5 and/or
CC       CXCR4 (corresponding to R5/macrophage, X4/T cell and R5X4/T cell and
CC       macrophage tropism), is used to trigger the fusion potential of the Env
CC       complex, and hence which cells the virus can infect. Binding to CCR5
CC       involves a region adjacent in addition to V3. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- DOMAIN: The membrane proximal external region (MPER) present in gp41 is
CC       a tryptophan-rich region recognized by the antibodies 2F5, Z13, and
CC       4E10. MPER seems to play a role in fusion. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- DOMAIN: The 17 amino acids long immunosuppressive region is present in
CC       many retroviral envelope proteins. Synthetic peptides derived from this
CC       relatively conserved sequence inhibit immune function in vitro and in
CC       vivo. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: The YXXL motif is involved in determining the exact site of
CC       viral release at the surface of infected mononuclear cells and promotes
CC       endocytosis. YXXL and di-leucine endocytosis motifs interact directly
CC       or indirectly with the clathrin adapter complexes, opperate
CC       independently, and their activities are not additive.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: The CD4-binding region is targeted by the antibody b12.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- PTM: Highly glycosylated by host. The high number of glycan on the
CC       protein is reffered to as 'glycan shield' because it contributes to
CC       hide protein sequence from adaptive immune system. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- PTM: Palmitoylation of the transmembrane protein and of Env polyprotein
CC       (prior to its proteolytic cleavage) is essential for their association
CC       with host cell membrane lipid rafts. Palmitoylation is therefore
CC       required for envelope trafficking to classical lipid rafts, but not for
CC       viral replication. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- PTM: Specific enzymatic cleavages in vivo yield mature proteins.
CC       Envelope glycoproteins are synthesized as an inactive precursor that is
CC       heavily N-glycosylated and processed likely by host cell furin in the
CC       Golgi to yield the mature SU and TM proteins. The cleavage site between
CC       SU and TM requires the minimal sequence [KR]-X-[KR]-R. About 2 of the 9
CC       disulfide bonds of gp41 are reduced by P4HB/PDI, following binding to
CC       CD4 receptor. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- MISCELLANEOUS: Inhibitors targeting HIV-1 viral envelope proteins are
CC       used as antiretroviral drugs. Attachment of virions to the cell surface
CC       via non-specific interactions and CD4 binding can be blocked by
CC       inhibitors that include cyanovirin-N, cyclotriazadisulfonamide analogs,
CC       PRO 2000, TNX 355 and PRO 542. In addition, BMS 806 can block CD4-
CC       induced conformational changes. Env interactions with the coreceptor
CC       molecules can be targeted by CCR5 antagonists including SCH-D,
CC       maraviroc (UK 427857) and aplaviroc (GW 873140), and the CXCR4
CC       antagonist AMD 070. Fusion of viral and cellular membranes can be
CC       inhibited by peptides such as enfuvirtide and tifuvirtide (T 1249).
CC       Resistance to inhibitors associated with mutations in Env are observed.
CC       Most of the time, single mutations confer only a modest reduction in
CC       drug susceptibility. Combination of several mutations is usually
CC       required to develop a high-level drug resistance. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- MISCELLANEOUS: HIV-1 lineages are divided in three main groups, M (for
CC       Major), O (for Outlier), and N (for New, or Non-M, Non-O). The vast
CC       majority of strains found worldwide belong to the group M. Group O
CC       seems to be endemic to and largely confined to Cameroon and neighboring
CC       countries in West Central Africa, where these viruses represent a small
CC       minority of HIV-1 strains. The group N is represented by a limited
CC       number of isolates from Cameroonian persons. The group M is further
CC       subdivided in 9 clades or subtypes (A to D, F to H, J and K).
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SIMILARITY: Belongs to the HIV-1 env protein family.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- WEB RESOURCE: Name=hivdb; Note=HIV drug resistance database;
CC       URL="https://hivdb.stanford.edu";
CC   -!- WEB RESOURCE: Name=HIV drug resistance mutations;
CC       URL="https://www.iasusa.org/content/hiv-drug-resistance-mutations";
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DR   EMBL; U52953; AAB61124.1; -; Genomic_DNA.
DR   SMR; O12164; -.
DR   GlyCosmos; O12164; 27 sites, No reported glycans.
DR   Proteomes; UP000007686; Segment.
DR   GO; GO:0044175; C:host cell endosome membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0016020; C:membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:0019031; C:viral envelope; IEA:UniProtKB-KW.
DR   GO; GO:0055036; C:virion membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005198; F:structural molecule activity; IEA:UniProtKB-UniRule.
DR   GO; GO:0075512; P:clathrin-dependent endocytosis of virus by host cell; IEA:UniProtKB-UniRule.
DR   GO; GO:0039654; P:fusion of virus membrane with host endosome membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:0019064; P:fusion of virus membrane with host plasma membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:1903905; P:positive regulation of establishment of T cell polarity; IEA:UniProtKB-UniRule.
DR   GO; GO:1903908; P:positive regulation of plasma membrane raft polarization; IEA:UniProtKB-UniRule.
DR   GO; GO:1903911; P:positive regulation of receptor clustering; IEA:UniProtKB-UniRule.
DR   GO; GO:0019082; P:viral protein processing; IEA:UniProtKB-UniRule.
DR   GO; GO:0019062; P:virion attachment to host cell; IEA:UniProtKB-UniRule.
DR   GO; GO:0019049; P:virus-mediated perturbation of host defense response; IEA:UniProtKB-UniRule.
DR   CDD; cd09909; HIV-1-like_HR1-HR2; 1.
DR   Gene3D; 1.10.287.210; -; 1.
DR   Gene3D; 2.170.40.20; Human immunodeficiency virus 1, Gp160, envelope glycoprotein; 2.
DR   Gene3D; 1.20.5.490; Single helix bin; 1.
DR   HAMAP; MF_04083; HIV_ENV; 1.
DR   InterPro; IPR036377; Gp120_core_sf.
DR   InterPro; IPR037527; Gp160.
DR   InterPro; IPR000328; GP41-like.
DR   InterPro; IPR000777; HIV1_Gp120.
DR   Pfam; PF00516; GP120; 2.
DR   Pfam; PF00517; GP41; 1.
DR   SUPFAM; SSF56502; gp120 core; 2.
DR   SUPFAM; SSF58069; Virus ectodomain; 1.
PE   3: Inferred from homology;
KW   AIDS; Apoptosis; Clathrin-mediated endocytosis of virus by host;
KW   Cleavage on pair of basic residues; Coiled coil; Disulfide bond;
KW   Fusion of virus membrane with host endosomal membrane;
KW   Fusion of virus membrane with host membrane; Glycoprotein;
KW   Host cell membrane; Host endosome; Host membrane; Host-virus interaction;
KW   Lipoprotein; Membrane; Palmitate; Reference proteome; Signal;
KW   Transmembrane; Transmembrane helix; Viral attachment to host cell;
KW   Viral envelope protein; Viral immunoevasion;
KW   Viral penetration into host cytoplasm; Virion; Virus endocytosis by host;
KW   Virus entry into host cell.
FT   SIGNAL          1..31
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CHAIN           32..856
FT                   /note="Envelope glycoprotein gp160"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000244654"
FT   CHAIN           32..504
FT                   /note="Surface protein gp120"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000244655"
FT   CHAIN           505..856
FT                   /note="Transmembrane protein gp41"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000244656"
FT   TOPO_DOM        32..677
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   TRANSMEM        678..698
FT                   /note="Helical"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   TOPO_DOM        699..856
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          130..150
FT                   /note="V1"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          151..194
FT                   /note="V2"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          294..327
FT                   /note="V3"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          360..370
FT                   /note="CD4-binding loop"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          381..411
FT                   /note="V4"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          454..464
FT                   /note="V5"
FT   REGION          456..464
FT                   /note="V5"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          505..525
FT                   /note="Fusion peptide"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          567..585
FT                   /note="Immunosuppression"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          655..676
FT                   /note="MPER; binding to GalCer"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          712..732
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COILED          626..660
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   MOTIF           705..708
FT                   /note="YXXL motif; contains endocytosis signal"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   SITE            504..505
FT                   /note="Cleavage; by host furin"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   LIPID           757
FT                   /note="S-palmitoyl cysteine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        87
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        132
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        139
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        150
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        154
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        180
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        184
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        195
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        228
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        232
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        239
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        260
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        274
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        287
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        293
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        299
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        329
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        336
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        382
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        388
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        394
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        398
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        441
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        604
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        609
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        618
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        630
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        53..73
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        118..203
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        125..194
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        130..151
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        216..245
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        226..237
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        294..328
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        374..438
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        381..411
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        591..597
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
SQ   SEQUENCE   856 AA;  97230 MW;  C805374C29BCEC5F CRC64;
     MRVEGIQRNW KQWWIWGILG FWMVMIYNVR GNLWVTVYYG VPVWKEAKTT LFCASDAKAY
     DAEVHNVWAT HACVPTDPNP QEMVLENVTE NFNMWENDMV EQMHQDIISL WDQSLKPCVK
     LTPLCVTLHC SNRTIDYNNR TDNMGGEIKN CSFNMTTEVR DKREKVHALF YRLDIVPLKN
     ESSNTSGDYR LINCNTSAIT QACPKVSFDP IPIHYCAPAG YAILKCNNKT FNGTGPCNNV
     STIQCTHGTK PVVSTQLLLN GSLAEEEIII RSKNLTDNVK TIIVHLNESV EINCTRPNNN
     TRKSIRIGPG QAFYATGEII GDIRQAHCNI SRTAWNKTLQ EVGKKLAEHF PNKAIKFAKH
     SGGDLEITTH SFNCRGEFFY CNTSSLFNST YTPNSTENIT GTENSIITIP CRIKQIINMW
     QGVGRAMYAP PIEGILTCRS NITGLLLTRD GGTGMHDTEI FRPEGGDMRD NWRSELYKYK
     VVEIKPLGIA PTKAKRRVVE REKRAVGIGA VFLGFLGAAG STMGAASITL TVQVRQLLSG
     IVQQQSNLLR AIEAQQHMLQ LTVWGIKQLQ TRVLAIERYL RDQQLLGIWG CSGKLICTTA
     VPWNSSWSNR SQEDIWNNMT WMQWDREISN YTNTIYRLLE DSQNQQEKNE QDLLALDKWQ
     NLWTWFGITN WLWYIKIFIK IVGGLIGLRI IFAVLSIVNR VRQGYSPLSF QTLTPNPRGP
     DRLGGIEEEG GEQDRDRSIR LVSGFLALAW DDLRSLCLFS YHRLRDLILI AARAVELLGR
     SSLRGIQRGW EILKYLGGLV QYWSLELKKS AISLFDTIAI AVAEGTDRII EVIQGIWRAI
     CNIPRRIRQG FEAALQ
//
ID   ENV_HV193               Reviewed;         846 AA.
AC   O89292;
DT   27-JUN-2006, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1998, sequence version 1.
DT   27-MAR-2024, entry version 123.
DE   RecName: Full=Envelope glycoprotein gp160 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   AltName: Full=Env polyprotein {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Contains:
DE     RecName: Full=Surface protein gp120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=SU {ECO:0000255|HAMAP-Rule:MF_04083};
DE     AltName: Full=Glycoprotein 120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=gp120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Contains:
DE     RecName: Full=Transmembrane protein gp41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=TM {ECO:0000255|HAMAP-Rule:MF_04083};
DE     AltName: Full=Glycoprotein 41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=gp41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Flags: Precursor;
GN   Name=env {ECO:0000255|HAMAP-Rule:MF_04083};
OS   Human immunodeficiency virus type 1 group M subtype F1 (isolate 93BR020)
OS   (HIV-1).
OC   Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC   Ortervirales; Retroviridae; Orthoretrovirinae; Lentivirus;
OC   Human immunodeficiency virus 1.
OX   NCBI_TaxID=388814;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=9621027; DOI=10.1128/jvi.72.7.5680-5698.1998;
RA   Gao F., Robertson D.L., Carruthers C.D., Morrison S.G., Jian B., Chen Y.,
RA   Barre-Sinoussi F., Girard M., Srinivasan A., Abimiku A.G., Shaw G.M.,
RA   Sharp P.M., Hahn B.H.;
RT   "A comprehensive panel of near-full-length clones and reference sequences
RT   for non-subtype B isolates of human immunodeficiency virus type 1.";
RL   J. Virol. 72:5680-5698(1998).
RN   [2]
RP   REVIEW.
RX   PubMed=12974773; DOI=10.1034/j.1600-0463.2003.11107803.x;
RA   Geijtenbeek T.B., van Kooyk Y.;
RT   "Pathogens target DC-SIGN to influence their fate DC-SIGN functions as a
RT   pathogen receptor with broad specificity.";
RL   APMIS 111:698-714(2003).
RN   [3]
RP   REVIEW.
RX   PubMed=12873764; DOI=10.1016/s0005-2736(03)00161-5;
RA   Gallo S.A., Finnegan C.M., Viard M., Raviv Y., Dimitrov A., Rawat S.S.,
RA   Puri A., Durell S., Blumenthal R.;
RT   "The HIV Env-mediated fusion reaction.";
RL   Biochim. Biophys. Acta 1614:36-50(2003).
RN   [4]
RP   REVIEW.
RX   PubMed=15719026; DOI=10.1038/sj.cdd.4401584;
RA   Perfettini J.-L., Castedo M., Roumier T., Andreau K., Nardacci R.,
RA   Piacentini M., Kroemer G.;
RT   "Mechanisms of apoptosis induction by the HIV-1 envelope.";
RL   Cell Death Differ. 12:916-923(2005).
RN   [5]
RP   REVIEW.
RX   PubMed=15725757; DOI=10.1089/aid.2005.21.171;
RA   Hartley O., Klasse P.J., Sattentau Q.J., Moore J.P.;
RT   "V3: HIV's switch-hitter.";
RL   AIDS Res. Hum. Retroviruses 21:171-189(2005).
RN   [6]
RP   REVIEW.
RX   PubMed=16114975; DOI=10.2165/00003495-200565130-00002;
RA   Reeves J.D., Piefer A.J.;
RT   "Emerging drug targets for antiretroviral therapy.";
RL   Drugs 65:1747-1766(2005).
RN   [7]
RP   REVIEW.
RX   PubMed=16437164; DOI=10.1038/sj.emboj.7600947;
RA   Lusso P.;
RT   "HIV and the chemokine system: 10 years later.";
RL   EMBO J. 25:447-456(2006).
CC   -!- FUNCTION: [Envelope glycoprotein gp160]: Oligomerizes in the host
CC       endoplasmic reticulum into predominantly trimers. In a second time,
CC       gp160 transits in the host Golgi, where glycosylation is completed. The
CC       precursor is then proteolytically cleaved in the trans-Golgi and
CC       thereby activated by cellular furin or furin-like proteases to produce
CC       gp120 and gp41. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- FUNCTION: [Surface protein gp120]: Attaches the virus to the host
CC       lymphoid cell by binding to the primary receptor CD4. This interaction
CC       induces a structural rearrangement creating a high affinity binding
CC       site for a chemokine coreceptor like CXCR4 and/or CCR5. Acts as a
CC       ligand for CD209/DC-SIGN and CLEC4M/DC-SIGNR, which are respectively
CC       found on dendritic cells (DCs), and on endothelial cells of liver
CC       sinusoids and lymph node sinuses. These interactions allow capture of
CC       viral particles at mucosal surfaces by these cells and subsequent
CC       transmission to permissive cells. HIV subverts the migration properties
CC       of dendritic cells to gain access to CD4+ T-cells in lymph nodes. Virus
CC       transmission to permissive T-cells occurs either in trans (without DCs
CC       infection, through viral capture and transmission), or in cis
CC       (following DCs productive infection, through the usual CD4-gp120
CC       interaction), thereby inducing a robust infection. In trans infection,
CC       bound virions remain infectious over days and it is proposed that they
CC       are not degraded, but protected in non-lysosomal acidic organelles
CC       within the DCs close to the cell membrane thus contributing to the
CC       viral infectious potential during DCs' migration from the periphery to
CC       the lymphoid tissues. On arrival at lymphoid tissues, intact virions
CC       recycle back to DCs' cell surface allowing virus transmission to CD4+
CC       T-cells. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- FUNCTION: [Transmembrane protein gp41]: Acts as a class I viral fusion
CC       protein. Under the current model, the protein has at least 3
CC       conformational states: pre-fusion native state, pre-hairpin
CC       intermediate state, and post-fusion hairpin state. During fusion of
CC       viral and target intracellular membranes, the coiled coil regions
CC       (heptad repeats) assume a trimer-of-hairpins structure, positioning the
CC       fusion peptide in close proximity to the C-terminal region of the
CC       ectodomain. The formation of this structure appears to drive apposition
CC       and subsequent fusion of viral and target cell membranes. Complete
CC       fusion occurs in host cell endosomes and is dynamin-dependent, however
CC       some lipid transfer might occur at the plasma membrane. The virus
CC       undergoes clathrin-dependent internalization long before endosomal
CC       fusion, thus minimizing the surface exposure of conserved viral
CC       epitopes during fusion and reducing the efficacy of inhibitors
CC       targeting these epitopes. Membranes fusion leads to delivery of the
CC       nucleocapsid into the cytoplasm. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBUNIT: [Surface protein gp120]: The mature envelope protein (Env)
CC       consists of a homotrimer of non-covalently associated gp120-gp41
CC       heterodimers. The resulting complex protrudes from the virus surface as
CC       a spike. There seems to be as few as 10 spikes on the average virion.
CC       Interacts with host CD4, CCR5 and CXCR4. Gp120 also interacts with the
CC       C-type lectins CD209/DC-SIGN and CLEC4M/DC-SIGNR (collectively referred
CC       to as DC-SIGN(R)). Gp120 and gp41 interact with GalCer. Gp120 interacts
CC       with host ITGA4/ITGB7 complex; on CD4+ T-cells, this interaction
CC       results in rapid activation of integrin ITGAL/LFA-1, which facilitates
CC       efficient cell-to-cell spreading of HIV-1. Gp120 interacts with cell-
CC       associated heparan sulfate; this interaction increases virus
CC       infectivity on permissive cells and may be involved in infection of
CC       CD4- cells. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBUNIT: [Transmembrane protein gp41]: The mature envelope protein
CC       (Env) consists of a homotrimer of non-covalently associated gp120-gp41
CC       heterodimers. The resulting complex protrudes from the virus surface as
CC       a spike. There seems to be as few as 10 spikes on the average virion.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBCELLULAR LOCATION: [Surface protein gp120]: Virion membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Peripheral membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host cell membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Peripheral membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host endosome membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Note=The surface protein is not
CC       anchored to the viral envelope, but associates with the extravirion
CC       surface through its binding to TM. It is probably concentrated at the
CC       site of budding and incorporated into the virions possibly by contacts
CC       between the cytoplasmic tail of Env and the N-terminus of Gag.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBCELLULAR LOCATION: [Transmembrane protein gp41]: Virion membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host cell membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host endosome membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Note=It is probably concentrated at
CC       the site of budding and incorporated into the virions possibly by
CC       contacts between the cytoplasmic tail of Env and the N-terminus of Gag.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: Some of the most genetically diverse regions of the viral
CC       genome are present in Env. They are called variable regions 1 through 5
CC       (V1 through V5). Coreceptor usage of gp120 is determined mainly by the
CC       primary structure of the third variable region (V3) in the outer domain
CC       of gp120. The sequence of V3 determines which coreceptor, CCR5 and/or
CC       CXCR4 (corresponding to R5/macrophage, X4/T cell and R5X4/T cell and
CC       macrophage tropism), is used to trigger the fusion potential of the Env
CC       complex, and hence which cells the virus can infect. Binding to CCR5
CC       involves a region adjacent in addition to V3. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- DOMAIN: The membrane proximal external region (MPER) present in gp41 is
CC       a tryptophan-rich region recognized by the antibodies 2F5, Z13, and
CC       4E10. MPER seems to play a role in fusion. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- DOMAIN: The 17 amino acids long immunosuppressive region is present in
CC       many retroviral envelope proteins. Synthetic peptides derived from this
CC       relatively conserved sequence inhibit immune function in vitro and in
CC       vivo. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: The YXXL motif is involved in determining the exact site of
CC       viral release at the surface of infected mononuclear cells and promotes
CC       endocytosis. YXXL and di-leucine endocytosis motifs interact directly
CC       or indirectly with the clathrin adapter complexes, opperate
CC       independently, and their activities are not additive.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: The CD4-binding region is targeted by the antibody b12.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- PTM: Highly glycosylated by host. The high number of glycan on the
CC       protein is reffered to as 'glycan shield' because it contributes to
CC       hide protein sequence from adaptive immune system. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- PTM: Palmitoylation of the transmembrane protein and of Env polyprotein
CC       (prior to its proteolytic cleavage) is essential for their association
CC       with host cell membrane lipid rafts. Palmitoylation is therefore
CC       required for envelope trafficking to classical lipid rafts, but not for
CC       viral replication. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- PTM: Specific enzymatic cleavages in vivo yield mature proteins.
CC       Envelope glycoproteins are synthesized as an inactive precursor that is
CC       heavily N-glycosylated and processed likely by host cell furin in the
CC       Golgi to yield the mature SU and TM proteins. The cleavage site between
CC       SU and TM requires the minimal sequence [KR]-X-[KR]-R. About 2 of the 9
CC       disulfide bonds of gp41 are reduced by P4HB/PDI, following binding to
CC       CD4 receptor. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- MISCELLANEOUS: Inhibitors targeting HIV-1 viral envelope proteins are
CC       used as antiretroviral drugs. Attachment of virions to the cell surface
CC       via non-specific interactions and CD4 binding can be blocked by
CC       inhibitors that include cyanovirin-N, cyclotriazadisulfonamide analogs,
CC       PRO 2000, TNX 355 and PRO 542. In addition, BMS 806 can block CD4-
CC       induced conformational changes. Env interactions with the coreceptor
CC       molecules can be targeted by CCR5 antagonists including SCH-D,
CC       maraviroc (UK 427857) and aplaviroc (GW 873140), and the CXCR4
CC       antagonist AMD 070. Fusion of viral and cellular membranes can be
CC       inhibited by peptides such as enfuvirtide and tifuvirtide (T 1249).
CC       Resistance to inhibitors associated with mutations in Env are observed.
CC       Most of the time, single mutations confer only a modest reduction in
CC       drug susceptibility. Combination of several mutations is usually
CC       required to develop a high-level drug resistance. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- MISCELLANEOUS: HIV-1 lineages are divided in three main groups, M (for
CC       Major), O (for Outlier), and N (for New, or Non-M, Non-O). The vast
CC       majority of strains found worldwide belong to the group M. Group O
CC       seems to be endemic to and largely confined to Cameroon and neighboring
CC       countries in West Central Africa, where these viruses represent a small
CC       minority of HIV-1 strains. The group N is represented by a limited
CC       number of isolates from Cameroonian persons. The group M is further
CC       subdivided in 9 clades or subtypes (A to D, F to H, J and K).
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SIMILARITY: Belongs to the HIV-1 env protein family.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- WEB RESOURCE: Name=hivdb; Note=HIV drug resistance database;
CC       URL="https://hivdb.stanford.edu";
CC   -!- WEB RESOURCE: Name=HIV drug resistance mutations;
CC       URL="https://www.iasusa.org/content/hiv-drug-resistance-mutations";
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DR   EMBL; AF005494; AAD03172.1; -; Genomic_DNA.
DR   SMR; O89292; -.
DR   GlyCosmos; O89292; 28 sites, No reported glycans.
DR   Proteomes; UP000007687; Segment.
DR   GO; GO:0044175; C:host cell endosome membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0016020; C:membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:0019031; C:viral envelope; IEA:UniProtKB-KW.
DR   GO; GO:0055036; C:virion membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005198; F:structural molecule activity; IEA:UniProtKB-UniRule.
DR   GO; GO:0075512; P:clathrin-dependent endocytosis of virus by host cell; IEA:UniProtKB-UniRule.
DR   GO; GO:0039654; P:fusion of virus membrane with host endosome membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:0019064; P:fusion of virus membrane with host plasma membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:1903905; P:positive regulation of establishment of T cell polarity; IEA:UniProtKB-UniRule.
DR   GO; GO:1903908; P:positive regulation of plasma membrane raft polarization; IEA:UniProtKB-UniRule.
DR   GO; GO:1903911; P:positive regulation of receptor clustering; IEA:UniProtKB-UniRule.
DR   GO; GO:0019082; P:viral protein processing; IEA:UniProtKB-UniRule.
DR   GO; GO:0019062; P:virion attachment to host cell; IEA:UniProtKB-UniRule.
DR   GO; GO:0019049; P:virus-mediated perturbation of host defense response; IEA:UniProtKB-UniRule.
DR   CDD; cd09909; HIV-1-like_HR1-HR2; 1.
DR   Gene3D; 1.10.287.210; -; 1.
DR   Gene3D; 2.170.40.20; Human immunodeficiency virus 1, Gp160, envelope glycoprotein; 2.
DR   Gene3D; 1.20.5.490; Single helix bin; 1.
DR   HAMAP; MF_04083; HIV_ENV; 1.
DR   InterPro; IPR036377; Gp120_core_sf.
DR   InterPro; IPR037527; Gp160.
DR   InterPro; IPR000328; GP41-like.
DR   InterPro; IPR000777; HIV1_Gp120.
DR   Pfam; PF00516; GP120; 1.
DR   Pfam; PF00517; GP41; 1.
DR   SUPFAM; SSF56502; gp120 core; 2.
DR   SUPFAM; SSF58069; Virus ectodomain; 1.
PE   3: Inferred from homology;
KW   AIDS; Apoptosis; Clathrin-mediated endocytosis of virus by host;
KW   Cleavage on pair of basic residues; Coiled coil; Disulfide bond;
KW   Fusion of virus membrane with host endosomal membrane;
KW   Fusion of virus membrane with host membrane; Glycoprotein;
KW   Host cell membrane; Host endosome; Host membrane; Host-virus interaction;
KW   Lipoprotein; Membrane; Palmitate; Reference proteome; Signal;
KW   Transmembrane; Transmembrane helix; Viral attachment to host cell;
KW   Viral envelope protein; Viral immunoevasion;
KW   Viral penetration into host cytoplasm; Virion; Virus endocytosis by host;
KW   Virus entry into host cell.
FT   SIGNAL          1..31
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CHAIN           32..846
FT                   /note="Envelope glycoprotein gp160"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000244660"
FT   CHAIN           32..501
FT                   /note="Surface protein gp120"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000244661"
FT   CHAIN           502..846
FT                   /note="Transmembrane protein gp41"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000244662"
FT   TOPO_DOM        32..674
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   TRANSMEM        675..695
FT                   /note="Helical"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   TOPO_DOM        696..846
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          130..157
FT                   /note="V1"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          158..198
FT                   /note="V2"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          298..331
FT                   /note="V3"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          364..374
FT                   /note="CD4-binding loop"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          385..409
FT                   /note="V4"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          452..461
FT                   /note="V5"
FT   REGION          453..461
FT                   /note="V5"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          502..522
FT                   /note="Fusion peptide"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          564..582
FT                   /note="Immunosuppression"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          652..673
FT                   /note="MPER; binding to GalCer"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          708..731
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COILED          623..657
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   MOTIF           702..705
FT                   /note="YXXL motif; contains endocytosis signal"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   MOTIF           845..846
FT                   /note="Di-leucine internalization motif"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   COMPBIAS        714..731
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   SITE            501..502
FT                   /note="Cleavage; by host furin"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   LIPID           754
FT                   /note="S-palmitoyl cysteine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        87
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        136
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        139
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        145
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        157
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        161
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        190
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        234
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        243
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        264
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        278
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        291
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        297
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        303
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        333
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        356
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        362
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        392
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        397
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        402
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        433
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        439
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        452
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        455
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        601
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        606
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        615
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        627
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        53..73
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        118..207
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        125..198
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        130..158
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        220..249
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        230..241
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        298..332
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        378..436
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        385..409
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        588..594
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
SQ   SEQUENCE   846 AA;  95565 MW;  CBBAA85FE53B5445 CRC64;
     MRVRGMQRNW QHLGKWGLLF LGTLIICNAA ENLWVTVYYG VPVWKEATTT LFCASDAKSY
     EKEAHNVWAT HACVPTDPNP QEVVLENVTE RFNMWENNMV EQMHTDIISL WDQSLKPCVK
     LTPLCVTLDC RNIATNGTND TIAINDTLKE DPEAIQNCSF NTTTEIRDKQ LKVHALFYKL
     DIVQINKDDN RTYRLINCDA STITQACPKV SWDPIPIHYC APAGYAILKC NEKNFTGTGS
     CKNVSTVQCT HGIKPVVSTQ LLLNGSLAEG EIVIRSQNIS DNAKTIIVHL NESVQINCTR
     PNNNTRKRIS LGPGRVFYTT GEIIGDIRKA HCNVSGTQWR NTLAKVKAKL GSYFPNATIK
     FNSSSGGDLE ITRHNFNCMG EFFYCNTDEL FNDTKFNDTG FNGTITLPCR IKQIVNMWQE
     VGRAMYANPI AGNITCNSNI TGLLLTRDGG LNSTNETFRP GGGNMKDNWR SELYKYKVVE
     IEPLGVAPTK AKRQVVKRER RAVGLGALFL GFLGAAGSTM GAASITLTVQ ARQLLSGIVQ
     QQSNLLRAIE AQQHLLQLTV WGIKQLQARV LAVERYLKDQ QLLGLWGCSG KLICTTNVPW
     NSSWSNKSLE EIWGNMTWME WEKEVSNYSK EIYRLIEDSQ NQQEKNEQEL LALDKWASLW
     NWFDITQWLW YIKIFIMIVG GLIGLRIVFT VLSIVNRVRK GYSPLSFQTH IPSPREPDRP
     EGIEEGGGEQ GKDRSVRLVT GFLALAWDDL RNLCLFSYRH LRDFILIAAR IVDRGLKRGW
     EALKYLGNLT QYWGQELKNS AISLLNATAI AVAEWTDRVI EALQRAGRAI LNIPRRIRQG
     LERALL
//
ID   ENV_HV196               Reviewed;         842 AA.
AC   Q9QBY2;
DT   27-JUN-2006, integrated into UniProtKB/Swiss-Prot.
DT   27-JUN-2006, sequence version 2.
DT   27-MAR-2024, entry version 117.
DE   RecName: Full=Envelope glycoprotein gp160 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   AltName: Full=Env polyprotein {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Contains:
DE     RecName: Full=Surface protein gp120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=SU {ECO:0000255|HAMAP-Rule:MF_04083};
DE     AltName: Full=Glycoprotein 120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=gp120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Contains:
DE     RecName: Full=Transmembrane protein gp41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=TM {ECO:0000255|HAMAP-Rule:MF_04083};
DE     AltName: Full=Glycoprotein 41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=gp41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Flags: Precursor;
GN   Name=env {ECO:0000255|HAMAP-Rule:MF_04083};
OS   Human immunodeficiency virus type 1 group M subtype K (isolate 96CM-MP535)
OS   (HIV-1).
OC   Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC   Ortervirales; Retroviridae; Orthoretrovirinae; Lentivirus;
OC   Human immunodeficiency virus 1.
OX   NCBI_TaxID=388906;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX   PubMed=10659053; DOI=10.1089/088922200309485;
RA   Triques K., Bourgeois A., Vidale N., Mpoudi-Ngole E., Mulanga-Kabeya C.,
RA   Nzilambi N., Torimiro N., Saman E., Delaporte E., Peeters M.;
RT   "Near-full-length genome sequencing of divergent African HIV type 1 subtype
RT   F viruses leads to the identification of a new HIV type 1 subtype
RT   designated K.";
RL   AIDS Res. Hum. Retroviruses 16:139-151(2000).
RN   [2]
RP   REVIEW.
RX   PubMed=12974773; DOI=10.1034/j.1600-0463.2003.11107803.x;
RA   Geijtenbeek T.B., van Kooyk Y.;
RT   "Pathogens target DC-SIGN to influence their fate DC-SIGN functions as a
RT   pathogen receptor with broad specificity.";
RL   APMIS 111:698-714(2003).
RN   [3]
RP   REVIEW.
RX   PubMed=12873764; DOI=10.1016/s0005-2736(03)00161-5;
RA   Gallo S.A., Finnegan C.M., Viard M., Raviv Y., Dimitrov A., Rawat S.S.,
RA   Puri A., Durell S., Blumenthal R.;
RT   "The HIV Env-mediated fusion reaction.";
RL   Biochim. Biophys. Acta 1614:36-50(2003).
RN   [4]
RP   REVIEW.
RX   PubMed=15719026; DOI=10.1038/sj.cdd.4401584;
RA   Perfettini J.-L., Castedo M., Roumier T., Andreau K., Nardacci R.,
RA   Piacentini M., Kroemer G.;
RT   "Mechanisms of apoptosis induction by the HIV-1 envelope.";
RL   Cell Death Differ. 12:916-923(2005).
RN   [5]
RP   REVIEW.
RX   PubMed=15725757; DOI=10.1089/aid.2005.21.171;
RA   Hartley O., Klasse P.J., Sattentau Q.J., Moore J.P.;
RT   "V3: HIV's switch-hitter.";
RL   AIDS Res. Hum. Retroviruses 21:171-189(2005).
RN   [6]
RP   REVIEW.
RX   PubMed=16114975; DOI=10.2165/00003495-200565130-00002;
RA   Reeves J.D., Piefer A.J.;
RT   "Emerging drug targets for antiretroviral therapy.";
RL   Drugs 65:1747-1766(2005).
RN   [7]
RP   REVIEW.
RX   PubMed=16437164; DOI=10.1038/sj.emboj.7600947;
RA   Lusso P.;
RT   "HIV and the chemokine system: 10 years later.";
RL   EMBO J. 25:447-456(2006).
CC   -!- FUNCTION: [Envelope glycoprotein gp160]: Oligomerizes in the host
CC       endoplasmic reticulum into predominantly trimers. In a second time,
CC       gp160 transits in the host Golgi, where glycosylation is completed. The
CC       precursor is then proteolytically cleaved in the trans-Golgi and
CC       thereby activated by cellular furin or furin-like proteases to produce
CC       gp120 and gp41. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- FUNCTION: [Surface protein gp120]: Attaches the virus to the host
CC       lymphoid cell by binding to the primary receptor CD4. This interaction
CC       induces a structural rearrangement creating a high affinity binding
CC       site for a chemokine coreceptor like CXCR4 and/or CCR5. Acts as a
CC       ligand for CD209/DC-SIGN and CLEC4M/DC-SIGNR, which are respectively
CC       found on dendritic cells (DCs), and on endothelial cells of liver
CC       sinusoids and lymph node sinuses. These interactions allow capture of
CC       viral particles at mucosal surfaces by these cells and subsequent
CC       transmission to permissive cells. HIV subverts the migration properties
CC       of dendritic cells to gain access to CD4+ T-cells in lymph nodes. Virus
CC       transmission to permissive T-cells occurs either in trans (without DCs
CC       infection, through viral capture and transmission), or in cis
CC       (following DCs productive infection, through the usual CD4-gp120
CC       interaction), thereby inducing a robust infection. In trans infection,
CC       bound virions remain infectious over days and it is proposed that they
CC       are not degraded, but protected in non-lysosomal acidic organelles
CC       within the DCs close to the cell membrane thus contributing to the
CC       viral infectious potential during DCs' migration from the periphery to
CC       the lymphoid tissues. On arrival at lymphoid tissues, intact virions
CC       recycle back to DCs' cell surface allowing virus transmission to CD4+
CC       T-cells. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- FUNCTION: [Transmembrane protein gp41]: Acts as a class I viral fusion
CC       protein. Under the current model, the protein has at least 3
CC       conformational states: pre-fusion native state, pre-hairpin
CC       intermediate state, and post-fusion hairpin state. During fusion of
CC       viral and target intracellular membranes, the coiled coil regions
CC       (heptad repeats) assume a trimer-of-hairpins structure, positioning the
CC       fusion peptide in close proximity to the C-terminal region of the
CC       ectodomain. The formation of this structure appears to drive apposition
CC       and subsequent fusion of viral and target cell membranes. Complete
CC       fusion occurs in host cell endosomes and is dynamin-dependent, however
CC       some lipid transfer might occur at the plasma membrane. The virus
CC       undergoes clathrin-dependent internalization long before endosomal
CC       fusion, thus minimizing the surface exposure of conserved viral
CC       epitopes during fusion and reducing the efficacy of inhibitors
CC       targeting these epitopes. Membranes fusion leads to delivery of the
CC       nucleocapsid into the cytoplasm. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBUNIT: [Surface protein gp120]: The mature envelope protein (Env)
CC       consists of a homotrimer of non-covalently associated gp120-gp41
CC       heterodimers. The resulting complex protrudes from the virus surface as
CC       a spike. There seems to be as few as 10 spikes on the average virion.
CC       Interacts with host CD4, CCR5 and CXCR4. Gp120 also interacts with the
CC       C-type lectins CD209/DC-SIGN and CLEC4M/DC-SIGNR (collectively referred
CC       to as DC-SIGN(R)). Gp120 and gp41 interact with GalCer. Gp120 interacts
CC       with host ITGA4/ITGB7 complex; on CD4+ T-cells, this interaction
CC       results in rapid activation of integrin ITGAL/LFA-1, which facilitates
CC       efficient cell-to-cell spreading of HIV-1. Gp120 interacts with cell-
CC       associated heparan sulfate; this interaction increases virus
CC       infectivity on permissive cells and may be involved in infection of
CC       CD4- cells. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBUNIT: [Transmembrane protein gp41]: The mature envelope protein
CC       (Env) consists of a homotrimer of non-covalently associated gp120-gp41
CC       heterodimers. The resulting complex protrudes from the virus surface as
CC       a spike. There seems to be as few as 10 spikes on the average virion.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBCELLULAR LOCATION: [Surface protein gp120]: Virion membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Peripheral membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host cell membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Peripheral membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host endosome membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Note=The surface protein is not
CC       anchored to the viral envelope, but associates with the extravirion
CC       surface through its binding to TM. It is probably concentrated at the
CC       site of budding and incorporated into the virions possibly by contacts
CC       between the cytoplasmic tail of Env and the N-terminus of Gag.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBCELLULAR LOCATION: [Transmembrane protein gp41]: Virion membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host cell membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host endosome membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Note=It is probably concentrated at
CC       the site of budding and incorporated into the virions possibly by
CC       contacts between the cytoplasmic tail of Env and the N-terminus of Gag.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: Some of the most genetically diverse regions of the viral
CC       genome are present in Env. They are called variable regions 1 through 5
CC       (V1 through V5). Coreceptor usage of gp120 is determined mainly by the
CC       primary structure of the third variable region (V3) in the outer domain
CC       of gp120. The sequence of V3 determines which coreceptor, CCR5 and/or
CC       CXCR4 (corresponding to R5/macrophage, X4/T cell and R5X4/T cell and
CC       macrophage tropism), is used to trigger the fusion potential of the Env
CC       complex, and hence which cells the virus can infect. Binding to CCR5
CC       involves a region adjacent in addition to V3. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- DOMAIN: The membrane proximal external region (MPER) present in gp41 is
CC       a tryptophan-rich region recognized by the antibodies 2F5, Z13, and
CC       4E10. MPER seems to play a role in fusion. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- DOMAIN: The 17 amino acids long immunosuppressive region is present in
CC       many retroviral envelope proteins. Synthetic peptides derived from this
CC       relatively conserved sequence inhibit immune function in vitro and in
CC       vivo. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: The YXXL motif is involved in determining the exact site of
CC       viral release at the surface of infected mononuclear cells and promotes
CC       endocytosis. YXXL and di-leucine endocytosis motifs interact directly
CC       or indirectly with the clathrin adapter complexes, opperate
CC       independently, and their activities are not additive.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: The CD4-binding region is targeted by the antibody b12.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- PTM: Highly glycosylated by host. The high number of glycan on the
CC       protein is reffered to as 'glycan shield' because it contributes to
CC       hide protein sequence from adaptive immune system. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- PTM: Palmitoylation of the transmembrane protein and of Env polyprotein
CC       (prior to its proteolytic cleavage) is essential for their association
CC       with host cell membrane lipid rafts. Palmitoylation is therefore
CC       required for envelope trafficking to classical lipid rafts, but not for
CC       viral replication. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- PTM: Specific enzymatic cleavages in vivo yield mature proteins.
CC       Envelope glycoproteins are synthesized as an inactive precursor that is
CC       heavily N-glycosylated and processed likely by host cell furin in the
CC       Golgi to yield the mature SU and TM proteins. The cleavage site between
CC       SU and TM requires the minimal sequence [KR]-X-[KR]-R. About 2 of the 9
CC       disulfide bonds of gp41 are reduced by P4HB/PDI, following binding to
CC       CD4 receptor. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- MISCELLANEOUS: Inhibitors targeting HIV-1 viral envelope proteins are
CC       used as antiretroviral drugs. Attachment of virions to the cell surface
CC       via non-specific interactions and CD4 binding can be blocked by
CC       inhibitors that include cyanovirin-N, cyclotriazadisulfonamide analogs,
CC       PRO 2000, TNX 355 and PRO 542. In addition, BMS 806 can block CD4-
CC       induced conformational changes. Env interactions with the coreceptor
CC       molecules can be targeted by CCR5 antagonists including SCH-D,
CC       maraviroc (UK 427857) and aplaviroc (GW 873140), and the CXCR4
CC       antagonist AMD 070. Fusion of viral and cellular membranes can be
CC       inhibited by peptides such as enfuvirtide and tifuvirtide (T 1249).
CC       Resistance to inhibitors associated with mutations in Env are observed.
CC       Most of the time, single mutations confer only a modest reduction in
CC       drug susceptibility. Combination of several mutations is usually
CC       required to develop a high-level drug resistance. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- MISCELLANEOUS: HIV-1 lineages are divided in three main groups, M (for
CC       Major), O (for Outlier), and N (for New, or Non-M, Non-O). The vast
CC       majority of strains found worldwide belong to the group M. Group O
CC       seems to be endemic to and largely confined to Cameroon and neighboring
CC       countries in West Central Africa, where these viruses represent a small
CC       minority of HIV-1 strains. The group N is represented by a limited
CC       number of isolates from Cameroonian persons. The group M is further
CC       subdivided in 9 clades or subtypes (A to D, F to H, J and K).
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SIMILARITY: Belongs to the HIV-1 env protein family.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=CAB58990.1; Type=Erroneous initiation;
CC   -!- WEB RESOURCE: Name=hivdb; Note=HIV drug resistance database;
CC       URL="https://hivdb.stanford.edu";
CC   -!- WEB RESOURCE: Name=HIV drug resistance mutations;
CC       URL="https://www.iasusa.org/content/hiv-drug-resistance-mutations";
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DR   EMBL; AJ249239; CAB58990.1; ALT_INIT; Genomic_RNA.
DR   SMR; Q9QBY2; -.
DR   GlyCosmos; Q9QBY2; 30 sites, No reported glycans.
DR   GO; GO:0044175; C:host cell endosome membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0016020; C:membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:0019031; C:viral envelope; IEA:UniProtKB-KW.
DR   GO; GO:0055036; C:virion membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005198; F:structural molecule activity; IEA:UniProtKB-UniRule.
DR   GO; GO:0075512; P:clathrin-dependent endocytosis of virus by host cell; IEA:UniProtKB-UniRule.
DR   GO; GO:0039654; P:fusion of virus membrane with host endosome membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:0019064; P:fusion of virus membrane with host plasma membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:1903905; P:positive regulation of establishment of T cell polarity; IEA:UniProtKB-UniRule.
DR   GO; GO:1903908; P:positive regulation of plasma membrane raft polarization; IEA:UniProtKB-UniRule.
DR   GO; GO:1903911; P:positive regulation of receptor clustering; IEA:UniProtKB-UniRule.
DR   GO; GO:0019082; P:viral protein processing; IEA:UniProtKB-UniRule.
DR   GO; GO:0019062; P:virion attachment to host cell; IEA:UniProtKB-UniRule.
DR   GO; GO:0019049; P:virus-mediated perturbation of host defense response; IEA:UniProtKB-UniRule.
DR   CDD; cd09909; HIV-1-like_HR1-HR2; 1.
DR   Gene3D; 1.10.287.210; -; 1.
DR   Gene3D; 2.170.40.20; Human immunodeficiency virus 1, Gp160, envelope glycoprotein; 2.
DR   Gene3D; 1.20.5.490; Single helix bin; 1.
DR   HAMAP; MF_04083; HIV_ENV; 1.
DR   InterPro; IPR036377; Gp120_core_sf.
DR   InterPro; IPR037527; Gp160.
DR   InterPro; IPR000328; GP41-like.
DR   InterPro; IPR000777; HIV1_Gp120.
DR   Pfam; PF00516; GP120; 2.
DR   Pfam; PF00517; GP41; 1.
DR   SUPFAM; SSF56502; gp120 core; 2.
DR   SUPFAM; SSF58069; Virus ectodomain; 1.
PE   3: Inferred from homology;
KW   AIDS; Apoptosis; Clathrin-mediated endocytosis of virus by host;
KW   Cleavage on pair of basic residues; Coiled coil; Disulfide bond;
KW   Fusion of virus membrane with host endosomal membrane;
KW   Fusion of virus membrane with host membrane; Glycoprotein;
KW   Host cell membrane; Host endosome; Host membrane; Host-virus interaction;
KW   Lipoprotein; Membrane; Palmitate; Signal; Transmembrane;
KW   Transmembrane helix; Viral attachment to host cell; Viral envelope protein;
KW   Viral immunoevasion; Viral penetration into host cytoplasm; Virion;
KW   Virus endocytosis by host; Virus entry into host cell.
FT   SIGNAL          1..31
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CHAIN           32..842
FT                   /note="Envelope glycoprotein gp160"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000244663"
FT   CHAIN           32..497
FT                   /note="Surface protein gp120"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000244664"
FT   CHAIN           498..842
FT                   /note="Transmembrane protein gp41"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000244665"
FT   TOPO_DOM        32..670
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   TRANSMEM        671..691
FT                   /note="Helical"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   TOPO_DOM        692..842
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          130..154
FT                   /note="V1"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          155..198
FT                   /note="V2"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          298..331
FT                   /note="V3"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          364..375
FT                   /note="CD4-binding loop"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          386..405
FT                   /note="V4"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          448..457
FT                   /note="V5"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          498..518
FT                   /note="Fusion peptide"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          560..578
FT                   /note="Immunosuppression"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          648..669
FT                   /note="MPER; binding to GalCer"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   COILED          619..653
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   MOTIF           698..701
FT                   /note="YXXL motif; contains endocytosis signal"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   MOTIF           841..842
FT                   /note="Di-leucine internalization motif"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   SITE            497..498
FT                   /note="Cleavage; by host furin"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   LIPID           750
FT                   /note="S-palmitoyl cysteine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        87
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        129
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        137
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        141
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        154
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        158
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        187
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        188
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        199
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        236
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        243
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        264
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        278
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        291
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        297
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        303
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        333
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        340
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        356
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        387
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        393
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        398
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        431
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        435
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        447
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        451
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        597
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        602
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        611
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        623
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        53..73
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        118..207
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        125..198
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        130..155
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        220..249
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        230..241
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        298..332
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        379..432
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        386..405
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        584..590
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
SQ   SEQUENCE   842 AA;  95231 MW;  666741C3456C90FA CRC64;
     MRVRGMQRNW QTLGNWGILF LGILIICSNA DKLWVTVYYG VPVWKEATPT LFCASDAKAY
     EKEVHNVWAT HACVPTDPNP QEVEMENVTE NFNMWKNNMV EQMHTDIISL WDESLKPCVE
     LTPLCVTLNC TDYKGTNSTN NATSTVVSPA EIKNCSFNIT TEIKDKKKKE SALFYRLDVL
     PLNGEGNNSS TEYRLINCNT STITQTCPKV TFEPIPIHYC APAGFAILKC KDKRFNGTGP
     CKNVSTVQCT HGIKPVVSTQ LLLNGSLAEE EIIIRSENIT DNTKNIIVQL NETVQINCTR
     PNNNTRKSIH MGPGKAFYTT GDIIGDIRQA HCNISGEKWN MTLSRVKEKL KEHFKNGTIT
     FKPPNPGGDP EILTHMFNCA GEFFYCNTTK LFNETGENGT ITLPCRIKQI INMWQKVGKA
     IYAPPIAGSI NCSSNITGMI LTRDGGNNTH NETFRPGGGD MRDNWRSELY KYKVVQIEPL
     GIAPTRARRR VVQREKRAVG LGAVFFGFLG AAGSTMGAAS ITLTVQARQL LSGIVQQQSN
     LLRAIEAQQH LLQLTVWGIK QLRARILAVE RYLKDQQLLG IWGCSGKLIC TTNVPWNSSW
     SNKSWEEIWN NMTWMEWEKE IGNYSDTIYK LIEESQTQQE KNEQDLLALD KWASLWNWFD
     ITKWLWYIKI FIMIIGGLIG LRIAFAVLSV VNRVRQGYSP LSFQTLIPTS RGADRPEGIE
     EEGGEQDKNR SVRLVSGFLA LAWDDLRNLC LFSYRQLRNL ILIVTRILER GLRGGWEALK
     YLWNLVQYWS QELKNSAISL LNTTAIAVAG GTDRIIEIGQ RAFRALLHIP RRIRQGLERA
     LL
//
ID   ENV_HV197               Reviewed;         851 AA.
AC   Q9QBZ8;
DT   27-JUN-2006, integrated into UniProtKB/Swiss-Prot.
DT   27-JUN-2006, sequence version 2.
DT   27-MAR-2024, entry version 118.
DE   RecName: Full=Envelope glycoprotein gp160 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   AltName: Full=Env polyprotein {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Contains:
DE     RecName: Full=Surface protein gp120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=SU {ECO:0000255|HAMAP-Rule:MF_04083};
DE     AltName: Full=Glycoprotein 120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=gp120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Contains:
DE     RecName: Full=Transmembrane protein gp41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=TM {ECO:0000255|HAMAP-Rule:MF_04083};
DE     AltName: Full=Glycoprotein 41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=gp41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Flags: Precursor;
GN   Name=env {ECO:0000255|HAMAP-Rule:MF_04083};
OS   Human immunodeficiency virus type 1 group M subtype K (isolate 97ZR-EQTB11)
OS   (HIV-1).
OC   Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC   Ortervirales; Retroviridae; Orthoretrovirinae; Lentivirus;
OC   Human immunodeficiency virus 1.
OX   NCBI_TaxID=388907;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX   PubMed=10659053; DOI=10.1089/088922200309485;
RA   Triques K., Bourgeois A., Vidale N., Mpoudi-Ngole E., Mulanga-Kabeya C.,
RA   Nzilambi N., Torimiro N., Saman E., Delaporte E., Peeters M.;
RT   "Near-full-length genome sequencing of divergent African HIV type 1 subtype
RT   F viruses leads to the identification of a new HIV type 1 subtype
RT   designated K.";
RL   AIDS Res. Hum. Retroviruses 16:139-151(2000).
RN   [2]
RP   REVIEW.
RX   PubMed=12974773; DOI=10.1034/j.1600-0463.2003.11107803.x;
RA   Geijtenbeek T.B., van Kooyk Y.;
RT   "Pathogens target DC-SIGN to influence their fate DC-SIGN functions as a
RT   pathogen receptor with broad specificity.";
RL   APMIS 111:698-714(2003).
RN   [3]
RP   REVIEW.
RX   PubMed=12873764; DOI=10.1016/s0005-2736(03)00161-5;
RA   Gallo S.A., Finnegan C.M., Viard M., Raviv Y., Dimitrov A., Rawat S.S.,
RA   Puri A., Durell S., Blumenthal R.;
RT   "The HIV Env-mediated fusion reaction.";
RL   Biochim. Biophys. Acta 1614:36-50(2003).
RN   [4]
RP   REVIEW.
RX   PubMed=15719026; DOI=10.1038/sj.cdd.4401584;
RA   Perfettini J.-L., Castedo M., Roumier T., Andreau K., Nardacci R.,
RA   Piacentini M., Kroemer G.;
RT   "Mechanisms of apoptosis induction by the HIV-1 envelope.";
RL   Cell Death Differ. 12:916-923(2005).
RN   [5]
RP   REVIEW.
RX   PubMed=15725757; DOI=10.1089/aid.2005.21.171;
RA   Hartley O., Klasse P.J., Sattentau Q.J., Moore J.P.;
RT   "V3: HIV's switch-hitter.";
RL   AIDS Res. Hum. Retroviruses 21:171-189(2005).
RN   [6]
RP   REVIEW.
RX   PubMed=16114975; DOI=10.2165/00003495-200565130-00002;
RA   Reeves J.D., Piefer A.J.;
RT   "Emerging drug targets for antiretroviral therapy.";
RL   Drugs 65:1747-1766(2005).
RN   [7]
RP   REVIEW.
RX   PubMed=16437164; DOI=10.1038/sj.emboj.7600947;
RA   Lusso P.;
RT   "HIV and the chemokine system: 10 years later.";
RL   EMBO J. 25:447-456(2006).
CC   -!- FUNCTION: [Envelope glycoprotein gp160]: Oligomerizes in the host
CC       endoplasmic reticulum into predominantly trimers. In a second time,
CC       gp160 transits in the host Golgi, where glycosylation is completed. The
CC       precursor is then proteolytically cleaved in the trans-Golgi and
CC       thereby activated by cellular furin or furin-like proteases to produce
CC       gp120 and gp41. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- FUNCTION: [Surface protein gp120]: Attaches the virus to the host
CC       lymphoid cell by binding to the primary receptor CD4. This interaction
CC       induces a structural rearrangement creating a high affinity binding
CC       site for a chemokine coreceptor like CXCR4 and/or CCR5. Acts as a
CC       ligand for CD209/DC-SIGN and CLEC4M/DC-SIGNR, which are respectively
CC       found on dendritic cells (DCs), and on endothelial cells of liver
CC       sinusoids and lymph node sinuses. These interactions allow capture of
CC       viral particles at mucosal surfaces by these cells and subsequent
CC       transmission to permissive cells. HIV subverts the migration properties
CC       of dendritic cells to gain access to CD4+ T-cells in lymph nodes. Virus
CC       transmission to permissive T-cells occurs either in trans (without DCs
CC       infection, through viral capture and transmission), or in cis
CC       (following DCs productive infection, through the usual CD4-gp120
CC       interaction), thereby inducing a robust infection. In trans infection,
CC       bound virions remain infectious over days and it is proposed that they
CC       are not degraded, but protected in non-lysosomal acidic organelles
CC       within the DCs close to the cell membrane thus contributing to the
CC       viral infectious potential during DCs' migration from the periphery to
CC       the lymphoid tissues. On arrival at lymphoid tissues, intact virions
CC       recycle back to DCs' cell surface allowing virus transmission to CD4+
CC       T-cells. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- FUNCTION: [Transmembrane protein gp41]: Acts as a class I viral fusion
CC       protein. Under the current model, the protein has at least 3
CC       conformational states: pre-fusion native state, pre-hairpin
CC       intermediate state, and post-fusion hairpin state. During fusion of
CC       viral and target intracellular membranes, the coiled coil regions
CC       (heptad repeats) assume a trimer-of-hairpins structure, positioning the
CC       fusion peptide in close proximity to the C-terminal region of the
CC       ectodomain. The formation of this structure appears to drive apposition
CC       and subsequent fusion of viral and target cell membranes. Complete
CC       fusion occurs in host cell endosomes and is dynamin-dependent, however
CC       some lipid transfer might occur at the plasma membrane. The virus
CC       undergoes clathrin-dependent internalization long before endosomal
CC       fusion, thus minimizing the surface exposure of conserved viral
CC       epitopes during fusion and reducing the efficacy of inhibitors
CC       targeting these epitopes. Membranes fusion leads to delivery of the
CC       nucleocapsid into the cytoplasm. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBUNIT: [Surface protein gp120]: The mature envelope protein (Env)
CC       consists of a homotrimer of non-covalently associated gp120-gp41
CC       heterodimers. The resulting complex protrudes from the virus surface as
CC       a spike. There seems to be as few as 10 spikes on the average virion.
CC       Interacts with host CD4, CCR5 and CXCR4. Gp120 also interacts with the
CC       C-type lectins CD209/DC-SIGN and CLEC4M/DC-SIGNR (collectively referred
CC       to as DC-SIGN(R)). Gp120 and gp41 interact with GalCer. Gp120 interacts
CC       with host ITGA4/ITGB7 complex; on CD4+ T-cells, this interaction
CC       results in rapid activation of integrin ITGAL/LFA-1, which facilitates
CC       efficient cell-to-cell spreading of HIV-1. Gp120 interacts with cell-
CC       associated heparan sulfate; this interaction increases virus
CC       infectivity on permissive cells and may be involved in infection of
CC       CD4- cells. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBUNIT: [Transmembrane protein gp41]: The mature envelope protein
CC       (Env) consists of a homotrimer of non-covalently associated gp120-gp41
CC       heterodimers. The resulting complex protrudes from the virus surface as
CC       a spike. There seems to be as few as 10 spikes on the average virion.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBCELLULAR LOCATION: [Surface protein gp120]: Virion membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Peripheral membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host cell membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Peripheral membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host endosome membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Note=The surface protein is not
CC       anchored to the viral envelope, but associates with the extravirion
CC       surface through its binding to TM. It is probably concentrated at the
CC       site of budding and incorporated into the virions possibly by contacts
CC       between the cytoplasmic tail of Env and the N-terminus of Gag.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBCELLULAR LOCATION: [Transmembrane protein gp41]: Virion membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host cell membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host endosome membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Note=It is probably concentrated at
CC       the site of budding and incorporated into the virions possibly by
CC       contacts between the cytoplasmic tail of Env and the N-terminus of Gag.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: Some of the most genetically diverse regions of the viral
CC       genome are present in Env. They are called variable regions 1 through 5
CC       (V1 through V5). Coreceptor usage of gp120 is determined mainly by the
CC       primary structure of the third variable region (V3) in the outer domain
CC       of gp120. The sequence of V3 determines which coreceptor, CCR5 and/or
CC       CXCR4 (corresponding to R5/macrophage, X4/T cell and R5X4/T cell and
CC       macrophage tropism), is used to trigger the fusion potential of the Env
CC       complex, and hence which cells the virus can infect. Binding to CCR5
CC       involves a region adjacent in addition to V3. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- DOMAIN: The membrane proximal external region (MPER) present in gp41 is
CC       a tryptophan-rich region recognized by the antibodies 2F5, Z13, and
CC       4E10. MPER seems to play a role in fusion. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- DOMAIN: The 17 amino acids long immunosuppressive region is present in
CC       many retroviral envelope proteins. Synthetic peptides derived from this
CC       relatively conserved sequence inhibit immune function in vitro and in
CC       vivo. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: The YXXL motif is involved in determining the exact site of
CC       viral release at the surface of infected mononuclear cells and promotes
CC       endocytosis. YXXL and di-leucine endocytosis motifs interact directly
CC       or indirectly with the clathrin adapter complexes, opperate
CC       independently, and their activities are not additive.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: The CD4-binding region is targeted by the antibody b12.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- PTM: Highly glycosylated by host. The high number of glycan on the
CC       protein is reffered to as 'glycan shield' because it contributes to
CC       hide protein sequence from adaptive immune system. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- PTM: Palmitoylation of the transmembrane protein and of Env polyprotein
CC       (prior to its proteolytic cleavage) is essential for their association
CC       with host cell membrane lipid rafts. Palmitoylation is therefore
CC       required for envelope trafficking to classical lipid rafts, but not for
CC       viral replication. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- PTM: Specific enzymatic cleavages in vivo yield mature proteins.
CC       Envelope glycoproteins are synthesized as an inactive precursor that is
CC       heavily N-glycosylated and processed likely by host cell furin in the
CC       Golgi to yield the mature SU and TM proteins. The cleavage site between
CC       SU and TM requires the minimal sequence [KR]-X-[KR]-R. About 2 of the 9
CC       disulfide bonds of gp41 are reduced by P4HB/PDI, following binding to
CC       CD4 receptor. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- MISCELLANEOUS: Inhibitors targeting HIV-1 viral envelope proteins are
CC       used as antiretroviral drugs. Attachment of virions to the cell surface
CC       via non-specific interactions and CD4 binding can be blocked by
CC       inhibitors that include cyanovirin-N, cyclotriazadisulfonamide analogs,
CC       PRO 2000, TNX 355 and PRO 542. In addition, BMS 806 can block CD4-
CC       induced conformational changes. Env interactions with the coreceptor
CC       molecules can be targeted by CCR5 antagonists including SCH-D,
CC       maraviroc (UK 427857) and aplaviroc (GW 873140), and the CXCR4
CC       antagonist AMD 070. Fusion of viral and cellular membranes can be
CC       inhibited by peptides such as enfuvirtide and tifuvirtide (T 1249).
CC       Resistance to inhibitors associated with mutations in Env are observed.
CC       Most of the time, single mutations confer only a modest reduction in
CC       drug susceptibility. Combination of several mutations is usually
CC       required to develop a high-level drug resistance. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- MISCELLANEOUS: HIV-1 lineages are divided in three main groups, M (for
CC       Major), O (for Outlier), and N (for New, or Non-M, Non-O). The vast
CC       majority of strains found worldwide belong to the group M. Group O
CC       seems to be endemic to and largely confined to Cameroon and neighboring
CC       countries in West Central Africa, where these viruses represent a small
CC       minority of HIV-1 strains. The group N is represented by a limited
CC       number of isolates from Cameroonian persons. The group M is further
CC       subdivided in 9 clades or subtypes (A to D, F to H, J and K).
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SIMILARITY: Belongs to the HIV-1 env protein family.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=CAB59009.1; Type=Erroneous initiation;
CC   -!- WEB RESOURCE: Name=hivdb; Note=HIV drug resistance database;
CC       URL="https://hivdb.stanford.edu";
CC   -!- WEB RESOURCE: Name=HIV drug resistance mutations;
CC       URL="https://www.iasusa.org/content/hiv-drug-resistance-mutations";
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DR   EMBL; AJ249235; CAB59009.1; ALT_INIT; Genomic_RNA.
DR   PIR; A53591; A53591.
DR   SMR; Q9QBZ8; -.
DR   GlyCosmos; Q9QBZ8; 25 sites, No reported glycans.
DR   ABCD; Q9QBZ8; 1 sequenced antibody.
DR   GO; GO:0044175; C:host cell endosome membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0016020; C:membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:0019031; C:viral envelope; IEA:UniProtKB-KW.
DR   GO; GO:0055036; C:virion membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005198; F:structural molecule activity; IEA:UniProtKB-UniRule.
DR   GO; GO:0075512; P:clathrin-dependent endocytosis of virus by host cell; IEA:UniProtKB-UniRule.
DR   GO; GO:0039654; P:fusion of virus membrane with host endosome membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:0019064; P:fusion of virus membrane with host plasma membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:1903905; P:positive regulation of establishment of T cell polarity; IEA:UniProtKB-UniRule.
DR   GO; GO:1903908; P:positive regulation of plasma membrane raft polarization; IEA:UniProtKB-UniRule.
DR   GO; GO:1903911; P:positive regulation of receptor clustering; IEA:UniProtKB-UniRule.
DR   GO; GO:0019082; P:viral protein processing; IEA:UniProtKB-UniRule.
DR   GO; GO:0019062; P:virion attachment to host cell; IEA:UniProtKB-UniRule.
DR   GO; GO:0019049; P:virus-mediated perturbation of host defense response; IEA:UniProtKB-UniRule.
DR   CDD; cd09909; HIV-1-like_HR1-HR2; 1.
DR   Gene3D; 1.10.287.210; -; 1.
DR   Gene3D; 2.170.40.20; Human immunodeficiency virus 1, Gp160, envelope glycoprotein; 2.
DR   Gene3D; 1.20.5.490; Single helix bin; 1.
DR   HAMAP; MF_04083; HIV_ENV; 1.
DR   InterPro; IPR036377; Gp120_core_sf.
DR   InterPro; IPR037527; Gp160.
DR   InterPro; IPR000328; GP41-like.
DR   InterPro; IPR000777; HIV1_Gp120.
DR   Pfam; PF00516; GP120; 1.
DR   Pfam; PF00517; GP41; 1.
DR   SUPFAM; SSF56502; gp120 core; 2.
DR   SUPFAM; SSF58069; Virus ectodomain; 1.
PE   3: Inferred from homology;
KW   AIDS; Apoptosis; Clathrin-mediated endocytosis of virus by host;
KW   Cleavage on pair of basic residues; Coiled coil; Disulfide bond;
KW   Fusion of virus membrane with host endosomal membrane;
KW   Fusion of virus membrane with host membrane; Glycoprotein;
KW   Host cell membrane; Host endosome; Host membrane; Host-virus interaction;
KW   Lipoprotein; Membrane; Palmitate; Signal; Transmembrane;
KW   Transmembrane helix; Viral attachment to host cell; Viral envelope protein;
KW   Viral immunoevasion; Viral penetration into host cytoplasm; Virion;
KW   Virus endocytosis by host; Virus entry into host cell.
FT   SIGNAL          1..31
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CHAIN           32..851
FT                   /note="Envelope glycoprotein gp160"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000244666"
FT   CHAIN           32..506
FT                   /note="Surface protein gp120"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000244667"
FT   CHAIN           507..851
FT                   /note="Transmembrane protein gp41"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000244668"
FT   TOPO_DOM        32..679
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   TRANSMEM        680..700
FT                   /note="Helical"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   TOPO_DOM        701..851
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          130..159
FT                   /note="V1"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          160..204
FT                   /note="V2"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          304..337
FT                   /note="V3"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          369..379
FT                   /note="CD4-binding loop"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          390..411
FT                   /note="V4"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          449..469
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          454..466
FT                   /note="V5"
FT   REGION          456..466
FT                   /note="V5"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          507..527
FT                   /note="Fusion peptide"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          569..587
FT                   /note="Immunosuppression"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          657..678
FT                   /note="MPER; binding to GalCer"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          713..737
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COILED          628..662
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   MOTIF           707..710
FT                   /note="YXXL motif; contains endocytosis signal"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   MOTIF           850..851
FT                   /note="Di-leucine internalization motif"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   COMPBIAS        723..737
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   SITE            506..507
FT                   /note="Cleavage; by host furin"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   LIPID           759
FT                   /note="S-palmitoyl cysteine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        87
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        132
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        136
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        143
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        148
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        159
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        163
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        193
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        205
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        238
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        242
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        249
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        270
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        303
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        309
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        339
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        346
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        361
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        435
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        441
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        455
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        606
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        611
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        620
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        632
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        53..73
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        118..213
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        125..204
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        130..160
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        226..255
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        236..247
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        304..338
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        383..438
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        390..411
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        593..599
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
SQ   SEQUENCE   851 AA;  96273 MW;  A11324005BE011E6 CRC64;
     MRAREIQRNW QHLGKRGILF LGILIICSAA NNLWVTVYYG VPVWKEATTT LFCASDAKAY
     ETEVHNVWAT HACVPTDPNP QEVVLENVTE NFNMWKNNMV EQMHTDIISL WDESLKPCVK
     LTPLCVTLTC TNVTNNRTNA NKNDTNINAT VTSTDEIKNC SFNITTELKD KKKRVSALFY
     KLDIVQIKQS EINQSESEDR LINCNTSTVT QACPKVSFEP IPIHYCAPAG FAILKCNNNT
     CNGTGPCTNV STVQCTHGIK PVVSTQLLLN GSLAEEEIII RSEDITKNTK NIIVQLNEAV
     EINCTRPSNN TRKSIHIGPG RAFYATGDII GDIRQAHCNI SGGQWNKTVN QVKKELGKHF
     NKTIIFQPSS GGDPQVTRHI FNCRGEFSYC DTTDTVDDTE EEEDTTITIP CRIKQIINMW
     QKVGQAIYAP PTAGNITCRS NITGMILTRD GGNDNNTRTE ETFRPGGGDM RDNWRSELYK
     YKVVQIEPLG IAPTRARRRV VQREKRAVGI GALFLGFLGA AGSTMGAASI TLTVQARQLL
     SGIVQQQNNL LRAIEAQQQM LQLTVWGIKQ LRARVLAVER YLRDQQLLGI WGCSGKLICT
     TNVPWNSSWS NKSQSEIWEN MTWMQWEKEI SNHTSTIYRL IEESQIQQEK NEQDLLALDK
     WASLWNWFDI SNWLWYIKIF IMIVGGLIGL RIVFTVLSVV NRVRQGYSPL SFQTLTPSPR
     GPDRPEGIEE GGGEQDKDRS VRLVSGFLAL AWDDLRNLCL FSYRHLRDLV LIATRILDRG
     LKGSWEALKY LWNLILYWGQ EIKNSAINLL NTTAIAVAEG TDRIIEIVYR AFRALLHIPR
     RIRQGFERLL L
//
ID   ENV_HV19N               Reviewed;         849 AA.
AC   O41803;
DT   27-JUN-2006, integrated into UniProtKB/Swiss-Prot.
DT   01-JAN-1998, sequence version 1.
DT   27-MAR-2024, entry version 122.
DE   RecName: Full=Envelope glycoprotein gp160 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   AltName: Full=Env polyprotein {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Contains:
DE     RecName: Full=Surface protein gp120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=SU {ECO:0000255|HAMAP-Rule:MF_04083};
DE     AltName: Full=Glycoprotein 120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=gp120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Contains:
DE     RecName: Full=Transmembrane protein gp41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=TM {ECO:0000255|HAMAP-Rule:MF_04083};
DE     AltName: Full=Glycoprotein 41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=gp41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Flags: Precursor;
GN   Name=env {ECO:0000255|HAMAP-Rule:MF_04083};
OS   Human immunodeficiency virus type 1 group M subtype G (isolate 92NG083)
OS   (HIV-1).
OC   Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC   Ortervirales; Retroviridae; Orthoretrovirinae; Lentivirus;
OC   Human immunodeficiency virus 1.
OX   NCBI_TaxID=388825;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=9621027; DOI=10.1128/jvi.72.7.5680-5698.1998;
RA   Gao F., Robertson D.L., Carruthers C.D., Morrison S.G., Jian B., Chen Y.,
RA   Barre-Sinoussi F., Girard M., Srinivasan A., Abimiku A.G., Shaw G.M.,
RA   Sharp P.M., Hahn B.H.;
RT   "A comprehensive panel of near-full-length clones and reference sequences
RT   for non-subtype B isolates of human immunodeficiency virus type 1.";
RL   J. Virol. 72:5680-5698(1998).
RN   [2]
RP   REVIEW.
RX   PubMed=12974773; DOI=10.1034/j.1600-0463.2003.11107803.x;
RA   Geijtenbeek T.B., van Kooyk Y.;
RT   "Pathogens target DC-SIGN to influence their fate DC-SIGN functions as a
RT   pathogen receptor with broad specificity.";
RL   APMIS 111:698-714(2003).
RN   [3]
RP   REVIEW.
RX   PubMed=12873764; DOI=10.1016/s0005-2736(03)00161-5;
RA   Gallo S.A., Finnegan C.M., Viard M., Raviv Y., Dimitrov A., Rawat S.S.,
RA   Puri A., Durell S., Blumenthal R.;
RT   "The HIV Env-mediated fusion reaction.";
RL   Biochim. Biophys. Acta 1614:36-50(2003).
RN   [4]
RP   REVIEW.
RX   PubMed=15719026; DOI=10.1038/sj.cdd.4401584;
RA   Perfettini J.-L., Castedo M., Roumier T., Andreau K., Nardacci R.,
RA   Piacentini M., Kroemer G.;
RT   "Mechanisms of apoptosis induction by the HIV-1 envelope.";
RL   Cell Death Differ. 12:916-923(2005).
RN   [5]
RP   REVIEW.
RX   PubMed=15725757; DOI=10.1089/aid.2005.21.171;
RA   Hartley O., Klasse P.J., Sattentau Q.J., Moore J.P.;
RT   "V3: HIV's switch-hitter.";
RL   AIDS Res. Hum. Retroviruses 21:171-189(2005).
RN   [6]
RP   REVIEW.
RX   PubMed=16114975; DOI=10.2165/00003495-200565130-00002;
RA   Reeves J.D., Piefer A.J.;
RT   "Emerging drug targets for antiretroviral therapy.";
RL   Drugs 65:1747-1766(2005).
RN   [7]
RP   REVIEW.
RX   PubMed=16437164; DOI=10.1038/sj.emboj.7600947;
RA   Lusso P.;
RT   "HIV and the chemokine system: 10 years later.";
RL   EMBO J. 25:447-456(2006).
CC   -!- FUNCTION: [Envelope glycoprotein gp160]: Oligomerizes in the host
CC       endoplasmic reticulum into predominantly trimers. In a second time,
CC       gp160 transits in the host Golgi, where glycosylation is completed. The
CC       precursor is then proteolytically cleaved in the trans-Golgi and
CC       thereby activated by cellular furin or furin-like proteases to produce
CC       gp120 and gp41. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- FUNCTION: [Surface protein gp120]: Attaches the virus to the host
CC       lymphoid cell by binding to the primary receptor CD4. This interaction
CC       induces a structural rearrangement creating a high affinity binding
CC       site for a chemokine coreceptor like CXCR4 and/or CCR5. Acts as a
CC       ligand for CD209/DC-SIGN and CLEC4M/DC-SIGNR, which are respectively
CC       found on dendritic cells (DCs), and on endothelial cells of liver
CC       sinusoids and lymph node sinuses. These interactions allow capture of
CC       viral particles at mucosal surfaces by these cells and subsequent
CC       transmission to permissive cells. HIV subverts the migration properties
CC       of dendritic cells to gain access to CD4+ T-cells in lymph nodes. Virus
CC       transmission to permissive T-cells occurs either in trans (without DCs
CC       infection, through viral capture and transmission), or in cis
CC       (following DCs productive infection, through the usual CD4-gp120
CC       interaction), thereby inducing a robust infection. In trans infection,
CC       bound virions remain infectious over days and it is proposed that they
CC       are not degraded, but protected in non-lysosomal acidic organelles
CC       within the DCs close to the cell membrane thus contributing to the
CC       viral infectious potential during DCs' migration from the periphery to
CC       the lymphoid tissues. On arrival at lymphoid tissues, intact virions
CC       recycle back to DCs' cell surface allowing virus transmission to CD4+
CC       T-cells. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- FUNCTION: [Transmembrane protein gp41]: Acts as a class I viral fusion
CC       protein. Under the current model, the protein has at least 3
CC       conformational states: pre-fusion native state, pre-hairpin
CC       intermediate state, and post-fusion hairpin state. During fusion of
CC       viral and target intracellular membranes, the coiled coil regions
CC       (heptad repeats) assume a trimer-of-hairpins structure, positioning the
CC       fusion peptide in close proximity to the C-terminal region of the
CC       ectodomain. The formation of this structure appears to drive apposition
CC       and subsequent fusion of viral and target cell membranes. Complete
CC       fusion occurs in host cell endosomes and is dynamin-dependent, however
CC       some lipid transfer might occur at the plasma membrane. The virus
CC       undergoes clathrin-dependent internalization long before endosomal
CC       fusion, thus minimizing the surface exposure of conserved viral
CC       epitopes during fusion and reducing the efficacy of inhibitors
CC       targeting these epitopes. Membranes fusion leads to delivery of the
CC       nucleocapsid into the cytoplasm. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBUNIT: [Surface protein gp120]: The mature envelope protein (Env)
CC       consists of a homotrimer of non-covalently associated gp120-gp41
CC       heterodimers. The resulting complex protrudes from the virus surface as
CC       a spike. There seems to be as few as 10 spikes on the average virion.
CC       Interacts with host CD4, CCR5 and CXCR4. Gp120 also interacts with the
CC       C-type lectins CD209/DC-SIGN and CLEC4M/DC-SIGNR (collectively referred
CC       to as DC-SIGN(R)). Gp120 and gp41 interact with GalCer. Gp120 interacts
CC       with host ITGA4/ITGB7 complex; on CD4+ T-cells, this interaction
CC       results in rapid activation of integrin ITGAL/LFA-1, which facilitates
CC       efficient cell-to-cell spreading of HIV-1. Gp120 interacts with cell-
CC       associated heparan sulfate; this interaction increases virus
CC       infectivity on permissive cells and may be involved in infection of
CC       CD4- cells. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBUNIT: [Transmembrane protein gp41]: The mature envelope protein
CC       (Env) consists of a homotrimer of non-covalently associated gp120-gp41
CC       heterodimers. The resulting complex protrudes from the virus surface as
CC       a spike. There seems to be as few as 10 spikes on the average virion.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBCELLULAR LOCATION: [Surface protein gp120]: Virion membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Peripheral membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host cell membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Peripheral membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host endosome membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Note=The surface protein is not
CC       anchored to the viral envelope, but associates with the extravirion
CC       surface through its binding to TM. It is probably concentrated at the
CC       site of budding and incorporated into the virions possibly by contacts
CC       between the cytoplasmic tail of Env and the N-terminus of Gag.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBCELLULAR LOCATION: [Transmembrane protein gp41]: Virion membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host cell membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host endosome membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Note=It is probably concentrated at
CC       the site of budding and incorporated into the virions possibly by
CC       contacts between the cytoplasmic tail of Env and the N-terminus of Gag.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: Some of the most genetically diverse regions of the viral
CC       genome are present in Env. They are called variable regions 1 through 5
CC       (V1 through V5). Coreceptor usage of gp120 is determined mainly by the
CC       primary structure of the third variable region (V3) in the outer domain
CC       of gp120. The sequence of V3 determines which coreceptor, CCR5 and/or
CC       CXCR4 (corresponding to R5/macrophage, X4/T cell and R5X4/T cell and
CC       macrophage tropism), is used to trigger the fusion potential of the Env
CC       complex, and hence which cells the virus can infect. Binding to CCR5
CC       involves a region adjacent in addition to V3. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- DOMAIN: The membrane proximal external region (MPER) present in gp41 is
CC       a tryptophan-rich region recognized by the antibodies 2F5, Z13, and
CC       4E10. MPER seems to play a role in fusion. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- DOMAIN: The 17 amino acids long immunosuppressive region is present in
CC       many retroviral envelope proteins. Synthetic peptides derived from this
CC       relatively conserved sequence inhibit immune function in vitro and in
CC       vivo. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: The YXXL motif is involved in determining the exact site of
CC       viral release at the surface of infected mononuclear cells and promotes
CC       endocytosis. YXXL and di-leucine endocytosis motifs interact directly
CC       or indirectly with the clathrin adapter complexes, opperate
CC       independently, and their activities are not additive.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: The CD4-binding region is targeted by the antibody b12.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- PTM: Highly glycosylated by host. The high number of glycan on the
CC       protein is reffered to as 'glycan shield' because it contributes to
CC       hide protein sequence from adaptive immune system. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- PTM: Palmitoylation of the transmembrane protein and of Env polyprotein
CC       (prior to its proteolytic cleavage) is essential for their association
CC       with host cell membrane lipid rafts. Palmitoylation is therefore
CC       required for envelope trafficking to classical lipid rafts, but not for
CC       viral replication. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- PTM: Specific enzymatic cleavages in vivo yield mature proteins.
CC       Envelope glycoproteins are synthesized as an inactive precursor that is
CC       heavily N-glycosylated and processed likely by host cell furin in the
CC       Golgi to yield the mature SU and TM proteins. The cleavage site between
CC       SU and TM requires the minimal sequence [KR]-X-[KR]-R. About 2 of the 9
CC       disulfide bonds of gp41 are reduced by P4HB/PDI, following binding to
CC       CD4 receptor. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- MISCELLANEOUS: Inhibitors targeting HIV-1 viral envelope proteins are
CC       used as antiretroviral drugs. Attachment of virions to the cell surface
CC       via non-specific interactions and CD4 binding can be blocked by
CC       inhibitors that include cyanovirin-N, cyclotriazadisulfonamide analogs,
CC       PRO 2000, TNX 355 and PRO 542. In addition, BMS 806 can block CD4-
CC       induced conformational changes. Env interactions with the coreceptor
CC       molecules can be targeted by CCR5 antagonists including SCH-D,
CC       maraviroc (UK 427857) and aplaviroc (GW 873140), and the CXCR4
CC       antagonist AMD 070. Fusion of viral and cellular membranes can be
CC       inhibited by peptides such as enfuvirtide and tifuvirtide (T 1249).
CC       Resistance to inhibitors associated with mutations in Env are observed.
CC       Most of the time, single mutations confer only a modest reduction in
CC       drug susceptibility. Combination of several mutations is usually
CC       required to develop a high-level drug resistance. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- MISCELLANEOUS: HIV-1 lineages are divided in three main groups, M (for
CC       Major), O (for Outlier), and N (for New, or Non-M, Non-O). The vast
CC       majority of strains found worldwide belong to the group M. Group O
CC       seems to be endemic to and largely confined to Cameroon and neighboring
CC       countries in West Central Africa, where these viruses represent a small
CC       minority of HIV-1 strains. The group N is represented by a limited
CC       number of isolates from Cameroonian persons. The group M is further
CC       subdivided in 9 clades or subtypes (A to D, F to H, J and K).
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SIMILARITY: Belongs to the HIV-1 env protein family.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- WEB RESOURCE: Name=hivdb; Note=HIV drug resistance database;
CC       URL="https://hivdb.stanford.edu";
CC   -!- WEB RESOURCE: Name=HIV drug resistance mutations;
CC       URL="https://www.iasusa.org/content/hiv-drug-resistance-mutations";
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DR   EMBL; U88826; AAC32655.1; -; Genomic_DNA.
DR   SMR; O41803; -.
DR   GlyCosmos; O41803; 26 sites, No reported glycans.
DR   GO; GO:0044175; C:host cell endosome membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0016020; C:membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:0019031; C:viral envelope; IEA:UniProtKB-KW.
DR   GO; GO:0055036; C:virion membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005198; F:structural molecule activity; IEA:UniProtKB-UniRule.
DR   GO; GO:0075512; P:clathrin-dependent endocytosis of virus by host cell; IEA:UniProtKB-UniRule.
DR   GO; GO:0039654; P:fusion of virus membrane with host endosome membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:0019064; P:fusion of virus membrane with host plasma membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:1903905; P:positive regulation of establishment of T cell polarity; IEA:UniProtKB-UniRule.
DR   GO; GO:1903908; P:positive regulation of plasma membrane raft polarization; IEA:UniProtKB-UniRule.
DR   GO; GO:1903911; P:positive regulation of receptor clustering; IEA:UniProtKB-UniRule.
DR   GO; GO:0019082; P:viral protein processing; IEA:UniProtKB-UniRule.
DR   GO; GO:0019062; P:virion attachment to host cell; IEA:UniProtKB-UniRule.
DR   GO; GO:0019049; P:virus-mediated perturbation of host defense response; IEA:UniProtKB-UniRule.
DR   CDD; cd09909; HIV-1-like_HR1-HR2; 1.
DR   Gene3D; 1.10.287.210; -; 1.
DR   Gene3D; 2.170.40.20; Human immunodeficiency virus 1, Gp160, envelope glycoprotein; 2.
DR   Gene3D; 1.20.5.490; Single helix bin; 1.
DR   HAMAP; MF_04083; HIV_ENV; 1.
DR   InterPro; IPR036377; Gp120_core_sf.
DR   InterPro; IPR037527; Gp160.
DR   InterPro; IPR000328; GP41-like.
DR   InterPro; IPR000777; HIV1_Gp120.
DR   Pfam; PF00516; GP120; 2.
DR   Pfam; PF00517; GP41; 1.
DR   SUPFAM; SSF56502; gp120 core; 2.
DR   SUPFAM; SSF58069; Virus ectodomain; 1.
PE   3: Inferred from homology;
KW   AIDS; Apoptosis; Clathrin-mediated endocytosis of virus by host;
KW   Cleavage on pair of basic residues; Coiled coil; Disulfide bond;
KW   Fusion of virus membrane with host endosomal membrane;
KW   Fusion of virus membrane with host membrane; Glycoprotein;
KW   Host cell membrane; Host endosome; Host membrane; Host-virus interaction;
KW   Lipoprotein; Membrane; Palmitate; Signal; Transmembrane;
KW   Transmembrane helix; Viral attachment to host cell; Viral envelope protein;
KW   Viral immunoevasion; Viral penetration into host cytoplasm; Virion;
KW   Virus endocytosis by host; Virus entry into host cell.
FT   SIGNAL          1..31
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CHAIN           32..849
FT                   /note="Envelope glycoprotein gp160"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000244657"
FT   CHAIN           32..497
FT                   /note="Surface protein gp120"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000244658"
FT   CHAIN           498..849
FT                   /note="Transmembrane protein gp41"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000244659"
FT   TOPO_DOM        32..670
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   TRANSMEM        671..691
FT                   /note="Helical"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   TOPO_DOM        692..849
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          130..153
FT                   /note="V1"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          154..194
FT                   /note="V2"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          294..327
FT                   /note="V3"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          360..370
FT                   /note="CD4-binding loop"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          381..403
FT                   /note="V4"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          446..457
FT                   /note="V5"
FT   REGION          448..457
FT                   /note="V5"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          498..518
FT                   /note="Fusion peptide"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          560..578
FT                   /note="Immunosuppression"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          648..669
FT                   /note="MPER; binding to GalCer"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          709..729
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COILED          619..653
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   MOTIF           698..701
FT                   /note="YXXL motif; contains endocytosis signal"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   MOTIF           848..849
FT                   /note="Di-leucine internalization motif"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   SITE            497..498
FT                   /note="Cleavage; by host furin"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   LIPID           750
FT                   /note="S-palmitoyl cysteine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        87
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        129
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        137
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        142
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        153
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        185
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        195
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        232
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        239
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        260
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        274
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        287
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        299
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        329
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        341
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        354
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        358
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        382
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        390
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        396
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        433
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        447
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        597
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        602
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        611
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        623
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        53..73
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        118..203
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        125..194
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        130..154
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        216..245
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        226..237
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        294..328
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        374..430
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        381..403
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        584..590
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
SQ   SEQUENCE   849 AA;  96397 MW;  9829273E97C65C8D CRC64;
     MRVKGIQRNW QHLWKWGTLI LGLVIICSAS DNLWVTVYYG VPVWEDADTP LFCASDAKSY
     SSEKHNVWAT HACVPTDPNP QEIAIENVTE NFNMWKNNMV EQMQEDIISL WEESLKPCVK
     LTPLCITLNC TNVNSANHTE ANNTVENKEE IKNCSFKITT ERGGKKKEEY ALFYKLDVVP
     ISNGNKTSYR LIHCNVSTIK QACPKVNFDP IPIHYCAPAG FAILKCRDKE YNGTGPCKNV
     STVQCTHGIK PVVSTQLLLN GSLAEEDIRI RSENFTDNTK VIIVQLNNSI EINCIRPNNN
     TRKSIPIGPG QAFYATGDII GDIRQAHCNV SRIKWREMLK NVTAQLRKIY NNKNITFNSS
     AGGDLEITTH SFNCRGEFFY CNTSGLFNNN ISNINNETIT LPCKIKQIVR MWQKVGQAMY
     ALPIAGNLVC KSNITGLILT RDGGNNNDST EETFRPGGGD MRDNWRSELY KYKTVKIKSL
     GVAPTRARRR VVEREKRAVG LGAVFLGFLG AAGSTMGAAS ITLTAQVRQL LSGIVQQQSN
     LLRAIEAQQH LLQLTVWGIK QLQSRVLAIE RYLKDQQLLG IWGCSGKLIC TTNVPWNTSW
     SNKSYNEIWD NMTWLEWERE IHNYTQHIYS LIEESQNQQE KNEQDLLALD KWASLWNWFD
     ISNWLWYIRI FIMIVGGLIG LRIVFAVLSI VNRVRQGYSP LSFQTLTHHQ REPDRLGKTE
     EGGGEQDRDR STRLVSGFLA LAWDDLRSLC LFSYHRLRDL VLIAARTVEL LGRSSLKGLR
     LGWEGLKYLW NLLLYWGREL KNSAINLLDT IAIATANGTD RVIEVAQRAY RAILNVPTRI
     RQGLERALL
//
ID   ENV_HV1A2               Reviewed;         855 AA.
AC   P03378;
DT   21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT   21-JUL-1986, sequence version 1.
DT   27-MAR-2024, entry version 158.
DE   RecName: Full=Envelope glycoprotein gp160 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   AltName: Full=Env polyprotein {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Contains:
DE     RecName: Full=Surface protein gp120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=SU {ECO:0000255|HAMAP-Rule:MF_04083};
DE     AltName: Full=Glycoprotein 120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=gp120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Contains:
DE     RecName: Full=Transmembrane protein gp41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=TM {ECO:0000255|HAMAP-Rule:MF_04083};
DE     AltName: Full=Glycoprotein 41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=gp41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Flags: Precursor;
GN   Name=env {ECO:0000255|HAMAP-Rule:MF_04083};
OS   Human immunodeficiency virus type 1 group M subtype B (isolate ARV2/SF2)
OS   (HIV-1).
OC   Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC   Ortervirales; Retroviridae; Orthoretrovirinae; Lentivirus;
OC   Human immunodeficiency virus 1.
OX   NCBI_TaxID=11685;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX   PubMed=2578227; DOI=10.1126/science.2578227;
RA   Sanchez-Pescador R., Power M.D., Barr P.J., Steimer K.S., Stempien M.M.,
RA   Brown-Shimer S.L., Gee W.W., Renard A., Randolph A., Levy J.A., Dina D.,
RA   Luciw P.A.;
RT   "Nucleotide sequence and expression of an AIDS-associated retrovirus (ARV-
RT   2).";
RL   Science 227:484-492(1985).
RN   [2]
RP   REVIEW.
RX   PubMed=12974773; DOI=10.1034/j.1600-0463.2003.11107803.x;
RA   Geijtenbeek T.B., van Kooyk Y.;
RT   "Pathogens target DC-SIGN to influence their fate DC-SIGN functions as a
RT   pathogen receptor with broad specificity.";
RL   APMIS 111:698-714(2003).
RN   [3]
RP   REVIEW.
RX   PubMed=12873764; DOI=10.1016/s0005-2736(03)00161-5;
RA   Gallo S.A., Finnegan C.M., Viard M., Raviv Y., Dimitrov A., Rawat S.S.,
RA   Puri A., Durell S., Blumenthal R.;
RT   "The HIV Env-mediated fusion reaction.";
RL   Biochim. Biophys. Acta 1614:36-50(2003).
RN   [4]
RP   REVIEW.
RX   PubMed=15719026; DOI=10.1038/sj.cdd.4401584;
RA   Perfettini J.-L., Castedo M., Roumier T., Andreau K., Nardacci R.,
RA   Piacentini M., Kroemer G.;
RT   "Mechanisms of apoptosis induction by the HIV-1 envelope.";
RL   Cell Death Differ. 12:916-923(2005).
RN   [5]
RP   REVIEW.
RX   PubMed=15725757; DOI=10.1089/aid.2005.21.171;
RA   Hartley O., Klasse P.J., Sattentau Q.J., Moore J.P.;
RT   "V3: HIV's switch-hitter.";
RL   AIDS Res. Hum. Retroviruses 21:171-189(2005).
RN   [6]
RP   REVIEW.
RX   PubMed=16114975; DOI=10.2165/00003495-200565130-00002;
RA   Reeves J.D., Piefer A.J.;
RT   "Emerging drug targets for antiretroviral therapy.";
RL   Drugs 65:1747-1766(2005).
RN   [7]
RP   REVIEW.
RX   PubMed=16437164; DOI=10.1038/sj.emboj.7600947;
RA   Lusso P.;
RT   "HIV and the chemokine system: 10 years later.";
RL   EMBO J. 25:447-456(2006).
CC   -!- FUNCTION: [Envelope glycoprotein gp160]: Oligomerizes in the host
CC       endoplasmic reticulum into predominantly trimers. In a second time,
CC       gp160 transits in the host Golgi, where glycosylation is completed. The
CC       precursor is then proteolytically cleaved in the trans-Golgi and
CC       thereby activated by cellular furin or furin-like proteases to produce
CC       gp120 and gp41. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- FUNCTION: [Surface protein gp120]: Attaches the virus to the host
CC       lymphoid cell by binding to the primary receptor CD4. This interaction
CC       induces a structural rearrangement creating a high affinity binding
CC       site for a chemokine coreceptor like CXCR4 and/or CCR5. Acts as a
CC       ligand for CD209/DC-SIGN and CLEC4M/DC-SIGNR, which are respectively
CC       found on dendritic cells (DCs), and on endothelial cells of liver
CC       sinusoids and lymph node sinuses. These interactions allow capture of
CC       viral particles at mucosal surfaces by these cells and subsequent
CC       transmission to permissive cells. HIV subverts the migration properties
CC       of dendritic cells to gain access to CD4+ T-cells in lymph nodes. Virus
CC       transmission to permissive T-cells occurs either in trans (without DCs
CC       infection, through viral capture and transmission), or in cis
CC       (following DCs productive infection, through the usual CD4-gp120
CC       interaction), thereby inducing a robust infection. In trans infection,
CC       bound virions remain infectious over days and it is proposed that they
CC       are not degraded, but protected in non-lysosomal acidic organelles
CC       within the DCs close to the cell membrane thus contributing to the
CC       viral infectious potential during DCs' migration from the periphery to
CC       the lymphoid tissues. On arrival at lymphoid tissues, intact virions
CC       recycle back to DCs' cell surface allowing virus transmission to CD4+
CC       T-cells. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- FUNCTION: [Transmembrane protein gp41]: Acts as a class I viral fusion
CC       protein. Under the current model, the protein has at least 3
CC       conformational states: pre-fusion native state, pre-hairpin
CC       intermediate state, and post-fusion hairpin state. During fusion of
CC       viral and target intracellular membranes, the coiled coil regions
CC       (heptad repeats) assume a trimer-of-hairpins structure, positioning the
CC       fusion peptide in close proximity to the C-terminal region of the
CC       ectodomain. The formation of this structure appears to drive apposition
CC       and subsequent fusion of viral and target cell membranes. Complete
CC       fusion occurs in host cell endosomes and is dynamin-dependent, however
CC       some lipid transfer might occur at the plasma membrane. The virus
CC       undergoes clathrin-dependent internalization long before endosomal
CC       fusion, thus minimizing the surface exposure of conserved viral
CC       epitopes during fusion and reducing the efficacy of inhibitors
CC       targeting these epitopes. Membranes fusion leads to delivery of the
CC       nucleocapsid into the cytoplasm. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBUNIT: [Surface protein gp120]: The mature envelope protein (Env)
CC       consists of a homotrimer of non-covalently associated gp120-gp41
CC       heterodimers. The resulting complex protrudes from the virus surface as
CC       a spike. There seems to be as few as 10 spikes on the average virion.
CC       Interacts with host CD4, CCR5 and CXCR4. Gp120 also interacts with the
CC       C-type lectins CD209/DC-SIGN and CLEC4M/DC-SIGNR (collectively referred
CC       to as DC-SIGN(R)). Gp120 and gp41 interact with GalCer. Gp120 interacts
CC       with host ITGA4/ITGB7 complex; on CD4+ T-cells, this interaction
CC       results in rapid activation of integrin ITGAL/LFA-1, which facilitates
CC       efficient cell-to-cell spreading of HIV-1. Gp120 interacts with cell-
CC       associated heparan sulfate; this interaction increases virus
CC       infectivity on permissive cells and may be involved in infection of
CC       CD4- cells. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBUNIT: [Transmembrane protein gp41]: The mature envelope protein
CC       (Env) consists of a homotrimer of non-covalently associated gp120-gp41
CC       heterodimers. The resulting complex protrudes from the virus surface as
CC       a spike. There seems to be as few as 10 spikes on the average virion.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBCELLULAR LOCATION: [Surface protein gp120]: Virion membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Peripheral membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host cell membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Peripheral membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host endosome membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Note=The surface protein is not
CC       anchored to the viral envelope, but associates with the extravirion
CC       surface through its binding to TM. It is probably concentrated at the
CC       site of budding and incorporated into the virions possibly by contacts
CC       between the cytoplasmic tail of Env and the N-terminus of Gag.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBCELLULAR LOCATION: [Transmembrane protein gp41]: Virion membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host cell membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host endosome membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Note=It is probably concentrated at
CC       the site of budding and incorporated into the virions possibly by
CC       contacts between the cytoplasmic tail of Env and the N-terminus of Gag.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: Some of the most genetically diverse regions of the viral
CC       genome are present in Env. They are called variable regions 1 through 5
CC       (V1 through V5). Coreceptor usage of gp120 is determined mainly by the
CC       primary structure of the third variable region (V3) in the outer domain
CC       of gp120. The sequence of V3 determines which coreceptor, CCR5 and/or
CC       CXCR4 (corresponding to R5/macrophage, X4/T cell and R5X4/T cell and
CC       macrophage tropism), is used to trigger the fusion potential of the Env
CC       complex, and hence which cells the virus can infect. Binding to CCR5
CC       involves a region adjacent in addition to V3. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- DOMAIN: The membrane proximal external region (MPER) present in gp41 is
CC       a tryptophan-rich region recognized by the antibodies 2F5, Z13, and
CC       4E10. MPER seems to play a role in fusion. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- DOMAIN: The 17 amino acids long immunosuppressive region is present in
CC       many retroviral envelope proteins. Synthetic peptides derived from this
CC       relatively conserved sequence inhibit immune function in vitro and in
CC       vivo. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: The YXXL motif is involved in determining the exact site of
CC       viral release at the surface of infected mononuclear cells and promotes
CC       endocytosis. YXXL and di-leucine endocytosis motifs interact directly
CC       or indirectly with the clathrin adapter complexes, opperate
CC       independently, and their activities are not additive.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: The CD4-binding region is targeted by the antibody b12.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- PTM: Highly glycosylated by host. The high number of glycan on the
CC       protein is reffered to as 'glycan shield' because it contributes to
CC       hide protein sequence from adaptive immune system. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- PTM: Palmitoylation of the transmembrane protein and of Env polyprotein
CC       (prior to its proteolytic cleavage) is essential for their association
CC       with host cell membrane lipid rafts. Palmitoylation is therefore
CC       required for envelope trafficking to classical lipid rafts, but not for
CC       viral replication. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- PTM: Specific enzymatic cleavages in vivo yield mature proteins.
CC       Envelope glycoproteins are synthesized as an inactive precursor that is
CC       heavily N-glycosylated and processed likely by host cell furin in the
CC       Golgi to yield the mature SU and TM proteins. The cleavage site between
CC       SU and TM requires the minimal sequence [KR]-X-[KR]-R. About 2 of the 9
CC       disulfide bonds of gp41 are reduced by P4HB/PDI, following binding to
CC       CD4 receptor. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- MISCELLANEOUS: Inhibitors targeting HIV-1 viral envelope proteins are
CC       used as antiretroviral drugs. Attachment of virions to the cell surface
CC       via non-specific interactions and CD4 binding can be blocked by
CC       inhibitors that include cyanovirin-N, cyclotriazadisulfonamide analogs,
CC       PRO 2000, TNX 355 and PRO 542. In addition, BMS 806 can block CD4-
CC       induced conformational changes. Env interactions with the coreceptor
CC       molecules can be targeted by CCR5 antagonists including SCH-D,
CC       maraviroc (UK 427857) and aplaviroc (GW 873140), and the CXCR4
CC       antagonist AMD 070. Fusion of viral and cellular membranes can be
CC       inhibited by peptides such as enfuvirtide and tifuvirtide (T 1249).
CC       Resistance to inhibitors associated with mutations in Env are observed.
CC       Most of the time, single mutations confer only a modest reduction in
CC       drug susceptibility. Combination of several mutations is usually
CC       required to develop a high-level drug resistance. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- MISCELLANEOUS: HIV-1 lineages are divided in three main groups, M (for
CC       Major), O (for Outlier), and N (for New, or Non-M, Non-O). The vast
CC       majority of strains found worldwide belong to the group M. Group O
CC       seems to be endemic to and largely confined to Cameroon and neighboring
CC       countries in West Central Africa, where these viruses represent a small
CC       minority of HIV-1 strains. The group N is represented by a limited
CC       number of isolates from Cameroonian persons. The group M is further
CC       subdivided in 9 clades or subtypes (A to D, F to H, J and K).
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SIMILARITY: Belongs to the HIV-1 env protein family.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- WEB RESOURCE: Name=hivdb; Note=HIV drug resistance database;
CC       URL="https://hivdb.stanford.edu";
CC   -!- WEB RESOURCE: Name=HIV drug resistance mutations;
CC       URL="https://www.iasusa.org/content/hiv-drug-resistance-mutations";
CC   ---------------------------------------------------------------------------
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DR   EMBL; K02007; AAB59882.1; -; Genomic_RNA.
DR   PIR; A03976; VCLJA2.
DR   PDB; 5DRZ; X-ray; 2.54 A; P/Q=582-617.
DR   PDBsum; 5DRZ; -.
DR   SMR; P03378; -.
DR   GlyCosmos; P03378; 30 sites, No reported glycans.
DR   iPTMnet; P03378; -.
DR   ABCD; P03378; 1 sequenced antibody.
DR   Reactome; R-HSA-5621480; Dectin-2 family.
DR   PRO; PR:P03378; -.
DR   Proteomes; UP000007688; Genome.
DR   GO; GO:0044175; C:host cell endosome membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0016020; C:membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:0019031; C:viral envelope; IEA:UniProtKB-KW.
DR   GO; GO:0055036; C:virion membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005198; F:structural molecule activity; IEA:UniProtKB-UniRule.
DR   GO; GO:0075512; P:clathrin-dependent endocytosis of virus by host cell; IEA:UniProtKB-UniRule.
DR   GO; GO:0039654; P:fusion of virus membrane with host endosome membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:0019064; P:fusion of virus membrane with host plasma membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:1903905; P:positive regulation of establishment of T cell polarity; IEA:UniProtKB-UniRule.
DR   GO; GO:1903908; P:positive regulation of plasma membrane raft polarization; IEA:UniProtKB-UniRule.
DR   GO; GO:1903911; P:positive regulation of receptor clustering; IEA:UniProtKB-UniRule.
DR   GO; GO:0019082; P:viral protein processing; IEA:UniProtKB-UniRule.
DR   GO; GO:0019062; P:virion attachment to host cell; IEA:UniProtKB-UniRule.
DR   GO; GO:0019049; P:virus-mediated perturbation of host defense response; IEA:UniProtKB-UniRule.
DR   CDD; cd09909; HIV-1-like_HR1-HR2; 1.
DR   Gene3D; 1.10.287.210; -; 1.
DR   Gene3D; 2.170.40.20; Human immunodeficiency virus 1, Gp160, envelope glycoprotein; 2.
DR   Gene3D; 1.20.5.490; Single helix bin; 1.
DR   HAMAP; MF_04083; HIV_ENV; 1.
DR   InterPro; IPR036377; Gp120_core_sf.
DR   InterPro; IPR037527; Gp160.
DR   InterPro; IPR000328; GP41-like.
DR   InterPro; IPR000777; HIV1_Gp120.
DR   Pfam; PF00516; GP120; 1.
DR   Pfam; PF00517; GP41; 1.
DR   SUPFAM; SSF56502; gp120 core; 2.
DR   SUPFAM; SSF58069; Virus ectodomain; 1.
PE   1: Evidence at protein level;
KW   3D-structure; AIDS; Apoptosis;
KW   Clathrin-mediated endocytosis of virus by host;
KW   Cleavage on pair of basic residues; Coiled coil; Disulfide bond;
KW   Fusion of virus membrane with host endosomal membrane;
KW   Fusion of virus membrane with host membrane; Glycoprotein;
KW   Host cell membrane; Host endosome; Host membrane; Host-virus interaction;
KW   Lipoprotein; Membrane; Palmitate; Reference proteome; Signal;
KW   Transmembrane; Transmembrane helix; Viral attachment to host cell;
KW   Viral envelope protein; Viral immunoevasion;
KW   Viral penetration into host cytoplasm; Virion; Virus endocytosis by host;
KW   Virus entry into host cell.
FT   SIGNAL          1..31
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CHAIN           32..855
FT                   /note="Envelope glycoprotein gp160"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000239473"
FT   CHAIN           32..509
FT                   /note="Surface protein gp120"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000038386"
FT   CHAIN           510..855
FT                   /note="Transmembrane protein gp41"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000038387"
FT   TOPO_DOM        32..683
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   TRANSMEM        684..704
FT                   /note="Helical"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   TOPO_DOM        705..855
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          130..154
FT                   /note="V1"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          155..199
FT                   /note="V2"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          299..332
FT                   /note="V3"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          366..376
FT                   /note="CD4-binding loop"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          387..415
FT                   /note="V4"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          458..469
FT                   /note="V5"
FT   REGION          460..469
FT                   /note="V5"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          510..531
FT                   /note="Fusion peptide"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          573..591
FT                   /note="Immunosuppression"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          661..682
FT                   /note="MPER; binding to GalCer"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          720..739
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COILED          632..666
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   MOTIF           711..714
FT                   /note="YXXL motif; contains endocytosis signal"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   MOTIF           854..855
FT                   /note="Di-leucine internalization motif"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   SITE            509..510
FT                   /note="Cleavage; by host furin"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   LIPID           763
FT                   /note="S-palmitoyl cysteine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        87
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        129
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        140
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        154
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        158
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        184
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        190
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        200
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        233
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        244
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        265
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        279
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        292
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        298
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        304
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        334
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        341
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        358
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        364
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        388
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        394
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        400
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        408
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        445
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        458
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        461
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        610
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        615
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        624
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        636
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        53..73
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        118..208
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        125..199
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        130..155
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        221..250
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        231..242
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        299..333
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        380..442
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        387..415
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        597..603
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   STRAND          595..600
FT                   /evidence="ECO:0007829|PDB:5DRZ"
FT   TURN            601..605
FT                   /evidence="ECO:0007829|PDB:5DRZ"
SQ   SEQUENCE   855 AA;  97438 MW;  A3BC20573AAC41A2 CRC64;
     MKVKGTRRNY QHLWRWGTLL LGMLMICSAT EKLWVTVYYG VPVWKEATTT LFCASDARAY
     DTEVHNVWAT HACVPTDPNP QEVVLGNVTE NFNMWKNNMV EQMQEDIISL WDQSLKPCVK
     LTPLCVTLNC TDLGKATNTN SSNWKEEIKG EIKNCSFNIT TSIRDKIQKE NALFRNLDVV
     PIDNASTTTN YTNYRLIHCN RSVITQACPK VSFEPIPIHY CTPAGFAILK CNNKTFNGKG
     PCTNVSTVQC THGIRPIVST QLLLNGSLAE EEVVIRSDNF TNNAKTIIVQ LNESVAINCT
     RPNNNTRKSI YIGPGRAFHT TGRIIGDIRK AHCNISRAQW NNTLEQIVKK LREQFGNNKT
     IVFNQSSGGD PEIVMHSFNC RGEFFYCNTT QLFNNTWRLN HTEGTKGNDT IILPCRIKQI
     INMWQEVGKA MYAPPIGGQI SCSSNITGLL LTRDGGTNVT NDTEVFRPGG GDMRDNWRSE
     LYKYKVIKIE PLGIAPTKAK RRVVQREKRA VGIVGAMFLG FLGAAGSTMG AVSLTLTVQA
     RQLLSGIVQQ QNNLLRAIEA QQHLLQLTVW GIKQLQARVL AVERYLRDQQ LLGIWGCSGK
     LICTTAVPWN ASWSNKSLED IWDNMTWMQW EREIDNYTNT IYTLLEESQN QQEKNEQELL
     ELDKWASLWN WFSITNWLWY IKIFIMIVGG LVGLRIVFAV LSIVNRVRQG YSPLSFQTRL
     PVPRGPDRPD GIEEEGGERD RDRSVRLVDG FLALIWEDLR SLCLFSYRRL RDLLLIAART
     VEILGHRGWE ALKYWWSLLQ YWIQELKNSA VSWLNATAIA VTEGTDRVIE VAQRAYRAIL
     HIHRRIRQGL ERLLL
//
ID   ENV_HV1B1               Reviewed;         856 AA.
AC   P03375; P03376;
DT   21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT   21-JUL-1986, sequence version 1.
DT   27-MAR-2024, entry version 180.
DE   RecName: Full=Envelope glycoprotein gp160 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   AltName: Full=Env polyprotein {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Contains:
DE     RecName: Full=Surface protein gp120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=SU {ECO:0000255|HAMAP-Rule:MF_04083};
DE     AltName: Full=Glycoprotein 120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=gp120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Contains:
DE     RecName: Full=Transmembrane protein gp41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=TM {ECO:0000255|HAMAP-Rule:MF_04083};
DE     AltName: Full=Glycoprotein 41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=gp41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Flags: Precursor;
GN   Name=env {ECO:0000255|HAMAP-Rule:MF_04083};
OS   Human immunodeficiency virus type 1 group M subtype B (isolate BH10)
OS   (HIV-1).
OC   Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC   Ortervirales; Retroviridae; Orthoretrovirinae; Lentivirus;
OC   Human immunodeficiency virus 1.
OX   NCBI_TaxID=11678;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX   PubMed=2578615; DOI=10.1038/313277a0;
RA   Ratner L., Haseltine W.A., Patarca R., Livak K.J., Starcich B.R.,
RA   Josephs S.F., Doran E.R., Rafalski J.A., Whitehorn E.A., Baumeister K.,
RA   Ivanoff L., Petteway S.R. Jr., Pearson M.L., Lautenberger J.A., Papas T.S.,
RA   Ghrayeb J., Chang N.T., Gallo R.C., Wong-Staal F.;
RT   "Complete nucleotide sequence of the AIDS virus, HTLV-III.";
RL   Nature 313:277-284(1985).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=Isolate PV22;
RX   PubMed=2982104; DOI=10.1038/313450a0;
RA   Muesing M.A., Smith D.H., Cabradilla C.D., Benton C.V., Lasky L.A.,
RA   Capon D.J.;
RT   "Nucleic acid structure and expression of the human AIDS/lymphadenopathy
RT   retrovirus.";
RL   Nature 313:450-458(1985).
RN   [3]
RP   PROTEOLYTIC PROCESSING OF POLYPROTEIN.
RX   PubMed=2450679; DOI=10.1016/0092-8674(88)90487-4;
RA   McCune J.M., Rabin L.B., Feinberg M.B., Lieberman M., Kosek J.C.,
RA   Reyes G.R., Weissman I.L.;
RT   "Endoproteolytic cleavage of gp160 is required for the activation of human
RT   immunodeficiency virus.";
RL   Cell 53:55-67(1988).
RN   [4]
RP   PROTEIN SEQUENCE OF C-TERMINUS, DISULFIDE BONDS, GLYCOSYLATION AT ASN-88;
RP   ASN-136; ASN-141; ASN-156; ASN-160; ASN-186; ASN-197; ASN-230; ASN-234;
RP   ASN-241; ASN-262; ASN-276; ASN-289; ASN-295; ASN-301; ASN-332; ASN-339;
RP   ASN-356; ASN-386; ASN-392; ASN-397; ASN-406; ASN-448 AND ASN-463, AND
RP   STRUCTURE OF CARBOHYDRATES.
RX   PubMed=2355006; DOI=10.1016/s0021-9258(18)86956-3;
RA   Leonard C.K., Spellman M.W., Riddle L., Harris R.J., Thomas J.N.,
RA   Gregory T.J.;
RT   "Assignment of intrachain disulfide bonds and characterization of potential
RT   glycosylation sites of the type 1 recombinant human immunodeficiency virus
RT   envelope glycoprotein (gp120) expressed in Chinese hamster ovary cells.";
RL   J. Biol. Chem. 265:10373-10382(1990).
RN   [5]
RP   INTERACTION OF GLYCOPROTEIN 120 WITH HOST CD4.
RX   PubMed=2214026; DOI=10.1128/jvi.64.11.5585-5593.1990;
RA   Crise B., Buonocore L., Rose J.K.;
RT   "CD4 is retained in the endoplasmic reticulum by the human immunodeficiency
RT   virus type 1 glycoprotein precursor.";
RL   J. Virol. 64:5585-5593(1990).
RN   [6]
RP   INTERACTION OF TRANSMEMBRANE PROTEIN GP41 WITH GALACTOSYL CERAMIDE.
RX   PubMed=11342649; DOI=10.4049/jimmunol.166.10.6257;
RA   Alfsen A., Iniguez P., Bouguyon E., Bomsel M.;
RT   "Secretory IgA specific for a conserved epitope on gp41 envelope
RT   glycoprotein inhibits epithelial transcytosis of HIV-1.";
RL   J. Immunol. 166:6257-6265(2001).
RN   [7]
RP   REDUCTION OF SURFACE PROTEIN GP120 DISULFIDE BONDS BY P4HB/PDI.
RX   PubMed=11181151; DOI=10.1086/318823;
RA   Fenouillet E., Barbouche R., Courageot J., Miquelis R.;
RT   "The catalytic activity of protein disulfide isomerase is involved in human
RT   immunodeficiency virus envelope-mediated membrane fusion after CD4 cell
RT   binding.";
RL   J. Infect. Dis. 183:744-752(2001).
RN   [8]
RP   REDUCTION OF SURFACE PROTEIN GP120 DISULFIDE BONDS BY P4HB/PDI.
RX   PubMed=12218052; DOI=10.1074/jbc.m205467200;
RA   Barbouche R., Miquelis R., Jones I.M., Fenouillet E.;
RT   "Protein-disulfide isomerase-mediated reduction of two disulfide bonds of
RT   HIV envelope glycoprotein 120 occurs post-CXCR4 binding and is required for
RT   fusion.";
RL   J. Biol. Chem. 278:3131-3136(2003).
RN   [9]
RP   REDUCTION OF SURFACE PROTEIN GP120 DISULFIDE BONDS BY P4HB/PDI.
RX   PubMed=14592831; DOI=10.1182/blood-2003-05-1390;
RA   Markovic I., Stantchev T.S., Fields K.H., Tiffany L.J., Tomic M.,
RA   Weiss C.D., Broder C.C., Strebel K., Clouse K.A.;
RT   "Thiol/disulfide exchange is a prerequisite for CXCR4-tropic HIV-1
RT   envelope-mediated T-cell fusion during viral entry.";
RL   Blood 103:1586-1594(2004).
RN   [10]
RP   REDUCTION OF SURFACE PROTEIN GP120 DISULFIDE BONDS BY P4HB/PDI.
RX   PubMed=15644496; DOI=10.1124/mol.104.008276;
RA   Barbouche R., Lortat-Jacob H., Jones I.M., Fenouillet E.;
RT   "Glycosaminoglycans and protein disulfide isomerase-mediated reduction of
RT   HIV Env.";
RL   Mol. Pharmacol. 67:1111-1118(2005).
RN   [11]
RP   REVIEW.
RX   PubMed=12974773; DOI=10.1034/j.1600-0463.2003.11107803.x;
RA   Geijtenbeek T.B., van Kooyk Y.;
RT   "Pathogens target DC-SIGN to influence their fate DC-SIGN functions as a
RT   pathogen receptor with broad specificity.";
RL   APMIS 111:698-714(2003).
RN   [12]
RP   REVIEW.
RX   PubMed=12873764; DOI=10.1016/s0005-2736(03)00161-5;
RA   Gallo S.A., Finnegan C.M., Viard M., Raviv Y., Dimitrov A., Rawat S.S.,
RA   Puri A., Durell S., Blumenthal R.;
RT   "The HIV Env-mediated fusion reaction.";
RL   Biochim. Biophys. Acta 1614:36-50(2003).
RN   [13]
RP   REVIEW.
RX   PubMed=15719026; DOI=10.1038/sj.cdd.4401584;
RA   Perfettini J.-L., Castedo M., Roumier T., Andreau K., Nardacci R.,
RA   Piacentini M., Kroemer G.;
RT   "Mechanisms of apoptosis induction by the HIV-1 envelope.";
RL   Cell Death Differ. 12:916-923(2005).
RN   [14]
RP   REVIEW.
RX   PubMed=15725757; DOI=10.1089/aid.2005.21.171;
RA   Hartley O., Klasse P.J., Sattentau Q.J., Moore J.P.;
RT   "V3: HIV's switch-hitter.";
RL   AIDS Res. Hum. Retroviruses 21:171-189(2005).
RN   [15]
RP   REVIEW.
RX   PubMed=16114975; DOI=10.2165/00003495-200565130-00002;
RA   Reeves J.D., Piefer A.J.;
RT   "Emerging drug targets for antiretroviral therapy.";
RL   Drugs 65:1747-1766(2005).
RN   [16]
RP   REVIEW.
RX   PubMed=16437164; DOI=10.1038/sj.emboj.7600947;
RA   Lusso P.;
RT   "HIV and the chemokine system: 10 years later.";
RL   EMBO J. 25:447-456(2006).
CC   -!- FUNCTION: [Envelope glycoprotein gp160]: Oligomerizes in the host
CC       endoplasmic reticulum into predominantly trimers. In a second time,
CC       gp160 transits in the host Golgi, where glycosylation is completed. The
CC       precursor is then proteolytically cleaved in the trans-Golgi and
CC       thereby activated by cellular furin or furin-like proteases to produce
CC       gp120 and gp41. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- FUNCTION: [Surface protein gp120]: Attaches the virus to the host
CC       lymphoid cell by binding to the primary receptor CD4. This interaction
CC       induces a structural rearrangement creating a high affinity binding
CC       site for a chemokine coreceptor like CXCR4 and/or CCR5. Acts as a
CC       ligand for CD209/DC-SIGN and CLEC4M/DC-SIGNR, which are respectively
CC       found on dendritic cells (DCs), and on endothelial cells of liver
CC       sinusoids and lymph node sinuses. These interactions allow capture of
CC       viral particles at mucosal surfaces by these cells and subsequent
CC       transmission to permissive cells. HIV subverts the migration properties
CC       of dendritic cells to gain access to CD4+ T-cells in lymph nodes. Virus
CC       transmission to permissive T-cells occurs either in trans (without DCs
CC       infection, through viral capture and transmission), or in cis
CC       (following DCs productive infection, through the usual CD4-gp120
CC       interaction), thereby inducing a robust infection. In trans infection,
CC       bound virions remain infectious over days and it is proposed that they
CC       are not degraded, but protected in non-lysosomal acidic organelles
CC       within the DCs close to the cell membrane thus contributing to the
CC       viral infectious potential during DCs' migration from the periphery to
CC       the lymphoid tissues. On arrival at lymphoid tissues, intact virions
CC       recycle back to DCs' cell surface allowing virus transmission to CD4+
CC       T-cells. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- FUNCTION: [Transmembrane protein gp41]: Acts as a class I viral fusion
CC       protein. Under the current model, the protein has at least 3
CC       conformational states: pre-fusion native state, pre-hairpin
CC       intermediate state, and post-fusion hairpin state. During fusion of
CC       viral and target intracellular membranes, the coiled coil regions
CC       (heptad repeats) assume a trimer-of-hairpins structure, positioning the
CC       fusion peptide in close proximity to the C-terminal region of the
CC       ectodomain. The formation of this structure appears to drive apposition
CC       and subsequent fusion of viral and target cell membranes. Complete
CC       fusion occurs in host cell endosomes and is dynamin-dependent, however
CC       some lipid transfer might occur at the plasma membrane. The virus
CC       undergoes clathrin-dependent internalization long before endosomal
CC       fusion, thus minimizing the surface exposure of conserved viral
CC       epitopes during fusion and reducing the efficacy of inhibitors
CC       targeting these epitopes. Membranes fusion leads to delivery of the
CC       nucleocapsid into the cytoplasm. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBUNIT: [Surface protein gp120]: The mature envelope protein (Env)
CC       consists of a homotrimer of non-covalently associated gp120-gp41
CC       heterodimers. The resulting complex protrudes from the virus surface as
CC       a spike. There seems to be as few as 10 spikes on the average virion.
CC       Interacts with host CD4, CCR5 and CXCR4. Gp120 also interacts with the
CC       C-type lectins CD209/DC-SIGN and CLEC4M/DC-SIGNR (collectively referred
CC       to as DC-SIGN(R)). Gp120 and gp41 interact with GalCer. Gp120 interacts
CC       with host ITGA4/ITGB7 complex; on CD4+ T-cells, this interaction
CC       results in rapid activation of integrin ITGAL/LFA-1, which facilitates
CC       efficient cell-to-cell spreading of HIV-1. Gp120 interacts with cell-
CC       associated heparan sulfate; this interaction increases virus
CC       infectivity on permissive cells and may be involved in infection of
CC       CD4- cells. {ECO:0000255|HAMAP-Rule:MF_04083,
CC       ECO:0000269|PubMed:2214026}.
CC   -!- SUBUNIT: [Transmembrane protein gp41]: The mature envelope protein
CC       (Env) consists of a homotrimer of non-covalently associated gp120-gp41
CC       heterodimers. The resulting complex protrudes from the virus surface as
CC       a spike. There seems to be as few as 10 spikes on the average virion.
CC       {ECO:0000255|HAMAP-Rule:MF_04083, ECO:0000269|PubMed:2214026}.
CC   -!- SUBCELLULAR LOCATION: [Surface protein gp120]: Virion membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Peripheral membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host cell membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Peripheral membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host endosome membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Note=The surface protein is not
CC       anchored to the viral envelope, but associates with the extravirion
CC       surface through its binding to TM. It is probably concentrated at the
CC       site of budding and incorporated into the virions possibly by contacts
CC       between the cytoplasmic tail of Env and the N-terminus of Gag.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBCELLULAR LOCATION: [Transmembrane protein gp41]: Virion membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host cell membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host endosome membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Note=It is probably concentrated at
CC       the site of budding and incorporated into the virions possibly by
CC       contacts between the cytoplasmic tail of Env and the N-terminus of Gag.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: Some of the most genetically diverse regions of the viral
CC       genome are present in Env. They are called variable regions 1 through 5
CC       (V1 through V5). Coreceptor usage of gp120 is determined mainly by the
CC       primary structure of the third variable region (V3) in the outer domain
CC       of gp120. The sequence of V3 determines which coreceptor, CCR5 and/or
CC       CXCR4 (corresponding to R5/macrophage, X4/T cell and R5X4/T cell and
CC       macrophage tropism), is used to trigger the fusion potential of the Env
CC       complex, and hence which cells the virus can infect. Binding to CCR5
CC       involves a region adjacent in addition to V3. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- DOMAIN: The membrane proximal external region (MPER) present in gp41 is
CC       a tryptophan-rich region recognized by the antibodies 2F5, Z13, and
CC       4E10. MPER seems to play a role in fusion. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- DOMAIN: The 17 amino acids long immunosuppressive region is present in
CC       many retroviral envelope proteins. Synthetic peptides derived from this
CC       relatively conserved sequence inhibit immune function in vitro and in
CC       vivo. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: The YXXL motif is involved in determining the exact site of
CC       viral release at the surface of infected mononuclear cells and promotes
CC       endocytosis. YXXL and di-leucine endocytosis motifs interact directly
CC       or indirectly with the clathrin adapter complexes, opperate
CC       independently, and their activities are not additive.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: The CD4-binding region is targeted by the antibody b12.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- PTM: Highly glycosylated by host. The high number of glycan on the
CC       protein is reffered to as 'glycan shield' because it contributes to
CC       hide protein sequence from adaptive immune system. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- PTM: Palmitoylation of the transmembrane protein and of Env polyprotein
CC       (prior to its proteolytic cleavage) is essential for their association
CC       with host cell membrane lipid rafts. Palmitoylation is therefore
CC       required for envelope trafficking to classical lipid rafts, but not for
CC       viral replication. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- PTM: Specific enzymatic cleavages in vivo yield mature proteins.
CC       Envelope glycoproteins are synthesized as an inactive precursor that is
CC       heavily N-glycosylated and processed likely by host cell furin in the
CC       Golgi to yield the mature SU and TM proteins. The cleavage site between
CC       SU and TM requires the minimal sequence [KR]-X-[KR]-R. About 2 of the 9
CC       disulfide bonds of gp41 are reduced by P4HB/PDI, following binding to
CC       CD4 receptor. {ECO:0000255|HAMAP-Rule:MF_04083,
CC       ECO:0000269|PubMed:12218052, ECO:0000269|PubMed:14592831,
CC       ECO:0000269|PubMed:15644496}.
CC   -!- MISCELLANEOUS: Inhibitors targeting HIV-1 viral envelope proteins are
CC       used as antiretroviral drugs. Attachment of virions to the cell surface
CC       via non-specific interactions and CD4 binding can be blocked by
CC       inhibitors that include cyanovirin-N, cyclotriazadisulfonamide analogs,
CC       PRO 2000, TNX 355 and PRO 542. In addition, BMS 806 can block CD4-
CC       induced conformational changes. Env interactions with the coreceptor
CC       molecules can be targeted by CCR5 antagonists including SCH-D,
CC       maraviroc (UK 427857) and aplaviroc (GW 873140), and the CXCR4
CC       antagonist AMD 070. Fusion of viral and cellular membranes can be
CC       inhibited by peptides such as enfuvirtide and tifuvirtide (T 1249).
CC       Resistance to inhibitors associated with mutations in Env are observed.
CC       Most of the time, single mutations confer only a modest reduction in
CC       drug susceptibility. Combination of several mutations is usually
CC       required to develop a high-level drug resistance. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- MISCELLANEOUS: HIV-1 lineages are divided in three main groups, M (for
CC       Major), O (for Outlier), and N (for New, or Non-M, Non-O). The vast
CC       majority of strains found worldwide belong to the group M. Group O
CC       seems to be endemic to and largely confined to Cameroon and neighboring
CC       countries in West Central Africa, where these viruses represent a small
CC       minority of HIV-1 strains. The group N is represented by a limited
CC       number of isolates from Cameroonian persons. The group M is further
CC       subdivided in 9 clades or subtypes (A to D, F to H, J and K).
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SIMILARITY: Belongs to the HIV-1 env protein family.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- WEB RESOURCE: Name=hivdb; Note=HIV drug resistance database;
CC       URL="https://hivdb.stanford.edu";
CC   -!- WEB RESOURCE: Name=HIV drug resistance mutations;
CC       URL="https://www.iasusa.org/content/hiv-drug-resistance-mutations";
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DR   EMBL; M15654; AAA44205.1; -; Genomic_RNA.
DR   EMBL; K02083; AAB59873.1; -; Genomic_DNA.
DR   EMBL; X01762; CAA25903.1; ALT_SEQ; Genomic_RNA.
DR   PIR; A03973; VCLJH3.
DR   PIR; A03974; VCLJVL.
DR   PDB; 2ARI; NMR; -; A=512-541.
DR   PDB; 3VGY; X-ray; 2.03 A; C=546-588.
DR   PDB; 3VH7; X-ray; 2.02 A; A/C/E=546-588.
DR   PDB; 3VU5; X-ray; 2.09 A; A=553-590.
DR   PDB; 3VU6; X-ray; 2.32 A; A=553-590.
DR   PDB; 3W19; X-ray; 1.28 A; C=553-590.
DR   PDB; 6ME1; X-ray; 1.97 A; E/F=512-521.
DR   PDBsum; 2ARI; -.
DR   PDBsum; 3VGY; -.
DR   PDBsum; 3VH7; -.
DR   PDBsum; 3VU5; -.
DR   PDBsum; 3VU6; -.
DR   PDBsum; 3W19; -.
DR   PDBsum; 6ME1; -.
DR   BMRB; P03375; -.
DR   SMR; P03375; -.
DR   MINT; P03375; -.
DR   ChEMBL; CHEMBL5057; -.
DR   GlyCosmos; P03375; 29 sites, No reported glycans.
DR   iPTMnet; P03375; -.
DR   ABCD; P03375; 2 sequenced antibodies.
DR   Reactome; R-HSA-5621480; Dectin-2 family.
DR   EvolutionaryTrace; P03375; -.
DR   Proteomes; UP000007690; Genome.
DR   Proteomes; UP000107234; Genome.
DR   Proteomes; UP000126245; Genome.
DR   GO; GO:0044175; C:host cell endosome membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0044220; C:host cell perinuclear region of cytoplasm; IDA:UniProtKB.
DR   GO; GO:0044538; C:host cell periphery; IDA:UniProtKB.
DR   GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0016020; C:membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:0019031; C:viral envelope; IEA:UniProtKB-KW.
DR   GO; GO:0055036; C:virion membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0042609; F:CD4 receptor binding; IPI:UniProtKB.
DR   GO; GO:0044877; F:protein-containing complex binding; IDA:UniProtKB.
DR   GO; GO:0005198; F:structural molecule activity; IEA:UniProtKB-UniRule.
DR   GO; GO:0075512; P:clathrin-dependent endocytosis of virus by host cell; IEA:UniProtKB-UniRule.
DR   GO; GO:0039654; P:fusion of virus membrane with host endosome membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:0019064; P:fusion of virus membrane with host plasma membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:1903905; P:positive regulation of establishment of T cell polarity; IEA:UniProtKB-UniRule.
DR   GO; GO:1903908; P:positive regulation of plasma membrane raft polarization; IEA:UniProtKB-UniRule.
DR   GO; GO:1903911; P:positive regulation of receptor clustering; IEA:UniProtKB-UniRule.
DR   GO; GO:0019082; P:viral protein processing; IEA:UniProtKB-UniRule.
DR   GO; GO:0019062; P:virion attachment to host cell; IEA:UniProtKB-UniRule.
DR   GO; GO:0019049; P:virus-mediated perturbation of host defense response; IEA:UniProtKB-UniRule.
DR   CDD; cd09909; HIV-1-like_HR1-HR2; 1.
DR   Gene3D; 1.10.287.210; -; 1.
DR   Gene3D; 2.170.40.20; Human immunodeficiency virus 1, Gp160, envelope glycoprotein; 2.
DR   Gene3D; 1.20.5.490; Single helix bin; 1.
DR   HAMAP; MF_04083; HIV_ENV; 1.
DR   InterPro; IPR036377; Gp120_core_sf.
DR   InterPro; IPR037527; Gp160.
DR   InterPro; IPR000328; GP41-like.
DR   InterPro; IPR000777; HIV1_Gp120.
DR   Pfam; PF00516; GP120; 1.
DR   Pfam; PF00517; GP41; 1.
DR   SUPFAM; SSF56502; gp120 core; 1.
DR   SUPFAM; SSF58069; Virus ectodomain; 1.
PE   1: Evidence at protein level;
KW   3D-structure; AIDS; Apoptosis;
KW   Clathrin-mediated endocytosis of virus by host;
KW   Cleavage on pair of basic residues; Coiled coil; Direct protein sequencing;
KW   Disulfide bond; Fusion of virus membrane with host endosomal membrane;
KW   Fusion of virus membrane with host membrane; Glycoprotein;
KW   Host cell membrane; Host endosome; Host membrane; Host-virus interaction;
KW   Lipoprotein; Membrane; Palmitate; Reference proteome; Signal;
KW   Transmembrane; Transmembrane helix; Viral attachment to host cell;
KW   Viral envelope protein; Viral immunoevasion;
KW   Viral penetration into host cytoplasm; Virion; Virus endocytosis by host;
KW   Virus entry into host cell.
FT   SIGNAL          1..32
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CHAIN           33..856
FT                   /note="Envelope glycoprotein gp160"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000239239"
FT   CHAIN           33..511
FT                   /note="Surface protein gp120"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000038371"
FT   CHAIN           512..856
FT                   /note="Transmembrane protein gp41"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000038372"
FT   TOPO_DOM        33..684
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   TRANSMEM        685..705
FT                   /note="Helical"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   TOPO_DOM        706..856
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          131..156
FT                   /note="V1"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          157..196
FT                   /note="V2"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          296..330
FT                   /note="V3"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          364..374
FT                   /note="CD4-binding loop"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          385..418
FT                   /note="V4"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          461..471
FT                   /note="V5"
FT   REGION          463..471
FT                   /note="V5"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          512..532
FT                   /note="Fusion peptide"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          574..592
FT                   /note="Immunosuppression"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          662..683
FT                   /note="MPER; binding to GalCer"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          662..667
FT                   /note="Involved in GalCer binding"
FT   REGION          721..740
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COILED          633..667
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   MOTIF           712..715
FT                   /note="YXXL motif; contains endocytosis signal"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   MOTIF           855..856
FT                   /note="Di-leucine internalization motif"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   SITE            511..512
FT                   /note="Cleavage; by host furin"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   LIPID           764
FT                   /note="S-palmitoyl cysteine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        88
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083,
FT                   ECO:0000269|PubMed:2355006"
FT   CARBOHYD        136
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083,
FT                   ECO:0000269|PubMed:2355006"
FT   CARBOHYD        141
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083,
FT                   ECO:0000269|PubMed:2355006"
FT   CARBOHYD        156
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083,
FT                   ECO:0000269|PubMed:2355006"
FT   CARBOHYD        160
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083,
FT                   ECO:0000269|PubMed:2355006"
FT   CARBOHYD        186
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083,
FT                   ECO:0000269|PubMed:2355006"
FT   CARBOHYD        197
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083,
FT                   ECO:0000269|PubMed:2355006"
FT   CARBOHYD        230
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083,
FT                   ECO:0000269|PubMed:2355006"
FT   CARBOHYD        234
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083,
FT                   ECO:0000269|PubMed:2355006"
FT   CARBOHYD        241
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083,
FT                   ECO:0000269|PubMed:2355006"
FT   CARBOHYD        262
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083,
FT                   ECO:0000269|PubMed:2355006"
FT   CARBOHYD        276
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083,
FT                   ECO:0000269|PubMed:2355006"
FT   CARBOHYD        289
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083,
FT                   ECO:0000269|PubMed:2355006"
FT   CARBOHYD        295
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083,
FT                   ECO:0000269|PubMed:2355006"
FT   CARBOHYD        301
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083,
FT                   ECO:0000269|PubMed:2355006"
FT   CARBOHYD        332
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083,
FT                   ECO:0000269|PubMed:2355006"
FT   CARBOHYD        339
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083,
FT                   ECO:0000269|PubMed:2355006"
FT   CARBOHYD        356
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083,
FT                   ECO:0000269|PubMed:2355006"
FT   CARBOHYD        386
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083,
FT                   ECO:0000269|PubMed:2355006"
FT   CARBOHYD        392
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083,
FT                   ECO:0000269|PubMed:2355006"
FT   CARBOHYD        397
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083,
FT                   ECO:0000269|PubMed:2355006"
FT   CARBOHYD        406
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083,
FT                   ECO:0000269|PubMed:2355006"
FT   CARBOHYD        448
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083,
FT                   ECO:0000269|PubMed:2355006"
FT   CARBOHYD        463
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083,
FT                   ECO:0000269|PubMed:2355006"
FT   CARBOHYD        611
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        616
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        625
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        637
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        674
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        54..74
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083,
FT                   ECO:0000269|PubMed:2355006"
FT   DISULFID        119..205
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083,
FT                   ECO:0000269|PubMed:2355006"
FT   DISULFID        126..196
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083,
FT                   ECO:0000269|PubMed:2355006"
FT   DISULFID        131..157
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083,
FT                   ECO:0000269|PubMed:2355006"
FT   DISULFID        218..247
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083,
FT                   ECO:0000269|PubMed:2355006"
FT   DISULFID        228..239
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083,
FT                   ECO:0000269|PubMed:2355006"
FT   DISULFID        296..331
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083,
FT                   ECO:0000269|PubMed:2355006"
FT   DISULFID        378..445
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083,
FT                   ECO:0000269|PubMed:2355006"
FT   DISULFID        385..418
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083,
FT                   ECO:0000269|PubMed:2355006"
FT   DISULFID        598..604
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   VARIANT         403
FT                   /note="K -> E (in strain: Isolate PV22)"
FT   VARIANT         423
FT                   /note="I -> F (in strain: Isolate PV22)"
FT   VARIANT         461
FT                   /note="S -> N (in strain: Isolate PV22)"
FT   VARIANT         668
FT                   /note="S -> N (in strain: Isolate PV22)"
FT   VARIANT         673
FT                   /note="F -> L (in strain: Isolate PV22)"
FT   VARIANT         704
FT                   /note="V -> I (in strain: Isolate PV22)"
FT   VARIANT         723
FT                   /note="I -> T (in strain: Isolate PV22)"
FT   VARIANT         737
FT                   /note="G -> D (in strain: Isolate PV22)"
FT   HELIX           516..530
FT                   /evidence="ECO:0007829|PDB:2ARI"
FT   TURN            531..533
FT                   /evidence="ECO:0007829|PDB:2ARI"
FT   STRAND          536..538
FT                   /evidence="ECO:0007829|PDB:2ARI"
FT   HELIX           554..589
FT                   /evidence="ECO:0007829|PDB:3W19"
SQ   SEQUENCE   856 AA;  97225 MW;  0BFFB1A18931BB27 CRC64;
     MRVKEKYQHL WRWGWRWGTM LLGMLMICSA TEKLWVTVYY GVPVWKEATT TLFCASDAKA
     YDTEVHNVWA THACVPTDPN PQEVVLVNVT ENFNMWKNDM VEQMHEDIIS LWDQSLKPCV
     KLTPLCVSLK CTDLKNDTNT NSSSGRMIME KGEIKNCSFN ISTSIRGKVQ KEYAFFYKLD
     IIPIDNDTTS YTLTSCNTSV ITQACPKVSF EPIPIHYCAP AGFAILKCNN KTFNGTGPCT
     NVSTVQCTHG IRPVVSTQLL LNGSLAEEEV VIRSANFTDN AKTIIVQLNQ SVEINCTRPN
     NNTRKSIRIQ RGPGRAFVTI GKIGNMRQAH CNISRAKWNN TLKQIDSKLR EQFGNNKTII
     FKQSSGGDPE IVTHSFNCGG EFFYCNSTQL FNSTWFNSTW STKGSNNTEG SDTITLPCRI
     KQIINMWQEV GKAMYAPPIS GQIRCSSNIT GLLLTRDGGN SNNESEIFRP GGGDMRDNWR
     SELYKYKVVK IEPLGVAPTK AKRRVVQREK RAVGIGALFL GFLGAAGSTM GAASMTLTVQ
     ARQLLSGIVQ QQNNLLRAIE AQQHLLQLTV WGIKQLQARI LAVERYLKDQ QLLGIWGCSG
     KLICTTAVPW NASWSNKSLE QIWNNMTWME WDREINNYTS LIHSLIEESQ NQQEKNEQEL
     LELDKWASLW NWFNITNWLW YIKLFIMIVG GLVGLRIVFA VLSVVNRVRQ GYSPLSFQTH
     LPIPRGPDRP EGIEEEGGER DRDRSIRLVN GSLALIWDDL RSLCLFSYHR LRDLLLIVTR
     IVELLGRRGW EALKYWWNLL QYWSQELKNS AVSLLNATAI AVAEGTDRVI EVVQGAYRAI
     RHIPRRIRQG LERILL
//
ID   ENV_HV1B8               Reviewed;         851 AA.
AC   P04582;
DT   13-AUG-1987, integrated into UniProtKB/Swiss-Prot.
DT   13-AUG-1987, sequence version 1.
DT   27-MAR-2024, entry version 158.
DE   RecName: Full=Envelope glycoprotein gp160 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   AltName: Full=Env polyprotein {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Contains:
DE     RecName: Full=Surface protein gp120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=SU {ECO:0000255|HAMAP-Rule:MF_04083};
DE     AltName: Full=Glycoprotein 120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=gp120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Contains:
DE     RecName: Full=Transmembrane protein gp41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=TM {ECO:0000255|HAMAP-Rule:MF_04083};
DE     AltName: Full=Glycoprotein 41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=gp41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Flags: Precursor;
GN   Name=env {ECO:0000255|HAMAP-Rule:MF_04083};
OS   Human immunodeficiency virus type 1 group M subtype B (isolate BH8)
OS   (HIV-1).
OC   Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC   Ortervirales; Retroviridae; Orthoretrovirinae; Lentivirus;
OC   Human immunodeficiency virus 1.
OX   NCBI_TaxID=11684;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX   PubMed=2578615; DOI=10.1038/313277a0;
RA   Ratner L., Haseltine W.A., Patarca R., Livak K.J., Starcich B.R.,
RA   Josephs S.F., Doran E.R., Rafalski J.A., Whitehorn E.A., Baumeister K.,
RA   Ivanoff L., Petteway S.R. Jr., Pearson M.L., Lautenberger J.A., Papas T.S.,
RA   Ghrayeb J., Chang N.T., Gallo R.C., Wong-Staal F.;
RT   "Complete nucleotide sequence of the AIDS virus, HTLV-III.";
RL   Nature 313:277-284(1985).
RN   [2]
RP   INTERACTION OF SURFACE PROTEIN GP120 WITH HUMAN CXCR4.
RX   PubMed=10074122; DOI=10.1128/jvi.73.4.2752-2761.1999;
RA   Doranz B.J., Orsini M.J., Turner J.D., Hoffman T.L., Berson J.F.,
RA   Hoxie J.A., Peiper S.C., Brass L.F., Doms R.W.;
RT   "Identification of CXCR4 domains that support coreceptor and chemokine
RT   receptor functions.";
RL   J. Virol. 73:2752-2761(1999).
RN   [3]
RP   REVIEW.
RX   PubMed=12974773; DOI=10.1034/j.1600-0463.2003.11107803.x;
RA   Geijtenbeek T.B., van Kooyk Y.;
RT   "Pathogens target DC-SIGN to influence their fate DC-SIGN functions as a
RT   pathogen receptor with broad specificity.";
RL   APMIS 111:698-714(2003).
RN   [4]
RP   REVIEW.
RX   PubMed=12873764; DOI=10.1016/s0005-2736(03)00161-5;
RA   Gallo S.A., Finnegan C.M., Viard M., Raviv Y., Dimitrov A., Rawat S.S.,
RA   Puri A., Durell S., Blumenthal R.;
RT   "The HIV Env-mediated fusion reaction.";
RL   Biochim. Biophys. Acta 1614:36-50(2003).
RN   [5]
RP   REVIEW.
RX   PubMed=15719026; DOI=10.1038/sj.cdd.4401584;
RA   Perfettini J.-L., Castedo M., Roumier T., Andreau K., Nardacci R.,
RA   Piacentini M., Kroemer G.;
RT   "Mechanisms of apoptosis induction by the HIV-1 envelope.";
RL   Cell Death Differ. 12:916-923(2005).
RN   [6]
RP   REVIEW.
RX   PubMed=15725757; DOI=10.1089/aid.2005.21.171;
RA   Hartley O., Klasse P.J., Sattentau Q.J., Moore J.P.;
RT   "V3: HIV's switch-hitter.";
RL   AIDS Res. Hum. Retroviruses 21:171-189(2005).
RN   [7]
RP   REVIEW.
RX   PubMed=16114975; DOI=10.2165/00003495-200565130-00002;
RA   Reeves J.D., Piefer A.J.;
RT   "Emerging drug targets for antiretroviral therapy.";
RL   Drugs 65:1747-1766(2005).
RN   [8]
RP   REVIEW.
RX   PubMed=16437164; DOI=10.1038/sj.emboj.7600947;
RA   Lusso P.;
RT   "HIV and the chemokine system: 10 years later.";
RL   EMBO J. 25:447-456(2006).
CC   -!- FUNCTION: [Envelope glycoprotein gp160]: Oligomerizes in the host
CC       endoplasmic reticulum into predominantly trimers. In a second time,
CC       gp160 transits in the host Golgi, where glycosylation is completed. The
CC       precursor is then proteolytically cleaved in the trans-Golgi and
CC       thereby activated by cellular furin or furin-like proteases to produce
CC       gp120 and gp41. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- FUNCTION: [Surface protein gp120]: Attaches the virus to the host
CC       lymphoid cell by binding to the primary receptor CD4. This interaction
CC       induces a structural rearrangement creating a high affinity binding
CC       site for a chemokine coreceptor like CXCR4 and/or CCR5. Acts as a
CC       ligand for CD209/DC-SIGN and CLEC4M/DC-SIGNR, which are respectively
CC       found on dendritic cells (DCs), and on endothelial cells of liver
CC       sinusoids and lymph node sinuses. These interactions allow capture of
CC       viral particles at mucosal surfaces by these cells and subsequent
CC       transmission to permissive cells. HIV subverts the migration properties
CC       of dendritic cells to gain access to CD4+ T-cells in lymph nodes. Virus
CC       transmission to permissive T-cells occurs either in trans (without DCs
CC       infection, through viral capture and transmission), or in cis
CC       (following DCs productive infection, through the usual CD4-gp120
CC       interaction), thereby inducing a robust infection. In trans infection,
CC       bound virions remain infectious over days and it is proposed that they
CC       are not degraded, but protected in non-lysosomal acidic organelles
CC       within the DCs close to the cell membrane thus contributing to the
CC       viral infectious potential during DCs' migration from the periphery to
CC       the lymphoid tissues. On arrival at lymphoid tissues, intact virions
CC       recycle back to DCs' cell surface allowing virus transmission to CD4+
CC       T-cells. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- FUNCTION: [Transmembrane protein gp41]: Acts as a class I viral fusion
CC       protein. Under the current model, the protein has at least 3
CC       conformational states: pre-fusion native state, pre-hairpin
CC       intermediate state, and post-fusion hairpin state. During fusion of
CC       viral and target intracellular membranes, the coiled coil regions
CC       (heptad repeats) assume a trimer-of-hairpins structure, positioning the
CC       fusion peptide in close proximity to the C-terminal region of the
CC       ectodomain. The formation of this structure appears to drive apposition
CC       and subsequent fusion of viral and target cell membranes. Complete
CC       fusion occurs in host cell endosomes and is dynamin-dependent, however
CC       some lipid transfer might occur at the plasma membrane. The virus
CC       undergoes clathrin-dependent internalization long before endosomal
CC       fusion, thus minimizing the surface exposure of conserved viral
CC       epitopes during fusion and reducing the efficacy of inhibitors
CC       targeting these epitopes. Membranes fusion leads to delivery of the
CC       nucleocapsid into the cytoplasm. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBUNIT: [Surface protein gp120]: The mature envelope protein (Env)
CC       consists of a homotrimer of non-covalently associated gp120-gp41
CC       heterodimers. The resulting complex protrudes from the virus surface as
CC       a spike. There seems to be as few as 10 spikes on the average virion.
CC       Interacts with host CD4, CCR5 and CXCR4. Gp120 also interacts with the
CC       C-type lectins CD209/DC-SIGN and CLEC4M/DC-SIGNR (collectively referred
CC       to as DC-SIGN(R)). Gp120 and gp41 interact with GalCer. Gp120 interacts
CC       with host ITGA4/ITGB7 complex; on CD4+ T-cells, this interaction
CC       results in rapid activation of integrin ITGAL/LFA-1, which facilitates
CC       efficient cell-to-cell spreading of HIV-1. Gp120 interacts with cell-
CC       associated heparan sulfate; this interaction increases virus
CC       infectivity on permissive cells and may be involved in infection of
CC       CD4- cells. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBUNIT: [Transmembrane protein gp41]: The mature envelope protein
CC       (Env) consists of a homotrimer of non-covalently associated gp120-gp41
CC       heterodimers. The resulting complex protrudes from the virus surface as
CC       a spike. There seems to be as few as 10 spikes on the average virion.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBCELLULAR LOCATION: [Surface protein gp120]: Virion membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Peripheral membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host cell membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Peripheral membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host endosome membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Note=The surface protein is not
CC       anchored to the viral envelope, but associates with the extravirion
CC       surface through its binding to TM. It is probably concentrated at the
CC       site of budding and incorporated into the virions possibly by contacts
CC       between the cytoplasmic tail of Env and the N-terminus of Gag.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBCELLULAR LOCATION: [Transmembrane protein gp41]: Virion membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host cell membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host endosome membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Note=It is probably concentrated at
CC       the site of budding and incorporated into the virions possibly by
CC       contacts between the cytoplasmic tail of Env and the N-terminus of Gag.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: Some of the most genetically diverse regions of the viral
CC       genome are present in Env. They are called variable regions 1 through 5
CC       (V1 through V5). Coreceptor usage of gp120 is determined mainly by the
CC       primary structure of the third variable region (V3) in the outer domain
CC       of gp120. The sequence of V3 determines which coreceptor, CCR5 and/or
CC       CXCR4 (corresponding to R5/macrophage, X4/T cell and R5X4/T cell and
CC       macrophage tropism), is used to trigger the fusion potential of the Env
CC       complex, and hence which cells the virus can infect. Binding to CCR5
CC       involves a region adjacent in addition to V3. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- DOMAIN: The membrane proximal external region (MPER) present in gp41 is
CC       a tryptophan-rich region recognized by the antibodies 2F5, Z13, and
CC       4E10. MPER seems to play a role in fusion. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- DOMAIN: The 17 amino acids long immunosuppressive region is present in
CC       many retroviral envelope proteins. Synthetic peptides derived from this
CC       relatively conserved sequence inhibit immune function in vitro and in
CC       vivo. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: The YXXL motif is involved in determining the exact site of
CC       viral release at the surface of infected mononuclear cells and promotes
CC       endocytosis. YXXL and di-leucine endocytosis motifs interact directly
CC       or indirectly with the clathrin adapter complexes, opperate
CC       independently, and their activities are not additive.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: The CD4-binding region is targeted by the antibody b12.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- PTM: Highly glycosylated by host. The high number of glycan on the
CC       protein is reffered to as 'glycan shield' because it contributes to
CC       hide protein sequence from adaptive immune system. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- PTM: Palmitoylation of the transmembrane protein and of Env polyprotein
CC       (prior to its proteolytic cleavage) is essential for their association
CC       with host cell membrane lipid rafts. Palmitoylation is therefore
CC       required for envelope trafficking to classical lipid rafts, but not for
CC       viral replication. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- PTM: Specific enzymatic cleavages in vivo yield mature proteins.
CC       Envelope glycoproteins are synthesized as an inactive precursor that is
CC       heavily N-glycosylated and processed likely by host cell furin in the
CC       Golgi to yield the mature SU and TM proteins. The cleavage site between
CC       SU and TM requires the minimal sequence [KR]-X-[KR]-R. About 2 of the 9
CC       disulfide bonds of gp41 are reduced by P4HB/PDI, following binding to
CC       CD4 receptor. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- MISCELLANEOUS: Inhibitors targeting HIV-1 viral envelope proteins are
CC       used as antiretroviral drugs. Attachment of virions to the cell surface
CC       via non-specific interactions and CD4 binding can be blocked by
CC       inhibitors that include cyanovirin-N, cyclotriazadisulfonamide analogs,
CC       PRO 2000, TNX 355 and PRO 542. In addition, BMS 806 can block CD4-
CC       induced conformational changes. Env interactions with the coreceptor
CC       molecules can be targeted by CCR5 antagonists including SCH-D,
CC       maraviroc (UK 427857) and aplaviroc (GW 873140), and the CXCR4
CC       antagonist AMD 070. Fusion of viral and cellular membranes can be
CC       inhibited by peptides such as enfuvirtide and tifuvirtide (T 1249).
CC       Resistance to inhibitors associated with mutations in Env are observed.
CC       Most of the time, single mutations confer only a modest reduction in
CC       drug susceptibility. Combination of several mutations is usually
CC       required to develop a high-level drug resistance. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- MISCELLANEOUS: HIV-1 lineages are divided in three main groups, M (for
CC       Major), O (for Outlier), and N (for New, or Non-M, Non-O). The vast
CC       majority of strains found worldwide belong to the group M. Group O
CC       seems to be endemic to and largely confined to Cameroon and neighboring
CC       countries in West Central Africa, where these viruses represent a small
CC       minority of HIV-1 strains. The group N is represented by a limited
CC       number of isolates from Cameroonian persons. The group M is further
CC       subdivided in 9 clades or subtypes (A to D, F to H, J and K).
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SIMILARITY: Belongs to the HIV-1 env protein family.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- WEB RESOURCE: Name=hivdb; Note=HIV drug resistance database;
CC       URL="https://hivdb.stanford.edu";
CC   -!- WEB RESOURCE: Name=HIV drug resistance mutations;
CC       URL="https://www.iasusa.org/content/hiv-drug-resistance-mutations";
CC   ---------------------------------------------------------------------------
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DR   EMBL; K02011; AAA44661.1; -; Genomic_RNA.
DR   PDB; 1DDH; X-ray; 3.10 A; P=311-320.
DR   PDB; 1HHG; X-ray; 2.60 A; C/F=192-200.
DR   PDB; 1QO3; X-ray; 2.30 A; P=311-320.
DR   PDB; 1SZT; X-ray; 2.40 A; A=541-650.
DR   PDB; 6TVU; X-ray; 1.25 A; BBB=616-645.
DR   PDBsum; 1DDH; -.
DR   PDBsum; 1HHG; -.
DR   PDBsum; 1QO3; -.
DR   PDBsum; 1SZT; -.
DR   PDBsum; 6TVU; -.
DR   BMRB; P04582; -.
DR   SMR; P04582; -.
DR   GlyConnect; 149; 1 N-Linked glycan.
DR   GlyCosmos; P04582; 27 sites, 2 glycans.
DR   Reactome; R-HSA-5621480; Dectin-2 family.
DR   EvolutionaryTrace; P04582; -.
DR   GO; GO:0044175; C:host cell endosome membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0016020; C:membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:0019031; C:viral envelope; IEA:UniProtKB-KW.
DR   GO; GO:0055036; C:virion membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005198; F:structural molecule activity; IEA:UniProtKB-UniRule.
DR   GO; GO:0075512; P:clathrin-dependent endocytosis of virus by host cell; IEA:UniProtKB-UniRule.
DR   GO; GO:0039654; P:fusion of virus membrane with host endosome membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:0019064; P:fusion of virus membrane with host plasma membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:1903905; P:positive regulation of establishment of T cell polarity; IEA:UniProtKB-UniRule.
DR   GO; GO:1903908; P:positive regulation of plasma membrane raft polarization; IEA:UniProtKB-UniRule.
DR   GO; GO:1903911; P:positive regulation of receptor clustering; IEA:UniProtKB-UniRule.
DR   GO; GO:0019082; P:viral protein processing; IEA:UniProtKB-UniRule.
DR   GO; GO:0019062; P:virion attachment to host cell; IEA:UniProtKB-UniRule.
DR   GO; GO:0019049; P:virus-mediated perturbation of host defense response; IEA:UniProtKB-UniRule.
DR   CDD; cd09909; HIV-1-like_HR1-HR2; 1.
DR   Gene3D; 1.10.287.210; -; 1.
DR   Gene3D; 2.170.40.20; Human immunodeficiency virus 1, Gp160, envelope glycoprotein; 2.
DR   Gene3D; 1.20.5.490; Single helix bin; 1.
DR   HAMAP; MF_04083; HIV_ENV; 1.
DR   InterPro; IPR036377; Gp120_core_sf.
DR   InterPro; IPR037527; Gp160.
DR   InterPro; IPR000328; GP41-like.
DR   InterPro; IPR000777; HIV1_Gp120.
DR   Pfam; PF00516; GP120; 1.
DR   Pfam; PF00517; GP41; 1.
DR   SUPFAM; SSF56502; gp120 core; 1.
DR   SUPFAM; SSF58069; Virus ectodomain; 1.
PE   1: Evidence at protein level;
KW   3D-structure; AIDS; Apoptosis;
KW   Clathrin-mediated endocytosis of virus by host;
KW   Cleavage on pair of basic residues; Coiled coil; Disulfide bond;
KW   Fusion of virus membrane with host endosomal membrane;
KW   Fusion of virus membrane with host membrane; Glycoprotein;
KW   Host cell membrane; Host endosome; Host membrane; Host-virus interaction;
KW   Lipoprotein; Membrane; Palmitate; Signal; Transmembrane;
KW   Transmembrane helix; Viral attachment to host cell; Viral envelope protein;
KW   Viral immunoevasion; Viral penetration into host cytoplasm; Virion;
KW   Virus endocytosis by host; Virus entry into host cell.
FT   SIGNAL          1..32
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CHAIN           33..851
FT                   /note="Envelope glycoprotein gp160"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000239472"
FT   CHAIN           33..506
FT                   /note="Surface protein gp120"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000038384"
FT   CHAIN           507..851
FT                   /note="Transmembrane protein gp41"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000038385"
FT   TOPO_DOM        33..679
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   TRANSMEM        680..700
FT                   /note="Helical"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   TOPO_DOM        701..851
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          131..156
FT                   /note="V1"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          157..196
FT                   /note="V2"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          296..330
FT                   /note="V3"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          364..374
FT                   /note="CD4-binding loop"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          385..413
FT                   /note="V4"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          456..466
FT                   /note="V5"
FT   REGION          458..466
FT                   /note="V5"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          507..527
FT                   /note="Fusion peptide"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          569..587
FT                   /note="Immunosuppression"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          657..678
FT                   /note="MPER; binding to GalCer"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          713..735
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COILED          628..662
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   MOTIF           707..710
FT                   /note="YXXL motif; contains endocytosis signal"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   MOTIF           850..851
FT                   /note="Di-leucine internalization motif"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   SITE            506..507
FT                   /note="Cleavage; by host furin"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   LIPID           759
FT                   /note="S-palmitoyl cysteine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        88
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        136
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        141
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        156
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        160
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        186
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        197
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        230
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        234
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        241
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        262
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        276
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        295
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        301
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        332
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        339
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        356
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        386
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        392
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        401
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        443
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        458
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        606
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        611
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        620
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        632
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        669
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        54..74
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        119..205
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        126..196
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        131..157
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        218..247
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        228..239
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        296..331
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        378..440
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        385..413
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        593..599
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
SQ   SEQUENCE   851 AA;  96644 MW;  D16A3C90857785F1 CRC64;
     MRVKEKYQHL WRWGWRWGTM LLGMLMICSA TEKLWVTVYF GVPVWKEATT TLFCASDAKA
     YDTEVHNVWA THACVPTDPN PQEVVLVNVT ENFNMWKNDM VEQMHEDIIS LWDQSLKPCV
     KLTPLCVSLK CTDLKNDTNT NSSSGRMIME KGEIKNCSFN ISTSKRGKVQ KEYAFFYKLD
     IIPIDNDTTS YTLTSCNTSV ITQACPKVSF EPIPIHYCAP AGFAILKCNN KTFNGTGPCT
     NVSTVQCTHG IRPVVSTQLL LNGSLAEEEV VIRSVNFTDN AKTIIVQLDT SVEINCTRPN
     NNTRKKIRIQ RGPGRAFVTI GKIGNMRQAH CNISRAKWNA TLKQIDSKLR EQFGNNKTII
     FKQSSGGDPE IVTHSFNCGG EFFYCNSTQL FNSTWSTKGS NNTEGSDTIT LPCRIKQIIN
     MWQEVGKAMY APPISGQIRC SSNITGLLLT RDGGNSNNES EIFRPGGGDM RDNWRSELYK
     YKVVKIEPLG VAPTKAKRRV VQREKRAVGI GALFLGFLGA AGSTMGAASM TLTVQARQLL
     SGIVQQQNNL LRAIEGQQHL LQLTVWGIKQ LQARILAVER YLKDQQLLGI WGCSGKLICT
     TAVPWNASWS NKSLEQIWNN MTWMEWDREI NNYTSLIHSL IEESQNQQEK NEQELLELDK
     WASLWNWFNI TNWLWYIKLF IMIVGGLVGL RIVFAVLSIV NRVRQGYSPL SFQTHLPNPR
     GPDRPEGIEE EGGERDRDRS IRLVNGSLAL IWDDLRSLCL FSYHRLRDLL LIVTRIVELL
     GRRGWEALKY WWNLLQYWSQ ELKNSAVNLL NATAIAVAEG TDRVIELVQA AYRAIRHIPR
     RIRQGLERIL L
//
ID   ENV_HV1B9               Reviewed;         853 AA.
AC   Q73372;
DT   03-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-2000, sequence version 2.
DT   27-MAR-2024, entry version 129.
DE   RecName: Full=Envelope glycoprotein gp160 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   AltName: Full=Env polyprotein {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Contains:
DE     RecName: Full=Surface protein gp120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=SU {ECO:0000255|HAMAP-Rule:MF_04083};
DE     AltName: Full=Glycoprotein 120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=gp120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Contains:
DE     RecName: Full=Transmembrane protein gp41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=TM {ECO:0000255|HAMAP-Rule:MF_04083};
DE     AltName: Full=Glycoprotein 41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=gp41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Flags: Precursor;
GN   Name=env {ECO:0000255|HAMAP-Rule:MF_04083};
OS   Human immunodeficiency virus type 1 group M subtype B (strain 89.6)
OS   (HIV-1).
OC   Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC   Ortervirales; Retroviridae; Orthoretrovirinae; Lentivirus;
OC   Human immunodeficiency virus 1.
OX   NCBI_TaxID=401671;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=1433527; DOI=10.1128/jvi.66.12.7517-7521.1992;
RA   Collman R., Balliet J.W., Gregory S.A., Friedman H., Kolson D.L.,
RA   Nathanson N., Srinivasan A.;
RT   "An infectious molecular clone of an unusual macrophage-tropic and highly
RT   cytopathic strain of human immunodeficiency virus type 1.";
RL   J. Virol. 66:7517-7521(1992).
CC   -!- FUNCTION: [Envelope glycoprotein gp160]: Oligomerizes in the host
CC       endoplasmic reticulum into predominantly trimers. In a second time,
CC       gp160 transits in the host Golgi, where glycosylation is completed. The
CC       precursor is then proteolytically cleaved in the trans-Golgi and
CC       thereby activated by cellular furin or furin-like proteases to produce
CC       gp120 and gp41. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- FUNCTION: [Surface protein gp120]: Attaches the virus to the host
CC       lymphoid cell by binding to the primary receptor CD4. This interaction
CC       induces a structural rearrangement creating a high affinity binding
CC       site for a chemokine coreceptor like CXCR4 and/or CCR5. Acts as a
CC       ligand for CD209/DC-SIGN and CLEC4M/DC-SIGNR, which are respectively
CC       found on dendritic cells (DCs), and on endothelial cells of liver
CC       sinusoids and lymph node sinuses. These interactions allow capture of
CC       viral particles at mucosal surfaces by these cells and subsequent
CC       transmission to permissive cells. HIV subverts the migration properties
CC       of dendritic cells to gain access to CD4+ T-cells in lymph nodes. Virus
CC       transmission to permissive T-cells occurs either in trans (without DCs
CC       infection, through viral capture and transmission), or in cis
CC       (following DCs productive infection, through the usual CD4-gp120
CC       interaction), thereby inducing a robust infection. In trans infection,
CC       bound virions remain infectious over days and it is proposed that they
CC       are not degraded, but protected in non-lysosomal acidic organelles
CC       within the DCs close to the cell membrane thus contributing to the
CC       viral infectious potential during DCs' migration from the periphery to
CC       the lymphoid tissues. On arrival at lymphoid tissues, intact virions
CC       recycle back to DCs' cell surface allowing virus transmission to CD4+
CC       T-cells. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- FUNCTION: [Transmembrane protein gp41]: Acts as a class I viral fusion
CC       protein. Under the current model, the protein has at least 3
CC       conformational states: pre-fusion native state, pre-hairpin
CC       intermediate state, and post-fusion hairpin state. During fusion of
CC       viral and target intracellular membranes, the coiled coil regions
CC       (heptad repeats) assume a trimer-of-hairpins structure, positioning the
CC       fusion peptide in close proximity to the C-terminal region of the
CC       ectodomain. The formation of this structure appears to drive apposition
CC       and subsequent fusion of viral and target cell membranes. Complete
CC       fusion occurs in host cell endosomes and is dynamin-dependent, however
CC       some lipid transfer might occur at the plasma membrane. The virus
CC       undergoes clathrin-dependent internalization long before endosomal
CC       fusion, thus minimizing the surface exposure of conserved viral
CC       epitopes during fusion and reducing the efficacy of inhibitors
CC       targeting these epitopes. Membranes fusion leads to delivery of the
CC       nucleocapsid into the cytoplasm. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBUNIT: [Surface protein gp120]: The mature envelope protein (Env)
CC       consists of a homotrimer of non-covalently associated gp120-gp41
CC       heterodimers. The resulting complex protrudes from the virus surface as
CC       a spike. There seems to be as few as 10 spikes on the average virion.
CC       Interacts with host CD4, CCR5 and CXCR4. Gp120 also interacts with the
CC       C-type lectins CD209/DC-SIGN and CLEC4M/DC-SIGNR (collectively referred
CC       to as DC-SIGN(R)). Gp120 and gp41 interact with GalCer. Gp120 interacts
CC       with host ITGA4/ITGB7 complex; on CD4+ T-cells, this interaction
CC       results in rapid activation of integrin ITGAL/LFA-1, which facilitates
CC       efficient cell-to-cell spreading of HIV-1. Gp120 interacts with cell-
CC       associated heparan sulfate; this interaction increases virus
CC       infectivity on permissive cells and may be involved in infection of
CC       CD4- cells. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBUNIT: [Transmembrane protein gp41]: The mature envelope protein
CC       (Env) consists of a homotrimer of non-covalently associated gp120-gp41
CC       heterodimers. The resulting complex protrudes from the virus surface as
CC       a spike. There seems to be as few as 10 spikes on the average virion.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBCELLULAR LOCATION: [Surface protein gp120]: Virion membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Peripheral membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host cell membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Peripheral membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host endosome membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Note=The surface protein is not
CC       anchored to the viral envelope, but associates with the extravirion
CC       surface through its binding to TM. It is probably concentrated at the
CC       site of budding and incorporated into the virions possibly by contacts
CC       between the cytoplasmic tail of Env and the N-terminus of Gag.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBCELLULAR LOCATION: [Transmembrane protein gp41]: Virion membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host cell membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host endosome membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Note=It is probably concentrated at
CC       the site of budding and incorporated into the virions possibly by
CC       contacts between the cytoplasmic tail of Env and the N-terminus of Gag.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: Some of the most genetically diverse regions of the viral
CC       genome are present in Env. They are called variable regions 1 through 5
CC       (V1 through V5). Coreceptor usage of gp120 is determined mainly by the
CC       primary structure of the third variable region (V3) in the outer domain
CC       of gp120. The sequence of V3 determines which coreceptor, CCR5 and/or
CC       CXCR4 (corresponding to R5/macrophage, X4/T cell and R5X4/T cell and
CC       macrophage tropism), is used to trigger the fusion potential of the Env
CC       complex, and hence which cells the virus can infect. Binding to CCR5
CC       involves a region adjacent in addition to V3. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- DOMAIN: The membrane proximal external region (MPER) present in gp41 is
CC       a tryptophan-rich region recognized by the antibodies 2F5, Z13, and
CC       4E10. MPER seems to play a role in fusion. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- DOMAIN: The 17 amino acids long immunosuppressive region is present in
CC       many retroviral envelope proteins. Synthetic peptides derived from this
CC       relatively conserved sequence inhibit immune function in vitro and in
CC       vivo. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: The YXXL motif is involved in determining the exact site of
CC       viral release at the surface of infected mononuclear cells and promotes
CC       endocytosis. YXXL and di-leucine endocytosis motifs interact directly
CC       or indirectly with the clathrin adapter complexes, opperate
CC       independently, and their activities are not additive.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: The CD4-binding region is targeted by the antibody b12.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- PTM: Highly glycosylated by host. The high number of glycan on the
CC       protein is reffered to as 'glycan shield' because it contributes to
CC       hide protein sequence from adaptive immune system. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- PTM: Palmitoylation of the transmembrane protein and of Env polyprotein
CC       (prior to its proteolytic cleavage) is essential for their association
CC       with host cell membrane lipid rafts. Palmitoylation is therefore
CC       required for envelope trafficking to classical lipid rafts, but not for
CC       viral replication. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- PTM: Specific enzymatic cleavages in vivo yield mature proteins.
CC       Envelope glycoproteins are synthesized as an inactive precursor that is
CC       heavily N-glycosylated and processed likely by host cell furin in the
CC       Golgi to yield the mature SU and TM proteins. The cleavage site between
CC       SU and TM requires the minimal sequence [KR]-X-[KR]-R. About 2 of the 9
CC       disulfide bonds of gp41 are reduced by P4HB/PDI, following binding to
CC       CD4 receptor. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- MISCELLANEOUS: Inhibitors targeting HIV-1 viral envelope proteins are
CC       used as antiretroviral drugs. Attachment of virions to the cell surface
CC       via non-specific interactions and CD4 binding can be blocked by
CC       inhibitors that include cyanovirin-N, cyclotriazadisulfonamide analogs,
CC       PRO 2000, TNX 355 and PRO 542. In addition, BMS 806 can block CD4-
CC       induced conformational changes. Env interactions with the coreceptor
CC       molecules can be targeted by CCR5 antagonists including SCH-D,
CC       maraviroc (UK 427857) and aplaviroc (GW 873140), and the CXCR4
CC       antagonist AMD 070. Fusion of viral and cellular membranes can be
CC       inhibited by peptides such as enfuvirtide and tifuvirtide (T 1249).
CC       Resistance to inhibitors associated with mutations in Env are observed.
CC       Most of the time, single mutations confer only a modest reduction in
CC       drug susceptibility. Combination of several mutations is usually
CC       required to develop a high-level drug resistance. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- MISCELLANEOUS: HIV-1 lineages are divided in three main groups, M (for
CC       Major), O (for Outlier), and N (for New, or Non-M, Non-O). The vast
CC       majority of strains found worldwide belong to the group M. Group O
CC       seems to be endemic to and largely confined to Cameroon and neighboring
CC       countries in West Central Africa, where these viruses represent a small
CC       minority of HIV-1 strains. The group N is represented by a limited
CC       number of isolates from Cameroonian persons. The group M is further
CC       subdivided in 9 clades or subtypes (A to D, F to H, J and K).
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SIMILARITY: Belongs to the HIV-1 env protein family.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- WEB RESOURCE: Name=hivdb; Note=HIV drug resistance database;
CC       URL="https://hivdb.stanford.edu";
CC   -!- WEB RESOURCE: Name=HIV drug resistance mutations;
CC       URL="https://www.iasusa.org/content/hiv-drug-resistance-mutations";
CC   ---------------------------------------------------------------------------
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DR   EMBL; U39362; AAA81043.2; -; Genomic_DNA.
DR   PDB; 4R4H; X-ray; 4.28 A; A=1-508.
DR   PDB; 5U3K; X-ray; 2.64 A; C/P=659-680.
DR   PDB; 5U3L; X-ray; 2.17 A; C/P=667-680.
DR   PDB; 5U3M; X-ray; 2.42 A; A=659-680.
DR   PDB; 5U3N; X-ray; 2.00 A; A=659-680.
DR   PDB; 5U3O; X-ray; 1.76 A; A=667-680.
DR   PDB; 6X58; X-ray; 3.26 A; E/F=666-679.
DR   PDBsum; 4R4H; -.
DR   PDBsum; 5U3K; -.
DR   PDBsum; 5U3L; -.
DR   PDBsum; 5U3M; -.
DR   PDBsum; 5U3N; -.
DR   PDBsum; 5U3O; -.
DR   PDBsum; 6X58; -.
DR   SMR; Q73372; -.
DR   GlyCosmos; Q73372; 28 sites, No reported glycans.
DR   Proteomes; UP000007691; Genome.
DR   GO; GO:0044175; C:host cell endosome membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0016020; C:membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:0019031; C:viral envelope; IEA:UniProtKB-KW.
DR   GO; GO:0055036; C:virion membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005198; F:structural molecule activity; IEA:UniProtKB-UniRule.
DR   GO; GO:0075512; P:clathrin-dependent endocytosis of virus by host cell; IEA:UniProtKB-UniRule.
DR   GO; GO:0039654; P:fusion of virus membrane with host endosome membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:0019064; P:fusion of virus membrane with host plasma membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:1903905; P:positive regulation of establishment of T cell polarity; IEA:UniProtKB-UniRule.
DR   GO; GO:1903908; P:positive regulation of plasma membrane raft polarization; IEA:UniProtKB-UniRule.
DR   GO; GO:1903911; P:positive regulation of receptor clustering; IEA:UniProtKB-UniRule.
DR   GO; GO:0019082; P:viral protein processing; IEA:UniProtKB-UniRule.
DR   GO; GO:0019062; P:virion attachment to host cell; IEA:UniProtKB-UniRule.
DR   GO; GO:0019049; P:virus-mediated perturbation of host defense response; IEA:UniProtKB-UniRule.
DR   CDD; cd09909; HIV-1-like_HR1-HR2; 1.
DR   Gene3D; 1.10.287.210; -; 1.
DR   Gene3D; 2.170.40.20; Human immunodeficiency virus 1, Gp160, envelope glycoprotein; 2.
DR   Gene3D; 1.20.5.490; Single helix bin; 1.
DR   HAMAP; MF_04083; HIV_ENV; 1.
DR   InterPro; IPR036377; Gp120_core_sf.
DR   InterPro; IPR037527; Gp160.
DR   InterPro; IPR000328; GP41-like.
DR   InterPro; IPR000777; HIV1_Gp120.
DR   Pfam; PF00516; GP120; 1.
DR   Pfam; PF00517; GP41; 1.
DR   SUPFAM; SSF56502; gp120 core; 2.
DR   SUPFAM; SSF58069; Virus ectodomain; 1.
PE   1: Evidence at protein level;
KW   3D-structure; AIDS; Apoptosis;
KW   Clathrin-mediated endocytosis of virus by host;
KW   Cleavage on pair of basic residues; Coiled coil; Disulfide bond;
KW   Fusion of virus membrane with host endosomal membrane;
KW   Fusion of virus membrane with host membrane; Glycoprotein;
KW   Host cell membrane; Host endosome; Host membrane; Host-virus interaction;
KW   Lipoprotein; Membrane; Palmitate; Reference proteome; Signal;
KW   Transmembrane; Transmembrane helix; Viral attachment to host cell;
KW   Viral envelope protein; Viral immunoevasion;
KW   Viral penetration into host cytoplasm; Virion; Virus endocytosis by host;
KW   Virus entry into host cell.
FT   SIGNAL          1..31
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CHAIN           32..853
FT                   /note="Envelope glycoprotein gp160"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000441237"
FT   CHAIN           32..508
FT                   /note="Surface protein gp120"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000441238"
FT   CHAIN           509..853
FT                   /note="Transmembrane protein gp41"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000250966"
FT   TOPO_DOM        32..681
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   TRANSMEM        682..702
FT                   /note="Helical"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   TOPO_DOM        703..853
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          130..157
FT                   /note="V1"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          158..198
FT                   /note="V2"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          298..331
FT                   /note="V3"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          364..374
FT                   /note="CD4-binding loop"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          385..414
FT                   /note="V4"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          459..468
FT                   /note="V5"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          509..529
FT                   /note="Fusion peptide"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          571..589
FT                   /note="Immunosuppression"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          659..680
FT                   /note="MPER; binding to GalCer"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          718..740
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COILED          630..664
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   MOTIF           709..712
FT                   /note="YXXL motif; contains endocytosis signal"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   MOTIF           852..853
FT                   /note="Di-leucine internalization motif"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   COMPBIAS        725..740
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   SITE            508..509
FT                   /note="Cleavage; by host furin"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   LIPID           761
FT                   /note="S-palmitoyl cysteine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   LIPID           834
FT                   /note="S-palmitoyl cysteine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        87
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        129
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        134
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        138
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        157
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        189
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        199
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        232
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        236
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        243
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        264
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        278
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        291
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        297
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        303
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        333
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        340
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        356
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        362
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        392
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        396
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        402
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        444
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        456
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        608
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        613
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        622
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        634
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        53..73
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        118..207
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        125..198
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        130..158
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        220..249
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        230..241
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        298..332
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        378..441
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        385..414
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        595..601
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   HELIX           669..680
FT                   /evidence="ECO:0007829|PDB:5U3O"
SQ   SEQUENCE   853 AA;  96944 MW;  BCB2ABC473EC57C8 CRC64;
     MRVKEIRKNW QHLRGGILLL GMLMICSAAK EKTWVTIYYG VPVWREATTT LFCASDAKAY
     DTEVHNVWAT HACVPTDPNP QEVVLGNVTE NFNMWKNNMV DQMHEDIISL WDESLKPCVK
     LTPLCVTLNC TNLNITKNTT NPTSSSWGMM EKGEIKNCSF YITTSIRNKV KKEYALFNRL
     DVVPIENTNN TKYRLISCNT SVITQACPKV SFQPIPIHYC VPAGFAMLKC NNKTFNGSGP
     CTNVSTVQCT HGIRPVVSTQ LLLNGSLAEE DIVIRSENFT DNAKTIIVQL NESVVINCTR
     PNNNTRRRLS IGPGRAFYAR RNIIGDIRQA HCNISRAKWN NTLQQIVIKL REKFRNKTIA
     FNQSSGGDPE IVMHSFNCGG EFFYCNTAQL FNSTWNVTGG TNGTEGNDII TLQCRIKQII
     NMWQKVGKAM YAPPITGQIR CSSNITGLLL TRDGGNSTET ETEIFRPGGG DMRDNWRSEL
     YKYKVVRIEP IGVAPTRAKR RTVQREKRAV GIGAVFLGFL GAAGSTMGAA SVTLTVQARL
     LLSGIVQQQN NLLRAIEAQQ HMLQLTVWGI KQLQARVLAL ERYLRDQQLM GIWGCSGKLI
     CTTSVPWNVS WSNKSVDDIW NNMTWMEWER EIDNYTDYIY DLLEKSQTQQ EKNEKELLEL
     DKWASLWNWF DITNWLWYIR LFIMIVGGLI GLRIVFAVLS IVNRVRQGYS PLSFQTLLPA
     SRGPDRPEGT EEEGGERDRD RSGPLVNGFL ALFWVDLRNL CLFLYHLLRN LLLIVTRIVE
     LLGRRGWEAL KYWWNLLQYW SQELKNSAVS LLNATAIAVA EGTDRVIKIV QRACRAIRNI
     PTRIRQGLER ALL
//
ID   ENV_HV1BN               Reviewed;         852 AA.
AC   P12488;
DT   01-OCT-1989, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-1989, sequence version 1.
DT   27-MAR-2024, entry version 154.
DE   RecName: Full=Envelope glycoprotein gp160 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   AltName: Full=Env polyprotein {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Contains:
DE     RecName: Full=Surface protein gp120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=SU {ECO:0000255|HAMAP-Rule:MF_04083};
DE     AltName: Full=Glycoprotein 120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=gp120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Contains:
DE     RecName: Full=Transmembrane protein gp41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=TM {ECO:0000255|HAMAP-Rule:MF_04083};
DE     AltName: Full=Glycoprotein 41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=gp41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Flags: Precursor;
GN   Name=env {ECO:0000255|HAMAP-Rule:MF_04083};
OS   Human immunodeficiency virus type 1 group M subtype B (isolate BRVA)
OS   (HIV-1).
OC   Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC   Ortervirales; Retroviridae; Orthoretrovirinae; Lentivirus;
OC   Human immunodeficiency virus 1.
OX   NCBI_TaxID=11693;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX   PubMed=2789516; DOI=10.1016/0042-6822(89)90406-6;
RA   Anand R., Thayer R., Srinivasan A., Nayyar S., Gardner M., Luciw P.,
RA   Dandekar S.;
RT   "Biological and molecular characterization of human immunodeficiency virus
RT   (HIV-1BR) from the brain of a patient with progressive dementia.";
RL   Virology 168:79-89(1989).
RN   [2]
RP   REVIEW.
RX   PubMed=12974773; DOI=10.1034/j.1600-0463.2003.11107803.x;
RA   Geijtenbeek T.B., van Kooyk Y.;
RT   "Pathogens target DC-SIGN to influence their fate DC-SIGN functions as a
RT   pathogen receptor with broad specificity.";
RL   APMIS 111:698-714(2003).
RN   [3]
RP   REVIEW.
RX   PubMed=12873764; DOI=10.1016/s0005-2736(03)00161-5;
RA   Gallo S.A., Finnegan C.M., Viard M., Raviv Y., Dimitrov A., Rawat S.S.,
RA   Puri A., Durell S., Blumenthal R.;
RT   "The HIV Env-mediated fusion reaction.";
RL   Biochim. Biophys. Acta 1614:36-50(2003).
RN   [4]
RP   REVIEW.
RX   PubMed=15719026; DOI=10.1038/sj.cdd.4401584;
RA   Perfettini J.-L., Castedo M., Roumier T., Andreau K., Nardacci R.,
RA   Piacentini M., Kroemer G.;
RT   "Mechanisms of apoptosis induction by the HIV-1 envelope.";
RL   Cell Death Differ. 12:916-923(2005).
RN   [5]
RP   REVIEW.
RX   PubMed=15725757; DOI=10.1089/aid.2005.21.171;
RA   Hartley O., Klasse P.J., Sattentau Q.J., Moore J.P.;
RT   "V3: HIV's switch-hitter.";
RL   AIDS Res. Hum. Retroviruses 21:171-189(2005).
RN   [6]
RP   REVIEW.
RX   PubMed=16114975; DOI=10.2165/00003495-200565130-00002;
RA   Reeves J.D., Piefer A.J.;
RT   "Emerging drug targets for antiretroviral therapy.";
RL   Drugs 65:1747-1766(2005).
RN   [7]
RP   REVIEW.
RX   PubMed=16437164; DOI=10.1038/sj.emboj.7600947;
RA   Lusso P.;
RT   "HIV and the chemokine system: 10 years later.";
RL   EMBO J. 25:447-456(2006).
CC   -!- FUNCTION: [Envelope glycoprotein gp160]: Oligomerizes in the host
CC       endoplasmic reticulum into predominantly trimers. In a second time,
CC       gp160 transits in the host Golgi, where glycosylation is completed. The
CC       precursor is then proteolytically cleaved in the trans-Golgi and
CC       thereby activated by cellular furin or furin-like proteases to produce
CC       gp120 and gp41. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- FUNCTION: [Surface protein gp120]: Attaches the virus to the host
CC       lymphoid cell by binding to the primary receptor CD4. This interaction
CC       induces a structural rearrangement creating a high affinity binding
CC       site for a chemokine coreceptor like CXCR4 and/or CCR5. Acts as a
CC       ligand for CD209/DC-SIGN and CLEC4M/DC-SIGNR, which are respectively
CC       found on dendritic cells (DCs), and on endothelial cells of liver
CC       sinusoids and lymph node sinuses. These interactions allow capture of
CC       viral particles at mucosal surfaces by these cells and subsequent
CC       transmission to permissive cells. HIV subverts the migration properties
CC       of dendritic cells to gain access to CD4+ T-cells in lymph nodes. Virus
CC       transmission to permissive T-cells occurs either in trans (without DCs
CC       infection, through viral capture and transmission), or in cis
CC       (following DCs productive infection, through the usual CD4-gp120
CC       interaction), thereby inducing a robust infection. In trans infection,
CC       bound virions remain infectious over days and it is proposed that they
CC       are not degraded, but protected in non-lysosomal acidic organelles
CC       within the DCs close to the cell membrane thus contributing to the
CC       viral infectious potential during DCs' migration from the periphery to
CC       the lymphoid tissues. On arrival at lymphoid tissues, intact virions
CC       recycle back to DCs' cell surface allowing virus transmission to CD4+
CC       T-cells. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- FUNCTION: [Transmembrane protein gp41]: Acts as a class I viral fusion
CC       protein. Under the current model, the protein has at least 3
CC       conformational states: pre-fusion native state, pre-hairpin
CC       intermediate state, and post-fusion hairpin state. During fusion of
CC       viral and target intracellular membranes, the coiled coil regions
CC       (heptad repeats) assume a trimer-of-hairpins structure, positioning the
CC       fusion peptide in close proximity to the C-terminal region of the
CC       ectodomain. The formation of this structure appears to drive apposition
CC       and subsequent fusion of viral and target cell membranes. Complete
CC       fusion occurs in host cell endosomes and is dynamin-dependent, however
CC       some lipid transfer might occur at the plasma membrane. The virus
CC       undergoes clathrin-dependent internalization long before endosomal
CC       fusion, thus minimizing the surface exposure of conserved viral
CC       epitopes during fusion and reducing the efficacy of inhibitors
CC       targeting these epitopes. Membranes fusion leads to delivery of the
CC       nucleocapsid into the cytoplasm. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBUNIT: [Surface protein gp120]: The mature envelope protein (Env)
CC       consists of a homotrimer of non-covalently associated gp120-gp41
CC       heterodimers. The resulting complex protrudes from the virus surface as
CC       a spike. There seems to be as few as 10 spikes on the average virion.
CC       Interacts with host CD4, CCR5 and CXCR4. Gp120 also interacts with the
CC       C-type lectins CD209/DC-SIGN and CLEC4M/DC-SIGNR (collectively referred
CC       to as DC-SIGN(R)). Gp120 and gp41 interact with GalCer. Gp120 interacts
CC       with host ITGA4/ITGB7 complex; on CD4+ T-cells, this interaction
CC       results in rapid activation of integrin ITGAL/LFA-1, which facilitates
CC       efficient cell-to-cell spreading of HIV-1. Gp120 interacts with cell-
CC       associated heparan sulfate; this interaction increases virus
CC       infectivity on permissive cells and may be involved in infection of
CC       CD4- cells. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBUNIT: [Transmembrane protein gp41]: The mature envelope protein
CC       (Env) consists of a homotrimer of non-covalently associated gp120-gp41
CC       heterodimers. The resulting complex protrudes from the virus surface as
CC       a spike. There seems to be as few as 10 spikes on the average virion.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBCELLULAR LOCATION: [Surface protein gp120]: Virion membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Peripheral membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host cell membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Peripheral membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host endosome membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Note=The surface protein is not
CC       anchored to the viral envelope, but associates with the extravirion
CC       surface through its binding to TM. It is probably concentrated at the
CC       site of budding and incorporated into the virions possibly by contacts
CC       between the cytoplasmic tail of Env and the N-terminus of Gag.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBCELLULAR LOCATION: [Transmembrane protein gp41]: Virion membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host cell membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host endosome membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Note=It is probably concentrated at
CC       the site of budding and incorporated into the virions possibly by
CC       contacts between the cytoplasmic tail of Env and the N-terminus of Gag.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: Some of the most genetically diverse regions of the viral
CC       genome are present in Env. They are called variable regions 1 through 5
CC       (V1 through V5). Coreceptor usage of gp120 is determined mainly by the
CC       primary structure of the third variable region (V3) in the outer domain
CC       of gp120. The sequence of V3 determines which coreceptor, CCR5 and/or
CC       CXCR4 (corresponding to R5/macrophage, X4/T cell and R5X4/T cell and
CC       macrophage tropism), is used to trigger the fusion potential of the Env
CC       complex, and hence which cells the virus can infect. Binding to CCR5
CC       involves a region adjacent in addition to V3. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- DOMAIN: The membrane proximal external region (MPER) present in gp41 is
CC       a tryptophan-rich region recognized by the antibodies 2F5, Z13, and
CC       4E10. MPER seems to play a role in fusion. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- DOMAIN: The 17 amino acids long immunosuppressive region is present in
CC       many retroviral envelope proteins. Synthetic peptides derived from this
CC       relatively conserved sequence inhibit immune function in vitro and in
CC       vivo. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: The YXXL motif is involved in determining the exact site of
CC       viral release at the surface of infected mononuclear cells and promotes
CC       endocytosis. YXXL and di-leucine endocytosis motifs interact directly
CC       or indirectly with the clathrin adapter complexes, opperate
CC       independently, and their activities are not additive.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: The CD4-binding region is targeted by the antibody b12.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- PTM: Highly glycosylated by host. The high number of glycan on the
CC       protein is reffered to as 'glycan shield' because it contributes to
CC       hide protein sequence from adaptive immune system. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- PTM: Palmitoylation of the transmembrane protein and of Env polyprotein
CC       (prior to its proteolytic cleavage) is essential for their association
CC       with host cell membrane lipid rafts. Palmitoylation is therefore
CC       required for envelope trafficking to classical lipid rafts, but not for
CC       viral replication. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- PTM: Specific enzymatic cleavages in vivo yield mature proteins.
CC       Envelope glycoproteins are synthesized as an inactive precursor that is
CC       heavily N-glycosylated and processed likely by host cell furin in the
CC       Golgi to yield the mature SU and TM proteins. The cleavage site between
CC       SU and TM requires the minimal sequence [KR]-X-[KR]-R. About 2 of the 9
CC       disulfide bonds of gp41 are reduced by P4HB/PDI, following binding to
CC       CD4 receptor. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- MISCELLANEOUS: Inhibitors targeting HIV-1 viral envelope proteins are
CC       used as antiretroviral drugs. Attachment of virions to the cell surface
CC       via non-specific interactions and CD4 binding can be blocked by
CC       inhibitors that include cyanovirin-N, cyclotriazadisulfonamide analogs,
CC       PRO 2000, TNX 355 and PRO 542. In addition, BMS 806 can block CD4-
CC       induced conformational changes. Env interactions with the coreceptor
CC       molecules can be targeted by CCR5 antagonists including SCH-D,
CC       maraviroc (UK 427857) and aplaviroc (GW 873140), and the CXCR4
CC       antagonist AMD 070. Fusion of viral and cellular membranes can be
CC       inhibited by peptides such as enfuvirtide and tifuvirtide (T 1249).
CC       Resistance to inhibitors associated with mutations in Env are observed.
CC       Most of the time, single mutations confer only a modest reduction in
CC       drug susceptibility. Combination of several mutations is usually
CC       required to develop a high-level drug resistance. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- MISCELLANEOUS: HIV-1 lineages are divided in three main groups, M (for
CC       Major), O (for Outlier), and N (for New, or Non-M, Non-O). The vast
CC       majority of strains found worldwide belong to the group M. Group O
CC       seems to be endemic to and largely confined to Cameroon and neighboring
CC       countries in West Central Africa, where these viruses represent a small
CC       minority of HIV-1 strains. The group N is represented by a limited
CC       number of isolates from Cameroonian persons. The group M is further
CC       subdivided in 9 clades or subtypes (A to D, F to H, J and K).
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SIMILARITY: Belongs to the HIV-1 env protein family.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- WEB RESOURCE: Name=hivdb; Note=HIV drug resistance database;
CC       URL="https://hivdb.stanford.edu";
CC   -!- WEB RESOURCE: Name=HIV drug resistance mutations;
CC       URL="https://www.iasusa.org/content/hiv-drug-resistance-mutations";
CC   ---------------------------------------------------------------------------
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DR   EMBL; M21098; AAA44221.1; -; Genomic_RNA.
DR   PIR; A31667; VCLJBR.
DR   PDB; 1IM7; NMR; -; A=591-603.
DR   PDB; 1J8N; NMR; -; A=591-603.
DR   PDB; 1J8Z; NMR; -; A=591-603.
DR   PDB; 1J9V; NMR; -; A=591-603.
DR   PDB; 1JAA; NMR; -; A=591-603.
DR   PDB; 1JAR; NMR; -; A=591-603.
DR   PDB; 1JC8; NMR; -; A=591-603.
DR   PDB; 1JCP; NMR; -; A=591-603.
DR   PDBsum; 1IM7; -.
DR   PDBsum; 1J8N; -.
DR   PDBsum; 1J8Z; -.
DR   PDBsum; 1J9V; -.
DR   PDBsum; 1JAA; -.
DR   PDBsum; 1JAR; -.
DR   PDBsum; 1JC8; -.
DR   PDBsum; 1JCP; -.
DR   BMRB; P12488; -.
DR   SMR; P12488; -.
DR   DrugBank; DB03320; 3-Amino-Alanine.
DR   DrugBank; DB02780; Beta-3-Cysteine.
DR   DrugBank; DB02904; Beta-3-Serine.
DR   DrugBank; DB11796; Fostemsavir.
DR   DrugBank; DB03817; L-2,4-diaminobutyric acid.
DR   GlyCosmos; P12488; 28 sites, No reported glycans.
DR   Reactome; R-HSA-5621480; Dectin-2 family.
DR   EvolutionaryTrace; P12488; -.
DR   GO; GO:0044175; C:host cell endosome membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0016020; C:membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:0019031; C:viral envelope; IEA:UniProtKB-KW.
DR   GO; GO:0055036; C:virion membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005198; F:structural molecule activity; IEA:UniProtKB-UniRule.
DR   GO; GO:0075512; P:clathrin-dependent endocytosis of virus by host cell; IEA:UniProtKB-UniRule.
DR   GO; GO:0039654; P:fusion of virus membrane with host endosome membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:0019064; P:fusion of virus membrane with host plasma membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:1903905; P:positive regulation of establishment of T cell polarity; IEA:UniProtKB-UniRule.
DR   GO; GO:1903908; P:positive regulation of plasma membrane raft polarization; IEA:UniProtKB-UniRule.
DR   GO; GO:1903911; P:positive regulation of receptor clustering; IEA:UniProtKB-UniRule.
DR   GO; GO:0019082; P:viral protein processing; IEA:UniProtKB-UniRule.
DR   GO; GO:0019062; P:virion attachment to host cell; IEA:UniProtKB-UniRule.
DR   GO; GO:0019049; P:virus-mediated perturbation of host defense response; IEA:UniProtKB-UniRule.
DR   CDD; cd09909; HIV-1-like_HR1-HR2; 1.
DR   Gene3D; 1.10.287.210; -; 1.
DR   Gene3D; 2.170.40.20; Human immunodeficiency virus 1, Gp160, envelope glycoprotein; 2.
DR   Gene3D; 1.20.5.490; Single helix bin; 1.
DR   HAMAP; MF_04083; HIV_ENV; 1.
DR   InterPro; IPR036377; Gp120_core_sf.
DR   InterPro; IPR037527; Gp160.
DR   InterPro; IPR000328; GP41-like.
DR   InterPro; IPR000777; HIV1_Gp120.
DR   Pfam; PF00516; GP120; 1.
DR   Pfam; PF00517; GP41; 1.
DR   SUPFAM; SSF56502; gp120 core; 2.
DR   SUPFAM; SSF58069; Virus ectodomain; 1.
PE   1: Evidence at protein level;
KW   3D-structure; AIDS; Apoptosis;
KW   Clathrin-mediated endocytosis of virus by host;
KW   Cleavage on pair of basic residues; Coiled coil; Disulfide bond;
KW   Fusion of virus membrane with host endosomal membrane;
KW   Fusion of virus membrane with host membrane; Glycoprotein;
KW   Host cell membrane; Host endosome; Host membrane; Host-virus interaction;
KW   Lipoprotein; Membrane; Palmitate; Signal; Transmembrane;
KW   Transmembrane helix; Viral attachment to host cell; Viral envelope protein;
KW   Viral immunoevasion; Viral penetration into host cytoplasm; Virion;
KW   Virus endocytosis by host; Virus entry into host cell.
FT   SIGNAL          1..32
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CHAIN           33..852
FT                   /note="Envelope glycoprotein gp160"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000441239"
FT   CHAIN           33..507
FT                   /note="Surface protein gp120"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000441240"
FT   CHAIN           508..852
FT                   /note="Transmembrane protein gp41"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000038403"
FT   TOPO_DOM        33..680
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   TRANSMEM        681..701
FT                   /note="Helical"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   TOPO_DOM        702..852
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          131..154
FT                   /note="V1"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          155..196
FT                   /note="V2"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          296..329
FT                   /note="V3"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          362..372
FT                   /note="CD4-binding loop"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          383..412
FT                   /note="V4"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          454..467
FT                   /note="V5"
FT   REGION          457..467
FT                   /note="V5"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          508..528
FT                   /note="Fusion peptide"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          570..588
FT                   /note="Immunosuppression"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          658..679
FT                   /note="MPER; binding to GalCer"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          715..741
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COILED          629..663
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   MOTIF           708..711
FT                   /note="YXXL motif; contains endocytosis signal"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   COMPBIAS        720..741
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   SITE            507..508
FT                   /note="Cleavage; by host furin"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        49
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        88
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        135
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        138
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        154
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        158
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        197
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        234
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        241
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        262
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        276
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        289
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        295
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        301
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        331
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        354
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        360
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        384
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        390
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        396
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        400
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        442
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        456
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        607
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        612
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        621
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        633
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        670
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        54..74
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        119..205
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        126..196
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        131..155
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        218..247
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        228..239
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        296..330
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        376..439
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        383..412
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        594..600
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   TURN            595..597
FT                   /evidence="ECO:0007829|PDB:1J8Z"
SQ   SEQUENCE   852 AA;  97203 MW;  2BB866345DEC915F CRC64;
     MRVKGIKKNY QHLWRWGGMM LLGILMICSA TDKLWVTVYY GVPVWKEANT TLFCASDAKA
     YDTEIHNVWA THACVPTDPN PQELVMGNVT ENFNMWKNDM VEQMHEDIIS LWDQSLKPCV
     KLTPLCVTLN CHDFNATNAT SNSGKMMEGG EMKNCSFNIT TSIRDKMQKE YALFYKLDIV
     PIDNDKTNTR YRLISCNTSV ITQACPKVTF EPIPIHYCAP AGFAILKCNN KKFNGTGPCT
     NVSTVQCTHG IRPVVSTQLL LNGSLAEEEV VIRSENFTNN VKTIIVQLNE SVEINCTRPN
     NNTRKRITMG PGRVYYTTGQ IIGDIRRAHC NLSRSKWENT LKQIVTKLRV QFKNKTIVFN
     RSSGGDPEIV MHSFNCGGEF FFCNTTQLFN STWYRNTTGN ITEGNSPITL PCRIKQIINM
     WQEVGKAMYA PPIRGQIKCS SNITGLLLTR DGGNNNETTD TEIFRPGGGN MRDNWRSELY
     KYKVVKIEPL GVAPTKAKRR VVQREKRAVG LGALFLGFLG AAGSTMGAAS LTLTVQARLL
     LSGIVQQQNN LLMAIEAQQH MLELTVWGIK QLQARVLAVE RYLKDQQLLG IWGCSGKLIC
     TTAVPWNASW SNKSLSDIWD NMTWMEWERE IDNYTNLIYS LIEDSQIQQE KNEKELLELD
     KWASLWNWFN ITNWLWYIKI FIMIVGGLIG LRIVFAVLSI VNRVRQGYSP LSFQTRLPGR
     RGPDRPEGIE EEGGERDRDR SSPLVDGFLA LFWVDLRSLF LFSYHRLRDL LLIVTRIVEL
     LGRRGWEVLK YWWNLLQYWS QELKNSAVSL LNATAIAVGE RTDRAIEVVQ RAFRAILHIP
     RRIRQGLERA LQ
//
ID   ENV_HV1BR               Reviewed;         861 AA.
AC   P03377; Q85582;
DT   21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT   21-JUL-1986, sequence version 1.
DT   27-MAR-2024, entry version 178.
DE   RecName: Full=Envelope glycoprotein gp160 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   AltName: Full=Env polyprotein {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Contains:
DE     RecName: Full=Surface protein gp120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=SU {ECO:0000255|HAMAP-Rule:MF_04083};
DE     AltName: Full=Glycoprotein 120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=gp120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Contains:
DE     RecName: Full=Transmembrane protein gp41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=TM {ECO:0000255|HAMAP-Rule:MF_04083};
DE     AltName: Full=Glycoprotein 41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=gp41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Flags: Precursor;
GN   Name=env {ECO:0000255|HAMAP-Rule:MF_04083};
OS   Human immunodeficiency virus type 1 group M subtype B (isolate BRU/LAI)
OS   (HIV-1).
OC   Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC   Ortervirales; Retroviridae; Orthoretrovirinae; Lentivirus;
OC   Human immunodeficiency virus 1.
OX   NCBI_TaxID=11686;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX   PubMed=2981635; DOI=10.1016/0092-8674(85)90303-4;
RA   Wain-Hobson S., Sonigo P., Danos O., Cole S., Alizon M.;
RT   "Nucleotide sequence of the AIDS virus, LAV.";
RL   Cell 40:9-17(1985).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RC   STRAIN=Clone pNL4-3;
RA   Buckler C.E.;
RL   Submitted (JUL-1989) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   SEQUENCE REVISION TO 537 AND 538.
RA   Strebel K.J., Martin M.A.;
RL   Submitted (MAY-2010) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   INTERACTION OF SURFACE PROTEIN GP120 WITH HUMAN CD209/DC-SIGN.
RX   PubMed=1518869; DOI=10.1073/pnas.89.17.8356;
RA   Curtis B.M., Scharnowske S., Watson A.J.;
RT   "Sequence and expression of a membrane-associated C-type lectin that
RT   exhibits CD4-independent binding of human immunodeficiency virus envelope
RT   glycoprotein gp 120.";
RL   Proc. Natl. Acad. Sci. U.S.A. 89:8356-8360(1992).
RN   [5]
RP   INTERACTION OF SURFACE PROTEIN GP120 WITH HOST CD209/DC-SIGN.
RC   STRAIN=Clone pNL4-3;
RX   PubMed=11312337; DOI=10.1128/jvi.75.10.4664-4672.2001;
RA   Pohlmann S., Baribaud F., Lee B., Leslie G.J., Sanchez M.D.,
RA   Hiebenthal-Millow K., Munch J., Kirchhoff F., Doms R.W.;
RT   "DC-SIGN interactions with human immunodeficiency virus type 1 and 2 and
RT   simian immunodeficiency virus.";
RL   J. Virol. 75:4664-4672(2001).
RN   [6]
RP   INTERACTION OF SURFACE PROTEIN GP120 WITH HUMAN CD209/DC-SIGN.
RC   STRAIN=Clone pNL4-3;
RX   PubMed=11825572; DOI=10.1016/s1074-7613(02)00259-5;
RA   Kwon D.S., Gregorio G., Bitton N., Hendrickson W.A., Littman D.R.;
RT   "DC-SIGN-mediated internalization of HIV is required for trans-enhancement
RT   of T cell infection.";
RL   Immunity 16:135-144(2002).
RN   [7]
RP   REDUCTION OF SURFACE PROTEIN GP120 DISULFIDE BONDS BY P4HB/PDI.
RX   PubMed=12218051; DOI=10.1074/jbc.m204547200;
RA   Gallina A., Hanley T.M., Mandel R., Trahey M., Broder C.C., Viglianti G.A.,
RA   Ryser H.J.;
RT   "Inhibitors of protein-disulfide isomerase prevent cleavage of disulfide
RT   bonds in receptor-bound glycoprotein 120 and prevent HIV-1 entry.";
RL   J. Biol. Chem. 277:50579-50588(2002).
RN   [8]
RP   PROTEOLYTIC PROCESSING OF POLYPROTEIN BY HOST FURIN.
RC   STRAIN=Clone pNL4-3;
RX   PubMed=15371436; DOI=10.1074/jbc.m403394200;
RA   Kibler K.V., Miyazato A., Yedavalli V.S.R.K., Dayton A.I., Jacobs B.L.,
RA   Dapolito G., Kim S.-J., Jeang K.-T.;
RT   "Polyarginine inhibits gp160 processing by furin and suppresses productive
RT   human immunodeficiency virus type 1 infection.";
RL   J. Biol. Chem. 279:49055-49063(2004).
RN   [9]
RP   ROLE OF PALMITOYLATION, AND MUTAGENESIS OF CYS-769.
RC   STRAIN=Clone pNL4-3;
RX   PubMed=15113929; DOI=10.1128/jvi.78.10.5500-5506.2004;
RA   Bhattacharya J., Peters P.J., Clapham P.R.;
RT   "Human immunodeficiency virus type 1 envelope glycoproteins that lack
RT   cytoplasmic domain cysteines: impact on association with membrane lipid
RT   rafts and incorporation onto budding virus particles.";
RL   J. Virol. 78:5500-5506(2004).
RN   [10]
RP   REDUCTION OF SURFACE PROTEIN GP120 DISULFIDE BONDS BY HUMAN TXN.
RC   STRAIN=Clone pNL4-3;
RX   PubMed=16507315; DOI=10.1016/j.virol.2006.01.041;
RA   Ou W., Silver J.;
RT   "Role of protein disulfide isomerase and other thiol-reactive proteins in
RT   HIV-1 envelope protein-mediated fusion.";
RL   Virology 350:406-417(2006).
RN   [11]
RP   DISULFIDE BONDS.
RX   PubMed=18653472; DOI=10.1091/mbc.e07-12-1282;
RA   van Anken E., Sanders R.W., Liscaljet I.M., Land A., Bontjer I.,
RA   Tillemans S., Nabatov A.A., Paxton W.A., Berkhout B., Braakman I.;
RT   "Only five of 10 strictly conserved disulfide bonds are essential for
RT   folding and eight for function of the HIV-1 envelope glycoprotein.";
RL   Mol. Biol. Cell 19:4298-4309(2008).
RN   [12]
RP   INTERACTION OF GP120 WITH HUMAN ITGA4/ITGB7 HETERODIMER, AND MUTAGENESIS OF
RP   184-LEU-ASP-185.
RC   STRAIN=Clone pNL4-3;
RX   PubMed=18264102; DOI=10.1038/ni1566;
RA   Arthos J., Cicala C., Martinelli E., Macleod K., Van Ryk D., Wei D.,
RA   Xiao Z., Veenstra T.D., Conrad T.P., Lempicki R.A., McLaughlin S.,
RA   Pascuccio M., Gopaul R., McNally J., Cruz C.C., Censoplano N., Chung E.,
RA   Reitano K.N., Kottilil S., Goode D.J., Fauci A.S.;
RT   "HIV-1 envelope protein binds to and signals through integrin alpha4beta7,
RT   the gut mucosal homing receptor for peripheral T cells.";
RL   Nat. Immunol. 9:301-309(2008).
RN   [13]
RP   REVIEW.
RX   PubMed=12974773; DOI=10.1034/j.1600-0463.2003.11107803.x;
RA   Geijtenbeek T.B., van Kooyk Y.;
RT   "Pathogens target DC-SIGN to influence their fate DC-SIGN functions as a
RT   pathogen receptor with broad specificity.";
RL   APMIS 111:698-714(2003).
RN   [14]
RP   REVIEW.
RX   PubMed=12873764; DOI=10.1016/s0005-2736(03)00161-5;
RA   Gallo S.A., Finnegan C.M., Viard M., Raviv Y., Dimitrov A., Rawat S.S.,
RA   Puri A., Durell S., Blumenthal R.;
RT   "The HIV Env-mediated fusion reaction.";
RL   Biochim. Biophys. Acta 1614:36-50(2003).
RN   [15]
RP   REVIEW.
RX   PubMed=15719026; DOI=10.1038/sj.cdd.4401584;
RA   Perfettini J.-L., Castedo M., Roumier T., Andreau K., Nardacci R.,
RA   Piacentini M., Kroemer G.;
RT   "Mechanisms of apoptosis induction by the HIV-1 envelope.";
RL   Cell Death Differ. 12:916-923(2005).
RN   [16]
RP   REVIEW.
RX   PubMed=15725757; DOI=10.1089/aid.2005.21.171;
RA   Hartley O., Klasse P.J., Sattentau Q.J., Moore J.P.;
RT   "V3: HIV's switch-hitter.";
RL   AIDS Res. Hum. Retroviruses 21:171-189(2005).
RN   [17]
RP   REVIEW.
RX   PubMed=16114975; DOI=10.2165/00003495-200565130-00002;
RA   Reeves J.D., Piefer A.J.;
RT   "Emerging drug targets for antiretroviral therapy.";
RL   Drugs 65:1747-1766(2005).
RN   [18]
RP   REVIEW.
RX   PubMed=16437164; DOI=10.1038/sj.emboj.7600947;
RA   Lusso P.;
RT   "HIV and the chemokine system: 10 years later.";
RL   EMBO J. 25:447-456(2006).
RN   [19]
RP   X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 537-670.
RX   PubMed=11026535; DOI=10.1016/s0968-0896(00)00155-3;
RA   Zhou G., Ferrer M., Chopra R., Kapoor T.M., Strassmaier T., Weissenhorn W.,
RA   Skehel J.J., Oprian D., Schreiber S.L., Harrison S.C., Wiley D.C.;
RT   "The structure of an HIV-1 specific cell entry inhibitor in complex with
RT   the HIV-1 gp41 trimeric core.";
RL   Bioorg. Med. Chem. 8:2219-2227(2000).
RN   [20]
RP   STRUCTURE BY FTIR OF 517-539.
RX   PubMed=11853678; DOI=10.1016/s0005-2736(01)00443-6;
RA   Gordon L.M., Mobley P.W., Pilpa R., Sherman M.A., Waring A.J.;
RT   "Conformational mapping of the N-terminal peptide of HIV-1 gp41 in membrane
RT   environments using (13)C-enhanced Fourier transform infrared
RT   spectroscopy.";
RL   Biochim. Biophys. Acta 1559:96-120(2002).
RN   [21]
RP   STRUCTURE BY FTIR OF 517-539.
RX   PubMed=15044732; DOI=10.1110/ps.03407704;
RA   Gordon L.M., Mobley P.W., Lee W., Eskandari S., Kaznessis Y.N.,
RA   Sherman M.A., Waring A.J.;
RT   "Conformational mapping of the N-terminal peptide of HIV-1 gp41 in lipid
RT   detergent and aqueous environments using 13C-enhanced Fourier transform
RT   infrared spectroscopy.";
RL   Protein Sci. 13:1012-1030(2004).
CC   -!- FUNCTION: [Envelope glycoprotein gp160]: Oligomerizes in the host
CC       endoplasmic reticulum into predominantly trimers. In a second time,
CC       gp160 transits in the host Golgi, where glycosylation is completed. The
CC       precursor is then proteolytically cleaved in the trans-Golgi and
CC       thereby activated by cellular furin or furin-like proteases to produce
CC       gp120 and gp41. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- FUNCTION: [Surface protein gp120]: Attaches the virus to the host
CC       lymphoid cell by binding to the primary receptor CD4. This interaction
CC       induces a structural rearrangement creating a high affinity binding
CC       site for a chemokine coreceptor like CXCR4 and/or CCR5. Acts as a
CC       ligand for CD209/DC-SIGN and CLEC4M/DC-SIGNR, which are respectively
CC       found on dendritic cells (DCs), and on endothelial cells of liver
CC       sinusoids and lymph node sinuses. These interactions allow capture of
CC       viral particles at mucosal surfaces by these cells and subsequent
CC       transmission to permissive cells. HIV subverts the migration properties
CC       of dendritic cells to gain access to CD4+ T-cells in lymph nodes. Virus
CC       transmission to permissive T-cells occurs either in trans (without DCs
CC       infection, through viral capture and transmission), or in cis
CC       (following DCs productive infection, through the usual CD4-gp120
CC       interaction), thereby inducing a robust infection. In trans infection,
CC       bound virions remain infectious over days and it is proposed that they
CC       are not degraded, but protected in non-lysosomal acidic organelles
CC       within the DCs close to the cell membrane thus contributing to the
CC       viral infectious potential during DCs' migration from the periphery to
CC       the lymphoid tissues. On arrival at lymphoid tissues, intact virions
CC       recycle back to DCs' cell surface allowing virus transmission to CD4+
CC       T-cells. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- FUNCTION: [Transmembrane protein gp41]: Acts as a class I viral fusion
CC       protein. Under the current model, the protein has at least 3
CC       conformational states: pre-fusion native state, pre-hairpin
CC       intermediate state, and post-fusion hairpin state. During fusion of
CC       viral and target intracellular membranes, the coiled coil regions
CC       (heptad repeats) assume a trimer-of-hairpins structure, positioning the
CC       fusion peptide in close proximity to the C-terminal region of the
CC       ectodomain. The formation of this structure appears to drive apposition
CC       and subsequent fusion of viral and target cell membranes. Complete
CC       fusion occurs in host cell endosomes and is dynamin-dependent, however
CC       some lipid transfer might occur at the plasma membrane. The virus
CC       undergoes clathrin-dependent internalization long before endosomal
CC       fusion, thus minimizing the surface exposure of conserved viral
CC       epitopes during fusion and reducing the efficacy of inhibitors
CC       targeting these epitopes. Membranes fusion leads to delivery of the
CC       nucleocapsid into the cytoplasm. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBUNIT: [Surface protein gp120]: The mature envelope protein (Env)
CC       consists of a homotrimer of non-covalently associated gp120-gp41
CC       heterodimers. The resulting complex protrudes from the virus surface as
CC       a spike. There seems to be as few as 10 spikes on the average virion.
CC       Interacts with host CD4, CCR5 and CXCR4. Gp120 also interacts with the
CC       C-type lectins CD209/DC-SIGN and CLEC4M/DC-SIGNR (collectively referred
CC       to as DC-SIGN(R)). Gp120 and gp41 interact with GalCer. Gp120 interacts
CC       with host ITGA4/ITGB7 complex; on CD4+ T-cells, this interaction
CC       results in rapid activation of integrin ITGAL/LFA-1, which facilitates
CC       efficient cell-to-cell spreading of HIV-1. Gp120 interacts with cell-
CC       associated heparan sulfate; this interaction increases virus
CC       infectivity on permissive cells and may be involved in infection of
CC       CD4- cells. {ECO:0000255|HAMAP-Rule:MF_04083,
CC       ECO:0000269|PubMed:11312337, ECO:0000269|PubMed:11825572,
CC       ECO:0000269|PubMed:1518869, ECO:0000269|PubMed:18264102}.
CC   -!- SUBUNIT: [Transmembrane protein gp41]: The mature envelope protein
CC       (Env) consists of a homotrimer of non-covalently associated gp120-gp41
CC       heterodimers. The resulting complex protrudes from the virus surface as
CC       a spike. There seems to be as few as 10 spikes on the average virion.
CC       {ECO:0000255|HAMAP-Rule:MF_04083, ECO:0000269|PubMed:11312337,
CC       ECO:0000269|PubMed:11825572, ECO:0000269|PubMed:1518869,
CC       ECO:0000269|PubMed:18264102}.
CC   -!- SUBCELLULAR LOCATION: [Surface protein gp120]: Virion membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Peripheral membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host cell membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Peripheral membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host endosome membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Note=The surface protein is not
CC       anchored to the viral envelope, but associates with the extravirion
CC       surface through its binding to TM. It is probably concentrated at the
CC       site of budding and incorporated into the virions possibly by contacts
CC       between the cytoplasmic tail of Env and the N-terminus of Gag.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBCELLULAR LOCATION: [Transmembrane protein gp41]: Virion membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host cell membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host endosome membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Note=It is probably concentrated at
CC       the site of budding and incorporated into the virions possibly by
CC       contacts between the cytoplasmic tail of Env and the N-terminus of Gag.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: Some of the most genetically diverse regions of the viral
CC       genome are present in Env. They are called variable regions 1 through 5
CC       (V1 through V5). Coreceptor usage of gp120 is determined mainly by the
CC       primary structure of the third variable region (V3) in the outer domain
CC       of gp120. The sequence of V3 determines which coreceptor, CCR5 and/or
CC       CXCR4 (corresponding to R5/macrophage, X4/T cell and R5X4/T cell and
CC       macrophage tropism), is used to trigger the fusion potential of the Env
CC       complex, and hence which cells the virus can infect. Binding to CCR5
CC       involves a region adjacent in addition to V3. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- DOMAIN: The membrane proximal external region (MPER) present in gp41 is
CC       a tryptophan-rich region recognized by the antibodies 2F5, Z13, and
CC       4E10. MPER seems to play a role in fusion. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- DOMAIN: The 17 amino acids long immunosuppressive region is present in
CC       many retroviral envelope proteins. Synthetic peptides derived from this
CC       relatively conserved sequence inhibit immune function in vitro and in
CC       vivo. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: The YXXL motif is involved in determining the exact site of
CC       viral release at the surface of infected mononuclear cells and promotes
CC       endocytosis. YXXL and di-leucine endocytosis motifs interact directly
CC       or indirectly with the clathrin adapter complexes, opperate
CC       independently, and their activities are not additive.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: The CD4-binding region is targeted by the antibody b12.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- PTM: Highly glycosylated by host. The high number of glycan on the
CC       protein is reffered to as 'glycan shield' because it contributes to
CC       hide protein sequence from adaptive immune system. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- PTM: Palmitoylation of the transmembrane protein and of Env polyprotein
CC       (prior to its proteolytic cleavage) is essential for their association
CC       with host cell membrane lipid rafts. Palmitoylation is therefore
CC       required for envelope trafficking to classical lipid rafts, but not for
CC       viral replication. {ECO:0000255|HAMAP-Rule:MF_04083,
CC       ECO:0000269|PubMed:15113929}.
CC   -!- PTM: Specific enzymatic cleavages in vivo yield mature proteins.
CC       Envelope glycoproteins are synthesized as an inactive precursor that is
CC       heavily N-glycosylated and processed likely by host cell furin in the
CC       Golgi to yield the mature SU and TM proteins. The cleavage site between
CC       SU and TM requires the minimal sequence [KR]-X-[KR]-R. About 2 of the 9
CC       disulfide bonds of gp41 are reduced by P4HB/PDI, following binding to
CC       CD4 receptor. {ECO:0000255|HAMAP-Rule:MF_04083,
CC       ECO:0000269|PubMed:15371436, ECO:0000269|PubMed:16507315}.
CC   -!- MISCELLANEOUS: Inhibitors targeting HIV-1 viral envelope proteins are
CC       used as antiretroviral drugs. Attachment of virions to the cell surface
CC       via non-specific interactions and CD4 binding can be blocked by
CC       inhibitors that include cyanovirin-N, cyclotriazadisulfonamide analogs,
CC       PRO 2000, TNX 355 and PRO 542. In addition, BMS 806 can block CD4-
CC       induced conformational changes. Env interactions with the coreceptor
CC       molecules can be targeted by CCR5 antagonists including SCH-D,
CC       maraviroc (UK 427857) and aplaviroc (GW 873140), and the CXCR4
CC       antagonist AMD 070. Fusion of viral and cellular membranes can be
CC       inhibited by peptides such as enfuvirtide and tifuvirtide (T 1249).
CC       Resistance to inhibitors associated with mutations in Env are observed.
CC       Most of the time, single mutations confer only a modest reduction in
CC       drug susceptibility. Combination of several mutations is usually
CC       required to develop a high-level drug resistance. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- MISCELLANEOUS: HIV-1 lineages are divided in three main groups, M (for
CC       Major), O (for Outlier), and N (for New, or Non-M, Non-O). The vast
CC       majority of strains found worldwide belong to the group M. Group O
CC       seems to be endemic to and largely confined to Cameroon and neighboring
CC       countries in West Central Africa, where these viruses represent a small
CC       minority of HIV-1 strains. The group N is represented by a limited
CC       number of isolates from Cameroonian persons. The group M is further
CC       subdivided in 9 clades or subtypes (A to D, F to H, J and K).
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SIMILARITY: Belongs to the HIV-1 env protein family.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- WEB RESOURCE: Name=hivdb; Note=HIV drug resistance database;
CC       URL="https://hivdb.stanford.edu";
CC   -!- WEB RESOURCE: Name=HIV drug resistance mutations;
CC       URL="https://www.iasusa.org/content/hiv-drug-resistance-mutations";
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DR   EMBL; K02013; AAB59751.1; -; Genomic_RNA.
DR   EMBL; A04321; CAA00352.1; -; Unassigned_RNA.
DR   EMBL; M19921; AAA44992.2; -; Genomic_RNA.
DR   PIR; A03975; VCLJLV.
DR   PDB; 1ENV; X-ray; 2.60 A; A=546-593, A=633-670.
DR   PDB; 1ERF; IR; -; A=517-539.
DR   PDB; 1FAV; X-ray; 3.00 A; A=546-595, C=639-670.
DR   PDB; 1JD8; NMR; -; A=600-612.
DR   PDB; 1P5A; IR; -; A=517-539.
DR   PDB; 1U6U; NMR; -; A=310-326.
DR   PDB; 1U6V; NMR; -; A=310-326.
DR   PDB; 2ZZO; X-ray; 2.20 A; C=633-666, N=551-586.
DR   PDB; 3G9R; X-ray; 2.00 A; A/B/C/D/E/F=667-689.
DR   PDB; 3MNW; X-ray; 2.20 A; P=657-676.
DR   PDB; 3VGX; X-ray; 1.74 A; C=558-595, D=626-657.
DR   PDB; 3VTP; X-ray; 1.90 A; C=555-595, D=631-666.
DR   PDB; 5WES; X-ray; 2.71 A; P=316-320.
DR   PDB; 5WET; X-ray; 2.64 A; P=316-321.
DR   PDB; 5WEU; X-ray; 1.58 A; P=316-325.
DR   PDB; 6R2G; X-ray; 1.90 A; C=632-666.
DR   PDBsum; 1ENV; -.
DR   PDBsum; 1ERF; -.
DR   PDBsum; 1FAV; -.
DR   PDBsum; 1JD8; -.
DR   PDBsum; 1P5A; -.
DR   PDBsum; 1U6U; -.
DR   PDBsum; 1U6V; -.
DR   PDBsum; 2ZZO; -.
DR   PDBsum; 3G9R; -.
DR   PDBsum; 3MNW; -.
DR   PDBsum; 3VGX; -.
DR   PDBsum; 3VTP; -.
DR   PDBsum; 5WES; -.
DR   PDBsum; 5WET; -.
DR   PDBsum; 5WEU; -.
DR   PDBsum; 6R2G; -.
DR   BMRB; P03377; -.
DR   SMR; P03377; -.
DR   IntAct; P03377; 1.
DR   BindingDB; P03377; -.
DR   ChEMBL; CHEMBL5826; -.
DR   GlyCosmos; P03377; 30 sites, No reported glycans.
DR   ABCD; P03377; 62 sequenced antibodies.
DR   Reactome; R-HSA-5621480; Dectin-2 family.
DR   EvolutionaryTrace; P03377; -.
DR   Proteomes; UP000007692; Genome.
DR   GO; GO:0044175; C:host cell endosome membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0016020; C:membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:0019031; C:viral envelope; IEA:UniProtKB-KW.
DR   GO; GO:0055036; C:virion membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005198; F:structural molecule activity; IEA:UniProtKB-UniRule.
DR   GO; GO:0075512; P:clathrin-dependent endocytosis of virus by host cell; IEA:UniProtKB-UniRule.
DR   GO; GO:0039654; P:fusion of virus membrane with host endosome membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:0019064; P:fusion of virus membrane with host plasma membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:1903905; P:positive regulation of establishment of T cell polarity; IEA:UniProtKB-UniRule.
DR   GO; GO:1903908; P:positive regulation of plasma membrane raft polarization; IEA:UniProtKB-UniRule.
DR   GO; GO:1903911; P:positive regulation of receptor clustering; IEA:UniProtKB-UniRule.
DR   GO; GO:0019082; P:viral protein processing; IEA:UniProtKB-UniRule.
DR   GO; GO:0019062; P:virion attachment to host cell; IEA:UniProtKB-UniRule.
DR   GO; GO:0019049; P:virus-mediated perturbation of host defense response; IEA:UniProtKB-UniRule.
DR   CDD; cd09909; HIV-1-like_HR1-HR2; 1.
DR   Gene3D; 1.10.287.210; -; 1.
DR   Gene3D; 2.170.40.20; Human immunodeficiency virus 1, Gp160, envelope glycoprotein; 2.
DR   Gene3D; 1.20.5.490; Single helix bin; 1.
DR   HAMAP; MF_04083; HIV_ENV; 1.
DR   InterPro; IPR036377; Gp120_core_sf.
DR   InterPro; IPR037527; Gp160.
DR   InterPro; IPR000328; GP41-like.
DR   InterPro; IPR000777; HIV1_Gp120.
DR   Pfam; PF00516; GP120; 1.
DR   Pfam; PF00517; GP41; 1.
DR   SUPFAM; SSF56502; gp120 core; 1.
DR   SUPFAM; SSF58069; Virus ectodomain; 1.
PE   1: Evidence at protein level;
KW   3D-structure; AIDS; Apoptosis;
KW   Clathrin-mediated endocytosis of virus by host;
KW   Cleavage on pair of basic residues; Coiled coil; Disulfide bond;
KW   Fusion of virus membrane with host endosomal membrane;
KW   Fusion of virus membrane with host membrane; Glycoprotein;
KW   Host cell membrane; Host endosome; Host membrane; Host-virus interaction;
KW   Lipoprotein; Membrane; Palmitate; Reference proteome; Signal;
KW   Transmembrane; Transmembrane helix; Viral attachment to host cell;
KW   Viral envelope protein; Viral immunoevasion;
KW   Viral penetration into host cytoplasm; Virion; Virus endocytosis by host;
KW   Virus entry into host cell.
FT   SIGNAL          1..32
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CHAIN           33..861
FT                   /note="Envelope glycoprotein gp160"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000239474"
FT   CHAIN           33..516
FT                   /note="Surface protein gp120"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000038388"
FT   CHAIN           517..861
FT                   /note="Transmembrane protein gp41"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000038389"
FT   TOPO_DOM        33..689
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   TRANSMEM        690..710
FT                   /note="Helical"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   TOPO_DOM        711..861
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          131..161
FT                   /note="V1"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          162..201
FT                   /note="V2"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          301..335
FT                   /note="V3"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          369..379
FT                   /note="CD4-binding loop"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          390..423
FT                   /note="V4"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          466..476
FT                   /note="V5"
FT   REGION          468..476
FT                   /note="V5"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          517..537
FT                   /note="Fusion peptide"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          579..597
FT                   /note="Immunosuppression"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          667..688
FT                   /note="MPER; binding to GalCer"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          723..747
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COILED          638..672
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   MOTIF           184..186
FT                   /note="Putative binding site to alpha-4/beta-7 integrin"
FT   MOTIF           717..720
FT                   /note="YXXL motif; contains endocytosis signal"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   MOTIF           860..861
FT                   /note="Di-leucine internalization motif"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   COMPBIAS        732..747
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   SITE            516..517
FT                   /note="Cleavage; by host furin"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   LIPID           769
FT                   /note="S-palmitoyl cysteine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   LIPID           842
FT                   /note="S-palmitoyl cysteine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        88
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        136
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        141
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        146
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        161
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        165
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        191
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        202
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        235
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        239
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        246
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        267
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        281
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        294
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        300
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        306
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        337
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        344
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        361
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        391
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        397
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        402
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        411
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        453
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        468
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        616
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        621
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        630
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        642
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        679
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        54..74
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083,
FT                   ECO:0000269|PubMed:18653472"
FT   DISULFID        119..210
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083,
FT                   ECO:0000269|PubMed:18653472"
FT   DISULFID        126..201
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083,
FT                   ECO:0000269|PubMed:18653472"
FT   DISULFID        131..162
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083,
FT                   ECO:0000269|PubMed:18653472"
FT   DISULFID        223..252
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083,
FT                   ECO:0000269|PubMed:18653472"
FT   DISULFID        233..244
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083,
FT                   ECO:0000269|PubMed:18653472"
FT   DISULFID        301..336
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083,
FT                   ECO:0000269|PubMed:18653472"
FT   DISULFID        383..450
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083,
FT                   ECO:0000269|PubMed:18653472"
FT   DISULFID        390..423
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083,
FT                   ECO:0000269|PubMed:18653472"
FT   DISULFID        603..609
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083,
FT                   ECO:0000269|PubMed:18653472"
FT   VARIANT         135..137
FT                   /note="GNA -> KND (in strain: Clone pNL4-3)"
FT   VARIANT         143..147
FT                   /note="Missing (in strain: Clone pNL4-3)"
FT   VARIANT         151..153
FT                   /note="EMM -> RMI (in strain: Clone pNL4-3)"
FT   VARIANT         172
FT                   /note="G -> D (in strain: Clone pNL4-3)"
FT   VARIANT         187
FT                   /note="I -> V (in strain: Clone pNL4-3)"
FT   VARIANT         192..193
FT                   /note="Missing (in strain: Clone pNL4-3)"
FT   VARIANT         197..199
FT                   /note="TLT -> RLI (in strain: Clone pNL4-3)"
FT   VARIANT         274
FT                   /note="E -> D (in strain: Clone pNL4-3)"
FT   VARIANT         295
FT                   /note="Q -> T (in strain: Clone pNL4-3)"
FT   VARIANT         538
FT                   /note="R -> A (in strain: Clone pNL4-3)"
FT   VARIANT         552
FT                   /note="G -> D (in strain: Clone pNL4-3)"
FT   VARIANT         689
FT                   /note="I -> L (in strain: Clone pNL4-3)"
FT   VARIANT         728
FT                   /note="T -> I (in strain: Clone pNL4-3)"
FT   VARIANT         818
FT                   /note="S -> N (in strain: Clone pNL4-3)"
FT   VARIANT         838..842
FT                   /note="VQGAC -> LQAAY (in strain: Clone pNL4-3)"
FT   MUTAGEN         184..185
FT                   /note="LD->AA: Partial loss of CD4-independent binding."
FT                   /evidence="ECO:0000269|PubMed:18264102"
FT   MUTAGEN         769
FT                   /note="C->F: Almost no effect on virions assembly and
FT                   infectivity."
FT                   /evidence="ECO:0000269|PubMed:15113929"
FT   STRAND          311..314
FT                   /evidence="ECO:0007829|PDB:1U6U"
FT   STRAND          322..325
FT                   /evidence="ECO:0007829|PDB:1U6U"
FT   HELIX           559..594
FT                   /evidence="ECO:0007829|PDB:3VGX"
FT   HELIX           606..614
FT                   /evidence="ECO:0007829|PDB:6R2G"
FT   HELIX           633..655
FT                   /evidence="ECO:0007829|PDB:3VGX"
FT   HELIX           668..689
FT                   /evidence="ECO:0007829|PDB:3G9R"
SQ   SEQUENCE   861 AA;  97488 MW;  04DE2B4D4E4FD63A CRC64;
     MRVKEKYQHL WRWGWKWGTM LLGILMICSA TEKLWVTVYY GVPVWKEATT TLFCASDAKA
     YDTEVHNVWA THACVPTDPN PQEVVLVNVT ENFNMWKNDM VEQMHEDIIS LWDQSLKPCV
     KLTPLCVSLK CTDLGNATNT NSSNTNSSSG EMMMEKGEIK NCSFNISTSI RGKVQKEYAF
     FYKLDIIPID NDTTSYTLTS CNTSVITQAC PKVSFEPIPI HYCAPAGFAI LKCNNKTFNG
     TGPCTNVSTV QCTHGIRPVV STQLLLNGSL AEEEVVIRSA NFTDNAKTII VQLNQSVEIN
     CTRPNNNTRK SIRIQRGPGR AFVTIGKIGN MRQAHCNISR AKWNATLKQI ASKLREQFGN
     NKTIIFKQSS GGDPEIVTHS FNCGGEFFYC NSTQLFNSTW FNSTWSTEGS NNTEGSDTIT
     LPCRIKQFIN MWQEVGKAMY APPISGQIRC SSNITGLLLT RDGGNNNNGS EIFRPGGGDM
     RDNWRSELYK YKVVKIEPLG VAPTKAKRRV VQREKRAVGI GALFLGFLGA AGSTMGARSM
     TLTVQARQLL SGIVQQQNNL LRAIEAQQHL LQLTVWGIKQ LQARILAVER YLKDQQLLGI
     WGCSGKLICT TAVPWNASWS NKSLEQIWNN MTWMEWDREI NNYTSLIHSL IEESQNQQEK
     NEQELLELDK WASLWNWFNI TNWLWYIKIF IMIVGGLVGL RIVFAVLSIV NRVRQGYSPL
     SFQTHLPTPR GPDRPEGIEE EGGERDRDRS IRLVNGSLAL IWDDLRSLCL FSYHRLRDLL
     LIVTRIVELL GRRGWEALKY WWNLLQYWSQ ELKNSAVSLL NATAIAVAEG TDRVIEVVQG
     ACRAIRHIPR RIRQGLERIL L
//
ID   ENV_HV1C4               Reviewed;         868 AA.
AC   P05879;
DT   01-NOV-1988, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1988, sequence version 1.
DT   27-MAR-2024, entry version 151.
DE   RecName: Full=Envelope glycoprotein gp160 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   AltName: Full=Env polyprotein {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Contains:
DE     RecName: Full=Surface protein gp120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=SU {ECO:0000255|HAMAP-Rule:MF_04083};
DE     AltName: Full=Glycoprotein 120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=gp120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Contains:
DE     RecName: Full=Transmembrane protein gp41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=TM {ECO:0000255|HAMAP-Rule:MF_04083};
DE     AltName: Full=Glycoprotein 41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=gp41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Flags: Precursor;
GN   Name=env {ECO:0000255|HAMAP-Rule:MF_04083};
OS   Human immunodeficiency virus type 1 group M subtype B (isolate CDC-451)
OS   (HIV-1).
OC   Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC   Ortervirales; Retroviridae; Orthoretrovirinae; Lentivirus;
OC   Human immunodeficiency virus 1.
OX   NCBI_TaxID=11687;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX   PubMed=3490666; DOI=10.1073/pnas.83.21.8380;
RA   Desai S.M., Kalyanaraman V.S., Casey J.M., Srinivasan A., Andersen P.R.,
RA   Devare S.G.;
RT   "Molecular cloning and primary nucleotide sequence analysis of a distinct
RT   human immunodeficiency virus isolate reveal significant divergence in its
RT   genomic sequences.";
RL   Proc. Natl. Acad. Sci. U.S.A. 83:8380-8384(1986).
RN   [2]
RP   PROTEIN SEQUENCE OF 34-43.
RX   PubMed=2187500; DOI=10.1089/aid.1990.6.371;
RA   Kalyanaraman V.S., Rodriguez V., Veronese F., Rahman R., Lusso P.,
RA   DeVico A.L., Copeland T., Oroszlan S., Gallo R.C., Sarngadharan M.G.;
RT   "Characterization of the secreted, native gp120 and gp160 of the human
RT   immunodeficiency virus type 1.";
RL   AIDS Res. Hum. Retroviruses 6:371-380(1990).
RN   [3]
RP   REVIEW.
RX   PubMed=12974773; DOI=10.1034/j.1600-0463.2003.11107803.x;
RA   Geijtenbeek T.B., van Kooyk Y.;
RT   "Pathogens target DC-SIGN to influence their fate DC-SIGN functions as a
RT   pathogen receptor with broad specificity.";
RL   APMIS 111:698-714(2003).
RN   [4]
RP   REVIEW.
RX   PubMed=12873764; DOI=10.1016/s0005-2736(03)00161-5;
RA   Gallo S.A., Finnegan C.M., Viard M., Raviv Y., Dimitrov A., Rawat S.S.,
RA   Puri A., Durell S., Blumenthal R.;
RT   "The HIV Env-mediated fusion reaction.";
RL   Biochim. Biophys. Acta 1614:36-50(2003).
RN   [5]
RP   REVIEW.
RX   PubMed=15719026; DOI=10.1038/sj.cdd.4401584;
RA   Perfettini J.-L., Castedo M., Roumier T., Andreau K., Nardacci R.,
RA   Piacentini M., Kroemer G.;
RT   "Mechanisms of apoptosis induction by the HIV-1 envelope.";
RL   Cell Death Differ. 12:916-923(2005).
RN   [6]
RP   REVIEW.
RX   PubMed=15725757; DOI=10.1089/aid.2005.21.171;
RA   Hartley O., Klasse P.J., Sattentau Q.J., Moore J.P.;
RT   "V3: HIV's switch-hitter.";
RL   AIDS Res. Hum. Retroviruses 21:171-189(2005).
RN   [7]
RP   REVIEW.
RX   PubMed=16114975; DOI=10.2165/00003495-200565130-00002;
RA   Reeves J.D., Piefer A.J.;
RT   "Emerging drug targets for antiretroviral therapy.";
RL   Drugs 65:1747-1766(2005).
RN   [8]
RP   REVIEW.
RX   PubMed=16437164; DOI=10.1038/sj.emboj.7600947;
RA   Lusso P.;
RT   "HIV and the chemokine system: 10 years later.";
RL   EMBO J. 25:447-456(2006).
CC   -!- FUNCTION: [Envelope glycoprotein gp160]: Oligomerizes in the host
CC       endoplasmic reticulum into predominantly trimers. In a second time,
CC       gp160 transits in the host Golgi, where glycosylation is completed. The
CC       precursor is then proteolytically cleaved in the trans-Golgi and
CC       thereby activated by cellular furin or furin-like proteases to produce
CC       gp120 and gp41. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- FUNCTION: [Surface protein gp120]: Attaches the virus to the host
CC       lymphoid cell by binding to the primary receptor CD4. This interaction
CC       induces a structural rearrangement creating a high affinity binding
CC       site for a chemokine coreceptor like CXCR4 and/or CCR5. Acts as a
CC       ligand for CD209/DC-SIGN and CLEC4M/DC-SIGNR, which are respectively
CC       found on dendritic cells (DCs), and on endothelial cells of liver
CC       sinusoids and lymph node sinuses. These interactions allow capture of
CC       viral particles at mucosal surfaces by these cells and subsequent
CC       transmission to permissive cells. HIV subverts the migration properties
CC       of dendritic cells to gain access to CD4+ T-cells in lymph nodes. Virus
CC       transmission to permissive T-cells occurs either in trans (without DCs
CC       infection, through viral capture and transmission), or in cis
CC       (following DCs productive infection, through the usual CD4-gp120
CC       interaction), thereby inducing a robust infection. In trans infection,
CC       bound virions remain infectious over days and it is proposed that they
CC       are not degraded, but protected in non-lysosomal acidic organelles
CC       within the DCs close to the cell membrane thus contributing to the
CC       viral infectious potential during DCs' migration from the periphery to
CC       the lymphoid tissues. On arrival at lymphoid tissues, intact virions
CC       recycle back to DCs' cell surface allowing virus transmission to CD4+
CC       T-cells. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- FUNCTION: [Transmembrane protein gp41]: Acts as a class I viral fusion
CC       protein. Under the current model, the protein has at least 3
CC       conformational states: pre-fusion native state, pre-hairpin
CC       intermediate state, and post-fusion hairpin state. During fusion of
CC       viral and target intracellular membranes, the coiled coil regions
CC       (heptad repeats) assume a trimer-of-hairpins structure, positioning the
CC       fusion peptide in close proximity to the C-terminal region of the
CC       ectodomain. The formation of this structure appears to drive apposition
CC       and subsequent fusion of viral and target cell membranes. Complete
CC       fusion occurs in host cell endosomes and is dynamin-dependent, however
CC       some lipid transfer might occur at the plasma membrane. The virus
CC       undergoes clathrin-dependent internalization long before endosomal
CC       fusion, thus minimizing the surface exposure of conserved viral
CC       epitopes during fusion and reducing the efficacy of inhibitors
CC       targeting these epitopes. Membranes fusion leads to delivery of the
CC       nucleocapsid into the cytoplasm. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBUNIT: [Surface protein gp120]: The mature envelope protein (Env)
CC       consists of a homotrimer of non-covalently associated gp120-gp41
CC       heterodimers. The resulting complex protrudes from the virus surface as
CC       a spike. There seems to be as few as 10 spikes on the average virion.
CC       Interacts with host CD4, CCR5 and CXCR4. Gp120 also interacts with the
CC       C-type lectins CD209/DC-SIGN and CLEC4M/DC-SIGNR (collectively referred
CC       to as DC-SIGN(R)). Gp120 and gp41 interact with GalCer. Gp120 interacts
CC       with host ITGA4/ITGB7 complex; on CD4+ T-cells, this interaction
CC       results in rapid activation of integrin ITGAL/LFA-1, which facilitates
CC       efficient cell-to-cell spreading of HIV-1. Gp120 interacts with cell-
CC       associated heparan sulfate; this interaction increases virus
CC       infectivity on permissive cells and may be involved in infection of
CC       CD4- cells. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBUNIT: [Transmembrane protein gp41]: The mature envelope protein
CC       (Env) consists of a homotrimer of non-covalently associated gp120-gp41
CC       heterodimers. The resulting complex protrudes from the virus surface as
CC       a spike. There seems to be as few as 10 spikes on the average virion.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBCELLULAR LOCATION: [Surface protein gp120]: Virion membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Peripheral membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host cell membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Peripheral membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host endosome membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Note=The surface protein is not
CC       anchored to the viral envelope, but associates with the extravirion
CC       surface through its binding to TM. It is probably concentrated at the
CC       site of budding and incorporated into the virions possibly by contacts
CC       between the cytoplasmic tail of Env and the N-terminus of Gag.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBCELLULAR LOCATION: [Transmembrane protein gp41]: Virion membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host cell membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host endosome membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Note=It is probably concentrated at
CC       the site of budding and incorporated into the virions possibly by
CC       contacts between the cytoplasmic tail of Env and the N-terminus of Gag.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: Some of the most genetically diverse regions of the viral
CC       genome are present in Env. They are called variable regions 1 through 5
CC       (V1 through V5). Coreceptor usage of gp120 is determined mainly by the
CC       primary structure of the third variable region (V3) in the outer domain
CC       of gp120. The sequence of V3 determines which coreceptor, CCR5 and/or
CC       CXCR4 (corresponding to R5/macrophage, X4/T cell and R5X4/T cell and
CC       macrophage tropism), is used to trigger the fusion potential of the Env
CC       complex, and hence which cells the virus can infect. Binding to CCR5
CC       involves a region adjacent in addition to V3. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- DOMAIN: The membrane proximal external region (MPER) present in gp41 is
CC       a tryptophan-rich region recognized by the antibodies 2F5, Z13, and
CC       4E10. MPER seems to play a role in fusion. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- DOMAIN: The 17 amino acids long immunosuppressive region is present in
CC       many retroviral envelope proteins. Synthetic peptides derived from this
CC       relatively conserved sequence inhibit immune function in vitro and in
CC       vivo. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: The YXXL motif is involved in determining the exact site of
CC       viral release at the surface of infected mononuclear cells and promotes
CC       endocytosis. YXXL and di-leucine endocytosis motifs interact directly
CC       or indirectly with the clathrin adapter complexes, opperate
CC       independently, and their activities are not additive.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: The CD4-binding region is targeted by the antibody b12.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- PTM: Highly glycosylated by host. The high number of glycan on the
CC       protein is reffered to as 'glycan shield' because it contributes to
CC       hide protein sequence from adaptive immune system. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- PTM: Palmitoylation of the transmembrane protein and of Env polyprotein
CC       (prior to its proteolytic cleavage) is essential for their association
CC       with host cell membrane lipid rafts. Palmitoylation is therefore
CC       required for envelope trafficking to classical lipid rafts, but not for
CC       viral replication. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- PTM: Specific enzymatic cleavages in vivo yield mature proteins.
CC       Envelope glycoproteins are synthesized as an inactive precursor that is
CC       heavily N-glycosylated and processed likely by host cell furin in the
CC       Golgi to yield the mature SU and TM proteins. The cleavage site between
CC       SU and TM requires the minimal sequence [KR]-X-[KR]-R. About 2 of the 9
CC       disulfide bonds of gp41 are reduced by P4HB/PDI, following binding to
CC       CD4 receptor. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- MISCELLANEOUS: Inhibitors targeting HIV-1 viral envelope proteins are
CC       used as antiretroviral drugs. Attachment of virions to the cell surface
CC       via non-specific interactions and CD4 binding can be blocked by
CC       inhibitors that include cyanovirin-N, cyclotriazadisulfonamide analogs,
CC       PRO 2000, TNX 355 and PRO 542. In addition, BMS 806 can block CD4-
CC       induced conformational changes. Env interactions with the coreceptor
CC       molecules can be targeted by CCR5 antagonists including SCH-D,
CC       maraviroc (UK 427857) and aplaviroc (GW 873140), and the CXCR4
CC       antagonist AMD 070. Fusion of viral and cellular membranes can be
CC       inhibited by peptides such as enfuvirtide and tifuvirtide (T 1249).
CC       Resistance to inhibitors associated with mutations in Env are observed.
CC       Most of the time, single mutations confer only a modest reduction in
CC       drug susceptibility. Combination of several mutations is usually
CC       required to develop a high-level drug resistance. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- MISCELLANEOUS: HIV-1 lineages are divided in three main groups, M (for
CC       Major), O (for Outlier), and N (for New, or Non-M, Non-O). The vast
CC       majority of strains found worldwide belong to the group M. Group O
CC       seems to be endemic to and largely confined to Cameroon and neighboring
CC       countries in West Central Africa, where these viruses represent a small
CC       minority of HIV-1 strains. The group N is represented by a limited
CC       number of isolates from Cameroonian persons. The group M is further
CC       subdivided in 9 clades or subtypes (A to D, F to H, J and K).
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SIMILARITY: Belongs to the HIV-1 env protein family.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- WEB RESOURCE: Name=hivdb; Note=HIV drug resistance database;
CC       URL="https://hivdb.stanford.edu";
CC   -!- WEB RESOURCE: Name=HIV drug resistance mutations;
CC       URL="https://www.iasusa.org/content/hiv-drug-resistance-mutations";
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DR   EMBL; AH002346; AAA44311.1; -; Genomic_RNA.
DR   PIR; C25523; VCLJH4.
DR   SMR; P05879; -.
DR   GlyCosmos; P05879; 30 sites, No reported glycans.
DR   Reactome; R-HSA-5621480; Dectin-2 family.
DR   PRO; PR:P05879; -.
DR   GO; GO:0044175; C:host cell endosome membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0016020; C:membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:0019031; C:viral envelope; IEA:UniProtKB-KW.
DR   GO; GO:0055036; C:virion membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005198; F:structural molecule activity; IEA:UniProtKB-UniRule.
DR   GO; GO:0075512; P:clathrin-dependent endocytosis of virus by host cell; IEA:UniProtKB-UniRule.
DR   GO; GO:0039654; P:fusion of virus membrane with host endosome membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:0019064; P:fusion of virus membrane with host plasma membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:1903905; P:positive regulation of establishment of T cell polarity; IEA:UniProtKB-UniRule.
DR   GO; GO:1903908; P:positive regulation of plasma membrane raft polarization; IEA:UniProtKB-UniRule.
DR   GO; GO:1903911; P:positive regulation of receptor clustering; IEA:UniProtKB-UniRule.
DR   GO; GO:0019082; P:viral protein processing; IEA:UniProtKB-UniRule.
DR   GO; GO:0019062; P:virion attachment to host cell; IEA:UniProtKB-UniRule.
DR   GO; GO:0019049; P:virus-mediated perturbation of host defense response; IEA:UniProtKB-UniRule.
DR   CDD; cd09909; HIV-1-like_HR1-HR2; 1.
DR   Gene3D; 1.10.287.210; -; 1.
DR   Gene3D; 2.170.40.20; Human immunodeficiency virus 1, Gp160, envelope glycoprotein; 2.
DR   Gene3D; 1.20.5.490; Single helix bin; 1.
DR   HAMAP; MF_04083; HIV_ENV; 1.
DR   InterPro; IPR036377; Gp120_core_sf.
DR   InterPro; IPR037527; Gp160.
DR   InterPro; IPR000328; GP41-like.
DR   InterPro; IPR000777; HIV1_Gp120.
DR   Pfam; PF00516; GP120; 1.
DR   Pfam; PF00517; GP41; 1.
DR   SUPFAM; SSF56502; gp120 core; 2.
DR   SUPFAM; SSF58069; Virus ectodomain; 1.
PE   1: Evidence at protein level;
KW   AIDS; Apoptosis; Clathrin-mediated endocytosis of virus by host;
KW   Cleavage on pair of basic residues; Coiled coil; Direct protein sequencing;
KW   Disulfide bond; Fusion of virus membrane with host endosomal membrane;
KW   Fusion of virus membrane with host membrane; Glycoprotein;
KW   Host cell membrane; Host endosome; Host membrane; Host-virus interaction;
KW   Lipoprotein; Membrane; Palmitate; Signal; Transmembrane;
KW   Transmembrane helix; Viral attachment to host cell; Viral envelope protein;
KW   Viral immunoevasion; Viral penetration into host cytoplasm; Virion;
KW   Virus endocytosis by host; Virus entry into host cell.
FT   SIGNAL          1..33
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083,
FT                   ECO:0000269|PubMed:2187500"
FT   CHAIN           34..868
FT                   /note="Envelope glycoprotein gp160"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000239475"
FT   CHAIN           34..522
FT                   /note="Surface protein gp120"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000038390"
FT   CHAIN           523..868
FT                   /note="Transmembrane protein gp41"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000038391"
FT   TOPO_DOM        34..696
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   TRANSMEM        697..717
FT                   /note="Helical"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   TOPO_DOM        718..868
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          132..162
FT                   /note="V1"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          163..207
FT                   /note="V2"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          307..340
FT                   /note="V3"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          373..383
FT                   /note="CD4-binding loop"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          394..429
FT                   /note="V4"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          472..482
FT                   /note="V5"
FT   REGION          474..482
FT                   /note="V5"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          523..544
FT                   /note="Fusion peptide"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          586..604
FT                   /note="Immunosuppression"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          674..695
FT                   /note="MPER; binding to GalCer"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          731..755
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COILED          645..679
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   MOTIF           724..727
FT                   /note="YXXL motif; contains endocytosis signal"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   MOTIF           867..868
FT                   /note="Di-leucine internalization motif"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   COMPBIAS        740..755
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   SITE            522..523
FT                   /note="Cleavage; by host furin"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   LIPID           776
FT                   /note="S-palmitoyl cysteine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        89
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        131
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        138
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        139
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        142
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        162
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        166
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        195
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        198
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        208
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        245
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        252
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        273
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        287
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        300
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        306
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        312
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        342
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        349
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        365
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        371
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        395
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        405
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        409
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        459
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        473
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        623
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        628
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        637
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        649
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        55..75
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        120..216
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        127..207
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        132..163
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        229..258
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        239..250
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        307..341
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        387..456
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        394..429
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        610..616
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
SQ   SEQUENCE   868 AA;  98699 MW;  A11527FC52A6F0C8 CRC64;
     MAMRAKGIRK NCQHLWRWGT MLLGMLMICS AAANLWVTVY YGVPVWKEAT TTLFCASDAK
     AYDTEAHNVW ATHACVPTNP NPQEVVLENV TENFNMWKNN MVEQMHEDII SLWDQSLKPC
     VKLTPLCVTL NCTDLNTNNT TNTTELSIIV VWEQRGKGEM RNCSFNITTS IRDKVQREYA
     LFYKLDVEPI DDNKNTTNNT KYRLINCNTS VITQACPKVS FEPIPIHYCT PTGFALLKCN
     DKKFNGTGPC TNVSTVQCTH GIRPVVSTQL LLNGSLAEEE VVIRSENFTN NAKTIIVQLN
     VSVEINCTRP NNHTRKRVTL GPGRVWYTTG EILGNIRQAH CNISRAQWNN TLQQIATTLR
     EQFGNKTIAF NQSSGGDPEI VMHSFNCGGE FFYCNSTQLF NSAWNVTSNG TWSVTRKQKD
     TGDIITLPCR IKQIINRWQV VGKAMYALPI KGLIRCSSNI TGLLLTRDGG GENQTTEIFR
     PGGGDMRDNW RSELYKYKVV KIEPLGVAPT KAKRRVVQRE KRAVGMLGAM FLGFLGAAGS
     TMGATSMALT VQARQLLSGI VQQQNNLLRA IKAQQHLLQL TVWGIKQLQA RILAVERYLK
     DQQLLGFWGC SGKLICTTAV PWNASWSNKT LDQIWNNMTW MEWDREIDNY THLIYTLIEE
     SQNQQEKNQQ ELLQLDKWAS LWTWSDITKW LWYIKIFIMI VGGLIGLRIV FAVLSIVNRV
     RQGYSPLSFQ TLLPNPRGPD RPEGTEEGGG ERGRDGSTRL VHGFLALVWD DLRSLCLFSY
     HRLRDLLLIV ARIVELLGRR GWEVLKYWWN LLQYWSQELK NSAVSLVNVT AIAVAEGTDR
     VIEVVQRIYR AFLHIPRRIR QGFERALL
//
ID   ENV_HV1EL               Reviewed;         853 AA.
AC   P04581;
DT   13-AUG-1987, integrated into UniProtKB/Swiss-Prot.
DT   13-AUG-1987, sequence version 1.
DT   27-MAR-2024, entry version 159.
DE   RecName: Full=Envelope glycoprotein gp160 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   AltName: Full=Env polyprotein {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Contains:
DE     RecName: Full=Surface protein gp120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=SU {ECO:0000255|HAMAP-Rule:MF_04083};
DE     AltName: Full=Glycoprotein 120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=gp120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Contains:
DE     RecName: Full=Transmembrane protein gp41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=TM {ECO:0000255|HAMAP-Rule:MF_04083};
DE     AltName: Full=Glycoprotein 41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=gp41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Flags: Precursor;
GN   Name=env {ECO:0000255|HAMAP-Rule:MF_04083};
OS   Human immunodeficiency virus type 1 group M subtype D (isolate ELI)
OS   (HIV-1).
OC   Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC   Ortervirales; Retroviridae; Orthoretrovirinae; Lentivirus;
OC   Human immunodeficiency virus 1.
OX   NCBI_TaxID=11689;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=2424612; DOI=10.1016/0092-8674(86)90860-3;
RA   Alizon M., Wain-Hobson S., Montagnier L., Sonigo P.;
RT   "Genetic variability of the AIDS virus: nucleotide sequence analysis of two
RT   isolates from African patients.";
RL   Cell 46:63-74(1986).
RN   [2]
RP   REVIEW.
RX   PubMed=12974773; DOI=10.1034/j.1600-0463.2003.11107803.x;
RA   Geijtenbeek T.B., van Kooyk Y.;
RT   "Pathogens target DC-SIGN to influence their fate DC-SIGN functions as a
RT   pathogen receptor with broad specificity.";
RL   APMIS 111:698-714(2003).
RN   [3]
RP   REVIEW.
RX   PubMed=12873764; DOI=10.1016/s0005-2736(03)00161-5;
RA   Gallo S.A., Finnegan C.M., Viard M., Raviv Y., Dimitrov A., Rawat S.S.,
RA   Puri A., Durell S., Blumenthal R.;
RT   "The HIV Env-mediated fusion reaction.";
RL   Biochim. Biophys. Acta 1614:36-50(2003).
RN   [4]
RP   REVIEW.
RX   PubMed=15719026; DOI=10.1038/sj.cdd.4401584;
RA   Perfettini J.-L., Castedo M., Roumier T., Andreau K., Nardacci R.,
RA   Piacentini M., Kroemer G.;
RT   "Mechanisms of apoptosis induction by the HIV-1 envelope.";
RL   Cell Death Differ. 12:916-923(2005).
RN   [5]
RP   REVIEW.
RX   PubMed=15725757; DOI=10.1089/aid.2005.21.171;
RA   Hartley O., Klasse P.J., Sattentau Q.J., Moore J.P.;
RT   "V3: HIV's switch-hitter.";
RL   AIDS Res. Hum. Retroviruses 21:171-189(2005).
RN   [6]
RP   REVIEW.
RX   PubMed=16114975; DOI=10.2165/00003495-200565130-00002;
RA   Reeves J.D., Piefer A.J.;
RT   "Emerging drug targets for antiretroviral therapy.";
RL   Drugs 65:1747-1766(2005).
RN   [7]
RP   REVIEW.
RX   PubMed=16437164; DOI=10.1038/sj.emboj.7600947;
RA   Lusso P.;
RT   "HIV and the chemokine system: 10 years later.";
RL   EMBO J. 25:447-456(2006).
CC   -!- FUNCTION: [Envelope glycoprotein gp160]: Oligomerizes in the host
CC       endoplasmic reticulum into predominantly trimers. In a second time,
CC       gp160 transits in the host Golgi, where glycosylation is completed. The
CC       precursor is then proteolytically cleaved in the trans-Golgi and
CC       thereby activated by cellular furin or furin-like proteases to produce
CC       gp120 and gp41. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- FUNCTION: [Surface protein gp120]: Attaches the virus to the host
CC       lymphoid cell by binding to the primary receptor CD4. This interaction
CC       induces a structural rearrangement creating a high affinity binding
CC       site for a chemokine coreceptor like CXCR4 and/or CCR5. Acts as a
CC       ligand for CD209/DC-SIGN and CLEC4M/DC-SIGNR, which are respectively
CC       found on dendritic cells (DCs), and on endothelial cells of liver
CC       sinusoids and lymph node sinuses. These interactions allow capture of
CC       viral particles at mucosal surfaces by these cells and subsequent
CC       transmission to permissive cells. HIV subverts the migration properties
CC       of dendritic cells to gain access to CD4+ T-cells in lymph nodes. Virus
CC       transmission to permissive T-cells occurs either in trans (without DCs
CC       infection, through viral capture and transmission), or in cis
CC       (following DCs productive infection, through the usual CD4-gp120
CC       interaction), thereby inducing a robust infection. In trans infection,
CC       bound virions remain infectious over days and it is proposed that they
CC       are not degraded, but protected in non-lysosomal acidic organelles
CC       within the DCs close to the cell membrane thus contributing to the
CC       viral infectious potential during DCs' migration from the periphery to
CC       the lymphoid tissues. On arrival at lymphoid tissues, intact virions
CC       recycle back to DCs' cell surface allowing virus transmission to CD4+
CC       T-cells. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- FUNCTION: [Transmembrane protein gp41]: Acts as a class I viral fusion
CC       protein. Under the current model, the protein has at least 3
CC       conformational states: pre-fusion native state, pre-hairpin
CC       intermediate state, and post-fusion hairpin state. During fusion of
CC       viral and target intracellular membranes, the coiled coil regions
CC       (heptad repeats) assume a trimer-of-hairpins structure, positioning the
CC       fusion peptide in close proximity to the C-terminal region of the
CC       ectodomain. The formation of this structure appears to drive apposition
CC       and subsequent fusion of viral and target cell membranes. Complete
CC       fusion occurs in host cell endosomes and is dynamin-dependent, however
CC       some lipid transfer might occur at the plasma membrane. The virus
CC       undergoes clathrin-dependent internalization long before endosomal
CC       fusion, thus minimizing the surface exposure of conserved viral
CC       epitopes during fusion and reducing the efficacy of inhibitors
CC       targeting these epitopes. Membranes fusion leads to delivery of the
CC       nucleocapsid into the cytoplasm. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBUNIT: [Surface protein gp120]: The mature envelope protein (Env)
CC       consists of a homotrimer of non-covalently associated gp120-gp41
CC       heterodimers. The resulting complex protrudes from the virus surface as
CC       a spike. There seems to be as few as 10 spikes on the average virion.
CC       Interacts with host CD4, CCR5 and CXCR4. Gp120 also interacts with the
CC       C-type lectins CD209/DC-SIGN and CLEC4M/DC-SIGNR (collectively referred
CC       to as DC-SIGN(R)). Gp120 and gp41 interact with GalCer. Gp120 interacts
CC       with host ITGA4/ITGB7 complex; on CD4+ T-cells, this interaction
CC       results in rapid activation of integrin ITGAL/LFA-1, which facilitates
CC       efficient cell-to-cell spreading of HIV-1. Gp120 interacts with cell-
CC       associated heparan sulfate; this interaction increases virus
CC       infectivity on permissive cells and may be involved in infection of
CC       CD4- cells. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBUNIT: [Transmembrane protein gp41]: The mature envelope protein
CC       (Env) consists of a homotrimer of non-covalently associated gp120-gp41
CC       heterodimers. The resulting complex protrudes from the virus surface as
CC       a spike. There seems to be as few as 10 spikes on the average virion.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBCELLULAR LOCATION: [Surface protein gp120]: Virion membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Peripheral membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host cell membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Peripheral membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host endosome membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Note=The surface protein is not
CC       anchored to the viral envelope, but associates with the extravirion
CC       surface through its binding to TM. It is probably concentrated at the
CC       site of budding and incorporated into the virions possibly by contacts
CC       between the cytoplasmic tail of Env and the N-terminus of Gag.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBCELLULAR LOCATION: [Transmembrane protein gp41]: Virion membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host cell membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host endosome membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Note=It is probably concentrated at
CC       the site of budding and incorporated into the virions possibly by
CC       contacts between the cytoplasmic tail of Env and the N-terminus of Gag.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: Some of the most genetically diverse regions of the viral
CC       genome are present in Env. They are called variable regions 1 through 5
CC       (V1 through V5). Coreceptor usage of gp120 is determined mainly by the
CC       primary structure of the third variable region (V3) in the outer domain
CC       of gp120. The sequence of V3 determines which coreceptor, CCR5 and/or
CC       CXCR4 (corresponding to R5/macrophage, X4/T cell and R5X4/T cell and
CC       macrophage tropism), is used to trigger the fusion potential of the Env
CC       complex, and hence which cells the virus can infect. Binding to CCR5
CC       involves a region adjacent in addition to V3. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- DOMAIN: The membrane proximal external region (MPER) present in gp41 is
CC       a tryptophan-rich region recognized by the antibodies 2F5, Z13, and
CC       4E10. MPER seems to play a role in fusion. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- DOMAIN: The 17 amino acids long immunosuppressive region is present in
CC       many retroviral envelope proteins. Synthetic peptides derived from this
CC       relatively conserved sequence inhibit immune function in vitro and in
CC       vivo. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: The YXXL motif is involved in determining the exact site of
CC       viral release at the surface of infected mononuclear cells and promotes
CC       endocytosis. YXXL and di-leucine endocytosis motifs interact directly
CC       or indirectly with the clathrin adapter complexes, opperate
CC       independently, and their activities are not additive.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: The CD4-binding region is targeted by the antibody b12.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- PTM: Highly glycosylated by host. The high number of glycan on the
CC       protein is reffered to as 'glycan shield' because it contributes to
CC       hide protein sequence from adaptive immune system. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- PTM: Palmitoylation of the transmembrane protein and of Env polyprotein
CC       (prior to its proteolytic cleavage) is essential for their association
CC       with host cell membrane lipid rafts. Palmitoylation is therefore
CC       required for envelope trafficking to classical lipid rafts, but not for
CC       viral replication. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- PTM: Specific enzymatic cleavages in vivo yield mature proteins.
CC       Envelope glycoproteins are synthesized as an inactive precursor that is
CC       heavily N-glycosylated and processed likely by host cell furin in the
CC       Golgi to yield the mature SU and TM proteins. The cleavage site between
CC       SU and TM requires the minimal sequence [KR]-X-[KR]-R. About 2 of the 9
CC       disulfide bonds of gp41 are reduced by P4HB/PDI, following binding to
CC       CD4 receptor. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- MISCELLANEOUS: Inhibitors targeting HIV-1 viral envelope proteins are
CC       used as antiretroviral drugs. Attachment of virions to the cell surface
CC       via non-specific interactions and CD4 binding can be blocked by
CC       inhibitors that include cyanovirin-N, cyclotriazadisulfonamide analogs,
CC       PRO 2000, TNX 355 and PRO 542. In addition, BMS 806 can block CD4-
CC       induced conformational changes. Env interactions with the coreceptor
CC       molecules can be targeted by CCR5 antagonists including SCH-D,
CC       maraviroc (UK 427857) and aplaviroc (GW 873140), and the CXCR4
CC       antagonist AMD 070. Fusion of viral and cellular membranes can be
CC       inhibited by peptides such as enfuvirtide and tifuvirtide (T 1249).
CC       Resistance to inhibitors associated with mutations in Env are observed.
CC       Most of the time, single mutations confer only a modest reduction in
CC       drug susceptibility. Combination of several mutations is usually
CC       required to develop a high-level drug resistance. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- MISCELLANEOUS: HIV-1 lineages are divided in three main groups, M (for
CC       Major), O (for Outlier), and N (for New, or Non-M, Non-O). The vast
CC       majority of strains found worldwide belong to the group M. Group O
CC       seems to be endemic to and largely confined to Cameroon and neighboring
CC       countries in West Central Africa, where these viruses represent a small
CC       minority of HIV-1 strains. The group N is represented by a limited
CC       number of isolates from Cameroonian persons. The group M is further
CC       subdivided in 9 clades or subtypes (A to D, F to H, J and K).
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SIMILARITY: Belongs to the HIV-1 env protein family.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- WEB RESOURCE: Name=hivdb; Note=HIV drug resistance database;
CC       URL="https://hivdb.stanford.edu";
CC   -!- WEB RESOURCE: Name=HIV drug resistance mutations;
CC       URL="https://www.iasusa.org/content/hiv-drug-resistance-mutations";
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DR   EMBL; K03454; AAA44329.1; -; Genomic_DNA.
DR   SMR; P04581; -.
DR   GlyCosmos; P04581; 31 sites, No reported glycans.
DR   Reactome; R-HSA-5621480; Dectin-2 family.
DR   Proteomes; UP000007693; Segment.
DR   GO; GO:0044175; C:host cell endosome membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0016020; C:membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:0019031; C:viral envelope; IEA:UniProtKB-KW.
DR   GO; GO:0055036; C:virion membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005198; F:structural molecule activity; IEA:UniProtKB-UniRule.
DR   GO; GO:0075512; P:clathrin-dependent endocytosis of virus by host cell; IEA:UniProtKB-UniRule.
DR   GO; GO:0039654; P:fusion of virus membrane with host endosome membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:0019064; P:fusion of virus membrane with host plasma membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:1903905; P:positive regulation of establishment of T cell polarity; IEA:UniProtKB-UniRule.
DR   GO; GO:1903908; P:positive regulation of plasma membrane raft polarization; IEA:UniProtKB-UniRule.
DR   GO; GO:1903911; P:positive regulation of receptor clustering; IEA:UniProtKB-UniRule.
DR   GO; GO:0019082; P:viral protein processing; IEA:UniProtKB-UniRule.
DR   GO; GO:0019062; P:virion attachment to host cell; IEA:UniProtKB-UniRule.
DR   GO; GO:0019049; P:virus-mediated perturbation of host defense response; IEA:UniProtKB-UniRule.
DR   CDD; cd09909; HIV-1-like_HR1-HR2; 1.
DR   Gene3D; 1.10.287.210; -; 1.
DR   Gene3D; 2.170.40.20; Human immunodeficiency virus 1, Gp160, envelope glycoprotein; 2.
DR   Gene3D; 1.20.5.490; Single helix bin; 1.
DR   HAMAP; MF_04083; HIV_ENV; 1.
DR   InterPro; IPR036377; Gp120_core_sf.
DR   InterPro; IPR037527; Gp160.
DR   InterPro; IPR000328; GP41-like.
DR   InterPro; IPR000777; HIV1_Gp120.
DR   Pfam; PF00516; GP120; 2.
DR   Pfam; PF00517; GP41; 1.
DR   SUPFAM; SSF56502; gp120 core; 2.
DR   SUPFAM; SSF58069; Virus ectodomain; 1.
PE   3: Inferred from homology;
KW   AIDS; Apoptosis; Clathrin-mediated endocytosis of virus by host;
KW   Cleavage on pair of basic residues; Coiled coil; Disulfide bond;
KW   Fusion of virus membrane with host endosomal membrane;
KW   Fusion of virus membrane with host membrane; Glycoprotein;
KW   Host cell membrane; Host endosome; Host membrane; Host-virus interaction;
KW   Lipoprotein; Membrane; Palmitate; Reference proteome; Signal;
KW   Transmembrane; Transmembrane helix; Viral attachment to host cell;
KW   Viral envelope protein; Viral immunoevasion;
KW   Viral penetration into host cytoplasm; Virion; Virus endocytosis by host;
KW   Virus entry into host cell.
FT   SIGNAL          1..31
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CHAIN           32..853
FT                   /note="Envelope glycoprotein gp160"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000239477"
FT   CHAIN           32..508
FT                   /note="Surface protein gp120"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000038394"
FT   CHAIN           509..853
FT                   /note="Transmembrane protein gp41"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000038395"
FT   TOPO_DOM        32..681
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   TRANSMEM        682..702
FT                   /note="Helical"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   TOPO_DOM        703..853
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          130..153
FT                   /note="V1"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          154..197
FT                   /note="V2"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          297..329
FT                   /note="V3"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          362..372
FT                   /note="CD4-binding loop"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          383..416
FT                   /note="V4"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          457..468
FT                   /note="V5"
FT   REGION          460..468
FT                   /note="V5"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          509..529
FT                   /note="Fusion peptide"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          571..589
FT                   /note="Immunosuppression"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          659..680
FT                   /note="MPER; binding to GalCer"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          716..738
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COILED          630..664
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   MOTIF           709..712
FT                   /note="YXXL motif; contains endocytosis signal"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   MOTIF           852..853
FT                   /note="Di-leucine internalization motif"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   SITE            508..509
FT                   /note="Cleavage; by host furin"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   LIPID           761
FT                   /note="S-palmitoyl cysteine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   LIPID           834
FT                   /note="S-palmitoyl cysteine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        87
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        129
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        137
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        143
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        153
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        157
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        183
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        188
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        198
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        235
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        242
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        263
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        277
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        290
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        331
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        353
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        384
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        390
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        394
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        400
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        405
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        406
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        411
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        445
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        458
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        459
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        462
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        608
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        613
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        622
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        634
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        53..73
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        118..206
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        125..197
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        130..154
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        219..248
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        229..240
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        297..330
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        376..442
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        383..416
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        595..601
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
SQ   SEQUENCE   853 AA;  96721 MW;  F9CD864DAA0D07A5 CRC64;
     MRARGIERNC QNWWKWGIML LGILMTCSAA DNLWVTVYYG VPVWKEATTT LFCASDAKSY
     ETEAHNIWAT HACVPTDPNP QEIALENVTE NFNMWKNNMV EQMHEDIISL WDQSLKPCVK
     LTPLCVTLNC SDELRNNGTM GNNVTTEEKG MKNCSFNVTT VLKDKKQQVY ALFYRLDIVP
     IDNDSSTNST NYRLINCNTS AITQACPKVS FEPIPIHYCA PAGFAILKCR DKKFNGTGPC
     TNVSTVQCTH GIRPVVSTQL LLNGSLAEEE VIIRSENLTN NAKNIIAHLN ESVKITCARP
     YQNTRQRTPI GLGQSLYTTR SRSIIGQAHC NISRAQWSKT LQQVARKLGT LLNKTIIKFK
     PSSGGDPEIT THSFNCGGEF FYCNTSGLFN STWNISAWNN ITESNNSTNT NITLQCRIKQ
     IIKMVAGRKA IYAPPIERNI LCSSNITGLL LTRDGGINNS TNETFRPGGG DMRDNWRSEL
     YKYKVVQIEP LGVAPTRAKR RVVEREKRAI GLGAMFLGFL GAAGSTMGAR SVTLTVQARQ
     LMSGIVQQQN NLLRAIEAQQ HLLQLTVWGI KQLQARILAV ERYLKDQQLL GIWGCSGKHI
     CTTNVPWNSS WSNRSLNEIW QNMTWMEWER EIDNYTGLIY SLIEESQTQQ EKNEKELLEL
     DKWASLWNWF SITQWLWYIK IFIMIIGGLI GLRIVFAVLS LVNRVRQGYS PLSFQTLLPA
     PRGPDRPEGT EEEGGERGRD RSVRLLNGFS ALIWDDLRSL CLFSYHRLRD LILIAVRIVE
     LLGRRGWDIL KYLWNLLQYW SQELRNSASS LFDAIAIAVA EGTDRVIEII QRACRAVLNI
     PRRIRQGLER SLL
//
ID   ENV_HV1ET               Reviewed;         851 AA.
AC   Q75008;
DT   27-JUN-2006, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1996, sequence version 1.
DT   27-MAR-2024, entry version 131.
DE   RecName: Full=Envelope glycoprotein gp160 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   AltName: Full=Env polyprotein {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Contains:
DE     RecName: Full=Surface protein gp120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=SU {ECO:0000255|HAMAP-Rule:MF_04083};
DE     AltName: Full=Glycoprotein 120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=gp120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Contains:
DE     RecName: Full=Transmembrane protein gp41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=TM {ECO:0000255|HAMAP-Rule:MF_04083};
DE     AltName: Full=Glycoprotein 41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=gp41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Flags: Precursor;
GN   Name=env {ECO:0000255|HAMAP-Rule:MF_04083};
OS   Human immunodeficiency virus type 1 group M subtype C (isolate ETH2220)
OS   (HIV-1).
OC   Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC   Ortervirales; Retroviridae; Orthoretrovirinae; Lentivirus;
OC   Human immunodeficiency virus 1.
OX   NCBI_TaxID=388796;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=8891112; DOI=10.1089/aid.1996.12.1329;
RA   Salminen M.O., Johansson B., Sonnerborg A., Ayehunie S., Gotte D.,
RA   Leinikki P., Burke D.S., McCutchan F.E.;
RT   "Full-length sequence of an ethiopian human immunodeficiency virus type 1
RT   (HIV-1) isolate of genetic subtype C.";
RL   AIDS Res. Hum. Retroviruses 12:1329-1339(1996).
RN   [2]
RP   REVIEW.
RX   PubMed=12974773; DOI=10.1034/j.1600-0463.2003.11107803.x;
RA   Geijtenbeek T.B., van Kooyk Y.;
RT   "Pathogens target DC-SIGN to influence their fate DC-SIGN functions as a
RT   pathogen receptor with broad specificity.";
RL   APMIS 111:698-714(2003).
RN   [3]
RP   REVIEW.
RX   PubMed=12873764; DOI=10.1016/s0005-2736(03)00161-5;
RA   Gallo S.A., Finnegan C.M., Viard M., Raviv Y., Dimitrov A., Rawat S.S.,
RA   Puri A., Durell S., Blumenthal R.;
RT   "The HIV Env-mediated fusion reaction.";
RL   Biochim. Biophys. Acta 1614:36-50(2003).
RN   [4]
RP   REVIEW.
RX   PubMed=15719026; DOI=10.1038/sj.cdd.4401584;
RA   Perfettini J.-L., Castedo M., Roumier T., Andreau K., Nardacci R.,
RA   Piacentini M., Kroemer G.;
RT   "Mechanisms of apoptosis induction by the HIV-1 envelope.";
RL   Cell Death Differ. 12:916-923(2005).
RN   [5]
RP   REVIEW.
RX   PubMed=15725757; DOI=10.1089/aid.2005.21.171;
RA   Hartley O., Klasse P.J., Sattentau Q.J., Moore J.P.;
RT   "V3: HIV's switch-hitter.";
RL   AIDS Res. Hum. Retroviruses 21:171-189(2005).
RN   [6]
RP   REVIEW.
RX   PubMed=16114975; DOI=10.2165/00003495-200565130-00002;
RA   Reeves J.D., Piefer A.J.;
RT   "Emerging drug targets for antiretroviral therapy.";
RL   Drugs 65:1747-1766(2005).
RN   [7]
RP   REVIEW.
RX   PubMed=16437164; DOI=10.1038/sj.emboj.7600947;
RA   Lusso P.;
RT   "HIV and the chemokine system: 10 years later.";
RL   EMBO J. 25:447-456(2006).
CC   -!- FUNCTION: [Envelope glycoprotein gp160]: Oligomerizes in the host
CC       endoplasmic reticulum into predominantly trimers. In a second time,
CC       gp160 transits in the host Golgi, where glycosylation is completed. The
CC       precursor is then proteolytically cleaved in the trans-Golgi and
CC       thereby activated by cellular furin or furin-like proteases to produce
CC       gp120 and gp41. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- FUNCTION: [Surface protein gp120]: Attaches the virus to the host
CC       lymphoid cell by binding to the primary receptor CD4. This interaction
CC       induces a structural rearrangement creating a high affinity binding
CC       site for a chemokine coreceptor like CXCR4 and/or CCR5. Acts as a
CC       ligand for CD209/DC-SIGN and CLEC4M/DC-SIGNR, which are respectively
CC       found on dendritic cells (DCs), and on endothelial cells of liver
CC       sinusoids and lymph node sinuses. These interactions allow capture of
CC       viral particles at mucosal surfaces by these cells and subsequent
CC       transmission to permissive cells. HIV subverts the migration properties
CC       of dendritic cells to gain access to CD4+ T-cells in lymph nodes. Virus
CC       transmission to permissive T-cells occurs either in trans (without DCs
CC       infection, through viral capture and transmission), or in cis
CC       (following DCs productive infection, through the usual CD4-gp120
CC       interaction), thereby inducing a robust infection. In trans infection,
CC       bound virions remain infectious over days and it is proposed that they
CC       are not degraded, but protected in non-lysosomal acidic organelles
CC       within the DCs close to the cell membrane thus contributing to the
CC       viral infectious potential during DCs' migration from the periphery to
CC       the lymphoid tissues. On arrival at lymphoid tissues, intact virions
CC       recycle back to DCs' cell surface allowing virus transmission to CD4+
CC       T-cells. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- FUNCTION: [Transmembrane protein gp41]: Acts as a class I viral fusion
CC       protein. Under the current model, the protein has at least 3
CC       conformational states: pre-fusion native state, pre-hairpin
CC       intermediate state, and post-fusion hairpin state. During fusion of
CC       viral and target intracellular membranes, the coiled coil regions
CC       (heptad repeats) assume a trimer-of-hairpins structure, positioning the
CC       fusion peptide in close proximity to the C-terminal region of the
CC       ectodomain. The formation of this structure appears to drive apposition
CC       and subsequent fusion of viral and target cell membranes. Complete
CC       fusion occurs in host cell endosomes and is dynamin-dependent, however
CC       some lipid transfer might occur at the plasma membrane. The virus
CC       undergoes clathrin-dependent internalization long before endosomal
CC       fusion, thus minimizing the surface exposure of conserved viral
CC       epitopes during fusion and reducing the efficacy of inhibitors
CC       targeting these epitopes. Membranes fusion leads to delivery of the
CC       nucleocapsid into the cytoplasm. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBUNIT: [Surface protein gp120]: The mature envelope protein (Env)
CC       consists of a homotrimer of non-covalently associated gp120-gp41
CC       heterodimers. The resulting complex protrudes from the virus surface as
CC       a spike. There seems to be as few as 10 spikes on the average virion.
CC       Interacts with host CD4, CCR5 and CXCR4. Gp120 also interacts with the
CC       C-type lectins CD209/DC-SIGN and CLEC4M/DC-SIGNR (collectively referred
CC       to as DC-SIGN(R)). Gp120 and gp41 interact with GalCer. Gp120 interacts
CC       with host ITGA4/ITGB7 complex; on CD4+ T-cells, this interaction
CC       results in rapid activation of integrin ITGAL/LFA-1, which facilitates
CC       efficient cell-to-cell spreading of HIV-1. Gp120 interacts with cell-
CC       associated heparan sulfate; this interaction increases virus
CC       infectivity on permissive cells and may be involved in infection of
CC       CD4- cells. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBUNIT: [Transmembrane protein gp41]: The mature envelope protein
CC       (Env) consists of a homotrimer of non-covalently associated gp120-gp41
CC       heterodimers. The resulting complex protrudes from the virus surface as
CC       a spike. There seems to be as few as 10 spikes on the average virion.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBCELLULAR LOCATION: [Surface protein gp120]: Virion membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Peripheral membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host cell membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Peripheral membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host endosome membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Note=The surface protein is not
CC       anchored to the viral envelope, but associates with the extravirion
CC       surface through its binding to TM. It is probably concentrated at the
CC       site of budding and incorporated into the virions possibly by contacts
CC       between the cytoplasmic tail of Env and the N-terminus of Gag.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBCELLULAR LOCATION: [Transmembrane protein gp41]: Virion membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host cell membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host endosome membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Note=It is probably concentrated at
CC       the site of budding and incorporated into the virions possibly by
CC       contacts between the cytoplasmic tail of Env and the N-terminus of Gag.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: Some of the most genetically diverse regions of the viral
CC       genome are present in Env. They are called variable regions 1 through 5
CC       (V1 through V5). Coreceptor usage of gp120 is determined mainly by the
CC       primary structure of the third variable region (V3) in the outer domain
CC       of gp120. The sequence of V3 determines which coreceptor, CCR5 and/or
CC       CXCR4 (corresponding to R5/macrophage, X4/T cell and R5X4/T cell and
CC       macrophage tropism), is used to trigger the fusion potential of the Env
CC       complex, and hence which cells the virus can infect. Binding to CCR5
CC       involves a region adjacent in addition to V3. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- DOMAIN: The membrane proximal external region (MPER) present in gp41 is
CC       a tryptophan-rich region recognized by the antibodies 2F5, Z13, and
CC       4E10. MPER seems to play a role in fusion. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- DOMAIN: The 17 amino acids long immunosuppressive region is present in
CC       many retroviral envelope proteins. Synthetic peptides derived from this
CC       relatively conserved sequence inhibit immune function in vitro and in
CC       vivo. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: The YXXL motif is involved in determining the exact site of
CC       viral release at the surface of infected mononuclear cells and promotes
CC       endocytosis. YXXL and di-leucine endocytosis motifs interact directly
CC       or indirectly with the clathrin adapter complexes, opperate
CC       independently, and their activities are not additive.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: The CD4-binding region is targeted by the antibody b12.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- PTM: Highly glycosylated by host. The high number of glycan on the
CC       protein is reffered to as 'glycan shield' because it contributes to
CC       hide protein sequence from adaptive immune system. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- PTM: Palmitoylation of the transmembrane protein and of Env polyprotein
CC       (prior to its proteolytic cleavage) is essential for their association
CC       with host cell membrane lipid rafts. Palmitoylation is therefore
CC       required for envelope trafficking to classical lipid rafts, but not for
CC       viral replication. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- PTM: Specific enzymatic cleavages in vivo yield mature proteins.
CC       Envelope glycoproteins are synthesized as an inactive precursor that is
CC       heavily N-glycosylated and processed likely by host cell furin in the
CC       Golgi to yield the mature SU and TM proteins. The cleavage site between
CC       SU and TM requires the minimal sequence [KR]-X-[KR]-R. About 2 of the 9
CC       disulfide bonds of gp41 are reduced by P4HB/PDI, following binding to
CC       CD4 receptor. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- MISCELLANEOUS: Inhibitors targeting HIV-1 viral envelope proteins are
CC       used as antiretroviral drugs. Attachment of virions to the cell surface
CC       via non-specific interactions and CD4 binding can be blocked by
CC       inhibitors that include cyanovirin-N, cyclotriazadisulfonamide analogs,
CC       PRO 2000, TNX 355 and PRO 542. In addition, BMS 806 can block CD4-
CC       induced conformational changes. Env interactions with the coreceptor
CC       molecules can be targeted by CCR5 antagonists including SCH-D,
CC       maraviroc (UK 427857) and aplaviroc (GW 873140), and the CXCR4
CC       antagonist AMD 070. Fusion of viral and cellular membranes can be
CC       inhibited by peptides such as enfuvirtide and tifuvirtide (T 1249).
CC       Resistance to inhibitors associated with mutations in Env are observed.
CC       Most of the time, single mutations confer only a modest reduction in
CC       drug susceptibility. Combination of several mutations is usually
CC       required to develop a high-level drug resistance. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- MISCELLANEOUS: HIV-1 lineages are divided in three main groups, M (for
CC       Major), O (for Outlier), and N (for New, or Non-M, Non-O). The vast
CC       majority of strains found worldwide belong to the group M. Group O
CC       seems to be endemic to and largely confined to Cameroon and neighboring
CC       countries in West Central Africa, where these viruses represent a small
CC       minority of HIV-1 strains. The group N is represented by a limited
CC       number of isolates from Cameroonian persons. The group M is further
CC       subdivided in 9 clades or subtypes (A to D, F to H, J and K).
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SIMILARITY: Belongs to the HIV-1 env protein family.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- WEB RESOURCE: Name=hivdb; Note=HIV drug resistance database;
CC       URL="https://hivdb.stanford.edu";
CC   -!- WEB RESOURCE: Name=HIV drug resistance mutations;
CC       URL="https://www.iasusa.org/content/hiv-drug-resistance-mutations";
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DR   EMBL; U46016; AAB36507.1; -; Genomic_DNA.
DR   SMR; Q75008; -.
DR   GlyCosmos; Q75008; 25 sites, No reported glycans.
DR   Proteomes; UP000007694; Segment.
DR   GO; GO:0044175; C:host cell endosome membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0016020; C:membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:0019031; C:viral envelope; IEA:UniProtKB-KW.
DR   GO; GO:0055036; C:virion membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005198; F:structural molecule activity; IEA:UniProtKB-UniRule.
DR   GO; GO:0075512; P:clathrin-dependent endocytosis of virus by host cell; IEA:UniProtKB-UniRule.
DR   GO; GO:0039654; P:fusion of virus membrane with host endosome membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:0019064; P:fusion of virus membrane with host plasma membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:1903905; P:positive regulation of establishment of T cell polarity; IEA:UniProtKB-UniRule.
DR   GO; GO:1903908; P:positive regulation of plasma membrane raft polarization; IEA:UniProtKB-UniRule.
DR   GO; GO:1903911; P:positive regulation of receptor clustering; IEA:UniProtKB-UniRule.
DR   GO; GO:0019082; P:viral protein processing; IEA:UniProtKB-UniRule.
DR   GO; GO:0019062; P:virion attachment to host cell; IEA:UniProtKB-UniRule.
DR   GO; GO:0019049; P:virus-mediated perturbation of host defense response; IEA:UniProtKB-UniRule.
DR   CDD; cd09909; HIV-1-like_HR1-HR2; 1.
DR   Gene3D; 1.10.287.210; -; 1.
DR   Gene3D; 2.170.40.20; Human immunodeficiency virus 1, Gp160, envelope glycoprotein; 2.
DR   Gene3D; 1.20.5.490; Single helix bin; 1.
DR   HAMAP; MF_04083; HIV_ENV; 1.
DR   InterPro; IPR036377; Gp120_core_sf.
DR   InterPro; IPR037527; Gp160.
DR   InterPro; IPR000328; GP41-like.
DR   InterPro; IPR000777; HIV1_Gp120.
DR   Pfam; PF00516; GP120; 2.
DR   Pfam; PF00517; GP41; 1.
DR   SUPFAM; SSF56502; gp120 core; 2.
DR   SUPFAM; SSF58069; Virus ectodomain; 1.
PE   3: Inferred from homology;
KW   AIDS; Apoptosis; Clathrin-mediated endocytosis of virus by host;
KW   Cleavage on pair of basic residues; Coiled coil; Disulfide bond;
KW   Fusion of virus membrane with host endosomal membrane;
KW   Fusion of virus membrane with host membrane; Glycoprotein;
KW   Host cell membrane; Host endosome; Host membrane; Host-virus interaction;
KW   Lipoprotein; Membrane; Palmitate; Signal; Transmembrane;
KW   Transmembrane helix; Viral attachment to host cell; Viral envelope protein;
KW   Viral immunoevasion; Viral penetration into host cytoplasm; Virion;
KW   Virus endocytosis by host; Virus entry into host cell.
FT   SIGNAL          1..31
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CHAIN           32..851
FT                   /note="Envelope glycoprotein gp160"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000244672"
FT   CHAIN           32..500
FT                   /note="Surface protein gp120"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000244673"
FT   CHAIN           501..851
FT                   /note="Transmembrane protein gp41"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000244674"
FT   TOPO_DOM        32..672
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   TRANSMEM        673..693
FT                   /note="Helical"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   TOPO_DOM        694..851
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          130..153
FT                   /note="V1"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          154..193
FT                   /note="V2"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          293..326
FT                   /note="V3"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          359..369
FT                   /note="CD4-binding loop"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          380..406
FT                   /note="V4"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          449..460
FT                   /note="V5"
FT   REGION          451..460
FT                   /note="V5"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          501..520
FT                   /note="Fusion peptide"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          562..580
FT                   /note="Immunosuppression"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          650..671
FT                   /note="MPER; binding to GalCer"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   COILED          621..655
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   MOTIF           700..703
FT                   /note="YXXL motif; contains endocytosis signal"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   SITE            500..501
FT                   /note="Cleavage; by host furin"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   LIPID           752
FT                   /note="S-palmitoyl cysteine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        87
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        135
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        141
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        153
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        157
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        183
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        194
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        238
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        259
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        273
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        286
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        298
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        328
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        335
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        351
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        381
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        387
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        395
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        401
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        436
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        599
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        604
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        613
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        625
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        662
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        53..73
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        118..202
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        125..193
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        130..154
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        215..244
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        225..236
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        293..327
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        373..433
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        380..406
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        586..592
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
SQ   SEQUENCE   851 AA;  96621 MW;  B813D6B431530569 CRC64;
     MKVMGIQRNC QQWWIWGILG FWMLMICNGM GNLWVTVYYG VPVWKDASPT LFCASDAKAY
     DTEVHNVWGT FACVPTDPSP QELGLENVTE NFNMWKNDMV EQMHQDIISL WDQGLKPCVK
     LTPLCVTLNC NAIKNNTKVT NNSINSANDE MKNCSFNITT ELRDKKRKAY ALFYKLDIVP
     LNNGSTDYRL INCNTSTITQ ACPKVSLDPI PIHYCAPAGY AILKCRDKTF TGTGPCHNVS
     TVQCTHGIKP VVSTQLLLNG SIAEGETIIR FENLTNNAKI IIVQLNESVE ITCTRPSNNT
     RESIRIGPGQ TFYATGDIIG DIRQAHCNIS EEKWNKTLQK VKEKLQKHFP NKTIEFKPSS
     GGDLEITTHS FNCGGEFFYC NTSNLFNSTK LELFNSSTNL NITLQCRIKQ IINMWQGVGR
     AMYAPPIEGI IMCRSNITGL LLTRDGAKEP HSTKEIFRPE GGDMRDNWRS ELYKYKVVEI
     KPLGVAPTKP KRRVVEREKR AALGALFLGF LGAAGSTMGA ASITLTVQAR QLLSGIVQQQ
     SNLLKAIEAQ QHMLQLTVWG IKQLQTRVLA IERHLRDQQL LGIWGCSGKL ICTTAVPWNS
     SWSNKSQEEI WDNMTWMQWD REISNYTDII YNLLEVSQNQ QDKNEKDLLA LDKWENLWNW
     FNITNWLWYI KIFIMIVGGV IGLRIIFAVL SIVNRVRQGY SPLSFQTLIP HPRGPDRLGG
     IEEEGGEQGR DRSIRLVNGF LAIFWDDLRS LCLFSYHRLR DLILIAARTV ELLGRSSLKG
     LQRGWETLKY LGSLVQYWGL ELKKSAINLL NTTAIVVGEG TDRFIELIQR IWRAFCNIPR
     RIRQGLEAAL Q
//
ID   ENV_HV1H2               Reviewed;         856 AA.
AC   P04578; O09779;
DT   13-AUG-1987, integrated into UniProtKB/Swiss-Prot.
DT   15-JUL-1999, sequence version 2.
DT   27-MAR-2024, entry version 205.
DE   RecName: Full=Envelope glycoprotein gp160 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   AltName: Full=Env polyprotein {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Contains:
DE     RecName: Full=Surface protein gp120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=SU {ECO:0000255|HAMAP-Rule:MF_04083};
DE     AltName: Full=Glycoprotein 120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=gp120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Contains:
DE     RecName: Full=Transmembrane protein gp41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=TM {ECO:0000255|HAMAP-Rule:MF_04083};
DE     AltName: Full=Glycoprotein 41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=gp41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Flags: Precursor;
GN   Name=env {ECO:0000255|HAMAP-Rule:MF_04083};
OS   Human immunodeficiency virus type 1 group M subtype B (isolate HXB2)
OS   (HIV-1).
OC   Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC   Ortervirales; Retroviridae; Orthoretrovirinae; Lentivirus;
OC   Human immunodeficiency virus 1.
OX   NCBI_TaxID=11706;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX   PubMed=3040055; DOI=10.1089/aid.1987.3.57;
RA   Ratner L., Fisher A., Jagodzinski L.L., Mitsuya H., Liou R.-S., Gallo R.C.,
RA   Wong-Staal F.;
RT   "Complete nucleotide sequences of functional clones of the AIDS virus.";
RL   AIDS Res. Hum. Retroviruses 3:57-69(1987).
RN   [2]
RP   SEQUENCE REVISION.
RA   Ratner L., Fisher A., Jagodzinski L.L., Mitsuya H., Liou R.-S., Gallo R.C.,
RA   Wong-Staal F.;
RL   Submitted (APR-1997) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   FUNCTION (ENVELOPE GLYCOPROTEIN GP160).
RX   PubMed=2450679; DOI=10.1016/0092-8674(88)90487-4;
RA   McCune J.M., Rabin L.B., Feinberg M.B., Lieberman M., Kosek J.C.,
RA   Reyes G.R., Weissman I.L.;
RT   "Endoproteolytic cleavage of gp160 is required for the activation of human
RT   immunodeficiency virus.";
RL   Cell 53:55-67(1988).
RN   [4]
RP   FUNCTION (TRANSMEMBRANE PROTEIN GP41).
RX   PubMed=2243396; DOI=10.1128/jvi.64.12.6314-6318.1990;
RA   Helseth E., Olshevsky U., Gabuzda D., Ardman B., Haseltine W., Sodroski J.;
RT   "Changes in the transmembrane region of the human immunodeficiency virus
RT   type 1 gp41 envelope glycoprotein affect membrane fusion.";
RL   J. Virol. 64:6314-6318(1990).
RN   [5]
RP   FUNCTION (ENVELOPE GLYCOPROTEIN GP160).
RX   PubMed=1360148; DOI=10.1038/360358a0;
RA   Hallenberger S., Bosch V., Angliker H., Shaw E., Klenk H.D., Garten W.;
RT   "Inhibition of furin-mediated cleavage activation of HIV-1 glycoprotein
RT   gp160.";
RL   Nature 360:358-361(1992).
RN   [6]
RP   IMMUNOSUPPRESSIVE REGION.
RX   PubMed=7986401;
RA   Denner J., Norley S., Kurth R.;
RT   "The immunosuppressive peptide of HIV-1: functional domains and immune
RT   response in AIDS patients.";
RL   AIDS 8:1063-1072(1994).
RN   [7]
RP   PALMITOYLATION AT CYS-764 AND CYS-837, AND MUTAGENESIS OF CYS-764 AND
RP   CYS-837.
RX   PubMed=7568235; DOI=10.1073/pnas.92.21.9871;
RA   Yang C., Spies C.P., Compans R.W.;
RT   "The human and simian immunodeficiency virus envelope glycoprotein
RT   transmembrane subunits are palmitoylated.";
RL   Proc. Natl. Acad. Sci. U.S.A. 92:9871-9875(1995).
RN   [8]
RP   INTERACTION OF SURFACE PROTEIN GP120 WITH GALACTOSYL CERAMIDE AND
RP   SULFO-GALACTOSYL CERAMIDE.
RX   PubMed=7494242; DOI=10.1128/jvi.69.12.7383-7390.1995;
RA   Harouse J.M., Collman R.G., Gonzalez-Scarano F.;
RT   "Human immunodeficiency virus type 1 infection of SK-N-MC cells: domains of
RT   gp120 involved in entry into a CD4-negative, galactosyl ceramide/3' sulfo-
RT   galactosyl ceramide-positive cell line.";
RL   J. Virol. 69:7383-7390(1995).
RN   [9]
RP   DOMAIN YXXL MOTIF.
RX   PubMed=10233963; DOI=10.1128/jvi.73.6.5010-5017.1999;
RA   Deschambeault J., Lalonde J.P., Cervantes-Acosta G., Lodge R., Cohen E.A.,
RA   Lemay G.;
RT   "Polarized human immunodeficiency virus budding in lymphocytes involves a
RT   tyrosine-based signal and favors cell-to-cell viral transmission.";
RL   J. Virol. 73:5010-5017(1999).
RN   [10]
RP   FUNCTION (SURFACE PROTEIN GP120).
RX   PubMed=11257134; DOI=10.1084/jem.193.6.671;
RA   Bashirova A.A., Geijtenbeek T.B.H., van Duijnhoven G.C.F., van Vliet S.J.,
RA   Eilering J.B.G., Martin M.P., Wu L., Martin T.D., Viebig N., Knolle P.A.,
RA   Kewalramani V.N., van Kooyk Y., Carrington M.;
RT   "A dendritic cell-specific intercellular adhesion molecule 3-grabbing
RT   nonintegrin (DC-SIGN)-related protein is highly expressed on human liver
RT   sinusoidal endothelial cells and promotes HIV-1 infection.";
RL   J. Exp. Med. 193:671-678(2001).
RN   [11]
RP   REVIEW.
RX   PubMed=12974773; DOI=10.1034/j.1600-0463.2003.11107803.x;
RA   Geijtenbeek T.B., van Kooyk Y.;
RT   "Pathogens target DC-SIGN to influence their fate DC-SIGN functions as a
RT   pathogen receptor with broad specificity.";
RL   APMIS 111:698-714(2003).
RN   [12]
RP   DISULFIDE BOND.
RX   PubMed=12218052; DOI=10.1074/jbc.m205467200;
RA   Barbouche R., Miquelis R., Jones I.M., Fenouillet E.;
RT   "Protein-disulfide isomerase-mediated reduction of two disulfide bonds of
RT   HIV envelope glycoprotein 120 occurs post-CXCR4 binding and is required for
RT   fusion.";
RL   J. Biol. Chem. 278:3131-3136(2003).
RN   [13]
RP   INTERACTION OF SURFACE PROTEIN GP120 WITH HOST CD209/DC-SIGN AND
RP   CLEC4M/DC-SIGNR.
RX   PubMed=12502850; DOI=10.1128/jvi.77.2.1337-1346.2003;
RA   Lin G., Simmons G., Poehlmann S., Baribaud F., Ni H., Leslie G.J.,
RA   Haggarty B.S., Bates P., Weissman D., Hoxie J.A., Doms R.W.;
RT   "Differential N-linked glycosylation of human immunodeficiency virus and
RT   Ebola virus envelope glycoproteins modulates interactions with DC-SIGN and
RT   DC-SIGNR.";
RL   J. Virol. 77:1337-1346(2003).
RN   [14]
RP   STOICHIOMETRY (ENVELOPE GLYCOPROTEIN GP160).
RX   PubMed=16160141; DOI=10.1128/jvi.79.19.12132-12147.2005;
RA   Yang X., Kurteva S., Ren X., Lee S., Sodroski J.;
RT   "Stoichiometry of envelope glycoprotein trimers in the entry of human
RT   immunodeficiency virus type 1.";
RL   J. Virol. 79:12132-12147(2005).
RN   [15]
RP   REVIEW.
RX   PubMed=12873764; DOI=10.1016/s0005-2736(03)00161-5;
RA   Gallo S.A., Finnegan C.M., Viard M., Raviv Y., Dimitrov A., Rawat S.S.,
RA   Puri A., Durell S., Blumenthal R.;
RT   "The HIV Env-mediated fusion reaction.";
RL   Biochim. Biophys. Acta 1614:36-50(2003).
RN   [16]
RP   REVIEW.
RX   PubMed=15719026; DOI=10.1038/sj.cdd.4401584;
RA   Perfettini J.-L., Castedo M., Roumier T., Andreau K., Nardacci R.,
RA   Piacentini M., Kroemer G.;
RT   "Mechanisms of apoptosis induction by the HIV-1 envelope.";
RL   Cell Death Differ. 12:916-923(2005).
RN   [17]
RP   REVIEW.
RX   PubMed=15725757; DOI=10.1089/aid.2005.21.171;
RA   Hartley O., Klasse P.J., Sattentau Q.J., Moore J.P.;
RT   "V3: HIV's switch-hitter.";
RL   AIDS Res. Hum. Retroviruses 21:171-189(2005).
RN   [18]
RP   REVIEW.
RX   PubMed=16114975; DOI=10.2165/00003495-200565130-00002;
RA   Reeves J.D., Piefer A.J.;
RT   "Emerging drug targets for antiretroviral therapy.";
RL   Drugs 65:1747-1766(2005).
RN   [19]
RP   REVIEW.
RX   PubMed=16437164; DOI=10.1038/sj.emboj.7600947;
RA   Lusso P.;
RT   "HIV and the chemokine system: 10 years later.";
RL   EMBO J. 25:447-456(2006).
RN   [20]
RP   DI-LEUCINE INTERNALIZATION MOTIF.
RX   PubMed=17108326; DOI=10.1091/mbc.e06-06-0535;
RA   Byland R., Vance P.J., Hoxie J.A., Marsh M.;
RT   "A conserved dileucine motif mediates clathrin and AP-2-dependent
RT   endocytosis of the HIV-1 envelope protein.";
RL   Mol. Biol. Cell 18:414-425(2007).
RN   [21]
RP   MEMBRANE-PROXIMAL EXTERNAL REGION.
RX   PubMed=18322034; DOI=10.1128/mmbr.00020-07;
RA   Montero M., van Houten N.E., Wang X., Scott J.K.;
RT   "The membrane-proximal external region of the human immunodeficiency virus
RT   type 1 envelope: dominant site of antibody neutralization and target for
RT   vaccine design.";
RL   Microbiol. Mol. Biol. Rev. 72:54-84(2008).
RN   [22]
RP   INTERACTION OF SURFACE PROTEIN GP120 WITH HEPARAN SULFATE.
RC   STRAIN=HXBC2;
RX   PubMed=18378683; DOI=10.1074/jbc.m800066200;
RA   Crublet E., Andrieu J.P., Vives R.R., Lortat-Jacob H.;
RT   "The HIV-1 envelope glycoprotein gp120 features four heparan sulfate
RT   binding domains, including the co-receptor binding site.";
RL   J. Biol. Chem. 283:15193-15200(2008).
RN   [23]
RP   FUNCTION.
RX   PubMed=19410541; DOI=10.1016/j.cell.2009.02.046;
RA   Miyauchi K., Kim Y., Latinovic O., Morozov V., Melikyan G.B.;
RT   "HIV enters cells via endocytosis and dynamin-dependent fusion with
RT   endosomes.";
RL   Cell 137:433-444(2009).
RN   [24]
RP   IMMUNOSUPPRESSIVE REGION.
RX   PubMed=23383108; DOI=10.1371/journal.pone.0055199;
RA   Denner J., Eschricht M., Lauck M., Semaan M., Schlaermann P., Ryu H.,
RA   Akyuez L.;
RT   "Modulation of cytokine release and gene expression by the
RT   immunosuppressive domain of gp41 of HIV-1.";
RL   PLoS ONE 8:E55199-E55199(2013).
RN   [25]
RP   GLYCOSYLATION AT ASN-88; ASN-156; ASN-160; ASN-197; ASN-234; ASN-262;
RP   ASN-276; ASN-295; ASN-332; ASN-339; ASN-386; ASN-392; ASN-448; ASN-611 AND
RP   ASN-637.
RC   STRAIN=BG505;
RX   PubMed=26972002; DOI=10.1016/j.celrep.2016.02.058;
RA   Behrens A.J., Vasiljevic S., Pritchard L.K., Harvey D.J., Andev R.S.,
RA   Krumm S.A., Struwe W.B., Cupo A., Kumar A., Zitzmann N., Seabright G.E.,
RA   Kramer H.B., Spencer D.I., Royle L., Lee J.H., Klasse P.J., Burton D.R.,
RA   Wilson I.A., Ward A.B., Sanders R.W., Moore J.P., Doores K.J., Crispin M.;
RT   "Composition and antigenic effects of individual glycan sites of a trimeric
RT   HIV-1 envelope glycoprotein.";
RL   Cell Rep. 14:2695-2706(2016).
RN   [26]
RP   GLYCOSYLATION.
RX   PubMed=28667249; DOI=10.1038/s41598-017-04532-9;
RA   Yang M., Huang J., Simon R., Wang L.X., MacKerell A.D. Jr.;
RT   "Conformational heterogeneity of the HIV envelope glycan shield.";
RL   Sci. Rep. 7:4435-4435(2017).
RN   [27]
RP   FUNCTION (ENVELOPE GLYCOPROTEIN GP160).
RX   PubMed=31091448; DOI=10.1016/j.celrep.2019.04.063;
RA   Braun E., Hotter D., Koepke L., Zech F., Gross R., Sparrer K.M.J.,
RA   Mueller J.A., Pfaller C.K., Heusinger E., Wombacher R., Sutter K.,
RA   Dittmer U., Winkler M., Simmons G., Jakobsen M.R., Conzelmann K.K.,
RA   Poehlmann S., Muench J., Fackler O.T., Kirchhoff F., Sauter D.;
RT   "Guanylate-binding proteins 2 and 5 exert broad antiviral activity by
RT   inhibiting furin-mediated processing of viral envelope proteins.";
RL   Cell Rep. 27:2092-2104(2019).
RN   [28]
RP   X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 628-661 AND 546-581.
RX   PubMed=9108481; DOI=10.1016/s0092-8674(00)80205-6;
RA   Chan D.C., Fass D., Berger J.M., Kim P.S.;
RT   "Core structure of gp41 from the HIV envelope glycoprotein.";
RL   Cell 89:263-273(1997).
RN   [29]
RP   X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) OF 83-127; 195-297; 330-396 AND
RP   410-492, AND GLYCOSYLATION AT ASN-197; ASN-262; ASN-276; ASN-289; ASN-295;
RP   ASN-332; ASN-339; ASN-386; ASN-392 AND ASN-448.
RX   PubMed=9641677; DOI=10.1038/31405;
RA   Kwong P.D., Wyatt R., Robinson J., Sweet R.W., Sodroski J.,
RA   Hendrickson W.A.;
RT   "Structure of an HIV gp120 envelope glycoprotein in complex with the CD4
RT   receptor and a neutralizing human antibody.";
RL   Nature 393:648-659(1998).
RN   [30]
RP   X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 546-579 AND 628-655.
RX   PubMed=10677212; DOI=10.1021/bi9921687;
RA   Shu W., Liu J., Ji H., Radigen L., Jiang S., Lu M.;
RT   "Helical interactions in the HIV-1 gp41 core reveal structural basis for
RT   the inhibitory activity of gp41 peptides.";
RL   Biochemistry 39:1634-1642(2000).
RN   [31]
RP   X-RAY CRYSTALLOGRAPHY (1.45 ANGSTROMS) OF 546-579 AND 628-655.
RX   PubMed=10636883; DOI=10.1074/jbc.275.3.1839;
RA   Shu W., Ji H., Lu M.;
RT   "Interactions between HIV-1 gp41 core and detergents and their implications
RT   for membrane fusion.";
RL   J. Biol. Chem. 275:1839-1845(2000).
RN   [32]
RP   X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF 83-127; 195-297 AND 330-492, AND
RP   GLYCOSYLATION AT ASN-197; ASN-234; ASN-262; ASN-276; ASN-289; ASN-295;
RP   ASN-339; ASN-386; ASN-392; ASN-448 AND ASN-463.
RX   PubMed=11188697; DOI=10.1016/s0969-2126(00)00547-5;
RA   Kwong P.D., Wyatt R., Majeed S., Robinson J., Sweet R.W., Sodroski J.,
RA   Hendrickson W.A.;
RT   "Structures of HIV-1 gp120 envelope glycoproteins from laboratory-adapted
RT   and primary isolates.";
RL   Structure 8:1329-1339(2000).
RN   [33]
RP   X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF 546-579 AND 628-655.
RX   PubMed=12044159; DOI=10.1021/bi025648y;
RA   Wang S., York J., Shu W., Stoller M.O., Nunberg J.H., Lu M.;
RT   "Interhelical interactions in the gp41 core: implications for activation of
RT   HIV-1 membrane fusion.";
RL   Biochemistry 41:7283-7292(2002).
RN   [34]
RP   X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 565-581.
RX   PubMed=12417739; DOI=10.1073/pnas.232566599;
RA   Sia S.K., Carr P.A., Cochran A.G., Malashkevich V.N., Kim P.S.;
RT   "Short constrained peptides that inhibit HIV-1 entry.";
RL   Proc. Natl. Acad. Sci. U.S.A. 99:14664-14669(2002).
RN   [35]
RP   STRUCTURE BY NMR OF 659-671.
RX   PubMed=12860131; DOI=10.1016/s0022-2836(03)00611-9;
RA   Barbato G., Bianchi E., Ingallinella P., Hurni W.H., Miller M.D.,
RA   Ciliberto G., Cortese R., Bazzo R., Shiver J.W., Pessi A.;
RT   "Structural analysis of the epitope of the anti-HIV antibody 2F5 sheds
RT   light into its mechanism of neutralization and HIV fusion.";
RL   J. Mol. Biol. 330:1101-1115(2003).
RN   [36]
RP   X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF 195-492, AND GLYCOSYLATION AT
RP   ASN-197; ASN-234; ASN-262; ASN-276; ASN-289; ASN-295; ASN-392; ASN-448 AND
RP   ASN-463.
RX   PubMed=14981267; DOI=10.1073/pnas.0308527100;
RA   Huang C.C., Venturi M., Majeed S., Moore M.J., Phogat S., Zhang M.Y.,
RA   Dimitrov D.S., Hendrickson W.A., Robinson J., Sodroski J., Wyatt R.,
RA   Choe H., Farzan M., Kwong P.D.;
RT   "Structural basis of tyrosine sulfation and VH-gene usage in antibodies
RT   that recognize the HIV type 1 coreceptor-binding site on gp120.";
RL   Proc. Natl. Acad. Sci. U.S.A. 101:2706-2711(2004).
RN   [37]
RP   X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 83-492, AND GLYCOSYLATION AT
RP   ASN-356.
RX   PubMed=17301785; DOI=10.1038/nature05580;
RA   Zhou T., Xu L., Dey B., Hessell A.J., Van Ryk D., Xiang S.H., Yang X.,
RA   Zhang M.Y., Zwick M.B., Arthos J., Burton D.R., Dimitrov D.S., Sodroski J.,
RA   Wyatt R., Nabel G.J., Kwong P.D.;
RT   "Structural definition of a conserved neutralization epitope on HIV-1
RT   gp120.";
RL   Nature 445:732-737(2007).
RN   [38]
RP   STRUCTURE BY NMR OF 662-683.
RX   PubMed=18191596; DOI=10.1016/j.immuni.2007.11.018;
RA   Sun Z.Y., Oh K.J., Kim M., Yu J., Brusic V., Song L., Qiao Z., Wang J.H.,
RA   Wagner G., Reinherz E.L.;
RT   "HIV-1 broadly neutralizing antibody extracts its epitope from a kinked
RT   gp41 ectodomain region on the viral membrane.";
RL   Immunity 28:52-63(2008).
RN   [39]
RP   X-RAY CRYSTALLOGRAPHY (2.05 ANGSTROMS) OF 660-670.
RX   PubMed=18824005; DOI=10.1016/j.jmb.2008.09.024;
RA   Julien J.P., Bryson S., Nieva J.L., Pai E.F.;
RT   "Structural details of HIV-1 recognition by the broadly neutralizing
RT   monoclonal antibody 2F5: epitope conformation, antigen-recognition loop
RT   mobility, and anion-binding site.";
RL   J. Mol. Biol. 384:377-392(2008).
RN   [40]
RP   STRUCTURE BY ELECTRON MICROSCOPY (20.00 ANGSTROMS) OF 90-124; 198-297;
RP   330-396 AND 410-492.
RX   PubMed=18668044; DOI=10.1038/nature07159;
RA   Liu J., Bartesaghi A., Borgnia M.J., Sapiro G., Subramaniam S.;
RT   "Molecular architecture of native HIV-1 gp120 trimers.";
RL   Nature 455:109-113(2008).
RN   [41]
RP   X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) OF 83-492, AND GLYCOSYLATION AT
RP   ASN-88 AND ASN-356.
RX   PubMed=19965434; DOI=10.1126/science.1175868;
RA   Chen L., Kwon Y.D., Zhou T., Wu X., O'Dell S., Cavacini L., Hessell A.J.,
RA   Pancera M., Tang M., Xu L., Yang Z.Y., Zhang M.Y., Arthos J., Burton D.R.,
RA   Dimitrov D.S., Nabel G.J., Posner M.R., Sodroski J., Wyatt R.,
RA   Mascola J.R., Kwong P.D.;
RT   "Structural basis of immune evasion at the site of CD4 attachment on HIV-1
RT   gp120.";
RL   Science 326:1123-1127(2009).
RN   [42]
RP   X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 543-582; 590-639; 625-662 AND
RP   654-688.
RX   PubMed=21124990; DOI=10.1371/journal.ppat.1001195;
RA   Sabin C., Corti D., Buzon V., Seaman M.S., Lutje Hulsik D., Hinz A.,
RA   Vanzetta F., Agatic G., Silacci C., Mainetti L., Scarlatti G., Sallusto F.,
RA   Weiss R., Lanzavecchia A., Weissenhorn W.;
RT   "Crystal structure and size-dependent neutralization properties of HK20, a
RT   human monoclonal antibody binding to the highly conserved heptad repeat 1
RT   of gp41.";
RL   PLoS Pathog. 6:E1001195-E1001195(2010).
RN   [43]
RP   X-RAY CRYSTALLOGRAPHY (3.25 ANGSTROMS) OF 254-297; 330-401; 412-419 AND
RP   445-477, AND GLYCOSYLATION AT ASN-332.
RX   PubMed=21998254; DOI=10.1126/science.1213256;
RA   Pejchal R., Doores K.J., Walker L.M., Khayat R., Huang P.S., Wang S.K.,
RA   Stanfield R.L., Julien J.P., Ramos A., Crispin M., Depetris R.,
RA   Katpally U., Marozsan A., Cupo A., Maloveste S., Liu Y., McBride R.,
RA   Ito Y., Sanders R.W., Ogohara C., Paulson J.C., Feizi T., Scanlan C.N.,
RA   Wong C.H., Moore J.P., Olson W.C., Ward A.B., Poignard P., Schief W.R.,
RA   Burton D.R., Wilson I.A.;
RT   "A potent and broad neutralizing antibody recognizes and penetrates the HIV
RT   glycan shield.";
RL   Science 334:1097-1103(2011).
RN   [44]
RP   X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 546-581.
RX   PubMed=22228771; DOI=10.1074/jbc.m111.317883;
RA   Yao X., Chong H., Zhang C., Waltersperger S., Wang M., Cui S., He Y.;
RT   "Broad antiviral activity and crystal structure of HIV-1 fusion inhibitor
RT   sifuvirtide.";
RL   J. Biol. Chem. 287:6788-6796(2012).
RN   [45]
RP   X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 254-399, AND GLYCOSYLATION AT
RP   ASN-262.
RX   PubMed=23539181; DOI=10.1126/science.1234150;
RA   Jardine J., Julien J.P., Menis S., Ota T., Kalyuzhniy O., McGuire A.,
RA   Sok D., Huang P.S., MacPherson S., Jones M., Nieusma T., Mathison J.,
RA   Baker D., Ward A.B., Burton D.R., Stamatatos L., Nemazee D., Wilson I.A.,
RA   Schief W.R.;
RT   "Rational HIV immunogen design to target specific germline B cell
RT   receptors.";
RL   Science 340:711-716(2013).
RN   [46]
RP   STRUCTURE BY NMR OF 657-683.
RX   PubMed=24075869; DOI=10.1016/j.jmb.2013.09.030;
RA   Sun Z.Y., Cheng Y., Kim M., Song L., Choi J., Kudahl U.J., Brusic V.,
RA   Chowdhury B., Yu L., Seaman M.S., Bellot G., Shih W.M., Wagner G.,
RA   Reinherz E.L.;
RT   "Disruption of helix-capping residues 671 and 674 reveals a role in HIV-1
RT   entry for a specialized hinge segment of the membrane proximal external
RT   region of gp41.";
RL   J. Mol. Biol. 426:1095-1108(2014).
CC   -!- FUNCTION: [Envelope glycoprotein gp160]: Oligomerizes in the host
CC       endoplasmic reticulum into predominantly trimers. In a second time,
CC       gp160 transits in the host Golgi, where glycosylation is completed. The
CC       precursor is then proteolytically cleaved in the trans-Golgi and
CC       thereby activated by cellular furin or furin-like proteases to produce
CC       gp120 and gp41. {ECO:0000255|HAMAP-Rule:MF_04083,
CC       ECO:0000269|PubMed:1360148, ECO:0000269|PubMed:2450679,
CC       ECO:0000269|PubMed:31091448}.
CC   -!- FUNCTION: [Surface protein gp120]: Attaches the virus to the host
CC       lymphoid cell by binding to the primary receptor CD4. This interaction
CC       induces a structural rearrangement creating a high affinity binding
CC       site for a chemokine coreceptor like CXCR4 and/or CCR5. Acts as a
CC       ligand for CD209/DC-SIGN and CLEC4M/DC-SIGNR, which are respectively
CC       found on dendritic cells (DCs), and on endothelial cells of liver
CC       sinusoids and lymph node sinuses. These interactions allow capture of
CC       viral particles at mucosal surfaces by these cells and subsequent
CC       transmission to permissive cells. HIV subverts the migration properties
CC       of dendritic cells to gain access to CD4+ T-cells in lymph nodes. Virus
CC       transmission to permissive T-cells occurs either in trans (without DCs
CC       infection, through viral capture and transmission), or in cis
CC       (following DCs productive infection, through the usual CD4-gp120
CC       interaction), thereby inducing a robust infection. In trans infection,
CC       bound virions remain infectious over days and it is proposed that they
CC       are not degraded, but protected in non-lysosomal acidic organelles
CC       within the DCs close to the cell membrane thus contributing to the
CC       viral infectious potential during DCs' migration from the periphery to
CC       the lymphoid tissues. On arrival at lymphoid tissues, intact virions
CC       recycle back to DCs' cell surface allowing virus transmission to CD4+
CC       T-cells. {ECO:0000255|HAMAP-Rule:MF_04083, ECO:0000269|PubMed:11257134,
CC       ECO:0000269|PubMed:19410541}.
CC   -!- FUNCTION: [Transmembrane protein gp41]: Acts as a class I viral fusion
CC       protein. Under the current model, the protein has at least 3
CC       conformational states: pre-fusion native state, pre-hairpin
CC       intermediate state, and post-fusion hairpin state. During fusion of
CC       viral and target intracellular membranes, the coiled coil regions
CC       (heptad repeats) assume a trimer-of-hairpins structure, positioning the
CC       fusion peptide in close proximity to the C-terminal region of the
CC       ectodomain. The formation of this structure appears to drive apposition
CC       and subsequent fusion of viral and target cell membranes. Complete
CC       fusion occurs in host cell endosomes and is dynamin-dependent, however
CC       some lipid transfer might occur at the plasma membrane. The virus
CC       undergoes clathrin-dependent internalization long before endosomal
CC       fusion, thus minimizing the surface exposure of conserved viral
CC       epitopes during fusion and reducing the efficacy of inhibitors
CC       targeting these epitopes. Membranes fusion leads to delivery of the
CC       nucleocapsid into the cytoplasm. {ECO:0000255|HAMAP-Rule:MF_04083,
CC       ECO:0000269|PubMed:19410541, ECO:0000269|PubMed:2243396}.
CC   -!- SUBUNIT: [Surface protein gp120]: The mature envelope protein (Env)
CC       consists of a homotrimer of non-covalently associated gp120-gp41
CC       heterodimers. The resulting complex protrudes from the virus surface as
CC       a spike. There seems to be as few as 10 spikes on the average virion.
CC       Interacts with host CD4, CCR5 and CXCR4. Gp120 also interacts with the
CC       C-type lectins CD209/DC-SIGN and CLEC4M/DC-SIGNR (collectively referred
CC       to as DC-SIGN(R)). Gp120 and gp41 interact with GalCer. Gp120 interacts
CC       with host ITGA4/ITGB7 complex; on CD4+ T-cells, this interaction
CC       results in rapid activation of integrin ITGAL/LFA-1, which facilitates
CC       efficient cell-to-cell spreading of HIV-1. Gp120 interacts with cell-
CC       associated heparan sulfate; this interaction increases virus
CC       infectivity on permissive cells and may be involved in infection of
CC       CD4- cells. {ECO:0000255|HAMAP-Rule:MF_04083,
CC       ECO:0000269|PubMed:12502850, ECO:0000269|PubMed:18378683,
CC       ECO:0000269|PubMed:7494242}.
CC   -!- SUBUNIT: [Transmembrane protein gp41]: The mature envelope protein
CC       (Env) consists of a homotrimer of non-covalently associated gp120-gp41
CC       heterodimers. The resulting complex protrudes from the virus surface as
CC       a spike. There seems to be as few as 10 spikes on the average virion.
CC       {ECO:0000255|HAMAP-Rule:MF_04083, ECO:0000269|PubMed:12502850,
CC       ECO:0000269|PubMed:18378683, ECO:0000269|PubMed:7494242}.
CC   -!- INTERACTION:
CC       P04578; P04608: tat; NbExp=4; IntAct=EBI-6163496, EBI-6164389;
CC       P04578; P27824: CANX; Xeno; NbExp=3; IntAct=EBI-6163496, EBI-355947;
CC       P04578; P01730: CD4; Xeno; NbExp=2; IntAct=EBI-6163496, EBI-353826;
CC       P04578; Q9ULD8: KCNH3; Xeno; NbExp=3; IntAct=EBI-6163496, EBI-8079227;
CC       PRO_0000038427; P01730: CD4; Xeno; NbExp=3; IntAct=EBI-6179761, EBI-353826;
CC       PRO_0000038428; PRO_0000038428 [P04578]: env; NbExp=2; IntAct=EBI-6179711, EBI-6179711;
CC       PRO_0000038428; P08962: CD63; Xeno; NbExp=4; IntAct=EBI-6179711, EBI-762053;
CC   -!- SUBCELLULAR LOCATION: [Surface protein gp120]: Virion membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Peripheral membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host cell membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Peripheral membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host endosome membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Note=The surface protein is not
CC       anchored to the viral envelope, but associates with the extravirion
CC       surface through its binding to TM. It is probably concentrated at the
CC       site of budding and incorporated into the virions possibly by contacts
CC       between the cytoplasmic tail of Env and the N-terminus of Gag.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBCELLULAR LOCATION: [Transmembrane protein gp41]: Virion membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host cell membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host endosome membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Note=It is probably concentrated at
CC       the site of budding and incorporated into the virions possibly by
CC       contacts between the cytoplasmic tail of Env and the N-terminus of Gag.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: Some of the most genetically diverse regions of the viral
CC       genome are present in Env. They are called variable regions 1 through 5
CC       (V1 through V5). Coreceptor usage of gp120 is determined mainly by the
CC       primary structure of the third variable region (V3) in the outer domain
CC       of gp120. The sequence of V3 determines which coreceptor, CCR5 and/or
CC       CXCR4 (corresponding to R5/macrophage, X4/T cell and R5X4/T cell and
CC       macrophage tropism), is used to trigger the fusion potential of the Env
CC       complex, and hence which cells the virus can infect. Binding to CCR5
CC       involves a region adjacent in addition to V3. {ECO:0000255|HAMAP-
CC       Rule:MF_04083, ECO:0000269|PubMed:10233963}.
CC   -!- DOMAIN: The membrane proximal external region (MPER) present in gp41 is
CC       a tryptophan-rich region recognized by the antibodies 2F5, Z13, and
CC       4E10. MPER seems to play a role in fusion. {ECO:0000255|HAMAP-
CC       Rule:MF_04083, ECO:0000269|PubMed:10233963}.
CC   -!- DOMAIN: The 17 amino acids long immunosuppressive region is present in
CC       many retroviral envelope proteins. Synthetic peptides derived from this
CC       relatively conserved sequence inhibit immune function in vitro and in
CC       vivo. {ECO:0000255|HAMAP-Rule:MF_04083, ECO:0000269|PubMed:23383108}.
CC   -!- DOMAIN: The YXXL motif is involved in determining the exact site of
CC       viral release at the surface of infected mononuclear cells and promotes
CC       endocytosis. YXXL and di-leucine endocytosis motifs interact directly
CC       or indirectly with the clathrin adapter complexes, opperate
CC       independently, and their activities are not additive.
CC       {ECO:0000255|HAMAP-Rule:MF_04083, ECO:0000269|PubMed:10233963}.
CC   -!- DOMAIN: The CD4-binding region is targeted by the antibody b12.
CC       {ECO:0000255|HAMAP-Rule:MF_04083, ECO:0000269|PubMed:10233963}.
CC   -!- PTM: Palmitoylation of the transmembrane protein and of Env polyprotein
CC       (prior to its proteolytic cleavage) is essential for their association
CC       with host cell membrane lipid rafts. Palmitoylation is therefore
CC       required for envelope trafficking to classical lipid rafts, but not for
CC       viral replication. {ECO:0000255|HAMAP-Rule:MF_04083,
CC       ECO:0000269|PubMed:7568235}.
CC   -!- PTM: Highly glycosylated by host. The high number of glycan on the
CC       protein is reffered to as 'glycan shield' because it contributes to
CC       hide protein sequence from adaptive immune system. {ECO:0000255|HAMAP-
CC       Rule:MF_04083, ECO:0000269|PubMed:26972002,
CC       ECO:0000269|PubMed:28667249}.
CC   -!- PTM: Specific enzymatic cleavages in vivo yield mature proteins.
CC       Envelope glycoproteins are synthesized as an inactive precursor that is
CC       heavily N-glycosylated and processed likely by host cell furin in the
CC       Golgi to yield the mature SU and TM proteins. The cleavage site between
CC       SU and TM requires the minimal sequence [KR]-X-[KR]-R. About 2 of the 9
CC       disulfide bonds of gp41 are reduced by P4HB/PDI, following binding to
CC       CD4 receptor. {ECO:0000255|HAMAP-Rule:MF_04083,
CC       ECO:0000269|PubMed:12218052, ECO:0000269|PubMed:2450679,
CC       ECO:0000269|PubMed:31091448}.
CC   -!- MISCELLANEOUS: Inhibitors targeting HIV-1 viral envelope proteins are
CC       used as antiretroviral drugs. Attachment of virions to the cell surface
CC       via non-specific interactions and CD4 binding can be blocked by
CC       inhibitors that include cyanovirin-N, cyclotriazadisulfonamide analogs,
CC       PRO 2000, TNX 355 and PRO 542. In addition, BMS 806 can block CD4-
CC       induced conformational changes. Env interactions with the coreceptor
CC       molecules can be targeted by CCR5 antagonists including SCH-D,
CC       maraviroc (UK 427857) and aplaviroc (GW 873140), and the CXCR4
CC       antagonist AMD 070. Fusion of viral and cellular membranes can be
CC       inhibited by peptides such as enfuvirtide and tifuvirtide (T 1249).
CC       Resistance to inhibitors associated with mutations in Env are observed.
CC       Most of the time, single mutations confer only a modest reduction in
CC       drug susceptibility. Combination of several mutations is usually
CC       required to develop a high-level drug resistance. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- MISCELLANEOUS: HIV-1 lineages are divided in three main groups, M (for
CC       Major), O (for Outlier), and N (for New, or Non-M, Non-O). The vast
CC       majority of strains found worldwide belong to the group M. Group O
CC       seems to be endemic to and largely confined to Cameroon and neighboring
CC       countries in West Central Africa, where these viruses represent a small
CC       minority of HIV-1 strains. The group N is represented by a limited
CC       number of isolates from Cameroonian persons. The group M is further
CC       subdivided in 9 clades or subtypes (A to D, F to H, J and K).
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SIMILARITY: Belongs to the HIV-1 env protein family.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- WEB RESOURCE: Name=hivdb; Note=HIV drug resistance database;
CC       URL="https://hivdb.stanford.edu";
CC   -!- WEB RESOURCE: Name=HIV drug resistance mutations;
CC       URL="https://www.iasusa.org/content/hiv-drug-resistance-mutations";
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DR   EMBL; K03455; AAB50262.1; -; Genomic_RNA.
DR   EMBL; AF038399; AAB99976.1; -; Genomic_DNA.
DR   EMBL; AF033819; AAC82596.1; -; Genomic_RNA.
DR   RefSeq; NP_057856.1; NC_001802.1.
DR   PDB; 1AIK; X-ray; 2.00 A; C=628-661, N=546-581.
DR   PDB; 1DF4; X-ray; 1.45 A; A=546-579, A=628-655.
DR   PDB; 1DF5; X-ray; 2.70 A; A=546-579, A=628-655.
DR   PDB; 1DLB; X-ray; 2.00 A; A=546-579, A=628-655.
DR   PDB; 1FAV; X-ray; 3.00 A; C=636-665.
DR   PDB; 1G9M; X-ray; 2.20 A; G=83-127, G=195-297, G=330-492.
DR   PDB; 1GC1; X-ray; 2.50 A; G=83-127, G=195-297, G=330-396, G=410-492.
DR   PDB; 1GZL; X-ray; 1.80 A; A/B=565-581, C/D=628-639.
DR   PDB; 1K33; X-ray; 1.75 A; A=546-579, A=628-655.
DR   PDB; 1K34; X-ray; 1.88 A; A=546-579, A=628-655.
DR   PDB; 1MZI; NMR; -; A=659-671.
DR   PDB; 1RZJ; X-ray; 2.20 A; G=195-492.
DR   PDB; 2CMR; X-ray; 2.00 A; A=543-662.
DR   PDB; 2ME1; NMR; -; A=657-683.
DR   PDB; 2MG1; NMR; -; A=683-704.
DR   PDB; 2MG2; NMR; -; A=675-693.
DR   PDB; 2MG3; NMR; -; A=675-693.
DR   PDB; 2NY7; X-ray; 2.30 A; G=83-492.
DR   PDB; 2PV6; NMR; -; A=662-683.
DR   PDB; 2XRA; X-ray; 2.30 A; A=543-662.
DR   PDB; 3D0V; X-ray; 2.05 A; C=660-670.
DR   PDB; 3DNL; EM; 20.00 A; A/D/G=90-124, B/E/H=198-297, B/E/H=330-396, C/F/I=410-492.
DR   PDB; 3DNN; EM; 20.00 A; A/D/G=90-124, B/E/H=198-297, B/E/H=330-396, C/F/I=410-492.
DR   PDB; 3DNO; EM; 20.00 A; A/D/G=90-124, B/E/H=198-297, B/E/H=330-396, C/F/I=410-492.
DR   PDB; 3DRO; X-ray; 3.90 A; P=659-671.
DR   PDB; 3IDX; X-ray; 2.50 A; G=83-492.
DR   PDB; 3IDY; X-ray; 3.20 A; A/G=83-492.
DR   PDB; 3J70; EM; -; D/P/U=31-500.
DR   PDB; 3MNZ; X-ray; 1.80 A; P=653-671.
DR   PDB; 3TYG; X-ray; 3.25 A; A=254-297, A=330-401.
DR   PDB; 3VIE; X-ray; 1.80 A; A/C/E=546-581.
DR   PDB; 4JPJ; X-ray; 2.50 A; A/B/C/D=254-399.
DR   PDB; 4JPK; X-ray; 2.40 A; A=254-399.
DR   PDB; 4YDV; X-ray; 2.70 A; P/Q=596-606.
DR   PDB; 4ZTO; X-ray; 2.30 A; P/Q=430-444.
DR   PDB; 5BN0; X-ray; 2.80 A; A/C/D=627-661, B/E/N=546-581.
DR   PDB; 5C0R; X-ray; 3.19 A; A=546-577, A=628-654.
DR   PDB; 5C0S; X-ray; 4.30 A; A=546-577, A=630-654.
DR   PDB; 5CIL; X-ray; 1.81 A; P=671-683.
DR   PDB; 5CIN; X-ray; 1.70 A; P=671-683.
DR   PDB; 5CMU; X-ray; 2.11 A; A/B/C=546-635.
DR   PDB; 5CMZ; X-ray; 2.57 A; A/C=546-590.
DR   PDB; 5CN0; X-ray; 1.90 A; A=546-581.
DR   PDB; 5DD0; X-ray; 2.49 A; P=660-670.
DR   PDB; 5GHW; X-ray; 2.40 A; P=664-690.
DR   PDB; 5H0N; X-ray; 2.80 A; A/C/E/G/I/K=536-581.
DR   PDB; 5HFL; X-ray; 2.29 A; A/B/C/D/E/F=546-581.
DR   PDB; 5HM1; X-ray; 2.96 A; D/E/F=582-596.
DR   PDB; 5IVX; X-ray; 2.10 A; P=311-320.
DR   PDB; 5KA5; X-ray; 1.80 A; A=543-582, A=625-661.
DR   PDB; 5KA6; X-ray; 1.85 A; A/B/C=543-582, A/B/C=625-661.
DR   PDB; 5NVP; NMR; -; A=655-671.
DR   PDB; 5NWU; NMR; -; A=514-528, A=655-671.
DR   PDB; 5NWW; NMR; -; A=655-671.
DR   PDB; 5TKJ; X-ray; 2.12 A; C/F/I/L=512-519.
DR   PDB; 5TKK; X-ray; 1.55 A; A=512-519.
DR   PDB; 5WDF; X-ray; 3.10 A; P/Q=668-683.
DR   PDB; 5X08; X-ray; 1.49 A; P=671-683.
DR   PDB; 5YB2; X-ray; 3.80 A; A/B/C/D/E/F/M=538-581.
DR   PDB; 5YB3; X-ray; 2.04 A; D/E/F=546-581.
DR   PDB; 5YB4; X-ray; 2.50 A; D/E/F=546-581.
DR   PDB; 5YC0; X-ray; 2.00 A; A/B/C/D/E/F=538-581.
DR   PDB; 5Z0W; X-ray; 1.90 A; E=546-581.
DR   PDB; 5ZCX; X-ray; 2.30 A; A/B/C=528-566, P/Q/W=638-673.
DR   PDB; 6B9K; NMR; -; A=311-320.
DR   PDB; 6BXP; X-ray; 1.45 A; C=2-11.
DR   PDB; 6BXQ; X-ray; 1.58 A; A=2-11.
DR   PDB; 6DE7; X-ray; 4.12 A; B=512-664.
DR   PDB; 6DLN; NMR; -; A/B/C=665-703.
DR   PDB; 6J5E; X-ray; 2.33 A; G/I/K=538-581.
DR   PDB; 6JQK; X-ray; 1.50 A; C=623-661, N=546-581.
DR   PDB; 6KTS; X-ray; 1.65 A; A/C/D=627-661, B/E/N=546-581.
DR   PDB; 6MQC; X-ray; 1.99 A; C/D=512-519.
DR   PDB; 6MQE; X-ray; 2.46 A; C/D=512-519.
DR   PDB; 6MQM; X-ray; 3.48 A; C/F/I/L=512-518.
DR   PDB; 6MQR; X-ray; 2.45 A; A=512-519.
DR   PDB; 6MQS; X-ray; 3.00 A; E/F=512-519.
DR   PDB; 6N16; X-ray; 2.30 A; E/F/G/I=512-519.
DR   PDB; 6NCP; X-ray; 2.76 A; E=512-520.
DR   PDB; 6NPR; X-ray; 2.37 A; P/R=311-320.
DR   PDB; 6O3G; X-ray; 3.65 A; G/I/Q/S=671-683.
DR   PDB; 6O3J; X-ray; 3.42 A; G/I=671-683.
DR   PDB; 6O3L; X-ray; 1.98 A; D/E=671-683.
DR   PDB; 6O42; X-ray; 2.60 A; G/I=671-683.
DR   PDB; 6P60; X-ray; 2.50 A; E/F/I/L=512-519.
DR   PDB; 6P7H; X-ray; 1.78 A; C=512-519.
DR   PDB; 6P8D; X-ray; 2.10 A; C/F=512-519.
DR   PDB; 6PDR; X-ray; 1.55 A; A=512-519.
DR   PDB; 6PDS; X-ray; 1.89 A; C/G=512-519.
DR   PDB; 6PDU; X-ray; 1.95 A; C=512-519.
DR   PDB; 6PEC; X-ray; 1.75 A; A=512-519.
DR   PDB; 6PEF; X-ray; 2.00 A; C/F=512-519.
DR   PDB; 6PSA; X-ray; 1.30 A; A=566-581.
DR   PDB; 6RYF; X-ray; 1.72 A; G=308-320.
DR   PDB; 6SNC; X-ray; 3.20 A; C/P=671-689.
DR   PDB; 6SND; X-ray; 3.10 A; C/P=671-689.
DR   PDB; 6SNE; X-ray; 3.90 A; J/N/O/P=649-711.
DR   PDB; 6UBI; X-ray; 1.90 A; C/F=512-519.
DR   PDB; 6UCE; X-ray; 1.38 A; C=512-519.
DR   PDB; 6UCF; X-ray; 1.29 A; A=512-519.
DR   PDB; 6UJU; NMR; -; A/B/C=677-788.
DR   PDB; 6UJV; NMR; -; A/B/C=660-788.
DR   PDB; 6WWC; X-ray; 2.56 A; C/F=512-519.
DR   PDB; 7AEJ; X-ray; 3.80 A; A/B/C=512-594, A/B/C=629-718.
DR   PDB; 7EKB; X-ray; 1.45 A; P=671-683.
DR   PDB; 7EKK; X-ray; 1.70 A; P=671-683.
DR   PDB; 7FF1; X-ray; 1.69 A; A/C/D=627-661, B/E/N=546-581.
DR   PDB; 7LOH; NMR; -; A/B/C=677-856.
DR   PDB; 7LOI; NMR; -; A/B/C=660-856.
DR   PDB; 7N05; X-ray; 1.70 A; E=596-610.
DR   PDB; 7N08; X-ray; 2.00 A; E/F/G=596-610.
DR   PDB; 7R73; X-ray; 1.76 A; G=44-64.
DR   PDB; 7R74; X-ray; 2.76 A; A/C=44-492.
DR   PDB; 7RDW; X-ray; 3.55 A; C/D/M/N=44-495.
DR   PDB; 8B6Y; NMR; -; A=671-690.
DR   PDB; 8F3A; X-ray; 1.20 A; A/B/C=540-581.
DR   PDB; 8F3B; X-ray; 2.00 A; A/B/C=540-586.
DR   PDBsum; 1AIK; -.
DR   PDBsum; 1DF4; -.
DR   PDBsum; 1DF5; -.
DR   PDBsum; 1DLB; -.
DR   PDBsum; 1FAV; -.
DR   PDBsum; 1G9M; -.
DR   PDBsum; 1GC1; -.
DR   PDBsum; 1GZL; -.
DR   PDBsum; 1K33; -.
DR   PDBsum; 1K34; -.
DR   PDBsum; 1MZI; -.
DR   PDBsum; 1RZJ; -.
DR   PDBsum; 2CMR; -.
DR   PDBsum; 2ME1; -.
DR   PDBsum; 2MG1; -.
DR   PDBsum; 2MG2; -.
DR   PDBsum; 2MG3; -.
DR   PDBsum; 2NY7; -.
DR   PDBsum; 2PV6; -.
DR   PDBsum; 2XRA; -.
DR   PDBsum; 3D0V; -.
DR   PDBsum; 3DNL; -.
DR   PDBsum; 3DNN; -.
DR   PDBsum; 3DNO; -.
DR   PDBsum; 3DRO; -.
DR   PDBsum; 3IDX; -.
DR   PDBsum; 3IDY; -.
DR   PDBsum; 3J70; -.
DR   PDBsum; 3MNZ; -.
DR   PDBsum; 3TYG; -.
DR   PDBsum; 3VIE; -.
DR   PDBsum; 4JPJ; -.
DR   PDBsum; 4JPK; -.
DR   PDBsum; 4YDV; -.
DR   PDBsum; 4ZTO; -.
DR   PDBsum; 5BN0; -.
DR   PDBsum; 5C0R; -.
DR   PDBsum; 5C0S; -.
DR   PDBsum; 5CIL; -.
DR   PDBsum; 5CIN; -.
DR   PDBsum; 5CMU; -.
DR   PDBsum; 5CMZ; -.
DR   PDBsum; 5CN0; -.
DR   PDBsum; 5DD0; -.
DR   PDBsum; 5GHW; -.
DR   PDBsum; 5H0N; -.
DR   PDBsum; 5HFL; -.
DR   PDBsum; 5HM1; -.
DR   PDBsum; 5IVX; -.
DR   PDBsum; 5KA5; -.
DR   PDBsum; 5KA6; -.
DR   PDBsum; 5NVP; -.
DR   PDBsum; 5NWU; -.
DR   PDBsum; 5NWW; -.
DR   PDBsum; 5TKJ; -.
DR   PDBsum; 5TKK; -.
DR   PDBsum; 5WDF; -.
DR   PDBsum; 5X08; -.
DR   PDBsum; 5YB2; -.
DR   PDBsum; 5YB3; -.
DR   PDBsum; 5YB4; -.
DR   PDBsum; 5YC0; -.
DR   PDBsum; 5Z0W; -.
DR   PDBsum; 5ZCX; -.
DR   PDBsum; 6B9K; -.
DR   PDBsum; 6BXP; -.
DR   PDBsum; 6BXQ; -.
DR   PDBsum; 6DE7; -.
DR   PDBsum; 6DLN; -.
DR   PDBsum; 6J5E; -.
DR   PDBsum; 6JQK; -.
DR   PDBsum; 6KTS; -.
DR   PDBsum; 6MQC; -.
DR   PDBsum; 6MQE; -.
DR   PDBsum; 6MQM; -.
DR   PDBsum; 6MQR; -.
DR   PDBsum; 6MQS; -.
DR   PDBsum; 6N16; -.
DR   PDBsum; 6NCP; -.
DR   PDBsum; 6NPR; -.
DR   PDBsum; 6O3G; -.
DR   PDBsum; 6O3J; -.
DR   PDBsum; 6O3L; -.
DR   PDBsum; 6O42; -.
DR   PDBsum; 6P60; -.
DR   PDBsum; 6P7H; -.
DR   PDBsum; 6P8D; -.
DR   PDBsum; 6PDR; -.
DR   PDBsum; 6PDS; -.
DR   PDBsum; 6PDU; -.
DR   PDBsum; 6PEC; -.
DR   PDBsum; 6PEF; -.
DR   PDBsum; 6PSA; -.
DR   PDBsum; 6RYF; -.
DR   PDBsum; 6SNC; -.
DR   PDBsum; 6SND; -.
DR   PDBsum; 6SNE; -.
DR   PDBsum; 6UBI; -.
DR   PDBsum; 6UCE; -.
DR   PDBsum; 6UCF; -.
DR   PDBsum; 6UJU; -.
DR   PDBsum; 6UJV; -.
DR   PDBsum; 6WWC; -.
DR   PDBsum; 7AEJ; -.
DR   PDBsum; 7EKB; -.
DR   PDBsum; 7EKK; -.
DR   PDBsum; 7FF1; -.
DR   PDBsum; 7LOH; -.
DR   PDBsum; 7LOI; -.
DR   PDBsum; 7N05; -.
DR   PDBsum; 7N08; -.
DR   PDBsum; 7R73; -.
DR   PDBsum; 7R74; -.
DR   PDBsum; 7RDW; -.
DR   PDBsum; 8B6Y; -.
DR   PDBsum; 8F3A; -.
DR   PDBsum; 8F3B; -.
DR   BMRB; P04578; -.
DR   SMR; P04578; -.
DR   BioGRID; 1205544; 157.
DR   DIP; DIP-58525N; -.
DR   IntAct; P04578; 141.
DR   MINT; P04578; -.
DR   BindingDB; P04578; -.
DR   ChEMBL; CHEMBL3520; -.
DR   TCDB; 1.G.16.1.3; the human immunodeficiency virus type 1 (hiv-1) fusion peptide (hiv-fp) family.
DR   GlyCosmos; P04578; 29 sites, No reported glycans.
DR   iPTMnet; P04578; -.
DR   SwissPalm; P04578; -.
DR   ABCD; P04578; 59 sequenced antibodies.
DR   GeneID; 155971; -.
DR   KEGG; vg:155971; -.
DR   Reactome; R-HSA-1462054; Alpha-defensins.
DR   Reactome; R-HSA-162588; Budding and maturation of HIV virion.
DR   Reactome; R-HSA-171286; Synthesis and processing of ENV and VPU.
DR   Reactome; R-HSA-173107; Binding and entry of HIV virion.
DR   Reactome; R-HSA-175474; Assembly Of The HIV Virion.
DR   Reactome; R-HSA-5621480; Dectin-2 family.
DR   EvolutionaryTrace; P04578; -.
DR   PRO; PR:P04578; -.
DR   Proteomes; UP000002241; Segment.
DR   Proteomes; UP000105453; Segment.
DR   GO; GO:0044175; C:host cell endosome membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0016020; C:membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:0019031; C:viral envelope; IEA:UniProtKB-KW.
DR   GO; GO:0055036; C:virion membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005198; F:structural molecule activity; IEA:UniProtKB-UniRule.
DR   GO; GO:0007015; P:actin filament organization; IDA:UniProtKB.
DR   GO; GO:0075512; P:clathrin-dependent endocytosis of virus by host cell; IEA:UniProtKB-UniRule.
DR   GO; GO:0042783; P:evasion of host immune response; EXP:DisProt.
DR   GO; GO:0039654; P:fusion of virus membrane with host endosome membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:0019064; P:fusion of virus membrane with host plasma membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:1903905; P:positive regulation of establishment of T cell polarity; IDA:UniProtKB.
DR   GO; GO:1903908; P:positive regulation of plasma membrane raft polarization; IDA:UniProtKB.
DR   GO; GO:1903911; P:positive regulation of receptor clustering; IDA:UniProtKB.
DR   GO; GO:0046718; P:viral entry into host cell; EXP:DisProt.
DR   GO; GO:0019082; P:viral protein processing; IEA:UniProtKB-UniRule.
DR   GO; GO:0019062; P:virion attachment to host cell; IEA:UniProtKB-UniRule.
DR   GO; GO:0019049; P:virus-mediated perturbation of host defense response; IEA:UniProtKB-UniRule.
DR   CDD; cd09909; HIV-1-like_HR1-HR2; 1.
DR   Gene3D; 1.10.287.210; -; 1.
DR   Gene3D; 2.170.40.20; Human immunodeficiency virus 1, Gp160, envelope glycoprotein; 2.
DR   Gene3D; 1.20.5.490; Single helix bin; 1.
DR   HAMAP; MF_04083; HIV_ENV; 1.
DR   InterPro; IPR036377; Gp120_core_sf.
DR   InterPro; IPR037527; Gp160.
DR   InterPro; IPR000328; GP41-like.
DR   InterPro; IPR000777; HIV1_Gp120.
DR   Pfam; PF00516; GP120; 1.
DR   Pfam; PF00517; GP41; 1.
DR   SUPFAM; SSF56502; gp120 core; 1.
DR   SUPFAM; SSF58069; Virus ectodomain; 1.
PE   1: Evidence at protein level;
KW   3D-structure; AIDS; Apoptosis;
KW   Clathrin-mediated endocytosis of virus by host;
KW   Cleavage on pair of basic residues; Coiled coil; Disulfide bond;
KW   Fusion of virus membrane with host endosomal membrane;
KW   Fusion of virus membrane with host membrane; Glycoprotein;
KW   Host cell membrane; Host endosome; Host membrane; Host-virus interaction;
KW   Lipoprotein; Membrane; Palmitate; Reference proteome; Signal;
KW   Transmembrane; Transmembrane helix; Viral attachment to host cell;
KW   Viral envelope protein; Viral immunoevasion;
KW   Viral penetration into host cytoplasm; Virion; Virus endocytosis by host;
KW   Virus entry into host cell.
FT   SIGNAL          1..32
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CHAIN           33..856
FT                   /note="Envelope glycoprotein gp160"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000239240"
FT   CHAIN           33..511
FT                   /note="Surface protein gp120"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000038427"
FT   CHAIN           512..856
FT                   /note="Transmembrane protein gp41"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000038428"
FT   TOPO_DOM        33..684
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   TRANSMEM        685..705
FT                   /note="Helical"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   TOPO_DOM        706..856
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          131..156
FT                   /note="V1"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          157..196
FT                   /note="V2"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          296..330
FT                   /note="V3"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          364..374
FT                   /note="CD4-binding loop"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          385..418
FT                   /note="V4"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          461..471
FT                   /note="V5"
FT   REGION          463..471
FT                   /note="V5"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          512..532
FT                   /note="Fusion peptide"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          574..592
FT                   /note="Immunosuppression"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083,
FT                   ECO:0000269|PubMed:23383108"
FT   REGION          662..683
FT                   /note="MPER; binding to GalCer"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          718..742
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COILED          633..667
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   MOTIF           712..715
FT                   /note="YXXL motif; contains endocytosis signal"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   MOTIF           855..856
FT                   /note="Di-leucine internalization motif"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   COMPBIAS        727..742
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   SITE            511..512
FT                   /note="Cleavage; by host furin"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   LIPID           764
FT                   /note="S-palmitoyl cysteine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083,
FT                   ECO:0000269|PubMed:7568235"
FT   LIPID           837
FT                   /note="S-palmitoyl cysteine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083,
FT                   ECO:0000269|PubMed:7568235"
FT   CARBOHYD        88
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083,
FT                   ECO:0000269|PubMed:19965434, ECO:0000269|PubMed:26972002"
FT   CARBOHYD        136
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        141
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        156
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083,
FT                   ECO:0000269|PubMed:26972002"
FT   CARBOHYD        160
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083,
FT                   ECO:0000269|PubMed:26972002"
FT   CARBOHYD        186
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        197
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083,
FT                   ECO:0000269|PubMed:11188697, ECO:0000269|PubMed:14981267,
FT                   ECO:0000269|PubMed:26972002, ECO:0000269|PubMed:9641677"
FT   CARBOHYD        230
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        234
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083,
FT                   ECO:0000269|PubMed:11188697, ECO:0000269|PubMed:14981267,
FT                   ECO:0000269|PubMed:26972002"
FT   CARBOHYD        241
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        262
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083,
FT                   ECO:0000269|PubMed:11188697, ECO:0000269|PubMed:14981267,
FT                   ECO:0000269|PubMed:23539181, ECO:0000269|PubMed:26972002,
FT                   ECO:0000269|PubMed:9641677"
FT   CARBOHYD        276
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083,
FT                   ECO:0000269|PubMed:11188697, ECO:0000269|PubMed:14981267,
FT                   ECO:0000269|PubMed:26972002, ECO:0000269|PubMed:9641677"
FT   CARBOHYD        289
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083,
FT                   ECO:0000269|PubMed:11188697, ECO:0000269|PubMed:14981267,
FT                   ECO:0000269|PubMed:9641677"
FT   CARBOHYD        295
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083,
FT                   ECO:0000269|PubMed:11188697, ECO:0000269|PubMed:14981267,
FT                   ECO:0000269|PubMed:26972002, ECO:0000269|PubMed:9641677"
FT   CARBOHYD        301
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        332
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083,
FT                   ECO:0000269|PubMed:21998254, ECO:0000269|PubMed:26972002,
FT                   ECO:0000269|PubMed:9641677"
FT   CARBOHYD        339
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083,
FT                   ECO:0000269|PubMed:11188697, ECO:0000269|PubMed:26972002,
FT                   ECO:0000269|PubMed:9641677"
FT   CARBOHYD        356
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083,
FT                   ECO:0000269|PubMed:17301785, ECO:0000269|PubMed:19965434,
FT                   ECO:0007744|PDB:2NY7, ECO:0007744|PDB:3IDX,
FT                   ECO:0007744|PDB:3IDY"
FT   CARBOHYD        386
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083,
FT                   ECO:0000269|PubMed:11188697, ECO:0000269|PubMed:26972002,
FT                   ECO:0000269|PubMed:9641677"
FT   CARBOHYD        392
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083,
FT                   ECO:0000269|PubMed:11188697, ECO:0000269|PubMed:14981267,
FT                   ECO:0000269|PubMed:26972002, ECO:0000269|PubMed:9641677"
FT   CARBOHYD        397
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        406
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        448
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083,
FT                   ECO:0000269|PubMed:11188697, ECO:0000269|PubMed:14981267,
FT                   ECO:0000269|PubMed:26972002, ECO:0000269|PubMed:9641677"
FT   CARBOHYD        463
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083,
FT                   ECO:0000269|PubMed:11188697, ECO:0000269|PubMed:14981267"
FT   CARBOHYD        611
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083,
FT                   ECO:0000269|PubMed:26972002"
FT   CARBOHYD        616
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        624
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        637
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083,
FT                   ECO:0000269|PubMed:26972002"
FT   CARBOHYD        674
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        54..74
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        119..205
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        126..196
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        131..157
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        218..247
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        228..239
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        296..331
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        378..445
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        385..418
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        598..604
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   MUTAGEN         764
FT                   /note="C->S: Complete loss of palmitoylation, decreased
FT                   association with host cell membrane lipid rafts, decreased
FT                   incorporation onto virions and severe reduction of
FT                   infectivity; when associated with S-837."
FT                   /evidence="ECO:0000269|PubMed:7568235"
FT   MUTAGEN         837
FT                   /note="C->S: Complete loss of palmitoylation, decreased
FT                   association with host cell membrane lipid rafts, decreased
FT                   incorporation onto virions and severe reduction of
FT                   infectivity; when associated with S-764."
FT                   /evidence="ECO:0000269|PubMed:7568235"
FT   STRAND          53..56
FT                   /evidence="ECO:0007829|PDB:7R73"
FT   STRAND          84..93
FT                   /evidence="ECO:0007829|PDB:1G9M"
FT   TURN            95..98
FT                   /evidence="ECO:0007829|PDB:2NY7"
FT   HELIX           99..113
FT                   /evidence="ECO:0007829|PDB:1G9M"
FT   STRAND          119..123
FT                   /evidence="ECO:0007829|PDB:1G9M"
FT   STRAND          199..201
FT                   /evidence="ECO:0007829|PDB:1G9M"
FT   STRAND          210..212
FT                   /evidence="ECO:0007829|PDB:2NY7"
FT   STRAND          215..218
FT                   /evidence="ECO:0007829|PDB:7R74"
FT   STRAND          223..228
FT                   /evidence="ECO:0007829|PDB:1G9M"
FT   STRAND          235..247
FT                   /evidence="ECO:0007829|PDB:1G9M"
FT   STRAND          251..254
FT                   /evidence="ECO:0007829|PDB:2NY7"
FT   STRAND          256..258
FT                   /evidence="ECO:0007829|PDB:1G9M"
FT   STRAND          260..262
FT                   /evidence="ECO:0007829|PDB:1G9M"
FT   STRAND          267..269
FT                   /evidence="ECO:0007829|PDB:1G9M"
FT   STRAND          271..273
FT                   /evidence="ECO:0007829|PDB:1G9M"
FT   STRAND          277..279
FT                   /evidence="ECO:0007829|PDB:1GC1"
FT   STRAND          280..282
FT                   /evidence="ECO:0007829|PDB:3TYG"
FT   STRAND          284..297
FT                   /evidence="ECO:0007829|PDB:1G9M"
FT   STRAND          303..305
FT                   /evidence="ECO:0007829|PDB:3TYG"
FT   TURN            312..314
FT                   /evidence="ECO:0007829|PDB:1G9M"
FT   STRAND          330..334
FT                   /evidence="ECO:0007829|PDB:1G9M"
FT   HELIX           335..352
FT                   /evidence="ECO:0007829|PDB:1G9M"
FT   STRAND          359..361
FT                   /evidence="ECO:0007829|PDB:1G9M"
FT   HELIX           369..372
FT                   /evidence="ECO:0007829|PDB:1G9M"
FT   STRAND          374..378
FT                   /evidence="ECO:0007829|PDB:1G9M"
FT   STRAND          381..385
FT                   /evidence="ECO:0007829|PDB:1G9M"
FT   HELIX           388..390
FT                   /evidence="ECO:0007829|PDB:1G9M"
FT   STRAND          393..395
FT                   /evidence="ECO:0007829|PDB:1G9M"
FT   STRAND          413..417
FT                   /evidence="ECO:0007829|PDB:1G9M"
FT   STRAND          420..425
FT                   /evidence="ECO:0007829|PDB:1G9M"
FT   STRAND          427..430
FT                   /evidence="ECO:0007829|PDB:1G9M"
FT   STRAND          432..434
FT                   /evidence="ECO:0007829|PDB:1G9M"
FT   TURN            440..442
FT                   /evidence="ECO:0007829|PDB:3IDX"
FT   STRAND          444..456
FT                   /evidence="ECO:0007829|PDB:1G9M"
FT   STRAND          466..470
FT                   /evidence="ECO:0007829|PDB:1G9M"
FT   HELIX           475..483
FT                   /evidence="ECO:0007829|PDB:1G9M"
FT   STRAND          486..490
FT                   /evidence="ECO:0007829|PDB:1G9M"
FT   HELIX           514..516
FT                   /evidence="ECO:0007829|PDB:5TKK"
FT   HELIX           540..580
FT                   /evidence="ECO:0007829|PDB:8F3A"
FT   HELIX           583..594
FT                   /evidence="ECO:0007829|PDB:5HM1"
FT   STRAND          597..601
FT                   /evidence="ECO:0007829|PDB:7N05"
FT   HELIX           604..606
FT                   /evidence="ECO:0007829|PDB:7N05"
FT   HELIX           626..628
FT                   /evidence="ECO:0007829|PDB:1K33"
FT   HELIX           629..650
FT                   /evidence="ECO:0007829|PDB:1DF4"
FT   HELIX           657..667
FT                   /evidence="ECO:0007829|PDB:3MNZ"
FT   TURN            668..670
FT                   /evidence="ECO:0007829|PDB:5NVP"
FT   HELIX           672..674
FT                   /evidence="ECO:0007829|PDB:7EKB"
FT   HELIX           675..683
FT                   /evidence="ECO:0007829|PDB:7EKB"
FT   HELIX           690..693
FT                   /evidence="ECO:0007829|PDB:2MG3"
FT   HELIX           698..709
FT                   /evidence="ECO:0007829|PDB:7LOH"
FT   STRAND          712..714
FT                   /evidence="ECO:0007829|PDB:6UJU"
FT   HELIX           742..745
FT                   /evidence="ECO:0007829|PDB:6UJU"
FT   HELIX           748..763
FT                   /evidence="ECO:0007829|PDB:6UJU"
FT   STRAND          766..769
FT                   /evidence="ECO:0007829|PDB:6UJU"
FT   HELIX           771..786
FT                   /evidence="ECO:0007829|PDB:6UJU"
FT   HELIX           788..790
FT                   /evidence="ECO:0007829|PDB:7LOI"
FT   HELIX           791..820
FT                   /evidence="ECO:0007829|PDB:7LOH"
FT   STRAND          822..824
FT                   /evidence="ECO:0007829|PDB:7LOH"
FT   HELIX           826..841
FT                   /evidence="ECO:0007829|PDB:7LOH"
FT   HELIX           847..854
FT                   /evidence="ECO:0007829|PDB:7LOH"
SQ   SEQUENCE   856 AA;  97213 MW;  6FAB16AF85107FE0 CRC64;
     MRVKEKYQHL WRWGWRWGTM LLGMLMICSA TEKLWVTVYY GVPVWKEATT TLFCASDAKA
     YDTEVHNVWA THACVPTDPN PQEVVLVNVT ENFNMWKNDM VEQMHEDIIS LWDQSLKPCV
     KLTPLCVSLK CTDLKNDTNT NSSSGRMIME KGEIKNCSFN ISTSIRGKVQ KEYAFFYKLD
     IIPIDNDTTS YKLTSCNTSV ITQACPKVSF EPIPIHYCAP AGFAILKCNN KTFNGTGPCT
     NVSTVQCTHG IRPVVSTQLL LNGSLAEEEV VIRSVNFTDN AKTIIVQLNT SVEINCTRPN
     NNTRKRIRIQ RGPGRAFVTI GKIGNMRQAH CNISRAKWNN TLKQIASKLR EQFGNNKTII
     FKQSSGGDPE IVTHSFNCGG EFFYCNSTQL FNSTWFNSTW STEGSNNTEG SDTITLPCRI
     KQIINMWQKV GKAMYAPPIS GQIRCSSNIT GLLLTRDGGN SNNESEIFRP GGGDMRDNWR
     SELYKYKVVK IEPLGVAPTK AKRRVVQREK RAVGIGALFL GFLGAAGSTM GAASMTLTVQ
     ARQLLSGIVQ QQNNLLRAIE AQQHLLQLTV WGIKQLQARI LAVERYLKDQ QLLGIWGCSG
     KLICTTAVPW NASWSNKSLE QIWNHTTWME WDREINNYTS LIHSLIEESQ NQQEKNEQEL
     LELDKWASLW NWFNITNWLW YIKLFIMIVG GLVGLRIVFA VLSIVNRVRQ GYSPLSFQTH
     LPTPRGPDRP EGIEEEGGER DRDRSIRLVN GSLALIWDDL RSLCLFSYHR LRDLLLIVTR
     IVELLGRRGW EALKYWWNLL QYWSQELKNS AVSLLNATAI AVAEGTDRVI EVVQGACRAI
     RHIPRRIRQG LERILL
//
ID   ENV_HV1H3               Reviewed;         856 AA.
AC   P04624;
DT   13-AUG-1987, integrated into UniProtKB/Swiss-Prot.
DT   01-FEB-1996, sequence version 3.
DT   27-MAR-2024, entry version 153.
DE   RecName: Full=Envelope glycoprotein gp160 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   AltName: Full=Env polyprotein {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Contains:
DE     RecName: Full=Surface protein gp120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=SU {ECO:0000255|HAMAP-Rule:MF_04083};
DE     AltName: Full=Glycoprotein 120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=gp120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Contains:
DE     RecName: Full=Transmembrane protein gp41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=TM {ECO:0000255|HAMAP-Rule:MF_04083};
DE     AltName: Full=Glycoprotein 41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=gp41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Flags: Precursor;
GN   Name=env {ECO:0000255|HAMAP-Rule:MF_04083};
OS   Human immunodeficiency virus type 1 group M subtype B (isolate HXB3)
OS   (HIV-1).
OC   Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC   Ortervirales; Retroviridae; Orthoretrovirinae; Lentivirus;
OC   Human immunodeficiency virus 1.
OX   NCBI_TaxID=11707;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX   PubMed=2988795; DOI=10.1016/s0092-8674(85)80078-7;
RA   Crowl R., Ganguly K., Gordon M., Conroy R., Schaber M., Kramer R.,
RA   Shaw G.M., Wong-Staal F., Reddy E.P.;
RT   "HTLV-III env gene products synthesized in E. coli are recognized by
RT   antibodies present in the sera of AIDS patients.";
RL   Cell 41:979-986(1985).
RN   [2]
RP   REVIEW.
RX   PubMed=12974773; DOI=10.1034/j.1600-0463.2003.11107803.x;
RA   Geijtenbeek T.B., van Kooyk Y.;
RT   "Pathogens target DC-SIGN to influence their fate DC-SIGN functions as a
RT   pathogen receptor with broad specificity.";
RL   APMIS 111:698-714(2003).
RN   [3]
RP   REVIEW.
RX   PubMed=12873764; DOI=10.1016/s0005-2736(03)00161-5;
RA   Gallo S.A., Finnegan C.M., Viard M., Raviv Y., Dimitrov A., Rawat S.S.,
RA   Puri A., Durell S., Blumenthal R.;
RT   "The HIV Env-mediated fusion reaction.";
RL   Biochim. Biophys. Acta 1614:36-50(2003).
RN   [4]
RP   REVIEW.
RX   PubMed=15719026; DOI=10.1038/sj.cdd.4401584;
RA   Perfettini J.-L., Castedo M., Roumier T., Andreau K., Nardacci R.,
RA   Piacentini M., Kroemer G.;
RT   "Mechanisms of apoptosis induction by the HIV-1 envelope.";
RL   Cell Death Differ. 12:916-923(2005).
RN   [5]
RP   REVIEW.
RX   PubMed=15725757; DOI=10.1089/aid.2005.21.171;
RA   Hartley O., Klasse P.J., Sattentau Q.J., Moore J.P.;
RT   "V3: HIV's switch-hitter.";
RL   AIDS Res. Hum. Retroviruses 21:171-189(2005).
RN   [6]
RP   REVIEW.
RX   PubMed=16114975; DOI=10.2165/00003495-200565130-00002;
RA   Reeves J.D., Piefer A.J.;
RT   "Emerging drug targets for antiretroviral therapy.";
RL   Drugs 65:1747-1766(2005).
RN   [7]
RP   REVIEW.
RX   PubMed=16437164; DOI=10.1038/sj.emboj.7600947;
RA   Lusso P.;
RT   "HIV and the chemokine system: 10 years later.";
RL   EMBO J. 25:447-456(2006).
CC   -!- FUNCTION: [Envelope glycoprotein gp160]: Oligomerizes in the host
CC       endoplasmic reticulum into predominantly trimers. In a second time,
CC       gp160 transits in the host Golgi, where glycosylation is completed. The
CC       precursor is then proteolytically cleaved in the trans-Golgi and
CC       thereby activated by cellular furin or furin-like proteases to produce
CC       gp120 and gp41. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- FUNCTION: [Surface protein gp120]: Attaches the virus to the host
CC       lymphoid cell by binding to the primary receptor CD4. This interaction
CC       induces a structural rearrangement creating a high affinity binding
CC       site for a chemokine coreceptor like CXCR4 and/or CCR5. Acts as a
CC       ligand for CD209/DC-SIGN and CLEC4M/DC-SIGNR, which are respectively
CC       found on dendritic cells (DCs), and on endothelial cells of liver
CC       sinusoids and lymph node sinuses. These interactions allow capture of
CC       viral particles at mucosal surfaces by these cells and subsequent
CC       transmission to permissive cells. HIV subverts the migration properties
CC       of dendritic cells to gain access to CD4+ T-cells in lymph nodes. Virus
CC       transmission to permissive T-cells occurs either in trans (without DCs
CC       infection, through viral capture and transmission), or in cis
CC       (following DCs productive infection, through the usual CD4-gp120
CC       interaction), thereby inducing a robust infection. In trans infection,
CC       bound virions remain infectious over days and it is proposed that they
CC       are not degraded, but protected in non-lysosomal acidic organelles
CC       within the DCs close to the cell membrane thus contributing to the
CC       viral infectious potential during DCs' migration from the periphery to
CC       the lymphoid tissues. On arrival at lymphoid tissues, intact virions
CC       recycle back to DCs' cell surface allowing virus transmission to CD4+
CC       T-cells. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- FUNCTION: [Transmembrane protein gp41]: Acts as a class I viral fusion
CC       protein. Under the current model, the protein has at least 3
CC       conformational states: pre-fusion native state, pre-hairpin
CC       intermediate state, and post-fusion hairpin state. During fusion of
CC       viral and target intracellular membranes, the coiled coil regions
CC       (heptad repeats) assume a trimer-of-hairpins structure, positioning the
CC       fusion peptide in close proximity to the C-terminal region of the
CC       ectodomain. The formation of this structure appears to drive apposition
CC       and subsequent fusion of viral and target cell membranes. Complete
CC       fusion occurs in host cell endosomes and is dynamin-dependent, however
CC       some lipid transfer might occur at the plasma membrane. The virus
CC       undergoes clathrin-dependent internalization long before endosomal
CC       fusion, thus minimizing the surface exposure of conserved viral
CC       epitopes during fusion and reducing the efficacy of inhibitors
CC       targeting these epitopes. Membranes fusion leads to delivery of the
CC       nucleocapsid into the cytoplasm. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBUNIT: [Surface protein gp120]: The mature envelope protein (Env)
CC       consists of a homotrimer of non-covalently associated gp120-gp41
CC       heterodimers. The resulting complex protrudes from the virus surface as
CC       a spike. There seems to be as few as 10 spikes on the average virion.
CC       Interacts with host CD4, CCR5 and CXCR4. Gp120 also interacts with the
CC       C-type lectins CD209/DC-SIGN and CLEC4M/DC-SIGNR (collectively referred
CC       to as DC-SIGN(R)). Gp120 and gp41 interact with GalCer. Gp120 interacts
CC       with host ITGA4/ITGB7 complex; on CD4+ T-cells, this interaction
CC       results in rapid activation of integrin ITGAL/LFA-1, which facilitates
CC       efficient cell-to-cell spreading of HIV-1. Gp120 interacts with cell-
CC       associated heparan sulfate; this interaction increases virus
CC       infectivity on permissive cells and may be involved in infection of
CC       CD4- cells. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBUNIT: [Transmembrane protein gp41]: The mature envelope protein
CC       (Env) consists of a homotrimer of non-covalently associated gp120-gp41
CC       heterodimers. The resulting complex protrudes from the virus surface as
CC       a spike. There seems to be as few as 10 spikes on the average virion.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBCELLULAR LOCATION: [Surface protein gp120]: Virion membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Peripheral membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host cell membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Peripheral membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host endosome membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Note=The surface protein is not
CC       anchored to the viral envelope, but associates with the extravirion
CC       surface through its binding to TM. It is probably concentrated at the
CC       site of budding and incorporated into the virions possibly by contacts
CC       between the cytoplasmic tail of Env and the N-terminus of Gag.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBCELLULAR LOCATION: [Transmembrane protein gp41]: Virion membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host cell membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host endosome membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Note=It is probably concentrated at
CC       the site of budding and incorporated into the virions possibly by
CC       contacts between the cytoplasmic tail of Env and the N-terminus of Gag.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: Some of the most genetically diverse regions of the viral
CC       genome are present in Env. They are called variable regions 1 through 5
CC       (V1 through V5). Coreceptor usage of gp120 is determined mainly by the
CC       primary structure of the third variable region (V3) in the outer domain
CC       of gp120. The sequence of V3 determines which coreceptor, CCR5 and/or
CC       CXCR4 (corresponding to R5/macrophage, X4/T cell and R5X4/T cell and
CC       macrophage tropism), is used to trigger the fusion potential of the Env
CC       complex, and hence which cells the virus can infect. Binding to CCR5
CC       involves a region adjacent in addition to V3. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- DOMAIN: The membrane proximal external region (MPER) present in gp41 is
CC       a tryptophan-rich region recognized by the antibodies 2F5, Z13, and
CC       4E10. MPER seems to play a role in fusion. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- DOMAIN: The 17 amino acids long immunosuppressive region is present in
CC       many retroviral envelope proteins. Synthetic peptides derived from this
CC       relatively conserved sequence inhibit immune function in vitro and in
CC       vivo. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: The YXXL motif is involved in determining the exact site of
CC       viral release at the surface of infected mononuclear cells and promotes
CC       endocytosis. YXXL and di-leucine endocytosis motifs interact directly
CC       or indirectly with the clathrin adapter complexes, opperate
CC       independently, and their activities are not additive.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: The CD4-binding region is targeted by the antibody b12.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- PTM: Highly glycosylated by host. The high number of glycan on the
CC       protein is reffered to as 'glycan shield' because it contributes to
CC       hide protein sequence from adaptive immune system. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- PTM: Palmitoylation of the transmembrane protein and of Env polyprotein
CC       (prior to its proteolytic cleavage) is essential for their association
CC       with host cell membrane lipid rafts. Palmitoylation is therefore
CC       required for envelope trafficking to classical lipid rafts, but not for
CC       viral replication. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- PTM: Specific enzymatic cleavages in vivo yield mature proteins.
CC       Envelope glycoproteins are synthesized as an inactive precursor that is
CC       heavily N-glycosylated and processed likely by host cell furin in the
CC       Golgi to yield the mature SU and TM proteins. The cleavage site between
CC       SU and TM requires the minimal sequence [KR]-X-[KR]-R. About 2 of the 9
CC       disulfide bonds of gp41 are reduced by P4HB/PDI, following binding to
CC       CD4 receptor. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- MISCELLANEOUS: Inhibitors targeting HIV-1 viral envelope proteins are
CC       used as antiretroviral drugs. Attachment of virions to the cell surface
CC       via non-specific interactions and CD4 binding can be blocked by
CC       inhibitors that include cyanovirin-N, cyclotriazadisulfonamide analogs,
CC       PRO 2000, TNX 355 and PRO 542. In addition, BMS 806 can block CD4-
CC       induced conformational changes. Env interactions with the coreceptor
CC       molecules can be targeted by CCR5 antagonists including SCH-D,
CC       maraviroc (UK 427857) and aplaviroc (GW 873140), and the CXCR4
CC       antagonist AMD 070. Fusion of viral and cellular membranes can be
CC       inhibited by peptides such as enfuvirtide and tifuvirtide (T 1249).
CC       Resistance to inhibitors associated with mutations in Env are observed.
CC       Most of the time, single mutations confer only a modest reduction in
CC       drug susceptibility. Combination of several mutations is usually
CC       required to develop a high-level drug resistance. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- MISCELLANEOUS: HIV-1 lineages are divided in three main groups, M (for
CC       Major), O (for Outlier), and N (for New, or Non-M, Non-O). The vast
CC       majority of strains found worldwide belong to the group M. Group O
CC       seems to be endemic to and largely confined to Cameroon and neighboring
CC       countries in West Central Africa, where these viruses represent a small
CC       minority of HIV-1 strains. The group N is represented by a limited
CC       number of isolates from Cameroonian persons. The group M is further
CC       subdivided in 9 clades or subtypes (A to D, F to H, J and K).
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SIMILARITY: Belongs to the HIV-1 env protein family.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- WEB RESOURCE: Name=hivdb; Note=HIV drug resistance database;
CC       URL="https://hivdb.stanford.edu";
CC   -!- WEB RESOURCE: Name=HIV drug resistance mutations;
CC       URL="https://www.iasusa.org/content/hiv-drug-resistance-mutations";
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DR   EMBL; M14100; AAA44679.1; -; Genomic_RNA.
DR   PDB; 1JAU; NMR; -; A=665-683.
DR   PDB; 1JAV; NMR; -; A=665-683.
DR   PDBsum; 1JAU; -.
DR   PDBsum; 1JAV; -.
DR   BMRB; P04624; -.
DR   SMR; P04624; -.
DR   GlyCosmos; P04624; 29 sites, No reported glycans.
DR   Reactome; R-HSA-5621480; Dectin-2 family.
DR   EvolutionaryTrace; P04624; -.
DR   GO; GO:0044175; C:host cell endosome membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0016020; C:membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:0019031; C:viral envelope; IEA:UniProtKB-KW.
DR   GO; GO:0055036; C:virion membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005198; F:structural molecule activity; IEA:UniProtKB-UniRule.
DR   GO; GO:0075512; P:clathrin-dependent endocytosis of virus by host cell; IEA:UniProtKB-UniRule.
DR   GO; GO:0039654; P:fusion of virus membrane with host endosome membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:0019064; P:fusion of virus membrane with host plasma membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:1903905; P:positive regulation of establishment of T cell polarity; IEA:UniProtKB-UniRule.
DR   GO; GO:1903908; P:positive regulation of plasma membrane raft polarization; IEA:UniProtKB-UniRule.
DR   GO; GO:1903911; P:positive regulation of receptor clustering; IEA:UniProtKB-UniRule.
DR   GO; GO:0019082; P:viral protein processing; IEA:UniProtKB-UniRule.
DR   GO; GO:0019062; P:virion attachment to host cell; IEA:UniProtKB-UniRule.
DR   GO; GO:0019049; P:virus-mediated perturbation of host defense response; IEA:UniProtKB-UniRule.
DR   CDD; cd09909; HIV-1-like_HR1-HR2; 1.
DR   Gene3D; 1.10.287.210; -; 1.
DR   Gene3D; 2.170.40.20; Human immunodeficiency virus 1, Gp160, envelope glycoprotein; 2.
DR   Gene3D; 1.20.5.490; Single helix bin; 1.
DR   HAMAP; MF_04083; HIV_ENV; 1.
DR   InterPro; IPR036377; Gp120_core_sf.
DR   InterPro; IPR037527; Gp160.
DR   InterPro; IPR000328; GP41-like.
DR   InterPro; IPR000777; HIV1_Gp120.
DR   Pfam; PF00516; GP120; 1.
DR   Pfam; PF00517; GP41; 1.
DR   SUPFAM; SSF56502; gp120 core; 1.
DR   SUPFAM; SSF58069; Virus ectodomain; 1.
PE   1: Evidence at protein level;
KW   3D-structure; AIDS; Apoptosis;
KW   Clathrin-mediated endocytosis of virus by host;
KW   Cleavage on pair of basic residues; Coiled coil; Disulfide bond;
KW   Fusion of virus membrane with host endosomal membrane;
KW   Fusion of virus membrane with host membrane; Glycoprotein;
KW   Host cell membrane; Host endosome; Host membrane; Host-virus interaction;
KW   Lipoprotein; Membrane; Palmitate; Signal; Transmembrane;
KW   Transmembrane helix; Viral attachment to host cell; Viral envelope protein;
KW   Viral immunoevasion; Viral penetration into host cytoplasm; Virion;
KW   Virus endocytosis by host; Virus entry into host cell.
FT   SIGNAL          1..32
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CHAIN           33..856
FT                   /note="Envelope glycoprotein gp160"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000239493"
FT   CHAIN           33..511
FT                   /note="Surface protein gp120"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000038429"
FT   CHAIN           512..856
FT                   /note="Transmembrane protein gp41"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000038430"
FT   TOPO_DOM        33..684
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   TRANSMEM        685..705
FT                   /note="Helical"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   TOPO_DOM        706..856
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          131..156
FT                   /note="V1"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          157..196
FT                   /note="V2"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          296..330
FT                   /note="V3"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          364..374
FT                   /note="CD4-binding loop"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          385..418
FT                   /note="V4"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          461..471
FT                   /note="V5"
FT   REGION          463..471
FT                   /note="V5"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          512..532
FT                   /note="Fusion peptide"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          574..592
FT                   /note="Immunosuppression"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          662..683
FT                   /note="MPER; binding to GalCer"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          720..740
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COILED          633..667
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   MOTIF           712..715
FT                   /note="YXXL motif; contains endocytosis signal"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   MOTIF           855..856
FT                   /note="Di-leucine internalization motif"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   SITE            511..512
FT                   /note="Cleavage; by host furin"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   LIPID           764
FT                   /note="S-palmitoyl cysteine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        88
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        136
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        141
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        156
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        160
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        186
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        197
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        230
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        234
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        241
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        262
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        276
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        289
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        295
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        301
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        332
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        339
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        356
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        386
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        392
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        397
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        406
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        448
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        463
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        611
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        616
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        624
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        637
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        674
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        119..205
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        126..196
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        131..157
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        218..247
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        228..239
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        296..331
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        378..445
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        385..418
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        598..604
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   HELIX           666..668
FT                   /evidence="ECO:0007829|PDB:1JAV"
FT   HELIX           670..673
FT                   /evidence="ECO:0007829|PDB:1JAU"
FT   HELIX           675..682
FT                   /evidence="ECO:0007829|PDB:1JAU"
SQ   SEQUENCE   856 AA;  97189 MW;  3373C68BB84C1AFC CRC64;
     MRVKEKYQHL WRWGWRWGTM LLGMLMICSA TEKLWVTVYY GVPVWKEATT TLFCASDAKA
     YDTEVHNVWA THAGVPTDPN PQEVVLVNVT ENFNMWKNDM VEQMHEDIIS LWDQSLKPCV
     KLTPLCVSLK CTDLKNDTNT NSSSGRMIME KGEIKNCSFN ISTSIRGKVQ KEYAFFYKLD
     IIPIDNDTTS YTLTSCNTSV ITQACPKVSF EPIPIHYCAP AGFAILKCNN KTFNGTGPCT
     NVSTVQCTHG IRPVVSTQLL LNGSLAEEEV VIRSVNFTDN AKTIIVQLNT SVEINCTRPN
     NNTRKKIRIQ RGPGRAFVTI GKIGNMRQAH CNISRAKWNA TLKQIASKLR EQFGNNKTII
     FKQSSGGDPE IVTHSFNCGG EFFYCNSTQL FNSTWFNSTW STEGSNNTEG SDTITLPCRI
     KQFINMWQEV GKAMYAPPIS GQIRCSSNIT GLLLTRDGGN NNNGSEIFRP GGGDMRDNWR
     SELYKYKVVK IEPLGVAPTK AKRRVVQREK RAVGIGALFL GFLGAAGSTM GAASMTLTVQ
     ARQLLSGIVQ QQNNLLRAIE AQQHLLQLTV WGIKQLQARI LAVERYLKDQ QLLGIWGCSG
     KLLCTTAVPW NASWSNKSLE QIWNHTTWME WDREINNYTS LIHSLIEESQ NQQEKNEQEL
     LELDKWASLW NWFNITNWLW YIKLFIMIVG GLVGLRIVFA VLSVVNRVRQ GYSPLSFQTH
     LPIPRGPDRP EGIEEEGGER DRDRSIRLVN GSLALIWDDL RSLCLFSYHR LRDLLLIVTR
     IVELLGRRGW EALKYWWNLL QYWSQELKNS AVSLLNATAI AVAEGTDRVI EVVQEAYRAI
     RHIPRRIRQG LERILL
//
ID   ENV_HV1J3               Reviewed;         867 AA.
AC   P12489;
DT   01-OCT-1989, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-1989, sequence version 1.
DT   27-MAR-2024, entry version 140.
DE   RecName: Full=Envelope glycoprotein gp160 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   AltName: Full=Env polyprotein {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Contains:
DE     RecName: Full=Surface protein gp120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=SU {ECO:0000255|HAMAP-Rule:MF_04083};
DE     AltName: Full=Glycoprotein 120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=gp120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Contains:
DE     RecName: Full=Transmembrane protein gp41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=TM {ECO:0000255|HAMAP-Rule:MF_04083};
DE     AltName: Full=Glycoprotein 41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=gp41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Flags: Precursor;
GN   Name=env {ECO:0000255|HAMAP-Rule:MF_04083};
OS   Human immunodeficiency virus type 1 group M subtype B (isolate JH32)
OS   (HIV-1).
OC   Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC   Ortervirales; Retroviridae; Orthoretrovirinae; Lentivirus;
OC   Human immunodeficiency virus 1.
OX   NCBI_TaxID=11694;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX   PubMed=2669897; DOI=10.1089/aid.1989.5.411;
RA   Komiyama N., Hattori N., Inoue J., Sakuma S., Kurimura T., Yoshida M.;
RT   "Nucleotide sequences of gag and env genes of a Japanese isolate of HIV-1
RT   and their expression in bacteria.";
RL   AIDS Res. Hum. Retroviruses 5:411-419(1989).
RN   [2]
RP   REVIEW.
RX   PubMed=12974773; DOI=10.1034/j.1600-0463.2003.11107803.x;
RA   Geijtenbeek T.B., van Kooyk Y.;
RT   "Pathogens target DC-SIGN to influence their fate DC-SIGN functions as a
RT   pathogen receptor with broad specificity.";
RL   APMIS 111:698-714(2003).
RN   [3]
RP   REVIEW.
RX   PubMed=12873764; DOI=10.1016/s0005-2736(03)00161-5;
RA   Gallo S.A., Finnegan C.M., Viard M., Raviv Y., Dimitrov A., Rawat S.S.,
RA   Puri A., Durell S., Blumenthal R.;
RT   "The HIV Env-mediated fusion reaction.";
RL   Biochim. Biophys. Acta 1614:36-50(2003).
RN   [4]
RP   REVIEW.
RX   PubMed=15719026; DOI=10.1038/sj.cdd.4401584;
RA   Perfettini J.-L., Castedo M., Roumier T., Andreau K., Nardacci R.,
RA   Piacentini M., Kroemer G.;
RT   "Mechanisms of apoptosis induction by the HIV-1 envelope.";
RL   Cell Death Differ. 12:916-923(2005).
RN   [5]
RP   REVIEW.
RX   PubMed=15725757; DOI=10.1089/aid.2005.21.171;
RA   Hartley O., Klasse P.J., Sattentau Q.J., Moore J.P.;
RT   "V3: HIV's switch-hitter.";
RL   AIDS Res. Hum. Retroviruses 21:171-189(2005).
RN   [6]
RP   REVIEW.
RX   PubMed=16114975; DOI=10.2165/00003495-200565130-00002;
RA   Reeves J.D., Piefer A.J.;
RT   "Emerging drug targets for antiretroviral therapy.";
RL   Drugs 65:1747-1766(2005).
RN   [7]
RP   REVIEW.
RX   PubMed=16437164; DOI=10.1038/sj.emboj.7600947;
RA   Lusso P.;
RT   "HIV and the chemokine system: 10 years later.";
RL   EMBO J. 25:447-456(2006).
CC   -!- FUNCTION: [Envelope glycoprotein gp160]: Oligomerizes in the host
CC       endoplasmic reticulum into predominantly trimers. In a second time,
CC       gp160 transits in the host Golgi, where glycosylation is completed. The
CC       precursor is then proteolytically cleaved in the trans-Golgi and
CC       thereby activated by cellular furin or furin-like proteases to produce
CC       gp120 and gp41. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- FUNCTION: [Surface protein gp120]: Attaches the virus to the host
CC       lymphoid cell by binding to the primary receptor CD4. This interaction
CC       induces a structural rearrangement creating a high affinity binding
CC       site for a chemokine coreceptor like CXCR4 and/or CCR5. Acts as a
CC       ligand for CD209/DC-SIGN and CLEC4M/DC-SIGNR, which are respectively
CC       found on dendritic cells (DCs), and on endothelial cells of liver
CC       sinusoids and lymph node sinuses. These interactions allow capture of
CC       viral particles at mucosal surfaces by these cells and subsequent
CC       transmission to permissive cells. HIV subverts the migration properties
CC       of dendritic cells to gain access to CD4+ T-cells in lymph nodes. Virus
CC       transmission to permissive T-cells occurs either in trans (without DCs
CC       infection, through viral capture and transmission), or in cis
CC       (following DCs productive infection, through the usual CD4-gp120
CC       interaction), thereby inducing a robust infection. In trans infection,
CC       bound virions remain infectious over days and it is proposed that they
CC       are not degraded, but protected in non-lysosomal acidic organelles
CC       within the DCs close to the cell membrane thus contributing to the
CC       viral infectious potential during DCs' migration from the periphery to
CC       the lymphoid tissues. On arrival at lymphoid tissues, intact virions
CC       recycle back to DCs' cell surface allowing virus transmission to CD4+
CC       T-cells. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- FUNCTION: [Transmembrane protein gp41]: Acts as a class I viral fusion
CC       protein. Under the current model, the protein has at least 3
CC       conformational states: pre-fusion native state, pre-hairpin
CC       intermediate state, and post-fusion hairpin state. During fusion of
CC       viral and target intracellular membranes, the coiled coil regions
CC       (heptad repeats) assume a trimer-of-hairpins structure, positioning the
CC       fusion peptide in close proximity to the C-terminal region of the
CC       ectodomain. The formation of this structure appears to drive apposition
CC       and subsequent fusion of viral and target cell membranes. Complete
CC       fusion occurs in host cell endosomes and is dynamin-dependent, however
CC       some lipid transfer might occur at the plasma membrane. The virus
CC       undergoes clathrin-dependent internalization long before endosomal
CC       fusion, thus minimizing the surface exposure of conserved viral
CC       epitopes during fusion and reducing the efficacy of inhibitors
CC       targeting these epitopes. Membranes fusion leads to delivery of the
CC       nucleocapsid into the cytoplasm. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBUNIT: [Surface protein gp120]: The mature envelope protein (Env)
CC       consists of a homotrimer of non-covalently associated gp120-gp41
CC       heterodimers. The resulting complex protrudes from the virus surface as
CC       a spike. There seems to be as few as 10 spikes on the average virion.
CC       Interacts with host CD4, CCR5 and CXCR4. Gp120 also interacts with the
CC       C-type lectins CD209/DC-SIGN and CLEC4M/DC-SIGNR (collectively referred
CC       to as DC-SIGN(R)). Gp120 and gp41 interact with GalCer. Gp120 interacts
CC       with host ITGA4/ITGB7 complex; on CD4+ T-cells, this interaction
CC       results in rapid activation of integrin ITGAL/LFA-1, which facilitates
CC       efficient cell-to-cell spreading of HIV-1. Gp120 interacts with cell-
CC       associated heparan sulfate; this interaction increases virus
CC       infectivity on permissive cells and may be involved in infection of
CC       CD4- cells. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBUNIT: [Transmembrane protein gp41]: The mature envelope protein
CC       (Env) consists of a homotrimer of non-covalently associated gp120-gp41
CC       heterodimers. The resulting complex protrudes from the virus surface as
CC       a spike. There seems to be as few as 10 spikes on the average virion.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBCELLULAR LOCATION: [Surface protein gp120]: Virion membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Peripheral membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host cell membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Peripheral membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host endosome membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Note=The surface protein is not
CC       anchored to the viral envelope, but associates with the extravirion
CC       surface through its binding to TM. It is probably concentrated at the
CC       site of budding and incorporated into the virions possibly by contacts
CC       between the cytoplasmic tail of Env and the N-terminus of Gag.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBCELLULAR LOCATION: [Transmembrane protein gp41]: Virion membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host cell membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host endosome membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Note=It is probably concentrated at
CC       the site of budding and incorporated into the virions possibly by
CC       contacts between the cytoplasmic tail of Env and the N-terminus of Gag.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: Some of the most genetically diverse regions of the viral
CC       genome are present in Env. They are called variable regions 1 through 5
CC       (V1 through V5). Coreceptor usage of gp120 is determined mainly by the
CC       primary structure of the third variable region (V3) in the outer domain
CC       of gp120. The sequence of V3 determines which coreceptor, CCR5 and/or
CC       CXCR4 (corresponding to R5/macrophage, X4/T cell and R5X4/T cell and
CC       macrophage tropism), is used to trigger the fusion potential of the Env
CC       complex, and hence which cells the virus can infect. Binding to CCR5
CC       involves a region adjacent in addition to V3. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- DOMAIN: The membrane proximal external region (MPER) present in gp41 is
CC       a tryptophan-rich region recognized by the antibodies 2F5, Z13, and
CC       4E10. MPER seems to play a role in fusion. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- DOMAIN: The 17 amino acids long immunosuppressive region is present in
CC       many retroviral envelope proteins. Synthetic peptides derived from this
CC       relatively conserved sequence inhibit immune function in vitro and in
CC       vivo. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: The YXXL motif is involved in determining the exact site of
CC       viral release at the surface of infected mononuclear cells and promotes
CC       endocytosis. YXXL and di-leucine endocytosis motifs interact directly
CC       or indirectly with the clathrin adapter complexes, opperate
CC       independently, and their activities are not additive.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: The CD4-binding region is targeted by the antibody b12.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- PTM: Highly glycosylated by host. The high number of glycan on the
CC       protein is reffered to as 'glycan shield' because it contributes to
CC       hide protein sequence from adaptive immune system. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- PTM: Palmitoylation of the transmembrane protein and of Env polyprotein
CC       (prior to its proteolytic cleavage) is essential for their association
CC       with host cell membrane lipid rafts. Palmitoylation is therefore
CC       required for envelope trafficking to classical lipid rafts, but not for
CC       viral replication. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- PTM: Specific enzymatic cleavages in vivo yield mature proteins.
CC       Envelope glycoproteins are synthesized as an inactive precursor that is
CC       heavily N-glycosylated and processed likely by host cell furin in the
CC       Golgi to yield the mature SU and TM proteins. The cleavage site between
CC       SU and TM requires the minimal sequence [KR]-X-[KR]-R. About 2 of the 9
CC       disulfide bonds of gp41 are reduced by P4HB/PDI, following binding to
CC       CD4 receptor. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- MISCELLANEOUS: Inhibitors targeting HIV-1 viral envelope proteins are
CC       used as antiretroviral drugs. Attachment of virions to the cell surface
CC       via non-specific interactions and CD4 binding can be blocked by
CC       inhibitors that include cyanovirin-N, cyclotriazadisulfonamide analogs,
CC       PRO 2000, TNX 355 and PRO 542. In addition, BMS 806 can block CD4-
CC       induced conformational changes. Env interactions with the coreceptor
CC       molecules can be targeted by CCR5 antagonists including SCH-D,
CC       maraviroc (UK 427857) and aplaviroc (GW 873140), and the CXCR4
CC       antagonist AMD 070. Fusion of viral and cellular membranes can be
CC       inhibited by peptides such as enfuvirtide and tifuvirtide (T 1249).
CC       Resistance to inhibitors associated with mutations in Env are observed.
CC       Most of the time, single mutations confer only a modest reduction in
CC       drug susceptibility. Combination of several mutations is usually
CC       required to develop a high-level drug resistance. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- MISCELLANEOUS: HIV-1 lineages are divided in three main groups, M (for
CC       Major), O (for Outlier), and N (for New, or Non-M, Non-O). The vast
CC       majority of strains found worldwide belong to the group M. Group O
CC       seems to be endemic to and largely confined to Cameroon and neighboring
CC       countries in West Central Africa, where these viruses represent a small
CC       minority of HIV-1 strains. The group N is represented by a limited
CC       number of isolates from Cameroonian persons. The group M is further
CC       subdivided in 9 clades or subtypes (A to D, F to H, J and K).
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SIMILARITY: Belongs to the HIV-1 env protein family.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- WEB RESOURCE: Name=hivdb; Note=HIV drug resistance database;
CC       URL="https://hivdb.stanford.edu";
CC   -!- WEB RESOURCE: Name=HIV drug resistance mutations;
CC       URL="https://www.iasusa.org/content/hiv-drug-resistance-mutations";
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DR   EMBL; AH003604; AAB03526.1; -; Genomic_RNA.
DR   SMR; P12489; -.
DR   GlyCosmos; P12489; 30 sites, No reported glycans.
DR   Reactome; R-HSA-5621480; Dectin-2 family.
DR   GO; GO:0044175; C:host cell endosome membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0016020; C:membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:0019031; C:viral envelope; IEA:UniProtKB-KW.
DR   GO; GO:0055036; C:virion membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005198; F:structural molecule activity; IEA:UniProtKB-UniRule.
DR   GO; GO:0075512; P:clathrin-dependent endocytosis of virus by host cell; IEA:UniProtKB-UniRule.
DR   GO; GO:0039654; P:fusion of virus membrane with host endosome membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:0019064; P:fusion of virus membrane with host plasma membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:1903905; P:positive regulation of establishment of T cell polarity; IEA:UniProtKB-UniRule.
DR   GO; GO:1903908; P:positive regulation of plasma membrane raft polarization; IEA:UniProtKB-UniRule.
DR   GO; GO:1903911; P:positive regulation of receptor clustering; IEA:UniProtKB-UniRule.
DR   GO; GO:0019082; P:viral protein processing; IEA:UniProtKB-UniRule.
DR   GO; GO:0019062; P:virion attachment to host cell; IEA:UniProtKB-UniRule.
DR   GO; GO:0019049; P:virus-mediated perturbation of host defense response; IEA:UniProtKB-UniRule.
DR   CDD; cd09909; HIV-1-like_HR1-HR2; 1.
DR   Gene3D; 1.10.287.210; -; 1.
DR   Gene3D; 2.170.40.20; Human immunodeficiency virus 1, Gp160, envelope glycoprotein; 2.
DR   Gene3D; 1.20.5.490; Single helix bin; 1.
DR   HAMAP; MF_04083; HIV_ENV; 1.
DR   InterPro; IPR036377; Gp120_core_sf.
DR   InterPro; IPR037527; Gp160.
DR   InterPro; IPR000328; GP41-like.
DR   InterPro; IPR000777; HIV1_Gp120.
DR   Pfam; PF00516; GP120; 1.
DR   Pfam; PF00517; GP41; 1.
DR   SUPFAM; SSF56502; gp120 core; 2.
DR   SUPFAM; SSF58069; Virus ectodomain; 1.
PE   3: Inferred from homology;
KW   AIDS; Apoptosis; Clathrin-mediated endocytosis of virus by host;
KW   Cleavage on pair of basic residues; Coiled coil; Disulfide bond;
KW   Fusion of virus membrane with host endosomal membrane;
KW   Fusion of virus membrane with host membrane; Glycoprotein;
KW   Host cell membrane; Host endosome; Host membrane; Host-virus interaction;
KW   Lipoprotein; Membrane; Palmitate; Signal; Transmembrane;
KW   Transmembrane helix; Viral attachment to host cell; Viral envelope protein;
KW   Viral immunoevasion; Viral penetration into host cytoplasm; Virion;
KW   Virus endocytosis by host; Virus entry into host cell.
FT   SIGNAL          1..31
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CHAIN           32..867
FT                   /note="Envelope glycoprotein gp160"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000239482"
FT   CHAIN           32..523
FT                   /note="Surface protein gp120"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000038404"
FT   CHAIN           524..867
FT                   /note="Transmembrane protein gp41"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000038405"
FT   TOPO_DOM        32..695
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   TRANSMEM        696..716
FT                   /note="Helical"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   TOPO_DOM        717..867
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          130..159
FT                   /note="V1"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          160..208
FT                   /note="V2"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          308..341
FT                   /note="V3"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          374..384
FT                   /note="CD4-binding loop"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          395..430
FT                   /note="V4"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          473..483
FT                   /note="V5"
FT   REGION          475..483
FT                   /note="V5"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          524..544
FT                   /note="Fusion peptide"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          585..603
FT                   /note="Immunosuppression"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          673..694
FT                   /note="MPER; binding to GalCer"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          730..755
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COILED          644..678
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   MOTIF           723..726
FT                   /note="YXXL motif; contains endocytosis signal"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   MOTIF           866..867
FT                   /note="Di-leucine internalization motif"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   COMPBIAS        738..755
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   SITE            523..524
FT                   /note="Cleavage; by host furin"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   LIPID           775
FT                   /note="S-palmitoyl cysteine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        87
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        135
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        140
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        143
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        159
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        163
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        188
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        189
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        199
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        209
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        246
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        253
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        274
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        288
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        307
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        350
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        366
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        372
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        396
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        402
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        408
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        412
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        418
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        423
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        460
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        475
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        622
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        627
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        636
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        648
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        53..73
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        118..217
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        125..208
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        130..160
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        230..259
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        240..251
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        308..342
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        388..457
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        395..430
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        609..615
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
SQ   SEQUENCE   867 AA;  98399 MW;  5F2310146B8E8680 CRC64;
     MRVKGIRKNY QHLWRWGTML LGILMICSAA EQLWVTVYYG VPVWKEAATT LFCASDAKAY
     DTEVHNVWAT HACVPTDPNP QEVVLENVTE KFNMWKNNMV EQMHEDIISL WDQSLKPCVK
     LTPLCVTLNC IDWGNDTSPN ATNTTSSGGE KMEKGEMKNC SFNITTSIRD KVQKEHALFY
     KHDVVPINNS TKDNIKNDNS TRYRLISCNT SVITQACPKI SFEPIPIHYC APAGFAIIKC
     NDKKFNGTGP CTNVSTVQCT HGIKPVVSTQ LLLNGSLAEE EVVIRSENFT DNAKTIIVQL
     KEPVVINCTR PSKTTRRRIH IGPGRAFYTT KQIAGDLRQA HCNINRARWN ATLKQIVGKL
     RKQFVNKTIV FNRSSGGDPE IVMHSFNCGG EFFYCNSTQL FNSTWLSNST WNDTEGSNNT
     GGNDTITLPC RIKQIINMWQ EVGKAMYAPP IEGQIRCSSN ITGLLLTRDG GDNQNETETF
     RPGGGNMRDN WRSELYKYKV VKIELLGVAP TKAKRRVVQR EKRAVGIGAV FLGFLGAAGS
     TMGASMTLTV QARLLLSGIV QQQNNLLRAI EGQQHLLQLT VWGIKQLQAR ILAVERYLKD
     QQLLGIWGCS GKLICTTAVP WNASWSNKSL EEIWDNMTWM EWEREIDNYT SLIYTLIEES
     QNQQEKNEQE LLGLDKWASL WNWFTITNWL WYIRIFIMIV GGLVGLRIVF TVLSIVNRVR
     QGYSPLSFQT RLPAPRGPDR PEGIEEEGGD RDRDRSGQLV DGLLAIIWVD LRSLCLFSYH
     RLRDLLLIVT RIVELLGRRG WEALKYWWNL LQYWSQELKN SAVSLFNAIA IAVAEGTDRV
     LKILQRAFRA ILHIPTRIRQ GLERALL
//
ID   ENV_HV1JR               Reviewed;         848 AA.
AC   P20871;
DT   01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
DT   01-FEB-1991, sequence version 1.
DT   27-MAR-2024, entry version 155.
DE   RecName: Full=Envelope glycoprotein gp160 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   AltName: Full=Env polyprotein {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Contains:
DE     RecName: Full=Surface protein gp120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=SU {ECO:0000255|HAMAP-Rule:MF_04083};
DE     AltName: Full=Glycoprotein 120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=gp120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Contains:
DE     RecName: Full=Transmembrane protein gp41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=TM {ECO:0000255|HAMAP-Rule:MF_04083};
DE     AltName: Full=Glycoprotein 41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=gp41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Flags: Precursor;
GN   Name=env {ECO:0000255|HAMAP-Rule:MF_04083};
OS   Human immunodeficiency virus type 1 group M subtype B (isolate JRCSF)
OS   (HIV-1).
OC   Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC   Ortervirales; Retroviridae; Orthoretrovirinae; Lentivirus;
OC   Human immunodeficiency virus 1.
OX   NCBI_TaxID=11688;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RA   Koyanagi S., Chen I.S.Y.;
RL   Submitted (DEC-1988) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   REVIEW.
RX   PubMed=12974773; DOI=10.1034/j.1600-0463.2003.11107803.x;
RA   Geijtenbeek T.B., van Kooyk Y.;
RT   "Pathogens target DC-SIGN to influence their fate DC-SIGN functions as a
RT   pathogen receptor with broad specificity.";
RL   APMIS 111:698-714(2003).
RN   [3]
RP   REVIEW.
RX   PubMed=12873764; DOI=10.1016/s0005-2736(03)00161-5;
RA   Gallo S.A., Finnegan C.M., Viard M., Raviv Y., Dimitrov A., Rawat S.S.,
RA   Puri A., Durell S., Blumenthal R.;
RT   "The HIV Env-mediated fusion reaction.";
RL   Biochim. Biophys. Acta 1614:36-50(2003).
RN   [4]
RP   REVIEW.
RX   PubMed=15719026; DOI=10.1038/sj.cdd.4401584;
RA   Perfettini J.-L., Castedo M., Roumier T., Andreau K., Nardacci R.,
RA   Piacentini M., Kroemer G.;
RT   "Mechanisms of apoptosis induction by the HIV-1 envelope.";
RL   Cell Death Differ. 12:916-923(2005).
RN   [5]
RP   REVIEW.
RX   PubMed=15725757; DOI=10.1089/aid.2005.21.171;
RA   Hartley O., Klasse P.J., Sattentau Q.J., Moore J.P.;
RT   "V3: HIV's switch-hitter.";
RL   AIDS Res. Hum. Retroviruses 21:171-189(2005).
RN   [6]
RP   REVIEW.
RX   PubMed=16114975; DOI=10.2165/00003495-200565130-00002;
RA   Reeves J.D., Piefer A.J.;
RT   "Emerging drug targets for antiretroviral therapy.";
RL   Drugs 65:1747-1766(2005).
RN   [7]
RP   REVIEW.
RX   PubMed=16437164; DOI=10.1038/sj.emboj.7600947;
RA   Lusso P.;
RT   "HIV and the chemokine system: 10 years later.";
RL   EMBO J. 25:447-456(2006).
CC   -!- FUNCTION: [Envelope glycoprotein gp160]: Oligomerizes in the host
CC       endoplasmic reticulum into predominantly trimers. In a second time,
CC       gp160 transits in the host Golgi, where glycosylation is completed. The
CC       precursor is then proteolytically cleaved in the trans-Golgi and
CC       thereby activated by cellular furin or furin-like proteases to produce
CC       gp120 and gp41. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- FUNCTION: [Surface protein gp120]: Attaches the virus to the host
CC       lymphoid cell by binding to the primary receptor CD4. This interaction
CC       induces a structural rearrangement creating a high affinity binding
CC       site for a chemokine coreceptor like CXCR4 and/or CCR5. Acts as a
CC       ligand for CD209/DC-SIGN and CLEC4M/DC-SIGNR, which are respectively
CC       found on dendritic cells (DCs), and on endothelial cells of liver
CC       sinusoids and lymph node sinuses. These interactions allow capture of
CC       viral particles at mucosal surfaces by these cells and subsequent
CC       transmission to permissive cells. HIV subverts the migration properties
CC       of dendritic cells to gain access to CD4+ T-cells in lymph nodes. Virus
CC       transmission to permissive T-cells occurs either in trans (without DCs
CC       infection, through viral capture and transmission), or in cis
CC       (following DCs productive infection, through the usual CD4-gp120
CC       interaction), thereby inducing a robust infection. In trans infection,
CC       bound virions remain infectious over days and it is proposed that they
CC       are not degraded, but protected in non-lysosomal acidic organelles
CC       within the DCs close to the cell membrane thus contributing to the
CC       viral infectious potential during DCs' migration from the periphery to
CC       the lymphoid tissues. On arrival at lymphoid tissues, intact virions
CC       recycle back to DCs' cell surface allowing virus transmission to CD4+
CC       T-cells. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- FUNCTION: [Transmembrane protein gp41]: Acts as a class I viral fusion
CC       protein. Under the current model, the protein has at least 3
CC       conformational states: pre-fusion native state, pre-hairpin
CC       intermediate state, and post-fusion hairpin state. During fusion of
CC       viral and target intracellular membranes, the coiled coil regions
CC       (heptad repeats) assume a trimer-of-hairpins structure, positioning the
CC       fusion peptide in close proximity to the C-terminal region of the
CC       ectodomain. The formation of this structure appears to drive apposition
CC       and subsequent fusion of viral and target cell membranes. Complete
CC       fusion occurs in host cell endosomes and is dynamin-dependent, however
CC       some lipid transfer might occur at the plasma membrane. The virus
CC       undergoes clathrin-dependent internalization long before endosomal
CC       fusion, thus minimizing the surface exposure of conserved viral
CC       epitopes during fusion and reducing the efficacy of inhibitors
CC       targeting these epitopes. Membranes fusion leads to delivery of the
CC       nucleocapsid into the cytoplasm. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBUNIT: [Surface protein gp120]: The mature envelope protein (Env)
CC       consists of a homotrimer of non-covalently associated gp120-gp41
CC       heterodimers. The resulting complex protrudes from the virus surface as
CC       a spike. There seems to be as few as 10 spikes on the average virion.
CC       Interacts with host CD4, CCR5 and CXCR4. Gp120 also interacts with the
CC       C-type lectins CD209/DC-SIGN and CLEC4M/DC-SIGNR (collectively referred
CC       to as DC-SIGN(R)). Gp120 and gp41 interact with GalCer. Gp120 interacts
CC       with host ITGA4/ITGB7 complex; on CD4+ T-cells, this interaction
CC       results in rapid activation of integrin ITGAL/LFA-1, which facilitates
CC       efficient cell-to-cell spreading of HIV-1. Gp120 interacts with cell-
CC       associated heparan sulfate; this interaction increases virus
CC       infectivity on permissive cells and may be involved in infection of
CC       CD4- cells. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBUNIT: [Transmembrane protein gp41]: The mature envelope protein
CC       (Env) consists of a homotrimer of non-covalently associated gp120-gp41
CC       heterodimers. The resulting complex protrudes from the virus surface as
CC       a spike. There seems to be as few as 10 spikes on the average virion.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBCELLULAR LOCATION: [Surface protein gp120]: Virion membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Peripheral membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host cell membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Peripheral membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host endosome membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Note=The surface protein is not
CC       anchored to the viral envelope, but associates with the extravirion
CC       surface through its binding to TM. It is probably concentrated at the
CC       site of budding and incorporated into the virions possibly by contacts
CC       between the cytoplasmic tail of Env and the N-terminus of Gag.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBCELLULAR LOCATION: [Transmembrane protein gp41]: Virion membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host cell membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host endosome membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Note=It is probably concentrated at
CC       the site of budding and incorporated into the virions possibly by
CC       contacts between the cytoplasmic tail of Env and the N-terminus of Gag.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: Some of the most genetically diverse regions of the viral
CC       genome are present in Env. They are called variable regions 1 through 5
CC       (V1 through V5). Coreceptor usage of gp120 is determined mainly by the
CC       primary structure of the third variable region (V3) in the outer domain
CC       of gp120. The sequence of V3 determines which coreceptor, CCR5 and/or
CC       CXCR4 (corresponding to R5/macrophage, X4/T cell and R5X4/T cell and
CC       macrophage tropism), is used to trigger the fusion potential of the Env
CC       complex, and hence which cells the virus can infect. Binding to CCR5
CC       involves a region adjacent in addition to V3. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- DOMAIN: The membrane proximal external region (MPER) present in gp41 is
CC       a tryptophan-rich region recognized by the antibodies 2F5, Z13, and
CC       4E10. MPER seems to play a role in fusion. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- DOMAIN: The 17 amino acids long immunosuppressive region is present in
CC       many retroviral envelope proteins. Synthetic peptides derived from this
CC       relatively conserved sequence inhibit immune function in vitro and in
CC       vivo. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: The YXXL motif is involved in determining the exact site of
CC       viral release at the surface of infected mononuclear cells and promotes
CC       endocytosis. YXXL and di-leucine endocytosis motifs interact directly
CC       or indirectly with the clathrin adapter complexes, opperate
CC       independently, and their activities are not additive.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: The CD4-binding region is targeted by the antibody b12.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- PTM: Highly glycosylated by host. The high number of glycan on the
CC       protein is reffered to as 'glycan shield' because it contributes to
CC       hide protein sequence from adaptive immune system. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- PTM: Palmitoylation of the transmembrane protein and of Env polyprotein
CC       (prior to its proteolytic cleavage) is essential for their association
CC       with host cell membrane lipid rafts. Palmitoylation is therefore
CC       required for envelope trafficking to classical lipid rafts, but not for
CC       viral replication. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- PTM: Specific enzymatic cleavages in vivo yield mature proteins.
CC       Envelope glycoproteins are synthesized as an inactive precursor that is
CC       heavily N-glycosylated and processed likely by host cell furin in the
CC       Golgi to yield the mature SU and TM proteins. The cleavage site between
CC       SU and TM requires the minimal sequence [KR]-X-[KR]-R. About 2 of the 9
CC       disulfide bonds of gp41 are reduced by P4HB/PDI, following binding to
CC       CD4 receptor. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- MISCELLANEOUS: Inhibitors targeting HIV-1 viral envelope proteins are
CC       used as antiretroviral drugs. Attachment of virions to the cell surface
CC       via non-specific interactions and CD4 binding can be blocked by
CC       inhibitors that include cyanovirin-N, cyclotriazadisulfonamide analogs,
CC       PRO 2000, TNX 355 and PRO 542. In addition, BMS 806 can block CD4-
CC       induced conformational changes. Env interactions with the coreceptor
CC       molecules can be targeted by CCR5 antagonists including SCH-D,
CC       maraviroc (UK 427857) and aplaviroc (GW 873140), and the CXCR4
CC       antagonist AMD 070. Fusion of viral and cellular membranes can be
CC       inhibited by peptides such as enfuvirtide and tifuvirtide (T 1249).
CC       Resistance to inhibitors associated with mutations in Env are observed.
CC       Most of the time, single mutations confer only a modest reduction in
CC       drug susceptibility. Combination of several mutations is usually
CC       required to develop a high-level drug resistance. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- MISCELLANEOUS: HIV-1 lineages are divided in three main groups, M (for
CC       Major), O (for Outlier), and N (for New, or Non-M, Non-O). The vast
CC       majority of strains found worldwide belong to the group M. Group O
CC       seems to be endemic to and largely confined to Cameroon and neighboring
CC       countries in West Central Africa, where these viruses represent a small
CC       minority of HIV-1 strains. The group N is represented by a limited
CC       number of isolates from Cameroonian persons. The group M is further
CC       subdivided in 9 clades or subtypes (A to D, F to H, J and K).
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SIMILARITY: Belongs to the HIV-1 env protein family.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- WEB RESOURCE: Name=hivdb; Note=HIV drug resistance database;
CC       URL="https://hivdb.stanford.edu";
CC   -!- WEB RESOURCE: Name=HIV drug resistance mutations;
CC       URL="https://www.iasusa.org/content/hiv-drug-resistance-mutations";
CC   ---------------------------------------------------------------------------
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DR   EMBL; M38429; AAB03749.1; -; Genomic_RNA.
DR   PDB; 1CE4; NMR; -; A=294-328.
DR   PDB; 2ESX; NMR; -; A=301-319.
DR   PDB; 2ESZ; NMR; -; A=301-319.
DR   PDB; 4R2G; X-ray; 3.28 A; A/E/K/O=91-300, A/E/K/O=317-484.
DR   PDB; 5V6L; X-ray; 2.55 A; P/Q=299-321.
DR   PDB; 5V6M; X-ray; 1.90 A; P=299-313.
DR   PDBsum; 1CE4; -.
DR   PDBsum; 2ESX; -.
DR   PDBsum; 2ESZ; -.
DR   PDBsum; 4R2G; -.
DR   PDBsum; 5V6L; -.
DR   PDBsum; 5V6M; -.
DR   BMRB; P20871; -.
DR   SMR; P20871; -.
DR   GlyCosmos; P20871; 27 sites, No reported glycans.
DR   iPTMnet; P20871; -.
DR   ABCD; P20871; 2 sequenced antibodies.
DR   Reactome; R-HSA-5621480; Dectin-2 family.
DR   EvolutionaryTrace; P20871; -.
DR   PRO; PR:P20871; -.
DR   Proteomes; UP000007695; Genome.
DR   GO; GO:0044175; C:host cell endosome membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0016020; C:membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:0019031; C:viral envelope; IEA:UniProtKB-KW.
DR   GO; GO:0055036; C:virion membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005198; F:structural molecule activity; IEA:UniProtKB-UniRule.
DR   GO; GO:0075512; P:clathrin-dependent endocytosis of virus by host cell; IEA:UniProtKB-UniRule.
DR   GO; GO:0039654; P:fusion of virus membrane with host endosome membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:0019064; P:fusion of virus membrane with host plasma membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:0030307; P:positive regulation of cell growth; IDA:UniProtKB.
DR   GO; GO:1903905; P:positive regulation of establishment of T cell polarity; IEA:UniProtKB-UniRule.
DR   GO; GO:1903908; P:positive regulation of plasma membrane raft polarization; IEA:UniProtKB-UniRule.
DR   GO; GO:1903911; P:positive regulation of receptor clustering; IEA:UniProtKB-UniRule.
DR   GO; GO:0019082; P:viral protein processing; IEA:UniProtKB-UniRule.
DR   GO; GO:0019062; P:virion attachment to host cell; IEA:UniProtKB-UniRule.
DR   GO; GO:0019049; P:virus-mediated perturbation of host defense response; IEA:UniProtKB-UniRule.
DR   CDD; cd09909; HIV-1-like_HR1-HR2; 1.
DR   Gene3D; 1.10.287.210; -; 1.
DR   Gene3D; 2.170.40.20; Human immunodeficiency virus 1, Gp160, envelope glycoprotein; 2.
DR   Gene3D; 1.20.5.490; Single helix bin; 1.
DR   HAMAP; MF_04083; HIV_ENV; 1.
DR   InterPro; IPR036377; Gp120_core_sf.
DR   InterPro; IPR037527; Gp160.
DR   InterPro; IPR000328; GP41-like.
DR   InterPro; IPR000777; HIV1_Gp120.
DR   Pfam; PF00516; GP120; 1.
DR   Pfam; PF00517; GP41; 1.
DR   SUPFAM; SSF56502; gp120 core; 2.
DR   SUPFAM; SSF58069; Virus ectodomain; 1.
PE   1: Evidence at protein level;
KW   3D-structure; AIDS; Apoptosis;
KW   Clathrin-mediated endocytosis of virus by host;
KW   Cleavage on pair of basic residues; Coiled coil; Disulfide bond;
KW   Fusion of virus membrane with host endosomal membrane;
KW   Fusion of virus membrane with host membrane; Glycoprotein;
KW   Host cell membrane; Host endosome; Host membrane; Host-virus interaction;
KW   Lipoprotein; Membrane; Palmitate; Reference proteome; Signal;
KW   Transmembrane; Transmembrane helix; Viral attachment to host cell;
KW   Viral envelope protein; Viral immunoevasion;
KW   Viral penetration into host cytoplasm; Virion; Virus endocytosis by host;
KW   Virus entry into host cell.
FT   SIGNAL          1..31
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CHAIN           32..848
FT                   /note="Envelope glycoprotein gp160"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000441241"
FT   CHAIN           32..503
FT                   /note="Surface protein gp120"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000441242"
FT   CHAIN           504..848
FT                   /note="Transmembrane protein gp41"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000038393"
FT   TOPO_DOM        32..676
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   TRANSMEM        677..697
FT                   /note="Helical"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   TOPO_DOM        698..848
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          130..153
FT                   /note="V1"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          154..194
FT                   /note="V2"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          294..327
FT                   /note="V3"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          360..370
FT                   /note="CD4-binding loop"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          381..410
FT                   /note="V4"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          452..463
FT                   /note="V5"
FT   REGION          454..463
FT                   /note="V5"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          504..524
FT                   /note="Fusion peptide"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          566..584
FT                   /note="Immunosuppression"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          654..675
FT                   /note="MPER; binding to GalCer"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          714..735
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COILED          625..659
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   MOTIF           704..707
FT                   /note="YXXL motif; contains endocytosis signal"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   MOTIF           847..848
FT                   /note="Di-leucine internalization motif"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   COMPBIAS        720..735
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   SITE            503..504
FT                   /note="Cleavage; by host furin"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        87
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        134
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        137
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        153
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        157
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        185
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        195
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        228
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        239
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        260
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        274
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        287
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        293
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        299
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        329
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        336
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        352
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        382
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        388
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        392
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        403
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        440
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        453
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        603
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        608
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        617
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        629
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        53..73
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        118..203
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        125..194
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        130..154
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        216..245
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        226..237
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        294..328
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        374..437
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        381..410
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        590..596
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   STRAND          221..226
FT                   /evidence="ECO:0007829|PDB:4R2G"
FT   STRAND          233..235
FT                   /evidence="ECO:0007829|PDB:4R2G"
FT   STRAND          238..245
FT                   /evidence="ECO:0007829|PDB:4R2G"
FT   STRAND          255..260
FT                   /evidence="ECO:0007829|PDB:4R2G"
FT   STRAND          265..267
FT                   /evidence="ECO:0007829|PDB:4R2G"
FT   STRAND          269..271
FT                   /evidence="ECO:0007829|PDB:4R2G"
FT   STRAND          282..296
FT                   /evidence="ECO:0007829|PDB:4R2G"
FT   HELIX           298..300
FT                   /evidence="ECO:0007829|PDB:1CE4"
FT   STRAND          308..310
FT                   /evidence="ECO:0007829|PDB:5V6M"
FT   HELIX           311..316
FT                   /evidence="ECO:0007829|PDB:5V6L"
FT   STRAND          327..331
FT                   /evidence="ECO:0007829|PDB:4R2G"
FT   HELIX           332..349
FT                   /evidence="ECO:0007829|PDB:4R2G"
FT   TURN            350..352
FT                   /evidence="ECO:0007829|PDB:4R2G"
FT   STRAND          354..357
FT                   /evidence="ECO:0007829|PDB:4R2G"
FT   STRAND          361..363
FT                   /evidence="ECO:0007829|PDB:4R2G"
FT   HELIX           365..368
FT                   /evidence="ECO:0007829|PDB:4R2G"
FT   STRAND          370..374
FT                   /evidence="ECO:0007829|PDB:4R2G"
FT   STRAND          377..381
FT                   /evidence="ECO:0007829|PDB:4R2G"
FT   HELIX           384..386
FT                   /evidence="ECO:0007829|PDB:4R2G"
FT   STRAND          389..399
FT                   /evidence="ECO:0007829|PDB:4R2G"
FT   STRAND          404..417
FT                   /evidence="ECO:0007829|PDB:4R2G"
FT   STRAND          419..426
FT                   /evidence="ECO:0007829|PDB:4R2G"
FT   STRAND          431..433
FT                   /evidence="ECO:0007829|PDB:4R2G"
FT   STRAND          435..448
FT                   /evidence="ECO:0007829|PDB:4R2G"
FT   STRAND          457..462
FT                   /evidence="ECO:0007829|PDB:4R2G"
FT   HELIX           467..475
FT                   /evidence="ECO:0007829|PDB:4R2G"
FT   STRAND          479..482
FT                   /evidence="ECO:0007829|PDB:4R2G"
SQ   SEQUENCE   848 AA;  96475 MW;  20767F51227EC3F3 CRC64;
     MRVKGIRKNY QHLWKGGILL LGTLMICSAV EKLWVTVYYG VPVWKETTTT LFCASDAKAY
     DTEVHNVWAT HACVPTDPNP QEVVLENVTE DFNMWKNNMV EQMQEDVINL WDQSLKPCVK
     LTPLCVTLNC KDVNATNTTS SSEGMMERGE IKNCSFNITK SIRDKVQKEY ALFYKLDVVP
     IDNKNNTKYR LISCNTSVIT QACPKVSFEP IPIHYCAPAG FAILKCNNKT FNGKGQCKNV
     STVQCTHGIR PVVSTQLLLN GSLAEEKVVI RSDNFTDNAK TIIVQLNESV KINCTRPSNN
     TRKSIHIGPG RAFYTTGEII GDIRQAHCNI SRAQWNNTLK QIVEKLREQF NNKTIVFTHS
     SGGDPEIVMH SFNCGGEFFY CNSTQLFNST WNDTEKSSGT EGNDTIILPC RIKQIINMWQ
     EVGKAMYAPP IKGQIRCSSN ITGLLLTRDG GKNESEIEIF RPGGGDMRDN WRSELYKYKV
     VKIEPLGVAP TKAKRRVVQR EKRAVGIGAL FLGFLGAAGS TMGARSMTLT VQARQLLSGI
     VQQQNNLLRA IEAQQHMLQL TVWGIKQLQA RVLAVERYLK DQQLMGIWGC SGKLICTTAV
     PWNTSWSNKS LDSIWNNMTW MEWEKEIENY TNTIYTLIEE SQIQQEKNEQ ELLELDKWAS
     LWNWFGITKW LWYIKIFIMI VGGLIGLRIV FSVLSIVNRV RQGYSPLSFQ TLLPATRGPD
     RPEGIEEEGG ERDRDRSGQL VNGFLALIWV DLRSLFLFSY HRLRDLLLTV TRIVELLGRR
     GWEILKYWWN LLQYWSQELK NSAVSLLNAT AIAVAEGTDR IIEVVQRVYR AILHIPTRIR
     QGLERALL
//
ID   ENV_HV1KB               Reviewed;         861 AA.
AC   P31819;
DT   01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
DT   01-JUL-1993, sequence version 1.
DT   27-MAR-2024, entry version 137.
DE   RecName: Full=Envelope glycoprotein gp160 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   AltName: Full=Env polyprotein {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Contains:
DE     RecName: Full=Surface protein gp120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=SU {ECO:0000255|HAMAP-Rule:MF_04083};
DE     AltName: Full=Glycoprotein 120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=gp120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Contains:
DE     RecName: Full=Transmembrane protein gp41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=TM {ECO:0000255|HAMAP-Rule:MF_04083};
DE     AltName: Full=Glycoprotein 41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=gp41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Flags: Precursor;
GN   Name=env {ECO:0000255|HAMAP-Rule:MF_04083};
OS   Human immunodeficiency virus type 1 group M subtype B (isolate KB-1/ETR)
OS   (HIV-1).
OC   Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC   Ortervirales; Retroviridae; Orthoretrovirinae; Lentivirus;
OC   Human immunodeficiency virus 1.
OX   NCBI_TaxID=36375;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=1322587; DOI=10.1016/0042-6822(92)90577-c;
RA   Shimizu H., Hasebe F., Tsuchie H., Morikawa S., Ushijima H., Kitamura T.;
RT   "Analysis of a human immunodeficiency virus type 1 isolate carrying a
RT   truncated transmembrane glycoprotein.";
RL   Virology 189:534-546(1992).
RN   [2]
RP   REVIEW.
RX   PubMed=12974773; DOI=10.1034/j.1600-0463.2003.11107803.x;
RA   Geijtenbeek T.B., van Kooyk Y.;
RT   "Pathogens target DC-SIGN to influence their fate DC-SIGN functions as a
RT   pathogen receptor with broad specificity.";
RL   APMIS 111:698-714(2003).
RN   [3]
RP   REVIEW.
RX   PubMed=12873764; DOI=10.1016/s0005-2736(03)00161-5;
RA   Gallo S.A., Finnegan C.M., Viard M., Raviv Y., Dimitrov A., Rawat S.S.,
RA   Puri A., Durell S., Blumenthal R.;
RT   "The HIV Env-mediated fusion reaction.";
RL   Biochim. Biophys. Acta 1614:36-50(2003).
RN   [4]
RP   REVIEW.
RX   PubMed=15719026; DOI=10.1038/sj.cdd.4401584;
RA   Perfettini J.-L., Castedo M., Roumier T., Andreau K., Nardacci R.,
RA   Piacentini M., Kroemer G.;
RT   "Mechanisms of apoptosis induction by the HIV-1 envelope.";
RL   Cell Death Differ. 12:916-923(2005).
RN   [5]
RP   REVIEW.
RX   PubMed=15725757; DOI=10.1089/aid.2005.21.171;
RA   Hartley O., Klasse P.J., Sattentau Q.J., Moore J.P.;
RT   "V3: HIV's switch-hitter.";
RL   AIDS Res. Hum. Retroviruses 21:171-189(2005).
RN   [6]
RP   REVIEW.
RX   PubMed=16114975; DOI=10.2165/00003495-200565130-00002;
RA   Reeves J.D., Piefer A.J.;
RT   "Emerging drug targets for antiretroviral therapy.";
RL   Drugs 65:1747-1766(2005).
RN   [7]
RP   REVIEW.
RX   PubMed=16437164; DOI=10.1038/sj.emboj.7600947;
RA   Lusso P.;
RT   "HIV and the chemokine system: 10 years later.";
RL   EMBO J. 25:447-456(2006).
CC   -!- FUNCTION: [Envelope glycoprotein gp160]: Oligomerizes in the host
CC       endoplasmic reticulum into predominantly trimers. In a second time,
CC       gp160 transits in the host Golgi, where glycosylation is completed. The
CC       precursor is then proteolytically cleaved in the trans-Golgi and
CC       thereby activated by cellular furin or furin-like proteases to produce
CC       gp120 and gp41. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- FUNCTION: [Surface protein gp120]: Attaches the virus to the host
CC       lymphoid cell by binding to the primary receptor CD4. This interaction
CC       induces a structural rearrangement creating a high affinity binding
CC       site for a chemokine coreceptor like CXCR4 and/or CCR5. Acts as a
CC       ligand for CD209/DC-SIGN and CLEC4M/DC-SIGNR, which are respectively
CC       found on dendritic cells (DCs), and on endothelial cells of liver
CC       sinusoids and lymph node sinuses. These interactions allow capture of
CC       viral particles at mucosal surfaces by these cells and subsequent
CC       transmission to permissive cells. HIV subverts the migration properties
CC       of dendritic cells to gain access to CD4+ T-cells in lymph nodes. Virus
CC       transmission to permissive T-cells occurs either in trans (without DCs
CC       infection, through viral capture and transmission), or in cis
CC       (following DCs productive infection, through the usual CD4-gp120
CC       interaction), thereby inducing a robust infection. In trans infection,
CC       bound virions remain infectious over days and it is proposed that they
CC       are not degraded, but protected in non-lysosomal acidic organelles
CC       within the DCs close to the cell membrane thus contributing to the
CC       viral infectious potential during DCs' migration from the periphery to
CC       the lymphoid tissues. On arrival at lymphoid tissues, intact virions
CC       recycle back to DCs' cell surface allowing virus transmission to CD4+
CC       T-cells. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- FUNCTION: [Transmembrane protein gp41]: Acts as a class I viral fusion
CC       protein. Under the current model, the protein has at least 3
CC       conformational states: pre-fusion native state, pre-hairpin
CC       intermediate state, and post-fusion hairpin state. During fusion of
CC       viral and target intracellular membranes, the coiled coil regions
CC       (heptad repeats) assume a trimer-of-hairpins structure, positioning the
CC       fusion peptide in close proximity to the C-terminal region of the
CC       ectodomain. The formation of this structure appears to drive apposition
CC       and subsequent fusion of viral and target cell membranes. Complete
CC       fusion occurs in host cell endosomes and is dynamin-dependent, however
CC       some lipid transfer might occur at the plasma membrane. The virus
CC       undergoes clathrin-dependent internalization long before endosomal
CC       fusion, thus minimizing the surface exposure of conserved viral
CC       epitopes during fusion and reducing the efficacy of inhibitors
CC       targeting these epitopes. Membranes fusion leads to delivery of the
CC       nucleocapsid into the cytoplasm. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBUNIT: [Surface protein gp120]: The mature envelope protein (Env)
CC       consists of a homotrimer of non-covalently associated gp120-gp41
CC       heterodimers. The resulting complex protrudes from the virus surface as
CC       a spike. There seems to be as few as 10 spikes on the average virion.
CC       Interacts with host CD4, CCR5 and CXCR4. Gp120 also interacts with the
CC       C-type lectins CD209/DC-SIGN and CLEC4M/DC-SIGNR (collectively referred
CC       to as DC-SIGN(R)). Gp120 and gp41 interact with GalCer. Gp120 interacts
CC       with host ITGA4/ITGB7 complex; on CD4+ T-cells, this interaction
CC       results in rapid activation of integrin ITGAL/LFA-1, which facilitates
CC       efficient cell-to-cell spreading of HIV-1. Gp120 interacts with cell-
CC       associated heparan sulfate; this interaction increases virus
CC       infectivity on permissive cells and may be involved in infection of
CC       CD4- cells. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBUNIT: [Transmembrane protein gp41]: The mature envelope protein
CC       (Env) consists of a homotrimer of non-covalently associated gp120-gp41
CC       heterodimers. The resulting complex protrudes from the virus surface as
CC       a spike. There seems to be as few as 10 spikes on the average virion.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBCELLULAR LOCATION: [Surface protein gp120]: Virion membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Peripheral membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host cell membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Peripheral membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host endosome membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Note=The surface protein is not
CC       anchored to the viral envelope, but associates with the extravirion
CC       surface through its binding to TM. It is probably concentrated at the
CC       site of budding and incorporated into the virions possibly by contacts
CC       between the cytoplasmic tail of Env and the N-terminus of Gag.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBCELLULAR LOCATION: [Transmembrane protein gp41]: Virion membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host cell membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host endosome membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Note=It is probably concentrated at
CC       the site of budding and incorporated into the virions possibly by
CC       contacts between the cytoplasmic tail of Env and the N-terminus of Gag.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: Some of the most genetically diverse regions of the viral
CC       genome are present in Env. They are called variable regions 1 through 5
CC       (V1 through V5). Coreceptor usage of gp120 is determined mainly by the
CC       primary structure of the third variable region (V3) in the outer domain
CC       of gp120. The sequence of V3 determines which coreceptor, CCR5 and/or
CC       CXCR4 (corresponding to R5/macrophage, X4/T cell and R5X4/T cell and
CC       macrophage tropism), is used to trigger the fusion potential of the Env
CC       complex, and hence which cells the virus can infect. Binding to CCR5
CC       involves a region adjacent in addition to V3. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- DOMAIN: The membrane proximal external region (MPER) present in gp41 is
CC       a tryptophan-rich region recognized by the antibodies 2F5, Z13, and
CC       4E10. MPER seems to play a role in fusion. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- DOMAIN: The 17 amino acids long immunosuppressive region is present in
CC       many retroviral envelope proteins. Synthetic peptides derived from this
CC       relatively conserved sequence inhibit immune function in vitro and in
CC       vivo. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: The YXXL motif is involved in determining the exact site of
CC       viral release at the surface of infected mononuclear cells and promotes
CC       endocytosis. YXXL and di-leucine endocytosis motifs interact directly
CC       or indirectly with the clathrin adapter complexes, opperate
CC       independently, and their activities are not additive.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: The CD4-binding region is targeted by the antibody b12.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- PTM: Highly glycosylated by host. The high number of glycan on the
CC       protein is reffered to as 'glycan shield' because it contributes to
CC       hide protein sequence from adaptive immune system. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- PTM: Palmitoylation of the transmembrane protein and of Env polyprotein
CC       (prior to its proteolytic cleavage) is essential for their association
CC       with host cell membrane lipid rafts. Palmitoylation is therefore
CC       required for envelope trafficking to classical lipid rafts, but not for
CC       viral replication. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- PTM: Specific enzymatic cleavages in vivo yield mature proteins.
CC       Envelope glycoproteins are synthesized as an inactive precursor that is
CC       heavily N-glycosylated and processed likely by host cell furin in the
CC       Golgi to yield the mature SU and TM proteins. The cleavage site between
CC       SU and TM requires the minimal sequence [KR]-X-[KR]-R. About 2 of the 9
CC       disulfide bonds of gp41 are reduced by P4HB/PDI, following binding to
CC       CD4 receptor. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- MISCELLANEOUS: Inhibitors targeting HIV-1 viral envelope proteins are
CC       used as antiretroviral drugs. Attachment of virions to the cell surface
CC       via non-specific interactions and CD4 binding can be blocked by
CC       inhibitors that include cyanovirin-N, cyclotriazadisulfonamide analogs,
CC       PRO 2000, TNX 355 and PRO 542. In addition, BMS 806 can block CD4-
CC       induced conformational changes. Env interactions with the coreceptor
CC       molecules can be targeted by CCR5 antagonists including SCH-D,
CC       maraviroc (UK 427857) and aplaviroc (GW 873140), and the CXCR4
CC       antagonist AMD 070. Fusion of viral and cellular membranes can be
CC       inhibited by peptides such as enfuvirtide and tifuvirtide (T 1249).
CC       Resistance to inhibitors associated with mutations in Env are observed.
CC       Most of the time, single mutations confer only a modest reduction in
CC       drug susceptibility. Combination of several mutations is usually
CC       required to develop a high-level drug resistance. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- MISCELLANEOUS: HIV-1 lineages are divided in three main groups, M (for
CC       Major), O (for Outlier), and N (for New, or Non-M, Non-O). The vast
CC       majority of strains found worldwide belong to the group M. Group O
CC       seems to be endemic to and largely confined to Cameroon and neighboring
CC       countries in West Central Africa, where these viruses represent a small
CC       minority of HIV-1 strains. The group N is represented by a limited
CC       number of isolates from Cameroonian persons. The group M is further
CC       subdivided in 9 clades or subtypes (A to D, F to H, J and K).
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SIMILARITY: Belongs to the HIV-1 env protein family.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- WEB RESOURCE: Name=hivdb; Note=HIV drug resistance database;
CC       URL="https://hivdb.stanford.edu";
CC   -!- WEB RESOURCE: Name=HIV drug resistance mutations;
CC       URL="https://www.iasusa.org/content/hiv-drug-resistance-mutations";
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DR   EMBL; D12582; BAA02124.1; ALT_SEQ; Genomic_DNA.
DR   PIR; A42995; VCLJKB.
DR   SMR; P31819; -.
DR   GlyCosmos; P31819; 30 sites, No reported glycans.
DR   Reactome; R-HSA-5621480; Dectin-2 family.
DR   GO; GO:0044175; C:host cell endosome membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0016020; C:membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:0019031; C:viral envelope; IEA:UniProtKB-KW.
DR   GO; GO:0055036; C:virion membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005198; F:structural molecule activity; IEA:UniProtKB-UniRule.
DR   GO; GO:0075512; P:clathrin-dependent endocytosis of virus by host cell; IEA:UniProtKB-UniRule.
DR   GO; GO:0039654; P:fusion of virus membrane with host endosome membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:0019064; P:fusion of virus membrane with host plasma membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:1903905; P:positive regulation of establishment of T cell polarity; IEA:UniProtKB-UniRule.
DR   GO; GO:1903908; P:positive regulation of plasma membrane raft polarization; IEA:UniProtKB-UniRule.
DR   GO; GO:1903911; P:positive regulation of receptor clustering; IEA:UniProtKB-UniRule.
DR   GO; GO:0019082; P:viral protein processing; IEA:UniProtKB-UniRule.
DR   GO; GO:0019062; P:virion attachment to host cell; IEA:UniProtKB-UniRule.
DR   GO; GO:0019049; P:virus-mediated perturbation of host defense response; IEA:UniProtKB-UniRule.
DR   CDD; cd09909; HIV-1-like_HR1-HR2; 1.
DR   Gene3D; 1.10.287.210; -; 1.
DR   Gene3D; 2.170.40.20; Human immunodeficiency virus 1, Gp160, envelope glycoprotein; 2.
DR   Gene3D; 1.20.5.490; Single helix bin; 1.
DR   HAMAP; MF_04083; HIV_ENV; 1.
DR   InterPro; IPR036377; Gp120_core_sf.
DR   InterPro; IPR037527; Gp160.
DR   InterPro; IPR000328; GP41-like.
DR   InterPro; IPR000777; HIV1_Gp120.
DR   Pfam; PF00516; GP120; 1.
DR   Pfam; PF00517; GP41; 1.
DR   SUPFAM; SSF56502; gp120 core; 2.
DR   SUPFAM; SSF58069; Virus ectodomain; 1.
PE   3: Inferred from homology;
KW   AIDS; Apoptosis; Clathrin-mediated endocytosis of virus by host;
KW   Cleavage on pair of basic residues; Coiled coil; Disulfide bond;
KW   Fusion of virus membrane with host endosomal membrane;
KW   Fusion of virus membrane with host membrane; Glycoprotein;
KW   Host cell membrane; Host endosome; Host membrane; Host-virus interaction;
KW   Lipoprotein; Membrane; Palmitate; Signal; Transmembrane;
KW   Transmembrane helix; Viral attachment to host cell; Viral envelope protein;
KW   Viral immunoevasion; Viral penetration into host cytoplasm; Virion;
KW   Virus endocytosis by host; Virus entry into host cell.
FT   SIGNAL          1..37
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CHAIN           38..861
FT                   /note="Envelope glycoprotein gp160"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000239468"
FT   CHAIN           38..517
FT                   /note="Surface protein gp120"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000038375"
FT   CHAIN           518..861
FT                   /note="Transmembrane protein gp41"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000038376"
FT   TOPO_DOM        38..690
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   TRANSMEM        691..711
FT                   /note="Helical"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   TOPO_DOM        712..861
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          136..159
FT                   /note="V1"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          160..203
FT                   /note="V2"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          303..336
FT                   /note="V3"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          369..379
FT                   /note="CD4-binding loop"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          390..419
FT                   /note="V4"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          462..477
FT                   /note="V5"
FT   REGION          464..477
FT                   /note="V5"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          518..538
FT                   /note="Fusion peptide"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          580..598
FT                   /note="Immunosuppression"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          668..689
FT                   /note="MPER; binding to GalCer"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          725..749
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COILED          639..673
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   MOTIF           718..721
FT                   /note="YXXL motif; contains endocytosis signal"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   MOTIF           860..861
FT                   /note="Di-leucine internalization motif"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   COMPBIAS        732..749
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   SITE            517..518
FT                   /note="Cleavage; by host furin"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   LIPID           769
FT                   /note="S-palmitoyl cysteine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        93
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        141
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        145
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        146
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        159
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        163
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        191
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        192
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        237
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        241
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        248
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        269
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        283
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        296
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        308
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        338
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        345
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        361
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        367
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        397
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        403
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        408
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        414
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        449
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        465
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        468
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        617
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        622
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        631
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        643
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        59..79
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        124..212
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        131..203
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        136..160
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        225..254
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        235..246
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        303..337
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        383..446
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        390..419
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        604..610
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
SQ   SEQUENCE   861 AA;  98116 MW;  3C06787658F0C9DA CRC64;
     MRVKEIRKNY QHLWRWGIML RWGTMLLGML MICSAAEQLW VTVYYGVPVW KEATTTLFCA
     SDAKAYDTEA HNVWATHACV PTDPNPQEVV LVNVTENFNM WKNNMVEQMH ENIISLWDQS
     LKPCVKLTPL CVTLHCTDLR NTTNNNSSIE EKMKGEIKNC SFNVTTNIRD KVQKEYALFY
     KLDVVPIDND NNSTNTCYRL ISCDTSVITQ ACPKVSFEPI PIHYCTPAGF ALLKCNNKTF
     NGTGPCKNVS TVQCTHGIRP VVSTQLLLNG SLAEEGVVIR SENFTDNVKT IIVQLNETVK
     INCIRPNNKT RKRVTMGPGR VYYTTGEIIG DIRQAHCNIS RAEWNKTLEQ IANKLRKQFE
     NKTIVFNQSS GGDPEIVMHN FNCGGEFFYC DSSQLFNSTH LSNGTWWNGT GPENITLPCR
     IKQIVNMWQE VGKAMYAPPI RGQIRCSSNI TGLLLTRDGG NTQNNNTNSS IEIFRPGGGD
     MRDNWRSELY KYKVVKIEPL GVAPTRAKRR VVQREKRAVG IGAVFLGFLG AAGSTMGAAA
     VTLTVQARQL LPGIVQQQNN LLRAIDAQQH LLQLTVWGIK QLQARVLAVE RYLKDQQLMG
     IWGCSGKFIC TTAVPWNTSW SNKSFNEIWD NMTWMEWERE INNYTNLIYN LIEESQNQQE
     KNEQDLLALD KWDSLWNWFS ITKWLWYIKI FIMIVGGLVG LRIVFTVLSI VNRVRQGYSP
     LSFQTRLPAR GPDRPEGIEE EGGERDRDRS GPLVDGLLAL IWVDLRSLCL FSYHRLRDLL
     LIVTRTVELL GRKGWEVLKY LWNLLQYWSQ ELKNSAVSLL NATAIAVAEG TDRVIEILQR
     TYRAILHIPV KIRQGLERAL L
//
ID   ENV_HV1LW               Reviewed;         856 AA.
AC   Q70626;
DT   15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1996, sequence version 1.
DT   27-MAR-2024, entry version 154.
DE   RecName: Full=Envelope glycoprotein gp160 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   AltName: Full=Env polyprotein {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Contains:
DE     RecName: Full=Surface protein gp120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=SU {ECO:0000255|HAMAP-Rule:MF_04083};
DE     AltName: Full=Glycoprotein 120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=gp120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Contains:
DE     RecName: Full=Transmembrane protein gp41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=TM {ECO:0000255|HAMAP-Rule:MF_04083};
DE     AltName: Full=Glycoprotein 41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=gp41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Flags: Precursor;
GN   Name=env {ECO:0000255|HAMAP-Rule:MF_04083};
OS   Human immunodeficiency virus type 1 group M subtype B (isolate LW123)
OS   (HIV-1).
OC   Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC   Ortervirales; Retroviridae; Orthoretrovirinae; Lentivirus;
OC   Human immunodeficiency virus 1.
OX   NCBI_TaxID=82834;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX   PubMed=7826699; DOI=10.1089/aid.1994.10.1143;
RA   Reitz M.S. Jr., Hall L., Robert-Guroff M., Lautenberger J.A., Hahn B.M.,
RA   Shaw G.M., Kong L.I., Weiss S.H., Waters D., Gallo R.C., Blattner W.;
RT   "Viral variability and serum antibody response in a laboratory worker
RT   infected with HIV type 1 (HTLV type IIIB).";
RL   AIDS Res. Hum. Retroviruses 10:1143-1155(1994).
RN   [2]
RP   REVIEW.
RX   PubMed=12974773; DOI=10.1034/j.1600-0463.2003.11107803.x;
RA   Geijtenbeek T.B., van Kooyk Y.;
RT   "Pathogens target DC-SIGN to influence their fate DC-SIGN functions as a
RT   pathogen receptor with broad specificity.";
RL   APMIS 111:698-714(2003).
RN   [3]
RP   REVIEW.
RX   PubMed=12873764; DOI=10.1016/s0005-2736(03)00161-5;
RA   Gallo S.A., Finnegan C.M., Viard M., Raviv Y., Dimitrov A., Rawat S.S.,
RA   Puri A., Durell S., Blumenthal R.;
RT   "The HIV Env-mediated fusion reaction.";
RL   Biochim. Biophys. Acta 1614:36-50(2003).
RN   [4]
RP   REVIEW.
RX   PubMed=15719026; DOI=10.1038/sj.cdd.4401584;
RA   Perfettini J.-L., Castedo M., Roumier T., Andreau K., Nardacci R.,
RA   Piacentini M., Kroemer G.;
RT   "Mechanisms of apoptosis induction by the HIV-1 envelope.";
RL   Cell Death Differ. 12:916-923(2005).
RN   [5]
RP   REVIEW.
RX   PubMed=15725757; DOI=10.1089/aid.2005.21.171;
RA   Hartley O., Klasse P.J., Sattentau Q.J., Moore J.P.;
RT   "V3: HIV's switch-hitter.";
RL   AIDS Res. Hum. Retroviruses 21:171-189(2005).
RN   [6]
RP   REVIEW.
RX   PubMed=16114975; DOI=10.2165/00003495-200565130-00002;
RA   Reeves J.D., Piefer A.J.;
RT   "Emerging drug targets for antiretroviral therapy.";
RL   Drugs 65:1747-1766(2005).
RN   [7]
RP   REVIEW.
RX   PubMed=16437164; DOI=10.1038/sj.emboj.7600947;
RA   Lusso P.;
RT   "HIV and the chemokine system: 10 years later.";
RL   EMBO J. 25:447-456(2006).
CC   -!- FUNCTION: [Envelope glycoprotein gp160]: Oligomerizes in the host
CC       endoplasmic reticulum into predominantly trimers. In a second time,
CC       gp160 transits in the host Golgi, where glycosylation is completed. The
CC       precursor is then proteolytically cleaved in the trans-Golgi and
CC       thereby activated by cellular furin or furin-like proteases to produce
CC       gp120 and gp41. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- FUNCTION: [Surface protein gp120]: Attaches the virus to the host
CC       lymphoid cell by binding to the primary receptor CD4. This interaction
CC       induces a structural rearrangement creating a high affinity binding
CC       site for a chemokine coreceptor like CXCR4 and/or CCR5. Acts as a
CC       ligand for CD209/DC-SIGN and CLEC4M/DC-SIGNR, which are respectively
CC       found on dendritic cells (DCs), and on endothelial cells of liver
CC       sinusoids and lymph node sinuses. These interactions allow capture of
CC       viral particles at mucosal surfaces by these cells and subsequent
CC       transmission to permissive cells. HIV subverts the migration properties
CC       of dendritic cells to gain access to CD4+ T-cells in lymph nodes. Virus
CC       transmission to permissive T-cells occurs either in trans (without DCs
CC       infection, through viral capture and transmission), or in cis
CC       (following DCs productive infection, through the usual CD4-gp120
CC       interaction), thereby inducing a robust infection. In trans infection,
CC       bound virions remain infectious over days and it is proposed that they
CC       are not degraded, but protected in non-lysosomal acidic organelles
CC       within the DCs close to the cell membrane thus contributing to the
CC       viral infectious potential during DCs' migration from the periphery to
CC       the lymphoid tissues. On arrival at lymphoid tissues, intact virions
CC       recycle back to DCs' cell surface allowing virus transmission to CD4+
CC       T-cells. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- FUNCTION: [Transmembrane protein gp41]: Acts as a class I viral fusion
CC       protein. Under the current model, the protein has at least 3
CC       conformational states: pre-fusion native state, pre-hairpin
CC       intermediate state, and post-fusion hairpin state. During fusion of
CC       viral and target intracellular membranes, the coiled coil regions
CC       (heptad repeats) assume a trimer-of-hairpins structure, positioning the
CC       fusion peptide in close proximity to the C-terminal region of the
CC       ectodomain. The formation of this structure appears to drive apposition
CC       and subsequent fusion of viral and target cell membranes. Complete
CC       fusion occurs in host cell endosomes and is dynamin-dependent, however
CC       some lipid transfer might occur at the plasma membrane. The virus
CC       undergoes clathrin-dependent internalization long before endosomal
CC       fusion, thus minimizing the surface exposure of conserved viral
CC       epitopes during fusion and reducing the efficacy of inhibitors
CC       targeting these epitopes. Membranes fusion leads to delivery of the
CC       nucleocapsid into the cytoplasm. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBUNIT: [Surface protein gp120]: The mature envelope protein (Env)
CC       consists of a homotrimer of non-covalently associated gp120-gp41
CC       heterodimers. The resulting complex protrudes from the virus surface as
CC       a spike. There seems to be as few as 10 spikes on the average virion.
CC       Interacts with host CD4, CCR5 and CXCR4. Gp120 also interacts with the
CC       C-type lectins CD209/DC-SIGN and CLEC4M/DC-SIGNR (collectively referred
CC       to as DC-SIGN(R)). Gp120 and gp41 interact with GalCer. Gp120 interacts
CC       with host ITGA4/ITGB7 complex; on CD4+ T-cells, this interaction
CC       results in rapid activation of integrin ITGAL/LFA-1, which facilitates
CC       efficient cell-to-cell spreading of HIV-1. Gp120 interacts with cell-
CC       associated heparan sulfate; this interaction increases virus
CC       infectivity on permissive cells and may be involved in infection of
CC       CD4- cells. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBUNIT: [Transmembrane protein gp41]: The mature envelope protein
CC       (Env) consists of a homotrimer of non-covalently associated gp120-gp41
CC       heterodimers. The resulting complex protrudes from the virus surface as
CC       a spike. There seems to be as few as 10 spikes on the average virion.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBCELLULAR LOCATION: [Surface protein gp120]: Virion membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Peripheral membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host cell membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Peripheral membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host endosome membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Note=The surface protein is not
CC       anchored to the viral envelope, but associates with the extravirion
CC       surface through its binding to TM. It is probably concentrated at the
CC       site of budding and incorporated into the virions possibly by contacts
CC       between the cytoplasmic tail of Env and the N-terminus of Gag.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBCELLULAR LOCATION: [Transmembrane protein gp41]: Virion membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host cell membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host endosome membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Note=It is probably concentrated at
CC       the site of budding and incorporated into the virions possibly by
CC       contacts between the cytoplasmic tail of Env and the N-terminus of Gag.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: Some of the most genetically diverse regions of the viral
CC       genome are present in Env. They are called variable regions 1 through 5
CC       (V1 through V5). Coreceptor usage of gp120 is determined mainly by the
CC       primary structure of the third variable region (V3) in the outer domain
CC       of gp120. The sequence of V3 determines which coreceptor, CCR5 and/or
CC       CXCR4 (corresponding to R5/macrophage, X4/T cell and R5X4/T cell and
CC       macrophage tropism), is used to trigger the fusion potential of the Env
CC       complex, and hence which cells the virus can infect. Binding to CCR5
CC       involves a region adjacent in addition to V3. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- DOMAIN: The membrane proximal external region (MPER) present in gp41 is
CC       a tryptophan-rich region recognized by the antibodies 2F5, Z13, and
CC       4E10. MPER seems to play a role in fusion. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- DOMAIN: The 17 amino acids long immunosuppressive region is present in
CC       many retroviral envelope proteins. Synthetic peptides derived from this
CC       relatively conserved sequence inhibit immune function in vitro and in
CC       vivo. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: The YXXL motif is involved in determining the exact site of
CC       viral release at the surface of infected mononuclear cells and promotes
CC       endocytosis. YXXL and di-leucine endocytosis motifs interact directly
CC       or indirectly with the clathrin adapter complexes, opperate
CC       independently, and their activities are not additive.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: The CD4-binding region is targeted by the antibody b12.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- PTM: Highly glycosylated by host. The high number of glycan on the
CC       protein is reffered to as 'glycan shield' because it contributes to
CC       hide protein sequence from adaptive immune system. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- PTM: Palmitoylation of the transmembrane protein and of Env polyprotein
CC       (prior to its proteolytic cleavage) is essential for their association
CC       with host cell membrane lipid rafts. Palmitoylation is therefore
CC       required for envelope trafficking to classical lipid rafts, but not for
CC       viral replication. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- PTM: Specific enzymatic cleavages in vivo yield mature proteins.
CC       Envelope glycoproteins are synthesized as an inactive precursor that is
CC       heavily N-glycosylated and processed likely by host cell furin in the
CC       Golgi to yield the mature SU and TM proteins. The cleavage site between
CC       SU and TM requires the minimal sequence [KR]-X-[KR]-R. About 2 of the 9
CC       disulfide bonds of gp41 are reduced by P4HB/PDI, following binding to
CC       CD4 receptor. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- MISCELLANEOUS: Inhibitors targeting HIV-1 viral envelope proteins are
CC       used as antiretroviral drugs. Attachment of virions to the cell surface
CC       via non-specific interactions and CD4 binding can be blocked by
CC       inhibitors that include cyanovirin-N, cyclotriazadisulfonamide analogs,
CC       PRO 2000, TNX 355 and PRO 542. In addition, BMS 806 can block CD4-
CC       induced conformational changes. Env interactions with the coreceptor
CC       molecules can be targeted by CCR5 antagonists including SCH-D,
CC       maraviroc (UK 427857) and aplaviroc (GW 873140), and the CXCR4
CC       antagonist AMD 070. Fusion of viral and cellular membranes can be
CC       inhibited by peptides such as enfuvirtide and tifuvirtide (T 1249).
CC       Resistance to inhibitors associated with mutations in Env are observed.
CC       Most of the time, single mutations confer only a modest reduction in
CC       drug susceptibility. Combination of several mutations is usually
CC       required to develop a high-level drug resistance. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- MISCELLANEOUS: HIV-1 lineages are divided in three main groups, M (for
CC       Major), O (for Outlier), and N (for New, or Non-M, Non-O). The vast
CC       majority of strains found worldwide belong to the group M. Group O
CC       seems to be endemic to and largely confined to Cameroon and neighboring
CC       countries in West Central Africa, where these viruses represent a small
CC       minority of HIV-1 strains. The group N is represented by a limited
CC       number of isolates from Cameroonian persons. The group M is further
CC       subdivided in 9 clades or subtypes (A to D, F to H, J and K).
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SIMILARITY: Belongs to the HIV-1 env protein family.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- WEB RESOURCE: Name=hivdb; Note=HIV drug resistance database;
CC       URL="https://hivdb.stanford.edu";
CC   -!- WEB RESOURCE: Name=HIV drug resistance mutations;
CC       URL="https://www.iasusa.org/content/hiv-drug-resistance-mutations";
CC   ---------------------------------------------------------------------------
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DR   EMBL; U12055; AAA76690.1; -; Genomic_RNA.
DR   PDB; 2X7R; X-ray; 2.00 A; A/D/N=528-581, B/C/E=629-683.
DR   PDB; 2Z2T; X-ray; 2.10 A; A/B/C=546-581.
DR   PDB; 3AHA; X-ray; 1.70 A; A/C/E=548-581, B/D/F=628-660.
DR   PDB; 3CP1; X-ray; 2.00 A; A=536-663.
DR   PDB; 3CYO; X-ray; 2.10 A; A=536-663.
DR   PDB; 3GWO; X-ray; 1.65 A; A/B=630-683.
DR   PDB; 3H00; X-ray; 2.20 A; A/B/C/D=636-674.
DR   PDB; 3H01; X-ray; 1.70 A; A/B=630-683.
DR   PDB; 4I48; X-ray; 2.80 A; C=192-200.
DR   PDB; 5HFM; X-ray; 2.30 A; A/B/C/D/E/F=539-581.
DR   PDB; 6X58; X-ray; 3.26 A; E/F=669-683.
DR   PDBsum; 2X7R; -.
DR   PDBsum; 2Z2T; -.
DR   PDBsum; 3AHA; -.
DR   PDBsum; 3CP1; -.
DR   PDBsum; 3CYO; -.
DR   PDBsum; 3GWO; -.
DR   PDBsum; 3H00; -.
DR   PDBsum; 3H01; -.
DR   PDBsum; 4I48; -.
DR   PDBsum; 5HFM; -.
DR   PDBsum; 6X58; -.
DR   SMR; Q70626; -.
DR   GlyConnect; 150; 20 N-Linked glycans.
DR   GlyCosmos; Q70626; 29 sites, 36 glycans.
DR   Reactome; R-HSA-5621480; Dectin-2 family.
DR   EvolutionaryTrace; Q70626; -.
DR   GO; GO:0044175; C:host cell endosome membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0016020; C:membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:0019031; C:viral envelope; IEA:UniProtKB-KW.
DR   GO; GO:0055036; C:virion membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005198; F:structural molecule activity; IEA:UniProtKB-UniRule.
DR   GO; GO:0075512; P:clathrin-dependent endocytosis of virus by host cell; IEA:UniProtKB-UniRule.
DR   GO; GO:0039654; P:fusion of virus membrane with host endosome membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:0019064; P:fusion of virus membrane with host plasma membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:1903905; P:positive regulation of establishment of T cell polarity; IEA:UniProtKB-UniRule.
DR   GO; GO:1903908; P:positive regulation of plasma membrane raft polarization; IEA:UniProtKB-UniRule.
DR   GO; GO:1903911; P:positive regulation of receptor clustering; IEA:UniProtKB-UniRule.
DR   GO; GO:0019082; P:viral protein processing; IEA:UniProtKB-UniRule.
DR   GO; GO:0019062; P:virion attachment to host cell; IEA:UniProtKB-UniRule.
DR   GO; GO:0019049; P:virus-mediated perturbation of host defense response; IEA:UniProtKB-UniRule.
DR   CDD; cd09909; HIV-1-like_HR1-HR2; 1.
DR   Gene3D; 1.10.287.210; -; 1.
DR   Gene3D; 2.170.40.20; Human immunodeficiency virus 1, Gp160, envelope glycoprotein; 2.
DR   Gene3D; 1.20.5.490; Single helix bin; 1.
DR   HAMAP; MF_04083; HIV_ENV; 1.
DR   InterPro; IPR036377; Gp120_core_sf.
DR   InterPro; IPR037527; Gp160.
DR   InterPro; IPR000328; GP41-like.
DR   InterPro; IPR000777; HIV1_Gp120.
DR   Pfam; PF00516; GP120; 1.
DR   Pfam; PF00517; GP41; 1.
DR   SUPFAM; SSF56502; gp120 core; 1.
DR   SUPFAM; SSF58069; Virus ectodomain; 1.
PE   1: Evidence at protein level;
KW   3D-structure; AIDS; Apoptosis;
KW   Clathrin-mediated endocytosis of virus by host;
KW   Cleavage on pair of basic residues; Coiled coil; Disulfide bond;
KW   Fusion of virus membrane with host endosomal membrane;
KW   Fusion of virus membrane with host membrane; Glycoprotein;
KW   Host cell membrane; Host endosome; Host membrane; Host-virus interaction;
KW   Lipoprotein; Membrane; Palmitate; Signal; Transmembrane;
KW   Transmembrane helix; Viral attachment to host cell; Viral envelope protein;
KW   Viral immunoevasion; Viral penetration into host cytoplasm; Virion;
KW   Virus endocytosis by host; Virus entry into host cell.
FT   SIGNAL          1..32
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CHAIN           33..856
FT                   /note="Envelope glycoprotein gp160"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000239467"
FT   CHAIN           33..511
FT                   /note="Surface protein gp120"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000038373"
FT   CHAIN           512..856
FT                   /note="Transmembrane protein gp41"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000038374"
FT   TOPO_DOM        33..684
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   TRANSMEM        685..705
FT                   /note="Helical"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   TOPO_DOM        706..856
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          131..156
FT                   /note="V1"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          157..196
FT                   /note="V2"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          296..330
FT                   /note="V3"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          364..374
FT                   /note="CD4-binding loop"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          385..418
FT                   /note="V4"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          461..471
FT                   /note="V5"
FT   REGION          463..471
FT                   /note="V5"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          512..532
FT                   /note="Fusion peptide"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          574..592
FT                   /note="Immunosuppression"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          662..683
FT                   /note="MPER; binding to GalCer"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          715..742
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COILED          633..667
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   MOTIF           855..856
FT                   /note="Di-leucine internalization motif"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   SITE            511..512
FT                   /note="Cleavage; by host furin"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   LIPID           764
FT                   /note="S-palmitoyl cysteine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   LIPID           837
FT                   /note="S-palmitoyl cysteine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        88
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        136
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        141
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        156
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        160
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        186
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        197
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        230
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        234
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        241
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        262
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        276
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        289
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        295
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        301
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        332
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        339
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        356
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        386
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        392
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        397
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        406
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        448
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        463
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        611
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        616
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        624
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        637
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        674
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        54..74
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        119..205
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        126..196
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        131..157
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        218..247
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        228..239
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        296..331
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        378..445
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        385..418
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        598..604
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   HELIX           535..540
FT                   /evidence="ECO:0007829|PDB:2X7R"
FT   HELIX           547..580
FT                   /evidence="ECO:0007829|PDB:3AHA"
FT   HELIX           633..682
FT                   /evidence="ECO:0007829|PDB:3GWO"
SQ   SEQUENCE   856 AA;  96938 MW;  0C241332CF7E6687 CRC64;
     MRVKEKYQHL RRWGWRWGTM LLGMLMICSA TEKLWVTVYY GVPVWKEATT TLFCASDAKA
     YDTEVHNVWA THACVPTDPN PQEVVLVNVT ENFNMWKNDM VEQMHEDIIS LWDQSLKPCV
     KLTPLCVSLK CTDLKNDTNT NSSSGGMIME KGEIKNCSFN ISTSIRGKVQ KEYAFFYKHD
     IIPIDNDTTS YTLTSCNTSV ITQACPKVSF EPIPIHYCAP AGFAILKCNN KTFNGTGPCT
     NVSTVQCTHG IKPVVSTQLL LNGSLAEEEV VIRSANLTDN VKTIIVQLNQ SVEINCTRPN
     NNTRKRIRIQ RGPGRTFVTI GKIGNMRQAH CNISRAKWNN TLKQIASKLR EQYGNNKTII
     FKQSSGGDLE IVTHSFNCGG EFFYCNSTQL FNSTWFNSTW STEGSNNTEG SDTITLPCRI
     KQIINMWQEV GKAMYAPPIS GQIRCSSNIT GLLLTRDGGN NNNGSEIFRP GGGDMRDNWR
     SELYKYKVVK IEPLGVAPTK AKRRVVQREK RAVGIGALFL GFLGAAGSTM GAASMTLTVQ
     ARQLLSGIVQ QQNNLLRAIE AQQHLLQLTV WGIKQLQARI LAVERYLKDQ QLLGIWGCSG
     KLICTTAVPW NASWSNKSLE QIWNHTTWME WDREINNYTS LIHSLIEESQ NQQEKNEQEL
     LELDKWASLW NWFNITNWLW YIKIFIMIVG GLVGLRIVFA VLSIVNRVRQ GHSPLSFQTH
     LPTPGGPDRP EGIEEEGGER DRDRSIRLVN GSLALIWDDL RSLCLFSYHR LRDLLLIVTR
     IVELLGRRGW EALKYWWNLL QYWSQELKNS AVSLLNATAI AVAEGTDRVI EVVQGACRAI
     RHIPRRIRQG LERILL
//
ID   ENV_HV1M2               Reviewed;         850 AA.
AC   Q9QBZ0;
DT   27-JUN-2006, integrated into UniProtKB/Swiss-Prot.
DT   27-JUN-2006, sequence version 2.
DT   27-MAR-2024, entry version 118.
DE   RecName: Full=Envelope glycoprotein gp160 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   AltName: Full=Env polyprotein {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Contains:
DE     RecName: Full=Surface protein gp120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=SU {ECO:0000255|HAMAP-Rule:MF_04083};
DE     AltName: Full=Glycoprotein 120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=gp120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Contains:
DE     RecName: Full=Transmembrane protein gp41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=TM {ECO:0000255|HAMAP-Rule:MF_04083};
DE     AltName: Full=Glycoprotein 41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=gp41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Flags: Precursor;
GN   Name=env {ECO:0000255|HAMAP-Rule:MF_04083};
OS   Human immunodeficiency virus type 1 group M subtype F2 (isolate MP257)
OS   (HIV-1).
OC   Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC   Ortervirales; Retroviridae; Orthoretrovirinae; Lentivirus;
OC   Human immunodeficiency virus 1.
OX   NCBI_TaxID=388823;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX   PubMed=10659053; DOI=10.1089/088922200309485;
RA   Triques K., Bourgeois A., Vidale N., Mpoudi-Ngole E., Mulanga-Kabeya C.,
RA   Nzilambi N., Torimiro N., Saman E., Delaporte E., Peeters M.;
RT   "Near-full-length genome sequencing of divergent African HIV type 1 subtype
RT   F viruses leads to the identification of a new HIV type 1 subtype
RT   designated K.";
RL   AIDS Res. Hum. Retroviruses 16:139-151(2000).
RN   [2]
RP   REVIEW.
RX   PubMed=12974773; DOI=10.1034/j.1600-0463.2003.11107803.x;
RA   Geijtenbeek T.B., van Kooyk Y.;
RT   "Pathogens target DC-SIGN to influence their fate DC-SIGN functions as a
RT   pathogen receptor with broad specificity.";
RL   APMIS 111:698-714(2003).
RN   [3]
RP   REVIEW.
RX   PubMed=12873764; DOI=10.1016/s0005-2736(03)00161-5;
RA   Gallo S.A., Finnegan C.M., Viard M., Raviv Y., Dimitrov A., Rawat S.S.,
RA   Puri A., Durell S., Blumenthal R.;
RT   "The HIV Env-mediated fusion reaction.";
RL   Biochim. Biophys. Acta 1614:36-50(2003).
RN   [4]
RP   REVIEW.
RX   PubMed=15719026; DOI=10.1038/sj.cdd.4401584;
RA   Perfettini J.-L., Castedo M., Roumier T., Andreau K., Nardacci R.,
RA   Piacentini M., Kroemer G.;
RT   "Mechanisms of apoptosis induction by the HIV-1 envelope.";
RL   Cell Death Differ. 12:916-923(2005).
RN   [5]
RP   REVIEW.
RX   PubMed=15725757; DOI=10.1089/aid.2005.21.171;
RA   Hartley O., Klasse P.J., Sattentau Q.J., Moore J.P.;
RT   "V3: HIV's switch-hitter.";
RL   AIDS Res. Hum. Retroviruses 21:171-189(2005).
RN   [6]
RP   REVIEW.
RX   PubMed=16114975; DOI=10.2165/00003495-200565130-00002;
RA   Reeves J.D., Piefer A.J.;
RT   "Emerging drug targets for antiretroviral therapy.";
RL   Drugs 65:1747-1766(2005).
RN   [7]
RP   REVIEW.
RX   PubMed=16437164; DOI=10.1038/sj.emboj.7600947;
RA   Lusso P.;
RT   "HIV and the chemokine system: 10 years later.";
RL   EMBO J. 25:447-456(2006).
CC   -!- FUNCTION: [Envelope glycoprotein gp160]: Oligomerizes in the host
CC       endoplasmic reticulum into predominantly trimers. In a second time,
CC       gp160 transits in the host Golgi, where glycosylation is completed. The
CC       precursor is then proteolytically cleaved in the trans-Golgi and
CC       thereby activated by cellular furin or furin-like proteases to produce
CC       gp120 and gp41. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- FUNCTION: [Surface protein gp120]: Attaches the virus to the host
CC       lymphoid cell by binding to the primary receptor CD4. This interaction
CC       induces a structural rearrangement creating a high affinity binding
CC       site for a chemokine coreceptor like CXCR4 and/or CCR5. Acts as a
CC       ligand for CD209/DC-SIGN and CLEC4M/DC-SIGNR, which are respectively
CC       found on dendritic cells (DCs), and on endothelial cells of liver
CC       sinusoids and lymph node sinuses. These interactions allow capture of
CC       viral particles at mucosal surfaces by these cells and subsequent
CC       transmission to permissive cells. HIV subverts the migration properties
CC       of dendritic cells to gain access to CD4+ T-cells in lymph nodes. Virus
CC       transmission to permissive T-cells occurs either in trans (without DCs
CC       infection, through viral capture and transmission), or in cis
CC       (following DCs productive infection, through the usual CD4-gp120
CC       interaction), thereby inducing a robust infection. In trans infection,
CC       bound virions remain infectious over days and it is proposed that they
CC       are not degraded, but protected in non-lysosomal acidic organelles
CC       within the DCs close to the cell membrane thus contributing to the
CC       viral infectious potential during DCs' migration from the periphery to
CC       the lymphoid tissues. On arrival at lymphoid tissues, intact virions
CC       recycle back to DCs' cell surface allowing virus transmission to CD4+
CC       T-cells. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- FUNCTION: [Transmembrane protein gp41]: Acts as a class I viral fusion
CC       protein. Under the current model, the protein has at least 3
CC       conformational states: pre-fusion native state, pre-hairpin
CC       intermediate state, and post-fusion hairpin state. During fusion of
CC       viral and target intracellular membranes, the coiled coil regions
CC       (heptad repeats) assume a trimer-of-hairpins structure, positioning the
CC       fusion peptide in close proximity to the C-terminal region of the
CC       ectodomain. The formation of this structure appears to drive apposition
CC       and subsequent fusion of viral and target cell membranes. Complete
CC       fusion occurs in host cell endosomes and is dynamin-dependent, however
CC       some lipid transfer might occur at the plasma membrane. The virus
CC       undergoes clathrin-dependent internalization long before endosomal
CC       fusion, thus minimizing the surface exposure of conserved viral
CC       epitopes during fusion and reducing the efficacy of inhibitors
CC       targeting these epitopes. Membranes fusion leads to delivery of the
CC       nucleocapsid into the cytoplasm. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBUNIT: [Surface protein gp120]: The mature envelope protein (Env)
CC       consists of a homotrimer of non-covalently associated gp120-gp41
CC       heterodimers. The resulting complex protrudes from the virus surface as
CC       a spike. There seems to be as few as 10 spikes on the average virion.
CC       Interacts with host CD4, CCR5 and CXCR4. Gp120 also interacts with the
CC       C-type lectins CD209/DC-SIGN and CLEC4M/DC-SIGNR (collectively referred
CC       to as DC-SIGN(R)). Gp120 and gp41 interact with GalCer. Gp120 interacts
CC       with host ITGA4/ITGB7 complex; on CD4+ T-cells, this interaction
CC       results in rapid activation of integrin ITGAL/LFA-1, which facilitates
CC       efficient cell-to-cell spreading of HIV-1. Gp120 interacts with cell-
CC       associated heparan sulfate; this interaction increases virus
CC       infectivity on permissive cells and may be involved in infection of
CC       CD4- cells. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBUNIT: [Transmembrane protein gp41]: The mature envelope protein
CC       (Env) consists of a homotrimer of non-covalently associated gp120-gp41
CC       heterodimers. The resulting complex protrudes from the virus surface as
CC       a spike. There seems to be as few as 10 spikes on the average virion.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBCELLULAR LOCATION: [Surface protein gp120]: Virion membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Peripheral membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host cell membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Peripheral membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host endosome membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Note=The surface protein is not
CC       anchored to the viral envelope, but associates with the extravirion
CC       surface through its binding to TM. It is probably concentrated at the
CC       site of budding and incorporated into the virions possibly by contacts
CC       between the cytoplasmic tail of Env and the N-terminus of Gag.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBCELLULAR LOCATION: [Transmembrane protein gp41]: Virion membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host cell membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host endosome membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Note=It is probably concentrated at
CC       the site of budding and incorporated into the virions possibly by
CC       contacts between the cytoplasmic tail of Env and the N-terminus of Gag.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: Some of the most genetically diverse regions of the viral
CC       genome are present in Env. They are called variable regions 1 through 5
CC       (V1 through V5). Coreceptor usage of gp120 is determined mainly by the
CC       primary structure of the third variable region (V3) in the outer domain
CC       of gp120. The sequence of V3 determines which coreceptor, CCR5 and/or
CC       CXCR4 (corresponding to R5/macrophage, X4/T cell and R5X4/T cell and
CC       macrophage tropism), is used to trigger the fusion potential of the Env
CC       complex, and hence which cells the virus can infect. Binding to CCR5
CC       involves a region adjacent in addition to V3. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- DOMAIN: The membrane proximal external region (MPER) present in gp41 is
CC       a tryptophan-rich region recognized by the antibodies 2F5, Z13, and
CC       4E10. MPER seems to play a role in fusion. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- DOMAIN: The 17 amino acids long immunosuppressive region is present in
CC       many retroviral envelope proteins. Synthetic peptides derived from this
CC       relatively conserved sequence inhibit immune function in vitro and in
CC       vivo. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: The YXXL motif is involved in determining the exact site of
CC       viral release at the surface of infected mononuclear cells and promotes
CC       endocytosis. YXXL and di-leucine endocytosis motifs interact directly
CC       or indirectly with the clathrin adapter complexes, opperate
CC       independently, and their activities are not additive.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: The CD4-binding region is targeted by the antibody b12.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- PTM: Highly glycosylated by host. The high number of glycan on the
CC       protein is reffered to as 'glycan shield' because it contributes to
CC       hide protein sequence from adaptive immune system. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- PTM: Palmitoylation of the transmembrane protein and of Env polyprotein
CC       (prior to its proteolytic cleavage) is essential for their association
CC       with host cell membrane lipid rafts. Palmitoylation is therefore
CC       required for envelope trafficking to classical lipid rafts, but not for
CC       viral replication. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- PTM: Specific enzymatic cleavages in vivo yield mature proteins.
CC       Envelope glycoproteins are synthesized as an inactive precursor that is
CC       heavily N-glycosylated and processed likely by host cell furin in the
CC       Golgi to yield the mature SU and TM proteins. The cleavage site between
CC       SU and TM requires the minimal sequence [KR]-X-[KR]-R. About 2 of the 9
CC       disulfide bonds of gp41 are reduced by P4HB/PDI, following binding to
CC       CD4 receptor. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- MISCELLANEOUS: Inhibitors targeting HIV-1 viral envelope proteins are
CC       used as antiretroviral drugs. Attachment of virions to the cell surface
CC       via non-specific interactions and CD4 binding can be blocked by
CC       inhibitors that include cyanovirin-N, cyclotriazadisulfonamide analogs,
CC       PRO 2000, TNX 355 and PRO 542. In addition, BMS 806 can block CD4-
CC       induced conformational changes. Env interactions with the coreceptor
CC       molecules can be targeted by CCR5 antagonists including SCH-D,
CC       maraviroc (UK 427857) and aplaviroc (GW 873140), and the CXCR4
CC       antagonist AMD 070. Fusion of viral and cellular membranes can be
CC       inhibited by peptides such as enfuvirtide and tifuvirtide (T 1249).
CC       Resistance to inhibitors associated with mutations in Env are observed.
CC       Most of the time, single mutations confer only a modest reduction in
CC       drug susceptibility. Combination of several mutations is usually
CC       required to develop a high-level drug resistance. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- MISCELLANEOUS: HIV-1 lineages are divided in three main groups, M (for
CC       Major), O (for Outlier), and N (for New, or Non-M, Non-O). The vast
CC       majority of strains found worldwide belong to the group M. Group O
CC       seems to be endemic to and largely confined to Cameroon and neighboring
CC       countries in West Central Africa, where these viruses represent a small
CC       minority of HIV-1 strains. The group N is represented by a limited
CC       number of isolates from Cameroonian persons. The group M is further
CC       subdivided in 9 clades or subtypes (A to D, F to H, J and K).
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SIMILARITY: Belongs to the HIV-1 env protein family.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=CAB58982.1; Type=Erroneous initiation;
CC   -!- WEB RESOURCE: Name=hivdb; Note=HIV drug resistance database;
CC       URL="https://hivdb.stanford.edu";
CC   -!- WEB RESOURCE: Name=HIV drug resistance mutations;
CC       URL="https://www.iasusa.org/content/hiv-drug-resistance-mutations";
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DR   EMBL; AJ249237; CAB58982.1; ALT_INIT; Genomic_RNA.
DR   SMR; Q9QBZ0; -.
DR   GlyCosmos; Q9QBZ0; 30 sites, No reported glycans.
DR   GO; GO:0044175; C:host cell endosome membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0016020; C:membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:0019031; C:viral envelope; IEA:UniProtKB-KW.
DR   GO; GO:0055036; C:virion membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005198; F:structural molecule activity; IEA:UniProtKB-UniRule.
DR   GO; GO:0075512; P:clathrin-dependent endocytosis of virus by host cell; IEA:UniProtKB-UniRule.
DR   GO; GO:0039654; P:fusion of virus membrane with host endosome membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:0019064; P:fusion of virus membrane with host plasma membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:1903905; P:positive regulation of establishment of T cell polarity; IEA:UniProtKB-UniRule.
DR   GO; GO:1903908; P:positive regulation of plasma membrane raft polarization; IEA:UniProtKB-UniRule.
DR   GO; GO:1903911; P:positive regulation of receptor clustering; IEA:UniProtKB-UniRule.
DR   GO; GO:0019082; P:viral protein processing; IEA:UniProtKB-UniRule.
DR   GO; GO:0019062; P:virion attachment to host cell; IEA:UniProtKB-UniRule.
DR   GO; GO:0019049; P:virus-mediated perturbation of host defense response; IEA:UniProtKB-UniRule.
DR   CDD; cd09909; HIV-1-like_HR1-HR2; 1.
DR   Gene3D; 1.10.287.210; -; 1.
DR   Gene3D; 2.170.40.20; Human immunodeficiency virus 1, Gp160, envelope glycoprotein; 2.
DR   Gene3D; 1.20.5.490; Single helix bin; 1.
DR   HAMAP; MF_04083; HIV_ENV; 1.
DR   InterPro; IPR036377; Gp120_core_sf.
DR   InterPro; IPR037527; Gp160.
DR   InterPro; IPR000328; GP41-like.
DR   InterPro; IPR000777; HIV1_Gp120.
DR   Pfam; PF00516; GP120; 1.
DR   Pfam; PF00517; GP41; 1.
DR   SUPFAM; SSF56502; gp120 core; 2.
DR   SUPFAM; SSF58069; Virus ectodomain; 1.
PE   3: Inferred from homology;
KW   AIDS; Apoptosis; Clathrin-mediated endocytosis of virus by host;
KW   Cleavage on pair of basic residues; Coiled coil; Disulfide bond;
KW   Fusion of virus membrane with host endosomal membrane;
KW   Fusion of virus membrane with host membrane; Glycoprotein;
KW   Host cell membrane; Host endosome; Host membrane; Host-virus interaction;
KW   Lipoprotein; Membrane; Palmitate; Signal; Transmembrane;
KW   Transmembrane helix; Viral attachment to host cell; Viral envelope protein;
KW   Viral immunoevasion; Viral penetration into host cytoplasm; Virion;
KW   Virus endocytosis by host; Virus entry into host cell.
FT   SIGNAL          1..31
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CHAIN           32..850
FT                   /note="Envelope glycoprotein gp160"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000244678"
FT   CHAIN           32..505
FT                   /note="Surface protein gp120"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000244679"
FT   CHAIN           506..850
FT                   /note="Transmembrane protein gp41"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000244680"
FT   TOPO_DOM        32..678
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   TRANSMEM        679..699
FT                   /note="Helical"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   TOPO_DOM        700..850
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          130..157
FT                   /note="V1"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          158..197
FT                   /note="V2"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          297..330
FT                   /note="V3"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          362..372
FT                   /note="CD4-binding loop"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          383..413
FT                   /note="V4"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          456..465
FT                   /note="V5"
FT   REGION          458..465
FT                   /note="V5"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          506..526
FT                   /note="Fusion peptide"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          568..586
FT                   /note="Immunosuppression"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          656..677
FT                   /note="MPER; binding to GalCer"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          716..736
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COILED          627..661
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   MOTIF           706..709
FT                   /note="YXXL motif; contains endocytosis signal"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   MOTIF           849..850
FT                   /note="Di-leucine internalization motif"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   SITE            505..506
FT                   /note="Cleavage; by host furin"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   LIPID           758
FT                   /note="S-palmitoyl cysteine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        87
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        129
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        136
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        141
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        142
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        148
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        157
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        161
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        186
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        189
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        198
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        231
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        235
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        242
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        263
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        277
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        296
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        302
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        332
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        354
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        384
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        390
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        401
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        406
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        443
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        457
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        605
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        610
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        619
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        631
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        53..73
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        118..206
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        125..197
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        130..158
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        219..248
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        229..240
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        297..331
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        376..440
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        383..413
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        592..598
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
SQ   SEQUENCE   850 AA;  96359 MW;  B4A7966CE7627B7B CRC64;
     MRVREMQRNW QHLGRWGLLF LGILIICSAA DKLWVTVYYG VPVWKEATTT LFCASDAKAY
     EREVHNVWAT YACVPTDPSP QELVLGNVSE KFNMWKNNMV DQMHEDIISL WDESLKPCVK
     LTPLCVTLNC TKAIINVTSS NNTTLAPNVT ISEEMKNCSF NITTEIRDKQ KKEYALFYKL
     DVVQINNSNT SYRLINCNTS TLTQACPKVS FDPIPIHYCA PAGFAILKCN NKTFNGTGLC
     RNVSTVQCTH GIKPVVSTQL LLNGSLAEEK MIIRSENISD NTKTIIVQFK NPVKINCTRP
     NNNTRRSIHI GPGRAFYATG EIIGDTRKAH CNISEKQWYD TLIKIATEFK DQYNKTVGFQ
     PSAGGDLEIT THSFNCRGEF FYCNTTILFN HTRVNDILSN NHTRENDTIT LPCRIKQIVN
     MWQRVGQAMY APPIAGKIQC NSNITGLLLT IDGGEGNESE TLRPGGGDMR DNWRSELYKY
     KVVKIEPLGV APTKAKRQVV QREKRAVGMG AMFLGFLGAA GSTMGAASIT LTVQARNLLS
     GIVQQQSNLL KAIEAQQHLL QLTVWGIKQL QARILAVERY LKDQQLLGIW GCSGKLICPT
     TVPWNLSWSN KSQDEIWGNM TWMEWEKEIG NYTDTIYRLI ESAQNQQEKN EQDLLALDKW
     DNLWNWFSIT RWLWYIEIFI MIIGSLIGLR IVFTVLSIIN RVRQGYSPLS LQTLIPNSRG
     PERPGGIEEE GGEQDKDRSI RLVSGFLALA WDDFRSLCVF SYHCLRNFIL IAARTVDKGL
     KRGWEVLKYL WNLAQYWGQE LKNSAISLLD RTAIAVAEGT DRIIEILQRA GRAVLNIPRR
     IRQGLERALL
//
ID   ENV_HV1MA               Reviewed;         859 AA.
AC   P04583;
DT   13-AUG-1987, integrated into UniProtKB/Swiss-Prot.
DT   13-AUG-1987, sequence version 1.
DT   27-MAR-2024, entry version 150.
DE   RecName: Full=Envelope glycoprotein gp160 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   AltName: Full=Env polyprotein {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Contains:
DE     RecName: Full=Surface protein gp120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=SU {ECO:0000255|HAMAP-Rule:MF_04083};
DE     AltName: Full=Glycoprotein 120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=gp120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Contains:
DE     RecName: Full=Transmembrane protein gp41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=TM {ECO:0000255|HAMAP-Rule:MF_04083};
DE     AltName: Full=Glycoprotein 41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=gp41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Flags: Precursor;
GN   Name=env {ECO:0000255|HAMAP-Rule:MF_04083};
OS   Human immunodeficiency virus type 1 group M subtype A (isolate MAL)
OS   (HIV-1).
OC   Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC   Ortervirales; Retroviridae; Orthoretrovirinae; Lentivirus;
OC   Human immunodeficiency virus 1.
OX   NCBI_TaxID=11697;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX   PubMed=2424612; DOI=10.1016/0092-8674(86)90860-3;
RA   Alizon M., Wain-Hobson S., Montagnier L., Sonigo P.;
RT   "Genetic variability of the AIDS virus: nucleotide sequence analysis of two
RT   isolates from African patients.";
RL   Cell 46:63-74(1986).
RN   [2]
RP   REVIEW.
RX   PubMed=12974773; DOI=10.1034/j.1600-0463.2003.11107803.x;
RA   Geijtenbeek T.B., van Kooyk Y.;
RT   "Pathogens target DC-SIGN to influence their fate DC-SIGN functions as a
RT   pathogen receptor with broad specificity.";
RL   APMIS 111:698-714(2003).
RN   [3]
RP   REVIEW.
RX   PubMed=12873764; DOI=10.1016/s0005-2736(03)00161-5;
RA   Gallo S.A., Finnegan C.M., Viard M., Raviv Y., Dimitrov A., Rawat S.S.,
RA   Puri A., Durell S., Blumenthal R.;
RT   "The HIV Env-mediated fusion reaction.";
RL   Biochim. Biophys. Acta 1614:36-50(2003).
RN   [4]
RP   REVIEW.
RX   PubMed=15719026; DOI=10.1038/sj.cdd.4401584;
RA   Perfettini J.-L., Castedo M., Roumier T., Andreau K., Nardacci R.,
RA   Piacentini M., Kroemer G.;
RT   "Mechanisms of apoptosis induction by the HIV-1 envelope.";
RL   Cell Death Differ. 12:916-923(2005).
RN   [5]
RP   REVIEW.
RX   PubMed=15725757; DOI=10.1089/aid.2005.21.171;
RA   Hartley O., Klasse P.J., Sattentau Q.J., Moore J.P.;
RT   "V3: HIV's switch-hitter.";
RL   AIDS Res. Hum. Retroviruses 21:171-189(2005).
RN   [6]
RP   REVIEW.
RX   PubMed=16114975; DOI=10.2165/00003495-200565130-00002;
RA   Reeves J.D., Piefer A.J.;
RT   "Emerging drug targets for antiretroviral therapy.";
RL   Drugs 65:1747-1766(2005).
RN   [7]
RP   REVIEW.
RX   PubMed=16437164; DOI=10.1038/sj.emboj.7600947;
RA   Lusso P.;
RT   "HIV and the chemokine system: 10 years later.";
RL   EMBO J. 25:447-456(2006).
CC   -!- FUNCTION: [Envelope glycoprotein gp160]: Oligomerizes in the host
CC       endoplasmic reticulum into predominantly trimers. In a second time,
CC       gp160 transits in the host Golgi, where glycosylation is completed. The
CC       precursor is then proteolytically cleaved in the trans-Golgi and
CC       thereby activated by cellular furin or furin-like proteases to produce
CC       gp120 and gp41. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- FUNCTION: [Surface protein gp120]: Attaches the virus to the host
CC       lymphoid cell by binding to the primary receptor CD4. This interaction
CC       induces a structural rearrangement creating a high affinity binding
CC       site for a chemokine coreceptor like CXCR4 and/or CCR5. Acts as a
CC       ligand for CD209/DC-SIGN and CLEC4M/DC-SIGNR, which are respectively
CC       found on dendritic cells (DCs), and on endothelial cells of liver
CC       sinusoids and lymph node sinuses. These interactions allow capture of
CC       viral particles at mucosal surfaces by these cells and subsequent
CC       transmission to permissive cells. HIV subverts the migration properties
CC       of dendritic cells to gain access to CD4+ T-cells in lymph nodes. Virus
CC       transmission to permissive T-cells occurs either in trans (without DCs
CC       infection, through viral capture and transmission), or in cis
CC       (following DCs productive infection, through the usual CD4-gp120
CC       interaction), thereby inducing a robust infection. In trans infection,
CC       bound virions remain infectious over days and it is proposed that they
CC       are not degraded, but protected in non-lysosomal acidic organelles
CC       within the DCs close to the cell membrane thus contributing to the
CC       viral infectious potential during DCs' migration from the periphery to
CC       the lymphoid tissues. On arrival at lymphoid tissues, intact virions
CC       recycle back to DCs' cell surface allowing virus transmission to CD4+
CC       T-cells. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- FUNCTION: [Transmembrane protein gp41]: Acts as a class I viral fusion
CC       protein. Under the current model, the protein has at least 3
CC       conformational states: pre-fusion native state, pre-hairpin
CC       intermediate state, and post-fusion hairpin state. During fusion of
CC       viral and target intracellular membranes, the coiled coil regions
CC       (heptad repeats) assume a trimer-of-hairpins structure, positioning the
CC       fusion peptide in close proximity to the C-terminal region of the
CC       ectodomain. The formation of this structure appears to drive apposition
CC       and subsequent fusion of viral and target cell membranes. Complete
CC       fusion occurs in host cell endosomes and is dynamin-dependent, however
CC       some lipid transfer might occur at the plasma membrane. The virus
CC       undergoes clathrin-dependent internalization long before endosomal
CC       fusion, thus minimizing the surface exposure of conserved viral
CC       epitopes during fusion and reducing the efficacy of inhibitors
CC       targeting these epitopes. Membranes fusion leads to delivery of the
CC       nucleocapsid into the cytoplasm. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBUNIT: [Surface protein gp120]: The mature envelope protein (Env)
CC       consists of a homotrimer of non-covalently associated gp120-gp41
CC       heterodimers. The resulting complex protrudes from the virus surface as
CC       a spike. There seems to be as few as 10 spikes on the average virion.
CC       Interacts with host CD4, CCR5 and CXCR4. Gp120 also interacts with the
CC       C-type lectins CD209/DC-SIGN and CLEC4M/DC-SIGNR (collectively referred
CC       to as DC-SIGN(R)). Gp120 and gp41 interact with GalCer. Gp120 interacts
CC       with host ITGA4/ITGB7 complex; on CD4+ T-cells, this interaction
CC       results in rapid activation of integrin ITGAL/LFA-1, which facilitates
CC       efficient cell-to-cell spreading of HIV-1. Gp120 interacts with cell-
CC       associated heparan sulfate; this interaction increases virus
CC       infectivity on permissive cells and may be involved in infection of
CC       CD4- cells. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBUNIT: [Transmembrane protein gp41]: The mature envelope protein
CC       (Env) consists of a homotrimer of non-covalently associated gp120-gp41
CC       heterodimers. The resulting complex protrudes from the virus surface as
CC       a spike. There seems to be as few as 10 spikes on the average virion.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBCELLULAR LOCATION: [Surface protein gp120]: Virion membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Peripheral membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host cell membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Peripheral membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host endosome membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Note=The surface protein is not
CC       anchored to the viral envelope, but associates with the extravirion
CC       surface through its binding to TM. It is probably concentrated at the
CC       site of budding and incorporated into the virions possibly by contacts
CC       between the cytoplasmic tail of Env and the N-terminus of Gag.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBCELLULAR LOCATION: [Transmembrane protein gp41]: Virion membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host cell membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host endosome membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Note=It is probably concentrated at
CC       the site of budding and incorporated into the virions possibly by
CC       contacts between the cytoplasmic tail of Env and the N-terminus of Gag.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: Some of the most genetically diverse regions of the viral
CC       genome are present in Env. They are called variable regions 1 through 5
CC       (V1 through V5). Coreceptor usage of gp120 is determined mainly by the
CC       primary structure of the third variable region (V3) in the outer domain
CC       of gp120. The sequence of V3 determines which coreceptor, CCR5 and/or
CC       CXCR4 (corresponding to R5/macrophage, X4/T cell and R5X4/T cell and
CC       macrophage tropism), is used to trigger the fusion potential of the Env
CC       complex, and hence which cells the virus can infect. Binding to CCR5
CC       involves a region adjacent in addition to V3. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- DOMAIN: The membrane proximal external region (MPER) present in gp41 is
CC       a tryptophan-rich region recognized by the antibodies 2F5, Z13, and
CC       4E10. MPER seems to play a role in fusion. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- DOMAIN: The 17 amino acids long immunosuppressive region is present in
CC       many retroviral envelope proteins. Synthetic peptides derived from this
CC       relatively conserved sequence inhibit immune function in vitro and in
CC       vivo. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: The YXXL motif is involved in determining the exact site of
CC       viral release at the surface of infected mononuclear cells and promotes
CC       endocytosis. YXXL and di-leucine endocytosis motifs interact directly
CC       or indirectly with the clathrin adapter complexes, opperate
CC       independently, and their activities are not additive.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: The CD4-binding region is targeted by the antibody b12.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- PTM: Highly glycosylated by host. The high number of glycan on the
CC       protein is reffered to as 'glycan shield' because it contributes to
CC       hide protein sequence from adaptive immune system. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- PTM: Palmitoylation of the transmembrane protein and of Env polyprotein
CC       (prior to its proteolytic cleavage) is essential for their association
CC       with host cell membrane lipid rafts. Palmitoylation is therefore
CC       required for envelope trafficking to classical lipid rafts, but not for
CC       viral replication. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- PTM: Specific enzymatic cleavages in vivo yield mature proteins.
CC       Envelope glycoproteins are synthesized as an inactive precursor that is
CC       heavily N-glycosylated and processed likely by host cell furin in the
CC       Golgi to yield the mature SU and TM proteins. The cleavage site between
CC       SU and TM requires the minimal sequence [KR]-X-[KR]-R. About 2 of the 9
CC       disulfide bonds of gp41 are reduced by P4HB/PDI, following binding to
CC       CD4 receptor. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- MISCELLANEOUS: Inhibitors targeting HIV-1 viral envelope proteins are
CC       used as antiretroviral drugs. Attachment of virions to the cell surface
CC       via non-specific interactions and CD4 binding can be blocked by
CC       inhibitors that include cyanovirin-N, cyclotriazadisulfonamide analogs,
CC       PRO 2000, TNX 355 and PRO 542. In addition, BMS 806 can block CD4-
CC       induced conformational changes. Env interactions with the coreceptor
CC       molecules can be targeted by CCR5 antagonists including SCH-D,
CC       maraviroc (UK 427857) and aplaviroc (GW 873140), and the CXCR4
CC       antagonist AMD 070. Fusion of viral and cellular membranes can be
CC       inhibited by peptides such as enfuvirtide and tifuvirtide (T 1249).
CC       Resistance to inhibitors associated with mutations in Env are observed.
CC       Most of the time, single mutations confer only a modest reduction in
CC       drug susceptibility. Combination of several mutations is usually
CC       required to develop a high-level drug resistance. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- MISCELLANEOUS: HIV-1 lineages are divided in three main groups, M (for
CC       Major), O (for Outlier), and N (for New, or Non-M, Non-O). The vast
CC       majority of strains found worldwide belong to the group M. Group O
CC       seems to be endemic to and largely confined to Cameroon and neighboring
CC       countries in West Central Africa, where these viruses represent a small
CC       minority of HIV-1 strains. The group N is represented by a limited
CC       number of isolates from Cameroonian persons. The group M is further
CC       subdivided in 9 clades or subtypes (A to D, F to H, J and K).
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SIMILARITY: Belongs to the HIV-1 env protein family.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- WEB RESOURCE: Name=hivdb; Note=HIV drug resistance database;
CC       URL="https://hivdb.stanford.edu";
CC   -!- WEB RESOURCE: Name=HIV drug resistance mutations;
CC       URL="https://www.iasusa.org/content/hiv-drug-resistance-mutations";
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DR   EMBL; X04415; CAA28016.1; -; Genomic_RNA.
DR   PIR; T01672; T01672.
DR   PDB; 2X4O; X-ray; 2.30 A; C/F=120-128.
DR   PDBsum; 2X4O; -.
DR   SMR; P04583; -.
DR   GlyCosmos; P04583; 28 sites, No reported glycans.
DR   Reactome; R-HSA-5621480; Dectin-2 family.
DR   EvolutionaryTrace; P04583; -.
DR   Proteomes; UP000007696; Genome.
DR   GO; GO:0044175; C:host cell endosome membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0016020; C:membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:0019031; C:viral envelope; IEA:UniProtKB-KW.
DR   GO; GO:0055036; C:virion membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005198; F:structural molecule activity; IEA:UniProtKB-UniRule.
DR   GO; GO:0075512; P:clathrin-dependent endocytosis of virus by host cell; IEA:UniProtKB-UniRule.
DR   GO; GO:0039654; P:fusion of virus membrane with host endosome membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:0019064; P:fusion of virus membrane with host plasma membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:1903905; P:positive regulation of establishment of T cell polarity; IEA:UniProtKB-UniRule.
DR   GO; GO:1903908; P:positive regulation of plasma membrane raft polarization; IEA:UniProtKB-UniRule.
DR   GO; GO:1903911; P:positive regulation of receptor clustering; IEA:UniProtKB-UniRule.
DR   GO; GO:0019082; P:viral protein processing; IEA:UniProtKB-UniRule.
DR   GO; GO:0019062; P:virion attachment to host cell; IEA:UniProtKB-UniRule.
DR   GO; GO:0019049; P:virus-mediated perturbation of host defense response; IEA:UniProtKB-UniRule.
DR   CDD; cd09909; HIV-1-like_HR1-HR2; 1.
DR   Gene3D; 1.10.287.210; -; 1.
DR   Gene3D; 2.170.40.20; Human immunodeficiency virus 1, Gp160, envelope glycoprotein; 2.
DR   Gene3D; 1.20.5.490; Single helix bin; 1.
DR   HAMAP; MF_04083; HIV_ENV; 1.
DR   InterPro; IPR036377; Gp120_core_sf.
DR   InterPro; IPR037527; Gp160.
DR   InterPro; IPR000328; GP41-like.
DR   InterPro; IPR000777; HIV1_Gp120.
DR   Pfam; PF00516; GP120; 1.
DR   Pfam; PF00517; GP41; 1.
DR   SUPFAM; SSF56502; gp120 core; 2.
DR   SUPFAM; SSF58069; Virus ectodomain; 1.
PE   1: Evidence at protein level;
KW   3D-structure; AIDS; Apoptosis;
KW   Clathrin-mediated endocytosis of virus by host;
KW   Cleavage on pair of basic residues; Coiled coil; Disulfide bond;
KW   Fusion of virus membrane with host endosomal membrane;
KW   Fusion of virus membrane with host membrane; Glycoprotein;
KW   Host cell membrane; Host endosome; Host membrane; Host-virus interaction;
KW   Lipoprotein; Membrane; Palmitate; Reference proteome; Signal;
KW   Transmembrane; Transmembrane helix; Viral attachment to host cell;
KW   Viral envelope protein; Viral immunoevasion;
KW   Viral penetration into host cytoplasm; Virion; Virus endocytosis by host;
KW   Virus entry into host cell.
FT   SIGNAL          1..31
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CHAIN           32..859
FT                   /note="Envelope glycoprotein gp160"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000441243"
FT   CHAIN           32..513
FT                   /note="Surface protein gp120"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000441244"
FT   CHAIN           514..859
FT                   /note="Transmembrane protein gp41"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000038411"
FT   TOPO_DOM        32..686
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   TRANSMEM        687..707
FT                   /note="Helical"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   TOPO_DOM        708..859
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          130..161
FT                   /note="V1"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          162..201
FT                   /note="V2"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          301..333
FT                   /note="V3"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          366..376
FT                   /note="CD4-binding loop"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          387..418
FT                   /note="V4"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          461..473
FT                   /note="V5"
FT   REGION          463..473
FT                   /note="V5"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          514..534
FT                   /note="Fusion peptide"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          576..594
FT                   /note="Immunosuppression"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          664..685
FT                   /note="MPER; binding to GalCer"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          721..744
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COILED          635..669
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   MOTIF           714..717
FT                   /note="YXXL motif; contains endocytosis signal"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   MOTIF           858..859
FT                   /note="Di-leucine internalization motif"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   SITE            513..514
FT                   /note="Cleavage; by host furin"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   LIPID           767
FT                   /note="S-palmitoyl cysteine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        87
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        129
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        134
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        139
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        146
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        161
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        193
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        202
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        239
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        246
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        267
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        281
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        294
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        300
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        306
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        337
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        357
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        364
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        388
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        394
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        406
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        448
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        460
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        467
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        613
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        618
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        627
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        639
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        53..73
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        118..210
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        125..201
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        130..162
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        223..252
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        233..244
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        301..334
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        380..445
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        387..418
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        600..606
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
SQ   SEQUENCE   859 AA;  97109 MW;  DBCF9AA52E3ABF29 CRC64;
     MRVREIQRNY QNWWRWGMML LGMLMTCSIA EDLWVTVYYG VPVWKEATTT LFCASDAKSY
     ETEVHNIWAT HACVPTDPNP QEIELENVTE GFNMWKNNMV EQMHEDIISL WDQSLKPCVK
     LTPLCVTLNC TNVNGTAVNG TNAGSNRTNA ELKMEIGEVK NCSFNITPVG SDKRQEYATF
     YNLDLVQIDD SDNSSYRLIN CNTSVITQAC PKVTFDPIPI HYCAPAGFAI LKCNDKKFNG
     TEICKNVSTV QCTHGIKPVV STQLLLNGSL AEEEIMIRSE NLTDNTKNII VQLNETVTIN
     CTRPGNNTRR GIHFGPGQAL YTTGIVGDIR RAYCTINETE WDKTLQQVAV KLGSLLNKTK
     IIFNSSSGGD PEITTHSFNC RGEFFYCNTS KLFNSTWQNN GARLSNSTES TGSITLPCRI
     KQIINMWQKT GKAMYAPPIA GVINCLSNIT GLILTRDGGN SSDNSDNETL RPGGGDMRDN
     WISELYKYKV VRIEPLGVAP TKAKRRVVER EKRAIGLGAM FLGFLGAAGS TMGAASLTLT
     VQARQLLSGI VQQQNNLLRA IEAQQHLLQL TVWGIKQLQA RVLAVERYLQ DQRLLGMWGC
     SGKHICTTFV PWNSSWSNRS LDDIWNNMTW MQWEKEISNY TGIIYNLIEE SQIQQEKNEK
     ELLELDKWAS LWNWFSISKW LWYIRIFIIV VGGLIGLRII FAVLSLVNRV RQGYSPLSLQ
     TLLPTPRGPP DRPEGIEEEG GEQGRGRSIR LVNGFSALIW DDLRNLCLFS YHRLRDLLLI
     ATRIVELLGR RGWEALKYLW NLLQYWGQEL KNSAISLLNT TAIAVAECTD RVIEIGQRFG
     RAILHIPRRI RQGFERALL
//
ID   ENV_HV1MF               Reviewed;         853 AA.
AC   P19551;
DT   01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
DT   01-FEB-1991, sequence version 1.
DT   27-MAR-2024, entry version 150.
DE   RecName: Full=Envelope glycoprotein gp160 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   AltName: Full=Env polyprotein {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Contains:
DE     RecName: Full=Surface protein gp120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=SU {ECO:0000255|HAMAP-Rule:MF_04083};
DE     AltName: Full=Glycoprotein 120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=gp120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Contains:
DE     RecName: Full=Transmembrane protein gp41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=TM {ECO:0000255|HAMAP-Rule:MF_04083};
DE     AltName: Full=Glycoprotein 41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=gp41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Flags: Precursor;
GN   Name=env {ECO:0000255|HAMAP-Rule:MF_04083};
OS   Human immunodeficiency virus type 1 group M subtype B (isolate MFA)
OS   (HIV-1).
OC   Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC   Ortervirales; Retroviridae; Orthoretrovirinae; Lentivirus;
OC   Human immunodeficiency virus 1.
OX   NCBI_TaxID=11704;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX   PubMed=1695254; DOI=10.1128/jvi.64.8.3792-3803.1990;
RA   Stevenson M., Haggerty S., Lamonica C., Mann A.M., Meier C., Wasiak A.;
RT   "Cloning and characterization of human immunodeficiency virus type 1
RT   variants diminished in the ability to induce syncytium-independent
RT   cytolysis.";
RL   J. Virol. 64:3792-3803(1990).
RN   [2]
RP   REVIEW.
RX   PubMed=12974773; DOI=10.1034/j.1600-0463.2003.11107803.x;
RA   Geijtenbeek T.B., van Kooyk Y.;
RT   "Pathogens target DC-SIGN to influence their fate DC-SIGN functions as a
RT   pathogen receptor with broad specificity.";
RL   APMIS 111:698-714(2003).
RN   [3]
RP   REVIEW.
RX   PubMed=12873764; DOI=10.1016/s0005-2736(03)00161-5;
RA   Gallo S.A., Finnegan C.M., Viard M., Raviv Y., Dimitrov A., Rawat S.S.,
RA   Puri A., Durell S., Blumenthal R.;
RT   "The HIV Env-mediated fusion reaction.";
RL   Biochim. Biophys. Acta 1614:36-50(2003).
RN   [4]
RP   REVIEW.
RX   PubMed=15719026; DOI=10.1038/sj.cdd.4401584;
RA   Perfettini J.-L., Castedo M., Roumier T., Andreau K., Nardacci R.,
RA   Piacentini M., Kroemer G.;
RT   "Mechanisms of apoptosis induction by the HIV-1 envelope.";
RL   Cell Death Differ. 12:916-923(2005).
RN   [5]
RP   REVIEW.
RX   PubMed=15725757; DOI=10.1089/aid.2005.21.171;
RA   Hartley O., Klasse P.J., Sattentau Q.J., Moore J.P.;
RT   "V3: HIV's switch-hitter.";
RL   AIDS Res. Hum. Retroviruses 21:171-189(2005).
RN   [6]
RP   REVIEW.
RX   PubMed=16114975; DOI=10.2165/00003495-200565130-00002;
RA   Reeves J.D., Piefer A.J.;
RT   "Emerging drug targets for antiretroviral therapy.";
RL   Drugs 65:1747-1766(2005).
RN   [7]
RP   REVIEW.
RX   PubMed=16437164; DOI=10.1038/sj.emboj.7600947;
RA   Lusso P.;
RT   "HIV and the chemokine system: 10 years later.";
RL   EMBO J. 25:447-456(2006).
CC   -!- FUNCTION: [Envelope glycoprotein gp160]: Oligomerizes in the host
CC       endoplasmic reticulum into predominantly trimers. In a second time,
CC       gp160 transits in the host Golgi, where glycosylation is completed. The
CC       precursor is then proteolytically cleaved in the trans-Golgi and
CC       thereby activated by cellular furin or furin-like proteases to produce
CC       gp120 and gp41. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- FUNCTION: [Surface protein gp120]: Attaches the virus to the host
CC       lymphoid cell by binding to the primary receptor CD4. This interaction
CC       induces a structural rearrangement creating a high affinity binding
CC       site for a chemokine coreceptor like CXCR4 and/or CCR5. Acts as a
CC       ligand for CD209/DC-SIGN and CLEC4M/DC-SIGNR, which are respectively
CC       found on dendritic cells (DCs), and on endothelial cells of liver
CC       sinusoids and lymph node sinuses. These interactions allow capture of
CC       viral particles at mucosal surfaces by these cells and subsequent
CC       transmission to permissive cells. HIV subverts the migration properties
CC       of dendritic cells to gain access to CD4+ T-cells in lymph nodes. Virus
CC       transmission to permissive T-cells occurs either in trans (without DCs
CC       infection, through viral capture and transmission), or in cis
CC       (following DCs productive infection, through the usual CD4-gp120
CC       interaction), thereby inducing a robust infection. In trans infection,
CC       bound virions remain infectious over days and it is proposed that they
CC       are not degraded, but protected in non-lysosomal acidic organelles
CC       within the DCs close to the cell membrane thus contributing to the
CC       viral infectious potential during DCs' migration from the periphery to
CC       the lymphoid tissues. On arrival at lymphoid tissues, intact virions
CC       recycle back to DCs' cell surface allowing virus transmission to CD4+
CC       T-cells. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- FUNCTION: [Transmembrane protein gp41]: Acts as a class I viral fusion
CC       protein. Under the current model, the protein has at least 3
CC       conformational states: pre-fusion native state, pre-hairpin
CC       intermediate state, and post-fusion hairpin state. During fusion of
CC       viral and target intracellular membranes, the coiled coil regions
CC       (heptad repeats) assume a trimer-of-hairpins structure, positioning the
CC       fusion peptide in close proximity to the C-terminal region of the
CC       ectodomain. The formation of this structure appears to drive apposition
CC       and subsequent fusion of viral and target cell membranes. Complete
CC       fusion occurs in host cell endosomes and is dynamin-dependent, however
CC       some lipid transfer might occur at the plasma membrane. The virus
CC       undergoes clathrin-dependent internalization long before endosomal
CC       fusion, thus minimizing the surface exposure of conserved viral
CC       epitopes during fusion and reducing the efficacy of inhibitors
CC       targeting these epitopes. Membranes fusion leads to delivery of the
CC       nucleocapsid into the cytoplasm. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBUNIT: [Surface protein gp120]: The mature envelope protein (Env)
CC       consists of a homotrimer of non-covalently associated gp120-gp41
CC       heterodimers. The resulting complex protrudes from the virus surface as
CC       a spike. There seems to be as few as 10 spikes on the average virion.
CC       Interacts with host CD4, CCR5 and CXCR4. Gp120 also interacts with the
CC       C-type lectins CD209/DC-SIGN and CLEC4M/DC-SIGNR (collectively referred
CC       to as DC-SIGN(R)). Gp120 and gp41 interact with GalCer. Gp120 interacts
CC       with host ITGA4/ITGB7 complex; on CD4+ T-cells, this interaction
CC       results in rapid activation of integrin ITGAL/LFA-1, which facilitates
CC       efficient cell-to-cell spreading of HIV-1. Gp120 interacts with cell-
CC       associated heparan sulfate; this interaction increases virus
CC       infectivity on permissive cells and may be involved in infection of
CC       CD4- cells. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBUNIT: [Transmembrane protein gp41]: The mature envelope protein
CC       (Env) consists of a homotrimer of non-covalently associated gp120-gp41
CC       heterodimers. The resulting complex protrudes from the virus surface as
CC       a spike. There seems to be as few as 10 spikes on the average virion.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBCELLULAR LOCATION: [Surface protein gp120]: Virion membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Peripheral membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host cell membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Peripheral membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host endosome membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Note=The surface protein is not
CC       anchored to the viral envelope, but associates with the extravirion
CC       surface through its binding to TM. It is probably concentrated at the
CC       site of budding and incorporated into the virions possibly by contacts
CC       between the cytoplasmic tail of Env and the N-terminus of Gag.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBCELLULAR LOCATION: [Transmembrane protein gp41]: Virion membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host cell membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host endosome membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Note=It is probably concentrated at
CC       the site of budding and incorporated into the virions possibly by
CC       contacts between the cytoplasmic tail of Env and the N-terminus of Gag.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: Some of the most genetically diverse regions of the viral
CC       genome are present in Env. They are called variable regions 1 through 5
CC       (V1 through V5). Coreceptor usage of gp120 is determined mainly by the
CC       primary structure of the third variable region (V3) in the outer domain
CC       of gp120. The sequence of V3 determines which coreceptor, CCR5 and/or
CC       CXCR4 (corresponding to R5/macrophage, X4/T cell and R5X4/T cell and
CC       macrophage tropism), is used to trigger the fusion potential of the Env
CC       complex, and hence which cells the virus can infect. Binding to CCR5
CC       involves a region adjacent in addition to V3. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- DOMAIN: The membrane proximal external region (MPER) present in gp41 is
CC       a tryptophan-rich region recognized by the antibodies 2F5, Z13, and
CC       4E10. MPER seems to play a role in fusion. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- DOMAIN: The 17 amino acids long immunosuppressive region is present in
CC       many retroviral envelope proteins. Synthetic peptides derived from this
CC       relatively conserved sequence inhibit immune function in vitro and in
CC       vivo. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: The YXXL motif is involved in determining the exact site of
CC       viral release at the surface of infected mononuclear cells and promotes
CC       endocytosis. YXXL and di-leucine endocytosis motifs interact directly
CC       or indirectly with the clathrin adapter complexes, opperate
CC       independently, and their activities are not additive.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: The CD4-binding region is targeted by the antibody b12.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- PTM: Highly glycosylated by host. The high number of glycan on the
CC       protein is reffered to as 'glycan shield' because it contributes to
CC       hide protein sequence from adaptive immune system. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- PTM: Palmitoylation of the transmembrane protein and of Env polyprotein
CC       (prior to its proteolytic cleavage) is essential for their association
CC       with host cell membrane lipid rafts. Palmitoylation is therefore
CC       required for envelope trafficking to classical lipid rafts, but not for
CC       viral replication. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- PTM: Specific enzymatic cleavages in vivo yield mature proteins.
CC       Envelope glycoproteins are synthesized as an inactive precursor that is
CC       heavily N-glycosylated and processed likely by host cell furin in the
CC       Golgi to yield the mature SU and TM proteins. The cleavage site between
CC       SU and TM requires the minimal sequence [KR]-X-[KR]-R. About 2 of the 9
CC       disulfide bonds of gp41 are reduced by P4HB/PDI, following binding to
CC       CD4 receptor. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- MISCELLANEOUS: Inhibitors targeting HIV-1 viral envelope proteins are
CC       used as antiretroviral drugs. Attachment of virions to the cell surface
CC       via non-specific interactions and CD4 binding can be blocked by
CC       inhibitors that include cyanovirin-N, cyclotriazadisulfonamide analogs,
CC       PRO 2000, TNX 355 and PRO 542. In addition, BMS 806 can block CD4-
CC       induced conformational changes. Env interactions with the coreceptor
CC       molecules can be targeted by CCR5 antagonists including SCH-D,
CC       maraviroc (UK 427857) and aplaviroc (GW 873140), and the CXCR4
CC       antagonist AMD 070. Fusion of viral and cellular membranes can be
CC       inhibited by peptides such as enfuvirtide and tifuvirtide (T 1249).
CC       Resistance to inhibitors associated with mutations in Env are observed.
CC       Most of the time, single mutations confer only a modest reduction in
CC       drug susceptibility. Combination of several mutations is usually
CC       required to develop a high-level drug resistance. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- MISCELLANEOUS: HIV-1 lineages are divided in three main groups, M (for
CC       Major), O (for Outlier), and N (for New, or Non-M, Non-O). The vast
CC       majority of strains found worldwide belong to the group M. Group O
CC       seems to be endemic to and largely confined to Cameroon and neighboring
CC       countries in West Central Africa, where these viruses represent a small
CC       minority of HIV-1 strains. The group N is represented by a limited
CC       number of isolates from Cameroonian persons. The group M is further
CC       subdivided in 9 clades or subtypes (A to D, F to H, J and K).
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SIMILARITY: Belongs to the HIV-1 env protein family.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- WEB RESOURCE: Name=hivdb; Note=HIV drug resistance database;
CC       URL="https://hivdb.stanford.edu";
CC   -!- WEB RESOURCE: Name=HIV drug resistance mutations;
CC       URL="https://www.iasusa.org/content/hiv-drug-resistance-mutations";
CC   ---------------------------------------------------------------------------
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DR   EMBL; M33943; AAA44850.1; -; Genomic_RNA.
DR   PDB; 2NXZ; X-ray; 2.04 A; A=83-490.
DR   PDB; 2NY0; X-ray; 2.20 A; A=83-490.
DR   PDB; 2NY2; X-ray; 2.00 A; A=86-490.
DR   PDB; 2NY4; X-ray; 2.00 A; A=83-490.
DR   PDB; 2NY5; X-ray; 2.50 A; G=83-490.
DR   PDB; 2PJV; NMR; -; A=510-532.
DR   PDB; 3ECB; X-ray; 1.70 A; P=309-318.
DR   PDBsum; 2NXZ; -.
DR   PDBsum; 2NY0; -.
DR   PDBsum; 2NY2; -.
DR   PDBsum; 2NY4; -.
DR   PDBsum; 2NY5; -.
DR   PDBsum; 2PJV; -.
DR   PDBsum; 3ECB; -.
DR   BMRB; P19551; -.
DR   SMR; P19551; -.
DR   GlyCosmos; P19551; 27 sites, No reported glycans.
DR   Reactome; R-HSA-5621480; Dectin-2 family.
DR   EvolutionaryTrace; P19551; -.
DR   GO; GO:0044175; C:host cell endosome membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0016020; C:membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:0019031; C:viral envelope; IEA:UniProtKB-KW.
DR   GO; GO:0055036; C:virion membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005198; F:structural molecule activity; IEA:UniProtKB-UniRule.
DR   GO; GO:0075512; P:clathrin-dependent endocytosis of virus by host cell; IEA:UniProtKB-UniRule.
DR   GO; GO:0039654; P:fusion of virus membrane with host endosome membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:0019064; P:fusion of virus membrane with host plasma membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:1903905; P:positive regulation of establishment of T cell polarity; IEA:UniProtKB-UniRule.
DR   GO; GO:1903908; P:positive regulation of plasma membrane raft polarization; IEA:UniProtKB-UniRule.
DR   GO; GO:1903911; P:positive regulation of receptor clustering; IEA:UniProtKB-UniRule.
DR   GO; GO:0019082; P:viral protein processing; IEA:UniProtKB-UniRule.
DR   GO; GO:0019062; P:virion attachment to host cell; IEA:UniProtKB-UniRule.
DR   GO; GO:0019049; P:virus-mediated perturbation of host defense response; IEA:UniProtKB-UniRule.
DR   CDD; cd09909; HIV-1-like_HR1-HR2; 1.
DR   Gene3D; 1.10.287.210; -; 1.
DR   Gene3D; 2.170.40.20; Human immunodeficiency virus 1, Gp160, envelope glycoprotein; 2.
DR   Gene3D; 1.20.5.490; Single helix bin; 1.
DR   HAMAP; MF_04083; HIV_ENV; 1.
DR   InterPro; IPR036377; Gp120_core_sf.
DR   InterPro; IPR037527; Gp160.
DR   InterPro; IPR000328; GP41-like.
DR   InterPro; IPR000777; HIV1_Gp120.
DR   Pfam; PF00516; GP120; 1.
DR   Pfam; PF00517; GP41; 1.
DR   SUPFAM; SSF56502; gp120 core; 1.
DR   SUPFAM; SSF58069; Virus ectodomain; 1.
PE   1: Evidence at protein level;
KW   3D-structure; AIDS; Apoptosis;
KW   Clathrin-mediated endocytosis of virus by host;
KW   Cleavage on pair of basic residues; Coiled coil; Disulfide bond;
KW   Fusion of virus membrane with host endosomal membrane;
KW   Fusion of virus membrane with host membrane; Glycoprotein;
KW   Host cell membrane; Host endosome; Host membrane; Host-virus interaction;
KW   Lipoprotein; Membrane; Palmitate; Signal; Transmembrane;
KW   Transmembrane helix; Viral attachment to host cell; Viral envelope protein;
KW   Viral immunoevasion; Viral penetration into host cytoplasm; Virion;
KW   Virus endocytosis by host; Virus entry into host cell.
FT   SIGNAL          1..32
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CHAIN           33..853
FT                   /note="Envelope glycoprotein gp160"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000239490"
FT   CHAIN           33..509
FT                   /note="Surface protein gp120"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000038421"
FT   CHAIN           510..853
FT                   /note="Transmembrane protein gp41"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000038422"
FT   TOPO_DOM        33..682
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   TRANSMEM        683..703
FT                   /note="Helical"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   TOPO_DOM        704..853
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          131..156
FT                   /note="V1"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          157..194
FT                   /note="V2"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          294..328
FT                   /note="V3"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          362..372
FT                   /note="CD4-binding loop"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          383..416
FT                   /note="V4"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          459..469
FT                   /note="V5"
FT   REGION          461..469
FT                   /note="V5"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          510..530
FT                   /note="Fusion peptide"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          572..590
FT                   /note="Immunosuppression"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          660..681
FT                   /note="MPER; binding to GalCer"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          717..741
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COILED          631..665
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   MOTIF           710..713
FT                   /note="YXXL motif; contains endocytosis signal"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   COMPBIAS        725..741
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   SITE            509..510
FT                   /note="Cleavage; by host furin"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   LIPID           762
FT                   /note="S-palmitoyl cysteine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        88
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        136
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        141
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        156
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        160
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        186
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        195
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        232
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        239
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        260
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        274
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        287
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        293
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        299
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        330
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        354
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        384
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        390
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        395
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        404
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        446
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        461
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        609
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        614
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        623
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        635
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        672
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        54..74
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        119..203
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        126..194
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        131..157
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        216..245
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        226..237
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        294..329
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        376..443
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        383..416
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        596..602
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   STRAND          84..88
FT                   /evidence="ECO:0007829|PDB:2NY0"
FT   STRAND          91..94
FT                   /evidence="ECO:0007829|PDB:2NY2"
FT   HELIX           99..115
FT                   /evidence="ECO:0007829|PDB:2NY2"
FT   STRAND          119..125
FT                   /evidence="ECO:0007829|PDB:2NY2"
FT   STRAND          195..200
FT                   /evidence="ECO:0007829|PDB:2NY2"
FT   STRAND          221..226
FT                   /evidence="ECO:0007829|PDB:2NY2"
FT   STRAND          233..245
FT                   /evidence="ECO:0007829|PDB:2NY2"
FT   STRAND          254..260
FT                   /evidence="ECO:0007829|PDB:2NY2"
FT   STRAND          265..267
FT                   /evidence="ECO:0007829|PDB:2NY2"
FT   STRAND          269..271
FT                   /evidence="ECO:0007829|PDB:2NY2"
FT   STRAND          282..295
FT                   /evidence="ECO:0007829|PDB:2NY2"
FT   TURN            310..312
FT                   /evidence="ECO:0007829|PDB:2NY2"
FT   STRAND          328..332
FT                   /evidence="ECO:0007829|PDB:2NY2"
FT   HELIX           333..351
FT                   /evidence="ECO:0007829|PDB:2NY2"
FT   STRAND          356..359
FT                   /evidence="ECO:0007829|PDB:2NY2"
FT   HELIX           367..370
FT                   /evidence="ECO:0007829|PDB:2NY2"
FT   STRAND          371..376
FT                   /evidence="ECO:0007829|PDB:2NY2"
FT   STRAND          379..383
FT                   /evidence="ECO:0007829|PDB:2NY2"
FT   HELIX           386..388
FT                   /evidence="ECO:0007829|PDB:2NY2"
FT   STRAND          391..393
FT                   /evidence="ECO:0007829|PDB:2NY2"
FT   STRAND          410..423
FT                   /evidence="ECO:0007829|PDB:2NY2"
FT   STRAND          425..428
FT                   /evidence="ECO:0007829|PDB:2NY2"
FT   STRAND          430..432
FT                   /evidence="ECO:0007829|PDB:2NY2"
FT   STRAND          442..454
FT                   /evidence="ECO:0007829|PDB:2NY2"
FT   STRAND          461..468
FT                   /evidence="ECO:0007829|PDB:2NY2"
FT   HELIX           473..481
FT                   /evidence="ECO:0007829|PDB:2NY2"
FT   STRAND          484..488
FT                   /evidence="ECO:0007829|PDB:2NY2"
SQ   SEQUENCE   853 AA;  96912 MW;  3377B993B6F22ABA CRC64;
     MRVKEKYQHL WRWGWKWGIM LLGILMICSA TENLWVTVYY GVPVWKEATT TLFCASDAKA
     YDTEVHNVCA THACVPTDPN PQEVILVNVT ENFDMWKNDM VEQMHEDIIS LWDQSLKPCV
     KLTPLCVNLK CTDLKNDTNT NSSNGRMIME KGEIKNCSFN ISTSIRNKVQ KEYAFFYKLD
     IRPIDNTTYR LISCNTSVIT QACPKVSFEP IPIHYCAPAG FAILKCNDKT FNGTGPCTNV
     STVQCTHGIR PVVSTQLLLN GSLAEEEGVI RSANFTDNAK TIIVQLNTSV EINCTRPNNN
     TRKSIRIQRG PGRAFVTIGK IGNMRQAHCN ISRAKWMSTL KQIASKLREQ FGNNKTVIFK
     QSSGGDPEIV THSFNCGGEF FYCNSTQLFN STWFNSTWST EGSNNTEGSD TITLPCRIKQ
     FINMWQEVGK AMYAPPISGQ IRCSSNITGL LLTRDGGKNT NESEVFRPGG GDMRDNWRSE
     LYKYKVVKIE TLGVAPTKAK RRVVQREKRA VGIGALFLGF LGAAGSTMGA ASMTLTVQAR
     QLLSGIVQQQ NNLLRAIEAQ QHLLQLTVWG IKQLQARILA VERYLKDQQL LGIWGCSGKL
     ICTTAVPWNA SWSNKSLEQF WNNMTWMEWD REINNYTSLI HSLIDESQNQ QEKNEQELLE
     LDKWASLWNW FNITNWLWYI KIFIMIVGGL VGLRIVFAVL SIVNRVRQGY SPLSFQTHLP
     NRGGPDRPEG IEEEGGERDR DRSVRLVNGS LALIWDDLRS LCLFSYHRLR DLLLIVTRIV
     ELLGRRGWEA LKYWWNLLQY WSQELKNSAV SLLNATAIAV AEGTDRVIEV VQGAYRAIRH
     IPRRIRQGLE RIL
//
ID   ENV_HV1MN               Reviewed;         856 AA.
AC   P05877;
DT   01-NOV-1988, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1988, sequence version 1.
DT   27-MAR-2024, entry version 181.
DE   RecName: Full=Envelope glycoprotein gp160 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   AltName: Full=Env polyprotein {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Contains:
DE     RecName: Full=Surface protein gp120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=SU {ECO:0000255|HAMAP-Rule:MF_04083};
DE     AltName: Full=Glycoprotein 120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=gp120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Contains:
DE     RecName: Full=Transmembrane protein gp41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=TM {ECO:0000255|HAMAP-Rule:MF_04083};
DE     AltName: Full=Glycoprotein 41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=gp41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Flags: Precursor;
GN   Name=env {ECO:0000255|HAMAP-Rule:MF_04083};
OS   Human immunodeficiency virus type 1 group M subtype B (isolate MN) (HIV-1).
OC   Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC   Ortervirales; Retroviridae; Orthoretrovirinae; Lentivirus;
OC   Human immunodeficiency virus 1.
OX   NCBI_TaxID=11696;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX   PubMed=3369091; DOI=10.1016/0042-6822(88)90568-5;
RA   Gurgo C., Guo H.-G., Franchini G., Aldovini A., Collalti E., Farrell K.,
RA   Wong-Staal F., Gallo R.C., Reitz M.S. Jr.;
RT   "Envelope sequences of two new United States HIV-1 isolates.";
RL   Virology 164:531-536(1988).
RN   [2]
RP   INTERACTION OF SURFACE PROTEIN GP120 WITH HUMAN CXCR4.
RX   PubMed=10074122; DOI=10.1128/jvi.73.4.2752-2761.1999;
RA   Doranz B.J., Orsini M.J., Turner J.D., Hoffman T.L., Berson J.F.,
RA   Hoxie J.A., Peiper S.C., Brass L.F., Doms R.W.;
RT   "Identification of CXCR4 domains that support coreceptor and chemokine
RT   receptor functions.";
RL   J. Virol. 73:2752-2761(1999).
RN   [3]
RP   REVIEW.
RX   PubMed=12974773; DOI=10.1034/j.1600-0463.2003.11107803.x;
RA   Geijtenbeek T.B., van Kooyk Y.;
RT   "Pathogens target DC-SIGN to influence their fate DC-SIGN functions as a
RT   pathogen receptor with broad specificity.";
RL   APMIS 111:698-714(2003).
RN   [4]
RP   REVIEW.
RX   PubMed=12873764; DOI=10.1016/s0005-2736(03)00161-5;
RA   Gallo S.A., Finnegan C.M., Viard M., Raviv Y., Dimitrov A., Rawat S.S.,
RA   Puri A., Durell S., Blumenthal R.;
RT   "The HIV Env-mediated fusion reaction.";
RL   Biochim. Biophys. Acta 1614:36-50(2003).
RN   [5]
RP   REVIEW.
RX   PubMed=15719026; DOI=10.1038/sj.cdd.4401584;
RA   Perfettini J.-L., Castedo M., Roumier T., Andreau K., Nardacci R.,
RA   Piacentini M., Kroemer G.;
RT   "Mechanisms of apoptosis induction by the HIV-1 envelope.";
RL   Cell Death Differ. 12:916-923(2005).
RN   [6]
RP   REVIEW.
RX   PubMed=15725757; DOI=10.1089/aid.2005.21.171;
RA   Hartley O., Klasse P.J., Sattentau Q.J., Moore J.P.;
RT   "V3: HIV's switch-hitter.";
RL   AIDS Res. Hum. Retroviruses 21:171-189(2005).
RN   [7]
RP   REVIEW.
RX   PubMed=16114975; DOI=10.2165/00003495-200565130-00002;
RA   Reeves J.D., Piefer A.J.;
RT   "Emerging drug targets for antiretroviral therapy.";
RL   Drugs 65:1747-1766(2005).
RN   [8]
RP   REVIEW.
RX   PubMed=16437164; DOI=10.1038/sj.emboj.7600947;
RA   Lusso P.;
RT   "HIV and the chemokine system: 10 years later.";
RL   EMBO J. 25:447-456(2006).
RN   [9]
RP   3D-STRUCTURE OF ENVELOPE GLYCOPROTEIN TRIMERS BY ELECTRON TOMOGRAPHY.
RX   PubMed=14668432; DOI=10.1073/pnas.2634931100;
RA   Zhu P., Chertova E., Bess J. Jr., Lifson J.D., Arthur L.O., Liu J.,
RA   Taylor K.A., Roux K.H.;
RT   "Electron tomography analysis of envelope glycoprotein trimers on HIV and
RT   simian immunodeficiency virus virions.";
RL   Proc. Natl. Acad. Sci. U.S.A. 100:15812-15817(2003).
CC   -!- FUNCTION: [Envelope glycoprotein gp160]: Oligomerizes in the host
CC       endoplasmic reticulum into predominantly trimers. In a second time,
CC       gp160 transits in the host Golgi, where glycosylation is completed. The
CC       precursor is then proteolytically cleaved in the trans-Golgi and
CC       thereby activated by cellular furin or furin-like proteases to produce
CC       gp120 and gp41. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- FUNCTION: [Surface protein gp120]: Attaches the virus to the host
CC       lymphoid cell by binding to the primary receptor CD4. This interaction
CC       induces a structural rearrangement creating a high affinity binding
CC       site for a chemokine coreceptor like CXCR4 and/or CCR5. Acts as a
CC       ligand for CD209/DC-SIGN and CLEC4M/DC-SIGNR, which are respectively
CC       found on dendritic cells (DCs), and on endothelial cells of liver
CC       sinusoids and lymph node sinuses. These interactions allow capture of
CC       viral particles at mucosal surfaces by these cells and subsequent
CC       transmission to permissive cells. HIV subverts the migration properties
CC       of dendritic cells to gain access to CD4+ T-cells in lymph nodes. Virus
CC       transmission to permissive T-cells occurs either in trans (without DCs
CC       infection, through viral capture and transmission), or in cis
CC       (following DCs productive infection, through the usual CD4-gp120
CC       interaction), thereby inducing a robust infection. In trans infection,
CC       bound virions remain infectious over days and it is proposed that they
CC       are not degraded, but protected in non-lysosomal acidic organelles
CC       within the DCs close to the cell membrane thus contributing to the
CC       viral infectious potential during DCs' migration from the periphery to
CC       the lymphoid tissues. On arrival at lymphoid tissues, intact virions
CC       recycle back to DCs' cell surface allowing virus transmission to CD4+
CC       T-cells. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- FUNCTION: [Transmembrane protein gp41]: Acts as a class I viral fusion
CC       protein. Under the current model, the protein has at least 3
CC       conformational states: pre-fusion native state, pre-hairpin
CC       intermediate state, and post-fusion hairpin state. During fusion of
CC       viral and target intracellular membranes, the coiled coil regions
CC       (heptad repeats) assume a trimer-of-hairpins structure, positioning the
CC       fusion peptide in close proximity to the C-terminal region of the
CC       ectodomain. The formation of this structure appears to drive apposition
CC       and subsequent fusion of viral and target cell membranes. Complete
CC       fusion occurs in host cell endosomes and is dynamin-dependent, however
CC       some lipid transfer might occur at the plasma membrane. The virus
CC       undergoes clathrin-dependent internalization long before endosomal
CC       fusion, thus minimizing the surface exposure of conserved viral
CC       epitopes during fusion and reducing the efficacy of inhibitors
CC       targeting these epitopes. Membranes fusion leads to delivery of the
CC       nucleocapsid into the cytoplasm. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBUNIT: [Surface protein gp120]: The mature envelope protein (Env)
CC       consists of a homotrimer of non-covalently associated gp120-gp41
CC       heterodimers. The resulting complex protrudes from the virus surface as
CC       a spike. There seems to be as few as 10 spikes on the average virion.
CC       Interacts with host CD4, CCR5 and CXCR4. Gp120 also interacts with the
CC       C-type lectins CD209/DC-SIGN and CLEC4M/DC-SIGNR (collectively referred
CC       to as DC-SIGN(R)). Gp120 and gp41 interact with GalCer. Gp120 interacts
CC       with host ITGA4/ITGB7 complex; on CD4+ T-cells, this interaction
CC       results in rapid activation of integrin ITGAL/LFA-1, which facilitates
CC       efficient cell-to-cell spreading of HIV-1. Gp120 interacts with cell-
CC       associated heparan sulfate; this interaction increases virus
CC       infectivity on permissive cells and may be involved in infection of
CC       CD4- cells. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBUNIT: [Transmembrane protein gp41]: The mature envelope protein
CC       (Env) consists of a homotrimer of non-covalently associated gp120-gp41
CC       heterodimers. The resulting complex protrudes from the virus surface as
CC       a spike. There seems to be as few as 10 spikes on the average virion.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- INTERACTION:
CC       P05877; P05877: env; NbExp=6; IntAct=EBI-9255299, EBI-9255299;
CC   -!- SUBCELLULAR LOCATION: [Surface protein gp120]: Virion membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Peripheral membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host cell membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Peripheral membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host endosome membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Note=The surface protein is not
CC       anchored to the viral envelope, but associates with the extravirion
CC       surface through its binding to TM. It is probably concentrated at the
CC       site of budding and incorporated into the virions possibly by contacts
CC       between the cytoplasmic tail of Env and the N-terminus of Gag.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBCELLULAR LOCATION: [Transmembrane protein gp41]: Virion membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host cell membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host endosome membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Note=It is probably concentrated at
CC       the site of budding and incorporated into the virions possibly by
CC       contacts between the cytoplasmic tail of Env and the N-terminus of Gag.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: Some of the most genetically diverse regions of the viral
CC       genome are present in Env. They are called variable regions 1 through 5
CC       (V1 through V5). Coreceptor usage of gp120 is determined mainly by the
CC       primary structure of the third variable region (V3) in the outer domain
CC       of gp120. The sequence of V3 determines which coreceptor, CCR5 and/or
CC       CXCR4 (corresponding to R5/macrophage, X4/T cell and R5X4/T cell and
CC       macrophage tropism), is used to trigger the fusion potential of the Env
CC       complex, and hence which cells the virus can infect. Binding to CCR5
CC       involves a region adjacent in addition to V3. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- DOMAIN: The membrane proximal external region (MPER) present in gp41 is
CC       a tryptophan-rich region recognized by the antibodies 2F5, Z13, and
CC       4E10. MPER seems to play a role in fusion. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- DOMAIN: The 17 amino acids long immunosuppressive region is present in
CC       many retroviral envelope proteins. Synthetic peptides derived from this
CC       relatively conserved sequence inhibit immune function in vitro and in
CC       vivo. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: The YXXL motif is involved in determining the exact site of
CC       viral release at the surface of infected mononuclear cells and promotes
CC       endocytosis. YXXL and di-leucine endocytosis motifs interact directly
CC       or indirectly with the clathrin adapter complexes, opperate
CC       independently, and their activities are not additive.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: The CD4-binding region is targeted by the antibody b12.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- PTM: Highly glycosylated by host. The high number of glycan on the
CC       protein is reffered to as 'glycan shield' because it contributes to
CC       hide protein sequence from adaptive immune system. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- PTM: Palmitoylation of the transmembrane protein and of Env polyprotein
CC       (prior to its proteolytic cleavage) is essential for their association
CC       with host cell membrane lipid rafts. Palmitoylation is therefore
CC       required for envelope trafficking to classical lipid rafts, but not for
CC       viral replication. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- PTM: Specific enzymatic cleavages in vivo yield mature proteins.
CC       Envelope glycoproteins are synthesized as an inactive precursor that is
CC       heavily N-glycosylated and processed likely by host cell furin in the
CC       Golgi to yield the mature SU and TM proteins. The cleavage site between
CC       SU and TM requires the minimal sequence [KR]-X-[KR]-R. About 2 of the 9
CC       disulfide bonds of gp41 are reduced by P4HB/PDI, following binding to
CC       CD4 receptor. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- MISCELLANEOUS: Inhibitors targeting HIV-1 viral envelope proteins are
CC       used as antiretroviral drugs. Attachment of virions to the cell surface
CC       via non-specific interactions and CD4 binding can be blocked by
CC       inhibitors that include cyanovirin-N, cyclotriazadisulfonamide analogs,
CC       PRO 2000, TNX 355 and PRO 542. In addition, BMS 806 can block CD4-
CC       induced conformational changes. Env interactions with the coreceptor
CC       molecules can be targeted by CCR5 antagonists including SCH-D,
CC       maraviroc (UK 427857) and aplaviroc (GW 873140), and the CXCR4
CC       antagonist AMD 070. Fusion of viral and cellular membranes can be
CC       inhibited by peptides such as enfuvirtide and tifuvirtide (T 1249).
CC       Resistance to inhibitors associated with mutations in Env are observed.
CC       Most of the time, single mutations confer only a modest reduction in
CC       drug susceptibility. Combination of several mutations is usually
CC       required to develop a high-level drug resistance. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- MISCELLANEOUS: HIV-1 lineages are divided in three main groups, M (for
CC       Major), O (for Outlier), and N (for New, or Non-M, Non-O). The vast
CC       majority of strains found worldwide belong to the group M. Group O
CC       seems to be endemic to and largely confined to Cameroon and neighboring
CC       countries in West Central Africa, where these viruses represent a small
CC       minority of HIV-1 strains. The group N is represented by a limited
CC       number of isolates from Cameroonian persons. The group M is further
CC       subdivided in 9 clades or subtypes (A to D, F to H, J and K).
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SIMILARITY: Belongs to the HIV-1 env protein family.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- WEB RESOURCE: Name=hivdb; Note=HIV drug resistance database;
CC       URL="https://hivdb.stanford.edu";
CC   -!- WEB RESOURCE: Name=HIV drug resistance mutations;
CC       URL="https://www.iasusa.org/content/hiv-drug-resistance-mutations";
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DR   EMBL; M17449; AAA44857.1; -; Genomic_RNA.
DR   PDB; 1ACY; X-ray; 3.00 A; P=306-328.
DR   PDB; 1AI1; X-ray; 2.80 A; P=306-328.
DR   PDB; 1F58; X-ray; 2.00 A; P=306-328.
DR   PDB; 1GGI; X-ray; 2.80 A; P/Q=310-323.
DR   PDB; 1K5M; X-ray; 2.70 A; B=314-325.
DR   PDB; 1NAK; X-ray; 2.57 A; P/Q=310-323.
DR   PDB; 1NIZ; NMR; -; A=309-324.
DR   PDB; 1NJ0; NMR; -; A=309-324.
DR   PDB; 1Q1J; X-ray; 2.50 A; P/Q=310-323.
DR   PDB; 2B0S; X-ray; 2.30 A; P=308-323.
DR   PDB; 2QSC; X-ray; 2.80 A; P=309-323.
DR   PDB; 3E6H; X-ray; 2.10 A; P=314-322.
DR   PDB; 3GO1; X-ray; 1.89 A; P=309-322.
DR   PDB; 3MLW; X-ray; 2.70 A; P/Q=306-328.
DR   PDB; 3MLX; X-ray; 1.90 A; P/Q=306-328.
DR   PDB; 3UJI; X-ray; 1.60 A; P=306-328.
DR   PDB; 4M1D; X-ray; 1.80 A; P/Q=311-322.
DR   PDB; 4XAW; X-ray; 1.47 A; P=672-684.
DR   PDB; 4XBE; X-ray; 1.76 A; P=672-684.
DR   PDB; 4XC1; X-ray; 1.63 A; P=672-684.
DR   PDB; 4XC3; X-ray; 1.63 A; P=672-684.
DR   PDB; 4XCF; X-ray; 1.43 A; P=672-684.
DR   PDB; 4XMK; X-ray; 3.18 A; P/Q/R=312-322.
DR   PDB; 5KD4; X-ray; 3.05 A; P/Q=314-321.
DR   PDB; 5KD7; X-ray; 2.35 A; E/H/K/P=314-321.
DR   PDB; 5T7G; X-ray; 1.96 A; P/Q=314-322.
DR   PDB; 6DB6; X-ray; 1.98 A; P=306-328.
DR   PDB; 6DB7; X-ray; 2.21 A; P/Q=306-328.
DR   PDB; 6MNS; X-ray; 2.70 A; P/Q=306-328.
DR   PDB; 6SH9; X-ray; 2.40 A; E=310-323.
DR   PDBsum; 1ACY; -.
DR   PDBsum; 1AI1; -.
DR   PDBsum; 1F58; -.
DR   PDBsum; 1GGI; -.
DR   PDBsum; 1K5M; -.
DR   PDBsum; 1NAK; -.
DR   PDBsum; 1NIZ; -.
DR   PDBsum; 1NJ0; -.
DR   PDBsum; 1Q1J; -.
DR   PDBsum; 2B0S; -.
DR   PDBsum; 2QSC; -.
DR   PDBsum; 3E6H; -.
DR   PDBsum; 3GO1; -.
DR   PDBsum; 3MLW; -.
DR   PDBsum; 3MLX; -.
DR   PDBsum; 3UJI; -.
DR   PDBsum; 4M1D; -.
DR   PDBsum; 4XAW; -.
DR   PDBsum; 4XBE; -.
DR   PDBsum; 4XC1; -.
DR   PDBsum; 4XC3; -.
DR   PDBsum; 4XCF; -.
DR   PDBsum; 4XMK; -.
DR   PDBsum; 5KD4; -.
DR   PDBsum; 5KD7; -.
DR   PDBsum; 5T7G; -.
DR   PDBsum; 6DB6; -.
DR   PDBsum; 6DB7; -.
DR   PDBsum; 6MNS; -.
DR   PDBsum; 6SH9; -.
DR   BMRB; P05877; -.
DR   SMR; P05877; -.
DR   MINT; P05877; -.
DR   GlyCosmos; P05877; 30 sites, No reported glycans.
DR   ABCD; P05877; 12 sequenced antibodies.
DR   Reactome; R-HSA-5621480; Dectin-2 family.
DR   EvolutionaryTrace; P05877; -.
DR   Proteomes; UP000007697; Genome.
DR   GO; GO:0044175; C:host cell endosome membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0016020; C:membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:0019031; C:viral envelope; IEA:UniProtKB-KW.
DR   GO; GO:0055036; C:virion membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR   GO; GO:0005198; F:structural molecule activity; IEA:UniProtKB-UniRule.
DR   GO; GO:0075512; P:clathrin-dependent endocytosis of virus by host cell; IEA:UniProtKB-UniRule.
DR   GO; GO:0039654; P:fusion of virus membrane with host endosome membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:0019064; P:fusion of virus membrane with host plasma membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:1903905; P:positive regulation of establishment of T cell polarity; IEA:UniProtKB-UniRule.
DR   GO; GO:1903908; P:positive regulation of plasma membrane raft polarization; IEA:UniProtKB-UniRule.
DR   GO; GO:1903911; P:positive regulation of receptor clustering; IEA:UniProtKB-UniRule.
DR   GO; GO:0019082; P:viral protein processing; IEA:UniProtKB-UniRule.
DR   GO; GO:0019062; P:virion attachment to host cell; IEA:UniProtKB-UniRule.
DR   GO; GO:0019049; P:virus-mediated perturbation of host defense response; IEA:UniProtKB-UniRule.
DR   CDD; cd09909; HIV-1-like_HR1-HR2; 1.
DR   Gene3D; 1.10.287.210; -; 1.
DR   Gene3D; 2.170.40.20; Human immunodeficiency virus 1, Gp160, envelope glycoprotein; 2.
DR   Gene3D; 1.20.5.490; Single helix bin; 1.
DR   HAMAP; MF_04083; HIV_ENV; 1.
DR   InterPro; IPR036377; Gp120_core_sf.
DR   InterPro; IPR037527; Gp160.
DR   InterPro; IPR000328; GP41-like.
DR   InterPro; IPR000777; HIV1_Gp120.
DR   Pfam; PF00516; GP120; 1.
DR   Pfam; PF00517; GP41; 1.
DR   SUPFAM; SSF56502; gp120 core; 2.
DR   SUPFAM; SSF58069; Virus ectodomain; 1.
PE   1: Evidence at protein level;
KW   3D-structure; AIDS; Apoptosis;
KW   Clathrin-mediated endocytosis of virus by host;
KW   Cleavage on pair of basic residues; Coiled coil; Disulfide bond;
KW   Fusion of virus membrane with host endosomal membrane;
KW   Fusion of virus membrane with host membrane; Glycoprotein;
KW   Host cell membrane; Host endosome; Host membrane; Host-virus interaction;
KW   Lipoprotein; Membrane; Palmitate; Reference proteome; Signal;
KW   Transmembrane; Transmembrane helix; Viral attachment to host cell;
KW   Viral envelope protein; Viral immunoevasion;
KW   Viral penetration into host cytoplasm; Virion; Virus endocytosis by host;
KW   Virus entry into host cell.
FT   SIGNAL          1..31
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CHAIN           32..856
FT                   /note="Envelope glycoprotein gp160"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000239484"
FT   CHAIN           32..513
FT                   /note="Surface protein gp120"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000038408"
FT   CHAIN           514..856
FT                   /note="Transmembrane protein gp41"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000038409"
FT   TOPO_DOM        32..685
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   TRANSMEM        686..706
FT                   /note="Helical"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   TOPO_DOM        707..856
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          130..161
FT                   /note="V1"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          162..201
FT                   /note="V2"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          301..334
FT                   /note="V3"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          367..377
FT                   /note="CD4-binding loop"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          388..418
FT                   /note="V4"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          421..433
FT                   /note="Essential for CD4-binding; epitope recognized by the
FT                   antibody YZ23"
FT   REGION          461..473
FT                   /note="V5"
FT   REGION          463..473
FT                   /note="V5"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          514..533
FT                   /note="Fusion peptide"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          575..593
FT                   /note="Immunosuppression"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          663..684
FT                   /note="MPER; binding to GalCer"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          717..744
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COILED          634..668
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   MOTIF           713..716
FT                   /note="YXXL motif; contains endocytosis signal"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   MOTIF           855..856
FT                   /note="Di-leucine internalization motif"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   COMPBIAS        728..744
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   SITE            513..514
FT                   /note="Cleavage; by host furin"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        87
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        129
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        135
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        140
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        141
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        146
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        161
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        165
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        191
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        202
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        246
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        267
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        281
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        294
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        300
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        336
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        343
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        359
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        365
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        395
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        401
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        405
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        406
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        413
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        448
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        465
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        612
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        617
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        626
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        638
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        53..73
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        118..210
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        125..201
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        130..162
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        223..252
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        233..244
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        301..335
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        381..445
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        388..418
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        599..605
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   HELIX           308..310
FT                   /evidence="ECO:0007829|PDB:3UJI"
FT   STRAND          311..315
FT                   /evidence="ECO:0007829|PDB:3UJI"
FT   TURN            316..318
FT                   /evidence="ECO:0007829|PDB:3UJI"
FT   STRAND          320..322
FT                   /evidence="ECO:0007829|PDB:4M1D"
FT   HELIX           673..675
FT                   /evidence="ECO:0007829|PDB:4XCF"
FT   HELIX           676..684
FT                   /evidence="ECO:0007829|PDB:4XCF"
SQ   SEQUENCE   856 AA;  97140 MW;  D197D809940BE732 CRC64;
     MRVKGIRRNY QHWWGWGTML LGLLMICSAT EKLWVTVYYG VPVWKEATTT LFCASDAKAY
     DTEVHNVWAT QACVPTDPNP QEVELVNVTE NFNMWKNNMV EQMHEDIISL WDQSLKPCVK
     LTPLCVTLNC TDLRNTTNTN NSTANNNSNS EGTIKGGEMK NCSFNITTSI RDKMQKEYAL
     LYKLDIVSID NDSTSYRLIS CNTSVITQAC PKISFEPIPI HYCAPAGFAI LKCNDKKFSG
     KGSCKNVSTV QCTHGIRPVV STQLLLNGSL AEEEVVIRSE NFTDNAKTII VHLNESVQIN
     CTRPNYNKRK RIHIGPGRAF YTTKNIIGTI RQAHCNISRA KWNDTLRQIV SKLKEQFKNK
     TIVFNQSSGG DPEIVMHSFN CGGEFFYCNT SPLFNSTWNG NNTWNNTTGS NNNITLQCKI
     KQIINMWQEV GKAMYAPPIE GQIRCSSNIT GLLLTRDGGK DTDTNDTEIF RPGGGDMRDN
     WRSELYKYKV VTIEPLGVAP TKAKRRVVQR EKRAAIGALF LGFLGAAGST MGAASVTLTV
     QARLLLSGIV QQQNNLLRAI EAQQHMLQLT VWGIKQLQAR VLAVERYLKD QQLLGFWGCS
     GKLICTTTVP WNASWSNKSL DDIWNNMTWM QWEREIDNYT SLIYSLLEKS QTQQEKNEQE
     LLELDKWASL WNWFDITNWL WYIKIFIMIV GGLVGLRIVF AVLSIVNRVR QGYSPLSLQT
     RPPVPRGPDR PEGIEEEGGE RDRDTSGRLV HGFLAIIWVD LRSLFLFSYH HRDLLLIAAR
     IVELLGRRGW EVLKYWWNLL QYWSQELKSS AVSLLNATAI AVAEGTDRVI EVLQRAGRAI
     LHIPTRIRQG LERALL
//
ID   ENV_HV1MP               Reviewed;         843 AA.
AC   Q9QBZ4;
DT   27-JUN-2006, integrated into UniProtKB/Swiss-Prot.
DT   27-JUN-2006, sequence version 2.
DT   27-MAR-2024, entry version 120.
DE   RecName: Full=Envelope glycoprotein gp160 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   AltName: Full=Env polyprotein {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Contains:
DE     RecName: Full=Surface protein gp120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=SU {ECO:0000255|HAMAP-Rule:MF_04083};
DE     AltName: Full=Glycoprotein 120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=gp120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Contains:
DE     RecName: Full=Transmembrane protein gp41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=TM {ECO:0000255|HAMAP-Rule:MF_04083};
DE     AltName: Full=Glycoprotein 41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=gp41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Flags: Precursor;
GN   Name=env {ECO:0000255|HAMAP-Rule:MF_04083};
OS   Human immunodeficiency virus type 1 group M subtype F2 (isolate MP255)
OS   (HIV-1).
OC   Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC   Ortervirales; Retroviridae; Orthoretrovirinae; Lentivirus;
OC   Human immunodeficiency virus 1.
OX   NCBI_TaxID=388815;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX   PubMed=10659053; DOI=10.1089/088922200309485;
RA   Triques K., Bourgeois A., Vidale N., Mpoudi-Ngole E., Mulanga-Kabeya C.,
RA   Nzilambi N., Torimiro N., Saman E., Delaporte E., Peeters M.;
RT   "Near-full-length genome sequencing of divergent African HIV type 1 subtype
RT   F viruses leads to the identification of a new HIV type 1 subtype
RT   designated K.";
RL   AIDS Res. Hum. Retroviruses 16:139-151(2000).
RN   [2]
RP   REVIEW.
RX   PubMed=12974773; DOI=10.1034/j.1600-0463.2003.11107803.x;
RA   Geijtenbeek T.B., van Kooyk Y.;
RT   "Pathogens target DC-SIGN to influence their fate DC-SIGN functions as a
RT   pathogen receptor with broad specificity.";
RL   APMIS 111:698-714(2003).
RN   [3]
RP   REVIEW.
RX   PubMed=12873764; DOI=10.1016/s0005-2736(03)00161-5;
RA   Gallo S.A., Finnegan C.M., Viard M., Raviv Y., Dimitrov A., Rawat S.S.,
RA   Puri A., Durell S., Blumenthal R.;
RT   "The HIV Env-mediated fusion reaction.";
RL   Biochim. Biophys. Acta 1614:36-50(2003).
RN   [4]
RP   REVIEW.
RX   PubMed=15719026; DOI=10.1038/sj.cdd.4401584;
RA   Perfettini J.-L., Castedo M., Roumier T., Andreau K., Nardacci R.,
RA   Piacentini M., Kroemer G.;
RT   "Mechanisms of apoptosis induction by the HIV-1 envelope.";
RL   Cell Death Differ. 12:916-923(2005).
RN   [5]
RP   REVIEW.
RX   PubMed=15725757; DOI=10.1089/aid.2005.21.171;
RA   Hartley O., Klasse P.J., Sattentau Q.J., Moore J.P.;
RT   "V3: HIV's switch-hitter.";
RL   AIDS Res. Hum. Retroviruses 21:171-189(2005).
RN   [6]
RP   REVIEW.
RX   PubMed=16114975; DOI=10.2165/00003495-200565130-00002;
RA   Reeves J.D., Piefer A.J.;
RT   "Emerging drug targets for antiretroviral therapy.";
RL   Drugs 65:1747-1766(2005).
RN   [7]
RP   REVIEW.
RX   PubMed=16437164; DOI=10.1038/sj.emboj.7600947;
RA   Lusso P.;
RT   "HIV and the chemokine system: 10 years later.";
RL   EMBO J. 25:447-456(2006).
CC   -!- FUNCTION: [Envelope glycoprotein gp160]: Oligomerizes in the host
CC       endoplasmic reticulum into predominantly trimers. In a second time,
CC       gp160 transits in the host Golgi, where glycosylation is completed. The
CC       precursor is then proteolytically cleaved in the trans-Golgi and
CC       thereby activated by cellular furin or furin-like proteases to produce
CC       gp120 and gp41. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- FUNCTION: [Surface protein gp120]: Attaches the virus to the host
CC       lymphoid cell by binding to the primary receptor CD4. This interaction
CC       induces a structural rearrangement creating a high affinity binding
CC       site for a chemokine coreceptor like CXCR4 and/or CCR5. Acts as a
CC       ligand for CD209/DC-SIGN and CLEC4M/DC-SIGNR, which are respectively
CC       found on dendritic cells (DCs), and on endothelial cells of liver
CC       sinusoids and lymph node sinuses. These interactions allow capture of
CC       viral particles at mucosal surfaces by these cells and subsequent
CC       transmission to permissive cells. HIV subverts the migration properties
CC       of dendritic cells to gain access to CD4+ T-cells in lymph nodes. Virus
CC       transmission to permissive T-cells occurs either in trans (without DCs
CC       infection, through viral capture and transmission), or in cis
CC       (following DCs productive infection, through the usual CD4-gp120
CC       interaction), thereby inducing a robust infection. In trans infection,
CC       bound virions remain infectious over days and it is proposed that they
CC       are not degraded, but protected in non-lysosomal acidic organelles
CC       within the DCs close to the cell membrane thus contributing to the
CC       viral infectious potential during DCs' migration from the periphery to
CC       the lymphoid tissues. On arrival at lymphoid tissues, intact virions
CC       recycle back to DCs' cell surface allowing virus transmission to CD4+
CC       T-cells. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- FUNCTION: [Transmembrane protein gp41]: Acts as a class I viral fusion
CC       protein. Under the current model, the protein has at least 3
CC       conformational states: pre-fusion native state, pre-hairpin
CC       intermediate state, and post-fusion hairpin state. During fusion of
CC       viral and target intracellular membranes, the coiled coil regions
CC       (heptad repeats) assume a trimer-of-hairpins structure, positioning the
CC       fusion peptide in close proximity to the C-terminal region of the
CC       ectodomain. The formation of this structure appears to drive apposition
CC       and subsequent fusion of viral and target cell membranes. Complete
CC       fusion occurs in host cell endosomes and is dynamin-dependent, however
CC       some lipid transfer might occur at the plasma membrane. The virus
CC       undergoes clathrin-dependent internalization long before endosomal
CC       fusion, thus minimizing the surface exposure of conserved viral
CC       epitopes during fusion and reducing the efficacy of inhibitors
CC       targeting these epitopes. Membranes fusion leads to delivery of the
CC       nucleocapsid into the cytoplasm. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBUNIT: [Surface protein gp120]: The mature envelope protein (Env)
CC       consists of a homotrimer of non-covalently associated gp120-gp41
CC       heterodimers. The resulting complex protrudes from the virus surface as
CC       a spike. There seems to be as few as 10 spikes on the average virion.
CC       Interacts with host CD4, CCR5 and CXCR4. Gp120 also interacts with the
CC       C-type lectins CD209/DC-SIGN and CLEC4M/DC-SIGNR (collectively referred
CC       to as DC-SIGN(R)). Gp120 and gp41 interact with GalCer. Gp120 interacts
CC       with host ITGA4/ITGB7 complex; on CD4+ T-cells, this interaction
CC       results in rapid activation of integrin ITGAL/LFA-1, which facilitates
CC       efficient cell-to-cell spreading of HIV-1. Gp120 interacts with cell-
CC       associated heparan sulfate; this interaction increases virus
CC       infectivity on permissive cells and may be involved in infection of
CC       CD4- cells. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBUNIT: [Transmembrane protein gp41]: The mature envelope protein
CC       (Env) consists of a homotrimer of non-covalently associated gp120-gp41
CC       heterodimers. The resulting complex protrudes from the virus surface as
CC       a spike. There seems to be as few as 10 spikes on the average virion.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBCELLULAR LOCATION: [Surface protein gp120]: Virion membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Peripheral membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host cell membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Peripheral membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host endosome membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Note=The surface protein is not
CC       anchored to the viral envelope, but associates with the extravirion
CC       surface through its binding to TM. It is probably concentrated at the
CC       site of budding and incorporated into the virions possibly by contacts
CC       between the cytoplasmic tail of Env and the N-terminus of Gag.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBCELLULAR LOCATION: [Transmembrane protein gp41]: Virion membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host cell membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host endosome membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Note=It is probably concentrated at
CC       the site of budding and incorporated into the virions possibly by
CC       contacts between the cytoplasmic tail of Env and the N-terminus of Gag.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: Some of the most genetically diverse regions of the viral
CC       genome are present in Env. They are called variable regions 1 through 5
CC       (V1 through V5). Coreceptor usage of gp120 is determined mainly by the
CC       primary structure of the third variable region (V3) in the outer domain
CC       of gp120. The sequence of V3 determines which coreceptor, CCR5 and/or
CC       CXCR4 (corresponding to R5/macrophage, X4/T cell and R5X4/T cell and
CC       macrophage tropism), is used to trigger the fusion potential of the Env
CC       complex, and hence which cells the virus can infect. Binding to CCR5
CC       involves a region adjacent in addition to V3. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- DOMAIN: The membrane proximal external region (MPER) present in gp41 is
CC       a tryptophan-rich region recognized by the antibodies 2F5, Z13, and
CC       4E10. MPER seems to play a role in fusion. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- DOMAIN: The 17 amino acids long immunosuppressive region is present in
CC       many retroviral envelope proteins. Synthetic peptides derived from this
CC       relatively conserved sequence inhibit immune function in vitro and in
CC       vivo. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: The YXXL motif is involved in determining the exact site of
CC       viral release at the surface of infected mononuclear cells and promotes
CC       endocytosis. YXXL and di-leucine endocytosis motifs interact directly
CC       or indirectly with the clathrin adapter complexes, opperate
CC       independently, and their activities are not additive.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: The CD4-binding region is targeted by the antibody b12.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- PTM: Highly glycosylated by host. The high number of glycan on the
CC       protein is reffered to as 'glycan shield' because it contributes to
CC       hide protein sequence from adaptive immune system. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- PTM: Palmitoylation of the transmembrane protein and of Env polyprotein
CC       (prior to its proteolytic cleavage) is essential for their association
CC       with host cell membrane lipid rafts. Palmitoylation is therefore
CC       required for envelope trafficking to classical lipid rafts, but not for
CC       viral replication. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- PTM: Specific enzymatic cleavages in vivo yield mature proteins.
CC       Envelope glycoproteins are synthesized as an inactive precursor that is
CC       heavily N-glycosylated and processed likely by host cell furin in the
CC       Golgi to yield the mature SU and TM proteins. The cleavage site between
CC       SU and TM requires the minimal sequence [KR]-X-[KR]-R. About 2 of the 9
CC       disulfide bonds of gp41 are reduced by P4HB/PDI, following binding to
CC       CD4 receptor. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- MISCELLANEOUS: Inhibitors targeting HIV-1 viral envelope proteins are
CC       used as antiretroviral drugs. Attachment of virions to the cell surface
CC       via non-specific interactions and CD4 binding can be blocked by
CC       inhibitors that include cyanovirin-N, cyclotriazadisulfonamide analogs,
CC       PRO 2000, TNX 355 and PRO 542. In addition, BMS 806 can block CD4-
CC       induced conformational changes. Env interactions with the coreceptor
CC       molecules can be targeted by CCR5 antagonists including SCH-D,
CC       maraviroc (UK 427857) and aplaviroc (GW 873140), and the CXCR4
CC       antagonist AMD 070. Fusion of viral and cellular membranes can be
CC       inhibited by peptides such as enfuvirtide and tifuvirtide (T 1249).
CC       Resistance to inhibitors associated with mutations in Env are observed.
CC       Most of the time, single mutations confer only a modest reduction in
CC       drug susceptibility. Combination of several mutations is usually
CC       required to develop a high-level drug resistance. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- MISCELLANEOUS: HIV-1 lineages are divided in three main groups, M (for
CC       Major), O (for Outlier), and N (for New, or Non-M, Non-O). The vast
CC       majority of strains found worldwide belong to the group M. Group O
CC       seems to be endemic to and largely confined to Cameroon and neighboring
CC       countries in West Central Africa, where these viruses represent a small
CC       minority of HIV-1 strains. The group N is represented by a limited
CC       number of isolates from Cameroonian persons. The group M is further
CC       subdivided in 9 clades or subtypes (A to D, F to H, J and K).
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SIMILARITY: Belongs to the HIV-1 env protein family.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=CAB58978.1; Type=Erroneous initiation;
CC   -!- WEB RESOURCE: Name=hivdb; Note=HIV drug resistance database;
CC       URL="https://hivdb.stanford.edu";
CC   -!- WEB RESOURCE: Name=HIV drug resistance mutations;
CC       URL="https://www.iasusa.org/content/hiv-drug-resistance-mutations";
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DR   EMBL; AJ249236; CAB58978.1; ALT_INIT; Genomic_RNA.
DR   SMR; Q9QBZ4; -.
DR   GlyCosmos; Q9QBZ4; 28 sites, No reported glycans.
DR   GO; GO:0044175; C:host cell endosome membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0016020; C:membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:0019031; C:viral envelope; IEA:UniProtKB-KW.
DR   GO; GO:0055036; C:virion membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005198; F:structural molecule activity; IEA:UniProtKB-UniRule.
DR   GO; GO:0075512; P:clathrin-dependent endocytosis of virus by host cell; IEA:UniProtKB-UniRule.
DR   GO; GO:0039654; P:fusion of virus membrane with host endosome membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:0019064; P:fusion of virus membrane with host plasma membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:1903905; P:positive regulation of establishment of T cell polarity; IEA:UniProtKB-UniRule.
DR   GO; GO:1903908; P:positive regulation of plasma membrane raft polarization; IEA:UniProtKB-UniRule.
DR   GO; GO:1903911; P:positive regulation of receptor clustering; IEA:UniProtKB-UniRule.
DR   GO; GO:0019082; P:viral protein processing; IEA:UniProtKB-UniRule.
DR   GO; GO:0019062; P:virion attachment to host cell; IEA:UniProtKB-UniRule.
DR   GO; GO:0019049; P:virus-mediated perturbation of host defense response; IEA:UniProtKB-UniRule.
DR   CDD; cd09909; HIV-1-like_HR1-HR2; 1.
DR   Gene3D; 1.10.287.210; -; 1.
DR   Gene3D; 2.170.40.20; Human immunodeficiency virus 1, Gp160, envelope glycoprotein; 2.
DR   Gene3D; 1.20.5.490; Single helix bin; 1.
DR   HAMAP; MF_04083; HIV_ENV; 1.
DR   InterPro; IPR036377; Gp120_core_sf.
DR   InterPro; IPR037527; Gp160.
DR   InterPro; IPR000328; GP41-like.
DR   InterPro; IPR000777; HIV1_Gp120.
DR   Pfam; PF00516; GP120; 2.
DR   Pfam; PF00517; GP41; 1.
DR   SUPFAM; SSF56502; gp120 core; 2.
DR   SUPFAM; SSF58069; Virus ectodomain; 1.
PE   3: Inferred from homology;
KW   AIDS; Apoptosis; Clathrin-mediated endocytosis of virus by host;
KW   Cleavage on pair of basic residues; Coiled coil; Disulfide bond;
KW   Fusion of virus membrane with host endosomal membrane;
KW   Fusion of virus membrane with host membrane; Glycoprotein;
KW   Host cell membrane; Host endosome; Host membrane; Host-virus interaction;
KW   Lipoprotein; Membrane; Palmitate; Signal; Transmembrane;
KW   Transmembrane helix; Viral attachment to host cell; Viral envelope protein;
KW   Viral immunoevasion; Viral penetration into host cytoplasm; Virion;
KW   Virus endocytosis by host; Virus entry into host cell.
FT   SIGNAL          1..33
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CHAIN           34..843
FT                   /note="Envelope glycoprotein gp160"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000244675"
FT   CHAIN           34..498
FT                   /note="Surface protein gp120"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000244676"
FT   CHAIN           499..843
FT                   /note="Transmembrane protein gp41"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000244677"
FT   TOPO_DOM        34..671
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   TRANSMEM        672..692
FT                   /note="Helical"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   TOPO_DOM        693..843
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          132..156
FT                   /note="V1"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          157..196
FT                   /note="V2"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          296..329
FT                   /note="V3"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          361..371
FT                   /note="CD4-binding loop"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          382..405
FT                   /note="V4"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          448..458
FT                   /note="V5"
FT   REGION          450..458
FT                   /note="V5"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          499..519
FT                   /note="Fusion peptide"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          561..579
FT                   /note="Immunosuppression"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          649..670
FT                   /note="MPER; binding to GalCer"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          709..731
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COILED          620..654
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   MOTIF           699..702
FT                   /note="YXXL motif; contains endocytosis signal"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   MOTIF           842..843
FT                   /note="Di-leucine internalization motif"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   COMPBIAS        716..731
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   SITE            498..499
FT                   /note="Cleavage; by host furin"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   LIPID           751
FT                   /note="S-palmitoyl cysteine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        30
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        89
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        131
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        136
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        143
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        156
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        160
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        186
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        197
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        234
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        262
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        276
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        289
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        301
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        333
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        338
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        343
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        353
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        359
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        383
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        389
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        395
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        400
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        435
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        598
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        603
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        612
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        624
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        55..75
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        120..205
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        127..196
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        132..157
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        218..247
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        228..239
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        296..330
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        375..432
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        585..591
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
SQ   SEQUENCE   843 AA;  95678 MW;  3400E7671F149501 CRC64;
     MRVREMQRNW QHLGKWGLLF LGILIICNAN ATDDLWVTVY YGVPVWKEPT TTLFCASDAK
     AYDPEVHNVW ATYACVPTDP NPQELVLGNV TENFNMWENN MVDQMHLDII SLWDQSLKPC
     VKSTPLCVTL NCTDVNITMS DINGTSLKED QGEIKNCSFN VTTELKDKKR KQQALFYRLD
     VEPIKNSSNI YKLISCNMST VTQACPKVSF DPIPIHYCAP AGYAILKCND KRFNGTGPCE
     KVSTVQCTHG IRPVVSTQLL LNGSLAQEDI IIRSKNITDN TKNIIVQFNR SVIIDCRRPN
     NNTRKGIRIG PGQTFFATGE IIGDIRKAYC NINRTLWNET LKNVSGEFKK HFNFSVAFNS
     SSGGDVEITT HSFNCRGEFF YYNTSGLFNE TEVANNTNEN ITLPCRIRQF VNMWQRIGRA
     MYAPPIEGEI QCTSNITGLL LTRDGSKDID GKEILRPIGG DMRDNWRSEL YKYKVVRIEP
     VGVAPTKAKR RVVQRAKRAV GMGAVLFGFL GAAGSTMGAA AITLTAQARQ LLSGIVQQQS
     NLLKAIEAQQ HLLQLTVWGI KQLQARILAV ERYLKDQQLL GIWGCSGKLI CTTNVRWNSS
     WSNKSYDDIW DNMTWMQWEK EIDNYTKTIY SLIEDAQNQQ ERNEQELLAL DKWDSLWSWF
     SITNWLWYIK IFIMIVGGLI GLRIVFAVLS VVNRVRQGYS PLSLQTLIPN PRGPDRPGGI
     EEEGGEPDRD RSMRLVSGFL PLTWDDLRSL CSFSYRHLRD LLLIAARTVD RGVKGGWEAL
     KYLWNLTQHW GRELKNSAIS LFDTIAIAVA EGTDRIIEVL QRAGRAVLHI PRRIRQGAER
     FLL
//
ID   ENV_HV1N5               Reviewed;         421 AA.
AC   P12490;
DT   01-OCT-1989, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-1989, sequence version 1.
DT   08-NOV-2023, entry version 105.
DE   RecName: Full=Truncated surface protein;
DE            Short=SU;
DE   AltName: Full=Glycoprotein 120;
DE            Short=gp120;
DE   Flags: Precursor;
GN   Name=env;
OS   Human immunodeficiency virus type 1 group M subtype B (isolate NY5)
OS   (HIV-1).
OC   Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC   Ortervirales; Retroviridae; Orthoretrovirinae; Lentivirus;
OC   Human immunodeficiency virus 1.
OX   NCBI_TaxID=11698;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=3014529; DOI=10.1073/pnas.83.14.5038;
RA   Willey R.W., Rutledge R.A., Dias S., Folks T., Theodore T., Buckler C.E.,
RA   Martin M.A.;
RT   "Identification of conserved and divergent domains within the envelope gene
RT   of the acquired immunodeficiency syndrome retrovirus.";
RL   Proc. Natl. Acad. Sci. U.S.A. 83:5038-5042(1986).
CC   -!- SUBCELLULAR LOCATION: Virion membrane {ECO:0000305}.
CC   -!- MISCELLANEOUS: HIV-1 lineages are divided in three main groups, M (for
CC       Major), O (for Outlier), and N (for New, or Non-M, Non-O). The vast
CC       majority of strains found worldwide belong to the group M. Group O
CC       seems to be endemic to and largely confined to Cameroon and neighboring
CC       countries in West Central Africa, where these viruses represent a small
CC       minority of HIV-1 strains. The group N is represented by a limited
CC       number of isolates from Cameroonian persons. The group M is further
CC       subdivided in 9 clades or subtypes (A to D, F to H, J and K).
CC   ---------------------------------------------------------------------------
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CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
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DR   EMBL; K03346; AAB02407.1; -; Genomic_DNA.
DR   PDB; 3MLR; X-ray; 1.80 A; P=296-315.
DR   PDB; 6DB5; X-ray; 2.60 A; P/Q=296-315.
DR   PDBsum; 3MLR; -.
DR   PDBsum; 6DB5; -.
DR   SMR; P12490; -.
DR   GlyCosmos; P12490; 24 sites, No reported glycans.
DR   Reactome; R-HSA-5621480; Dectin-2 family.
DR   GO; GO:0016020; C:membrane; IEA:UniProtKB-KW.
DR   GO; GO:0019031; C:viral envelope; IEA:InterPro.
DR   GO; GO:0055036; C:virion membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0075512; P:clathrin-dependent endocytosis of virus by host cell; IEA:UniProtKB-KW.
DR   GO; GO:0039654; P:fusion of virus membrane with host endosome membrane; IEA:UniProtKB-KW.
DR   GO; GO:0019062; P:virion attachment to host cell; IEA:UniProtKB-KW.
DR   Gene3D; 2.170.40.20; Human immunodeficiency virus 1, Gp160, envelope glycoprotein; 2.
DR   InterPro; IPR036377; Gp120_core_sf.
DR   InterPro; IPR000777; HIV1_Gp120.
DR   Pfam; PF00516; GP120; 2.
DR   SUPFAM; SSF56502; gp120 core; 2.
PE   1: Evidence at protein level;
KW   3D-structure; AIDS; Clathrin-mediated endocytosis of virus by host;
KW   Disulfide bond; Fusion of virus membrane with host endosomal membrane;
KW   Fusion of virus membrane with host membrane; Glycoprotein;
KW   Host-virus interaction; Membrane; Signal; Viral attachment to host cell;
KW   Viral penetration into host cytoplasm; Virion; Virus endocytosis by host;
KW   Virus entry into host cell.
FT   SIGNAL          1..31
FT                   /evidence="ECO:0000250"
FT   CHAIN           32..421
FT                   /note="Truncated surface protein"
FT                   /id="PRO_0000038412"
FT   REGION          130..151
FT                   /note="V1"
FT   REGION          152..191
FT                   /note="V2"
FT   REGION          291..324
FT                   /note="V3"
FT   REGION          357..367
FT                   /note="CD4-binding loop"
FT                   /evidence="ECO:0000250"
FT   REGION          378..410
FT                   /note="V4"
FT   CARBOHYD        87
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        97
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        129
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        135
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        140
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        151
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        155
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        183
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        192
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        229
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        236
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        257
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        271
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        284
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        290
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        296
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        326
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        333
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        349
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        355
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        385
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        391
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        395
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        403
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255"
FT   DISULFID        53..73
FT                   /evidence="ECO:0000250"
FT   DISULFID        118..200
FT                   /evidence="ECO:0000250"
FT   DISULFID        125..191
FT                   /evidence="ECO:0000250"
FT   DISULFID        130..152
FT                   /evidence="ECO:0000250"
FT   DISULFID        213..242
FT                   /evidence="ECO:0000250"
FT   DISULFID        223..234
FT                   /evidence="ECO:0000250"
FT   DISULFID        291..325
FT                   /evidence="ECO:0000250"
FT   DISULFID        378..410
FT                   /evidence="ECO:0000250"
FT   STRAND          302..305
FT                   /evidence="ECO:0007829|PDB:3MLR"
FT   STRAND          308..310
FT                   /evidence="ECO:0007829|PDB:3MLR"
SQ   SEQUENCE   421 AA;  47493 MW;  25A575719C22967B CRC64;
     MRAKGTRKNY QHLWRWGTML LGMLMICSAA EQLWVTVYYG VPVWKEATTT LFCASDAKAY
     DTEVHNVWAT HACVPTDPNP QEVVLQNVTE NFNMWKNNTV EQMHEDIISL WDQSLKPCVK
     STPLCVTLNC TDLTNATYAN GSSEERGEIR NCSFNVTTII RNKIQKEYAL FYRLDIVPID
     KDNTSYTLIN CNTSVITQAC PKVSFEPIPI HYCAPAGFAI LKCNDKKFNG TGPCTNVSTV
     QCTHGIKPVV STQLLLNGSL AEGEVVIRSE NFTNNAKTII VQLNKSVEIN CTRPNNNTKK
     GIAIGPGRTL YAREKIIGDI RQAHCNISKA KWNDTLKQIV TKLKEQFRNK TIVFNQSSGG
     DPEIVMHSFN CGGEFFYCKT TQLFNSTWLF NSTWNDTERS DNNETIIIPC RIKQIINSGR
     K
//
ID   ENV_HV1ND               Reviewed;         846 AA.
AC   P18799;
DT   01-NOV-1990, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1990, sequence version 1.
DT   27-MAR-2024, entry version 146.
DE   RecName: Full=Envelope glycoprotein gp160 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   AltName: Full=Env polyprotein {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Contains:
DE     RecName: Full=Surface protein gp120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=SU {ECO:0000255|HAMAP-Rule:MF_04083};
DE     AltName: Full=Glycoprotein 120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=gp120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Contains:
DE     RecName: Full=Transmembrane protein gp41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=TM {ECO:0000255|HAMAP-Rule:MF_04083};
DE     AltName: Full=Glycoprotein 41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=gp41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Flags: Precursor;
GN   Name=env {ECO:0000255|HAMAP-Rule:MF_04083};
OS   Human immunodeficiency virus type 1 group M subtype D (isolate NDK)
OS   (HIV-1).
OC   Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC   Ortervirales; Retroviridae; Orthoretrovirinae; Lentivirus;
OC   Human immunodeficiency virus 1.
OX   NCBI_TaxID=11695;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=2806917; DOI=10.1016/0378-1119(89)90188-1;
RA   Spire B., Sire J., Zachar V., Rey F., Barre-Sinoussi F., Galibert F.,
RA   Hampe A., Chermann J.C.;
RT   "Nucleotide sequence of HIV1-NDK: a highly cytopathic strain of the human
RT   immunodeficiency virus.";
RL   Gene 81:275-284(1989).
RN   [2]
RP   INTERACTION OF SURFACE PROTEIN GP120 WITH GALACTOSYL CERAMIDE.
RX   PubMed=8464878; DOI=10.1073/pnas.90.7.2700;
RA   Fantini J., Cook D.G., Nathanson N., Spitalnik S.L., Gonzalez-Scarano F.;
RT   "Infection of colonic epithelial cell lines by type 1 human
RT   immunodeficiency virus is associated with cell surface expression of
RT   galactosylceramide, a potential alternative gp120 receptor.";
RL   Proc. Natl. Acad. Sci. U.S.A. 90:2700-2704(1993).
RN   [3]
RP   REVIEW.
RX   PubMed=12974773; DOI=10.1034/j.1600-0463.2003.11107803.x;
RA   Geijtenbeek T.B., van Kooyk Y.;
RT   "Pathogens target DC-SIGN to influence their fate DC-SIGN functions as a
RT   pathogen receptor with broad specificity.";
RL   APMIS 111:698-714(2003).
RN   [4]
RP   REVIEW.
RX   PubMed=12873764; DOI=10.1016/s0005-2736(03)00161-5;
RA   Gallo S.A., Finnegan C.M., Viard M., Raviv Y., Dimitrov A., Rawat S.S.,
RA   Puri A., Durell S., Blumenthal R.;
RT   "The HIV Env-mediated fusion reaction.";
RL   Biochim. Biophys. Acta 1614:36-50(2003).
RN   [5]
RP   REVIEW.
RX   PubMed=15719026; DOI=10.1038/sj.cdd.4401584;
RA   Perfettini J.-L., Castedo M., Roumier T., Andreau K., Nardacci R.,
RA   Piacentini M., Kroemer G.;
RT   "Mechanisms of apoptosis induction by the HIV-1 envelope.";
RL   Cell Death Differ. 12:916-923(2005).
RN   [6]
RP   REVIEW.
RX   PubMed=15725757; DOI=10.1089/aid.2005.21.171;
RA   Hartley O., Klasse P.J., Sattentau Q.J., Moore J.P.;
RT   "V3: HIV's switch-hitter.";
RL   AIDS Res. Hum. Retroviruses 21:171-189(2005).
RN   [7]
RP   REVIEW.
RX   PubMed=16114975; DOI=10.2165/00003495-200565130-00002;
RA   Reeves J.D., Piefer A.J.;
RT   "Emerging drug targets for antiretroviral therapy.";
RL   Drugs 65:1747-1766(2005).
RN   [8]
RP   REVIEW.
RX   PubMed=16437164; DOI=10.1038/sj.emboj.7600947;
RA   Lusso P.;
RT   "HIV and the chemokine system: 10 years later.";
RL   EMBO J. 25:447-456(2006).
CC   -!- FUNCTION: [Envelope glycoprotein gp160]: Oligomerizes in the host
CC       endoplasmic reticulum into predominantly trimers. In a second time,
CC       gp160 transits in the host Golgi, where glycosylation is completed. The
CC       precursor is then proteolytically cleaved in the trans-Golgi and
CC       thereby activated by cellular furin or furin-like proteases to produce
CC       gp120 and gp41. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- FUNCTION: [Surface protein gp120]: Attaches the virus to the host
CC       lymphoid cell by binding to the primary receptor CD4. This interaction
CC       induces a structural rearrangement creating a high affinity binding
CC       site for a chemokine coreceptor like CXCR4 and/or CCR5. Acts as a
CC       ligand for CD209/DC-SIGN and CLEC4M/DC-SIGNR, which are respectively
CC       found on dendritic cells (DCs), and on endothelial cells of liver
CC       sinusoids and lymph node sinuses. These interactions allow capture of
CC       viral particles at mucosal surfaces by these cells and subsequent
CC       transmission to permissive cells. HIV subverts the migration properties
CC       of dendritic cells to gain access to CD4+ T-cells in lymph nodes. Virus
CC       transmission to permissive T-cells occurs either in trans (without DCs
CC       infection, through viral capture and transmission), or in cis
CC       (following DCs productive infection, through the usual CD4-gp120
CC       interaction), thereby inducing a robust infection. In trans infection,
CC       bound virions remain infectious over days and it is proposed that they
CC       are not degraded, but protected in non-lysosomal acidic organelles
CC       within the DCs close to the cell membrane thus contributing to the
CC       viral infectious potential during DCs' migration from the periphery to
CC       the lymphoid tissues. On arrival at lymphoid tissues, intact virions
CC       recycle back to DCs' cell surface allowing virus transmission to CD4+
CC       T-cells. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- FUNCTION: [Transmembrane protein gp41]: Acts as a class I viral fusion
CC       protein. Under the current model, the protein has at least 3
CC       conformational states: pre-fusion native state, pre-hairpin
CC       intermediate state, and post-fusion hairpin state. During fusion of
CC       viral and target intracellular membranes, the coiled coil regions
CC       (heptad repeats) assume a trimer-of-hairpins structure, positioning the
CC       fusion peptide in close proximity to the C-terminal region of the
CC       ectodomain. The formation of this structure appears to drive apposition
CC       and subsequent fusion of viral and target cell membranes. Complete
CC       fusion occurs in host cell endosomes and is dynamin-dependent, however
CC       some lipid transfer might occur at the plasma membrane. The virus
CC       undergoes clathrin-dependent internalization long before endosomal
CC       fusion, thus minimizing the surface exposure of conserved viral
CC       epitopes during fusion and reducing the efficacy of inhibitors
CC       targeting these epitopes. Membranes fusion leads to delivery of the
CC       nucleocapsid into the cytoplasm. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBUNIT: [Surface protein gp120]: The mature envelope protein (Env)
CC       consists of a homotrimer of non-covalently associated gp120-gp41
CC       heterodimers. The resulting complex protrudes from the virus surface as
CC       a spike. There seems to be as few as 10 spikes on the average virion.
CC       Interacts with host CD4, CCR5 and CXCR4. Gp120 also interacts with the
CC       C-type lectins CD209/DC-SIGN and CLEC4M/DC-SIGNR (collectively referred
CC       to as DC-SIGN(R)). Gp120 and gp41 interact with GalCer. Gp120 interacts
CC       with host ITGA4/ITGB7 complex; on CD4+ T-cells, this interaction
CC       results in rapid activation of integrin ITGAL/LFA-1, which facilitates
CC       efficient cell-to-cell spreading of HIV-1. Gp120 interacts with cell-
CC       associated heparan sulfate; this interaction increases virus
CC       infectivity on permissive cells and may be involved in infection of
CC       CD4- cells. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBUNIT: [Transmembrane protein gp41]: The mature envelope protein
CC       (Env) consists of a homotrimer of non-covalently associated gp120-gp41
CC       heterodimers. The resulting complex protrudes from the virus surface as
CC       a spike. There seems to be as few as 10 spikes on the average virion.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBCELLULAR LOCATION: [Surface protein gp120]: Virion membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Peripheral membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host cell membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Peripheral membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host endosome membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Note=The surface protein is not
CC       anchored to the viral envelope, but associates with the extravirion
CC       surface through its binding to TM. It is probably concentrated at the
CC       site of budding and incorporated into the virions possibly by contacts
CC       between the cytoplasmic tail of Env and the N-terminus of Gag.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBCELLULAR LOCATION: [Transmembrane protein gp41]: Virion membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host cell membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host endosome membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Note=It is probably concentrated at
CC       the site of budding and incorporated into the virions possibly by
CC       contacts between the cytoplasmic tail of Env and the N-terminus of Gag.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: Some of the most genetically diverse regions of the viral
CC       genome are present in Env. They are called variable regions 1 through 5
CC       (V1 through V5). Coreceptor usage of gp120 is determined mainly by the
CC       primary structure of the third variable region (V3) in the outer domain
CC       of gp120. The sequence of V3 determines which coreceptor, CCR5 and/or
CC       CXCR4 (corresponding to R5/macrophage, X4/T cell and R5X4/T cell and
CC       macrophage tropism), is used to trigger the fusion potential of the Env
CC       complex, and hence which cells the virus can infect. Binding to CCR5
CC       involves a region adjacent in addition to V3. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- DOMAIN: The membrane proximal external region (MPER) present in gp41 is
CC       a tryptophan-rich region recognized by the antibodies 2F5, Z13, and
CC       4E10. MPER seems to play a role in fusion. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- DOMAIN: The 17 amino acids long immunosuppressive region is present in
CC       many retroviral envelope proteins. Synthetic peptides derived from this
CC       relatively conserved sequence inhibit immune function in vitro and in
CC       vivo. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: The YXXL motif is involved in determining the exact site of
CC       viral release at the surface of infected mononuclear cells and promotes
CC       endocytosis. YXXL and di-leucine endocytosis motifs interact directly
CC       or indirectly with the clathrin adapter complexes, opperate
CC       independently, and their activities are not additive.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: The CD4-binding region is targeted by the antibody b12.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- PTM: Highly glycosylated by host. The high number of glycan on the
CC       protein is reffered to as 'glycan shield' because it contributes to
CC       hide protein sequence from adaptive immune system. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- PTM: Palmitoylation of the transmembrane protein and of Env polyprotein
CC       (prior to its proteolytic cleavage) is essential for their association
CC       with host cell membrane lipid rafts. Palmitoylation is therefore
CC       required for envelope trafficking to classical lipid rafts, but not for
CC       viral replication. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- PTM: Specific enzymatic cleavages in vivo yield mature proteins.
CC       Envelope glycoproteins are synthesized as an inactive precursor that is
CC       heavily N-glycosylated and processed likely by host cell furin in the
CC       Golgi to yield the mature SU and TM proteins. The cleavage site between
CC       SU and TM requires the minimal sequence [KR]-X-[KR]-R. About 2 of the 9
CC       disulfide bonds of gp41 are reduced by P4HB/PDI, following binding to
CC       CD4 receptor. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- MISCELLANEOUS: Inhibitors targeting HIV-1 viral envelope proteins are
CC       used as antiretroviral drugs. Attachment of virions to the cell surface
CC       via non-specific interactions and CD4 binding can be blocked by
CC       inhibitors that include cyanovirin-N, cyclotriazadisulfonamide analogs,
CC       PRO 2000, TNX 355 and PRO 542. In addition, BMS 806 can block CD4-
CC       induced conformational changes. Env interactions with the coreceptor
CC       molecules can be targeted by CCR5 antagonists including SCH-D,
CC       maraviroc (UK 427857) and aplaviroc (GW 873140), and the CXCR4
CC       antagonist AMD 070. Fusion of viral and cellular membranes can be
CC       inhibited by peptides such as enfuvirtide and tifuvirtide (T 1249).
CC       Resistance to inhibitors associated with mutations in Env are observed.
CC       Most of the time, single mutations confer only a modest reduction in
CC       drug susceptibility. Combination of several mutations is usually
CC       required to develop a high-level drug resistance. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- MISCELLANEOUS: HIV-1 lineages are divided in three main groups, M (for
CC       Major), O (for Outlier), and N (for New, or Non-M, Non-O). The vast
CC       majority of strains found worldwide belong to the group M. Group O
CC       seems to be endemic to and largely confined to Cameroon and neighboring
CC       countries in West Central Africa, where these viruses represent a small
CC       minority of HIV-1 strains. The group N is represented by a limited
CC       number of isolates from Cameroonian persons. The group M is further
CC       subdivided in 9 clades or subtypes (A to D, F to H, J and K).
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SIMILARITY: Belongs to the HIV-1 env protein family.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- WEB RESOURCE: Name=hivdb; Note=HIV drug resistance database;
CC       URL="https://hivdb.stanford.edu";
CC   -!- WEB RESOURCE: Name=HIV drug resistance mutations;
CC       URL="https://www.iasusa.org/content/hiv-drug-resistance-mutations";
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DR   EMBL; M27323; AAA44873.1; -; Genomic_DNA.
DR   PIR; JQ0066; VCLJND.
DR   SMR; P18799; -.
DR   GlyCosmos; P18799; 24 sites, No reported glycans.
DR   Reactome; R-HSA-5621480; Dectin-2 family.
DR   GO; GO:0044175; C:host cell endosome membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0016020; C:membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:0019031; C:viral envelope; IEA:UniProtKB-KW.
DR   GO; GO:0055036; C:virion membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005198; F:structural molecule activity; IEA:UniProtKB-UniRule.
DR   GO; GO:0075512; P:clathrin-dependent endocytosis of virus by host cell; IEA:UniProtKB-UniRule.
DR   GO; GO:0039654; P:fusion of virus membrane with host endosome membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:0019064; P:fusion of virus membrane with host plasma membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:1903905; P:positive regulation of establishment of T cell polarity; IEA:UniProtKB-UniRule.
DR   GO; GO:1903908; P:positive regulation of plasma membrane raft polarization; IEA:UniProtKB-UniRule.
DR   GO; GO:1903911; P:positive regulation of receptor clustering; IEA:UniProtKB-UniRule.
DR   GO; GO:0019082; P:viral protein processing; IEA:UniProtKB-UniRule.
DR   GO; GO:0019062; P:virion attachment to host cell; IEA:UniProtKB-UniRule.
DR   GO; GO:0019049; P:virus-mediated perturbation of host defense response; IEA:UniProtKB-UniRule.
DR   CDD; cd09909; HIV-1-like_HR1-HR2; 1.
DR   Gene3D; 1.10.287.210; -; 1.
DR   Gene3D; 2.170.40.20; Human immunodeficiency virus 1, Gp160, envelope glycoprotein; 2.
DR   Gene3D; 1.20.5.490; Single helix bin; 1.
DR   HAMAP; MF_04083; HIV_ENV; 1.
DR   InterPro; IPR036377; Gp120_core_sf.
DR   InterPro; IPR037527; Gp160.
DR   InterPro; IPR000328; GP41-like.
DR   InterPro; IPR000777; HIV1_Gp120.
DR   Pfam; PF00516; GP120; 2.
DR   Pfam; PF00517; GP41; 1.
DR   SUPFAM; SSF56502; gp120 core; 1.
DR   SUPFAM; SSF58069; Virus ectodomain; 1.
PE   1: Evidence at protein level;
KW   AIDS; Apoptosis; Clathrin-mediated endocytosis of virus by host;
KW   Cleavage on pair of basic residues; Coiled coil; Disulfide bond;
KW   Fusion of virus membrane with host endosomal membrane;
KW   Fusion of virus membrane with host membrane; Glycoprotein;
KW   Host cell membrane; Host endosome; Host membrane; Host-virus interaction;
KW   Lipoprotein; Membrane; Palmitate; Signal; Transmembrane;
KW   Transmembrane helix; Viral attachment to host cell; Viral envelope protein;
KW   Viral immunoevasion; Viral penetration into host cytoplasm; Virion;
KW   Virus endocytosis by host; Virus entry into host cell.
FT   SIGNAL          1..31
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CHAIN           32..846
FT                   /note="Envelope glycoprotein gp160"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000239483"
FT   CHAIN           32..501
FT                   /note="Surface protein gp120"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000038406"
FT   CHAIN           502..846
FT                   /note="Transmembrane protein gp41"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000038407"
FT   TOPO_DOM        32..674
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   TRANSMEM        675..695
FT                   /note="Helical"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   TOPO_DOM        696..846
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          130..151
FT                   /note="V1"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          152..191
FT                   /note="V2"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          291..327
FT                   /note="V3"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          360..370
FT                   /note="CD4-binding loop"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          381..408
FT                   /note="V4"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          450..461
FT                   /note="V5"
FT   REGION          453..461
FT                   /note="V5"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          502..522
FT                   /note="Fusion peptide"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          564..582
FT                   /note="Immunosuppression"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          652..673
FT                   /note="MPER; binding to GalCer"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   COILED          623..657
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   MOTIF           702..705
FT                   /note="YXXL motif; contains endocytosis signal"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   MOTIF           845..846
FT                   /note="Di-leucine internalization motif"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   SITE            501..502
FT                   /note="Cleavage; by host furin"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   LIPID           754
FT                   /note="S-palmitoyl cysteine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   LIPID           827
FT                   /note="S-palmitoyl cysteine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        87
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        129
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        151
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        179
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        182
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        229
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        236
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        257
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        271
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        284
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        290
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        351
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        382
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        388
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        392
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        395
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        401
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        438
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        451
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        452
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        601
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        606
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        615
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        627
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        53..73
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        118..200
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        125..191
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        130..152
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        213..242
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        223..234
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        291..328
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        374..435
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        381..408
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        588..594
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
SQ   SEQUENCE   846 AA;  96476 MW;  8A3B9DA527DE2E83 CRC64;
     MRAREKERNC QNLWKWGIML LGMLMTCSAA EDLWVTVYYG VPIWKEATTT LFCASDAKAY
     KKEAHNIWAT HACVPTDPNP QEIELENVTE NFNMWKNNMV EQMHEDIISL WDQSLKPCVK
     LTPLCVTLNC TDELRNSKGN GKVEEEEKRK NCSFNVRDKR EQVYALFYKL DIVPIDNNNR
     TNSTNYRLIN CDTSTITQAC PKISFEPIPI HFCAPAGFAI LKCRDKKFNG TGPCSNVSTV
     QCTHGIRPVV STQLLLNGSL AEEEIIIRSE NLTNNVKTII VQLNASIVIN CTRPYKYTRQ
     RTSIGLRQSL YTITGKKKKT GYIGQAHCKI SRAEWNKALQ QVATKLGNLL NKTTITFKPS
     SGGDPEITSH MLNCGGDFFY CNTSRLFNST WNQTNSTGFN NGTVTLPCRI KQIVNLWQRV
     GKAMYAPPIE GLIKCSSNIT GLLLTRDGGA NNSSHETIRP GGGDMRDNWR SELYKYKVVK
     IEPIGVAPTK ARRRVVEREK RAIGLGAVFL GFLGAAGSTM GAASVTLTVQ ARQLMSGIVH
     QQNNLLRAIE AQQHLLQLTV WGIKQLQARV LAVERYLRDQ QLLGIWGCSG RHICTTNVPW
     NSSWSNRSLD EIWQNMTWME WEREIDNYTG LIYSLIEESQ IQQEKNEKEL LELDKWASLW
     NWFSITKWLW YIKLFIMIVG GLIGLRIVFA VLSVVNRVRQ GYSPLSFQTL LPVPRGPDRP
     EEIEEEGGER GRDRSIRLVN GLFALFWDDL RNLCLFSYHR LRDSILIAAR IVELLGRRGW
     EALKYLWNLL QYWSQELRNS ASSLLDTIAI AVAERTDRVI EVVQRACRAI LNVPRRIRQG
     LERLLL
//
ID   ENV_HV1OY               Reviewed;         855 AA.
AC   P20888;
DT   01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
DT   01-FEB-1991, sequence version 1.
DT   27-MAR-2024, entry version 141.
DE   RecName: Full=Envelope glycoprotein gp160 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   AltName: Full=Env polyprotein {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Contains:
DE     RecName: Full=Surface protein gp120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=SU {ECO:0000255|HAMAP-Rule:MF_04083};
DE     AltName: Full=Glycoprotein 120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=gp120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Contains:
DE     RecName: Full=Transmembrane protein gp41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=TM {ECO:0000255|HAMAP-Rule:MF_04083};
DE     AltName: Full=Glycoprotein 41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=gp41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Flags: Precursor;
GN   Name=env {ECO:0000255|HAMAP-Rule:MF_04083};
OS   Human immunodeficiency virus type 1 group M subtype B (isolate OYI)
OS   (HIV-1).
OC   Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC   Ortervirales; Retroviridae; Orthoretrovirinae; Lentivirus;
OC   Human immunodeficiency virus 1.
OX   NCBI_TaxID=11699;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX   PubMed=2559749; DOI=10.1097/00002030-198911000-00004;
RA   Huet T., Dazza M.C., Brun-Vezinet F., Roelants G.E., Wain-Hobson S.;
RT   "A highly defective HIV-1 strain isolated from a healthy Gabonese
RT   individual presenting an atypical western blot.";
RL   AIDS 3:707-715(1989).
RN   [2]
RP   REVIEW.
RX   PubMed=12974773; DOI=10.1034/j.1600-0463.2003.11107803.x;
RA   Geijtenbeek T.B., van Kooyk Y.;
RT   "Pathogens target DC-SIGN to influence their fate DC-SIGN functions as a
RT   pathogen receptor with broad specificity.";
RL   APMIS 111:698-714(2003).
RN   [3]
RP   REVIEW.
RX   PubMed=12873764; DOI=10.1016/s0005-2736(03)00161-5;
RA   Gallo S.A., Finnegan C.M., Viard M., Raviv Y., Dimitrov A., Rawat S.S.,
RA   Puri A., Durell S., Blumenthal R.;
RT   "The HIV Env-mediated fusion reaction.";
RL   Biochim. Biophys. Acta 1614:36-50(2003).
RN   [4]
RP   REVIEW.
RX   PubMed=15719026; DOI=10.1038/sj.cdd.4401584;
RA   Perfettini J.-L., Castedo M., Roumier T., Andreau K., Nardacci R.,
RA   Piacentini M., Kroemer G.;
RT   "Mechanisms of apoptosis induction by the HIV-1 envelope.";
RL   Cell Death Differ. 12:916-923(2005).
RN   [5]
RP   REVIEW.
RX   PubMed=15725757; DOI=10.1089/aid.2005.21.171;
RA   Hartley O., Klasse P.J., Sattentau Q.J., Moore J.P.;
RT   "V3: HIV's switch-hitter.";
RL   AIDS Res. Hum. Retroviruses 21:171-189(2005).
RN   [6]
RP   REVIEW.
RX   PubMed=16114975; DOI=10.2165/00003495-200565130-00002;
RA   Reeves J.D., Piefer A.J.;
RT   "Emerging drug targets for antiretroviral therapy.";
RL   Drugs 65:1747-1766(2005).
RN   [7]
RP   REVIEW.
RX   PubMed=16437164; DOI=10.1038/sj.emboj.7600947;
RA   Lusso P.;
RT   "HIV and the chemokine system: 10 years later.";
RL   EMBO J. 25:447-456(2006).
CC   -!- FUNCTION: [Envelope glycoprotein gp160]: Oligomerizes in the host
CC       endoplasmic reticulum into predominantly trimers. In a second time,
CC       gp160 transits in the host Golgi, where glycosylation is completed. The
CC       precursor is then proteolytically cleaved in the trans-Golgi and
CC       thereby activated by cellular furin or furin-like proteases to produce
CC       gp120 and gp41. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- FUNCTION: [Surface protein gp120]: Attaches the virus to the host
CC       lymphoid cell by binding to the primary receptor CD4. This interaction
CC       induces a structural rearrangement creating a high affinity binding
CC       site for a chemokine coreceptor like CXCR4 and/or CCR5. Acts as a
CC       ligand for CD209/DC-SIGN and CLEC4M/DC-SIGNR, which are respectively
CC       found on dendritic cells (DCs), and on endothelial cells of liver
CC       sinusoids and lymph node sinuses. These interactions allow capture of
CC       viral particles at mucosal surfaces by these cells and subsequent
CC       transmission to permissive cells. HIV subverts the migration properties
CC       of dendritic cells to gain access to CD4+ T-cells in lymph nodes. Virus
CC       transmission to permissive T-cells occurs either in trans (without DCs
CC       infection, through viral capture and transmission), or in cis
CC       (following DCs productive infection, through the usual CD4-gp120
CC       interaction), thereby inducing a robust infection. In trans infection,
CC       bound virions remain infectious over days and it is proposed that they
CC       are not degraded, but protected in non-lysosomal acidic organelles
CC       within the DCs close to the cell membrane thus contributing to the
CC       viral infectious potential during DCs' migration from the periphery to
CC       the lymphoid tissues. On arrival at lymphoid tissues, intact virions
CC       recycle back to DCs' cell surface allowing virus transmission to CD4+
CC       T-cells. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- FUNCTION: [Transmembrane protein gp41]: Acts as a class I viral fusion
CC       protein. Under the current model, the protein has at least 3
CC       conformational states: pre-fusion native state, pre-hairpin
CC       intermediate state, and post-fusion hairpin state. During fusion of
CC       viral and target intracellular membranes, the coiled coil regions
CC       (heptad repeats) assume a trimer-of-hairpins structure, positioning the
CC       fusion peptide in close proximity to the C-terminal region of the
CC       ectodomain. The formation of this structure appears to drive apposition
CC       and subsequent fusion of viral and target cell membranes. Complete
CC       fusion occurs in host cell endosomes and is dynamin-dependent, however
CC       some lipid transfer might occur at the plasma membrane. The virus
CC       undergoes clathrin-dependent internalization long before endosomal
CC       fusion, thus minimizing the surface exposure of conserved viral
CC       epitopes during fusion and reducing the efficacy of inhibitors
CC       targeting these epitopes. Membranes fusion leads to delivery of the
CC       nucleocapsid into the cytoplasm. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBUNIT: [Surface protein gp120]: The mature envelope protein (Env)
CC       consists of a homotrimer of non-covalently associated gp120-gp41
CC       heterodimers. The resulting complex protrudes from the virus surface as
CC       a spike. There seems to be as few as 10 spikes on the average virion.
CC       Interacts with host CD4, CCR5 and CXCR4. Gp120 also interacts with the
CC       C-type lectins CD209/DC-SIGN and CLEC4M/DC-SIGNR (collectively referred
CC       to as DC-SIGN(R)). Gp120 and gp41 interact with GalCer. Gp120 interacts
CC       with host ITGA4/ITGB7 complex; on CD4+ T-cells, this interaction
CC       results in rapid activation of integrin ITGAL/LFA-1, which facilitates
CC       efficient cell-to-cell spreading of HIV-1. Gp120 interacts with cell-
CC       associated heparan sulfate; this interaction increases virus
CC       infectivity on permissive cells and may be involved in infection of
CC       CD4- cells. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBUNIT: [Transmembrane protein gp41]: The mature envelope protein
CC       (Env) consists of a homotrimer of non-covalently associated gp120-gp41
CC       heterodimers. The resulting complex protrudes from the virus surface as
CC       a spike. There seems to be as few as 10 spikes on the average virion.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBCELLULAR LOCATION: [Surface protein gp120]: Virion membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Peripheral membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host cell membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Peripheral membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host endosome membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Note=The surface protein is not
CC       anchored to the viral envelope, but associates with the extravirion
CC       surface through its binding to TM. It is probably concentrated at the
CC       site of budding and incorporated into the virions possibly by contacts
CC       between the cytoplasmic tail of Env and the N-terminus of Gag.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBCELLULAR LOCATION: [Transmembrane protein gp41]: Virion membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host cell membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host endosome membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Note=It is probably concentrated at
CC       the site of budding and incorporated into the virions possibly by
CC       contacts between the cytoplasmic tail of Env and the N-terminus of Gag.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: Some of the most genetically diverse regions of the viral
CC       genome are present in Env. They are called variable regions 1 through 5
CC       (V1 through V5). Coreceptor usage of gp120 is determined mainly by the
CC       primary structure of the third variable region (V3) in the outer domain
CC       of gp120. The sequence of V3 determines which coreceptor, CCR5 and/or
CC       CXCR4 (corresponding to R5/macrophage, X4/T cell and R5X4/T cell and
CC       macrophage tropism), is used to trigger the fusion potential of the Env
CC       complex, and hence which cells the virus can infect. Binding to CCR5
CC       involves a region adjacent in addition to V3. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- DOMAIN: The membrane proximal external region (MPER) present in gp41 is
CC       a tryptophan-rich region recognized by the antibodies 2F5, Z13, and
CC       4E10. MPER seems to play a role in fusion. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- DOMAIN: The 17 amino acids long immunosuppressive region is present in
CC       many retroviral envelope proteins. Synthetic peptides derived from this
CC       relatively conserved sequence inhibit immune function in vitro and in
CC       vivo. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: The YXXL motif is involved in determining the exact site of
CC       viral release at the surface of infected mononuclear cells and promotes
CC       endocytosis. YXXL and di-leucine endocytosis motifs interact directly
CC       or indirectly with the clathrin adapter complexes, opperate
CC       independently, and their activities are not additive.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: The CD4-binding region is targeted by the antibody b12.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- PTM: Highly glycosylated by host. The high number of glycan on the
CC       protein is reffered to as 'glycan shield' because it contributes to
CC       hide protein sequence from adaptive immune system. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- PTM: Palmitoylation of the transmembrane protein and of Env polyprotein
CC       (prior to its proteolytic cleavage) is essential for their association
CC       with host cell membrane lipid rafts. Palmitoylation is therefore
CC       required for envelope trafficking to classical lipid rafts, but not for
CC       viral replication. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- PTM: Specific enzymatic cleavages in vivo yield mature proteins.
CC       Envelope glycoproteins are synthesized as an inactive precursor that is
CC       heavily N-glycosylated and processed likely by host cell furin in the
CC       Golgi to yield the mature SU and TM proteins. The cleavage site between
CC       SU and TM requires the minimal sequence [KR]-X-[KR]-R. About 2 of the 9
CC       disulfide bonds of gp41 are reduced by P4HB/PDI, following binding to
CC       CD4 receptor. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- MISCELLANEOUS: Inhibitors targeting HIV-1 viral envelope proteins are
CC       used as antiretroviral drugs. Attachment of virions to the cell surface
CC       via non-specific interactions and CD4 binding can be blocked by
CC       inhibitors that include cyanovirin-N, cyclotriazadisulfonamide analogs,
CC       PRO 2000, TNX 355 and PRO 542. In addition, BMS 806 can block CD4-
CC       induced conformational changes. Env interactions with the coreceptor
CC       molecules can be targeted by CCR5 antagonists including SCH-D,
CC       maraviroc (UK 427857) and aplaviroc (GW 873140), and the CXCR4
CC       antagonist AMD 070. Fusion of viral and cellular membranes can be
CC       inhibited by peptides such as enfuvirtide and tifuvirtide (T 1249).
CC       Resistance to inhibitors associated with mutations in Env are observed.
CC       Most of the time, single mutations confer only a modest reduction in
CC       drug susceptibility. Combination of several mutations is usually
CC       required to develop a high-level drug resistance. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- MISCELLANEOUS: HIV-1 lineages are divided in three main groups, M (for
CC       Major), O (for Outlier), and N (for New, or Non-M, Non-O). The vast
CC       majority of strains found worldwide belong to the group M. Group O
CC       seems to be endemic to and largely confined to Cameroon and neighboring
CC       countries in West Central Africa, where these viruses represent a small
CC       minority of HIV-1 strains. The group N is represented by a limited
CC       number of isolates from Cameroonian persons. The group M is further
CC       subdivided in 9 clades or subtypes (A to D, F to H, J and K).
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SIMILARITY: Belongs to the HIV-1 env protein family.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- WEB RESOURCE: Name=hivdb; Note=HIV drug resistance database;
CC       URL="https://hivdb.stanford.edu";
CC   -!- WEB RESOURCE: Name=HIV drug resistance mutations;
CC       URL="https://www.iasusa.org/content/hiv-drug-resistance-mutations";
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DR   EMBL; M26727; AAA83397.1; -; Genomic_RNA.
DR   SMR; P20888; -.
DR   GlyCosmos; P20888; 26 sites, No reported glycans.
DR   Reactome; R-HSA-5621480; Dectin-2 family.
DR   GO; GO:0044175; C:host cell endosome membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0016020; C:membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:0019031; C:viral envelope; IEA:UniProtKB-KW.
DR   GO; GO:0055036; C:virion membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005198; F:structural molecule activity; IEA:UniProtKB-UniRule.
DR   GO; GO:0075512; P:clathrin-dependent endocytosis of virus by host cell; IEA:UniProtKB-UniRule.
DR   GO; GO:0039654; P:fusion of virus membrane with host endosome membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:0019064; P:fusion of virus membrane with host plasma membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:1903905; P:positive regulation of establishment of T cell polarity; IEA:UniProtKB-UniRule.
DR   GO; GO:1903908; P:positive regulation of plasma membrane raft polarization; IEA:UniProtKB-UniRule.
DR   GO; GO:1903911; P:positive regulation of receptor clustering; IEA:UniProtKB-UniRule.
DR   GO; GO:0019082; P:viral protein processing; IEA:UniProtKB-UniRule.
DR   GO; GO:0019062; P:virion attachment to host cell; IEA:UniProtKB-UniRule.
DR   GO; GO:0019049; P:virus-mediated perturbation of host defense response; IEA:UniProtKB-UniRule.
DR   CDD; cd09909; HIV-1-like_HR1-HR2; 1.
DR   Gene3D; 1.10.287.210; -; 1.
DR   Gene3D; 2.170.40.20; Human immunodeficiency virus 1, Gp160, envelope glycoprotein; 2.
DR   Gene3D; 1.20.5.490; Single helix bin; 1.
DR   HAMAP; MF_04083; HIV_ENV; 1.
DR   InterPro; IPR036377; Gp120_core_sf.
DR   InterPro; IPR037527; Gp160.
DR   InterPro; IPR000328; GP41-like.
DR   InterPro; IPR000777; HIV1_Gp120.
DR   Pfam; PF00516; GP120; 1.
DR   Pfam; PF00517; GP41; 1.
DR   SUPFAM; SSF56502; gp120 core; 2.
DR   SUPFAM; SSF58069; Virus ectodomain; 1.
PE   3: Inferred from homology;
KW   AIDS; Apoptosis; Clathrin-mediated endocytosis of virus by host;
KW   Cleavage on pair of basic residues; Coiled coil; Disulfide bond;
KW   Fusion of virus membrane with host endosomal membrane;
KW   Fusion of virus membrane with host membrane; Glycoprotein;
KW   Host cell membrane; Host endosome; Host membrane; Host-virus interaction;
KW   Lipoprotein; Membrane; Palmitate; Signal; Transmembrane;
KW   Transmembrane helix; Viral attachment to host cell; Viral envelope protein;
KW   Viral immunoevasion; Viral penetration into host cytoplasm; Virion;
KW   Virus endocytosis by host; Virus entry into host cell.
FT   SIGNAL          1..31
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CHAIN           32..855
FT                   /note="Envelope glycoprotein gp160"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000239486"
FT   CHAIN           32..509
FT                   /note="Surface protein gp120"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000038413"
FT   CHAIN           510..855
FT                   /note="Transmembrane protein gp41"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000038414"
FT   TOPO_DOM        32..683
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   TRANSMEM        684..704
FT                   /note="Helical"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   TOPO_DOM        705..855
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          130..161
FT                   /note="V1"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          162..201
FT                   /note="V2"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          301..334
FT                   /note="V3"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          367..377
FT                   /note="CD4-binding loop"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          388..415
FT                   /note="V4"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          458..469
FT                   /note="V5"
FT   REGION          460..469
FT                   /note="V5"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          510..531
FT                   /note="Fusion peptide"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          573..591
FT                   /note="Immunosuppression"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          661..682
FT                   /note="MPER; binding to GalCer"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          718..742
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COILED          632..666
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   MOTIF           711..714
FT                   /note="YXXL motif; contains endocytosis signal"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   MOTIF           854..855
FT                   /note="Di-leucine internalization motif"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   COMPBIAS        726..742
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   SITE            509..510
FT                   /note="Cleavage; by host furin"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   LIPID           763
FT                   /note="S-palmitoyl cysteine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        87
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        134
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        142
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        145
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        161
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        165
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        192
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        202
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        239
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        246
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        267
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        281
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        294
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        300
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        306
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        336
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        359
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        389
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        395
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        399
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        405
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        458
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        610
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        615
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        624
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        636
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        53..73
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        118..210
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        125..201
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        130..162
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        223..252
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        233..244
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        301..335
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        381..442
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        388..415
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        597..603
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
SQ   SEQUENCE   855 AA;  97476 MW;  9CF82A607ADD62DA CRC64;
     MTARGTRKNY QRLWRWGTML LGMLMICSAA ENLWVTVYYG VPVWKEATTT LFCASDARAY
     ATEVHNVWAT HACVPTDPNP QEVVLGNVTE NFDMWKNNMV EQMQEDIISL WDQSLKPCVK
     LTPLCVTLDC TDVNTTSSSL RNATNTTSSS WETMEKGELK NCSFNTTTSI RDKMQEQYAL
     FYKLDVLPID KNDTKFRLIH CNTSTITQAC PKISFEPIPM HYCTPAGFAI LKCNDKKFNG
     TGPCTNVSTV QCTHGIKPVV STQLLLNGSL AEEEVIIRSS NFTNNAKIII VQLNKSVEIN
     CTRPNNNTRN RISIGPGRAF HTTKQIIGDI RQAHCNLSRA TWEKTLEQIA TKLRKQFRNK
     TIAFDRSSGG DPEIVMHSFN CGGEFFYCNT SQLFNSTWND TTRANSTEVT ITLPCRIKQI
     VNMWQEVGKA MYAPPISGQI RCSSKITGLL LTRDGGKNTT NGIEIFRPAG GDMRDNWRSE
     LYKYKVVKIE PLGVAPTKAR RRVVQREKRA VGMLGAMFLG FLGAAGSTMG ARSMTLTVQA
     RQLLSGIVQQ QNNLLRAIEA QQHLLQLTVW GIKQLQARVL AVERYLKDQQ LLGIWGCSGK
     LICTTTVPWN ASWSNKSLNE IWDNMTWMQW EREIDNYTHL IYTLIEESQN QQEKNEQELL
     ELDKWAGLWS WFSITNWLWY IRIFIIIVGG LVGLRIVFAV LSIVNRVRQG YSPLSFQTRL
     PTQRGPDRPE GIEEEGGERD RDRSGRLVDG FLALIWDDLR SLCLFSYHRL RDLILIVARI
     VELLGRRGWE VLKYWWNLLQ YWSQELKNSV ISLLNATAIA VAEGTDRVIE IVQRAYRAFL
     NIPRRIRQGL ERALL
//
ID   ENV_HV1RH               Reviewed;         865 AA.
AC   P04579;
DT   13-AUG-1987, integrated into UniProtKB/Swiss-Prot.
DT   13-AUG-1987, sequence version 1.
DT   27-MAR-2024, entry version 156.
DE   RecName: Full=Envelope glycoprotein gp160 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   AltName: Full=Env polyprotein {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Contains:
DE     RecName: Full=Surface protein gp120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=SU {ECO:0000255|HAMAP-Rule:MF_04083};
DE     AltName: Full=Glycoprotein 120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=gp120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Contains:
DE     RecName: Full=Transmembrane protein gp41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=TM {ECO:0000255|HAMAP-Rule:MF_04083};
DE     AltName: Full=Glycoprotein 41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=gp41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Flags: Precursor;
GN   Name=env {ECO:0000255|HAMAP-Rule:MF_04083};
OS   Human immunodeficiency virus type 1 group M subtype B (isolate RF/HAT3)
OS   (HIV-1).
OC   Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC   Ortervirales; Retroviridae; Orthoretrovirinae; Lentivirus;
OC   Human immunodeficiency virus 1.
OX   NCBI_TaxID=11701;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX   PubMed=2423250; DOI=10.1016/0092-8674(86)90778-6;
RA   Starcich B.R., Hahn B.H., Shaw G.M., McNeely P.D., Modrow S., Wolf H.,
RA   Parks E.S., Parks W.P., Josephs S.F., Gallo R.C., Wong-Staal F.;
RT   "Identification and characterization of conserved and variable regions in
RT   the envelope gene of HTLV-III/LAV, the retrovirus of AIDS.";
RL   Cell 45:637-648(1986).
RN   [2]
RP   REVIEW.
RX   PubMed=12974773; DOI=10.1034/j.1600-0463.2003.11107803.x;
RA   Geijtenbeek T.B., van Kooyk Y.;
RT   "Pathogens target DC-SIGN to influence their fate DC-SIGN functions as a
RT   pathogen receptor with broad specificity.";
RL   APMIS 111:698-714(2003).
RN   [3]
RP   REVIEW.
RX   PubMed=12873764; DOI=10.1016/s0005-2736(03)00161-5;
RA   Gallo S.A., Finnegan C.M., Viard M., Raviv Y., Dimitrov A., Rawat S.S.,
RA   Puri A., Durell S., Blumenthal R.;
RT   "The HIV Env-mediated fusion reaction.";
RL   Biochim. Biophys. Acta 1614:36-50(2003).
RN   [4]
RP   REVIEW.
RX   PubMed=15719026; DOI=10.1038/sj.cdd.4401584;
RA   Perfettini J.-L., Castedo M., Roumier T., Andreau K., Nardacci R.,
RA   Piacentini M., Kroemer G.;
RT   "Mechanisms of apoptosis induction by the HIV-1 envelope.";
RL   Cell Death Differ. 12:916-923(2005).
RN   [5]
RP   REVIEW.
RX   PubMed=15725757; DOI=10.1089/aid.2005.21.171;
RA   Hartley O., Klasse P.J., Sattentau Q.J., Moore J.P.;
RT   "V3: HIV's switch-hitter.";
RL   AIDS Res. Hum. Retroviruses 21:171-189(2005).
RN   [6]
RP   REVIEW.
RX   PubMed=16114975; DOI=10.2165/00003495-200565130-00002;
RA   Reeves J.D., Piefer A.J.;
RT   "Emerging drug targets for antiretroviral therapy.";
RL   Drugs 65:1747-1766(2005).
RN   [7]
RP   REVIEW.
RX   PubMed=16437164; DOI=10.1038/sj.emboj.7600947;
RA   Lusso P.;
RT   "HIV and the chemokine system: 10 years later.";
RL   EMBO J. 25:447-456(2006).
CC   -!- FUNCTION: [Envelope glycoprotein gp160]: Oligomerizes in the host
CC       endoplasmic reticulum into predominantly trimers. In a second time,
CC       gp160 transits in the host Golgi, where glycosylation is completed. The
CC       precursor is then proteolytically cleaved in the trans-Golgi and
CC       thereby activated by cellular furin or furin-like proteases to produce
CC       gp120 and gp41. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- FUNCTION: [Surface protein gp120]: Attaches the virus to the host
CC       lymphoid cell by binding to the primary receptor CD4. This interaction
CC       induces a structural rearrangement creating a high affinity binding
CC       site for a chemokine coreceptor like CXCR4 and/or CCR5. Acts as a
CC       ligand for CD209/DC-SIGN and CLEC4M/DC-SIGNR, which are respectively
CC       found on dendritic cells (DCs), and on endothelial cells of liver
CC       sinusoids and lymph node sinuses. These interactions allow capture of
CC       viral particles at mucosal surfaces by these cells and subsequent
CC       transmission to permissive cells. HIV subverts the migration properties
CC       of dendritic cells to gain access to CD4+ T-cells in lymph nodes. Virus
CC       transmission to permissive T-cells occurs either in trans (without DCs
CC       infection, through viral capture and transmission), or in cis
CC       (following DCs productive infection, through the usual CD4-gp120
CC       interaction), thereby inducing a robust infection. In trans infection,
CC       bound virions remain infectious over days and it is proposed that they
CC       are not degraded, but protected in non-lysosomal acidic organelles
CC       within the DCs close to the cell membrane thus contributing to the
CC       viral infectious potential during DCs' migration from the periphery to
CC       the lymphoid tissues. On arrival at lymphoid tissues, intact virions
CC       recycle back to DCs' cell surface allowing virus transmission to CD4+
CC       T-cells. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- FUNCTION: [Transmembrane protein gp41]: Acts as a class I viral fusion
CC       protein. Under the current model, the protein has at least 3
CC       conformational states: pre-fusion native state, pre-hairpin
CC       intermediate state, and post-fusion hairpin state. During fusion of
CC       viral and target intracellular membranes, the coiled coil regions
CC       (heptad repeats) assume a trimer-of-hairpins structure, positioning the
CC       fusion peptide in close proximity to the C-terminal region of the
CC       ectodomain. The formation of this structure appears to drive apposition
CC       and subsequent fusion of viral and target cell membranes. Complete
CC       fusion occurs in host cell endosomes and is dynamin-dependent, however
CC       some lipid transfer might occur at the plasma membrane. The virus
CC       undergoes clathrin-dependent internalization long before endosomal
CC       fusion, thus minimizing the surface exposure of conserved viral
CC       epitopes during fusion and reducing the efficacy of inhibitors
CC       targeting these epitopes. Membranes fusion leads to delivery of the
CC       nucleocapsid into the cytoplasm. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBUNIT: [Surface protein gp120]: The mature envelope protein (Env)
CC       consists of a homotrimer of non-covalently associated gp120-gp41
CC       heterodimers. The resulting complex protrudes from the virus surface as
CC       a spike. There seems to be as few as 10 spikes on the average virion.
CC       Interacts with host CD4, CCR5 and CXCR4. Gp120 also interacts with the
CC       C-type lectins CD209/DC-SIGN and CLEC4M/DC-SIGNR (collectively referred
CC       to as DC-SIGN(R)). Gp120 and gp41 interact with GalCer. Gp120 interacts
CC       with host ITGA4/ITGB7 complex; on CD4+ T-cells, this interaction
CC       results in rapid activation of integrin ITGAL/LFA-1, which facilitates
CC       efficient cell-to-cell spreading of HIV-1. Gp120 interacts with cell-
CC       associated heparan sulfate; this interaction increases virus
CC       infectivity on permissive cells and may be involved in infection of
CC       CD4- cells. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBUNIT: [Transmembrane protein gp41]: The mature envelope protein
CC       (Env) consists of a homotrimer of non-covalently associated gp120-gp41
CC       heterodimers. The resulting complex protrudes from the virus surface as
CC       a spike. There seems to be as few as 10 spikes on the average virion.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBCELLULAR LOCATION: [Surface protein gp120]: Virion membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Peripheral membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host cell membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Peripheral membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host endosome membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Note=The surface protein is not
CC       anchored to the viral envelope, but associates with the extravirion
CC       surface through its binding to TM. It is probably concentrated at the
CC       site of budding and incorporated into the virions possibly by contacts
CC       between the cytoplasmic tail of Env and the N-terminus of Gag.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBCELLULAR LOCATION: [Transmembrane protein gp41]: Virion membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host cell membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host endosome membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Note=It is probably concentrated at
CC       the site of budding and incorporated into the virions possibly by
CC       contacts between the cytoplasmic tail of Env and the N-terminus of Gag.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: Some of the most genetically diverse regions of the viral
CC       genome are present in Env. They are called variable regions 1 through 5
CC       (V1 through V5). Coreceptor usage of gp120 is determined mainly by the
CC       primary structure of the third variable region (V3) in the outer domain
CC       of gp120. The sequence of V3 determines which coreceptor, CCR5 and/or
CC       CXCR4 (corresponding to R5/macrophage, X4/T cell and R5X4/T cell and
CC       macrophage tropism), is used to trigger the fusion potential of the Env
CC       complex, and hence which cells the virus can infect. Binding to CCR5
CC       involves a region adjacent in addition to V3. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- DOMAIN: The membrane proximal external region (MPER) present in gp41 is
CC       a tryptophan-rich region recognized by the antibodies 2F5, Z13, and
CC       4E10. MPER seems to play a role in fusion. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- DOMAIN: The 17 amino acids long immunosuppressive region is present in
CC       many retroviral envelope proteins. Synthetic peptides derived from this
CC       relatively conserved sequence inhibit immune function in vitro and in
CC       vivo. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: The YXXL motif is involved in determining the exact site of
CC       viral release at the surface of infected mononuclear cells and promotes
CC       endocytosis. YXXL and di-leucine endocytosis motifs interact directly
CC       or indirectly with the clathrin adapter complexes, opperate
CC       independently, and their activities are not additive.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: The CD4-binding region is targeted by the antibody b12.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- PTM: Highly glycosylated by host. The high number of glycan on the
CC       protein is reffered to as 'glycan shield' because it contributes to
CC       hide protein sequence from adaptive immune system. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- PTM: Palmitoylation of the transmembrane protein and of Env polyprotein
CC       (prior to its proteolytic cleavage) is essential for their association
CC       with host cell membrane lipid rafts. Palmitoylation is therefore
CC       required for envelope trafficking to classical lipid rafts, but not for
CC       viral replication. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- PTM: Specific enzymatic cleavages in vivo yield mature proteins.
CC       Envelope glycoproteins are synthesized as an inactive precursor that is
CC       heavily N-glycosylated and processed likely by host cell furin in the
CC       Golgi to yield the mature SU and TM proteins. The cleavage site between
CC       SU and TM requires the minimal sequence [KR]-X-[KR]-R. About 2 of the 9
CC       disulfide bonds of gp41 are reduced by P4HB/PDI, following binding to
CC       CD4 receptor. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- MISCELLANEOUS: Inhibitors targeting HIV-1 viral envelope proteins are
CC       used as antiretroviral drugs. Attachment of virions to the cell surface
CC       via non-specific interactions and CD4 binding can be blocked by
CC       inhibitors that include cyanovirin-N, cyclotriazadisulfonamide analogs,
CC       PRO 2000, TNX 355 and PRO 542. In addition, BMS 806 can block CD4-
CC       induced conformational changes. Env interactions with the coreceptor
CC       molecules can be targeted by CCR5 antagonists including SCH-D,
CC       maraviroc (UK 427857) and aplaviroc (GW 873140), and the CXCR4
CC       antagonist AMD 070. Fusion of viral and cellular membranes can be
CC       inhibited by peptides such as enfuvirtide and tifuvirtide (T 1249).
CC       Resistance to inhibitors associated with mutations in Env are observed.
CC       Most of the time, single mutations confer only a modest reduction in
CC       drug susceptibility. Combination of several mutations is usually
CC       required to develop a high-level drug resistance. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- MISCELLANEOUS: HIV-1 lineages are divided in three main groups, M (for
CC       Major), O (for Outlier), and N (for New, or Non-M, Non-O). The vast
CC       majority of strains found worldwide belong to the group M. Group O
CC       seems to be endemic to and largely confined to Cameroon and neighboring
CC       countries in West Central Africa, where these viruses represent a small
CC       minority of HIV-1 strains. The group N is represented by a limited
CC       number of isolates from Cameroonian persons. The group M is further
CC       subdivided in 9 clades or subtypes (A to D, F to H, J and K).
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SIMILARITY: Belongs to the HIV-1 env protein family.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- WEB RESOURCE: Name=hivdb; Note=HIV drug resistance database;
CC       URL="https://hivdb.stanford.edu";
CC   -!- WEB RESOURCE: Name=HIV drug resistance mutations;
CC       URL="https://www.iasusa.org/content/hiv-drug-resistance-mutations";
CC   ---------------------------------------------------------------------------
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DR   EMBL; M17451; AAA45057.1; -; Genomic_RNA.
DR   BMRB; P04579; -.
DR   SMR; P04579; -.
DR   GlyCosmos; P04579; 32 sites, No reported glycans.
DR   Reactome; R-HSA-5621480; Dectin-2 family.
DR   Proteomes; UP000007699; Segment.
DR   GO; GO:0044175; C:host cell endosome membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0016020; C:membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:0019031; C:viral envelope; IEA:UniProtKB-KW.
DR   GO; GO:0055036; C:virion membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005198; F:structural molecule activity; IEA:UniProtKB-UniRule.
DR   GO; GO:0075512; P:clathrin-dependent endocytosis of virus by host cell; IEA:UniProtKB-UniRule.
DR   GO; GO:0039654; P:fusion of virus membrane with host endosome membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:0019064; P:fusion of virus membrane with host plasma membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:1903905; P:positive regulation of establishment of T cell polarity; IEA:UniProtKB-UniRule.
DR   GO; GO:1903908; P:positive regulation of plasma membrane raft polarization; IEA:UniProtKB-UniRule.
DR   GO; GO:1903911; P:positive regulation of receptor clustering; IEA:UniProtKB-UniRule.
DR   GO; GO:0019082; P:viral protein processing; IEA:UniProtKB-UniRule.
DR   GO; GO:0019062; P:virion attachment to host cell; IEA:UniProtKB-UniRule.
DR   GO; GO:0019049; P:virus-mediated perturbation of host defense response; IEA:UniProtKB-UniRule.
DR   CDD; cd09909; HIV-1-like_HR1-HR2; 1.
DR   Gene3D; 1.10.287.210; -; 1.
DR   Gene3D; 2.170.40.20; Human immunodeficiency virus 1, Gp160, envelope glycoprotein; 2.
DR   Gene3D; 1.20.5.490; Single helix bin; 1.
DR   HAMAP; MF_04083; HIV_ENV; 1.
DR   InterPro; IPR036377; Gp120_core_sf.
DR   InterPro; IPR037527; Gp160.
DR   InterPro; IPR000328; GP41-like.
DR   InterPro; IPR000777; HIV1_Gp120.
DR   Pfam; PF00516; GP120; 1.
DR   Pfam; PF00517; GP41; 1.
DR   SUPFAM; SSF56502; gp120 core; 2.
DR   SUPFAM; SSF58069; Virus ectodomain; 1.
PE   3: Inferred from homology;
KW   AIDS; Apoptosis; Clathrin-mediated endocytosis of virus by host;
KW   Cleavage on pair of basic residues; Coiled coil; Disulfide bond;
KW   Fusion of virus membrane with host endosomal membrane;
KW   Fusion of virus membrane with host membrane; Glycoprotein;
KW   Host cell membrane; Host endosome; Host membrane; Host-virus interaction;
KW   Lipoprotein; Membrane; Palmitate; Reference proteome; Signal;
KW   Transmembrane; Transmembrane helix; Viral attachment to host cell;
KW   Viral envelope protein; Viral immunoevasion;
KW   Viral penetration into host cytoplasm; Virion; Virus endocytosis by host;
KW   Virus entry into host cell.
FT   SIGNAL          1..31
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CHAIN           32..865
FT                   /note="Envelope glycoprotein gp160"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000441245"
FT   CHAIN           32..519
FT                   /note="Surface protein gp120"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000441246"
FT   CHAIN           520..865
FT                   /note="Transmembrane protein gp41"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000038418"
FT   TOPO_DOM        32..693
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   TRANSMEM        694..714
FT                   /note="Helical"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   TOPO_DOM        715..865
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          130..156
FT                   /note="V1"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          157..209
FT                   /note="V2"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          309..342
FT                   /note="V3"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          375..385
FT                   /note="CD4-binding loop"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          396..425
FT                   /note="V4"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          468..479
FT                   /note="V5"
FT   REGION          470..479
FT                   /note="V5"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          520..541
FT                   /note="Fusion peptide"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          583..601
FT                   /note="Immunosuppression"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          671..692
FT                   /note="MPER; binding to GalCer"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          728..754
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COILED          642..676
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   MOTIF           721..724
FT                   /note="YXXL motif; contains endocytosis signal"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   MOTIF           864..865
FT                   /note="Di-leucine internalization motif"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   COMPBIAS        736..754
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   SITE            519..520
FT                   /note="Cleavage; by host furin"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   LIPID           773
FT                   /note="S-palmitoyl cysteine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        87
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        129
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        136
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        139
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        156
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        193
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        194
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        197
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        198
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        203
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        210
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        247
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        254
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        275
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        289
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        302
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        308
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        314
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        344
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        351
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        367
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        397
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        403
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        407
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        413
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        418
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        455
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        471
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        620
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        625
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        634
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        646
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        53..73
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        118..218
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        125..209
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        130..157
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        231..260
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        241..252
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        309..343
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        389..452
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        396..425
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        607..613
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
SQ   SEQUENCE   865 AA;  97809 MW;  28828BC2314ADCAC CRC64;
     MRVMEMRKNC QHLWKWGTML LGMLMICSAA EDLWVTVYYG VPVWKEATTT LFCASEAKAY
     KTEVHNVWAK HACVPTDPNP QEVLLENVTE NFNMWKNNMV EQMHEDIISL WDQSLKPCVK
     LTPLCVTLNC TDANLNGTNV TSSSGGTMME NGEIKNCSFQ VTTSRRDKTQ KKYALFYKLD
     VVPIEKGNIS PKNNTSNNTS YGNYTLIHCN SSVITQACPK VSFEPIPIHY CTPAGFAILK
     CNDKKFNGTG PCKNVSTVQC THGIRPVVST QLLLNGSLAE EEVVIRSENF TDNVKTIIVQ
     LNASVQINCT RPNNNTRKSI TKGPGRVIYA TGQIIGDIRK AHCNLSRAQW NNTLKQVVTK
     LREQFDNKTI VFTSSSGGDP EIVLHSFNCG GEFFYCNTTQ LFNSTWNSTE GSNNTGGNDT
     ITLPCRIKQI VNMWQEVGKA MYAPPISGQI KCISNITGLL LTRDGGEDTT NTTEIFRLGG
     GNMRDNWRSE LYKYKVVRIE PLGVAPTRAK RRVVQREKRA VGTIGAMFLG FLGAAGSTMG
     AGSITLTVQA RHLLSGIVQQ QNNLLRAIEA QQHLLQLTVW GIKQLQARVL AVERYLRDQQ
     LLGIWGCSGK LICTTTVPWN ASWSNKSLNM IWNNMTWMQW EREIDNYTGI IYNLLEESQN
     QQEKNEQELL ELDKWANLWN WFDITQWLWY IRIFIMIVGG LVGLKIVFAV LSIVNRVRQG
     YSPLSFQTHL PAPRGPDRPE GIEGEGGERD RDRSGGAVNG FLTLIWDDLW TLCSFSYHRL
     RDLLLIVVRI VELLGRRGWE ALKYWWNLLQ YWSQELKNSA VSLLNTTAIA VAEGTDRIIE
     VAQRILRAFL HIPRRIRQGL ERALL
//
ID   ENV_HV1S1               Reviewed;         847 AA.
AC   P19550;
DT   01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
DT   01-FEB-1991, sequence version 1.
DT   27-MAR-2024, entry version 151.
DE   RecName: Full=Envelope glycoprotein gp160 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   AltName: Full=Env polyprotein {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Contains:
DE     RecName: Full=Surface protein gp120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=SU {ECO:0000255|HAMAP-Rule:MF_04083};
DE     AltName: Full=Glycoprotein 120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=gp120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Contains:
DE     RecName: Full=Transmembrane protein gp41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=TM {ECO:0000255|HAMAP-Rule:MF_04083};
DE     AltName: Full=Glycoprotein 41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=gp41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Flags: Precursor;
GN   Name=env {ECO:0000255|HAMAP-Rule:MF_04083};
OS   Human immunodeficiency virus type 1 group M subtype B (isolate SF162)
OS   (HIV-1).
OC   Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC   Ortervirales; Retroviridae; Orthoretrovirinae; Lentivirus;
OC   Human immunodeficiency virus 1.
OX   NCBI_TaxID=11691;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX   PubMed=2384920; DOI=10.1128/jvi.64.9.4390-4398.1990;
RA   Cheng-Mayer C., Quiroga M., Tung J.W., Dina D., Levy J.A.;
RT   "Viral determinants of human immunodeficiency virus type 1 T-cell or
RT   macrophage tropism, cytopathogenicity, and CD4 antigen modulation.";
RL   J. Virol. 64:4390-4398(1990).
RN   [2]
RP   REVIEW.
RX   PubMed=12974773; DOI=10.1034/j.1600-0463.2003.11107803.x;
RA   Geijtenbeek T.B., van Kooyk Y.;
RT   "Pathogens target DC-SIGN to influence their fate DC-SIGN functions as a
RT   pathogen receptor with broad specificity.";
RL   APMIS 111:698-714(2003).
RN   [3]
RP   REVIEW.
RX   PubMed=12873764; DOI=10.1016/s0005-2736(03)00161-5;
RA   Gallo S.A., Finnegan C.M., Viard M., Raviv Y., Dimitrov A., Rawat S.S.,
RA   Puri A., Durell S., Blumenthal R.;
RT   "The HIV Env-mediated fusion reaction.";
RL   Biochim. Biophys. Acta 1614:36-50(2003).
RN   [4]
RP   REVIEW.
RX   PubMed=15719026; DOI=10.1038/sj.cdd.4401584;
RA   Perfettini J.-L., Castedo M., Roumier T., Andreau K., Nardacci R.,
RA   Piacentini M., Kroemer G.;
RT   "Mechanisms of apoptosis induction by the HIV-1 envelope.";
RL   Cell Death Differ. 12:916-923(2005).
RN   [5]
RP   REVIEW.
RX   PubMed=15725757; DOI=10.1089/aid.2005.21.171;
RA   Hartley O., Klasse P.J., Sattentau Q.J., Moore J.P.;
RT   "V3: HIV's switch-hitter.";
RL   AIDS Res. Hum. Retroviruses 21:171-189(2005).
RN   [6]
RP   REVIEW.
RX   PubMed=16114975; DOI=10.2165/00003495-200565130-00002;
RA   Reeves J.D., Piefer A.J.;
RT   "Emerging drug targets for antiretroviral therapy.";
RL   Drugs 65:1747-1766(2005).
RN   [7]
RP   REVIEW.
RX   PubMed=16437164; DOI=10.1038/sj.emboj.7600947;
RA   Lusso P.;
RT   "HIV and the chemokine system: 10 years later.";
RL   EMBO J. 25:447-456(2006).
CC   -!- FUNCTION: [Envelope glycoprotein gp160]: Oligomerizes in the host
CC       endoplasmic reticulum into predominantly trimers. In a second time,
CC       gp160 transits in the host Golgi, where glycosylation is completed. The
CC       precursor is then proteolytically cleaved in the trans-Golgi and
CC       thereby activated by cellular furin or furin-like proteases to produce
CC       gp120 and gp41. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- FUNCTION: [Surface protein gp120]: Attaches the virus to the host
CC       lymphoid cell by binding to the primary receptor CD4. This interaction
CC       induces a structural rearrangement creating a high affinity binding
CC       site for a chemokine coreceptor like CXCR4 and/or CCR5. Acts as a
CC       ligand for CD209/DC-SIGN and CLEC4M/DC-SIGNR, which are respectively
CC       found on dendritic cells (DCs), and on endothelial cells of liver
CC       sinusoids and lymph node sinuses. These interactions allow capture of
CC       viral particles at mucosal surfaces by these cells and subsequent
CC       transmission to permissive cells. HIV subverts the migration properties
CC       of dendritic cells to gain access to CD4+ T-cells in lymph nodes. Virus
CC       transmission to permissive T-cells occurs either in trans (without DCs
CC       infection, through viral capture and transmission), or in cis
CC       (following DCs productive infection, through the usual CD4-gp120
CC       interaction), thereby inducing a robust infection. In trans infection,
CC       bound virions remain infectious over days and it is proposed that they
CC       are not degraded, but protected in non-lysosomal acidic organelles
CC       within the DCs close to the cell membrane thus contributing to the
CC       viral infectious potential during DCs' migration from the periphery to
CC       the lymphoid tissues. On arrival at lymphoid tissues, intact virions
CC       recycle back to DCs' cell surface allowing virus transmission to CD4+
CC       T-cells. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- FUNCTION: [Transmembrane protein gp41]: Acts as a class I viral fusion
CC       protein. Under the current model, the protein has at least 3
CC       conformational states: pre-fusion native state, pre-hairpin
CC       intermediate state, and post-fusion hairpin state. During fusion of
CC       viral and target intracellular membranes, the coiled coil regions
CC       (heptad repeats) assume a trimer-of-hairpins structure, positioning the
CC       fusion peptide in close proximity to the C-terminal region of the
CC       ectodomain. The formation of this structure appears to drive apposition
CC       and subsequent fusion of viral and target cell membranes. Complete
CC       fusion occurs in host cell endosomes and is dynamin-dependent, however
CC       some lipid transfer might occur at the plasma membrane. The virus
CC       undergoes clathrin-dependent internalization long before endosomal
CC       fusion, thus minimizing the surface exposure of conserved viral
CC       epitopes during fusion and reducing the efficacy of inhibitors
CC       targeting these epitopes. Membranes fusion leads to delivery of the
CC       nucleocapsid into the cytoplasm. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBUNIT: [Surface protein gp120]: The mature envelope protein (Env)
CC       consists of a homotrimer of non-covalently associated gp120-gp41
CC       heterodimers. The resulting complex protrudes from the virus surface as
CC       a spike. There seems to be as few as 10 spikes on the average virion.
CC       Interacts with host CD4, CCR5 and CXCR4. Gp120 also interacts with the
CC       C-type lectins CD209/DC-SIGN and CLEC4M/DC-SIGNR (collectively referred
CC       to as DC-SIGN(R)). Gp120 and gp41 interact with GalCer. Gp120 interacts
CC       with host ITGA4/ITGB7 complex; on CD4+ T-cells, this interaction
CC       results in rapid activation of integrin ITGAL/LFA-1, which facilitates
CC       efficient cell-to-cell spreading of HIV-1. Gp120 interacts with cell-
CC       associated heparan sulfate; this interaction increases virus
CC       infectivity on permissive cells and may be involved in infection of
CC       CD4- cells. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBUNIT: [Transmembrane protein gp41]: The mature envelope protein
CC       (Env) consists of a homotrimer of non-covalently associated gp120-gp41
CC       heterodimers. The resulting complex protrudes from the virus surface as
CC       a spike. There seems to be as few as 10 spikes on the average virion.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBCELLULAR LOCATION: [Surface protein gp120]: Virion membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Peripheral membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host cell membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Peripheral membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host endosome membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Note=The surface protein is not
CC       anchored to the viral envelope, but associates with the extravirion
CC       surface through its binding to TM. It is probably concentrated at the
CC       site of budding and incorporated into the virions possibly by contacts
CC       between the cytoplasmic tail of Env and the N-terminus of Gag.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBCELLULAR LOCATION: [Transmembrane protein gp41]: Virion membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host cell membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host endosome membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Note=It is probably concentrated at
CC       the site of budding and incorporated into the virions possibly by
CC       contacts between the cytoplasmic tail of Env and the N-terminus of Gag.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: Some of the most genetically diverse regions of the viral
CC       genome are present in Env. They are called variable regions 1 through 5
CC       (V1 through V5). Coreceptor usage of gp120 is determined mainly by the
CC       primary structure of the third variable region (V3) in the outer domain
CC       of gp120. The sequence of V3 determines which coreceptor, CCR5 and/or
CC       CXCR4 (corresponding to R5/macrophage, X4/T cell and R5X4/T cell and
CC       macrophage tropism), is used to trigger the fusion potential of the Env
CC       complex, and hence which cells the virus can infect. Binding to CCR5
CC       involves a region adjacent in addition to V3. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- DOMAIN: The membrane proximal external region (MPER) present in gp41 is
CC       a tryptophan-rich region recognized by the antibodies 2F5, Z13, and
CC       4E10. MPER seems to play a role in fusion. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- DOMAIN: The 17 amino acids long immunosuppressive region is present in
CC       many retroviral envelope proteins. Synthetic peptides derived from this
CC       relatively conserved sequence inhibit immune function in vitro and in
CC       vivo. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: The YXXL motif is involved in determining the exact site of
CC       viral release at the surface of infected mononuclear cells and promotes
CC       endocytosis. YXXL and di-leucine endocytosis motifs interact directly
CC       or indirectly with the clathrin adapter complexes, opperate
CC       independently, and their activities are not additive.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: The CD4-binding region is targeted by the antibody b12.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- PTM: Highly glycosylated by host. The high number of glycan on the
CC       protein is reffered to as 'glycan shield' because it contributes to
CC       hide protein sequence from adaptive immune system. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- PTM: Palmitoylation of the transmembrane protein and of Env polyprotein
CC       (prior to its proteolytic cleavage) is essential for their association
CC       with host cell membrane lipid rafts. Palmitoylation is therefore
CC       required for envelope trafficking to classical lipid rafts, but not for
CC       viral replication. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- PTM: Specific enzymatic cleavages in vivo yield mature proteins.
CC       Envelope glycoproteins are synthesized as an inactive precursor that is
CC       heavily N-glycosylated and processed likely by host cell furin in the
CC       Golgi to yield the mature SU and TM proteins. The cleavage site between
CC       SU and TM requires the minimal sequence [KR]-X-[KR]-R. About 2 of the 9
CC       disulfide bonds of gp41 are reduced by P4HB/PDI, following binding to
CC       CD4 receptor. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- MISCELLANEOUS: Inhibitors targeting HIV-1 viral envelope proteins are
CC       used as antiretroviral drugs. Attachment of virions to the cell surface
CC       via non-specific interactions and CD4 binding can be blocked by
CC       inhibitors that include cyanovirin-N, cyclotriazadisulfonamide analogs,
CC       PRO 2000, TNX 355 and PRO 542. In addition, BMS 806 can block CD4-
CC       induced conformational changes. Env interactions with the coreceptor
CC       molecules can be targeted by CCR5 antagonists including SCH-D,
CC       maraviroc (UK 427857) and aplaviroc (GW 873140), and the CXCR4
CC       antagonist AMD 070. Fusion of viral and cellular membranes can be
CC       inhibited by peptides such as enfuvirtide and tifuvirtide (T 1249).
CC       Resistance to inhibitors associated with mutations in Env are observed.
CC       Most of the time, single mutations confer only a modest reduction in
CC       drug susceptibility. Combination of several mutations is usually
CC       required to develop a high-level drug resistance. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- MISCELLANEOUS: HIV-1 lineages are divided in three main groups, M (for
CC       Major), O (for Outlier), and N (for New, or Non-M, Non-O). The vast
CC       majority of strains found worldwide belong to the group M. Group O
CC       seems to be endemic to and largely confined to Cameroon and neighboring
CC       countries in West Central Africa, where these viruses represent a small
CC       minority of HIV-1 strains. The group N is represented by a limited
CC       number of isolates from Cameroonian persons. The group M is further
CC       subdivided in 9 clades or subtypes (A to D, F to H, J and K).
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SIMILARITY: Belongs to the HIV-1 env protein family.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- WEB RESOURCE: Name=hivdb; Note=HIV drug resistance database;
CC       URL="https://hivdb.stanford.edu";
CC   -!- WEB RESOURCE: Name=HIV drug resistance mutations;
CC       URL="https://www.iasusa.org/content/hiv-drug-resistance-mutations";
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DR   EMBL; M65024; AAA45072.1; -; Genomic_RNA.
DR   PDB; 8FAD; EM; 4.00 A; B/D/F=511-648.
DR   PDBsum; 8FAD; -.
DR   SMR; P19550; -.
DR   BindingDB; P19550; -.
DR   ChEMBL; CHEMBL2396504; -.
DR   GlyCosmos; P19550; 25 sites, No reported glycans.
DR   ABCD; P19550; 7 sequenced antibodies.
DR   Reactome; R-HSA-5621480; Dectin-2 family.
DR   GO; GO:0044175; C:host cell endosome membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0016020; C:membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:0019031; C:viral envelope; IEA:UniProtKB-KW.
DR   GO; GO:0055036; C:virion membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005198; F:structural molecule activity; IEA:UniProtKB-UniRule.
DR   GO; GO:0075512; P:clathrin-dependent endocytosis of virus by host cell; IEA:UniProtKB-UniRule.
DR   GO; GO:0039654; P:fusion of virus membrane with host endosome membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:0019064; P:fusion of virus membrane with host plasma membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:1903905; P:positive regulation of establishment of T cell polarity; IEA:UniProtKB-UniRule.
DR   GO; GO:1903908; P:positive regulation of plasma membrane raft polarization; IEA:UniProtKB-UniRule.
DR   GO; GO:1903911; P:positive regulation of receptor clustering; IEA:UniProtKB-UniRule.
DR   GO; GO:0019082; P:viral protein processing; IEA:UniProtKB-UniRule.
DR   GO; GO:0019062; P:virion attachment to host cell; IEA:UniProtKB-UniRule.
DR   GO; GO:0019049; P:virus-mediated perturbation of host defense response; IEA:UniProtKB-UniRule.
DR   CDD; cd09909; HIV-1-like_HR1-HR2; 1.
DR   Gene3D; 1.10.287.210; -; 1.
DR   Gene3D; 2.170.40.20; Human immunodeficiency virus 1, Gp160, envelope glycoprotein; 2.
DR   Gene3D; 1.20.5.490; Single helix bin; 1.
DR   HAMAP; MF_04083; HIV_ENV; 1.
DR   InterPro; IPR036377; Gp120_core_sf.
DR   InterPro; IPR037527; Gp160.
DR   InterPro; IPR000328; GP41-like.
DR   InterPro; IPR000777; HIV1_Gp120.
DR   Pfam; PF00516; GP120; 2.
DR   Pfam; PF00517; GP41; 1.
DR   SUPFAM; SSF56502; gp120 core; 2.
DR   SUPFAM; SSF58069; Virus ectodomain; 1.
PE   1: Evidence at protein level;
KW   3D-structure; AIDS; Apoptosis;
KW   Clathrin-mediated endocytosis of virus by host;
KW   Cleavage on pair of basic residues; Coiled coil; Disulfide bond;
KW   Fusion of virus membrane with host endosomal membrane;
KW   Fusion of virus membrane with host membrane; Glycoprotein;
KW   Host cell membrane; Host endosome; Host membrane; Host-virus interaction;
KW   Lipoprotein; Membrane; Palmitate; Signal; Transmembrane;
KW   Transmembrane helix; Viral attachment to host cell; Viral envelope protein;
KW   Viral immunoevasion; Viral penetration into host cytoplasm; Virion;
KW   Virus endocytosis by host; Virus entry into host cell.
FT   SIGNAL          1..31
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CHAIN           32..847
FT                   /note="Envelope glycoprotein gp160"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000239479"
FT   CHAIN           32..502
FT                   /note="Surface protein gp120"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000038398"
FT   CHAIN           503..847
FT                   /note="Transmembrane protein gp41"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000038399"
FT   TOPO_DOM        32..675
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   TRANSMEM        676..696
FT                   /note="Helical"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   TOPO_DOM        697..847
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          130..154
FT                   /note="V1"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          155..194
FT                   /note="V2"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          294..327
FT                   /note="V3"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          360..370
FT                   /note="CD4-binding loop"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          381..408
FT                   /note="V4"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          451..462
FT                   /note="V5"
FT   REGION          453..462
FT                   /note="V5"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          503..523
FT                   /note="Fusion peptide"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          565..583
FT                   /note="Immunosuppression"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          653..674
FT                   /note="MPER; binding to GalCer"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          710..736
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COILED          624..658
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   MOTIF           703..706
FT                   /note="YXXL motif; contains endocytosis signal"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   MOTIF           846..847
FT                   /note="Di-leucine internalization motif"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   COMPBIAS        718..736
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   SITE            502..503
FT                   /note="Cleavage; by host furin"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   LIPID           755
FT                   /note="S-palmitoyl cysteine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        87
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        135
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        154
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        186
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        195
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        232
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        239
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        260
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        274
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        293
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        299
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        329
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        336
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        352
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        382
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        388
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        392
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        398
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        401
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        438
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        454
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        602
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        607
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        616
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        628
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        53..73
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        118..203
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        125..194
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        130..155
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        216..245
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        226..237
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        294..328
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        374..435
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        381..408
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        589..595
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
SQ   SEQUENCE   847 AA;  96136 MW;  0A901317FD7FF2AB CRC64;
     MRVKGIRKNY QHLWRGGTLL LGMLMICSAV EKLWVTVYYG VPVWKEATTT LFCASDAKAY
     DTEVHNVWAT HACVPTDPNP QEIVLENVTE NFNMWKNNMV EQMHEDIISL WDQSLKPCVK
     LTPLCVTLHC TNLKNATNTK SSNWKEMDRG EIKNCSFKVT TSIRNKMQKE YALFYKLDVV
     PIDNDNTSYK LINCNTSVIT QACPKVSFEP IPIHYCAPAG FAILKCNDKK FNGSGPCTNV
     STVQCTHGIR PVVSTQLLLN GSLAEEGVVI RSENFTDNAK TIIVQLKESV EINCTRPNNN
     TRKSITIGPG RAFYATGDII GDIRQAHCNI SGEKWNNTLK QIVTKLQAQF GNKTIVFKQS
     SGGDPEIVMH SFNCGGEFFY CNSTQLFNST WNNTIGPNNT NGTITLPCRI KQIINRWQEV
     GKAMYAPPIR GQIRCSSNIT GLLLTRDGGK EISNTTEIFR PGGGDMRDNW RSELYKYKVV
     KIEPLGVAPT KAKRRVVQRE KRAVTLGAMF LGFLGAAGST MGARSLTLTV QARQLLSGIV
     QQQNNLLRAI EAQQHLLQLT VWGIKQLQAR VLAVERYLKD QQLLGIWGCS GKLICTTAVP
     WNASWSNKSL DQIWNNMTWM EWEREIDNYT NLIYTLIEES QNQQEKNEQE LLELDKWASL
     WNWFDISKWL WYIKIFIMIV GGLVGLRIVF TVLSIVNRVR QGYSPLSFQT RFPAPRGPDR
     PEGIEEEGGE RDRDRSSPLV HGLLALIWDD LRSLCLFSYH RLRDLILIAA RIVELLGRRG
     WEALKYWGNL LQYWIQELKN SAVSLFDAIA IAVAEGTDRI IEVAQRIGRA FLHIPRRIRQ
     GFERALL
//
ID   ENV_HV1S2               Reviewed;         848 AA.
AC   Q9WC60;
DT   27-JUN-2006, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1999, sequence version 1.
DT   27-MAR-2024, entry version 118.
DE   RecName: Full=Envelope glycoprotein gp160 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   AltName: Full=Env polyprotein {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Contains:
DE     RecName: Full=Surface protein gp120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=SU {ECO:0000255|HAMAP-Rule:MF_04083};
DE     AltName: Full=Glycoprotein 120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=gp120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Contains:
DE     RecName: Full=Transmembrane protein gp41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=TM {ECO:0000255|HAMAP-Rule:MF_04083};
DE     AltName: Full=Glycoprotein 41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=gp41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Flags: Precursor;
GN   Name=env {ECO:0000255|HAMAP-Rule:MF_04083};
OS   Human immunodeficiency virus type 1 group M subtype J (isolate SE9280)
OS   (HIV-1).
OC   Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC   Ortervirales; Retroviridae; Orthoretrovirinae; Lentivirus;
OC   Human immunodeficiency virus 1.
OX   NCBI_TaxID=388905;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=10052760; DOI=10.1089/088922299311475;
RA   Laukkanen T., Albert J., Liitsola K., Green S.D., Carr J.K., Leitner T.,
RA   McCutchan F.E., Salminen M.O.;
RT   "Virtually full-length sequences of HIV type 1 subtype J reference
RT   strains.";
RL   AIDS Res. Hum. Retroviruses 15:293-297(1999).
RN   [2]
RP   REVIEW.
RX   PubMed=12974773; DOI=10.1034/j.1600-0463.2003.11107803.x;
RA   Geijtenbeek T.B., van Kooyk Y.;
RT   "Pathogens target DC-SIGN to influence their fate DC-SIGN functions as a
RT   pathogen receptor with broad specificity.";
RL   APMIS 111:698-714(2003).
RN   [3]
RP   REVIEW.
RX   PubMed=12873764; DOI=10.1016/s0005-2736(03)00161-5;
RA   Gallo S.A., Finnegan C.M., Viard M., Raviv Y., Dimitrov A., Rawat S.S.,
RA   Puri A., Durell S., Blumenthal R.;
RT   "The HIV Env-mediated fusion reaction.";
RL   Biochim. Biophys. Acta 1614:36-50(2003).
RN   [4]
RP   REVIEW.
RX   PubMed=15719026; DOI=10.1038/sj.cdd.4401584;
RA   Perfettini J.-L., Castedo M., Roumier T., Andreau K., Nardacci R.,
RA   Piacentini M., Kroemer G.;
RT   "Mechanisms of apoptosis induction by the HIV-1 envelope.";
RL   Cell Death Differ. 12:916-923(2005).
RN   [5]
RP   REVIEW.
RX   PubMed=15725757; DOI=10.1089/aid.2005.21.171;
RA   Hartley O., Klasse P.J., Sattentau Q.J., Moore J.P.;
RT   "V3: HIV's switch-hitter.";
RL   AIDS Res. Hum. Retroviruses 21:171-189(2005).
RN   [6]
RP   REVIEW.
RX   PubMed=16114975; DOI=10.2165/00003495-200565130-00002;
RA   Reeves J.D., Piefer A.J.;
RT   "Emerging drug targets for antiretroviral therapy.";
RL   Drugs 65:1747-1766(2005).
RN   [7]
RP   REVIEW.
RX   PubMed=16437164; DOI=10.1038/sj.emboj.7600947;
RA   Lusso P.;
RT   "HIV and the chemokine system: 10 years later.";
RL   EMBO J. 25:447-456(2006).
CC   -!- FUNCTION: [Envelope glycoprotein gp160]: Oligomerizes in the host
CC       endoplasmic reticulum into predominantly trimers. In a second time,
CC       gp160 transits in the host Golgi, where glycosylation is completed. The
CC       precursor is then proteolytically cleaved in the trans-Golgi and
CC       thereby activated by cellular furin or furin-like proteases to produce
CC       gp120 and gp41. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- FUNCTION: [Surface protein gp120]: Attaches the virus to the host
CC       lymphoid cell by binding to the primary receptor CD4. This interaction
CC       induces a structural rearrangement creating a high affinity binding
CC       site for a chemokine coreceptor like CXCR4 and/or CCR5. Acts as a
CC       ligand for CD209/DC-SIGN and CLEC4M/DC-SIGNR, which are respectively
CC       found on dendritic cells (DCs), and on endothelial cells of liver
CC       sinusoids and lymph node sinuses. These interactions allow capture of
CC       viral particles at mucosal surfaces by these cells and subsequent
CC       transmission to permissive cells. HIV subverts the migration properties
CC       of dendritic cells to gain access to CD4+ T-cells in lymph nodes. Virus
CC       transmission to permissive T-cells occurs either in trans (without DCs
CC       infection, through viral capture and transmission), or in cis
CC       (following DCs productive infection, through the usual CD4-gp120
CC       interaction), thereby inducing a robust infection. In trans infection,
CC       bound virions remain infectious over days and it is proposed that they
CC       are not degraded, but protected in non-lysosomal acidic organelles
CC       within the DCs close to the cell membrane thus contributing to the
CC       viral infectious potential during DCs' migration from the periphery to
CC       the lymphoid tissues. On arrival at lymphoid tissues, intact virions
CC       recycle back to DCs' cell surface allowing virus transmission to CD4+
CC       T-cells. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- FUNCTION: [Transmembrane protein gp41]: Acts as a class I viral fusion
CC       protein. Under the current model, the protein has at least 3
CC       conformational states: pre-fusion native state, pre-hairpin
CC       intermediate state, and post-fusion hairpin state. During fusion of
CC       viral and target intracellular membranes, the coiled coil regions
CC       (heptad repeats) assume a trimer-of-hairpins structure, positioning the
CC       fusion peptide in close proximity to the C-terminal region of the
CC       ectodomain. The formation of this structure appears to drive apposition
CC       and subsequent fusion of viral and target cell membranes. Complete
CC       fusion occurs in host cell endosomes and is dynamin-dependent, however
CC       some lipid transfer might occur at the plasma membrane. The virus
CC       undergoes clathrin-dependent internalization long before endosomal
CC       fusion, thus minimizing the surface exposure of conserved viral
CC       epitopes during fusion and reducing the efficacy of inhibitors
CC       targeting these epitopes. Membranes fusion leads to delivery of the
CC       nucleocapsid into the cytoplasm. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBUNIT: [Surface protein gp120]: The mature envelope protein (Env)
CC       consists of a homotrimer of non-covalently associated gp120-gp41
CC       heterodimers. The resulting complex protrudes from the virus surface as
CC       a spike. There seems to be as few as 10 spikes on the average virion.
CC       Interacts with host CD4, CCR5 and CXCR4. Gp120 also interacts with the
CC       C-type lectins CD209/DC-SIGN and CLEC4M/DC-SIGNR (collectively referred
CC       to as DC-SIGN(R)). Gp120 and gp41 interact with GalCer. Gp120 interacts
CC       with host ITGA4/ITGB7 complex; on CD4+ T-cells, this interaction
CC       results in rapid activation of integrin ITGAL/LFA-1, which facilitates
CC       efficient cell-to-cell spreading of HIV-1. Gp120 interacts with cell-
CC       associated heparan sulfate; this interaction increases virus
CC       infectivity on permissive cells and may be involved in infection of
CC       CD4- cells. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBUNIT: [Transmembrane protein gp41]: The mature envelope protein
CC       (Env) consists of a homotrimer of non-covalently associated gp120-gp41
CC       heterodimers. The resulting complex protrudes from the virus surface as
CC       a spike. There seems to be as few as 10 spikes on the average virion.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBCELLULAR LOCATION: [Surface protein gp120]: Virion membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Peripheral membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host cell membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Peripheral membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host endosome membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Note=The surface protein is not
CC       anchored to the viral envelope, but associates with the extravirion
CC       surface through its binding to TM. It is probably concentrated at the
CC       site of budding and incorporated into the virions possibly by contacts
CC       between the cytoplasmic tail of Env and the N-terminus of Gag.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBCELLULAR LOCATION: [Transmembrane protein gp41]: Virion membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host cell membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host endosome membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Note=It is probably concentrated at
CC       the site of budding and incorporated into the virions possibly by
CC       contacts between the cytoplasmic tail of Env and the N-terminus of Gag.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: Some of the most genetically diverse regions of the viral
CC       genome are present in Env. They are called variable regions 1 through 5
CC       (V1 through V5). Coreceptor usage of gp120 is determined mainly by the
CC       primary structure of the third variable region (V3) in the outer domain
CC       of gp120. The sequence of V3 determines which coreceptor, CCR5 and/or
CC       CXCR4 (corresponding to R5/macrophage, X4/T cell and R5X4/T cell and
CC       macrophage tropism), is used to trigger the fusion potential of the Env
CC       complex, and hence which cells the virus can infect. Binding to CCR5
CC       involves a region adjacent in addition to V3. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- DOMAIN: The membrane proximal external region (MPER) present in gp41 is
CC       a tryptophan-rich region recognized by the antibodies 2F5, Z13, and
CC       4E10. MPER seems to play a role in fusion. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- DOMAIN: The 17 amino acids long immunosuppressive region is present in
CC       many retroviral envelope proteins. Synthetic peptides derived from this
CC       relatively conserved sequence inhibit immune function in vitro and in
CC       vivo. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: The YXXL motif is involved in determining the exact site of
CC       viral release at the surface of infected mononuclear cells and promotes
CC       endocytosis. YXXL and di-leucine endocytosis motifs interact directly
CC       or indirectly with the clathrin adapter complexes, opperate
CC       independently, and their activities are not additive.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: The CD4-binding region is targeted by the antibody b12.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- PTM: Highly glycosylated by host. The high number of glycan on the
CC       protein is reffered to as 'glycan shield' because it contributes to
CC       hide protein sequence from adaptive immune system. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- PTM: Palmitoylation of the transmembrane protein and of Env polyprotein
CC       (prior to its proteolytic cleavage) is essential for their association
CC       with host cell membrane lipid rafts. Palmitoylation is therefore
CC       required for envelope trafficking to classical lipid rafts, but not for
CC       viral replication. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- PTM: Specific enzymatic cleavages in vivo yield mature proteins.
CC       Envelope glycoproteins are synthesized as an inactive precursor that is
CC       heavily N-glycosylated and processed likely by host cell furin in the
CC       Golgi to yield the mature SU and TM proteins. The cleavage site between
CC       SU and TM requires the minimal sequence [KR]-X-[KR]-R. About 2 of the 9
CC       disulfide bonds of gp41 are reduced by P4HB/PDI, following binding to
CC       CD4 receptor. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- MISCELLANEOUS: Inhibitors targeting HIV-1 viral envelope proteins are
CC       used as antiretroviral drugs. Attachment of virions to the cell surface
CC       via non-specific interactions and CD4 binding can be blocked by
CC       inhibitors that include cyanovirin-N, cyclotriazadisulfonamide analogs,
CC       PRO 2000, TNX 355 and PRO 542. In addition, BMS 806 can block CD4-
CC       induced conformational changes. Env interactions with the coreceptor
CC       molecules can be targeted by CCR5 antagonists including SCH-D,
CC       maraviroc (UK 427857) and aplaviroc (GW 873140), and the CXCR4
CC       antagonist AMD 070. Fusion of viral and cellular membranes can be
CC       inhibited by peptides such as enfuvirtide and tifuvirtide (T 1249).
CC       Resistance to inhibitors associated with mutations in Env are observed.
CC       Most of the time, single mutations confer only a modest reduction in
CC       drug susceptibility. Combination of several mutations is usually
CC       required to develop a high-level drug resistance. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- MISCELLANEOUS: HIV-1 lineages are divided in three main groups, M (for
CC       Major), O (for Outlier), and N (for New, or Non-M, Non-O). The vast
CC       majority of strains found worldwide belong to the group M. Group O
CC       seems to be endemic to and largely confined to Cameroon and neighboring
CC       countries in West Central Africa, where these viruses represent a small
CC       minority of HIV-1 strains. The group N is represented by a limited
CC       number of isolates from Cameroonian persons. The group M is further
CC       subdivided in 9 clades or subtypes (A to D, F to H, J and K).
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SIMILARITY: Belongs to the HIV-1 env protein family.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- WEB RESOURCE: Name=hivdb; Note=HIV drug resistance database;
CC       URL="https://hivdb.stanford.edu";
CC   -!- WEB RESOURCE: Name=HIV drug resistance mutations;
CC       URL="https://www.iasusa.org/content/hiv-drug-resistance-mutations";
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DR   EMBL; AF082394; AAD17761.1; -; Genomic_DNA.
DR   GlyCosmos; Q9WC60; 29 sites, No reported glycans.
DR   GO; GO:0044175; C:host cell endosome membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0016020; C:membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:0019031; C:viral envelope; IEA:UniProtKB-KW.
DR   GO; GO:0055036; C:virion membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005198; F:structural molecule activity; IEA:UniProtKB-UniRule.
DR   GO; GO:0075512; P:clathrin-dependent endocytosis of virus by host cell; IEA:UniProtKB-UniRule.
DR   GO; GO:0039654; P:fusion of virus membrane with host endosome membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:0019064; P:fusion of virus membrane with host plasma membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:1903905; P:positive regulation of establishment of T cell polarity; IEA:UniProtKB-UniRule.
DR   GO; GO:1903908; P:positive regulation of plasma membrane raft polarization; IEA:UniProtKB-UniRule.
DR   GO; GO:1903911; P:positive regulation of receptor clustering; IEA:UniProtKB-UniRule.
DR   GO; GO:0019082; P:viral protein processing; IEA:UniProtKB-UniRule.
DR   GO; GO:0019062; P:virion attachment to host cell; IEA:UniProtKB-UniRule.
DR   GO; GO:0019049; P:virus-mediated perturbation of host defense response; IEA:UniProtKB-UniRule.
DR   CDD; cd09909; HIV-1-like_HR1-HR2; 1.
DR   Gene3D; 1.10.287.210; -; 1.
DR   Gene3D; 2.170.40.20; Human immunodeficiency virus 1, Gp160, envelope glycoprotein; 2.
DR   Gene3D; 1.20.5.490; Single helix bin; 1.
DR   HAMAP; MF_04083; HIV_ENV; 1.
DR   InterPro; IPR036377; Gp120_core_sf.
DR   InterPro; IPR037527; Gp160.
DR   InterPro; IPR000328; GP41-like.
DR   InterPro; IPR000777; HIV1_Gp120.
DR   Pfam; PF00516; GP120; 2.
DR   Pfam; PF00517; GP41; 1.
DR   SUPFAM; SSF56502; gp120 core; 2.
DR   SUPFAM; SSF58069; Virus ectodomain; 1.
PE   3: Inferred from homology;
KW   AIDS; Apoptosis; Clathrin-mediated endocytosis of virus by host;
KW   Cleavage on pair of basic residues; Coiled coil; Disulfide bond;
KW   Fusion of virus membrane with host endosomal membrane;
KW   Fusion of virus membrane with host membrane; Glycoprotein;
KW   Host cell membrane; Host endosome; Host membrane; Host-virus interaction;
KW   Lipoprotein; Membrane; Palmitate; Signal; Transmembrane;
KW   Transmembrane helix; Viral attachment to host cell; Viral envelope protein;
KW   Viral immunoevasion; Viral penetration into host cytoplasm; Virion;
KW   Virus endocytosis by host; Virus entry into host cell.
FT   SIGNAL          1..28
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CHAIN           29..848
FT                   /note="Envelope glycoprotein gp160"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000244687"
FT   CHAIN           29..503
FT                   /note="Surface protein gp120"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000244688"
FT   CHAIN           504..848
FT                   /note="Transmembrane protein gp41"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000244689"
FT   TOPO_DOM        29..676
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   TRANSMEM        677..697
FT                   /note="Helical"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   TOPO_DOM        698..848
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          127..150
FT                   /note="V1"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          151..190
FT                   /note="V2"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          290..323
FT                   /note="V3"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          355..365
FT                   /note="CD4-binding loop"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          376..406
FT                   /note="V4"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          444..465
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          451..463
FT                   /note="V5"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          504..524
FT                   /note="Fusion peptide"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          566..584
FT                   /note="Immunosuppression"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          654..675
FT                   /note="MPER; binding to GalCer"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   COILED          625..659
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   MOTIF           704..707
FT                   /note="YXXL motif; contains endocytosis signal"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   MOTIF           847..848
FT                   /note="Di-leucine internalization motif"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   SITE            503..504
FT                   /note="Cleavage; by host furin"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   LIPID           756
FT                   /note="S-palmitoyl cysteine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        84
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        126
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        129
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        135
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        139
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        150
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        154
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        191
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        228
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        235
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        256
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        270
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        283
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        295
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        325
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        347
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        351
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        377
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        383
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        395
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        430
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        436
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        451
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        455
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        603
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        608
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        617
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        629
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        666
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        50..70
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        115..199
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        122..190
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        127..151
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        212..241
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        222..233
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        290..324
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        369..433
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        376..406
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        590..596
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
SQ   SEQUENCE   848 AA;  95488 MW;  1FF5F2385E98E36E CRC64;
     METQKNWQTL WRGGLMIFGM LMICKAKEDL WVTVYYGVPV WKDAKTTLFC ASDAKAYSTE
     KHNVWATHAC VPTDPSPQEM NLPNVTENFN MWKNDMVDQM QEDIISVWDE SLKPCVKITP
     LCVTLNCSNI TSNSNTTSNS SVSSPDIMTN CSFNITTEIR NKRKQEYALF YRQDVVPIDS
     NNKNYILINC NTSVIKQACP KVSFQPIPIH YCAPAGFAIL KCNDKNFNGT GSCKNVSTVQ
     CTHGIKPVVS TQLLLNGSIA EGDIIIRSEN ISDNAKNIIV QLNKTVEIVC YRPNNNTRKG
     IHMGPGQVLY ATGEIIGNIR ETHCNISERD WSNTLRRVAT KLREHFNKTI NFTSPSGGDI
     EIVTHSFNCG GEFLYCNTSK LFNSSWDKNS IEATNDTSXA TITIPCKIKQ IVRMWQRTGQ
     AIYAPPIAGN ITCTSNITGL LLTRDGGNRG NGSENGTETF RPTGGNMKDN WRSELYKYKV
     VEIEPLGVAP TKAKRRVVER EKRAVGIGAV FLGFLGTAGS TMGAASITLT VQVRQLLSGI
     VQQQSNLLKA IEAQQHLLKL TVWGIKQLQA RVLAVERYLK DQQLLGIWGC SGKLICTTNV
     PWNASWSNKS YEDIWENMTW IQWEREINNY TGIIYSLIEE AQNQQENNEK DLLALDKWTN
     LWNWFNISNW LWYIKIFIMI IGGLIGLRII FAVLAIVNRV RQGYSPLSFQ TLIPNPTEAD
     RPGGIEEGGG EQGRTRSIRL VNGFLALAWD DLRNLCLFSY HRLRDFVLIA ARTVGTLGLR
     GWEILKYLVN LVWYWGQELK NSAISLLNTT AIAVAEGTDR IIEIAQRAFR AILHIPRRIR
     QGLERALL
//
ID   ENV_HV1S3               Reviewed;         852 AA.
AC   P19549;
DT   01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
DT   01-FEB-1991, sequence version 1.
DT   27-MAR-2024, entry version 150.
DE   RecName: Full=Envelope glycoprotein gp160 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   AltName: Full=Env polyprotein {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Contains:
DE     RecName: Full=Surface protein gp120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=SU {ECO:0000255|HAMAP-Rule:MF_04083};
DE     AltName: Full=Glycoprotein 120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=gp120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Contains:
DE     RecName: Full=Transmembrane protein gp41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=TM {ECO:0000255|HAMAP-Rule:MF_04083};
DE     AltName: Full=Glycoprotein 41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=gp41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Flags: Precursor;
GN   Name=env {ECO:0000255|HAMAP-Rule:MF_04083};
OS   Human immunodeficiency virus type 1 group M subtype B (isolate SF33)
OS   (HIV-1).
OC   Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC   Ortervirales; Retroviridae; Orthoretrovirinae; Lentivirus;
OC   Human immunodeficiency virus 1.
OX   NCBI_TaxID=11690;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=2370688; DOI=10.1128/jvi.64.8.4016-4020.1990;
RA   York-Higgins D., Cheng-Mayer C., Bauer D., Levy J.A., Dina D.;
RT   "Human immunodeficiency virus type 1 cellular host range, replication, and
RT   cytopathicity are linked to the envelope region of the viral genome.";
RL   J. Virol. 64:4016-4020(1990).
RN   [2]
RP   REVIEW.
RX   PubMed=12974773; DOI=10.1034/j.1600-0463.2003.11107803.x;
RA   Geijtenbeek T.B., van Kooyk Y.;
RT   "Pathogens target DC-SIGN to influence their fate DC-SIGN functions as a
RT   pathogen receptor with broad specificity.";
RL   APMIS 111:698-714(2003).
RN   [3]
RP   REVIEW.
RX   PubMed=12873764; DOI=10.1016/s0005-2736(03)00161-5;
RA   Gallo S.A., Finnegan C.M., Viard M., Raviv Y., Dimitrov A., Rawat S.S.,
RA   Puri A., Durell S., Blumenthal R.;
RT   "The HIV Env-mediated fusion reaction.";
RL   Biochim. Biophys. Acta 1614:36-50(2003).
RN   [4]
RP   REVIEW.
RX   PubMed=15719026; DOI=10.1038/sj.cdd.4401584;
RA   Perfettini J.-L., Castedo M., Roumier T., Andreau K., Nardacci R.,
RA   Piacentini M., Kroemer G.;
RT   "Mechanisms of apoptosis induction by the HIV-1 envelope.";
RL   Cell Death Differ. 12:916-923(2005).
RN   [5]
RP   REVIEW.
RX   PubMed=15725757; DOI=10.1089/aid.2005.21.171;
RA   Hartley O., Klasse P.J., Sattentau Q.J., Moore J.P.;
RT   "V3: HIV's switch-hitter.";
RL   AIDS Res. Hum. Retroviruses 21:171-189(2005).
RN   [6]
RP   REVIEW.
RX   PubMed=16114975; DOI=10.2165/00003495-200565130-00002;
RA   Reeves J.D., Piefer A.J.;
RT   "Emerging drug targets for antiretroviral therapy.";
RL   Drugs 65:1747-1766(2005).
RN   [7]
RP   REVIEW.
RX   PubMed=16437164; DOI=10.1038/sj.emboj.7600947;
RA   Lusso P.;
RT   "HIV and the chemokine system: 10 years later.";
RL   EMBO J. 25:447-456(2006).
CC   -!- FUNCTION: [Envelope glycoprotein gp160]: Oligomerizes in the host
CC       endoplasmic reticulum into predominantly trimers. In a second time,
CC       gp160 transits in the host Golgi, where glycosylation is completed. The
CC       precursor is then proteolytically cleaved in the trans-Golgi and
CC       thereby activated by cellular furin or furin-like proteases to produce
CC       gp120 and gp41. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- FUNCTION: [Surface protein gp120]: Attaches the virus to the host
CC       lymphoid cell by binding to the primary receptor CD4. This interaction
CC       induces a structural rearrangement creating a high affinity binding
CC       site for a chemokine coreceptor like CXCR4 and/or CCR5. Acts as a
CC       ligand for CD209/DC-SIGN and CLEC4M/DC-SIGNR, which are respectively
CC       found on dendritic cells (DCs), and on endothelial cells of liver
CC       sinusoids and lymph node sinuses. These interactions allow capture of
CC       viral particles at mucosal surfaces by these cells and subsequent
CC       transmission to permissive cells. HIV subverts the migration properties
CC       of dendritic cells to gain access to CD4+ T-cells in lymph nodes. Virus
CC       transmission to permissive T-cells occurs either in trans (without DCs
CC       infection, through viral capture and transmission), or in cis
CC       (following DCs productive infection, through the usual CD4-gp120
CC       interaction), thereby inducing a robust infection. In trans infection,
CC       bound virions remain infectious over days and it is proposed that they
CC       are not degraded, but protected in non-lysosomal acidic organelles
CC       within the DCs close to the cell membrane thus contributing to the
CC       viral infectious potential during DCs' migration from the periphery to
CC       the lymphoid tissues. On arrival at lymphoid tissues, intact virions
CC       recycle back to DCs' cell surface allowing virus transmission to CD4+
CC       T-cells. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- FUNCTION: [Transmembrane protein gp41]: Acts as a class I viral fusion
CC       protein. Under the current model, the protein has at least 3
CC       conformational states: pre-fusion native state, pre-hairpin
CC       intermediate state, and post-fusion hairpin state. During fusion of
CC       viral and target intracellular membranes, the coiled coil regions
CC       (heptad repeats) assume a trimer-of-hairpins structure, positioning the
CC       fusion peptide in close proximity to the C-terminal region of the
CC       ectodomain. The formation of this structure appears to drive apposition
CC       and subsequent fusion of viral and target cell membranes. Complete
CC       fusion occurs in host cell endosomes and is dynamin-dependent, however
CC       some lipid transfer might occur at the plasma membrane. The virus
CC       undergoes clathrin-dependent internalization long before endosomal
CC       fusion, thus minimizing the surface exposure of conserved viral
CC       epitopes during fusion and reducing the efficacy of inhibitors
CC       targeting these epitopes. Membranes fusion leads to delivery of the
CC       nucleocapsid into the cytoplasm. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBUNIT: [Surface protein gp120]: The mature envelope protein (Env)
CC       consists of a homotrimer of non-covalently associated gp120-gp41
CC       heterodimers. The resulting complex protrudes from the virus surface as
CC       a spike. There seems to be as few as 10 spikes on the average virion.
CC       Interacts with host CD4, CCR5 and CXCR4. Gp120 also interacts with the
CC       C-type lectins CD209/DC-SIGN and CLEC4M/DC-SIGNR (collectively referred
CC       to as DC-SIGN(R)). Gp120 and gp41 interact with GalCer. Gp120 interacts
CC       with host ITGA4/ITGB7 complex; on CD4+ T-cells, this interaction
CC       results in rapid activation of integrin ITGAL/LFA-1, which facilitates
CC       efficient cell-to-cell spreading of HIV-1. Gp120 interacts with cell-
CC       associated heparan sulfate; this interaction increases virus
CC       infectivity on permissive cells and may be involved in infection of
CC       CD4- cells. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBUNIT: [Transmembrane protein gp41]: The mature envelope protein
CC       (Env) consists of a homotrimer of non-covalently associated gp120-gp41
CC       heterodimers. The resulting complex protrudes from the virus surface as
CC       a spike. There seems to be as few as 10 spikes on the average virion.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBCELLULAR LOCATION: [Surface protein gp120]: Virion membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Peripheral membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host cell membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Peripheral membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host endosome membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Note=The surface protein is not
CC       anchored to the viral envelope, but associates with the extravirion
CC       surface through its binding to TM. It is probably concentrated at the
CC       site of budding and incorporated into the virions possibly by contacts
CC       between the cytoplasmic tail of Env and the N-terminus of Gag.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBCELLULAR LOCATION: [Transmembrane protein gp41]: Virion membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host cell membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host endosome membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Note=It is probably concentrated at
CC       the site of budding and incorporated into the virions possibly by
CC       contacts between the cytoplasmic tail of Env and the N-terminus of Gag.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: Some of the most genetically diverse regions of the viral
CC       genome are present in Env. They are called variable regions 1 through 5
CC       (V1 through V5). Coreceptor usage of gp120 is determined mainly by the
CC       primary structure of the third variable region (V3) in the outer domain
CC       of gp120. The sequence of V3 determines which coreceptor, CCR5 and/or
CC       CXCR4 (corresponding to R5/macrophage, X4/T cell and R5X4/T cell and
CC       macrophage tropism), is used to trigger the fusion potential of the Env
CC       complex, and hence which cells the virus can infect. Binding to CCR5
CC       involves a region adjacent in addition to V3. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- DOMAIN: The membrane proximal external region (MPER) present in gp41 is
CC       a tryptophan-rich region recognized by the antibodies 2F5, Z13, and
CC       4E10. MPER seems to play a role in fusion. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- DOMAIN: The 17 amino acids long immunosuppressive region is present in
CC       many retroviral envelope proteins. Synthetic peptides derived from this
CC       relatively conserved sequence inhibit immune function in vitro and in
CC       vivo. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: The YXXL motif is involved in determining the exact site of
CC       viral release at the surface of infected mononuclear cells and promotes
CC       endocytosis. YXXL and di-leucine endocytosis motifs interact directly
CC       or indirectly with the clathrin adapter complexes, opperate
CC       independently, and their activities are not additive.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: The CD4-binding region is targeted by the antibody b12.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- PTM: Highly glycosylated by host. The high number of glycan on the
CC       protein is reffered to as 'glycan shield' because it contributes to
CC       hide protein sequence from adaptive immune system. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- PTM: Palmitoylation of the transmembrane protein and of Env polyprotein
CC       (prior to its proteolytic cleavage) is essential for their association
CC       with host cell membrane lipid rafts. Palmitoylation is therefore
CC       required for envelope trafficking to classical lipid rafts, but not for
CC       viral replication. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- PTM: Specific enzymatic cleavages in vivo yield mature proteins.
CC       Envelope glycoproteins are synthesized as an inactive precursor that is
CC       heavily N-glycosylated and processed likely by host cell furin in the
CC       Golgi to yield the mature SU and TM proteins. The cleavage site between
CC       SU and TM requires the minimal sequence [KR]-X-[KR]-R. About 2 of the 9
CC       disulfide bonds of gp41 are reduced by P4HB/PDI, following binding to
CC       CD4 receptor. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- MISCELLANEOUS: Inhibitors targeting HIV-1 viral envelope proteins are
CC       used as antiretroviral drugs. Attachment of virions to the cell surface
CC       via non-specific interactions and CD4 binding can be blocked by
CC       inhibitors that include cyanovirin-N, cyclotriazadisulfonamide analogs,
CC       PRO 2000, TNX 355 and PRO 542. In addition, BMS 806 can block CD4-
CC       induced conformational changes. Env interactions with the coreceptor
CC       molecules can be targeted by CCR5 antagonists including SCH-D,
CC       maraviroc (UK 427857) and aplaviroc (GW 873140), and the CXCR4
CC       antagonist AMD 070. Fusion of viral and cellular membranes can be
CC       inhibited by peptides such as enfuvirtide and tifuvirtide (T 1249).
CC       Resistance to inhibitors associated with mutations in Env are observed.
CC       Most of the time, single mutations confer only a modest reduction in
CC       drug susceptibility. Combination of several mutations is usually
CC       required to develop a high-level drug resistance. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- MISCELLANEOUS: HIV-1 lineages are divided in three main groups, M (for
CC       Major), O (for Outlier), and N (for New, or Non-M, Non-O). The vast
CC       majority of strains found worldwide belong to the group M. Group O
CC       seems to be endemic to and largely confined to Cameroon and neighboring
CC       countries in West Central Africa, where these viruses represent a small
CC       minority of HIV-1 strains. The group N is represented by a limited
CC       number of isolates from Cameroonian persons. The group M is further
CC       subdivided in 9 clades or subtypes (A to D, F to H, J and K).
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SIMILARITY: Belongs to the HIV-1 env protein family.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- WEB RESOURCE: Name=hivdb; Note=HIV drug resistance database;
CC       URL="https://hivdb.stanford.edu";
CC   -!- WEB RESOURCE: Name=HIV drug resistance mutations;
CC       URL="https://www.iasusa.org/content/hiv-drug-resistance-mutations";
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DR   EMBL; AY352275; AAQ17031.1; -; Genomic_DNA.
DR   PDB; 1MEQ; NMR; -; A=484-506.
DR   PDBsum; 1MEQ; -.
DR   SMR; P19549; -.
DR   GlyCosmos; P19549; 28 sites, No reported glycans.
DR   Reactome; R-HSA-5621480; Dectin-2 family.
DR   EvolutionaryTrace; P19549; -.
DR   GO; GO:0044175; C:host cell endosome membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0016020; C:membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:0019031; C:viral envelope; IEA:UniProtKB-KW.
DR   GO; GO:0055036; C:virion membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005198; F:structural molecule activity; IEA:UniProtKB-UniRule.
DR   GO; GO:0075512; P:clathrin-dependent endocytosis of virus by host cell; IEA:UniProtKB-UniRule.
DR   GO; GO:0039654; P:fusion of virus membrane with host endosome membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:0019064; P:fusion of virus membrane with host plasma membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:1903905; P:positive regulation of establishment of T cell polarity; IEA:UniProtKB-UniRule.
DR   GO; GO:1903908; P:positive regulation of plasma membrane raft polarization; IEA:UniProtKB-UniRule.
DR   GO; GO:1903911; P:positive regulation of receptor clustering; IEA:UniProtKB-UniRule.
DR   GO; GO:0019082; P:viral protein processing; IEA:UniProtKB-UniRule.
DR   GO; GO:0019062; P:virion attachment to host cell; IEA:UniProtKB-UniRule.
DR   GO; GO:0019049; P:virus-mediated perturbation of host defense response; IEA:UniProtKB-UniRule.
DR   CDD; cd09909; HIV-1-like_HR1-HR2; 1.
DR   Gene3D; 1.10.287.210; -; 1.
DR   Gene3D; 2.170.40.20; Human immunodeficiency virus 1, Gp160, envelope glycoprotein; 2.
DR   Gene3D; 1.20.5.490; Single helix bin; 1.
DR   HAMAP; MF_04083; HIV_ENV; 1.
DR   InterPro; IPR036377; Gp120_core_sf.
DR   InterPro; IPR037527; Gp160.
DR   InterPro; IPR000328; GP41-like.
DR   InterPro; IPR000777; HIV1_Gp120.
DR   Pfam; PF00516; GP120; 1.
DR   Pfam; PF00517; GP41; 1.
DR   SUPFAM; SSF56502; gp120 core; 2.
DR   SUPFAM; SSF58069; Virus ectodomain; 1.
PE   1: Evidence at protein level;
KW   3D-structure; AIDS; Apoptosis;
KW   Clathrin-mediated endocytosis of virus by host;
KW   Cleavage on pair of basic residues; Coiled coil; Disulfide bond;
KW   Fusion of virus membrane with host endosomal membrane;
KW   Fusion of virus membrane with host membrane; Glycoprotein;
KW   Host cell membrane; Host endosome; Host membrane; Host-virus interaction;
KW   Lipoprotein; Membrane; Palmitate; Signal; Transmembrane;
KW   Transmembrane helix; Viral attachment to host cell; Viral envelope protein;
KW   Viral immunoevasion; Viral penetration into host cytoplasm; Virion;
KW   Virus endocytosis by host; Virus entry into host cell.
FT   SIGNAL          1..31
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CHAIN           32..852
FT                   /note="Envelope glycoprotein gp160"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000239478"
FT   CHAIN           32..506
FT                   /note="Surface protein gp120"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000038396"
FT   CHAIN           507..852
FT                   /note="Transmembrane protein gp41"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000038397"
FT   TOPO_DOM        32..680
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   TRANSMEM        681..701
FT                   /note="Helical"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   TOPO_DOM        702..852
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          130..155
FT                   /note="V1"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          156..197
FT                   /note="V2"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          297..330
FT                   /note="V3"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          363..373
FT                   /note="CD4-binding loop"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          384..412
FT                   /note="V4"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          455..466
FT                   /note="V5"
FT   REGION          457..466
FT                   /note="V5"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          507..528
FT                   /note="Fusion peptide"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          570..588
FT                   /note="Immunosuppression"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          658..679
FT                   /note="MPER; binding to GalCer"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          717..739
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COILED          629..663
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   MOTIF           708..711
FT                   /note="YXXL motif; contains endocytosis signal"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   MOTIF           851..852
FT                   /note="Di-leucine internalization motif"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   COMPBIAS        724..739
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   SITE            506..507
FT                   /note="Cleavage; by host furin"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   LIPID           760
FT                   /note="S-palmitoyl cysteine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        87
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        129
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        136
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        141
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        142
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        155
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        159
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        189
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        198
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        242
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        263
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        277
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        290
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        296
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        332
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        339
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        355
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        385
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        391
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        397
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        401
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        405
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        442
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        457
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        607
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        612
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        621
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        633
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        53..73
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        118..206
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        125..197
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        130..156
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        219..248
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        229..240
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        297..331
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        377..439
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        384..412
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        594..600
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   TURN            488..490
FT                   /evidence="ECO:0007829|PDB:1MEQ"
FT   HELIX           494..504
FT                   /evidence="ECO:0007829|PDB:1MEQ"
SQ   SEQUENCE   852 AA;  96663 MW;  EE7BBF8D23C9910D CRC64;
     MRARETRKNY QCLWRWGTML LGMLMICSAA ENLWVTVYYG VPVWKDATTT LFCASDAKAY
     DTEVHNVWAT HACVPTDPNP QEVVLGNVTE NFNMWKNNMV DQMHEDIVSL WDQSLKPCVK
     LTPLCVTLNC TDYLGNATNT NNSSGGTVEK EEIKNCSFNI TTGIRDKVQK AYAYFYKLDV
     VPIDDDNTNT SYRLIHCNSS VITQTCPKVS FEPIPIHYCA PAGFAILKCN NKKFSGKGQC
     TNVSTVQCTH GIKPVVSTQL LLNGSLAEEE VVIRSDNFTN NAKTILVQLN VSVEINCTRP
     NNNRRRRITS GPGKVLYTTG EIIGDIRKAY CNISRAKWNK TLEQVATKLR EQFGNKTIVF
     KQSSGGDPEI VMHSFNCRGE FFYCNTTKLF NSTWNENSTW NATGNDTITL PCRIKQIINM
     WQEVGKAMYA PPIEGQIRCS SNITGLLLTR DGGGDKNSTT EIFRPAGGNM KDNWRSELYK
     YKVVKIEPLG VAPTKAKRRV VQREKRAVGV IGAMFLGFLG AAGSTMGAAS ITLTVQARKL
     LSGIVQQQNN LLRAIEAQQH LLQLTVWGIK QLQARVLAVE RYLRDQQLLG IWGCSGKLIC
     TTTVPWNTSW SNKSLDKIWN NMTWMEWERE IDNYTSLIYT LLEESQNQQE KNEQELLELD
     KWASLWNWFS ITNWLWYIRI FIMIVGGLIG LRIIFAVLSI VNRVRQGYSP LSFQTLIPAQ
     RGPDRPEGIE EGGGERDRDR STRLVNGFLA LFWDDLRSLC LFSYHRLTDL LLIVARIVEL
     LGRRGWEVLK YWWNLLLYWS QELKNSAVSL LNATAIAVAE GTDRVIEVVQ RVGRAILHIP
     TRIRQGFERA LL
//
ID   ENV_HV1S9               Reviewed;         850 AA.
AC   Q9WC69;
DT   27-JUN-2006, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1999, sequence version 1.
DT   27-MAR-2024, entry version 118.
DE   RecName: Full=Envelope glycoprotein gp160 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   AltName: Full=Env polyprotein {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Contains:
DE     RecName: Full=Surface protein gp120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=SU {ECO:0000255|HAMAP-Rule:MF_04083};
DE     AltName: Full=Glycoprotein 120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=gp120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Contains:
DE     RecName: Full=Transmembrane protein gp41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=TM {ECO:0000255|HAMAP-Rule:MF_04083};
DE     AltName: Full=Glycoprotein 41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=gp41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Flags: Precursor;
GN   Name=env {ECO:0000255|HAMAP-Rule:MF_04083};
OS   Human immunodeficiency virus type 1 group M subtype J (isolate SE9173)
OS   (HIV-1).
OC   Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC   Ortervirales; Retroviridae; Orthoretrovirinae; Lentivirus;
OC   Human immunodeficiency virus 1.
OX   NCBI_TaxID=388904;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=10052760; DOI=10.1089/088922299311475;
RA   Laukkanen T., Albert J., Liitsola K., Green S.D., Carr J.K., Leitner T.,
RA   McCutchan F.E., Salminen M.O.;
RT   "Virtually full-length sequences of HIV type 1 subtype J reference
RT   strains.";
RL   AIDS Res. Hum. Retroviruses 15:293-297(1999).
RN   [2]
RP   REVIEW.
RX   PubMed=12974773; DOI=10.1034/j.1600-0463.2003.11107803.x;
RA   Geijtenbeek T.B., van Kooyk Y.;
RT   "Pathogens target DC-SIGN to influence their fate DC-SIGN functions as a
RT   pathogen receptor with broad specificity.";
RL   APMIS 111:698-714(2003).
RN   [3]
RP   REVIEW.
RX   PubMed=12873764; DOI=10.1016/s0005-2736(03)00161-5;
RA   Gallo S.A., Finnegan C.M., Viard M., Raviv Y., Dimitrov A., Rawat S.S.,
RA   Puri A., Durell S., Blumenthal R.;
RT   "The HIV Env-mediated fusion reaction.";
RL   Biochim. Biophys. Acta 1614:36-50(2003).
RN   [4]
RP   REVIEW.
RX   PubMed=15719026; DOI=10.1038/sj.cdd.4401584;
RA   Perfettini J.-L., Castedo M., Roumier T., Andreau K., Nardacci R.,
RA   Piacentini M., Kroemer G.;
RT   "Mechanisms of apoptosis induction by the HIV-1 envelope.";
RL   Cell Death Differ. 12:916-923(2005).
RN   [5]
RP   REVIEW.
RX   PubMed=15725757; DOI=10.1089/aid.2005.21.171;
RA   Hartley O., Klasse P.J., Sattentau Q.J., Moore J.P.;
RT   "V3: HIV's switch-hitter.";
RL   AIDS Res. Hum. Retroviruses 21:171-189(2005).
RN   [6]
RP   REVIEW.
RX   PubMed=16114975; DOI=10.2165/00003495-200565130-00002;
RA   Reeves J.D., Piefer A.J.;
RT   "Emerging drug targets for antiretroviral therapy.";
RL   Drugs 65:1747-1766(2005).
RN   [7]
RP   REVIEW.
RX   PubMed=16437164; DOI=10.1038/sj.emboj.7600947;
RA   Lusso P.;
RT   "HIV and the chemokine system: 10 years later.";
RL   EMBO J. 25:447-456(2006).
CC   -!- FUNCTION: [Envelope glycoprotein gp160]: Oligomerizes in the host
CC       endoplasmic reticulum into predominantly trimers. In a second time,
CC       gp160 transits in the host Golgi, where glycosylation is completed. The
CC       precursor is then proteolytically cleaved in the trans-Golgi and
CC       thereby activated by cellular furin or furin-like proteases to produce
CC       gp120 and gp41. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- FUNCTION: [Surface protein gp120]: Attaches the virus to the host
CC       lymphoid cell by binding to the primary receptor CD4. This interaction
CC       induces a structural rearrangement creating a high affinity binding
CC       site for a chemokine coreceptor like CXCR4 and/or CCR5. Acts as a
CC       ligand for CD209/DC-SIGN and CLEC4M/DC-SIGNR, which are respectively
CC       found on dendritic cells (DCs), and on endothelial cells of liver
CC       sinusoids and lymph node sinuses. These interactions allow capture of
CC       viral particles at mucosal surfaces by these cells and subsequent
CC       transmission to permissive cells. HIV subverts the migration properties
CC       of dendritic cells to gain access to CD4+ T-cells in lymph nodes. Virus
CC       transmission to permissive T-cells occurs either in trans (without DCs
CC       infection, through viral capture and transmission), or in cis
CC       (following DCs productive infection, through the usual CD4-gp120
CC       interaction), thereby inducing a robust infection. In trans infection,
CC       bound virions remain infectious over days and it is proposed that they
CC       are not degraded, but protected in non-lysosomal acidic organelles
CC       within the DCs close to the cell membrane thus contributing to the
CC       viral infectious potential during DCs' migration from the periphery to
CC       the lymphoid tissues. On arrival at lymphoid tissues, intact virions
CC       recycle back to DCs' cell surface allowing virus transmission to CD4+
CC       T-cells. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- FUNCTION: [Transmembrane protein gp41]: Acts as a class I viral fusion
CC       protein. Under the current model, the protein has at least 3
CC       conformational states: pre-fusion native state, pre-hairpin
CC       intermediate state, and post-fusion hairpin state. During fusion of
CC       viral and target intracellular membranes, the coiled coil regions
CC       (heptad repeats) assume a trimer-of-hairpins structure, positioning the
CC       fusion peptide in close proximity to the C-terminal region of the
CC       ectodomain. The formation of this structure appears to drive apposition
CC       and subsequent fusion of viral and target cell membranes. Complete
CC       fusion occurs in host cell endosomes and is dynamin-dependent, however
CC       some lipid transfer might occur at the plasma membrane. The virus
CC       undergoes clathrin-dependent internalization long before endosomal
CC       fusion, thus minimizing the surface exposure of conserved viral
CC       epitopes during fusion and reducing the efficacy of inhibitors
CC       targeting these epitopes. Membranes fusion leads to delivery of the
CC       nucleocapsid into the cytoplasm. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBUNIT: [Surface protein gp120]: The mature envelope protein (Env)
CC       consists of a homotrimer of non-covalently associated gp120-gp41
CC       heterodimers. The resulting complex protrudes from the virus surface as
CC       a spike. There seems to be as few as 10 spikes on the average virion.
CC       Interacts with host CD4, CCR5 and CXCR4. Gp120 also interacts with the
CC       C-type lectins CD209/DC-SIGN and CLEC4M/DC-SIGNR (collectively referred
CC       to as DC-SIGN(R)). Gp120 and gp41 interact with GalCer. Gp120 interacts
CC       with host ITGA4/ITGB7 complex; on CD4+ T-cells, this interaction
CC       results in rapid activation of integrin ITGAL/LFA-1, which facilitates
CC       efficient cell-to-cell spreading of HIV-1. Gp120 interacts with cell-
CC       associated heparan sulfate; this interaction increases virus
CC       infectivity on permissive cells and may be involved in infection of
CC       CD4- cells. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBUNIT: [Transmembrane protein gp41]: The mature envelope protein
CC       (Env) consists of a homotrimer of non-covalently associated gp120-gp41
CC       heterodimers. The resulting complex protrudes from the virus surface as
CC       a spike. There seems to be as few as 10 spikes on the average virion.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBCELLULAR LOCATION: [Surface protein gp120]: Virion membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Peripheral membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host cell membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Peripheral membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host endosome membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Note=The surface protein is not
CC       anchored to the viral envelope, but associates with the extravirion
CC       surface through its binding to TM. It is probably concentrated at the
CC       site of budding and incorporated into the virions possibly by contacts
CC       between the cytoplasmic tail of Env and the N-terminus of Gag.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBCELLULAR LOCATION: [Transmembrane protein gp41]: Virion membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host cell membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host endosome membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Note=It is probably concentrated at
CC       the site of budding and incorporated into the virions possibly by
CC       contacts between the cytoplasmic tail of Env and the N-terminus of Gag.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: Some of the most genetically diverse regions of the viral
CC       genome are present in Env. They are called variable regions 1 through 5
CC       (V1 through V5). Coreceptor usage of gp120 is determined mainly by the
CC       primary structure of the third variable region (V3) in the outer domain
CC       of gp120. The sequence of V3 determines which coreceptor, CCR5 and/or
CC       CXCR4 (corresponding to R5/macrophage, X4/T cell and R5X4/T cell and
CC       macrophage tropism), is used to trigger the fusion potential of the Env
CC       complex, and hence which cells the virus can infect. Binding to CCR5
CC       involves a region adjacent in addition to V3. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- DOMAIN: The membrane proximal external region (MPER) present in gp41 is
CC       a tryptophan-rich region recognized by the antibodies 2F5, Z13, and
CC       4E10. MPER seems to play a role in fusion. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- DOMAIN: The 17 amino acids long immunosuppressive region is present in
CC       many retroviral envelope proteins. Synthetic peptides derived from this
CC       relatively conserved sequence inhibit immune function in vitro and in
CC       vivo. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: The YXXL motif is involved in determining the exact site of
CC       viral release at the surface of infected mononuclear cells and promotes
CC       endocytosis. YXXL and di-leucine endocytosis motifs interact directly
CC       or indirectly with the clathrin adapter complexes, opperate
CC       independently, and their activities are not additive.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: The CD4-binding region is targeted by the antibody b12.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- PTM: Highly glycosylated by host. The high number of glycan on the
CC       protein is reffered to as 'glycan shield' because it contributes to
CC       hide protein sequence from adaptive immune system. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- PTM: Palmitoylation of the transmembrane protein and of Env polyprotein
CC       (prior to its proteolytic cleavage) is essential for their association
CC       with host cell membrane lipid rafts. Palmitoylation is therefore
CC       required for envelope trafficking to classical lipid rafts, but not for
CC       viral replication. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- PTM: Specific enzymatic cleavages in vivo yield mature proteins.
CC       Envelope glycoproteins are synthesized as an inactive precursor that is
CC       heavily N-glycosylated and processed likely by host cell furin in the
CC       Golgi to yield the mature SU and TM proteins. The cleavage site between
CC       SU and TM requires the minimal sequence [KR]-X-[KR]-R. About 2 of the 9
CC       disulfide bonds of gp41 are reduced by P4HB/PDI, following binding to
CC       CD4 receptor. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- MISCELLANEOUS: Inhibitors targeting HIV-1 viral envelope proteins are
CC       used as antiretroviral drugs. Attachment of virions to the cell surface
CC       via non-specific interactions and CD4 binding can be blocked by
CC       inhibitors that include cyanovirin-N, cyclotriazadisulfonamide analogs,
CC       PRO 2000, TNX 355 and PRO 542. In addition, BMS 806 can block CD4-
CC       induced conformational changes. Env interactions with the coreceptor
CC       molecules can be targeted by CCR5 antagonists including SCH-D,
CC       maraviroc (UK 427857) and aplaviroc (GW 873140), and the CXCR4
CC       antagonist AMD 070. Fusion of viral and cellular membranes can be
CC       inhibited by peptides such as enfuvirtide and tifuvirtide (T 1249).
CC       Resistance to inhibitors associated with mutations in Env are observed.
CC       Most of the time, single mutations confer only a modest reduction in
CC       drug susceptibility. Combination of several mutations is usually
CC       required to develop a high-level drug resistance. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- MISCELLANEOUS: HIV-1 lineages are divided in three main groups, M (for
CC       Major), O (for Outlier), and N (for New, or Non-M, Non-O). The vast
CC       majority of strains found worldwide belong to the group M. Group O
CC       seems to be endemic to and largely confined to Cameroon and neighboring
CC       countries in West Central Africa, where these viruses represent a small
CC       minority of HIV-1 strains. The group N is represented by a limited
CC       number of isolates from Cameroonian persons. The group M is further
CC       subdivided in 9 clades or subtypes (A to D, F to H, J and K).
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SIMILARITY: Belongs to the HIV-1 env protein family.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- WEB RESOURCE: Name=hivdb; Note=HIV drug resistance database;
CC       URL="https://hivdb.stanford.edu";
CC   -!- WEB RESOURCE: Name=HIV drug resistance mutations;
CC       URL="https://www.iasusa.org/content/hiv-drug-resistance-mutations";
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DR   EMBL; AF082395; AAD17768.1; -; Genomic_DNA.
DR   GlyCosmos; Q9WC69; 32 sites, No reported glycans.
DR   GO; GO:0044175; C:host cell endosome membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0016020; C:membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:0019031; C:viral envelope; IEA:UniProtKB-KW.
DR   GO; GO:0055036; C:virion membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005198; F:structural molecule activity; IEA:UniProtKB-UniRule.
DR   GO; GO:0075512; P:clathrin-dependent endocytosis of virus by host cell; IEA:UniProtKB-UniRule.
DR   GO; GO:0039654; P:fusion of virus membrane with host endosome membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:0019064; P:fusion of virus membrane with host plasma membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:1903905; P:positive regulation of establishment of T cell polarity; IEA:UniProtKB-UniRule.
DR   GO; GO:1903908; P:positive regulation of plasma membrane raft polarization; IEA:UniProtKB-UniRule.
DR   GO; GO:1903911; P:positive regulation of receptor clustering; IEA:UniProtKB-UniRule.
DR   GO; GO:0019082; P:viral protein processing; IEA:UniProtKB-UniRule.
DR   GO; GO:0019062; P:virion attachment to host cell; IEA:UniProtKB-UniRule.
DR   GO; GO:0019049; P:virus-mediated perturbation of host defense response; IEA:UniProtKB-UniRule.
DR   CDD; cd09909; HIV-1-like_HR1-HR2; 1.
DR   Gene3D; 1.10.287.210; -; 1.
DR   Gene3D; 2.170.40.20; Human immunodeficiency virus 1, Gp160, envelope glycoprotein; 2.
DR   Gene3D; 1.20.5.490; Single helix bin; 1.
DR   HAMAP; MF_04083; HIV_ENV; 1.
DR   InterPro; IPR036377; Gp120_core_sf.
DR   InterPro; IPR037527; Gp160.
DR   InterPro; IPR000328; GP41-like.
DR   InterPro; IPR000777; HIV1_Gp120.
DR   Pfam; PF00516; GP120; 1.
DR   Pfam; PF00517; GP41; 1.
DR   SUPFAM; SSF56502; gp120 core; 2.
DR   SUPFAM; SSF58069; Virus ectodomain; 1.
PE   3: Inferred from homology;
KW   AIDS; Apoptosis; Clathrin-mediated endocytosis of virus by host;
KW   Cleavage on pair of basic residues; Coiled coil; Disulfide bond;
KW   Fusion of virus membrane with host endosomal membrane;
KW   Fusion of virus membrane with host membrane; Glycoprotein;
KW   Host cell membrane; Host endosome; Host membrane; Host-virus interaction;
KW   Lipoprotein; Membrane; Palmitate; Signal; Transmembrane;
KW   Transmembrane helix; Viral attachment to host cell; Viral envelope protein;
KW   Viral immunoevasion; Viral penetration into host cytoplasm; Virion;
KW   Virus endocytosis by host; Virus entry into host cell.
FT   SIGNAL          1..28
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CHAIN           29..850
FT                   /note="Envelope glycoprotein gp160"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000244684"
FT   CHAIN           29..505
FT                   /note="Surface protein gp120"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000244685"
FT   CHAIN           506..850
FT                   /note="Transmembrane protein gp41"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000244686"
FT   TOPO_DOM        29..678
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   TRANSMEM        679..699
FT                   /note="Helical"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   TOPO_DOM        700..850
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          127..152
FT                   /note="V1"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          153..192
FT                   /note="V2"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          292..325
FT                   /note="V3"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          357..367
FT                   /note="CD4-binding loop"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          378..409
FT                   /note="V4"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          447..467
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          453..465
FT                   /note="V5"
FT   REGION          454..465
FT                   /note="V5"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          506..526
FT                   /note="Fusion peptide"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          568..586
FT                   /note="Immunosuppression"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          656..677
FT                   /note="MPER; binding to GalCer"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   COILED          627..661
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   MOTIF           706..709
FT                   /note="YXXL motif; contains endocytosis signal"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   MOTIF           849..850
FT                   /note="Di-leucine internalization motif"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   SITE            505..506
FT                   /note="Cleavage; by host furin"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   LIPID           758
FT                   /note="S-palmitoyl cysteine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        84
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        126
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        133
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        134
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        139
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        152
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        156
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        184
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        193
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        226
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        230
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        237
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        258
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        272
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        285
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        297
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        327
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        334
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        349
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        379
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        385
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        397
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        402
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        433
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        439
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        453
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        457
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        605
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        610
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        619
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        631
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        668
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        50..70
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        115..201
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        122..192
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        127..153
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        214..243
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        224..235
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        292..326
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        371..436
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        378..409
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        592..598
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
SQ   SEQUENCE   850 AA;  95858 MW;  738E4F5492C877C9 CRC64;
     METQTSWLSL WRWGLMIFGM LMICSARENL WVTVYYGVPV WRDAKTTLFC ASDAKAYSTE
     KHNVWATHAC VPTDPNPQEM SLPNVTENFN MWKNDMVDQM QEDIISVWDE SLKPCVKITP
     LCVTLNCSDV NSNNSTDSNS SASNNSPEIM KNCSFNVTTE IRNKRKQEYA LFYRQDVVPI
     NSDNKSYILI NCNTSVIKQA CPKVSFQPIP IHYCAPAGFA ILKCNNKTFN GTGPCKNVST
     VQCTHGIKPV VSTQLLLNGS VAEGDIIIRS ENISDNAKNI IVQLNDTVEI VCTRPNNNTR
     KGIHMGPGQV LYATGEIIGD IRKAYCNISR KDWNNTLRRV AKKLREHFNK TIDFTSPSGG
     DIEITTHSFN CGGEFFYCNT STLFNSSWDE NNIKDTNSTN DNTTITIPCK IKQIVRMWQR
     TGQAIYAPPI AGNITCKSNI TGLLLTRDGG NRNGSENGTE TFRPTGGNMK DNWRSELYKY
     KVVELEPLGV APTKAKRRVV EREKRAVGIG AVFLGFLGTA GSTMGAASIT LTVQVRQLLS
     GIVQQQSNLL KAIXAQQHLL KLTVWGIKQL QARVLAVERY LKDQQLLGIW GCSGKLICTT
     NVPWNASWSN KSYEDIWENM TWIQWEREIN NYTGIIYSLI EEAQNQQETN EKDLLALDKW
     TNLWNWFNIS NWLWYIKIFI MIIGGLIGLR IIFAVLAIVN RVRQGYSPLS FQTLIPNPTE
     ADRPGGIEEG GGEQGRTRSI RLVNGFLALA WDDLRSLCLF SYHRLRDFVL IAARTVGTLG
     LRGWEILKYL VNLVWYWGQE LKNSAISLLN TTAIAVAEGT DRIIEIAQRA FRAILHIPRR
     IRQGLERALL
//
ID   ENV_HV1SC               Reviewed;         856 AA.
AC   P05878;
DT   01-NOV-1988, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1988, sequence version 1.
DT   27-MAR-2024, entry version 152.
DE   RecName: Full=Envelope glycoprotein gp160 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   AltName: Full=Env polyprotein {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Contains:
DE     RecName: Full=Surface protein gp120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=SU {ECO:0000255|HAMAP-Rule:MF_04083};
DE     AltName: Full=Glycoprotein 120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=gp120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Contains:
DE     RecName: Full=Transmembrane protein gp41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=TM {ECO:0000255|HAMAP-Rule:MF_04083};
DE     AltName: Full=Glycoprotein 41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=gp41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Flags: Precursor;
GN   Name=env {ECO:0000255|HAMAP-Rule:MF_04083};
OS   Human immunodeficiency virus type 1 group M subtype B (isolate SC) (HIV-1).
OC   Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC   Ortervirales; Retroviridae; Orthoretrovirinae; Lentivirus;
OC   Human immunodeficiency virus 1.
OX   NCBI_TaxID=11702;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX   PubMed=3369091; DOI=10.1016/0042-6822(88)90568-5;
RA   Gurgo C., Guo H.-G., Franchini G., Aldovini A., Collalti E., Farrell K.,
RA   Wong-Staal F., Gallo R.C., Reitz M.S. Jr.;
RT   "Envelope sequences of two new United States HIV-1 isolates.";
RL   Virology 164:531-536(1988).
RN   [2]
RP   REVIEW.
RX   PubMed=12974773; DOI=10.1034/j.1600-0463.2003.11107803.x;
RA   Geijtenbeek T.B., van Kooyk Y.;
RT   "Pathogens target DC-SIGN to influence their fate DC-SIGN functions as a
RT   pathogen receptor with broad specificity.";
RL   APMIS 111:698-714(2003).
RN   [3]
RP   REVIEW.
RX   PubMed=12873764; DOI=10.1016/s0005-2736(03)00161-5;
RA   Gallo S.A., Finnegan C.M., Viard M., Raviv Y., Dimitrov A., Rawat S.S.,
RA   Puri A., Durell S., Blumenthal R.;
RT   "The HIV Env-mediated fusion reaction.";
RL   Biochim. Biophys. Acta 1614:36-50(2003).
RN   [4]
RP   REVIEW.
RX   PubMed=15719026; DOI=10.1038/sj.cdd.4401584;
RA   Perfettini J.-L., Castedo M., Roumier T., Andreau K., Nardacci R.,
RA   Piacentini M., Kroemer G.;
RT   "Mechanisms of apoptosis induction by the HIV-1 envelope.";
RL   Cell Death Differ. 12:916-923(2005).
RN   [5]
RP   REVIEW.
RX   PubMed=15725757; DOI=10.1089/aid.2005.21.171;
RA   Hartley O., Klasse P.J., Sattentau Q.J., Moore J.P.;
RT   "V3: HIV's switch-hitter.";
RL   AIDS Res. Hum. Retroviruses 21:171-189(2005).
RN   [6]
RP   REVIEW.
RX   PubMed=16114975; DOI=10.2165/00003495-200565130-00002;
RA   Reeves J.D., Piefer A.J.;
RT   "Emerging drug targets for antiretroviral therapy.";
RL   Drugs 65:1747-1766(2005).
RN   [7]
RP   REVIEW.
RX   PubMed=16437164; DOI=10.1038/sj.emboj.7600947;
RA   Lusso P.;
RT   "HIV and the chemokine system: 10 years later.";
RL   EMBO J. 25:447-456(2006).
CC   -!- FUNCTION: [Envelope glycoprotein gp160]: Oligomerizes in the host
CC       endoplasmic reticulum into predominantly trimers. In a second time,
CC       gp160 transits in the host Golgi, where glycosylation is completed. The
CC       precursor is then proteolytically cleaved in the trans-Golgi and
CC       thereby activated by cellular furin or furin-like proteases to produce
CC       gp120 and gp41. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- FUNCTION: [Surface protein gp120]: Attaches the virus to the host
CC       lymphoid cell by binding to the primary receptor CD4. This interaction
CC       induces a structural rearrangement creating a high affinity binding
CC       site for a chemokine coreceptor like CXCR4 and/or CCR5. Acts as a
CC       ligand for CD209/DC-SIGN and CLEC4M/DC-SIGNR, which are respectively
CC       found on dendritic cells (DCs), and on endothelial cells of liver
CC       sinusoids and lymph node sinuses. These interactions allow capture of
CC       viral particles at mucosal surfaces by these cells and subsequent
CC       transmission to permissive cells. HIV subverts the migration properties
CC       of dendritic cells to gain access to CD4+ T-cells in lymph nodes. Virus
CC       transmission to permissive T-cells occurs either in trans (without DCs
CC       infection, through viral capture and transmission), or in cis
CC       (following DCs productive infection, through the usual CD4-gp120
CC       interaction), thereby inducing a robust infection. In trans infection,
CC       bound virions remain infectious over days and it is proposed that they
CC       are not degraded, but protected in non-lysosomal acidic organelles
CC       within the DCs close to the cell membrane thus contributing to the
CC       viral infectious potential during DCs' migration from the periphery to
CC       the lymphoid tissues. On arrival at lymphoid tissues, intact virions
CC       recycle back to DCs' cell surface allowing virus transmission to CD4+
CC       T-cells. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- FUNCTION: [Transmembrane protein gp41]: Acts as a class I viral fusion
CC       protein. Under the current model, the protein has at least 3
CC       conformational states: pre-fusion native state, pre-hairpin
CC       intermediate state, and post-fusion hairpin state. During fusion of
CC       viral and target intracellular membranes, the coiled coil regions
CC       (heptad repeats) assume a trimer-of-hairpins structure, positioning the
CC       fusion peptide in close proximity to the C-terminal region of the
CC       ectodomain. The formation of this structure appears to drive apposition
CC       and subsequent fusion of viral and target cell membranes. Complete
CC       fusion occurs in host cell endosomes and is dynamin-dependent, however
CC       some lipid transfer might occur at the plasma membrane. The virus
CC       undergoes clathrin-dependent internalization long before endosomal
CC       fusion, thus minimizing the surface exposure of conserved viral
CC       epitopes during fusion and reducing the efficacy of inhibitors
CC       targeting these epitopes. Membranes fusion leads to delivery of the
CC       nucleocapsid into the cytoplasm. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBUNIT: [Surface protein gp120]: The mature envelope protein (Env)
CC       consists of a homotrimer of non-covalently associated gp120-gp41
CC       heterodimers. The resulting complex protrudes from the virus surface as
CC       a spike. There seems to be as few as 10 spikes on the average virion.
CC       Interacts with host CD4, CCR5 and CXCR4. Gp120 also interacts with the
CC       C-type lectins CD209/DC-SIGN and CLEC4M/DC-SIGNR (collectively referred
CC       to as DC-SIGN(R)). Gp120 and gp41 interact with GalCer. Gp120 interacts
CC       with host ITGA4/ITGB7 complex; on CD4+ T-cells, this interaction
CC       results in rapid activation of integrin ITGAL/LFA-1, which facilitates
CC       efficient cell-to-cell spreading of HIV-1. Gp120 interacts with cell-
CC       associated heparan sulfate; this interaction increases virus
CC       infectivity on permissive cells and may be involved in infection of
CC       CD4- cells. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBUNIT: [Transmembrane protein gp41]: The mature envelope protein
CC       (Env) consists of a homotrimer of non-covalently associated gp120-gp41
CC       heterodimers. The resulting complex protrudes from the virus surface as
CC       a spike. There seems to be as few as 10 spikes on the average virion.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBCELLULAR LOCATION: [Surface protein gp120]: Virion membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Peripheral membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host cell membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Peripheral membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host endosome membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Note=The surface protein is not
CC       anchored to the viral envelope, but associates with the extravirion
CC       surface through its binding to TM. It is probably concentrated at the
CC       site of budding and incorporated into the virions possibly by contacts
CC       between the cytoplasmic tail of Env and the N-terminus of Gag.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBCELLULAR LOCATION: [Transmembrane protein gp41]: Virion membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host cell membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host endosome membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Note=It is probably concentrated at
CC       the site of budding and incorporated into the virions possibly by
CC       contacts between the cytoplasmic tail of Env and the N-terminus of Gag.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: Some of the most genetically diverse regions of the viral
CC       genome are present in Env. They are called variable regions 1 through 5
CC       (V1 through V5). Coreceptor usage of gp120 is determined mainly by the
CC       primary structure of the third variable region (V3) in the outer domain
CC       of gp120. The sequence of V3 determines which coreceptor, CCR5 and/or
CC       CXCR4 (corresponding to R5/macrophage, X4/T cell and R5X4/T cell and
CC       macrophage tropism), is used to trigger the fusion potential of the Env
CC       complex, and hence which cells the virus can infect. Binding to CCR5
CC       involves a region adjacent in addition to V3. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- DOMAIN: The membrane proximal external region (MPER) present in gp41 is
CC       a tryptophan-rich region recognized by the antibodies 2F5, Z13, and
CC       4E10. MPER seems to play a role in fusion. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- DOMAIN: The 17 amino acids long immunosuppressive region is present in
CC       many retroviral envelope proteins. Synthetic peptides derived from this
CC       relatively conserved sequence inhibit immune function in vitro and in
CC       vivo. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: The YXXL motif is involved in determining the exact site of
CC       viral release at the surface of infected mononuclear cells and promotes
CC       endocytosis. YXXL and di-leucine endocytosis motifs interact directly
CC       or indirectly with the clathrin adapter complexes, opperate
CC       independently, and their activities are not additive.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: The CD4-binding region is targeted by the antibody b12.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- PTM: Highly glycosylated by host. The high number of glycan on the
CC       protein is reffered to as 'glycan shield' because it contributes to
CC       hide protein sequence from adaptive immune system. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- PTM: Palmitoylation of the transmembrane protein and of Env polyprotein
CC       (prior to its proteolytic cleavage) is essential for their association
CC       with host cell membrane lipid rafts. Palmitoylation is therefore
CC       required for envelope trafficking to classical lipid rafts, but not for
CC       viral replication. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- PTM: Specific enzymatic cleavages in vivo yield mature proteins.
CC       Envelope glycoproteins are synthesized as an inactive precursor that is
CC       heavily N-glycosylated and processed likely by host cell furin in the
CC       Golgi to yield the mature SU and TM proteins. The cleavage site between
CC       SU and TM requires the minimal sequence [KR]-X-[KR]-R. About 2 of the 9
CC       disulfide bonds of gp41 are reduced by P4HB/PDI, following binding to
CC       CD4 receptor. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- MISCELLANEOUS: Inhibitors targeting HIV-1 viral envelope proteins are
CC       used as antiretroviral drugs. Attachment of virions to the cell surface
CC       via non-specific interactions and CD4 binding can be blocked by
CC       inhibitors that include cyanovirin-N, cyclotriazadisulfonamide analogs,
CC       PRO 2000, TNX 355 and PRO 542. In addition, BMS 806 can block CD4-
CC       induced conformational changes. Env interactions with the coreceptor
CC       molecules can be targeted by CCR5 antagonists including SCH-D,
CC       maraviroc (UK 427857) and aplaviroc (GW 873140), and the CXCR4
CC       antagonist AMD 070. Fusion of viral and cellular membranes can be
CC       inhibited by peptides such as enfuvirtide and tifuvirtide (T 1249).
CC       Resistance to inhibitors associated with mutations in Env are observed.
CC       Most of the time, single mutations confer only a modest reduction in
CC       drug susceptibility. Combination of several mutations is usually
CC       required to develop a high-level drug resistance. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- MISCELLANEOUS: HIV-1 lineages are divided in three main groups, M (for
CC       Major), O (for Outlier), and N (for New, or Non-M, Non-O). The vast
CC       majority of strains found worldwide belong to the group M. Group O
CC       seems to be endemic to and largely confined to Cameroon and neighboring
CC       countries in West Central Africa, where these viruses represent a small
CC       minority of HIV-1 strains. The group N is represented by a limited
CC       number of isolates from Cameroonian persons. The group M is further
CC       subdivided in 9 clades or subtypes (A to D, F to H, J and K).
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SIMILARITY: Belongs to the HIV-1 env protein family.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- WEB RESOURCE: Name=hivdb; Note=HIV drug resistance database;
CC       URL="https://hivdb.stanford.edu";
CC   -!- WEB RESOURCE: Name=HIV drug resistance mutations;
CC       URL="https://www.iasusa.org/content/hiv-drug-resistance-mutations";
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DR   EMBL; M17450; -; NOT_ANNOTATED_CDS; Genomic_RNA.
DR   PDB; 2M8M; NMR; -; A=656-683.
DR   PDB; 2M8O; NMR; -; A=656-683.
DR   PDB; 3E6F; X-ray; 2.41 A; P=309-317.
DR   PDBsum; 2M8M; -.
DR   PDBsum; 2M8O; -.
DR   PDBsum; 3E6F; -.
DR   SMR; P05878; -.
DR   GlyCosmos; P05878; 31 sites, No reported glycans.
DR   ABCD; P05878; 2 sequenced antibodies.
DR   Reactome; R-HSA-5621480; Dectin-2 family.
DR   GO; GO:0044175; C:host cell endosome membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0016020; C:membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:0019031; C:viral envelope; IEA:UniProtKB-KW.
DR   GO; GO:0055036; C:virion membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005198; F:structural molecule activity; IEA:UniProtKB-UniRule.
DR   GO; GO:0075512; P:clathrin-dependent endocytosis of virus by host cell; IEA:UniProtKB-UniRule.
DR   GO; GO:0039654; P:fusion of virus membrane with host endosome membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:0019064; P:fusion of virus membrane with host plasma membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:1903905; P:positive regulation of establishment of T cell polarity; IEA:UniProtKB-UniRule.
DR   GO; GO:1903908; P:positive regulation of plasma membrane raft polarization; IEA:UniProtKB-UniRule.
DR   GO; GO:1903911; P:positive regulation of receptor clustering; IEA:UniProtKB-UniRule.
DR   GO; GO:0019082; P:viral protein processing; IEA:UniProtKB-UniRule.
DR   GO; GO:0019062; P:virion attachment to host cell; IEA:UniProtKB-UniRule.
DR   GO; GO:0019049; P:virus-mediated perturbation of host defense response; IEA:UniProtKB-UniRule.
DR   CDD; cd09909; HIV-1-like_HR1-HR2; 1.
DR   Gene3D; 1.10.287.210; -; 1.
DR   Gene3D; 2.170.40.20; Human immunodeficiency virus 1, Gp160, envelope glycoprotein; 2.
DR   Gene3D; 1.20.5.490; Single helix bin; 1.
DR   HAMAP; MF_04083; HIV_ENV; 1.
DR   InterPro; IPR036377; Gp120_core_sf.
DR   InterPro; IPR037527; Gp160.
DR   InterPro; IPR000328; GP41-like.
DR   InterPro; IPR000777; HIV1_Gp120.
DR   Pfam; PF00516; GP120; 1.
DR   Pfam; PF00517; GP41; 1.
DR   SUPFAM; SSF56502; gp120 core; 2.
DR   SUPFAM; SSF58069; Virus ectodomain; 1.
PE   1: Evidence at protein level;
KW   3D-structure; AIDS; Apoptosis;
KW   Clathrin-mediated endocytosis of virus by host;
KW   Cleavage on pair of basic residues; Coiled coil; Disulfide bond;
KW   Fusion of virus membrane with host endosomal membrane;
KW   Fusion of virus membrane with host membrane; Glycoprotein;
KW   Host cell membrane; Host endosome; Host membrane; Host-virus interaction;
KW   Lipoprotein; Membrane; Palmitate; Signal; Transmembrane;
KW   Transmembrane helix; Viral attachment to host cell; Viral envelope protein;
KW   Viral immunoevasion; Viral penetration into host cytoplasm; Virion;
KW   Virus endocytosis by host; Virus entry into host cell.
FT   SIGNAL          1..31
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CHAIN           32..856
FT                   /note="Envelope glycoprotein gp160"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000239489"
FT   CHAIN           32..510
FT                   /note="Surface protein gp120"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000038419"
FT   CHAIN           511..856
FT                   /note="Transmembrane protein gp41"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000038420"
FT   TOPO_DOM        32..684
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   TRANSMEM        685..705
FT                   /note="Helical"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   TOPO_DOM        706..856
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          130..159
FT                   /note="V1"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          160..197
FT                   /note="V2"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          296..329
FT                   /note="V3"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          362..372
FT                   /note="CD4-binding loop"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          383..412
FT                   /note="V4"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          450..472
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          455..470
FT                   /note="V5"
FT   REGION          457..470
FT                   /note="V5"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          511..532
FT                   /note="Fusion peptide"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          574..592
FT                   /note="Immunosuppression"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          662..683
FT                   /note="MPER; binding to GalCer"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          718..742
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COILED          633..667
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   MOTIF           712..715
FT                   /note="YXXL motif; contains endocytosis signal"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   COMPBIAS        450..464
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        727..742
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   SITE            510..511
FT                   /note="Cleavage; by host furin"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   SITE            760
FT                   /note="In-frame UAG termination codon"
FT   LIPID           764
FT                   /note="S-palmitoyl cysteine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        87
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        129
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        135
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        140
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        143
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        159
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        163
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        189
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        198
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        234
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        241
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        262
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        276
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        295
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        301
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        302
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        331
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        338
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        354
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        360
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        384
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        394
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        400
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        405
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        442
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        457
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        611
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        616
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        625
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        637
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        674
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        53..73
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        118..206
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        125..197
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        130..160
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        219..247
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        228..239
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        296..330
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        376..439
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        383..412
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        598..604
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   HELIX           658..682
FT                   /evidence="ECO:0007829|PDB:2M8M"
SQ   SEQUENCE   856 AA;  97056 MW;  DAF4DA600EBA7A08 CRC64;
     MRVKGSGRNY QHLWRWGTML LGILMICSAA EQLWVTVYYG VPVWKEATTT LFCASDAKAY
     DTEVHNIWAT HACVPTDPNP QEVVLGNVTE NFNMWKNNMV EQMHEDIISL WDQSLKPCVK
     LTPLCVTLNC TNLRNDTSTN ATNTTSSNRG KMEGGEMTNC SFNITTSIRS KVQKEYALFY
     KLDVVPIDNT SYTLINCNTS VITQACPKVS FEPIPIHYCA RWFAILNCNN KKFNGTGPCT
     NVSTVQCTHG IRPVVSTHLL LNGSLAEEEV VLRSENFTDN AKTIIVQLKE AVEINCTRPN
     NNTTRSIHIG PGRAFYATGD IIGDIRQAHC NISRAKWNNT LKQIVIKLRD QFENKTIIFN
     RSSGGDPEIV MHSFNCGGEF FYCNSTQLFS STWNGTEGSN NTGGNDTITL PCRIKEIINM
     WQEVGKAMYA PPIKGQVKCS SNITGLLLTR DGGNSKNGSK NENTEIFRPG GGDMRDNWRS
     ELYKYKVVKI EPLGVAPTKA KRRVVQREKR AVGTIGAMFL GFLGAAGSTM GATSMTLTVQ
     ARLLLSGIVQ QQNNLLRAIE AQQHLLQLTV WGIKQLQARV LAVERYLRDQ QLLGIWGCSG
     KLICTTTVPW NTSWSNKSLD KIWGNMTWME WEREIDNYTS LIYTLIEESQ NQQEKNEQEL
     LELDKWASLW NWFNITNWLW YIKIFIMIVG GLVGLRIVFT VLSIVNRVRQ GYSPLSFQTR
     LPSQRGPDRP EGIEEEGGER DRDRSGRLVD GFLAIIWVDX RSLCLFSYHR LRDLLLIVTR
     IVELLGRRGW EALKYWWNLL QYWSQELRNS AVSFVNATAI AVAEGTDRVI ELLQRAFRAI
     LHIPTRIRQG LERALQ
//
ID   ENV_HV1V9               Reviewed;         859 AA.
AC   Q9Q714;
DT   27-JUN-2006, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-2000, sequence version 1.
DT   27-MAR-2024, entry version 124.
DE   RecName: Full=Envelope glycoprotein gp160 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   AltName: Full=Env polyprotein {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Contains:
DE     RecName: Full=Surface protein gp120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=SU {ECO:0000255|HAMAP-Rule:MF_04083};
DE     AltName: Full=Glycoprotein 120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=gp120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Contains:
DE     RecName: Full=Transmembrane protein gp41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=TM {ECO:0000255|HAMAP-Rule:MF_04083};
DE     AltName: Full=Glycoprotein 41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=gp41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Flags: Precursor;
GN   Name=env {ECO:0000255|HAMAP-Rule:MF_04083};
OS   Human immunodeficiency virus type 1 group M subtype H (isolate VI991)
OS   (HIV-1).
OC   Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC   Ortervirales; Retroviridae; Orthoretrovirinae; Lentivirus;
OC   Human immunodeficiency virus 1.
OX   NCBI_TaxID=388888;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=10983640; DOI=10.1097/00002030-200007280-00009;
RA   Janssens W., Laukkanen T., Salminen M.O., Carr J.K., Van der Auwera G.,
RA   Heyndrickx L., van der Groen G., McCutchan F.E.;
RT   "HIV-1 subtype H near-full length genome reference strains and analysis of
RT   subtype-H-containing inter-subtype recombinants.";
RL   AIDS 14:1533-1543(2000).
RN   [2]
RP   REVIEW.
RX   PubMed=12974773; DOI=10.1034/j.1600-0463.2003.11107803.x;
RA   Geijtenbeek T.B., van Kooyk Y.;
RT   "Pathogens target DC-SIGN to influence their fate DC-SIGN functions as a
RT   pathogen receptor with broad specificity.";
RL   APMIS 111:698-714(2003).
RN   [3]
RP   REVIEW.
RX   PubMed=12873764; DOI=10.1016/s0005-2736(03)00161-5;
RA   Gallo S.A., Finnegan C.M., Viard M., Raviv Y., Dimitrov A., Rawat S.S.,
RA   Puri A., Durell S., Blumenthal R.;
RT   "The HIV Env-mediated fusion reaction.";
RL   Biochim. Biophys. Acta 1614:36-50(2003).
RN   [4]
RP   REVIEW.
RX   PubMed=15719026; DOI=10.1038/sj.cdd.4401584;
RA   Perfettini J.-L., Castedo M., Roumier T., Andreau K., Nardacci R.,
RA   Piacentini M., Kroemer G.;
RT   "Mechanisms of apoptosis induction by the HIV-1 envelope.";
RL   Cell Death Differ. 12:916-923(2005).
RN   [5]
RP   REVIEW.
RX   PubMed=15725757; DOI=10.1089/aid.2005.21.171;
RA   Hartley O., Klasse P.J., Sattentau Q.J., Moore J.P.;
RT   "V3: HIV's switch-hitter.";
RL   AIDS Res. Hum. Retroviruses 21:171-189(2005).
RN   [6]
RP   REVIEW.
RX   PubMed=16114975; DOI=10.2165/00003495-200565130-00002;
RA   Reeves J.D., Piefer A.J.;
RT   "Emerging drug targets for antiretroviral therapy.";
RL   Drugs 65:1747-1766(2005).
RN   [7]
RP   REVIEW.
RX   PubMed=16437164; DOI=10.1038/sj.emboj.7600947;
RA   Lusso P.;
RT   "HIV and the chemokine system: 10 years later.";
RL   EMBO J. 25:447-456(2006).
CC   -!- FUNCTION: [Envelope glycoprotein gp160]: Oligomerizes in the host
CC       endoplasmic reticulum into predominantly trimers. In a second time,
CC       gp160 transits in the host Golgi, where glycosylation is completed. The
CC       precursor is then proteolytically cleaved in the trans-Golgi and
CC       thereby activated by cellular furin or furin-like proteases to produce
CC       gp120 and gp41. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- FUNCTION: [Surface protein gp120]: Attaches the virus to the host
CC       lymphoid cell by binding to the primary receptor CD4. This interaction
CC       induces a structural rearrangement creating a high affinity binding
CC       site for a chemokine coreceptor like CXCR4 and/or CCR5. Acts as a
CC       ligand for CD209/DC-SIGN and CLEC4M/DC-SIGNR, which are respectively
CC       found on dendritic cells (DCs), and on endothelial cells of liver
CC       sinusoids and lymph node sinuses. These interactions allow capture of
CC       viral particles at mucosal surfaces by these cells and subsequent
CC       transmission to permissive cells. HIV subverts the migration properties
CC       of dendritic cells to gain access to CD4+ T-cells in lymph nodes. Virus
CC       transmission to permissive T-cells occurs either in trans (without DCs
CC       infection, through viral capture and transmission), or in cis
CC       (following DCs productive infection, through the usual CD4-gp120
CC       interaction), thereby inducing a robust infection. In trans infection,
CC       bound virions remain infectious over days and it is proposed that they
CC       are not degraded, but protected in non-lysosomal acidic organelles
CC       within the DCs close to the cell membrane thus contributing to the
CC       viral infectious potential during DCs' migration from the periphery to
CC       the lymphoid tissues. On arrival at lymphoid tissues, intact virions
CC       recycle back to DCs' cell surface allowing virus transmission to CD4+
CC       T-cells. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- FUNCTION: [Transmembrane protein gp41]: Acts as a class I viral fusion
CC       protein. Under the current model, the protein has at least 3
CC       conformational states: pre-fusion native state, pre-hairpin
CC       intermediate state, and post-fusion hairpin state. During fusion of
CC       viral and target intracellular membranes, the coiled coil regions
CC       (heptad repeats) assume a trimer-of-hairpins structure, positioning the
CC       fusion peptide in close proximity to the C-terminal region of the
CC       ectodomain. The formation of this structure appears to drive apposition
CC       and subsequent fusion of viral and target cell membranes. Complete
CC       fusion occurs in host cell endosomes and is dynamin-dependent, however
CC       some lipid transfer might occur at the plasma membrane. The virus
CC       undergoes clathrin-dependent internalization long before endosomal
CC       fusion, thus minimizing the surface exposure of conserved viral
CC       epitopes during fusion and reducing the efficacy of inhibitors
CC       targeting these epitopes. Membranes fusion leads to delivery of the
CC       nucleocapsid into the cytoplasm. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBUNIT: [Surface protein gp120]: The mature envelope protein (Env)
CC       consists of a homotrimer of non-covalently associated gp120-gp41
CC       heterodimers. The resulting complex protrudes from the virus surface as
CC       a spike. There seems to be as few as 10 spikes on the average virion.
CC       Interacts with host CD4, CCR5 and CXCR4. Gp120 also interacts with the
CC       C-type lectins CD209/DC-SIGN and CLEC4M/DC-SIGNR (collectively referred
CC       to as DC-SIGN(R)). Gp120 and gp41 interact with GalCer. Gp120 interacts
CC       with host ITGA4/ITGB7 complex; on CD4+ T-cells, this interaction
CC       results in rapid activation of integrin ITGAL/LFA-1, which facilitates
CC       efficient cell-to-cell spreading of HIV-1. Gp120 interacts with cell-
CC       associated heparan sulfate; this interaction increases virus
CC       infectivity on permissive cells and may be involved in infection of
CC       CD4- cells. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBUNIT: [Transmembrane protein gp41]: The mature envelope protein
CC       (Env) consists of a homotrimer of non-covalently associated gp120-gp41
CC       heterodimers. The resulting complex protrudes from the virus surface as
CC       a spike. There seems to be as few as 10 spikes on the average virion.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBCELLULAR LOCATION: [Surface protein gp120]: Virion membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Peripheral membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host cell membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Peripheral membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host endosome membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Note=The surface protein is not
CC       anchored to the viral envelope, but associates with the extravirion
CC       surface through its binding to TM. It is probably concentrated at the
CC       site of budding and incorporated into the virions possibly by contacts
CC       between the cytoplasmic tail of Env and the N-terminus of Gag.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBCELLULAR LOCATION: [Transmembrane protein gp41]: Virion membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host cell membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host endosome membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Note=It is probably concentrated at
CC       the site of budding and incorporated into the virions possibly by
CC       contacts between the cytoplasmic tail of Env and the N-terminus of Gag.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: Some of the most genetically diverse regions of the viral
CC       genome are present in Env. They are called variable regions 1 through 5
CC       (V1 through V5). Coreceptor usage of gp120 is determined mainly by the
CC       primary structure of the third variable region (V3) in the outer domain
CC       of gp120. The sequence of V3 determines which coreceptor, CCR5 and/or
CC       CXCR4 (corresponding to R5/macrophage, X4/T cell and R5X4/T cell and
CC       macrophage tropism), is used to trigger the fusion potential of the Env
CC       complex, and hence which cells the virus can infect. Binding to CCR5
CC       involves a region adjacent in addition to V3. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- DOMAIN: The membrane proximal external region (MPER) present in gp41 is
CC       a tryptophan-rich region recognized by the antibodies 2F5, Z13, and
CC       4E10. MPER seems to play a role in fusion. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- DOMAIN: The 17 amino acids long immunosuppressive region is present in
CC       many retroviral envelope proteins. Synthetic peptides derived from this
CC       relatively conserved sequence inhibit immune function in vitro and in
CC       vivo. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: The YXXL motif is involved in determining the exact site of
CC       viral release at the surface of infected mononuclear cells and promotes
CC       endocytosis. YXXL and di-leucine endocytosis motifs interact directly
CC       or indirectly with the clathrin adapter complexes, opperate
CC       independently, and their activities are not additive.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: The CD4-binding region is targeted by the antibody b12.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- PTM: Highly glycosylated by host. The high number of glycan on the
CC       protein is reffered to as 'glycan shield' because it contributes to
CC       hide protein sequence from adaptive immune system. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- PTM: Palmitoylation of the transmembrane protein and of Env polyprotein
CC       (prior to its proteolytic cleavage) is essential for their association
CC       with host cell membrane lipid rafts. Palmitoylation is therefore
CC       required for envelope trafficking to classical lipid rafts, but not for
CC       viral replication. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- PTM: Specific enzymatic cleavages in vivo yield mature proteins.
CC       Envelope glycoproteins are synthesized as an inactive precursor that is
CC       heavily N-glycosylated and processed likely by host cell furin in the
CC       Golgi to yield the mature SU and TM proteins. The cleavage site between
CC       SU and TM requires the minimal sequence [KR]-X-[KR]-R. About 2 of the 9
CC       disulfide bonds of gp41 are reduced by P4HB/PDI, following binding to
CC       CD4 receptor. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- MISCELLANEOUS: Inhibitors targeting HIV-1 viral envelope proteins are
CC       used as antiretroviral drugs. Attachment of virions to the cell surface
CC       via non-specific interactions and CD4 binding can be blocked by
CC       inhibitors that include cyanovirin-N, cyclotriazadisulfonamide analogs,
CC       PRO 2000, TNX 355 and PRO 542. In addition, BMS 806 can block CD4-
CC       induced conformational changes. Env interactions with the coreceptor
CC       molecules can be targeted by CCR5 antagonists including SCH-D,
CC       maraviroc (UK 427857) and aplaviroc (GW 873140), and the CXCR4
CC       antagonist AMD 070. Fusion of viral and cellular membranes can be
CC       inhibited by peptides such as enfuvirtide and tifuvirtide (T 1249).
CC       Resistance to inhibitors associated with mutations in Env are observed.
CC       Most of the time, single mutations confer only a modest reduction in
CC       drug susceptibility. Combination of several mutations is usually
CC       required to develop a high-level drug resistance. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- MISCELLANEOUS: HIV-1 lineages are divided in three main groups, M (for
CC       Major), O (for Outlier), and N (for New, or Non-M, Non-O). The vast
CC       majority of strains found worldwide belong to the group M. Group O
CC       seems to be endemic to and largely confined to Cameroon and neighboring
CC       countries in West Central Africa, where these viruses represent a small
CC       minority of HIV-1 strains. The group N is represented by a limited
CC       number of isolates from Cameroonian persons. The group M is further
CC       subdivided in 9 clades or subtypes (A to D, F to H, J and K).
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SIMILARITY: Belongs to the HIV-1 env protein family.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- WEB RESOURCE: Name=hivdb; Note=HIV drug resistance database;
CC       URL="https://hivdb.stanford.edu";
CC   -!- WEB RESOURCE: Name=HIV drug resistance mutations;
CC       URL="https://www.iasusa.org/content/hiv-drug-resistance-mutations";
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DR   EMBL; AF190127; AAF18394.1; -; Genomic_DNA.
DR   PDB; 3UJJ; X-ray; 2.00 A; P=305-327.
DR   PDB; 7Z7C; X-ray; 1.22 A; B=309-330.
DR   PDB; 8AED; X-ray; 1.17 A; C/D=306-329.
DR   PDBsum; 3UJJ; -.
DR   PDBsum; 7Z7C; -.
DR   PDBsum; 8AED; -.
DR   SMR; Q9Q714; -.
DR   GlyCosmos; Q9Q714; 32 sites, No reported glycans.
DR   GO; GO:0044175; C:host cell endosome membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0016020; C:membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:0019031; C:viral envelope; IEA:UniProtKB-KW.
DR   GO; GO:0055036; C:virion membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005198; F:structural molecule activity; IEA:UniProtKB-UniRule.
DR   GO; GO:0075512; P:clathrin-dependent endocytosis of virus by host cell; IEA:UniProtKB-UniRule.
DR   GO; GO:0039654; P:fusion of virus membrane with host endosome membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:0019064; P:fusion of virus membrane with host plasma membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:1903905; P:positive regulation of establishment of T cell polarity; IEA:UniProtKB-UniRule.
DR   GO; GO:1903908; P:positive regulation of plasma membrane raft polarization; IEA:UniProtKB-UniRule.
DR   GO; GO:1903911; P:positive regulation of receptor clustering; IEA:UniProtKB-UniRule.
DR   GO; GO:0019082; P:viral protein processing; IEA:UniProtKB-UniRule.
DR   GO; GO:0019062; P:virion attachment to host cell; IEA:UniProtKB-UniRule.
DR   GO; GO:0019049; P:virus-mediated perturbation of host defense response; IEA:UniProtKB-UniRule.
DR   CDD; cd09909; HIV-1-like_HR1-HR2; 1.
DR   Gene3D; 1.10.287.210; -; 1.
DR   Gene3D; 2.170.40.20; Human immunodeficiency virus 1, Gp160, envelope glycoprotein; 2.
DR   Gene3D; 1.20.5.490; Single helix bin; 1.
DR   HAMAP; MF_04083; HIV_ENV; 1.
DR   InterPro; IPR036377; Gp120_core_sf.
DR   InterPro; IPR037527; Gp160.
DR   InterPro; IPR000328; GP41-like.
DR   InterPro; IPR000777; HIV1_Gp120.
DR   Pfam; PF00516; GP120; 1.
DR   Pfam; PF00517; GP41; 1.
DR   SUPFAM; SSF56502; gp120 core; 2.
DR   SUPFAM; SSF58069; Virus ectodomain; 1.
PE   1: Evidence at protein level;
KW   3D-structure; AIDS; Apoptosis;
KW   Clathrin-mediated endocytosis of virus by host;
KW   Cleavage on pair of basic residues; Coiled coil; Disulfide bond;
KW   Fusion of virus membrane with host endosomal membrane;
KW   Fusion of virus membrane with host membrane; Glycoprotein;
KW   Host cell membrane; Host endosome; Host membrane; Host-virus interaction;
KW   Lipoprotein; Membrane; Palmitate; Signal; Transmembrane;
KW   Transmembrane helix; Viral attachment to host cell; Viral envelope protein;
KW   Viral immunoevasion; Viral penetration into host cytoplasm; Virion;
KW   Virus endocytosis by host; Virus entry into host cell.
FT   SIGNAL          1..28
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CHAIN           29..859
FT                   /note="Envelope glycoprotein gp160"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000244693"
FT   CHAIN           29..514
FT                   /note="Surface protein gp120"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000244694"
FT   CHAIN           515..859
FT                   /note="Transmembrane protein gp41"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000244695"
FT   TOPO_DOM        29..687
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   TRANSMEM        688..708
FT                   /note="Helical"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   TOPO_DOM        709..859
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          127..154
FT                   /note="V1"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          155..199
FT                   /note="V2"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          300..333
FT                   /note="V3"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          366..376
FT                   /note="CD4-binding loop"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          387..423
FT                   /note="V4"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          466..474
FT                   /note="V5"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          515..535
FT                   /note="Fusion peptide"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          577..595
FT                   /note="Immunosuppression"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          665..686
FT                   /note="MPER; binding to GalCer"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          724..743
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COILED          636..670
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   MOTIF           715..718
FT                   /note="YXXL motif; contains endocytosis signal"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   MOTIF           858..859
FT                   /note="Di-leucine internalization motif"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   SITE            514..515
FT                   /note="Cleavage; by host furin"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   LIPID           767
FT                   /note="S-palmitoyl cysteine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        84
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        131
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        134
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        139
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        140
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        154
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        158
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        188
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        200
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        237
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        244
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        265
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        280
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        299
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        305
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        335
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        342
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        358
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        388
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        394
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        399
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        404
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        410
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        418
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        447
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        453
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        464
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        468
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        614
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        619
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        628
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        640
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        50..70
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        115..208
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        122..199
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        127..155
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        221..250
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        231..242
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        300..334
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        380..450
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        387..423
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        601..607
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   STRAND          312..314
FT                   /evidence="ECO:0007829|PDB:3UJJ"
FT   HELIX           317..327
FT                   /evidence="ECO:0007829|PDB:8AED"
SQ   SEQUENCE   859 AA;  97577 MW;  ECD8CE2BF28A452D CRC64;
     METQRNYPSL WRWGTLILGM LLICSVVGNL WVTVYYGVPV WKEAKTTLFC ASDAKAYDTE
     RHNVWATHAC VPTDPNPQEM VLENVTETFN MWVNDMVEQM HTDIISLWDQ SLKPCVKLTP
     LCVTLDCSSV NATNVTKSNN STDINIGEIQ EQRNCSFNVT TAIRDKNQKV HALFYRADIV
     QIDEGERNKS DNHYRLINCN TSVIKQACPK VSFEPIPIHY CAPAGFAILK CNGKKFNGTG
     PCTNVSTVQC THGIRPVVST QLLLNGSLAE VEEVIIRSKN ITDNTKNIIV QLNEPVQINC
     TRTGNNTRKS IRIGPGQAFY ATGDIIGDIR RAYCNISGKQ WNETLHKVIT KLGSYFDNKT
     IILQPPAGGD IEIITHSFNC GGEFFYCNTT KLFNSTWTNS SYTNDTYNSN STEDITGNIT
     LQCKIKQIVN MWQRVGQAMY APPIRGNITC ISNITGLILT FDRNNTNNVT FRPGGGDMRD
     NWRSELYKYK VVKIEPLGVA PTEARRRVVE REKRAVGMGA FFLGFLGAAG STMGAASITL
     TVQARQLLSG IVQQQSNLLR AIQAQQHMLQ LTVWGIKQLQ ARVLAVERYL KDQQLLGIWG
     CSGKLICTTN VPWNSSWSNK SLDEIWDNMT WMEWDKQINN YTDEIYRLLE VSQNQQEKNE
     QDLLALDKWA NLWNWFSITN WLWYIRIFIM IVGGIIGLRI VFAVLSIVNR VRQGYSPLSL
     QTLIPNQRGP DRPREIEEEG GEQDRDRSIR LVNGFLPLVW EDLRNLCLFS YRRLRDLLSI
     VARTVELLGR RGWEALKLLG NLLLYWGQEL KNSAISLLNT TAIAVAEGTD RIIELVQRAW
     RAILHIPRRI RQGFERALL
//
ID   ENV_HV1VI               Reviewed;         832 AA.
AC   Q9QSQ7;
DT   27-JUN-2006, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-2000, sequence version 1.
DT   27-MAR-2024, entry version 129.
DE   RecName: Full=Envelope glycoprotein gp160 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   AltName: Full=Env polyprotein {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Contains:
DE     RecName: Full=Surface protein gp120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=SU {ECO:0000255|HAMAP-Rule:MF_04083};
DE     AltName: Full=Glycoprotein 120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=gp120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Contains:
DE     RecName: Full=Transmembrane protein gp41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=TM {ECO:0000255|HAMAP-Rule:MF_04083};
DE     AltName: Full=Glycoprotein 41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=gp41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Flags: Precursor;
GN   Name=env {ECO:0000255|HAMAP-Rule:MF_04083};
OS   Human immunodeficiency virus type 1 group M subtype F1 (isolate VI850)
OS   (HIV-1).
OC   Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC   Ortervirales; Retroviridae; Orthoretrovirinae; Lentivirus;
OC   Human immunodeficiency virus 1.
OX   NCBI_TaxID=388813;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=10725202; DOI=10.1006/viro.2000.0214;
RA   Laukkanen T., Carr J.K., Janssens W., Liitsola K., Gotte D.,
RA   McCutchan F.E., Op de Coul E., Cornelissen M., Heyndrickx L.,
RA   van der Groen G., Salminen M.O.;
RT   "Virtually full-length subtype F and F/D recombinant HIV-1 from Africa and
RT   South America.";
RL   Virology 269:95-104(2000).
RN   [2]
RP   REVIEW.
RX   PubMed=12974773; DOI=10.1034/j.1600-0463.2003.11107803.x;
RA   Geijtenbeek T.B., van Kooyk Y.;
RT   "Pathogens target DC-SIGN to influence their fate DC-SIGN functions as a
RT   pathogen receptor with broad specificity.";
RL   APMIS 111:698-714(2003).
RN   [3]
RP   REVIEW.
RX   PubMed=12873764; DOI=10.1016/s0005-2736(03)00161-5;
RA   Gallo S.A., Finnegan C.M., Viard M., Raviv Y., Dimitrov A., Rawat S.S.,
RA   Puri A., Durell S., Blumenthal R.;
RT   "The HIV Env-mediated fusion reaction.";
RL   Biochim. Biophys. Acta 1614:36-50(2003).
RN   [4]
RP   REVIEW.
RX   PubMed=15719026; DOI=10.1038/sj.cdd.4401584;
RA   Perfettini J.-L., Castedo M., Roumier T., Andreau K., Nardacci R.,
RA   Piacentini M., Kroemer G.;
RT   "Mechanisms of apoptosis induction by the HIV-1 envelope.";
RL   Cell Death Differ. 12:916-923(2005).
RN   [5]
RP   REVIEW.
RX   PubMed=15725757; DOI=10.1089/aid.2005.21.171;
RA   Hartley O., Klasse P.J., Sattentau Q.J., Moore J.P.;
RT   "V3: HIV's switch-hitter.";
RL   AIDS Res. Hum. Retroviruses 21:171-189(2005).
RN   [6]
RP   REVIEW.
RX   PubMed=16114975; DOI=10.2165/00003495-200565130-00002;
RA   Reeves J.D., Piefer A.J.;
RT   "Emerging drug targets for antiretroviral therapy.";
RL   Drugs 65:1747-1766(2005).
RN   [7]
RP   REVIEW.
RX   PubMed=16437164; DOI=10.1038/sj.emboj.7600947;
RA   Lusso P.;
RT   "HIV and the chemokine system: 10 years later.";
RL   EMBO J. 25:447-456(2006).
CC   -!- FUNCTION: [Envelope glycoprotein gp160]: Oligomerizes in the host
CC       endoplasmic reticulum into predominantly trimers. In a second time,
CC       gp160 transits in the host Golgi, where glycosylation is completed. The
CC       precursor is then proteolytically cleaved in the trans-Golgi and
CC       thereby activated by cellular furin or furin-like proteases to produce
CC       gp120 and gp41. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- FUNCTION: [Surface protein gp120]: Attaches the virus to the host
CC       lymphoid cell by binding to the primary receptor CD4. This interaction
CC       induces a structural rearrangement creating a high affinity binding
CC       site for a chemokine coreceptor like CXCR4 and/or CCR5. Acts as a
CC       ligand for CD209/DC-SIGN and CLEC4M/DC-SIGNR, which are respectively
CC       found on dendritic cells (DCs), and on endothelial cells of liver
CC       sinusoids and lymph node sinuses. These interactions allow capture of
CC       viral particles at mucosal surfaces by these cells and subsequent
CC       transmission to permissive cells. HIV subverts the migration properties
CC       of dendritic cells to gain access to CD4+ T-cells in lymph nodes. Virus
CC       transmission to permissive T-cells occurs either in trans (without DCs
CC       infection, through viral capture and transmission), or in cis
CC       (following DCs productive infection, through the usual CD4-gp120
CC       interaction), thereby inducing a robust infection. In trans infection,
CC       bound virions remain infectious over days and it is proposed that they
CC       are not degraded, but protected in non-lysosomal acidic organelles
CC       within the DCs close to the cell membrane thus contributing to the
CC       viral infectious potential during DCs' migration from the periphery to
CC       the lymphoid tissues. On arrival at lymphoid tissues, intact virions
CC       recycle back to DCs' cell surface allowing virus transmission to CD4+
CC       T-cells. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- FUNCTION: [Transmembrane protein gp41]: Acts as a class I viral fusion
CC       protein. Under the current model, the protein has at least 3
CC       conformational states: pre-fusion native state, pre-hairpin
CC       intermediate state, and post-fusion hairpin state. During fusion of
CC       viral and target intracellular membranes, the coiled coil regions
CC       (heptad repeats) assume a trimer-of-hairpins structure, positioning the
CC       fusion peptide in close proximity to the C-terminal region of the
CC       ectodomain. The formation of this structure appears to drive apposition
CC       and subsequent fusion of viral and target cell membranes. Complete
CC       fusion occurs in host cell endosomes and is dynamin-dependent, however
CC       some lipid transfer might occur at the plasma membrane. The virus
CC       undergoes clathrin-dependent internalization long before endosomal
CC       fusion, thus minimizing the surface exposure of conserved viral
CC       epitopes during fusion and reducing the efficacy of inhibitors
CC       targeting these epitopes. Membranes fusion leads to delivery of the
CC       nucleocapsid into the cytoplasm. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBUNIT: [Surface protein gp120]: The mature envelope protein (Env)
CC       consists of a homotrimer of non-covalently associated gp120-gp41
CC       heterodimers. The resulting complex protrudes from the virus surface as
CC       a spike. There seems to be as few as 10 spikes on the average virion.
CC       Interacts with host CD4, CCR5 and CXCR4. Gp120 also interacts with the
CC       C-type lectins CD209/DC-SIGN and CLEC4M/DC-SIGNR (collectively referred
CC       to as DC-SIGN(R)). Gp120 and gp41 interact with GalCer. Gp120 interacts
CC       with host ITGA4/ITGB7 complex; on CD4+ T-cells, this interaction
CC       results in rapid activation of integrin ITGAL/LFA-1, which facilitates
CC       efficient cell-to-cell spreading of HIV-1. Gp120 interacts with cell-
CC       associated heparan sulfate; this interaction increases virus
CC       infectivity on permissive cells and may be involved in infection of
CC       CD4- cells. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBUNIT: [Transmembrane protein gp41]: The mature envelope protein
CC       (Env) consists of a homotrimer of non-covalently associated gp120-gp41
CC       heterodimers. The resulting complex protrudes from the virus surface as
CC       a spike. There seems to be as few as 10 spikes on the average virion.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBCELLULAR LOCATION: [Surface protein gp120]: Virion membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Peripheral membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host cell membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Peripheral membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host endosome membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Note=The surface protein is not
CC       anchored to the viral envelope, but associates with the extravirion
CC       surface through its binding to TM. It is probably concentrated at the
CC       site of budding and incorporated into the virions possibly by contacts
CC       between the cytoplasmic tail of Env and the N-terminus of Gag.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBCELLULAR LOCATION: [Transmembrane protein gp41]: Virion membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host cell membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host endosome membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Note=It is probably concentrated at
CC       the site of budding and incorporated into the virions possibly by
CC       contacts between the cytoplasmic tail of Env and the N-terminus of Gag.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: Some of the most genetically diverse regions of the viral
CC       genome are present in Env. They are called variable regions 1 through 5
CC       (V1 through V5). Coreceptor usage of gp120 is determined mainly by the
CC       primary structure of the third variable region (V3) in the outer domain
CC       of gp120. The sequence of V3 determines which coreceptor, CCR5 and/or
CC       CXCR4 (corresponding to R5/macrophage, X4/T cell and R5X4/T cell and
CC       macrophage tropism), is used to trigger the fusion potential of the Env
CC       complex, and hence which cells the virus can infect. Binding to CCR5
CC       involves a region adjacent in addition to V3. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- DOMAIN: The membrane proximal external region (MPER) present in gp41 is
CC       a tryptophan-rich region recognized by the antibodies 2F5, Z13, and
CC       4E10. MPER seems to play a role in fusion. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- DOMAIN: The 17 amino acids long immunosuppressive region is present in
CC       many retroviral envelope proteins. Synthetic peptides derived from this
CC       relatively conserved sequence inhibit immune function in vitro and in
CC       vivo. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: The YXXL motif is involved in determining the exact site of
CC       viral release at the surface of infected mononuclear cells and promotes
CC       endocytosis. YXXL and di-leucine endocytosis motifs interact directly
CC       or indirectly with the clathrin adapter complexes, opperate
CC       independently, and their activities are not additive.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: The CD4-binding region is targeted by the antibody b12.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- PTM: Highly glycosylated by host. The high number of glycan on the
CC       protein is reffered to as 'glycan shield' because it contributes to
CC       hide protein sequence from adaptive immune system. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- PTM: Palmitoylation of the transmembrane protein and of Env polyprotein
CC       (prior to its proteolytic cleavage) is essential for their association
CC       with host cell membrane lipid rafts. Palmitoylation is therefore
CC       required for envelope trafficking to classical lipid rafts, but not for
CC       viral replication. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- PTM: Specific enzymatic cleavages in vivo yield mature proteins.
CC       Envelope glycoproteins are synthesized as an inactive precursor that is
CC       heavily N-glycosylated and processed likely by host cell furin in the
CC       Golgi to yield the mature SU and TM proteins. The cleavage site between
CC       SU and TM requires the minimal sequence [KR]-X-[KR]-R. About 2 of the 9
CC       disulfide bonds of gp41 are reduced by P4HB/PDI, following binding to
CC       CD4 receptor. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- MISCELLANEOUS: Inhibitors targeting HIV-1 viral envelope proteins are
CC       used as antiretroviral drugs. Attachment of virions to the cell surface
CC       via non-specific interactions and CD4 binding can be blocked by
CC       inhibitors that include cyanovirin-N, cyclotriazadisulfonamide analogs,
CC       PRO 2000, TNX 355 and PRO 542. In addition, BMS 806 can block CD4-
CC       induced conformational changes. Env interactions with the coreceptor
CC       molecules can be targeted by CCR5 antagonists including SCH-D,
CC       maraviroc (UK 427857) and aplaviroc (GW 873140), and the CXCR4
CC       antagonist AMD 070. Fusion of viral and cellular membranes can be
CC       inhibited by peptides such as enfuvirtide and tifuvirtide (T 1249).
CC       Resistance to inhibitors associated with mutations in Env are observed.
CC       Most of the time, single mutations confer only a modest reduction in
CC       drug susceptibility. Combination of several mutations is usually
CC       required to develop a high-level drug resistance. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- MISCELLANEOUS: HIV-1 lineages are divided in three main groups, M (for
CC       Major), O (for Outlier), and N (for New, or Non-M, Non-O). The vast
CC       majority of strains found worldwide belong to the group M. Group O
CC       seems to be endemic to and largely confined to Cameroon and neighboring
CC       countries in West Central Africa, where these viruses represent a small
CC       minority of HIV-1 strains. The group N is represented by a limited
CC       number of isolates from Cameroonian persons. The group M is further
CC       subdivided in 9 clades or subtypes (A to D, F to H, J and K).
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SIMILARITY: Belongs to the HIV-1 env protein family.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- WEB RESOURCE: Name=hivdb; Note=HIV drug resistance database;
CC       URL="https://hivdb.stanford.edu";
CC   -!- WEB RESOURCE: Name=HIV drug resistance mutations;
CC       URL="https://www.iasusa.org/content/hiv-drug-resistance-mutations";
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DR   EMBL; AF077336; AAD46094.1; -; Genomic_DNA.
DR   SMR; Q9QSQ7; -.
DR   GlyCosmos; Q9QSQ7; 29 sites, No reported glycans.
DR   Proteomes; UP000007418; Segment.
DR   GO; GO:0044175; C:host cell endosome membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0016020; C:membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:0019031; C:viral envelope; IEA:UniProtKB-KW.
DR   GO; GO:0055036; C:virion membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005198; F:structural molecule activity; IEA:UniProtKB-UniRule.
DR   GO; GO:0075512; P:clathrin-dependent endocytosis of virus by host cell; IEA:UniProtKB-UniRule.
DR   GO; GO:0039654; P:fusion of virus membrane with host endosome membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:0019064; P:fusion of virus membrane with host plasma membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:1903905; P:positive regulation of establishment of T cell polarity; IEA:UniProtKB-UniRule.
DR   GO; GO:1903908; P:positive regulation of plasma membrane raft polarization; IEA:UniProtKB-UniRule.
DR   GO; GO:1903911; P:positive regulation of receptor clustering; IEA:UniProtKB-UniRule.
DR   GO; GO:0019082; P:viral protein processing; IEA:UniProtKB-UniRule.
DR   GO; GO:0019062; P:virion attachment to host cell; IEA:UniProtKB-UniRule.
DR   GO; GO:0019049; P:virus-mediated perturbation of host defense response; IEA:UniProtKB-UniRule.
DR   CDD; cd09909; HIV-1-like_HR1-HR2; 1.
DR   Gene3D; 1.10.287.210; -; 1.
DR   Gene3D; 2.170.40.20; Human immunodeficiency virus 1, Gp160, envelope glycoprotein; 2.
DR   Gene3D; 1.20.5.490; Single helix bin; 1.
DR   HAMAP; MF_04083; HIV_ENV; 1.
DR   InterPro; IPR036377; Gp120_core_sf.
DR   InterPro; IPR037527; Gp160.
DR   InterPro; IPR000328; GP41-like.
DR   InterPro; IPR000777; HIV1_Gp120.
DR   Pfam; PF00516; GP120; 2.
DR   Pfam; PF00517; GP41; 1.
DR   SUPFAM; SSF56502; gp120 core; 2.
DR   SUPFAM; SSF58069; Virus ectodomain; 1.
PE   3: Inferred from homology;
KW   AIDS; Apoptosis; Clathrin-mediated endocytosis of virus by host;
KW   Cleavage on pair of basic residues; Coiled coil; Disulfide bond;
KW   Fusion of virus membrane with host endosomal membrane;
KW   Fusion of virus membrane with host membrane; Glycoprotein;
KW   Host cell membrane; Host endosome; Host membrane; Host-virus interaction;
KW   Lipoprotein; Membrane; Palmitate; Reference proteome; Signal;
KW   Transmembrane; Transmembrane helix; Viral attachment to host cell;
KW   Viral envelope protein; Viral immunoevasion;
KW   Viral penetration into host cytoplasm; Virion; Virus endocytosis by host;
KW   Virus entry into host cell.
FT   SIGNAL          1..31
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CHAIN           32..832
FT                   /note="Envelope glycoprotein gp160"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000244690"
FT   CHAIN           32..487
FT                   /note="Surface protein gp120"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000244691"
FT   CHAIN           488..832
FT                   /note="Transmembrane protein gp41"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000244692"
FT   TOPO_DOM        32..660
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   TRANSMEM        661..681
FT                   /note="Helical"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   TOPO_DOM        682..832
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          130..146
FT                   /note="V1"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          147..187
FT                   /note="V2"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          287..320
FT                   /note="V3"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          354..364
FT                   /note="CD4-binding loop"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          375..395
FT                   /note="V4"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          438..447
FT                   /note="V5"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          488..508
FT                   /note="Fusion peptide"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          550..568
FT                   /note="Immunosuppression"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          638..659
FT                   /note="MPER; binding to GalCer"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          695..717
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COILED          609..643
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   MOTIF           688..691
FT                   /note="YXXL motif; contains endocytosis signal"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   MOTIF           831..832
FT                   /note="Di-leucine internalization motif"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   SITE            487..488
FT                   /note="Cleavage; by host furin"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   LIPID           740
FT                   /note="S-palmitoyl cysteine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        87
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        129
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        132
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        135
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        146
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        150
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        177
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        178
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        188
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        225
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        232
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        253
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        267
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        280
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        286
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        292
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        322
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        329
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        345
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        352
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        382
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        388
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        419
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        425
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        437
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        587
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        592
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        601
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        613
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        53..73
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        118..196
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        125..187
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        130..147
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        209..238
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        219..230
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        287..321
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        368..422
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        375..395
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        574..580
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
SQ   SEQUENCE   832 AA;  93810 MW;  4CE00FD6D9DE269B CRC64;
     MRVRGMQRNW QHLGKWGLLF LGILIICNAA DNLWVTVYYG VPVWKEATTT LFCASDAKAY
     EREAHNVWAT HACVPTDPNP QEVFLKNVTE NFDMWKNNMV EQMHTDIISL WDQSLKPCVK
     LTPLCVTLNC TNATNNSQEK PGAMQNCSFN MTTEVRDKKL KLSALFYRLD IVPIGNNNSS
     EYRLINCNTS TITQACPKVS WDPIPIHYCA PAGYAILKCN DKRFNGTGPC KNVSTVQCTH
     GIKPVVSTQL LLNGSLAEEG IVIRSQNISN NAKTIIVHLN ESVQINCTRP NNNTRKGIHL
     GPGQTFYATG AIIGDIRKAH CNISGTQWNN TLEYVKAELK SHFPNNTAIK FNQSSGGDLE
     ITMHSFNCRG EFFYCDTSGL FNDTGSNNGT ITLPCRIKQI VNMWQGVGRA MYTSPIAGNI
     TCNSNITGLL LTRDGGNESN IETFRPEGGN MKDNWRSELY KYKVVEIEPL GVAPTKAKRQ
     VVQREKRAAG LGALFLGFLG DSREHMGAAS ITLTVQARQL LSGIVQQQNN LLRAIEAQQH
     LLQLTVWGIK QLQARVLAVE RYLKDQQLLG IWGCSGKLIC TTNVPWNSSW SNKSQEEIWN
     NMTWMEWEKE ISNYSNIIYK LIEESQNQQE KNEQELLALD KWASLWNWFD ISNWLWYIKI
     FIMIVGGLIG LRIVFAVLSI VNRVRKGYSP LSLQTLIPSP RGPDRPEGIE EGGGEQGKDR
     SVRLVTGFLA LAWDDLRNLC LFSYRHLRDF ILIAARIVDR GLRRGWEALK YLGNLTRYWS
     QELKNSAISL FNTTAIVVAE GTDRIIEVLQ RAGRAVLNIP RRIRQGAERA LL
//
ID   ENV_HV1W1               Reviewed;         856 AA.
AC   P31872;
DT   01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
DT   01-JUL-1993, sequence version 1.
DT   27-MAR-2024, entry version 138.
DE   RecName: Full=Envelope glycoprotein gp160 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   AltName: Full=Env polyprotein {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Contains:
DE     RecName: Full=Surface protein gp120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=SU {ECO:0000255|HAMAP-Rule:MF_04083};
DE     AltName: Full=Glycoprotein 120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=gp120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Contains:
DE     RecName: Full=Transmembrane protein gp41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=TM {ECO:0000255|HAMAP-Rule:MF_04083};
DE     AltName: Full=Glycoprotein 41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=gp41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Flags: Precursor;
GN   Name=env {ECO:0000255|HAMAP-Rule:MF_04083};
OS   Human immunodeficiency virus type 1 group M subtype B (isolate WMJ1)
OS   (HIV-1).
OC   Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC   Ortervirales; Retroviridae; Orthoretrovirinae; Lentivirus;
OC   Human immunodeficiency virus 1.
OX   NCBI_TaxID=31678;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX   PubMed=2423250; DOI=10.1016/0092-8674(86)90778-6;
RA   Starcich B.R., Hahn B.H., Shaw G.M., McNeely P.D., Modrow S., Wolf H.,
RA   Parks E.S., Parks W.P., Josephs S.F., Gallo R.C., Wong-Staal F.;
RT   "Identification and characterization of conserved and variable regions in
RT   the envelope gene of HTLV-III/LAV, the retrovirus of AIDS.";
RL   Cell 45:637-648(1986).
RN   [2]
RP   REVIEW.
RX   PubMed=12974773; DOI=10.1034/j.1600-0463.2003.11107803.x;
RA   Geijtenbeek T.B., van Kooyk Y.;
RT   "Pathogens target DC-SIGN to influence their fate DC-SIGN functions as a
RT   pathogen receptor with broad specificity.";
RL   APMIS 111:698-714(2003).
RN   [3]
RP   REVIEW.
RX   PubMed=12873764; DOI=10.1016/s0005-2736(03)00161-5;
RA   Gallo S.A., Finnegan C.M., Viard M., Raviv Y., Dimitrov A., Rawat S.S.,
RA   Puri A., Durell S., Blumenthal R.;
RT   "The HIV Env-mediated fusion reaction.";
RL   Biochim. Biophys. Acta 1614:36-50(2003).
RN   [4]
RP   REVIEW.
RX   PubMed=15719026; DOI=10.1038/sj.cdd.4401584;
RA   Perfettini J.-L., Castedo M., Roumier T., Andreau K., Nardacci R.,
RA   Piacentini M., Kroemer G.;
RT   "Mechanisms of apoptosis induction by the HIV-1 envelope.";
RL   Cell Death Differ. 12:916-923(2005).
RN   [5]
RP   REVIEW.
RX   PubMed=15725757; DOI=10.1089/aid.2005.21.171;
RA   Hartley O., Klasse P.J., Sattentau Q.J., Moore J.P.;
RT   "V3: HIV's switch-hitter.";
RL   AIDS Res. Hum. Retroviruses 21:171-189(2005).
RN   [6]
RP   REVIEW.
RX   PubMed=16114975; DOI=10.2165/00003495-200565130-00002;
RA   Reeves J.D., Piefer A.J.;
RT   "Emerging drug targets for antiretroviral therapy.";
RL   Drugs 65:1747-1766(2005).
RN   [7]
RP   REVIEW.
RX   PubMed=16437164; DOI=10.1038/sj.emboj.7600947;
RA   Lusso P.;
RT   "HIV and the chemokine system: 10 years later.";
RL   EMBO J. 25:447-456(2006).
CC   -!- FUNCTION: [Envelope glycoprotein gp160]: Oligomerizes in the host
CC       endoplasmic reticulum into predominantly trimers. In a second time,
CC       gp160 transits in the host Golgi, where glycosylation is completed. The
CC       precursor is then proteolytically cleaved in the trans-Golgi and
CC       thereby activated by cellular furin or furin-like proteases to produce
CC       gp120 and gp41. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- FUNCTION: [Surface protein gp120]: Attaches the virus to the host
CC       lymphoid cell by binding to the primary receptor CD4. This interaction
CC       induces a structural rearrangement creating a high affinity binding
CC       site for a chemokine coreceptor like CXCR4 and/or CCR5. Acts as a
CC       ligand for CD209/DC-SIGN and CLEC4M/DC-SIGNR, which are respectively
CC       found on dendritic cells (DCs), and on endothelial cells of liver
CC       sinusoids and lymph node sinuses. These interactions allow capture of
CC       viral particles at mucosal surfaces by these cells and subsequent
CC       transmission to permissive cells. HIV subverts the migration properties
CC       of dendritic cells to gain access to CD4+ T-cells in lymph nodes. Virus
CC       transmission to permissive T-cells occurs either in trans (without DCs
CC       infection, through viral capture and transmission), or in cis
CC       (following DCs productive infection, through the usual CD4-gp120
CC       interaction), thereby inducing a robust infection. In trans infection,
CC       bound virions remain infectious over days and it is proposed that they
CC       are not degraded, but protected in non-lysosomal acidic organelles
CC       within the DCs close to the cell membrane thus contributing to the
CC       viral infectious potential during DCs' migration from the periphery to
CC       the lymphoid tissues. On arrival at lymphoid tissues, intact virions
CC       recycle back to DCs' cell surface allowing virus transmission to CD4+
CC       T-cells. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- FUNCTION: [Transmembrane protein gp41]: Acts as a class I viral fusion
CC       protein. Under the current model, the protein has at least 3
CC       conformational states: pre-fusion native state, pre-hairpin
CC       intermediate state, and post-fusion hairpin state. During fusion of
CC       viral and target intracellular membranes, the coiled coil regions
CC       (heptad repeats) assume a trimer-of-hairpins structure, positioning the
CC       fusion peptide in close proximity to the C-terminal region of the
CC       ectodomain. The formation of this structure appears to drive apposition
CC       and subsequent fusion of viral and target cell membranes. Complete
CC       fusion occurs in host cell endosomes and is dynamin-dependent, however
CC       some lipid transfer might occur at the plasma membrane. The virus
CC       undergoes clathrin-dependent internalization long before endosomal
CC       fusion, thus minimizing the surface exposure of conserved viral
CC       epitopes during fusion and reducing the efficacy of inhibitors
CC       targeting these epitopes. Membranes fusion leads to delivery of the
CC       nucleocapsid into the cytoplasm. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBUNIT: [Surface protein gp120]: The mature envelope protein (Env)
CC       consists of a homotrimer of non-covalently associated gp120-gp41
CC       heterodimers. The resulting complex protrudes from the virus surface as
CC       a spike. There seems to be as few as 10 spikes on the average virion.
CC       Interacts with host CD4, CCR5 and CXCR4. Gp120 also interacts with the
CC       C-type lectins CD209/DC-SIGN and CLEC4M/DC-SIGNR (collectively referred
CC       to as DC-SIGN(R)). Gp120 and gp41 interact with GalCer. Gp120 interacts
CC       with host ITGA4/ITGB7 complex; on CD4+ T-cells, this interaction
CC       results in rapid activation of integrin ITGAL/LFA-1, which facilitates
CC       efficient cell-to-cell spreading of HIV-1. Gp120 interacts with cell-
CC       associated heparan sulfate; this interaction increases virus
CC       infectivity on permissive cells and may be involved in infection of
CC       CD4- cells. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBUNIT: [Transmembrane protein gp41]: The mature envelope protein
CC       (Env) consists of a homotrimer of non-covalently associated gp120-gp41
CC       heterodimers. The resulting complex protrudes from the virus surface as
CC       a spike. There seems to be as few as 10 spikes on the average virion.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBCELLULAR LOCATION: [Surface protein gp120]: Virion membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Peripheral membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host cell membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Peripheral membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host endosome membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Note=The surface protein is not
CC       anchored to the viral envelope, but associates with the extravirion
CC       surface through its binding to TM. It is probably concentrated at the
CC       site of budding and incorporated into the virions possibly by contacts
CC       between the cytoplasmic tail of Env and the N-terminus of Gag.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBCELLULAR LOCATION: [Transmembrane protein gp41]: Virion membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host cell membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host endosome membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Note=It is probably concentrated at
CC       the site of budding and incorporated into the virions possibly by
CC       contacts between the cytoplasmic tail of Env and the N-terminus of Gag.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: Some of the most genetically diverse regions of the viral
CC       genome are present in Env. They are called variable regions 1 through 5
CC       (V1 through V5). Coreceptor usage of gp120 is determined mainly by the
CC       primary structure of the third variable region (V3) in the outer domain
CC       of gp120. The sequence of V3 determines which coreceptor, CCR5 and/or
CC       CXCR4 (corresponding to R5/macrophage, X4/T cell and R5X4/T cell and
CC       macrophage tropism), is used to trigger the fusion potential of the Env
CC       complex, and hence which cells the virus can infect. Binding to CCR5
CC       involves a region adjacent in addition to V3. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- DOMAIN: The membrane proximal external region (MPER) present in gp41 is
CC       a tryptophan-rich region recognized by the antibodies 2F5, Z13, and
CC       4E10. MPER seems to play a role in fusion. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- DOMAIN: The 17 amino acids long immunosuppressive region is present in
CC       many retroviral envelope proteins. Synthetic peptides derived from this
CC       relatively conserved sequence inhibit immune function in vitro and in
CC       vivo. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: The YXXL motif is involved in determining the exact site of
CC       viral release at the surface of infected mononuclear cells and promotes
CC       endocytosis. YXXL and di-leucine endocytosis motifs interact directly
CC       or indirectly with the clathrin adapter complexes, opperate
CC       independently, and their activities are not additive.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: The CD4-binding region is targeted by the antibody b12.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- PTM: Highly glycosylated by host. The high number of glycan on the
CC       protein is reffered to as 'glycan shield' because it contributes to
CC       hide protein sequence from adaptive immune system. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- PTM: Palmitoylation of the transmembrane protein and of Env polyprotein
CC       (prior to its proteolytic cleavage) is essential for their association
CC       with host cell membrane lipid rafts. Palmitoylation is therefore
CC       required for envelope trafficking to classical lipid rafts, but not for
CC       viral replication. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- PTM: Specific enzymatic cleavages in vivo yield mature proteins.
CC       Envelope glycoproteins are synthesized as an inactive precursor that is
CC       heavily N-glycosylated and processed likely by host cell furin in the
CC       Golgi to yield the mature SU and TM proteins. The cleavage site between
CC       SU and TM requires the minimal sequence [KR]-X-[KR]-R. About 2 of the 9
CC       disulfide bonds of gp41 are reduced by P4HB/PDI, following binding to
CC       CD4 receptor. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- MISCELLANEOUS: Inhibitors targeting HIV-1 viral envelope proteins are
CC       used as antiretroviral drugs. Attachment of virions to the cell surface
CC       via non-specific interactions and CD4 binding can be blocked by
CC       inhibitors that include cyanovirin-N, cyclotriazadisulfonamide analogs,
CC       PRO 2000, TNX 355 and PRO 542. In addition, BMS 806 can block CD4-
CC       induced conformational changes. Env interactions with the coreceptor
CC       molecules can be targeted by CCR5 antagonists including SCH-D,
CC       maraviroc (UK 427857) and aplaviroc (GW 873140), and the CXCR4
CC       antagonist AMD 070. Fusion of viral and cellular membranes can be
CC       inhibited by peptides such as enfuvirtide and tifuvirtide (T 1249).
CC       Resistance to inhibitors associated with mutations in Env are observed.
CC       Most of the time, single mutations confer only a modest reduction in
CC       drug susceptibility. Combination of several mutations is usually
CC       required to develop a high-level drug resistance. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- MISCELLANEOUS: HIV-1 lineages are divided in three main groups, M (for
CC       Major), O (for Outlier), and N (for New, or Non-M, Non-O). The vast
CC       majority of strains found worldwide belong to the group M. Group O
CC       seems to be endemic to and largely confined to Cameroon and neighboring
CC       countries in West Central Africa, where these viruses represent a small
CC       minority of HIV-1 strains. The group N is represented by a limited
CC       number of isolates from Cameroonian persons. The group M is further
CC       subdivided in 9 clades or subtypes (A to D, F to H, J and K).
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SIMILARITY: Belongs to the HIV-1 env protein family.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- WEB RESOURCE: Name=hivdb; Note=HIV drug resistance database;
CC       URL="https://hivdb.stanford.edu";
CC   -!- WEB RESOURCE: Name=HIV drug resistance mutations;
CC       URL="https://www.iasusa.org/content/hiv-drug-resistance-mutations";
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DR   PIR; A24774; VCLJ3W.
DR   PDB; 1LB0; NMR; -; A=659-671.
DR   PDB; 1LCX; NMR; -; A=659-671.
DR   PDBsum; 1LB0; -.
DR   PDBsum; 1LCX; -.
DR   SMR; P31872; -.
DR   GlyCosmos; P31872; 26 sites, No reported glycans.
DR   Reactome; R-HSA-5621480; Dectin-2 family.
DR   EvolutionaryTrace; P31872; -.
DR   GO; GO:0044175; C:host cell endosome membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0016020; C:membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:0019031; C:viral envelope; IEA:UniProtKB-KW.
DR   GO; GO:0055036; C:virion membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005198; F:structural molecule activity; IEA:UniProtKB-UniRule.
DR   GO; GO:0075512; P:clathrin-dependent endocytosis of virus by host cell; IEA:UniProtKB-UniRule.
DR   GO; GO:0039654; P:fusion of virus membrane with host endosome membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:0019064; P:fusion of virus membrane with host plasma membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:1903905; P:positive regulation of establishment of T cell polarity; IEA:UniProtKB-UniRule.
DR   GO; GO:1903908; P:positive regulation of plasma membrane raft polarization; IEA:UniProtKB-UniRule.
DR   GO; GO:1903911; P:positive regulation of receptor clustering; IEA:UniProtKB-UniRule.
DR   GO; GO:0019082; P:viral protein processing; IEA:UniProtKB-UniRule.
DR   GO; GO:0019062; P:virion attachment to host cell; IEA:UniProtKB-UniRule.
DR   GO; GO:0019049; P:virus-mediated perturbation of host defense response; IEA:UniProtKB-UniRule.
DR   CDD; cd09909; HIV-1-like_HR1-HR2; 1.
DR   Gene3D; 1.10.287.210; -; 1.
DR   Gene3D; 2.170.40.20; Human immunodeficiency virus 1, Gp160, envelope glycoprotein; 2.
DR   Gene3D; 1.20.5.490; Single helix bin; 1.
DR   HAMAP; MF_04083; HIV_ENV; 1.
DR   InterPro; IPR036377; Gp120_core_sf.
DR   InterPro; IPR037527; Gp160.
DR   InterPro; IPR000328; GP41-like.
DR   InterPro; IPR000777; HIV1_Gp120.
DR   Pfam; PF00516; GP120; 2.
DR   Pfam; PF00517; GP41; 1.
DR   SUPFAM; SSF56502; gp120 core; 2.
DR   SUPFAM; SSF58069; Virus ectodomain; 1.
PE   1: Evidence at protein level;
KW   3D-structure; AIDS; Apoptosis;
KW   Clathrin-mediated endocytosis of virus by host;
KW   Cleavage on pair of basic residues; Coiled coil; Disulfide bond;
KW   Fusion of virus membrane with host endosomal membrane;
KW   Fusion of virus membrane with host membrane; Glycoprotein;
KW   Host cell membrane; Host endosome; Host membrane; Host-virus interaction;
KW   Lipoprotein; Membrane; Palmitate; Signal; Transmembrane;
KW   Transmembrane helix; Viral attachment to host cell; Viral envelope protein;
KW   Viral immunoevasion; Viral penetration into host cytoplasm; Virion;
KW   Virus endocytosis by host; Virus entry into host cell.
FT   SIGNAL          1..31
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CHAIN           32..856
FT                   /note="Envelope glycoprotein gp160"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000239491"
FT   CHAIN           32..510
FT                   /note="Surface protein gp120"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000038423"
FT   CHAIN           511..856
FT                   /note="Transmembrane protein gp41"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000038424"
FT   TOPO_DOM        32..684
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   TRANSMEM        685..705
FT                   /note="Helical"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   TOPO_DOM        706..856
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          130..151
FT                   /note="V1"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          152..196
FT                   /note="V2"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          296..329
FT                   /note="V3"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          362..372
FT                   /note="CD4-binding loop"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          383..417
FT                   /note="V4"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          460..470
FT                   /note="V5"
FT   REGION          462..470
FT                   /note="V5"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          511..532
FT                   /note="Fusion peptide"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          574..592
FT                   /note="Immunosuppression"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          662..683
FT                   /note="MPER; binding to GalCer"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          716..742
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COILED          633..667
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   MOTIF           712..715
FT                   /note="YXXL motif; contains endocytosis signal"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   MOTIF           855..856
FT                   /note="Di-leucine internalization motif"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   COMPBIAS        727..742
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   SITE            510..511
FT                   /note="Cleavage; by host furin"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   LIPID           764
FT                   /note="S-palmitoyl cysteine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   LIPID           837
FT                   /note="S-palmitoyl cysteine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        87
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        134
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        140
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        151
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        155
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        183
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        197
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        234
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        241
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        262
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        276
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        289
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        295
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        331
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        338
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        354
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        360
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        390
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        394
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        404
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        447
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        459
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        611
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        616
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        625
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        637
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        53..73
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        118..205
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        125..196
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        130..152
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        218..247
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        228..239
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        296..330
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        376..444
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        383..417
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        598..604
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   HELIX           662..670
FT                   /evidence="ECO:0007829|PDB:1LB0"
SQ   SEQUENCE   856 AA;  97526 MW;  DB68D1E49C404DE9 CRC64;
     MRVKGIRRNC QHLWIWGTML FGMWMICSAV EQLWVTVYYG VPVWKEATTT LFCASDAKAY
     STEAHKVWAT HACVPTNPNP QEVVLENVTE NFNMWKNNMV EQMHEDIISL WDQSLKPCVK
     LTPLCVTLNC IDKNITDWEN KTIIGGGEVK NCSFNITTSI RDKVHKEYAL FYKLDVVPIK
     SNNDSSTYTR YRLIHCNTSV ITQACSKVSF EPIPIHYCAP AGFAILKCND KKFNGTGPCT
     NVSTVQCTHG IRPVVSTQLL LNGSLAEEEI VIRSENFTDN AKTIIVHLNE SVEINCTRPN
     NNVRRRHIHI GPGRAFYTGE IRGNIRQAHC NISRAKWNNT LKQIVEKLRE QFKNKTIVFN
     HSSGGDPEIV THSFNCGGEF FYCDSTQLFN STWNVTGIST EGNNNTEENG DTITLPCRIK
     QIINMWQGVG KAMYAPPIGG QIRCSSNITG LLLTRDGGNS SSREEIFRPG GGNMRDNWRS
     ELYKYKVVKI EPLGVAPTKA KRRVVQREKR AVGAIGAMFL GFLGAAGSTM GAASLTLTVQ
     ARQLLSGIVQ QQNNLLRAIE AQQHLLQLTV WGIKQLQARV LAVERYLRDQ QLLGIWGCSG
     KLICTTTVPW NASWSNKSMD QIWNNMTWME WEREIDNYTS LIYNLIEESQ NQQEKNEQEL
     LELDKWASLW NWFSITNWLW YIKIFIMIVG GLVGLRIVFS VLSIVNRVRQ GYSPLSFQTH
     LPTPRGPDRP EGTEEEGGER DRDRSVRLVH GFLALIWDDL RSLCLFSYHR LRDLLLIVTR
     IVELLGRRGW EALKYWWNLL QYWSKELKNS AVGLLNAIAI AVAEGTDRVI EVVQRICRAI
     IHIPRRIRQG LERALL
//
ID   ENV_HV1W2               Reviewed;         847 AA.
AC   P05880;
DT   01-NOV-1988, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1988, sequence version 1.
DT   27-MAR-2024, entry version 149.
DE   RecName: Full=Envelope glycoprotein gp160 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   AltName: Full=Env polyprotein {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Contains:
DE     RecName: Full=Surface protein gp120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=SU {ECO:0000255|HAMAP-Rule:MF_04083};
DE     AltName: Full=Glycoprotein 120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=gp120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Contains:
DE     RecName: Full=Transmembrane protein gp41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=TM {ECO:0000255|HAMAP-Rule:MF_04083};
DE     AltName: Full=Glycoprotein 41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=gp41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Flags: Precursor;
GN   Name=env {ECO:0000255|HAMAP-Rule:MF_04083};
OS   Human immunodeficiency virus type 1 group M subtype B (isolate WMJ22)
OS   (HIV-1).
OC   Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC   Ortervirales; Retroviridae; Orthoretrovirinae; Lentivirus;
OC   Human immunodeficiency virus 1.
OX   NCBI_TaxID=11705;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX   PubMed=3012778; DOI=10.1126/science.3012778;
RA   Hahn B.H., Shaw G.M., Taylor M.E., Redfield R.R., Markham P.D.,
RA   Salahuddin S.Z., Wong-Staal F., Gallo R.C., Parks E.S., Parks W.P.;
RT   "Genetic variation in HTLV-III/LAV over time in patients with AIDS or at
RT   risk for AIDS.";
RL   Science 232:1548-1553(1986).
RN   [2]
RP   REVIEW.
RX   PubMed=12974773; DOI=10.1034/j.1600-0463.2003.11107803.x;
RA   Geijtenbeek T.B., van Kooyk Y.;
RT   "Pathogens target DC-SIGN to influence their fate DC-SIGN functions as a
RT   pathogen receptor with broad specificity.";
RL   APMIS 111:698-714(2003).
RN   [3]
RP   REVIEW.
RX   PubMed=12873764; DOI=10.1016/s0005-2736(03)00161-5;
RA   Gallo S.A., Finnegan C.M., Viard M., Raviv Y., Dimitrov A., Rawat S.S.,
RA   Puri A., Durell S., Blumenthal R.;
RT   "The HIV Env-mediated fusion reaction.";
RL   Biochim. Biophys. Acta 1614:36-50(2003).
RN   [4]
RP   REVIEW.
RX   PubMed=15719026; DOI=10.1038/sj.cdd.4401584;
RA   Perfettini J.-L., Castedo M., Roumier T., Andreau K., Nardacci R.,
RA   Piacentini M., Kroemer G.;
RT   "Mechanisms of apoptosis induction by the HIV-1 envelope.";
RL   Cell Death Differ. 12:916-923(2005).
RN   [5]
RP   REVIEW.
RX   PubMed=15725757; DOI=10.1089/aid.2005.21.171;
RA   Hartley O., Klasse P.J., Sattentau Q.J., Moore J.P.;
RT   "V3: HIV's switch-hitter.";
RL   AIDS Res. Hum. Retroviruses 21:171-189(2005).
RN   [6]
RP   REVIEW.
RX   PubMed=16114975; DOI=10.2165/00003495-200565130-00002;
RA   Reeves J.D., Piefer A.J.;
RT   "Emerging drug targets for antiretroviral therapy.";
RL   Drugs 65:1747-1766(2005).
RN   [7]
RP   REVIEW.
RX   PubMed=16437164; DOI=10.1038/sj.emboj.7600947;
RA   Lusso P.;
RT   "HIV and the chemokine system: 10 years later.";
RL   EMBO J. 25:447-456(2006).
CC   -!- FUNCTION: [Envelope glycoprotein gp160]: Oligomerizes in the host
CC       endoplasmic reticulum into predominantly trimers. In a second time,
CC       gp160 transits in the host Golgi, where glycosylation is completed. The
CC       precursor is then proteolytically cleaved in the trans-Golgi and
CC       thereby activated by cellular furin or furin-like proteases to produce
CC       gp120 and gp41. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- FUNCTION: [Surface protein gp120]: Attaches the virus to the host
CC       lymphoid cell by binding to the primary receptor CD4. This interaction
CC       induces a structural rearrangement creating a high affinity binding
CC       site for a chemokine coreceptor like CXCR4 and/or CCR5. Acts as a
CC       ligand for CD209/DC-SIGN and CLEC4M/DC-SIGNR, which are respectively
CC       found on dendritic cells (DCs), and on endothelial cells of liver
CC       sinusoids and lymph node sinuses. These interactions allow capture of
CC       viral particles at mucosal surfaces by these cells and subsequent
CC       transmission to permissive cells. HIV subverts the migration properties
CC       of dendritic cells to gain access to CD4+ T-cells in lymph nodes. Virus
CC       transmission to permissive T-cells occurs either in trans (without DCs
CC       infection, through viral capture and transmission), or in cis
CC       (following DCs productive infection, through the usual CD4-gp120
CC       interaction), thereby inducing a robust infection. In trans infection,
CC       bound virions remain infectious over days and it is proposed that they
CC       are not degraded, but protected in non-lysosomal acidic organelles
CC       within the DCs close to the cell membrane thus contributing to the
CC       viral infectious potential during DCs' migration from the periphery to
CC       the lymphoid tissues. On arrival at lymphoid tissues, intact virions
CC       recycle back to DCs' cell surface allowing virus transmission to CD4+
CC       T-cells. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- FUNCTION: [Transmembrane protein gp41]: Acts as a class I viral fusion
CC       protein. Under the current model, the protein has at least 3
CC       conformational states: pre-fusion native state, pre-hairpin
CC       intermediate state, and post-fusion hairpin state. During fusion of
CC       viral and target intracellular membranes, the coiled coil regions
CC       (heptad repeats) assume a trimer-of-hairpins structure, positioning the
CC       fusion peptide in close proximity to the C-terminal region of the
CC       ectodomain. The formation of this structure appears to drive apposition
CC       and subsequent fusion of viral and target cell membranes. Complete
CC       fusion occurs in host cell endosomes and is dynamin-dependent, however
CC       some lipid transfer might occur at the plasma membrane. The virus
CC       undergoes clathrin-dependent internalization long before endosomal
CC       fusion, thus minimizing the surface exposure of conserved viral
CC       epitopes during fusion and reducing the efficacy of inhibitors
CC       targeting these epitopes. Membranes fusion leads to delivery of the
CC       nucleocapsid into the cytoplasm. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBUNIT: [Surface protein gp120]: The mature envelope protein (Env)
CC       consists of a homotrimer of non-covalently associated gp120-gp41
CC       heterodimers. The resulting complex protrudes from the virus surface as
CC       a spike. There seems to be as few as 10 spikes on the average virion.
CC       Interacts with host CD4, CCR5 and CXCR4. Gp120 also interacts with the
CC       C-type lectins CD209/DC-SIGN and CLEC4M/DC-SIGNR (collectively referred
CC       to as DC-SIGN(R)). Gp120 and gp41 interact with GalCer. Gp120 interacts
CC       with host ITGA4/ITGB7 complex; on CD4+ T-cells, this interaction
CC       results in rapid activation of integrin ITGAL/LFA-1, which facilitates
CC       efficient cell-to-cell spreading of HIV-1. Gp120 interacts with cell-
CC       associated heparan sulfate; this interaction increases virus
CC       infectivity on permissive cells and may be involved in infection of
CC       CD4- cells. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBUNIT: [Transmembrane protein gp41]: The mature envelope protein
CC       (Env) consists of a homotrimer of non-covalently associated gp120-gp41
CC       heterodimers. The resulting complex protrudes from the virus surface as
CC       a spike. There seems to be as few as 10 spikes on the average virion.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBCELLULAR LOCATION: [Surface protein gp120]: Virion membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Peripheral membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host cell membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Peripheral membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host endosome membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Note=The surface protein is not
CC       anchored to the viral envelope, but associates with the extravirion
CC       surface through its binding to TM. It is probably concentrated at the
CC       site of budding and incorporated into the virions possibly by contacts
CC       between the cytoplasmic tail of Env and the N-terminus of Gag.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBCELLULAR LOCATION: [Transmembrane protein gp41]: Virion membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host cell membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host endosome membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Note=It is probably concentrated at
CC       the site of budding and incorporated into the virions possibly by
CC       contacts between the cytoplasmic tail of Env and the N-terminus of Gag.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: Some of the most genetically diverse regions of the viral
CC       genome are present in Env. They are called variable regions 1 through 5
CC       (V1 through V5). Coreceptor usage of gp120 is determined mainly by the
CC       primary structure of the third variable region (V3) in the outer domain
CC       of gp120. The sequence of V3 determines which coreceptor, CCR5 and/or
CC       CXCR4 (corresponding to R5/macrophage, X4/T cell and R5X4/T cell and
CC       macrophage tropism), is used to trigger the fusion potential of the Env
CC       complex, and hence which cells the virus can infect. Binding to CCR5
CC       involves a region adjacent in addition to V3. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- DOMAIN: The membrane proximal external region (MPER) present in gp41 is
CC       a tryptophan-rich region recognized by the antibodies 2F5, Z13, and
CC       4E10. MPER seems to play a role in fusion. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- DOMAIN: The 17 amino acids long immunosuppressive region is present in
CC       many retroviral envelope proteins. Synthetic peptides derived from this
CC       relatively conserved sequence inhibit immune function in vitro and in
CC       vivo. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: The YXXL motif is involved in determining the exact site of
CC       viral release at the surface of infected mononuclear cells and promotes
CC       endocytosis. YXXL and di-leucine endocytosis motifs interact directly
CC       or indirectly with the clathrin adapter complexes, opperate
CC       independently, and their activities are not additive.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: The CD4-binding region is targeted by the antibody b12.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- PTM: Highly glycosylated by host. The high number of glycan on the
CC       protein is reffered to as 'glycan shield' because it contributes to
CC       hide protein sequence from adaptive immune system. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- PTM: Palmitoylation of the transmembrane protein and of Env polyprotein
CC       (prior to its proteolytic cleavage) is essential for their association
CC       with host cell membrane lipid rafts. Palmitoylation is therefore
CC       required for envelope trafficking to classical lipid rafts, but not for
CC       viral replication. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- PTM: Specific enzymatic cleavages in vivo yield mature proteins.
CC       Envelope glycoproteins are synthesized as an inactive precursor that is
CC       heavily N-glycosylated and processed likely by host cell furin in the
CC       Golgi to yield the mature SU and TM proteins. The cleavage site between
CC       SU and TM requires the minimal sequence [KR]-X-[KR]-R. About 2 of the 9
CC       disulfide bonds of gp41 are reduced by P4HB/PDI, following binding to
CC       CD4 receptor. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- MISCELLANEOUS: Inhibitors targeting HIV-1 viral envelope proteins are
CC       used as antiretroviral drugs. Attachment of virions to the cell surface
CC       via non-specific interactions and CD4 binding can be blocked by
CC       inhibitors that include cyanovirin-N, cyclotriazadisulfonamide analogs,
CC       PRO 2000, TNX 355 and PRO 542. In addition, BMS 806 can block CD4-
CC       induced conformational changes. Env interactions with the coreceptor
CC       molecules can be targeted by CCR5 antagonists including SCH-D,
CC       maraviroc (UK 427857) and aplaviroc (GW 873140), and the CXCR4
CC       antagonist AMD 070. Fusion of viral and cellular membranes can be
CC       inhibited by peptides such as enfuvirtide and tifuvirtide (T 1249).
CC       Resistance to inhibitors associated with mutations in Env are observed.
CC       Most of the time, single mutations confer only a modest reduction in
CC       drug susceptibility. Combination of several mutations is usually
CC       required to develop a high-level drug resistance. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- MISCELLANEOUS: HIV-1 lineages are divided in three main groups, M (for
CC       Major), O (for Outlier), and N (for New, or Non-M, Non-O). The vast
CC       majority of strains found worldwide belong to the group M. Group O
CC       seems to be endemic to and largely confined to Cameroon and neighboring
CC       countries in West Central Africa, where these viruses represent a small
CC       minority of HIV-1 strains. The group N is represented by a limited
CC       number of isolates from Cameroonian persons. The group M is further
CC       subdivided in 9 clades or subtypes (A to D, F to H, J and K).
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SIMILARITY: Belongs to the HIV-1 env protein family.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- WEB RESOURCE: Name=hivdb; Note=HIV drug resistance database;
CC       URL="https://hivdb.stanford.edu";
CC   -!- WEB RESOURCE: Name=HIV drug resistance mutations;
CC       URL="https://www.iasusa.org/content/hiv-drug-resistance-mutations";
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DR   EMBL; AH003669; AAB12990.1; -; Genomic_RNA.
DR   PDB; 2FX7; X-ray; 1.76 A; P=662-677.
DR   PDB; 2FX8; X-ray; 2.20 A; P/Q/R/S=662-673.
DR   PDB; 2FX9; X-ray; 2.10 A; P/Q=662-671.
DR   PDB; 4WY7; X-ray; 2.10 A; P=662-674.
DR   PDB; 6VPX; EM; 5.00 A; G/I/J=662-677.
DR   PDBsum; 2FX7; -.
DR   PDBsum; 2FX8; -.
DR   PDBsum; 2FX9; -.
DR   PDBsum; 4WY7; -.
DR   PDBsum; 6VPX; -.
DR   SMR; P05880; -.
DR   GlyCosmos; P05880; 28 sites, No reported glycans.
DR   Reactome; R-HSA-5621480; Dectin-2 family.
DR   EvolutionaryTrace; P05880; -.
DR   GO; GO:0044175; C:host cell endosome membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0016020; C:membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:0019031; C:viral envelope; IEA:UniProtKB-KW.
DR   GO; GO:0055036; C:virion membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005198; F:structural molecule activity; IEA:UniProtKB-UniRule.
DR   GO; GO:0075512; P:clathrin-dependent endocytosis of virus by host cell; IEA:UniProtKB-UniRule.
DR   GO; GO:0039654; P:fusion of virus membrane with host endosome membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:0019064; P:fusion of virus membrane with host plasma membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:1903905; P:positive regulation of establishment of T cell polarity; IEA:UniProtKB-UniRule.
DR   GO; GO:1903908; P:positive regulation of plasma membrane raft polarization; IEA:UniProtKB-UniRule.
DR   GO; GO:1903911; P:positive regulation of receptor clustering; IEA:UniProtKB-UniRule.
DR   GO; GO:0019082; P:viral protein processing; IEA:UniProtKB-UniRule.
DR   GO; GO:0019062; P:virion attachment to host cell; IEA:UniProtKB-UniRule.
DR   GO; GO:0019049; P:virus-mediated perturbation of host defense response; IEA:UniProtKB-UniRule.
DR   CDD; cd09909; HIV-1-like_HR1-HR2; 1.
DR   Gene3D; 1.10.287.210; -; 1.
DR   Gene3D; 2.170.40.20; Human immunodeficiency virus 1, Gp160, envelope glycoprotein; 2.
DR   Gene3D; 1.20.5.490; Single helix bin; 1.
DR   HAMAP; MF_04083; HIV_ENV; 1.
DR   InterPro; IPR036377; Gp120_core_sf.
DR   InterPro; IPR037527; Gp160.
DR   InterPro; IPR000328; GP41-like.
DR   InterPro; IPR000777; HIV1_Gp120.
DR   Pfam; PF00516; GP120; 2.
DR   Pfam; PF00517; GP41; 1.
DR   SUPFAM; SSF56502; gp120 core; 2.
DR   SUPFAM; SSF58069; Virus ectodomain; 1.
PE   1: Evidence at protein level;
KW   3D-structure; AIDS; Apoptosis;
KW   Clathrin-mediated endocytosis of virus by host;
KW   Cleavage on pair of basic residues; Coiled coil; Disulfide bond;
KW   Fusion of virus membrane with host endosomal membrane;
KW   Fusion of virus membrane with host membrane; Glycoprotein;
KW   Host cell membrane; Host endosome; Host membrane; Host-virus interaction;
KW   Lipoprotein; Membrane; Palmitate; Signal; Transmembrane;
KW   Transmembrane helix; Viral attachment to host cell; Viral envelope protein;
KW   Viral immunoevasion; Viral penetration into host cytoplasm; Virion;
KW   Virus endocytosis by host; Virus entry into host cell.
FT   SIGNAL          1..31
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CHAIN           32..847
FT                   /note="Envelope glycoprotein gp160"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000239492"
FT   CHAIN           32..501
FT                   /note="Surface protein gp120"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000038425"
FT   CHAIN           502..847
FT                   /note="Transmembrane protein gp41"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000038426"
FT   TOPO_DOM        32..675
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   TRANSMEM        676..696
FT                   /note="Helical"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   TOPO_DOM        697..847
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          130..151
FT                   /note="V1"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          152..193
FT                   /note="V2"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          293..325
FT                   /note="V3"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          358..368
FT                   /note="CD4-binding loop"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          379..408
FT                   /note="V4"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          451..461
FT                   /note="V5"
FT   REGION          453..461
FT                   /note="V5"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          502..523
FT                   /note="Fusion peptide"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          565..583
FT                   /note="Immunosuppression"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          653..674
FT                   /note="MPER; binding to GalCer"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          709..731
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COILED          624..658
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   MOTIF           703..706
FT                   /note="YXXL motif; contains endocytosis signal"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   MOTIF           846..847
FT                   /note="Di-leucine internalization motif"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   SITE            501..502
FT                   /note="Cleavage; by host furin"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   LIPID           755
FT                   /note="S-palmitoyl cysteine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   LIPID           828
FT                   /note="S-palmitoyl cysteine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        87
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        134
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        140
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        151
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        155
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        183
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        184
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        194
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        231
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        238
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        259
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        273
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        286
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        292
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        327
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        334
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        350
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        356
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        380
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        386
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        390
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        400
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        438
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        450
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        602
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        607
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        616
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        628
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        53..73
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        118..202
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        125..193
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        130..152
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        215..244
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        225..236
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        293..326
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        372..435
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        379..408
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        589..595
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   HELIX           663..665
FT                   /evidence="ECO:0007829|PDB:2FX7"
FT   HELIX           666..676
FT                   /evidence="ECO:0007829|PDB:2FX7"
SQ   SEQUENCE   847 AA;  96466 MW;  CD1E33D73AA5BCAE CRC64;
     MRVKGIMRNC QHLWIWGTML FGMWMICSAV EQLWVTVYYG VPVWKEATTT LFCASDAKAY
     STEAHNVWAT HACVPTDPNP QEVILGNVTE NFNMWKNNMV EQMHEDIISL WDQSLKPCVK
     LTPLCVTLNC IDKNITDWKN TTIIGGGEVK NCSFNITTSR RDKVHKEYAL FYKLDVVPIK
     GDNNSSRYRL INCNTSVITQ ACPKVSFEPI PIHYCAPAGF AILKCNDKKF NGTGPCTNVS
     TVQCTHGIRP VVSTQLLLNG SLAEEEIVIR SENFTDNAKT IIVHLNESVE INCTRPYNNV
     RRSLSIGPGR AFRTREIIGI IRQAHCNISR AKWNNTLKQI VEKLREQFKN KTIVFNHSSG
     GDPEIVTHSF NCGGEFFYCN STQLFNSTWN GTDIKGDNKN STLITLPCRI KQIINMWQGV
     GKAMYAPPIQ GQIRCSSNIT GLLLTRDGGN SSSREEIFRP GGGNMRDNWR SELYKYKVVR
     IEPLGVAPTK AKRRVVQREK RAVGTIGAMF LGFLGAAGST MGAGSLTLTV QARQLLSGIV
     QQQNNLLRAI DAQQHLLQLT VWGIKQLQAR VLAVERYLRD QQLLGIWGCS GKLICTTTVP
     WNASWSNKSM NQIWDNLTWM EWEREIDNYT SIIYSLIEES QNQQGKNEQE LLELDKWASL
     WNWFDITNWL WYIKIFIMIV GGLIGLRIVF TVLSIVNRVR QGYSPLSFQT HLPTPRGPDR
     PEGIEEEGGE RDRDRSVRLV HGFLALIWDD LRSLCLFSYH RLRDLLLIVK RIVELLGRRG
     WEALKYWWNL LQYWSKELKN SAVGLLNAIA IAVAEGTDRV IEVVQRICRA IIHIPRRIRQ
     GLERALL
//
ID   ENV_HV1Y2               Reviewed;         843 AA.
AC   P35961;
DT   01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT   01-JUN-1994, sequence version 1.
DT   27-MAR-2024, entry version 176.
DE   RecName: Full=Envelope glycoprotein gp160 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   AltName: Full=Env polyprotein {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Contains:
DE     RecName: Full=Surface protein gp120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=SU {ECO:0000255|HAMAP-Rule:MF_04083};
DE     AltName: Full=Glycoprotein 120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=gp120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Contains:
DE     RecName: Full=Transmembrane protein gp41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=TM {ECO:0000255|HAMAP-Rule:MF_04083};
DE     AltName: Full=Glycoprotein 41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=gp41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Flags: Precursor;
GN   Name=env {ECO:0000255|HAMAP-Rule:MF_04083};
OS   Human immunodeficiency virus type 1 group M subtype B (isolate YU-2)
OS   (HIV-1).
OC   Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC   Ortervirales; Retroviridae; Orthoretrovirinae; Lentivirus;
OC   Human immunodeficiency virus 1.
OX   NCBI_TaxID=362651;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX   PubMed=1404605; DOI=10.1128/jvi.66.11.6587-6600.1992;
RA   Li Y., Hui H., Burgess C.J., Price R.W., Sharp P.M., Hahn B.H., Shaw G.M.;
RT   "Complete nucleotide sequence, genome organization, and biological
RT   properties of human immunodeficiency virus type 1 in vivo: evidence for
RT   limited defectiveness and complementation.";
RL   J. Virol. 66:6587-6600(1992).
RN   [2]
RP   INTERACTION OF SURFACE PROTEIN GP120 WITH HUMAN CCR5.
RX   PubMed=9632396; DOI=10.1126/science.280.5371.1949;
RA   Rizzuto C.D., Wyatt R., Hernandez-Ramos N., Sun Y., Kwong P.D.,
RA   Hendrickson W.A., Sodroski J.;
RT   "A conserved HIV gp120 glycoprotein structure involved in chemokine
RT   receptor binding.";
RL   Science 280:1949-1953(1998).
RN   [3]
RP   REVIEW.
RX   PubMed=12974773; DOI=10.1034/j.1600-0463.2003.11107803.x;
RA   Geijtenbeek T.B., van Kooyk Y.;
RT   "Pathogens target DC-SIGN to influence their fate DC-SIGN functions as a
RT   pathogen receptor with broad specificity.";
RL   APMIS 111:698-714(2003).
RN   [4]
RP   REVIEW.
RX   PubMed=12873764; DOI=10.1016/s0005-2736(03)00161-5;
RA   Gallo S.A., Finnegan C.M., Viard M., Raviv Y., Dimitrov A., Rawat S.S.,
RA   Puri A., Durell S., Blumenthal R.;
RT   "The HIV Env-mediated fusion reaction.";
RL   Biochim. Biophys. Acta 1614:36-50(2003).
RN   [5]
RP   REVIEW.
RX   PubMed=15719026; DOI=10.1038/sj.cdd.4401584;
RA   Perfettini J.-L., Castedo M., Roumier T., Andreau K., Nardacci R.,
RA   Piacentini M., Kroemer G.;
RT   "Mechanisms of apoptosis induction by the HIV-1 envelope.";
RL   Cell Death Differ. 12:916-923(2005).
RN   [6]
RP   REVIEW.
RX   PubMed=15725757; DOI=10.1089/aid.2005.21.171;
RA   Hartley O., Klasse P.J., Sattentau Q.J., Moore J.P.;
RT   "V3: HIV's switch-hitter.";
RL   AIDS Res. Hum. Retroviruses 21:171-189(2005).
RN   [7]
RP   REVIEW.
RX   PubMed=16114975; DOI=10.2165/00003495-200565130-00002;
RA   Reeves J.D., Piefer A.J.;
RT   "Emerging drug targets for antiretroviral therapy.";
RL   Drugs 65:1747-1766(2005).
RN   [8]
RP   REVIEW.
RX   PubMed=16437164; DOI=10.1038/sj.emboj.7600947;
RA   Lusso P.;
RT   "HIV and the chemokine system: 10 years later.";
RL   EMBO J. 25:447-456(2006).
CC   -!- FUNCTION: [Envelope glycoprotein gp160]: Oligomerizes in the host
CC       endoplasmic reticulum into predominantly trimers. In a second time,
CC       gp160 transits in the host Golgi, where glycosylation is completed. The
CC       precursor is then proteolytically cleaved in the trans-Golgi and
CC       thereby activated by cellular furin or furin-like proteases to produce
CC       gp120 and gp41. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- FUNCTION: [Surface protein gp120]: Attaches the virus to the host
CC       lymphoid cell by binding to the primary receptor CD4. This interaction
CC       induces a structural rearrangement creating a high affinity binding
CC       site for a chemokine coreceptor like CXCR4 and/or CCR5. Acts as a
CC       ligand for CD209/DC-SIGN and CLEC4M/DC-SIGNR, which are respectively
CC       found on dendritic cells (DCs), and on endothelial cells of liver
CC       sinusoids and lymph node sinuses. These interactions allow capture of
CC       viral particles at mucosal surfaces by these cells and subsequent
CC       transmission to permissive cells. HIV subverts the migration properties
CC       of dendritic cells to gain access to CD4+ T-cells in lymph nodes. Virus
CC       transmission to permissive T-cells occurs either in trans (without DCs
CC       infection, through viral capture and transmission), or in cis
CC       (following DCs productive infection, through the usual CD4-gp120
CC       interaction), thereby inducing a robust infection. In trans infection,
CC       bound virions remain infectious over days and it is proposed that they
CC       are not degraded, but protected in non-lysosomal acidic organelles
CC       within the DCs close to the cell membrane thus contributing to the
CC       viral infectious potential during DCs' migration from the periphery to
CC       the lymphoid tissues. On arrival at lymphoid tissues, intact virions
CC       recycle back to DCs' cell surface allowing virus transmission to CD4+
CC       T-cells. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- FUNCTION: [Transmembrane protein gp41]: Acts as a class I viral fusion
CC       protein. Under the current model, the protein has at least 3
CC       conformational states: pre-fusion native state, pre-hairpin
CC       intermediate state, and post-fusion hairpin state. During fusion of
CC       viral and target intracellular membranes, the coiled coil regions
CC       (heptad repeats) assume a trimer-of-hairpins structure, positioning the
CC       fusion peptide in close proximity to the C-terminal region of the
CC       ectodomain. The formation of this structure appears to drive apposition
CC       and subsequent fusion of viral and target cell membranes. Complete
CC       fusion occurs in host cell endosomes and is dynamin-dependent, however
CC       some lipid transfer might occur at the plasma membrane. The virus
CC       undergoes clathrin-dependent internalization long before endosomal
CC       fusion, thus minimizing the surface exposure of conserved viral
CC       epitopes during fusion and reducing the efficacy of inhibitors
CC       targeting these epitopes. Membranes fusion leads to delivery of the
CC       nucleocapsid into the cytoplasm. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBUNIT: [Surface protein gp120]: The mature envelope protein (Env)
CC       consists of a homotrimer of non-covalently associated gp120-gp41
CC       heterodimers. The resulting complex protrudes from the virus surface as
CC       a spike. There seems to be as few as 10 spikes on the average virion.
CC       Interacts with host CD4, CCR5 and CXCR4. Gp120 also interacts with the
CC       C-type lectins CD209/DC-SIGN and CLEC4M/DC-SIGNR (collectively referred
CC       to as DC-SIGN(R)). Gp120 and gp41 interact with GalCer. Gp120 interacts
CC       with host ITGA4/ITGB7 complex; on CD4+ T-cells, this interaction
CC       results in rapid activation of integrin ITGAL/LFA-1, which facilitates
CC       efficient cell-to-cell spreading of HIV-1. Gp120 interacts with cell-
CC       associated heparan sulfate; this interaction increases virus
CC       infectivity on permissive cells and may be involved in infection of
CC       CD4- cells. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBUNIT: [Transmembrane protein gp41]: The mature envelope protein
CC       (Env) consists of a homotrimer of non-covalently associated gp120-gp41
CC       heterodimers. The resulting complex protrudes from the virus surface as
CC       a spike. There seems to be as few as 10 spikes on the average virion.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBCELLULAR LOCATION: [Surface protein gp120]: Virion membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Peripheral membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host cell membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Peripheral membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host endosome membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Note=The surface protein is not
CC       anchored to the viral envelope, but associates with the extravirion
CC       surface through its binding to TM. It is probably concentrated at the
CC       site of budding and incorporated into the virions possibly by contacts
CC       between the cytoplasmic tail of Env and the N-terminus of Gag.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBCELLULAR LOCATION: [Transmembrane protein gp41]: Virion membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host cell membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host endosome membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Note=It is probably concentrated at
CC       the site of budding and incorporated into the virions possibly by
CC       contacts between the cytoplasmic tail of Env and the N-terminus of Gag.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: Some of the most genetically diverse regions of the viral
CC       genome are present in Env. They are called variable regions 1 through 5
CC       (V1 through V5). Coreceptor usage of gp120 is determined mainly by the
CC       primary structure of the third variable region (V3) in the outer domain
CC       of gp120. The sequence of V3 determines which coreceptor, CCR5 and/or
CC       CXCR4 (corresponding to R5/macrophage, X4/T cell and R5X4/T cell and
CC       macrophage tropism), is used to trigger the fusion potential of the Env
CC       complex, and hence which cells the virus can infect. Binding to CCR5
CC       involves a region adjacent in addition to V3. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- DOMAIN: The membrane proximal external region (MPER) present in gp41 is
CC       a tryptophan-rich region recognized by the antibodies 2F5, Z13, and
CC       4E10. MPER seems to play a role in fusion. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- DOMAIN: The 17 amino acids long immunosuppressive region is present in
CC       many retroviral envelope proteins. Synthetic peptides derived from this
CC       relatively conserved sequence inhibit immune function in vitro and in
CC       vivo. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: The YXXL motif is involved in determining the exact site of
CC       viral release at the surface of infected mononuclear cells and promotes
CC       endocytosis. YXXL and di-leucine endocytosis motifs interact directly
CC       or indirectly with the clathrin adapter complexes, opperate
CC       independently, and their activities are not additive.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: The CD4-binding region is targeted by the antibody b12.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- PTM: Highly glycosylated by host. The high number of glycan on the
CC       protein is reffered to as 'glycan shield' because it contributes to
CC       hide protein sequence from adaptive immune system. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- PTM: Palmitoylation of the transmembrane protein and of Env polyprotein
CC       (prior to its proteolytic cleavage) is essential for their association
CC       with host cell membrane lipid rafts. Palmitoylation is therefore
CC       required for envelope trafficking to classical lipid rafts, but not for
CC       viral replication. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- PTM: Specific enzymatic cleavages in vivo yield mature proteins.
CC       Envelope glycoproteins are synthesized as an inactive precursor that is
CC       heavily N-glycosylated and processed likely by host cell furin in the
CC       Golgi to yield the mature SU and TM proteins. The cleavage site between
CC       SU and TM requires the minimal sequence [KR]-X-[KR]-R. About 2 of the 9
CC       disulfide bonds of gp41 are reduced by P4HB/PDI, following binding to
CC       CD4 receptor. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- MISCELLANEOUS: Inhibitors targeting HIV-1 viral envelope proteins are
CC       used as antiretroviral drugs. Attachment of virions to the cell surface
CC       via non-specific interactions and CD4 binding can be blocked by
CC       inhibitors that include cyanovirin-N, cyclotriazadisulfonamide analogs,
CC       PRO 2000, TNX 355 and PRO 542. In addition, BMS 806 can block CD4-
CC       induced conformational changes. Env interactions with the coreceptor
CC       molecules can be targeted by CCR5 antagonists including SCH-D,
CC       maraviroc (UK 427857) and aplaviroc (GW 873140), and the CXCR4
CC       antagonist AMD 070. Fusion of viral and cellular membranes can be
CC       inhibited by peptides such as enfuvirtide and tifuvirtide (T 1249).
CC       Resistance to inhibitors associated with mutations in Env are observed.
CC       Most of the time, single mutations confer only a modest reduction in
CC       drug susceptibility. Combination of several mutations is usually
CC       required to develop a high-level drug resistance. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- MISCELLANEOUS: HIV-1 lineages are divided in three main groups, M (for
CC       Major), O (for Outlier), and N (for New, or Non-M, Non-O). The vast
CC       majority of strains found worldwide belong to the group M. Group O
CC       seems to be endemic to and largely confined to Cameroon and neighboring
CC       countries in West Central Africa, where these viruses represent a small
CC       minority of HIV-1 strains. The group N is represented by a limited
CC       number of isolates from Cameroonian persons. The group M is further
CC       subdivided in 9 clades or subtypes (A to D, F to H, J and K).
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SIMILARITY: Belongs to the HIV-1 env protein family.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- WEB RESOURCE: Name=hivdb; Note=HIV drug resistance database;
CC       URL="https://hivdb.stanford.edu";
CC   -!- WEB RESOURCE: Name=HIV drug resistance mutations;
CC       URL="https://www.iasusa.org/content/hiv-drug-resistance-mutations";
CC   ---------------------------------------------------------------------------
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DR   EMBL; M93258; -; NOT_ANNOTATED_CDS; Genomic_RNA.
DR   PIR; H44001; H44001.
DR   PDB; 1G9N; X-ray; 2.90 A; G=82-126, G=191-293, G=325-479.
DR   PDB; 1RZK; X-ray; 2.90 A; G=82-479.
DR   PDB; 1YYL; X-ray; 2.75 A; G/P=82-126, G/P=191-293, G/P=325-483.
DR   PDB; 1YYM; X-ray; 2.20 A; G/P=82-126, G/P=191-296, G/P=325-483.
DR   PDB; 2I5Y; X-ray; 2.20 A; G/P=82-126, G/P=191-293, G/P=325-479.
DR   PDB; 2I60; X-ray; 2.40 A; G/P=82-126, G/P=191-293, G/P=325-479.
DR   PDB; 2NY7; X-ray; 2.30 A; G=158-479.
DR   PDB; 2QAD; X-ray; 3.30 A; A/E=88-120, A/E=195-479.
DR   PDB; 3HI1; X-ray; 2.90 A; G/J=89-122, G/J=195-479.
DR   PDB; 3TGQ; X-ray; 3.40 A; A/B/C/D=43-479.
DR   PDB; 4DVR; X-ray; 2.50 A; G=82-122, G=199-301, G=324-484.
DR   PDB; 4JO3; X-ray; 2.60 A; P/Q=313-327.
DR   PDB; 4JZW; X-ray; 1.78 A; A/G=43-479.
DR   PDB; 4JZZ; X-ray; 1.49 A; A=43-479.
DR   PDB; 4K0A; X-ray; 2.13 A; A=43-479.
DR   PDB; 4KA2; X-ray; 1.79 A; A=43-479.
DR   PDB; 4LAJ; X-ray; 2.14 A; A/B/F/J=43-479.
DR   PDB; 4R4F; X-ray; 3.51 A; A=43-479.
DR   PDB; 4RQS; X-ray; 4.49 A; G=82-126, G=191-293, G=325-479.
DR   PDB; 4RWY; X-ray; 2.13 A; A=43-479.
DR   PDB; 5A7X; EM; 17.00 A; A/E/I=82-479.
DR   PDB; 5A8H; EM; 23.00 A; A/G/M=82-479.
DR   PDBsum; 1G9N; -.
DR   PDBsum; 1RZK; -.
DR   PDBsum; 1YYL; -.
DR   PDBsum; 1YYM; -.
DR   PDBsum; 2I5Y; -.
DR   PDBsum; 2I60; -.
DR   PDBsum; 2NY7; -.
DR   PDBsum; 2QAD; -.
DR   PDBsum; 3HI1; -.
DR   PDBsum; 3TGQ; -.
DR   PDBsum; 4DVR; -.
DR   PDBsum; 4JO3; -.
DR   PDBsum; 4JZW; -.
DR   PDBsum; 4JZZ; -.
DR   PDBsum; 4K0A; -.
DR   PDBsum; 4KA2; -.
DR   PDBsum; 4LAJ; -.
DR   PDBsum; 4R4F; -.
DR   PDBsum; 4RQS; -.
DR   PDBsum; 4RWY; -.
DR   PDBsum; 5A7X; -.
DR   PDBsum; 5A8H; -.
DR   SMR; P35961; -.
DR   DIP; DIP-48439N; -.
DR   IntAct; P35961; 1.
DR   BindingDB; P35961; -.
DR   ChEMBL; CHEMBL6180; -.
DR   DrugBank; DB11854; Astodrimer.
DR   DrugBank; DB04639; Biphenylalanine.
DR   GlyCosmos; P35961; 27 sites, No reported glycans.
DR   ABCD; P35961; 6 sequenced antibodies.
DR   Reactome; R-HSA-5621480; Dectin-2 family.
DR   EvolutionaryTrace; P35961; -.
DR   Proteomes; UP000007419; Genome.
DR   GO; GO:0044175; C:host cell endosome membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0016020; C:membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:0019031; C:viral envelope; IEA:UniProtKB-KW.
DR   GO; GO:0055036; C:virion membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005198; F:structural molecule activity; IEA:UniProtKB-UniRule.
DR   GO; GO:0075512; P:clathrin-dependent endocytosis of virus by host cell; IEA:UniProtKB-UniRule.
DR   GO; GO:0039654; P:fusion of virus membrane with host endosome membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:0019064; P:fusion of virus membrane with host plasma membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:1903905; P:positive regulation of establishment of T cell polarity; IEA:UniProtKB-UniRule.
DR   GO; GO:1903908; P:positive regulation of plasma membrane raft polarization; IEA:UniProtKB-UniRule.
DR   GO; GO:1903911; P:positive regulation of receptor clustering; IEA:UniProtKB-UniRule.
DR   GO; GO:0019082; P:viral protein processing; IEA:UniProtKB-UniRule.
DR   GO; GO:0019062; P:virion attachment to host cell; IEA:UniProtKB-UniRule.
DR   GO; GO:0019049; P:virus-mediated perturbation of host defense response; IEA:UniProtKB-UniRule.
DR   CDD; cd09909; HIV-1-like_HR1-HR2; 1.
DR   Gene3D; 1.10.287.210; -; 1.
DR   Gene3D; 2.170.40.20; Human immunodeficiency virus 1, Gp160, envelope glycoprotein; 2.
DR   Gene3D; 1.20.5.490; Single helix bin; 1.
DR   HAMAP; MF_04083; HIV_ENV; 1.
DR   InterPro; IPR036377; Gp120_core_sf.
DR   InterPro; IPR037527; Gp160.
DR   InterPro; IPR000328; GP41-like.
DR   InterPro; IPR000777; HIV1_Gp120.
DR   Pfam; PF00516; GP120; 1.
DR   Pfam; PF00517; GP41; 1.
DR   SUPFAM; SSF56502; gp120 core; 2.
DR   SUPFAM; SSF58069; Virus ectodomain; 1.
PE   1: Evidence at protein level;
KW   3D-structure; AIDS; Apoptosis;
KW   Clathrin-mediated endocytosis of virus by host;
KW   Cleavage on pair of basic residues; Coiled coil; Disulfide bond;
KW   Fusion of virus membrane with host endosomal membrane;
KW   Fusion of virus membrane with host membrane; Glycoprotein;
KW   Host cell membrane; Host endosome; Host membrane; Host-virus interaction;
KW   Lipoprotein; Membrane; Palmitate; Signal; Transmembrane;
KW   Transmembrane helix; Viral attachment to host cell; Viral envelope protein;
KW   Viral immunoevasion; Viral penetration into host cytoplasm; Virion;
KW   Virus endocytosis by host; Virus entry into host cell.
FT   SIGNAL          1..31
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CHAIN           32..843
FT                   /note="Envelope glycoprotein gp160"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000239469"
FT   CHAIN           32..498
FT                   /note="Surface protein gp120"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000038377"
FT   CHAIN           499..843
FT                   /note="Transmembrane protein gp41"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000038378"
FT   TOPO_DOM        32..671
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   TRANSMEM        672..692
FT                   /note="Helical"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   TOPO_DOM        693..843
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          130..154
FT                   /note="V1"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          155..192
FT                   /note="V2"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          292..325
FT                   /note="V3"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          359..369
FT                   /note="CD4-binding loop"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          380..405
FT                   /note="V4"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          448..458
FT                   /note="V5"
FT   REGION          450..458
FT                   /note="V5"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          499..519
FT                   /note="Fusion peptide"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          561..579
FT                   /note="Immunosuppression"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          649..670
FT                   /note="MPER; binding to GalCer"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          706..731
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COILED          620..654
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   MOTIF           699..702
FT                   /note="YXXL motif; contains endocytosis signal"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   MOTIF           842..843
FT                   /note="Di-leucine internalization motif"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   COMPBIAS        714..731
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   SITE            498..499
FT                   /note="Cleavage; by host furin"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   LIPID           751
FT                   /note="S-palmitoyl cysteine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        87
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        129
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        135
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        138
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        154
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        158
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        184
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        193
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        230
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        237
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        258
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        272
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        285
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        291
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        297
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        327
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        351
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        381
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        389
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        395
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        400
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        435
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        450
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        598
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        603
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        612
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        624
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        53..73
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        118..201
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        125..192
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        130..155
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        214..243
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        224..235
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        292..326
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        373..432
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        380..405
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        585..591
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   STRAND          52..55
FT                   /evidence="ECO:0007829|PDB:4JZZ"
FT   STRAND          59..61
FT                   /evidence="ECO:0007829|PDB:3TGQ"
FT   HELIX           64..72
FT                   /evidence="ECO:0007829|PDB:4JZZ"
FT   STRAND          73..75
FT                   /evidence="ECO:0007829|PDB:4JZZ"
FT   STRAND          82..84
FT                   /evidence="ECO:0007829|PDB:4JZZ"
FT   STRAND          90..93
FT                   /evidence="ECO:0007829|PDB:4JZZ"
FT   HELIX           94..96
FT                   /evidence="ECO:0007829|PDB:4RWY"
FT   HELIX           98..114
FT                   /evidence="ECO:0007829|PDB:4JZZ"
FT   STRAND          118..122
FT                   /evidence="ECO:0007829|PDB:4JZZ"
FT   STRAND          127..129
FT                   /evidence="ECO:0007829|PDB:1G9N"
FT   STRAND          195..198
FT                   /evidence="ECO:0007829|PDB:4JZZ"
FT   STRAND          201..204
FT                   /evidence="ECO:0007829|PDB:3HI1"
FT   STRAND          211..214
FT                   /evidence="ECO:0007829|PDB:4JZZ"
FT   STRAND          219..224
FT                   /evidence="ECO:0007829|PDB:4JZZ"
FT   STRAND          231..243
FT                   /evidence="ECO:0007829|PDB:4JZZ"
FT   STRAND          252..258
FT                   /evidence="ECO:0007829|PDB:4JZZ"
FT   STRAND          263..265
FT                   /evidence="ECO:0007829|PDB:4JZZ"
FT   STRAND          267..269
FT                   /evidence="ECO:0007829|PDB:4JZZ"
FT   STRAND          276..278
FT                   /evidence="ECO:0007829|PDB:4DVR"
FT   STRAND          280..294
FT                   /evidence="ECO:0007829|PDB:4JZZ"
FT   STRAND          298..300
FT                   /evidence="ECO:0007829|PDB:2QAD"
FT   TURN            306..308
FT                   /evidence="ECO:0007829|PDB:1G9N"
FT   STRAND          323..329
FT                   /evidence="ECO:0007829|PDB:4JZZ"
FT   HELIX           330..348
FT                   /evidence="ECO:0007829|PDB:4JZZ"
FT   STRAND          350..352
FT                   /evidence="ECO:0007829|PDB:2QAD"
FT   STRAND          353..356
FT                   /evidence="ECO:0007829|PDB:4JZZ"
FT   HELIX           364..367
FT                   /evidence="ECO:0007829|PDB:4JZZ"
FT   STRAND          369..373
FT                   /evidence="ECO:0007829|PDB:4JZZ"
FT   STRAND          376..380
FT                   /evidence="ECO:0007829|PDB:4JZZ"
FT   HELIX           383..385
FT                   /evidence="ECO:0007829|PDB:4JZZ"
FT   STRAND          388..391
FT                   /evidence="ECO:0007829|PDB:1RZK"
FT   HELIX           392..394
FT                   /evidence="ECO:0007829|PDB:4LAJ"
FT   TURN            396..398
FT                   /evidence="ECO:0007829|PDB:2QAD"
FT   STRAND          400..412
FT                   /evidence="ECO:0007829|PDB:4JZZ"
FT   STRAND          414..421
FT                   /evidence="ECO:0007829|PDB:4JZZ"
FT   STRAND          426..429
FT                   /evidence="ECO:0007829|PDB:1YYM"
FT   STRAND          430..443
FT                   /evidence="ECO:0007829|PDB:4JZZ"
FT   STRAND          446..449
FT                   /evidence="ECO:0007829|PDB:2I5Y"
FT   STRAND          452..457
FT                   /evidence="ECO:0007829|PDB:4JZZ"
FT   HELIX           462..470
FT                   /evidence="ECO:0007829|PDB:4JZZ"
FT   STRAND          473..477
FT                   /evidence="ECO:0007829|PDB:4JZZ"
SQ   SEQUENCE   843 AA;  95648 MW;  C69DFD971C918B71 CRC64;
     MRATEIRKNY QHLWKGGTLL LGMLMICSAA EQLWVTVYYG VPVWKEATTT LFCASDAKAY
     DTEVHNVWAT HACVPTDPNP QEVKLENVTE NFNMWKNNMV EQMHEDIISL WDQSLKPCVK
     LTPLCVTLNC TDLRNATNTT SSSWETMEKG EIKNCSFNIT TSIRDKVQKE YALFYNLDVV
     PIDNASYRLI SCNTSVITQA CPKVSFEPIP IHYCAPAGFA ILKCNDKKFN GTGPCTNVST
     VQCTHGIRPV VSTQLLLNGS LAEEEIVIRS ENFTNNAKTI IVQLNESVVI NCTRPNNNTR
     KSINIGPGRA LYTTGEIIGD IRQAHCNLSK TQWENTLEQI AIKLKEQFGN NKTIIFNPSS
     GGDPEIVTHS FNCGGEFFYC NSTQLFTWND TRKLNNTGRN ITLPCRIKQI INMWQEVGKA
     MYAPPIRGQI RCSSNITGLL LTRDGGKDTN GTEIFRPGGG DMRDNWRSEL YKYKVVKIEP
     LGVAPTKAKR RVVQREKRAV GLGALFLGFL GAAGSTMGAA SITLTVQARQ LLSGIVQQQN
     NLLRAIEAQQ HLLQLTVWGI KQLQARVLAV ERYLRDQQLL GIWGCSGKLI CTTTVPWNTS
     WSNKSLNEIW DNMTWMKWER EIDNYTHIIY SLIEQSQNQQ EKNEQELLAL DKWASLWNWF
     DITKWLWYIK IFIMIVGGLI GLRIVFVVLS IVNRVRQGYS PLSFQTHLPA QRGPDRPDGI
     EEEGGERDRD RSGPLVDGFL AIIWVDLRSL CLFSYHRLRD LLLIVTRIVE LLGRRGWGVL
     KYWWNLLQYW IQELKNSAVS LLNATAIAVA EGTDRVIEIL QRAFRAVLHI PVRIRQGLER
     ALL
//
ID   ENV_HV1Z2               Reviewed;         853 AA.
AC   P12487;
DT   01-OCT-1989, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-1989, sequence version 1.
DT   27-MAR-2024, entry version 154.
DE   RecName: Full=Envelope glycoprotein gp160 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   AltName: Full=Env polyprotein {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Contains:
DE     RecName: Full=Surface protein gp120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=SU {ECO:0000255|HAMAP-Rule:MF_04083};
DE     AltName: Full=Glycoprotein 120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=gp120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Contains:
DE     RecName: Full=Transmembrane protein gp41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=TM {ECO:0000255|HAMAP-Rule:MF_04083};
DE     AltName: Full=Glycoprotein 41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=gp41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Flags: Precursor;
GN   Name=env {ECO:0000255|HAMAP-Rule:MF_04083};
OS   Human immunodeficiency virus type 1 group M subtype D (isolate Z2/CDC-Z34)
OS   (HIV-1).
OC   Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC   Ortervirales; Retroviridae; Orthoretrovirinae; Lentivirus;
OC   Human immunodeficiency virus 1.
OX   NCBI_TaxID=11683;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RA   Theodore T., Buckler-White A.J.;
RL   Submitted (JUL-1989) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   REVIEW.
RX   PubMed=12974773; DOI=10.1034/j.1600-0463.2003.11107803.x;
RA   Geijtenbeek T.B., van Kooyk Y.;
RT   "Pathogens target DC-SIGN to influence their fate DC-SIGN functions as a
RT   pathogen receptor with broad specificity.";
RL   APMIS 111:698-714(2003).
RN   [3]
RP   REVIEW.
RX   PubMed=12873764; DOI=10.1016/s0005-2736(03)00161-5;
RA   Gallo S.A., Finnegan C.M., Viard M., Raviv Y., Dimitrov A., Rawat S.S.,
RA   Puri A., Durell S., Blumenthal R.;
RT   "The HIV Env-mediated fusion reaction.";
RL   Biochim. Biophys. Acta 1614:36-50(2003).
RN   [4]
RP   REVIEW.
RX   PubMed=15719026; DOI=10.1038/sj.cdd.4401584;
RA   Perfettini J.-L., Castedo M., Roumier T., Andreau K., Nardacci R.,
RA   Piacentini M., Kroemer G.;
RT   "Mechanisms of apoptosis induction by the HIV-1 envelope.";
RL   Cell Death Differ. 12:916-923(2005).
RN   [5]
RP   REVIEW.
RX   PubMed=15725757; DOI=10.1089/aid.2005.21.171;
RA   Hartley O., Klasse P.J., Sattentau Q.J., Moore J.P.;
RT   "V3: HIV's switch-hitter.";
RL   AIDS Res. Hum. Retroviruses 21:171-189(2005).
RN   [6]
RP   REVIEW.
RX   PubMed=16114975; DOI=10.2165/00003495-200565130-00002;
RA   Reeves J.D., Piefer A.J.;
RT   "Emerging drug targets for antiretroviral therapy.";
RL   Drugs 65:1747-1766(2005).
RN   [7]
RP   REVIEW.
RX   PubMed=16437164; DOI=10.1038/sj.emboj.7600947;
RA   Lusso P.;
RT   "HIV and the chemokine system: 10 years later.";
RL   EMBO J. 25:447-456(2006).
CC   -!- FUNCTION: [Envelope glycoprotein gp160]: Oligomerizes in the host
CC       endoplasmic reticulum into predominantly trimers. In a second time,
CC       gp160 transits in the host Golgi, where glycosylation is completed. The
CC       precursor is then proteolytically cleaved in the trans-Golgi and
CC       thereby activated by cellular furin or furin-like proteases to produce
CC       gp120 and gp41. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- FUNCTION: [Surface protein gp120]: Attaches the virus to the host
CC       lymphoid cell by binding to the primary receptor CD4. This interaction
CC       induces a structural rearrangement creating a high affinity binding
CC       site for a chemokine coreceptor like CXCR4 and/or CCR5. Acts as a
CC       ligand for CD209/DC-SIGN and CLEC4M/DC-SIGNR, which are respectively
CC       found on dendritic cells (DCs), and on endothelial cells of liver
CC       sinusoids and lymph node sinuses. These interactions allow capture of
CC       viral particles at mucosal surfaces by these cells and subsequent
CC       transmission to permissive cells. HIV subverts the migration properties
CC       of dendritic cells to gain access to CD4+ T-cells in lymph nodes. Virus
CC       transmission to permissive T-cells occurs either in trans (without DCs
CC       infection, through viral capture and transmission), or in cis
CC       (following DCs productive infection, through the usual CD4-gp120
CC       interaction), thereby inducing a robust infection. In trans infection,
CC       bound virions remain infectious over days and it is proposed that they
CC       are not degraded, but protected in non-lysosomal acidic organelles
CC       within the DCs close to the cell membrane thus contributing to the
CC       viral infectious potential during DCs' migration from the periphery to
CC       the lymphoid tissues. On arrival at lymphoid tissues, intact virions
CC       recycle back to DCs' cell surface allowing virus transmission to CD4+
CC       T-cells. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- FUNCTION: [Transmembrane protein gp41]: Acts as a class I viral fusion
CC       protein. Under the current model, the protein has at least 3
CC       conformational states: pre-fusion native state, pre-hairpin
CC       intermediate state, and post-fusion hairpin state. During fusion of
CC       viral and target intracellular membranes, the coiled coil regions
CC       (heptad repeats) assume a trimer-of-hairpins structure, positioning the
CC       fusion peptide in close proximity to the C-terminal region of the
CC       ectodomain. The formation of this structure appears to drive apposition
CC       and subsequent fusion of viral and target cell membranes. Complete
CC       fusion occurs in host cell endosomes and is dynamin-dependent, however
CC       some lipid transfer might occur at the plasma membrane. The virus
CC       undergoes clathrin-dependent internalization long before endosomal
CC       fusion, thus minimizing the surface exposure of conserved viral
CC       epitopes during fusion and reducing the efficacy of inhibitors
CC       targeting these epitopes. Membranes fusion leads to delivery of the
CC       nucleocapsid into the cytoplasm. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBUNIT: [Surface protein gp120]: The mature envelope protein (Env)
CC       consists of a homotrimer of non-covalently associated gp120-gp41
CC       heterodimers. The resulting complex protrudes from the virus surface as
CC       a spike. There seems to be as few as 10 spikes on the average virion.
CC       Interacts with host CD4, CCR5 and CXCR4. Gp120 also interacts with the
CC       C-type lectins CD209/DC-SIGN and CLEC4M/DC-SIGNR (collectively referred
CC       to as DC-SIGN(R)). Gp120 and gp41 interact with GalCer. Gp120 interacts
CC       with host ITGA4/ITGB7 complex; on CD4+ T-cells, this interaction
CC       results in rapid activation of integrin ITGAL/LFA-1, which facilitates
CC       efficient cell-to-cell spreading of HIV-1. Gp120 interacts with cell-
CC       associated heparan sulfate; this interaction increases virus
CC       infectivity on permissive cells and may be involved in infection of
CC       CD4- cells. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBUNIT: [Transmembrane protein gp41]: The mature envelope protein
CC       (Env) consists of a homotrimer of non-covalently associated gp120-gp41
CC       heterodimers. The resulting complex protrudes from the virus surface as
CC       a spike. There seems to be as few as 10 spikes on the average virion.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBCELLULAR LOCATION: [Surface protein gp120]: Virion membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Peripheral membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host cell membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Peripheral membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host endosome membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Note=The surface protein is not
CC       anchored to the viral envelope, but associates with the extravirion
CC       surface through its binding to TM. It is probably concentrated at the
CC       site of budding and incorporated into the virions possibly by contacts
CC       between the cytoplasmic tail of Env and the N-terminus of Gag.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBCELLULAR LOCATION: [Transmembrane protein gp41]: Virion membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host cell membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host endosome membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Note=It is probably concentrated at
CC       the site of budding and incorporated into the virions possibly by
CC       contacts between the cytoplasmic tail of Env and the N-terminus of Gag.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: Some of the most genetically diverse regions of the viral
CC       genome are present in Env. They are called variable regions 1 through 5
CC       (V1 through V5). Coreceptor usage of gp120 is determined mainly by the
CC       primary structure of the third variable region (V3) in the outer domain
CC       of gp120. The sequence of V3 determines which coreceptor, CCR5 and/or
CC       CXCR4 (corresponding to R5/macrophage, X4/T cell and R5X4/T cell and
CC       macrophage tropism), is used to trigger the fusion potential of the Env
CC       complex, and hence which cells the virus can infect. Binding to CCR5
CC       involves a region adjacent in addition to V3. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- DOMAIN: The membrane proximal external region (MPER) present in gp41 is
CC       a tryptophan-rich region recognized by the antibodies 2F5, Z13, and
CC       4E10. MPER seems to play a role in fusion. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- DOMAIN: The 17 amino acids long immunosuppressive region is present in
CC       many retroviral envelope proteins. Synthetic peptides derived from this
CC       relatively conserved sequence inhibit immune function in vitro and in
CC       vivo. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: The YXXL motif is involved in determining the exact site of
CC       viral release at the surface of infected mononuclear cells and promotes
CC       endocytosis. YXXL and di-leucine endocytosis motifs interact directly
CC       or indirectly with the clathrin adapter complexes, opperate
CC       independently, and their activities are not additive.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: The CD4-binding region is targeted by the antibody b12.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- PTM: Highly glycosylated by host. The high number of glycan on the
CC       protein is reffered to as 'glycan shield' because it contributes to
CC       hide protein sequence from adaptive immune system. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- PTM: Palmitoylation of the transmembrane protein and of Env polyprotein
CC       (prior to its proteolytic cleavage) is essential for their association
CC       with host cell membrane lipid rafts. Palmitoylation is therefore
CC       required for envelope trafficking to classical lipid rafts, but not for
CC       viral replication. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- PTM: Specific enzymatic cleavages in vivo yield mature proteins.
CC       Envelope glycoproteins are synthesized as an inactive precursor that is
CC       heavily N-glycosylated and processed likely by host cell furin in the
CC       Golgi to yield the mature SU and TM proteins. The cleavage site between
CC       SU and TM requires the minimal sequence [KR]-X-[KR]-R. About 2 of the 9
CC       disulfide bonds of gp41 are reduced by P4HB/PDI, following binding to
CC       CD4 receptor. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- MISCELLANEOUS: Inhibitors targeting HIV-1 viral envelope proteins are
CC       used as antiretroviral drugs. Attachment of virions to the cell surface
CC       via non-specific interactions and CD4 binding can be blocked by
CC       inhibitors that include cyanovirin-N, cyclotriazadisulfonamide analogs,
CC       PRO 2000, TNX 355 and PRO 542. In addition, BMS 806 can block CD4-
CC       induced conformational changes. Env interactions with the coreceptor
CC       molecules can be targeted by CCR5 antagonists including SCH-D,
CC       maraviroc (UK 427857) and aplaviroc (GW 873140), and the CXCR4
CC       antagonist AMD 070. Fusion of viral and cellular membranes can be
CC       inhibited by peptides such as enfuvirtide and tifuvirtide (T 1249).
CC       Resistance to inhibitors associated with mutations in Env are observed.
CC       Most of the time, single mutations confer only a modest reduction in
CC       drug susceptibility. Combination of several mutations is usually
CC       required to develop a high-level drug resistance. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- MISCELLANEOUS: HIV-1 lineages are divided in three main groups, M (for
CC       Major), O (for Outlier), and N (for New, or Non-M, Non-O). The vast
CC       majority of strains found worldwide belong to the group M. Group O
CC       seems to be endemic to and largely confined to Cameroon and neighboring
CC       countries in West Central Africa, where these viruses represent a small
CC       minority of HIV-1 strains. The group N is represented by a limited
CC       number of isolates from Cameroonian persons. The group M is further
CC       subdivided in 9 clades or subtypes (A to D, F to H, J and K).
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SIMILARITY: Belongs to the HIV-1 env protein family.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- WEB RESOURCE: Name=hivdb; Note=HIV drug resistance database;
CC       URL="https://hivdb.stanford.edu";
CC   -!- WEB RESOURCE: Name=HIV drug resistance mutations;
CC       URL="https://www.iasusa.org/content/hiv-drug-resistance-mutations";
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DR   EMBL; M22639; AAA45370.1; -; Genomic_RNA.
DR   PIR; S54384; S54384.
DR   PDB; 3UIA; X-ray; 2.00 A; A/B/C=537-589.
DR   PDBsum; 3UIA; -.
DR   SMR; P12487; -.
DR   GlyCosmos; P12487; 30 sites, No reported glycans.
DR   Reactome; R-HSA-5621480; Dectin-2 family.
DR   GO; GO:0044175; C:host cell endosome membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0016020; C:membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:0019031; C:viral envelope; IEA:UniProtKB-KW.
DR   GO; GO:0055036; C:virion membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005198; F:structural molecule activity; IEA:UniProtKB-UniRule.
DR   GO; GO:0075512; P:clathrin-dependent endocytosis of virus by host cell; IEA:UniProtKB-UniRule.
DR   GO; GO:0039654; P:fusion of virus membrane with host endosome membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:0019064; P:fusion of virus membrane with host plasma membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:1903905; P:positive regulation of establishment of T cell polarity; IEA:UniProtKB-UniRule.
DR   GO; GO:1903908; P:positive regulation of plasma membrane raft polarization; IEA:UniProtKB-UniRule.
DR   GO; GO:1903911; P:positive regulation of receptor clustering; IEA:UniProtKB-UniRule.
DR   GO; GO:0019082; P:viral protein processing; IEA:UniProtKB-UniRule.
DR   GO; GO:0019062; P:virion attachment to host cell; IEA:UniProtKB-UniRule.
DR   GO; GO:0019049; P:virus-mediated perturbation of host defense response; IEA:UniProtKB-UniRule.
DR   CDD; cd09909; HIV-1-like_HR1-HR2; 1.
DR   Gene3D; 1.10.287.210; -; 1.
DR   Gene3D; 2.170.40.20; Human immunodeficiency virus 1, Gp160, envelope glycoprotein; 2.
DR   Gene3D; 1.20.5.490; Single helix bin; 1.
DR   HAMAP; MF_04083; HIV_ENV; 1.
DR   InterPro; IPR036377; Gp120_core_sf.
DR   InterPro; IPR037527; Gp160.
DR   InterPro; IPR000328; GP41-like.
DR   InterPro; IPR000777; HIV1_Gp120.
DR   Pfam; PF00516; GP120; 2.
DR   Pfam; PF00517; GP41; 1.
DR   SUPFAM; SSF56502; gp120 core; 1.
DR   SUPFAM; SSF58069; Virus ectodomain; 1.
PE   1: Evidence at protein level;
KW   3D-structure; AIDS; Apoptosis;
KW   Clathrin-mediated endocytosis of virus by host;
KW   Cleavage on pair of basic residues; Coiled coil; Disulfide bond;
KW   Fusion of virus membrane with host endosomal membrane;
KW   Fusion of virus membrane with host membrane; Glycoprotein;
KW   Host cell membrane; Host endosome; Host membrane; Host-virus interaction;
KW   Lipoprotein; Membrane; Palmitate; Signal; Transmembrane;
KW   Transmembrane helix; Viral attachment to host cell; Viral envelope protein;
KW   Viral immunoevasion; Viral penetration into host cytoplasm; Virion;
KW   Virus endocytosis by host; Virus entry into host cell.
FT   SIGNAL          1..31
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CHAIN           32..853
FT                   /note="Envelope glycoprotein gp160"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000239471"
FT   CHAIN           32..508
FT                   /note="Surface protein gp120"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000038382"
FT   CHAIN           509..853
FT                   /note="Transmembrane protein gp41"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000038383"
FT   TOPO_DOM        32..681
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   TRANSMEM        682..702
FT                   /note="Helical"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   TOPO_DOM        703..853
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          130..153
FT                   /note="V1"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          154..197
FT                   /note="V2"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          297..329
FT                   /note="V3"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          362..372
FT                   /note="CD4-binding loop"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          383..415
FT                   /note="V4"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          457..468
FT                   /note="V5"
FT   REGION          460..468
FT                   /note="V5"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          509..529
FT                   /note="Fusion peptide"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          571..589
FT                   /note="Immunosuppression"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          659..680
FT                   /note="MPER; binding to GalCer"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   COILED          630..664
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   MOTIF           709..712
FT                   /note="YXXL motif; contains endocytosis signal"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   MOTIF           852..853
FT                   /note="Di-leucine internalization motif"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   SITE            508..509
FT                   /note="Cleavage; by host furin"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   LIPID           761
FT                   /note="S-palmitoyl cysteine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   LIPID           834
FT                   /note="S-palmitoyl cysteine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        87
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        137
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        144
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        153
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        157
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        185
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        188
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        198
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        235
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        242
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        263
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        277
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        290
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        296
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        331
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        338
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        353
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        384
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        390
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        402
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        441
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        445
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        458
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        459
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        462
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        608
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        613
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        622
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        634
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        671
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        53..73
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        118..206
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        125..197
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        130..154
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        219..248
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        229..240
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        297..330
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        376..442
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        383..415
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        595..601
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   HELIX           538..587
FT                   /evidence="ECO:0007829|PDB:3UIA"
SQ   SEQUENCE   853 AA;  97044 MW;  849B0B8CBAFF7008 CRC64;
     MRVRGIERNC QNLWKWGIML LGILMTCSNA DNLWVTVYYG VPVWKEATTT LFCASDAKSY
     KTEAHNIWAT HACVPTDPNP QEIELENVTE NFNMWRNNMV EQMHEDIISL WDQSLKPCVK
     LTPLCVTLNC IDEVMENVTM KNNNVTEEIR MKNCSFNITT VVRDKTKQVH ALFYRLDIVP
     IDNDNSTNST NYRLINCNTS AITQACPKVS FEPIPIHYCA PAGFAILKCR DKRFNGTGPC
     TNVSTVQCTH GIRPVVSTQL LLNGSLAEEE IIIRSENLTN NAKIIIVQLN ESVAINCTRP
     YRNIRQRTSI GLGQALYTTK TRSIIGQAYC NISKNEWNKT LQQVAIKLGN LLNKTTIIFK
     PSSGGDPEIT THSFNCGGEF FYCNTSGLFN STWDISKSEW ANSTESDDKP ITLQCRIKQI
     INMWQGVGKA MYAPPIEGQI NCSSNITGLL LTRDGGTNNS SNETFRPGGG DMRDNWRSEL
     YKYKVVKIEP LGVAPTRAKR RVVEREKRAI GLGAMFLGFL GAAGSTMGAR SLTLTVQARQ
     LLSGIVQQQN NLLRAIEAQQ HLLQLTVWGI KQLQARILAV ERYLKDQQLL GIWGCSGKLI
     CTTTVPWNSS WSNRSLNDIW QNMTWMEWER EIDNYTGLIY RLIEESQTQQ EKNEQELLEL
     DKWASLWNWF NITQWLWYIK IFIMIVGGLI GLRIVFAVLS LVNRVRQGYS PLSFQTLLPA
     PRGPDRPEGI EEEGGERGRD RSIRLVNGFS ALIWDDLRNL CLFSYHRLRD LILIAARIVE
     LLGRRGWEAL KYLWNLLQYW SRELKNSASS LLDTIAIAVA EGTDRVIEIV RRACRAVLHI
     PTRIRQGLER LLL
//
ID   ENV_HV1Z3               Reviewed;         460 AA.
AC   P12491;
DT   01-OCT-1989, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-1989, sequence version 1.
DT   08-NOV-2023, entry version 103.
DE   RecName: Full=Truncated surface protein;
DE            Short=SU;
DE   AltName: Full=Glycoprotein 120;
DE            Short=gp120;
DE   Flags: Precursor;
GN   Name=env;
OS   Human immunodeficiency virus type 1 group M subtype U (isolate Z3) (HIV-1).
OC   Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC   Ortervirales; Retroviridae; Orthoretrovirinae; Lentivirus;
OC   Human immunodeficiency virus 1.
OX   NCBI_TaxID=11680;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX   PubMed=3014529; DOI=10.1073/pnas.83.14.5038;
RA   Willey R.W., Rutledge R.A., Dias S., Folks T., Theodore T., Buckler C.E.,
RA   Martin M.A.;
RT   "Identification of conserved and divergent domains within the envelope gene
RT   of the acquired immunodeficiency syndrome retrovirus.";
RL   Proc. Natl. Acad. Sci. U.S.A. 83:5038-5042(1986).
CC   -!- SUBCELLULAR LOCATION: Virion membrane {ECO:0000305}.
CC   -!- MISCELLANEOUS: Though this sequence contains a complete Env coding
CC       region, insertion of an extra nucleotide creates a stop codon prior to
CC       the normal termination; the authors suggest that this variation can
CC       account for the lack of infectivity of this clone.
CC   -!- MISCELLANEOUS: HIV-1 lineages are divided in three main groups, M (for
CC       Major), O (for Outlier), and N (for New, or Non-M, Non-O). The vast
CC       majority of strains found worldwide belong to the group M. Group O
CC       seems to be endemic to and largely confined to Cameroon and neighboring
CC       countries in West Central Africa, where these viruses represent a small
CC       minority of HIV-1 strains. The group N is represented by a limited
CC       number of isolates from Cameroonian persons. The group M is further
CC       subdivided in 9 clades or subtypes (A to D, F to H, J and K).
CC   ---------------------------------------------------------------------------
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CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; K03347; AAA45372.1; -; Genomic_RNA.
DR   EMBL; K03347; AAA45373.1; -; Genomic_RNA.
DR   SMR; P12491; -.
DR   GlyCosmos; P12491; 23 sites, No reported glycans.
DR   Reactome; R-HSA-5621480; Dectin-2 family.
DR   GO; GO:0016020; C:membrane; IEA:UniProtKB-KW.
DR   GO; GO:0019031; C:viral envelope; IEA:InterPro.
DR   GO; GO:0055036; C:virion membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0075512; P:clathrin-dependent endocytosis of virus by host cell; IEA:UniProtKB-KW.
DR   GO; GO:0039654; P:fusion of virus membrane with host endosome membrane; IEA:UniProtKB-KW.
DR   GO; GO:0019062; P:virion attachment to host cell; IEA:UniProtKB-KW.
DR   Gene3D; 2.170.40.20; Human immunodeficiency virus 1, Gp160, envelope glycoprotein; 2.
DR   InterPro; IPR036377; Gp120_core_sf.
DR   InterPro; IPR000777; HIV1_Gp120.
DR   Pfam; PF00516; GP120; 2.
DR   SUPFAM; SSF56502; gp120 core; 1.
PE   3: Inferred from homology;
KW   AIDS; Clathrin-mediated endocytosis of virus by host; Disulfide bond;
KW   Fusion of virus membrane with host endosomal membrane;
KW   Fusion of virus membrane with host membrane; Glycoprotein;
KW   Host-virus interaction; Membrane; Signal; Viral attachment to host cell;
KW   Viral penetration into host cytoplasm; Virion; Virus endocytosis by host;
KW   Virus entry into host cell.
FT   SIGNAL          1..31
FT                   /evidence="ECO:0000250"
FT   CHAIN           32..460
FT                   /note="Truncated surface protein"
FT                   /id="PRO_0000038379"
FT   REGION          130..148
FT                   /note="V1"
FT   REGION          149..193
FT                   /note="V2"
FT   REGION          293..325
FT                   /note="V3"
FT   REGION          358..368
FT                   /note="CD4-binding loop"
FT                   /evidence="ECO:0000250"
FT   REGION          379..412
FT                   /note="V4"
FT   CARBOHYD        87
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        135
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        139
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        148
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        177
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        180
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        181
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        194
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        231
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        238
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        259
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        273
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        286
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        292
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        327
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        350
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        356
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        380
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        390
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        396
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        403
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        407
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        442
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255"
FT   DISULFID        53..73
FT                   /evidence="ECO:0000250"
FT   DISULFID        118..202
FT                   /evidence="ECO:0000250"
FT   DISULFID        125..193
FT                   /evidence="ECO:0000250"
FT   DISULFID        130..149
FT                   /evidence="ECO:0000250"
FT   DISULFID        215..244
FT                   /evidence="ECO:0000250"
FT   DISULFID        225..236
FT                   /evidence="ECO:0000250"
FT   DISULFID        293..326
FT                   /evidence="ECO:0000250"
FT   DISULFID        372..439
FT                   /evidence="ECO:0000250"
FT   DISULFID        379..412
FT                   /evidence="ECO:0000250"
FT   DISULFID        397..404
FT                   /evidence="ECO:0000250"
SQ   SEQUENCE   460 AA;  51298 MW;  27E97EB75C7EFF50 CRC64;
     MRVKEIQRNY QHLWKWSLII LGMIMICKAI EKSWVTVYYG VPVWKDAETT LFCASDAKAY
     EKESHNVWAT HACVPSDPSP QELVLGNVTE NFNMWKNKMV EQMHEDIISL WDQSLKPCVK
     LTFLCVTLNC IDVKNSTNNN TEEATITNCS FKVPTELKDK TETVHTLFYK LDVVPLNVTN
     NSSISSTYRL INCNTSTITQ ACPKVSFEPI PIHYCAPAGF AILKCNDKKF NGTGPCKNVS
     TVQCTHGIRP VVSTQLLLNG SLSEEEVIIR SENITNNAKT IIVQLNETVK INCTRPGSDK
     KIRQSIRIGP GKVFYAKGGI TGQAHCNITD GEWRNTLQQV AIALRRQFNN KSIIFNSSSG
     GDIEITTHTF NCGGEFFYCN TSELFTGIWN GTWDKNCTST ESNCTGNITL PCRIKQVVRT
     WQGVGQAMYA PPIEGTIRCS SNITGLLLTR DGGNGKCNSK
//
ID   ENV_HV1Z6               Reviewed;         855 AA.
AC   P04580;
DT   13-AUG-1987, integrated into UniProtKB/Swiss-Prot.
DT   13-AUG-1987, sequence version 1.
DT   27-MAR-2024, entry version 160.
DE   RecName: Full=Envelope glycoprotein gp160 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   AltName: Full=Env polyprotein {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Contains:
DE     RecName: Full=Surface protein gp120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=SU {ECO:0000255|HAMAP-Rule:MF_04083};
DE     AltName: Full=Glycoprotein 120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=gp120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Contains:
DE     RecName: Full=Transmembrane protein gp41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=TM {ECO:0000255|HAMAP-Rule:MF_04083};
DE     AltName: Full=Glycoprotein 41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=gp41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Flags: Precursor;
GN   Name=env {ECO:0000255|HAMAP-Rule:MF_04083};
OS   Human immunodeficiency virus type 1 group M subtype D (isolate Z6) (HIV-1).
OC   Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC   Ortervirales; Retroviridae; Orthoretrovirinae; Lentivirus;
OC   Human immunodeficiency virus 1.
OX   NCBI_TaxID=11708;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX   PubMed=3036660; DOI=10.1016/0378-1119(87)90396-9;
RA   Srinivasan A., Anand R., York D., Ranganathan P., Feorino P.,
RA   Schochetman G., Curran J., Kalyanaraman V.S., Luciw P.A.,
RA   Sanchez-Pescador R.;
RT   "Molecular characterization of human immunodeficiency virus from Zaire:
RT   nucleotide sequence analysis identifies conserved and variable domains in
RT   the envelope gene.";
RL   Gene 52:71-82(1987).
RN   [2]
RP   REVIEW.
RX   PubMed=12974773; DOI=10.1034/j.1600-0463.2003.11107803.x;
RA   Geijtenbeek T.B., van Kooyk Y.;
RT   "Pathogens target DC-SIGN to influence their fate DC-SIGN functions as a
RT   pathogen receptor with broad specificity.";
RL   APMIS 111:698-714(2003).
RN   [3]
RP   REVIEW.
RX   PubMed=12873764; DOI=10.1016/s0005-2736(03)00161-5;
RA   Gallo S.A., Finnegan C.M., Viard M., Raviv Y., Dimitrov A., Rawat S.S.,
RA   Puri A., Durell S., Blumenthal R.;
RT   "The HIV Env-mediated fusion reaction.";
RL   Biochim. Biophys. Acta 1614:36-50(2003).
RN   [4]
RP   REVIEW.
RX   PubMed=15719026; DOI=10.1038/sj.cdd.4401584;
RA   Perfettini J.-L., Castedo M., Roumier T., Andreau K., Nardacci R.,
RA   Piacentini M., Kroemer G.;
RT   "Mechanisms of apoptosis induction by the HIV-1 envelope.";
RL   Cell Death Differ. 12:916-923(2005).
RN   [5]
RP   REVIEW.
RX   PubMed=15725757; DOI=10.1089/aid.2005.21.171;
RA   Hartley O., Klasse P.J., Sattentau Q.J., Moore J.P.;
RT   "V3: HIV's switch-hitter.";
RL   AIDS Res. Hum. Retroviruses 21:171-189(2005).
RN   [6]
RP   REVIEW.
RX   PubMed=16114975; DOI=10.2165/00003495-200565130-00002;
RA   Reeves J.D., Piefer A.J.;
RT   "Emerging drug targets for antiretroviral therapy.";
RL   Drugs 65:1747-1766(2005).
RN   [7]
RP   REVIEW.
RX   PubMed=16437164; DOI=10.1038/sj.emboj.7600947;
RA   Lusso P.;
RT   "HIV and the chemokine system: 10 years later.";
RL   EMBO J. 25:447-456(2006).
CC   -!- FUNCTION: [Envelope glycoprotein gp160]: Oligomerizes in the host
CC       endoplasmic reticulum into predominantly trimers. In a second time,
CC       gp160 transits in the host Golgi, where glycosylation is completed. The
CC       precursor is then proteolytically cleaved in the trans-Golgi and
CC       thereby activated by cellular furin or furin-like proteases to produce
CC       gp120 and gp41. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- FUNCTION: [Surface protein gp120]: Attaches the virus to the host
CC       lymphoid cell by binding to the primary receptor CD4. This interaction
CC       induces a structural rearrangement creating a high affinity binding
CC       site for a chemokine coreceptor like CXCR4 and/or CCR5. Acts as a
CC       ligand for CD209/DC-SIGN and CLEC4M/DC-SIGNR, which are respectively
CC       found on dendritic cells (DCs), and on endothelial cells of liver
CC       sinusoids and lymph node sinuses. These interactions allow capture of
CC       viral particles at mucosal surfaces by these cells and subsequent
CC       transmission to permissive cells. HIV subverts the migration properties
CC       of dendritic cells to gain access to CD4+ T-cells in lymph nodes. Virus
CC       transmission to permissive T-cells occurs either in trans (without DCs
CC       infection, through viral capture and transmission), or in cis
CC       (following DCs productive infection, through the usual CD4-gp120
CC       interaction), thereby inducing a robust infection. In trans infection,
CC       bound virions remain infectious over days and it is proposed that they
CC       are not degraded, but protected in non-lysosomal acidic organelles
CC       within the DCs close to the cell membrane thus contributing to the
CC       viral infectious potential during DCs' migration from the periphery to
CC       the lymphoid tissues. On arrival at lymphoid tissues, intact virions
CC       recycle back to DCs' cell surface allowing virus transmission to CD4+
CC       T-cells. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- FUNCTION: [Transmembrane protein gp41]: Acts as a class I viral fusion
CC       protein. Under the current model, the protein has at least 3
CC       conformational states: pre-fusion native state, pre-hairpin
CC       intermediate state, and post-fusion hairpin state. During fusion of
CC       viral and target intracellular membranes, the coiled coil regions
CC       (heptad repeats) assume a trimer-of-hairpins structure, positioning the
CC       fusion peptide in close proximity to the C-terminal region of the
CC       ectodomain. The formation of this structure appears to drive apposition
CC       and subsequent fusion of viral and target cell membranes. Complete
CC       fusion occurs in host cell endosomes and is dynamin-dependent, however
CC       some lipid transfer might occur at the plasma membrane. The virus
CC       undergoes clathrin-dependent internalization long before endosomal
CC       fusion, thus minimizing the surface exposure of conserved viral
CC       epitopes during fusion and reducing the efficacy of inhibitors
CC       targeting these epitopes. Membranes fusion leads to delivery of the
CC       nucleocapsid into the cytoplasm. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBUNIT: [Surface protein gp120]: The mature envelope protein (Env)
CC       consists of a homotrimer of non-covalently associated gp120-gp41
CC       heterodimers. The resulting complex protrudes from the virus surface as
CC       a spike. There seems to be as few as 10 spikes on the average virion.
CC       Interacts with host CD4, CCR5 and CXCR4. Gp120 also interacts with the
CC       C-type lectins CD209/DC-SIGN and CLEC4M/DC-SIGNR (collectively referred
CC       to as DC-SIGN(R)). Gp120 and gp41 interact with GalCer. Gp120 interacts
CC       with host ITGA4/ITGB7 complex; on CD4+ T-cells, this interaction
CC       results in rapid activation of integrin ITGAL/LFA-1, which facilitates
CC       efficient cell-to-cell spreading of HIV-1. Gp120 interacts with cell-
CC       associated heparan sulfate; this interaction increases virus
CC       infectivity on permissive cells and may be involved in infection of
CC       CD4- cells. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBUNIT: [Transmembrane protein gp41]: The mature envelope protein
CC       (Env) consists of a homotrimer of non-covalently associated gp120-gp41
CC       heterodimers. The resulting complex protrudes from the virus surface as
CC       a spike. There seems to be as few as 10 spikes on the average virion.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBCELLULAR LOCATION: [Surface protein gp120]: Virion membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Peripheral membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host cell membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Peripheral membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host endosome membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Note=The surface protein is not
CC       anchored to the viral envelope, but associates with the extravirion
CC       surface through its binding to TM. It is probably concentrated at the
CC       site of budding and incorporated into the virions possibly by contacts
CC       between the cytoplasmic tail of Env and the N-terminus of Gag.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBCELLULAR LOCATION: [Transmembrane protein gp41]: Virion membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host cell membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host endosome membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Note=It is probably concentrated at
CC       the site of budding and incorporated into the virions possibly by
CC       contacts between the cytoplasmic tail of Env and the N-terminus of Gag.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: Some of the most genetically diverse regions of the viral
CC       genome are present in Env. They are called variable regions 1 through 5
CC       (V1 through V5). Coreceptor usage of gp120 is determined mainly by the
CC       primary structure of the third variable region (V3) in the outer domain
CC       of gp120. The sequence of V3 determines which coreceptor, CCR5 and/or
CC       CXCR4 (corresponding to R5/macrophage, X4/T cell and R5X4/T cell and
CC       macrophage tropism), is used to trigger the fusion potential of the Env
CC       complex, and hence which cells the virus can infect. Binding to CCR5
CC       involves a region adjacent in addition to V3. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- DOMAIN: The membrane proximal external region (MPER) present in gp41 is
CC       a tryptophan-rich region recognized by the antibodies 2F5, Z13, and
CC       4E10. MPER seems to play a role in fusion. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- DOMAIN: The 17 amino acids long immunosuppressive region is present in
CC       many retroviral envelope proteins. Synthetic peptides derived from this
CC       relatively conserved sequence inhibit immune function in vitro and in
CC       vivo. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: The YXXL motif is involved in determining the exact site of
CC       viral release at the surface of infected mononuclear cells and promotes
CC       endocytosis. YXXL and di-leucine endocytosis motifs interact directly
CC       or indirectly with the clathrin adapter complexes, opperate
CC       independently, and their activities are not additive.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: The CD4-binding region is targeted by the antibody b12.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- PTM: Highly glycosylated by host. The high number of glycan on the
CC       protein is reffered to as 'glycan shield' because it contributes to
CC       hide protein sequence from adaptive immune system. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- PTM: Palmitoylation of the transmembrane protein and of Env polyprotein
CC       (prior to its proteolytic cleavage) is essential for their association
CC       with host cell membrane lipid rafts. Palmitoylation is therefore
CC       required for envelope trafficking to classical lipid rafts, but not for
CC       viral replication. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- PTM: Specific enzymatic cleavages in vivo yield mature proteins.
CC       Envelope glycoproteins are synthesized as an inactive precursor that is
CC       heavily N-glycosylated and processed likely by host cell furin in the
CC       Golgi to yield the mature SU and TM proteins. The cleavage site between
CC       SU and TM requires the minimal sequence [KR]-X-[KR]-R. About 2 of the 9
CC       disulfide bonds of gp41 are reduced by P4HB/PDI, following binding to
CC       CD4 receptor. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- MISCELLANEOUS: Inhibitors targeting HIV-1 viral envelope proteins are
CC       used as antiretroviral drugs. Attachment of virions to the cell surface
CC       via non-specific interactions and CD4 binding can be blocked by
CC       inhibitors that include cyanovirin-N, cyclotriazadisulfonamide analogs,
CC       PRO 2000, TNX 355 and PRO 542. In addition, BMS 806 can block CD4-
CC       induced conformational changes. Env interactions with the coreceptor
CC       molecules can be targeted by CCR5 antagonists including SCH-D,
CC       maraviroc (UK 427857) and aplaviroc (GW 873140), and the CXCR4
CC       antagonist AMD 070. Fusion of viral and cellular membranes can be
CC       inhibited by peptides such as enfuvirtide and tifuvirtide (T 1249).
CC       Resistance to inhibitors associated with mutations in Env are observed.
CC       Most of the time, single mutations confer only a modest reduction in
CC       drug susceptibility. Combination of several mutations is usually
CC       required to develop a high-level drug resistance. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- MISCELLANEOUS: HIV-1 lineages are divided in three main groups, M (for
CC       Major), O (for Outlier), and N (for New, or Non-M, Non-O). The vast
CC       majority of strains found worldwide belong to the group M. Group O
CC       seems to be endemic to and largely confined to Cameroon and neighboring
CC       countries in West Central Africa, where these viruses represent a small
CC       minority of HIV-1 strains. The group N is represented by a limited
CC       number of isolates from Cameroonian persons. The group M is further
CC       subdivided in 9 clades or subtypes (A to D, F to H, J and K).
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SIMILARITY: Belongs to the HIV-1 env protein family.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- WEB RESOURCE: Name=hivdb; Note=HIV drug resistance database;
CC       URL="https://hivdb.stanford.edu";
CC   -!- WEB RESOURCE: Name=HIV drug resistance mutations;
CC       URL="https://www.iasusa.org/content/hiv-drug-resistance-mutations";
CC   ---------------------------------------------------------------------------
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DR   EMBL; K03458; AAA45380.1; -; Genomic_RNA.
DR   PIR; D26192; VCLJZR.
DR   PDB; 1TJH; X-ray; 2.10 A; P=659-669.
DR   PDB; 1TJI; X-ray; 2.20 A; P=653-669.
DR   PDB; 3F4Y; X-ray; 2.00 A; A/B/C=545-580.
DR   PDB; 3F50; X-ray; 2.80 A; A=545-580.
DR   PDB; 3G7A; X-ray; 2.80 A; A=545-580.
DR   PDB; 3MOA; X-ray; 2.30 A; P=653-669.
DR   PDB; 3MOB; X-ray; 2.60 A; P=659-669.
DR   PDB; 3MOD; X-ray; 2.20 A; P=659-669.
DR   PDB; 4I2L; X-ray; 1.43 A; C=549-589.
DR   PDBsum; 1TJH; -.
DR   PDBsum; 1TJI; -.
DR   PDBsum; 3F4Y; -.
DR   PDBsum; 3F50; -.
DR   PDBsum; 3G7A; -.
DR   PDBsum; 3MOA; -.
DR   PDBsum; 3MOB; -.
DR   PDBsum; 3MOD; -.
DR   PDBsum; 4I2L; -.
DR   SMR; P04580; -.
DR   MINT; P04580; -.
DR   GlyCosmos; P04580; 32 sites, No reported glycans.
DR   ABCD; P04580; 1 sequenced antibody.
DR   Reactome; R-HSA-5621480; Dectin-2 family.
DR   EvolutionaryTrace; P04580; -.
DR   GO; GO:0044175; C:host cell endosome membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0016020; C:membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:0019031; C:viral envelope; IEA:UniProtKB-KW.
DR   GO; GO:0055036; C:virion membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005198; F:structural molecule activity; IEA:UniProtKB-UniRule.
DR   GO; GO:0075512; P:clathrin-dependent endocytosis of virus by host cell; IEA:UniProtKB-UniRule.
DR   GO; GO:0039654; P:fusion of virus membrane with host endosome membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:0019064; P:fusion of virus membrane with host plasma membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:1903905; P:positive regulation of establishment of T cell polarity; IEA:UniProtKB-UniRule.
DR   GO; GO:1903908; P:positive regulation of plasma membrane raft polarization; IEA:UniProtKB-UniRule.
DR   GO; GO:1903911; P:positive regulation of receptor clustering; IEA:UniProtKB-UniRule.
DR   GO; GO:0019082; P:viral protein processing; IEA:UniProtKB-UniRule.
DR   GO; GO:0019062; P:virion attachment to host cell; IEA:UniProtKB-UniRule.
DR   GO; GO:0019049; P:virus-mediated perturbation of host defense response; IEA:UniProtKB-UniRule.
DR   CDD; cd09909; HIV-1-like_HR1-HR2; 1.
DR   Gene3D; 1.10.287.210; -; 1.
DR   Gene3D; 2.170.40.20; Human immunodeficiency virus 1, Gp160, envelope glycoprotein; 2.
DR   Gene3D; 1.20.5.490; Single helix bin; 1.
DR   HAMAP; MF_04083; HIV_ENV; 1.
DR   InterPro; IPR036377; Gp120_core_sf.
DR   InterPro; IPR037527; Gp160.
DR   InterPro; IPR000328; GP41-like.
DR   InterPro; IPR000777; HIV1_Gp120.
DR   Pfam; PF00516; GP120; 2.
DR   Pfam; PF00517; GP41; 1.
DR   SUPFAM; SSF56502; gp120 core; 2.
DR   SUPFAM; SSF58069; Virus ectodomain; 1.
PE   1: Evidence at protein level;
KW   3D-structure; AIDS; Apoptosis;
KW   Clathrin-mediated endocytosis of virus by host;
KW   Cleavage on pair of basic residues; Coiled coil; Disulfide bond;
KW   Fusion of virus membrane with host endosomal membrane;
KW   Fusion of virus membrane with host membrane; Glycoprotein;
KW   Host cell membrane; Host endosome; Host membrane; Host-virus interaction;
KW   Lipoprotein; Membrane; Palmitate; Signal; Transmembrane;
KW   Transmembrane helix; Viral attachment to host cell; Viral envelope protein;
KW   Viral immunoevasion; Viral penetration into host cytoplasm; Virion;
KW   Virus endocytosis by host; Virus entry into host cell.
FT   SIGNAL          1..31
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CHAIN           32..855
FT                   /note="Envelope glycoprotein gp160"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000441247"
FT   CHAIN           32..510
FT                   /note="Surface protein gp120"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000441248"
FT   CHAIN           511..855
FT                   /note="Transmembrane protein gp41"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000038432"
FT   TOPO_DOM        32..683
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   TRANSMEM        684..704
FT                   /note="Helical"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   TOPO_DOM        705..855
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          130..154
FT                   /note="V1"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          155..198
FT                   /note="V2"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          298..331
FT                   /note="V3"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          364..374
FT                   /note="CD4-binding loop"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          385..417
FT                   /note="V4"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          459..470
FT                   /note="V5"
FT   REGION          462..470
FT                   /note="V5"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          511..531
FT                   /note="Fusion peptide"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          573..591
FT                   /note="Immunosuppression"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          661..682
FT                   /note="MPER; binding to GalCer"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   COILED          632..666
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   MOTIF           711..714
FT                   /note="YXXL motif; contains endocytosis signal"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   MOTIF           854..855
FT                   /note="Di-leucine internalization motif"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   SITE            510..511
FT                   /note="Cleavage; by host furin"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   LIPID           763
FT                   /note="S-palmitoyl cysteine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        87
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        129
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        140
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        145
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        154
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        158
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        186
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        189
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        199
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        236
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        243
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        264
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        278
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        291
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        297
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        333
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        340
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        355
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        386
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        392
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        398
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        404
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        443
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        447
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        460
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        461
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        464
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        610
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        615
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        624
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        636
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        673
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        53..73
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        118..207
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        125..198
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        130..155
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        220..249
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        230..241
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        298..332
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        378..444
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        385..417
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        597..603
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   HELIX           551..588
FT                   /evidence="ECO:0007829|PDB:4I2L"
FT   TURN            664..667
FT                   /evidence="ECO:0007829|PDB:1TJH"
SQ   SEQUENCE   855 AA;  96971 MW;  3B4D3D6E239C3457 CRC64;
     MRAREIERNC PNLWKWGIML LGILMICSAA DNLWVTVYYG VPVWKEATTT LFCASDAKSY
     KTEAHNIWAT HACVPTDPNP QEIELENVTE NFNMWRNNMV EQIHEDIISL WDQSLKPCVK
     LTPLCVTLNC TDESDEWMGN VTGKNVTEDI RMKNCSFNIT TVVRDKTKQV HALFYRLDIV
     PIDNDNSTNS TNYRLINCNT SAITQACPKV SFEPIPIHYC APAGFAILKC RDKRFNGTGP
     CTNVSTVQCT HGIRPVVSTQ LLLNGSLAEE EIIIRSENLT NNAKIIIVQL NESVAINCTR
     PYKNTRQSTP IGLGQALYTT RGRTKIIGQA HCNISKEDWN KTLQRVAIKL GNLLNKTTII
     FKPSSGGDAE ITTHSFNCGG EFFYCNTSGL FNSTWNINNS EGANSTESDN KLITLQCRIK
     QIINMWQGVG KAMYAPPIEG QINCSSNITG LLLTRDGGTN NSSNETFRPG GGDMRDNWRS
     ELYKYKVVKI EPLGVAPTKA KRRVVEREKR AIGLGAMFLG FLGAAGSTMG AASVTLTVQA
     RQLMSGIVQQ QNNLLRAIEA QQHLLQLTVW GIKQLQARIL AVERYLKDQQ LLGIWGCSGK
     LICTTTVPWN SSWSNRSLND IWQNMTWMEW EREIDNYTGL IYRLIEESQT QQEKNEQELL
     ELDKWASLWN WFNITQWLWY IKIFIMIVGG LIGLRIVFAV LSLVNRVRQG YSPLSFQTLL
     PAPREPDRPE GIEEEGGERG RDRSIRLVNG FSALIWDDLR NLCLFSYHRL RDLILIAARI
     VELLGRRGWE ALKYLWNLLQ YWSRELRNSA SSLLDTIAIA VAEGTDRVIE IVRRTYRAVL
     NVPTRIRQGL ERLLL
//
ID   ENV_HV1Z8               Reviewed;         863 AA.
AC   P05882;
DT   01-NOV-1988, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1988, sequence version 1.
DT   27-MAR-2024, entry version 145.
DE   RecName: Full=Envelope glycoprotein gp160 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   AltName: Full=Env polyprotein {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Contains:
DE     RecName: Full=Surface protein gp120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=SU {ECO:0000255|HAMAP-Rule:MF_04083};
DE     AltName: Full=Glycoprotein 120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=gp120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Contains:
DE     RecName: Full=Transmembrane protein gp41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=TM {ECO:0000255|HAMAP-Rule:MF_04083};
DE     AltName: Full=Glycoprotein 41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=gp41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Flags: Precursor;
GN   Name=env {ECO:0000255|HAMAP-Rule:MF_04083};
OS   Human immunodeficiency virus type 1 group M subtype D (isolate Z84)
OS   (HIV-1).
OC   Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC   Ortervirales; Retroviridae; Orthoretrovirinae; Lentivirus;
OC   Human immunodeficiency virus 1.
OX   NCBI_TaxID=11681;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX   PubMed=3395517; DOI=10.1089/aid.1988.4.165;
RA   Yourno J., Josephs S.F., Reitz M.S. Jr., Zagury D., Wong-Staal F.,
RA   Gallo R.C.;
RT   "Nucleotide sequence analysis of the env gene of a new Zairian isolate of
RT   HIV-1.";
RL   AIDS Res. Hum. Retroviruses 4:165-173(1988).
RN   [2]
RP   REVIEW.
RX   PubMed=12974773; DOI=10.1034/j.1600-0463.2003.11107803.x;
RA   Geijtenbeek T.B., van Kooyk Y.;
RT   "Pathogens target DC-SIGN to influence their fate DC-SIGN functions as a
RT   pathogen receptor with broad specificity.";
RL   APMIS 111:698-714(2003).
RN   [3]
RP   REVIEW.
RX   PubMed=12873764; DOI=10.1016/s0005-2736(03)00161-5;
RA   Gallo S.A., Finnegan C.M., Viard M., Raviv Y., Dimitrov A., Rawat S.S.,
RA   Puri A., Durell S., Blumenthal R.;
RT   "The HIV Env-mediated fusion reaction.";
RL   Biochim. Biophys. Acta 1614:36-50(2003).
RN   [4]
RP   REVIEW.
RX   PubMed=15719026; DOI=10.1038/sj.cdd.4401584;
RA   Perfettini J.-L., Castedo M., Roumier T., Andreau K., Nardacci R.,
RA   Piacentini M., Kroemer G.;
RT   "Mechanisms of apoptosis induction by the HIV-1 envelope.";
RL   Cell Death Differ. 12:916-923(2005).
RN   [5]
RP   REVIEW.
RX   PubMed=15725757; DOI=10.1089/aid.2005.21.171;
RA   Hartley O., Klasse P.J., Sattentau Q.J., Moore J.P.;
RT   "V3: HIV's switch-hitter.";
RL   AIDS Res. Hum. Retroviruses 21:171-189(2005).
RN   [6]
RP   REVIEW.
RX   PubMed=16114975; DOI=10.2165/00003495-200565130-00002;
RA   Reeves J.D., Piefer A.J.;
RT   "Emerging drug targets for antiretroviral therapy.";
RL   Drugs 65:1747-1766(2005).
RN   [7]
RP   REVIEW.
RX   PubMed=16437164; DOI=10.1038/sj.emboj.7600947;
RA   Lusso P.;
RT   "HIV and the chemokine system: 10 years later.";
RL   EMBO J. 25:447-456(2006).
CC   -!- FUNCTION: [Envelope glycoprotein gp160]: Oligomerizes in the host
CC       endoplasmic reticulum into predominantly trimers. In a second time,
CC       gp160 transits in the host Golgi, where glycosylation is completed. The
CC       precursor is then proteolytically cleaved in the trans-Golgi and
CC       thereby activated by cellular furin or furin-like proteases to produce
CC       gp120 and gp41. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- FUNCTION: [Surface protein gp120]: Attaches the virus to the host
CC       lymphoid cell by binding to the primary receptor CD4. This interaction
CC       induces a structural rearrangement creating a high affinity binding
CC       site for a chemokine coreceptor like CXCR4 and/or CCR5. Acts as a
CC       ligand for CD209/DC-SIGN and CLEC4M/DC-SIGNR, which are respectively
CC       found on dendritic cells (DCs), and on endothelial cells of liver
CC       sinusoids and lymph node sinuses. These interactions allow capture of
CC       viral particles at mucosal surfaces by these cells and subsequent
CC       transmission to permissive cells. HIV subverts the migration properties
CC       of dendritic cells to gain access to CD4+ T-cells in lymph nodes. Virus
CC       transmission to permissive T-cells occurs either in trans (without DCs
CC       infection, through viral capture and transmission), or in cis
CC       (following DCs productive infection, through the usual CD4-gp120
CC       interaction), thereby inducing a robust infection. In trans infection,
CC       bound virions remain infectious over days and it is proposed that they
CC       are not degraded, but protected in non-lysosomal acidic organelles
CC       within the DCs close to the cell membrane thus contributing to the
CC       viral infectious potential during DCs' migration from the periphery to
CC       the lymphoid tissues. On arrival at lymphoid tissues, intact virions
CC       recycle back to DCs' cell surface allowing virus transmission to CD4+
CC       T-cells. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- FUNCTION: [Transmembrane protein gp41]: Acts as a class I viral fusion
CC       protein. Under the current model, the protein has at least 3
CC       conformational states: pre-fusion native state, pre-hairpin
CC       intermediate state, and post-fusion hairpin state. During fusion of
CC       viral and target intracellular membranes, the coiled coil regions
CC       (heptad repeats) assume a trimer-of-hairpins structure, positioning the
CC       fusion peptide in close proximity to the C-terminal region of the
CC       ectodomain. The formation of this structure appears to drive apposition
CC       and subsequent fusion of viral and target cell membranes. Complete
CC       fusion occurs in host cell endosomes and is dynamin-dependent, however
CC       some lipid transfer might occur at the plasma membrane. The virus
CC       undergoes clathrin-dependent internalization long before endosomal
CC       fusion, thus minimizing the surface exposure of conserved viral
CC       epitopes during fusion and reducing the efficacy of inhibitors
CC       targeting these epitopes. Membranes fusion leads to delivery of the
CC       nucleocapsid into the cytoplasm. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBUNIT: [Surface protein gp120]: The mature envelope protein (Env)
CC       consists of a homotrimer of non-covalently associated gp120-gp41
CC       heterodimers. The resulting complex protrudes from the virus surface as
CC       a spike. There seems to be as few as 10 spikes on the average virion.
CC       Interacts with host CD4, CCR5 and CXCR4. Gp120 also interacts with the
CC       C-type lectins CD209/DC-SIGN and CLEC4M/DC-SIGNR (collectively referred
CC       to as DC-SIGN(R)). Gp120 and gp41 interact with GalCer. Gp120 interacts
CC       with host ITGA4/ITGB7 complex; on CD4+ T-cells, this interaction
CC       results in rapid activation of integrin ITGAL/LFA-1, which facilitates
CC       efficient cell-to-cell spreading of HIV-1. Gp120 interacts with cell-
CC       associated heparan sulfate; this interaction increases virus
CC       infectivity on permissive cells and may be involved in infection of
CC       CD4- cells. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBUNIT: [Transmembrane protein gp41]: The mature envelope protein
CC       (Env) consists of a homotrimer of non-covalently associated gp120-gp41
CC       heterodimers. The resulting complex protrudes from the virus surface as
CC       a spike. There seems to be as few as 10 spikes on the average virion.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBCELLULAR LOCATION: [Surface protein gp120]: Virion membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Peripheral membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host cell membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Peripheral membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host endosome membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Note=The surface protein is not
CC       anchored to the viral envelope, but associates with the extravirion
CC       surface through its binding to TM. It is probably concentrated at the
CC       site of budding and incorporated into the virions possibly by contacts
CC       between the cytoplasmic tail of Env and the N-terminus of Gag.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBCELLULAR LOCATION: [Transmembrane protein gp41]: Virion membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host cell membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host endosome membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Note=It is probably concentrated at
CC       the site of budding and incorporated into the virions possibly by
CC       contacts between the cytoplasmic tail of Env and the N-terminus of Gag.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: Some of the most genetically diverse regions of the viral
CC       genome are present in Env. They are called variable regions 1 through 5
CC       (V1 through V5). Coreceptor usage of gp120 is determined mainly by the
CC       primary structure of the third variable region (V3) in the outer domain
CC       of gp120. The sequence of V3 determines which coreceptor, CCR5 and/or
CC       CXCR4 (corresponding to R5/macrophage, X4/T cell and R5X4/T cell and
CC       macrophage tropism), is used to trigger the fusion potential of the Env
CC       complex, and hence which cells the virus can infect. Binding to CCR5
CC       involves a region adjacent in addition to V3. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- DOMAIN: The membrane proximal external region (MPER) present in gp41 is
CC       a tryptophan-rich region recognized by the antibodies 2F5, Z13, and
CC       4E10. MPER seems to play a role in fusion. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- DOMAIN: The 17 amino acids long immunosuppressive region is present in
CC       many retroviral envelope proteins. Synthetic peptides derived from this
CC       relatively conserved sequence inhibit immune function in vitro and in
CC       vivo. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: The YXXL motif is involved in determining the exact site of
CC       viral release at the surface of infected mononuclear cells and promotes
CC       endocytosis. YXXL and di-leucine endocytosis motifs interact directly
CC       or indirectly with the clathrin adapter complexes, opperate
CC       independently, and their activities are not additive.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: The CD4-binding region is targeted by the antibody b12.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- PTM: Highly glycosylated by host. The high number of glycan on the
CC       protein is reffered to as 'glycan shield' because it contributes to
CC       hide protein sequence from adaptive immune system. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- PTM: Palmitoylation of the transmembrane protein and of Env polyprotein
CC       (prior to its proteolytic cleavage) is essential for their association
CC       with host cell membrane lipid rafts. Palmitoylation is therefore
CC       required for envelope trafficking to classical lipid rafts, but not for
CC       viral replication. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- PTM: Specific enzymatic cleavages in vivo yield mature proteins.
CC       Envelope glycoproteins are synthesized as an inactive precursor that is
CC       heavily N-glycosylated and processed likely by host cell furin in the
CC       Golgi to yield the mature SU and TM proteins. The cleavage site between
CC       SU and TM requires the minimal sequence [KR]-X-[KR]-R. About 2 of the 9
CC       disulfide bonds of gp41 are reduced by P4HB/PDI, following binding to
CC       CD4 receptor. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- MISCELLANEOUS: Inhibitors targeting HIV-1 viral envelope proteins are
CC       used as antiretroviral drugs. Attachment of virions to the cell surface
CC       via non-specific interactions and CD4 binding can be blocked by
CC       inhibitors that include cyanovirin-N, cyclotriazadisulfonamide analogs,
CC       PRO 2000, TNX 355 and PRO 542. In addition, BMS 806 can block CD4-
CC       induced conformational changes. Env interactions with the coreceptor
CC       molecules can be targeted by CCR5 antagonists including SCH-D,
CC       maraviroc (UK 427857) and aplaviroc (GW 873140), and the CXCR4
CC       antagonist AMD 070. Fusion of viral and cellular membranes can be
CC       inhibited by peptides such as enfuvirtide and tifuvirtide (T 1249).
CC       Resistance to inhibitors associated with mutations in Env are observed.
CC       Most of the time, single mutations confer only a modest reduction in
CC       drug susceptibility. Combination of several mutations is usually
CC       required to develop a high-level drug resistance. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- MISCELLANEOUS: HIV-1 lineages are divided in three main groups, M (for
CC       Major), O (for Outlier), and N (for New, or Non-M, Non-O). The vast
CC       majority of strains found worldwide belong to the group M. Group O
CC       seems to be endemic to and largely confined to Cameroon and neighboring
CC       countries in West Central Africa, where these viruses represent a small
CC       minority of HIV-1 strains. The group N is represented by a limited
CC       number of isolates from Cameroonian persons. The group M is further
CC       subdivided in 9 clades or subtypes (A to D, F to H, J and K).
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SIMILARITY: Belongs to the HIV-1 env protein family.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- WEB RESOURCE: Name=hivdb; Note=HIV drug resistance database;
CC       URL="https://hivdb.stanford.edu";
CC   -!- WEB RESOURCE: Name=HIV drug resistance mutations;
CC       URL="https://www.iasusa.org/content/hiv-drug-resistance-mutations";
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DR   EMBL; J03653; AAA44684.1; -; Genomic_RNA.
DR   SMR; P05882; -.
DR   GlyCosmos; P05882; 30 sites, No reported glycans.
DR   Reactome; R-HSA-5621480; Dectin-2 family.
DR   GO; GO:0044175; C:host cell endosome membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0016020; C:membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:0019031; C:viral envelope; IEA:UniProtKB-KW.
DR   GO; GO:0055036; C:virion membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005198; F:structural molecule activity; IEA:UniProtKB-UniRule.
DR   GO; GO:0075512; P:clathrin-dependent endocytosis of virus by host cell; IEA:UniProtKB-UniRule.
DR   GO; GO:0039654; P:fusion of virus membrane with host endosome membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:0019064; P:fusion of virus membrane with host plasma membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:1903905; P:positive regulation of establishment of T cell polarity; IEA:UniProtKB-UniRule.
DR   GO; GO:1903908; P:positive regulation of plasma membrane raft polarization; IEA:UniProtKB-UniRule.
DR   GO; GO:1903911; P:positive regulation of receptor clustering; IEA:UniProtKB-UniRule.
DR   GO; GO:0019082; P:viral protein processing; IEA:UniProtKB-UniRule.
DR   GO; GO:0019062; P:virion attachment to host cell; IEA:UniProtKB-UniRule.
DR   GO; GO:0019049; P:virus-mediated perturbation of host defense response; IEA:UniProtKB-UniRule.
DR   CDD; cd09909; HIV-1-like_HR1-HR2; 1.
DR   Gene3D; 1.10.287.210; -; 1.
DR   Gene3D; 2.170.40.20; Human immunodeficiency virus 1, Gp160, envelope glycoprotein; 2.
DR   Gene3D; 1.20.5.490; Single helix bin; 1.
DR   HAMAP; MF_04083; HIV_ENV; 1.
DR   InterPro; IPR036377; Gp120_core_sf.
DR   InterPro; IPR037527; Gp160.
DR   InterPro; IPR000328; GP41-like.
DR   InterPro; IPR000777; HIV1_Gp120.
DR   Pfam; PF00516; GP120; 1.
DR   Pfam; PF00517; GP41; 1.
DR   SUPFAM; SSF56502; gp120 core; 2.
DR   SUPFAM; SSF58069; Virus ectodomain; 1.
PE   3: Inferred from homology;
KW   AIDS; Apoptosis; Clathrin-mediated endocytosis of virus by host;
KW   Cleavage on pair of basic residues; Coiled coil; Disulfide bond;
KW   Fusion of virus membrane with host endosomal membrane;
KW   Fusion of virus membrane with host membrane; Glycoprotein;
KW   Host cell membrane; Host endosome; Host membrane; Host-virus interaction;
KW   Lipoprotein; Membrane; Palmitate; Signal; Transmembrane;
KW   Transmembrane helix; Viral attachment to host cell; Viral envelope protein;
KW   Viral immunoevasion; Viral penetration into host cytoplasm; Virion;
KW   Virus endocytosis by host; Virus entry into host cell.
FT   SIGNAL          1..31
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CHAIN           32..863
FT                   /note="Envelope glycoprotein gp160"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000239470"
FT   CHAIN           32..518
FT                   /note="Surface protein gp120"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000038380"
FT   CHAIN           519..863
FT                   /note="Transmembrane protein gp41"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000038381"
FT   TOPO_DOM        32..691
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   TRANSMEM        692..712
FT                   /note="Helical"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   TOPO_DOM        713..863
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          130..159
FT                   /note="V1"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          160..208
FT                   /note="V2"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          308..341
FT                   /note="V3"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          374..384
FT                   /note="CD4-binding loop"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          395..425
FT                   /note="V4"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          467..478
FT                   /note="V5"
FT   REGION          470..478
FT                   /note="V5"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          519..539
FT                   /note="Fusion peptide"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          581..599
FT                   /note="Immunosuppression"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          669..690
FT                   /note="MPER; binding to GalCer"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          729..748
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COILED          640..674
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   MOTIF           719..722
FT                   /note="YXXL motif; contains endocytosis signal"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   MOTIF           862..863
FT                   /note="Di-leucine internalization motif"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   SITE            518..519
FT                   /note="Cleavage; by host furin"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   LIPID           771
FT                   /note="S-palmitoyl cysteine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        87
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        129
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        136
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        142
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        143
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        159
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        163
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        194
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        199
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        209
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        246
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        274
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        288
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        301
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        307
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        343
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        350
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        365
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        396
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        402
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        406
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        412
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        455
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        468
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        469
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        472
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        618
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        623
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        632
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        644
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        53..73
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        118..217
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        125..208
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        130..160
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        230..259
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        240..251
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        308..342
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        388..452
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        395..425
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        605..611
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
SQ   SEQUENCE   863 AA;  97743 MW;  B729CB5A6FAD1641 CRC64;
     MRVMGIRMNY QHLWKWGIML LGILMTCSVA EDLWVTVYYG VPVWKEATTT LFCASDAKSY
     EPEAHNIWAT HACVPTDPNP REIEMENVTE NFNMWKNNMV EQMHEDIISL WDQNLKPCVK
     LTPLCVTLNC TNAGGNKTTN GNNTTNQEEQ MMEKGEMKNC SFNITTVISD KKKQVHALFY
     RLDVVPIDDD NSANTSNTNY TNYRLINCNT SAITQACPKV TFEPIPIHYC APAGFAILKC
     KDKKFNGTGP CKKVSTVQCT HGIRPVVSTQ LLLNGSLAEE EIIIRSENLT NNVKTIIVHL
     NESVEINCTR PDNKITRQST PIGLGQALYT TRIKGDIRQA YCNISAAAWN KTLQQVAKKL
     GDLLNQTTII FKPPAGGDPE ITTHSFNCGG EFFYCNTSRL FNSTWNSSTW NNDTLNSEGT
     IKLPCRIKQI INMWQGVGKA MYAPPIEGLI KCTSNITGLL LTRDGGVNNS TNETFRPGGG
     DMKDNWRNEL YKYKVVRIEP LGIAPTRAKR RVVEREKRAI GLGAVFLGFL GAAGSTMGAV
     SVALTGQARQ LLSGIVQQQN NLLRAIEAQQ HMLQLTVWGI KQLQARVLAV ESYLKDQQLL
     GIWGCSGKHI CTTTVPWNSS WSNKSLEEIW NNMTWIEWER EIDNYTGVIY SLIENSQIQQ
     EKNEQDLLQL DKWASLWNWF SITKWLWYIK IFIMIVGGLI GLRIVFTVLS LVNRVRQGYS
     PLSFQTLLPA PRGPDRPEGI EEEGGEQGRD RSIRLVNGFS ALFWDDLRNL CLFSYHRLRD
     LILIATRIVE LLGRRGWEAI KYLWSLLQYW TQELKNSFIS LLNATAIAVA EGTDRIIELI
     RRAFRAVLHI PRRVRQGLER ALL
//
ID   ENV_HV1ZH               Reviewed;         856 AA.
AC   P05881;
DT   01-NOV-1988, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1988, sequence version 1.
DT   27-MAR-2024, entry version 146.
DE   RecName: Full=Envelope glycoprotein gp160 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   AltName: Full=Env polyprotein {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Contains:
DE     RecName: Full=Surface protein gp120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=SU {ECO:0000255|HAMAP-Rule:MF_04083};
DE     AltName: Full=Glycoprotein 120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=gp120 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Contains:
DE     RecName: Full=Transmembrane protein gp41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=TM {ECO:0000255|HAMAP-Rule:MF_04083};
DE     AltName: Full=Glycoprotein 41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE              Short=gp41 {ECO:0000255|HAMAP-Rule:MF_04083};
DE   Flags: Precursor;
GN   Name=env {ECO:0000255|HAMAP-Rule:MF_04083};
OS   Human immunodeficiency virus type 1 group M subtype A (isolate Z321)
OS   (HIV-1).
OC   Viruses; Riboviria; Pararnavirae; Artverviricota; Revtraviricetes;
OC   Ortervirales; Retroviridae; Orthoretrovirinae; Lentivirus;
OC   Human immunodeficiency virus 1.
OX   NCBI_TaxID=11692;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX   PubMed=2713163; DOI=10.1089/aid.1989.5.121;
RA   Srinivasan A., York D., Butler D. Jr., Jannoun-Nasr R., Getchell J.,
RA   McCormick J., Ou C.Y., Myers G., Smith T., Chen E.;
RT   "Molecular characterization of HIV-1 isolated from a serum collected in
RT   1976: nucleotide sequence comparison to recent isolates and generation of
RT   hybrid HIV.";
RL   AIDS Res. Hum. Retroviruses 5:121-129(1989).
RN   [2]
RP   REVIEW.
RX   PubMed=12974773; DOI=10.1034/j.1600-0463.2003.11107803.x;
RA   Geijtenbeek T.B., van Kooyk Y.;
RT   "Pathogens target DC-SIGN to influence their fate DC-SIGN functions as a
RT   pathogen receptor with broad specificity.";
RL   APMIS 111:698-714(2003).
RN   [3]
RP   REVIEW.
RX   PubMed=12873764; DOI=10.1016/s0005-2736(03)00161-5;
RA   Gallo S.A., Finnegan C.M., Viard M., Raviv Y., Dimitrov A., Rawat S.S.,
RA   Puri A., Durell S., Blumenthal R.;
RT   "The HIV Env-mediated fusion reaction.";
RL   Biochim. Biophys. Acta 1614:36-50(2003).
RN   [4]
RP   REVIEW.
RX   PubMed=15719026; DOI=10.1038/sj.cdd.4401584;
RA   Perfettini J.-L., Castedo M., Roumier T., Andreau K., Nardacci R.,
RA   Piacentini M., Kroemer G.;
RT   "Mechanisms of apoptosis induction by the HIV-1 envelope.";
RL   Cell Death Differ. 12:916-923(2005).
RN   [5]
RP   REVIEW.
RX   PubMed=15725757; DOI=10.1089/aid.2005.21.171;
RA   Hartley O., Klasse P.J., Sattentau Q.J., Moore J.P.;
RT   "V3: HIV's switch-hitter.";
RL   AIDS Res. Hum. Retroviruses 21:171-189(2005).
RN   [6]
RP   REVIEW.
RX   PubMed=16114975; DOI=10.2165/00003495-200565130-00002;
RA   Reeves J.D., Piefer A.J.;
RT   "Emerging drug targets for antiretroviral therapy.";
RL   Drugs 65:1747-1766(2005).
RN   [7]
RP   REVIEW.
RX   PubMed=16437164; DOI=10.1038/sj.emboj.7600947;
RA   Lusso P.;
RT   "HIV and the chemokine system: 10 years later.";
RL   EMBO J. 25:447-456(2006).
CC   -!- FUNCTION: [Envelope glycoprotein gp160]: Oligomerizes in the host
CC       endoplasmic reticulum into predominantly trimers. In a second time,
CC       gp160 transits in the host Golgi, where glycosylation is completed. The
CC       precursor is then proteolytically cleaved in the trans-Golgi and
CC       thereby activated by cellular furin or furin-like proteases to produce
CC       gp120 and gp41. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- FUNCTION: [Surface protein gp120]: Attaches the virus to the host
CC       lymphoid cell by binding to the primary receptor CD4. This interaction
CC       induces a structural rearrangement creating a high affinity binding
CC       site for a chemokine coreceptor like CXCR4 and/or CCR5. Acts as a
CC       ligand for CD209/DC-SIGN and CLEC4M/DC-SIGNR, which are respectively
CC       found on dendritic cells (DCs), and on endothelial cells of liver
CC       sinusoids and lymph node sinuses. These interactions allow capture of
CC       viral particles at mucosal surfaces by these cells and subsequent
CC       transmission to permissive cells. HIV subverts the migration properties
CC       of dendritic cells to gain access to CD4+ T-cells in lymph nodes. Virus
CC       transmission to permissive T-cells occurs either in trans (without DCs
CC       infection, through viral capture and transmission), or in cis
CC       (following DCs productive infection, through the usual CD4-gp120
CC       interaction), thereby inducing a robust infection. In trans infection,
CC       bound virions remain infectious over days and it is proposed that they
CC       are not degraded, but protected in non-lysosomal acidic organelles
CC       within the DCs close to the cell membrane thus contributing to the
CC       viral infectious potential during DCs' migration from the periphery to
CC       the lymphoid tissues. On arrival at lymphoid tissues, intact virions
CC       recycle back to DCs' cell surface allowing virus transmission to CD4+
CC       T-cells. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- FUNCTION: [Transmembrane protein gp41]: Acts as a class I viral fusion
CC       protein. Under the current model, the protein has at least 3
CC       conformational states: pre-fusion native state, pre-hairpin
CC       intermediate state, and post-fusion hairpin state. During fusion of
CC       viral and target intracellular membranes, the coiled coil regions
CC       (heptad repeats) assume a trimer-of-hairpins structure, positioning the
CC       fusion peptide in close proximity to the C-terminal region of the
CC       ectodomain. The formation of this structure appears to drive apposition
CC       and subsequent fusion of viral and target cell membranes. Complete
CC       fusion occurs in host cell endosomes and is dynamin-dependent, however
CC       some lipid transfer might occur at the plasma membrane. The virus
CC       undergoes clathrin-dependent internalization long before endosomal
CC       fusion, thus minimizing the surface exposure of conserved viral
CC       epitopes during fusion and reducing the efficacy of inhibitors
CC       targeting these epitopes. Membranes fusion leads to delivery of the
CC       nucleocapsid into the cytoplasm. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBUNIT: [Surface protein gp120]: The mature envelope protein (Env)
CC       consists of a homotrimer of non-covalently associated gp120-gp41
CC       heterodimers. The resulting complex protrudes from the virus surface as
CC       a spike. There seems to be as few as 10 spikes on the average virion.
CC       Interacts with host CD4, CCR5 and CXCR4. Gp120 also interacts with the
CC       C-type lectins CD209/DC-SIGN and CLEC4M/DC-SIGNR (collectively referred
CC       to as DC-SIGN(R)). Gp120 and gp41 interact with GalCer. Gp120 interacts
CC       with host ITGA4/ITGB7 complex; on CD4+ T-cells, this interaction
CC       results in rapid activation of integrin ITGAL/LFA-1, which facilitates
CC       efficient cell-to-cell spreading of HIV-1. Gp120 interacts with cell-
CC       associated heparan sulfate; this interaction increases virus
CC       infectivity on permissive cells and may be involved in infection of
CC       CD4- cells. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBUNIT: [Transmembrane protein gp41]: The mature envelope protein
CC       (Env) consists of a homotrimer of non-covalently associated gp120-gp41
CC       heterodimers. The resulting complex protrudes from the virus surface as
CC       a spike. There seems to be as few as 10 spikes on the average virion.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBCELLULAR LOCATION: [Surface protein gp120]: Virion membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Peripheral membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host cell membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Peripheral membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host endosome membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Note=The surface protein is not
CC       anchored to the viral envelope, but associates with the extravirion
CC       surface through its binding to TM. It is probably concentrated at the
CC       site of budding and incorporated into the virions possibly by contacts
CC       between the cytoplasmic tail of Env and the N-terminus of Gag.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SUBCELLULAR LOCATION: [Transmembrane protein gp41]: Virion membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host cell membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Host endosome membrane
CC       {ECO:0000255|HAMAP-Rule:MF_04083}; Single-pass type I membrane protein
CC       {ECO:0000255|HAMAP-Rule:MF_04083}. Note=It is probably concentrated at
CC       the site of budding and incorporated into the virions possibly by
CC       contacts between the cytoplasmic tail of Env and the N-terminus of Gag.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: Some of the most genetically diverse regions of the viral
CC       genome are present in Env. They are called variable regions 1 through 5
CC       (V1 through V5). Coreceptor usage of gp120 is determined mainly by the
CC       primary structure of the third variable region (V3) in the outer domain
CC       of gp120. The sequence of V3 determines which coreceptor, CCR5 and/or
CC       CXCR4 (corresponding to R5/macrophage, X4/T cell and R5X4/T cell and
CC       macrophage tropism), is used to trigger the fusion potential of the Env
CC       complex, and hence which cells the virus can infect. Binding to CCR5
CC       involves a region adjacent in addition to V3. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- DOMAIN: The membrane proximal external region (MPER) present in gp41 is
CC       a tryptophan-rich region recognized by the antibodies 2F5, Z13, and
CC       4E10. MPER seems to play a role in fusion. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- DOMAIN: The 17 amino acids long immunosuppressive region is present in
CC       many retroviral envelope proteins. Synthetic peptides derived from this
CC       relatively conserved sequence inhibit immune function in vitro and in
CC       vivo. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: The YXXL motif is involved in determining the exact site of
CC       viral release at the surface of infected mononuclear cells and promotes
CC       endocytosis. YXXL and di-leucine endocytosis motifs interact directly
CC       or indirectly with the clathrin adapter complexes, opperate
CC       independently, and their activities are not additive.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- DOMAIN: The CD4-binding region is targeted by the antibody b12.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- PTM: Highly glycosylated by host. The high number of glycan on the
CC       protein is reffered to as 'glycan shield' because it contributes to
CC       hide protein sequence from adaptive immune system. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- PTM: Palmitoylation of the transmembrane protein and of Env polyprotein
CC       (prior to its proteolytic cleavage) is essential for their association
CC       with host cell membrane lipid rafts. Palmitoylation is therefore
CC       required for envelope trafficking to classical lipid rafts, but not for
CC       viral replication. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- PTM: Specific enzymatic cleavages in vivo yield mature proteins.
CC       Envelope glycoproteins are synthesized as an inactive precursor that is
CC       heavily N-glycosylated and processed likely by host cell furin in the
CC       Golgi to yield the mature SU and TM proteins. The cleavage site between
CC       SU and TM requires the minimal sequence [KR]-X-[KR]-R. About 2 of the 9
CC       disulfide bonds of gp41 are reduced by P4HB/PDI, following binding to
CC       CD4 receptor. {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- MISCELLANEOUS: Inhibitors targeting HIV-1 viral envelope proteins are
CC       used as antiretroviral drugs. Attachment of virions to the cell surface
CC       via non-specific interactions and CD4 binding can be blocked by
CC       inhibitors that include cyanovirin-N, cyclotriazadisulfonamide analogs,
CC       PRO 2000, TNX 355 and PRO 542. In addition, BMS 806 can block CD4-
CC       induced conformational changes. Env interactions with the coreceptor
CC       molecules can be targeted by CCR5 antagonists including SCH-D,
CC       maraviroc (UK 427857) and aplaviroc (GW 873140), and the CXCR4
CC       antagonist AMD 070. Fusion of viral and cellular membranes can be
CC       inhibited by peptides such as enfuvirtide and tifuvirtide (T 1249).
CC       Resistance to inhibitors associated with mutations in Env are observed.
CC       Most of the time, single mutations confer only a modest reduction in
CC       drug susceptibility. Combination of several mutations is usually
CC       required to develop a high-level drug resistance. {ECO:0000255|HAMAP-
CC       Rule:MF_04083}.
CC   -!- MISCELLANEOUS: HIV-1 lineages are divided in three main groups, M (for
CC       Major), O (for Outlier), and N (for New, or Non-M, Non-O). The vast
CC       majority of strains found worldwide belong to the group M. Group O
CC       seems to be endemic to and largely confined to Cameroon and neighboring
CC       countries in West Central Africa, where these viruses represent a small
CC       minority of HIV-1 strains. The group N is represented by a limited
CC       number of isolates from Cameroonian persons. The group M is further
CC       subdivided in 9 clades or subtypes (A to D, F to H, J and K).
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- SIMILARITY: Belongs to the HIV-1 env protein family.
CC       {ECO:0000255|HAMAP-Rule:MF_04083}.
CC   -!- WEB RESOURCE: Name=hivdb; Note=HIV drug resistance database;
CC       URL="https://hivdb.stanford.edu";
CC   -!- WEB RESOURCE: Name=HIV drug resistance mutations;
CC       URL="https://www.iasusa.org/content/hiv-drug-resistance-mutations";
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DR   EMBL; M15896; AAB53948.1; -; Genomic_RNA.
DR   PIR; A44963; A44963.
DR   SMR; P05881; -.
DR   GlyCosmos; P05881; 28 sites, No reported glycans.
DR   ABCD; P05881; 1 sequenced antibody.
DR   Reactome; R-HSA-5621480; Dectin-2 family.
DR   GO; GO:0044175; C:host cell endosome membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0016020; C:membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:0019031; C:viral envelope; IEA:UniProtKB-KW.
DR   GO; GO:0055036; C:virion membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005198; F:structural molecule activity; IEA:UniProtKB-UniRule.
DR   GO; GO:0075512; P:clathrin-dependent endocytosis of virus by host cell; IEA:UniProtKB-UniRule.
DR   GO; GO:0039654; P:fusion of virus membrane with host endosome membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:0019064; P:fusion of virus membrane with host plasma membrane; IEA:UniProtKB-UniRule.
DR   GO; GO:1903905; P:positive regulation of establishment of T cell polarity; IEA:UniProtKB-UniRule.
DR   GO; GO:1903908; P:positive regulation of plasma membrane raft polarization; IEA:UniProtKB-UniRule.
DR   GO; GO:1903911; P:positive regulation of receptor clustering; IEA:UniProtKB-UniRule.
DR   GO; GO:0019082; P:viral protein processing; IEA:UniProtKB-UniRule.
DR   GO; GO:0019062; P:virion attachment to host cell; IEA:UniProtKB-UniRule.
DR   GO; GO:0019049; P:virus-mediated perturbation of host defense response; IEA:UniProtKB-UniRule.
DR   CDD; cd09909; HIV-1-like_HR1-HR2; 1.
DR   Gene3D; 1.10.287.210; -; 1.
DR   Gene3D; 2.170.40.20; Human immunodeficiency virus 1, Gp160, envelope glycoprotein; 2.
DR   Gene3D; 1.20.5.490; Single helix bin; 1.
DR   HAMAP; MF_04083; HIV_ENV; 1.
DR   InterPro; IPR036377; Gp120_core_sf.
DR   InterPro; IPR037527; Gp160.
DR   InterPro; IPR000328; GP41-like.
DR   InterPro; IPR000777; HIV1_Gp120.
DR   Pfam; PF00516; GP120; 2.
DR   Pfam; PF00517; GP41; 1.
DR   SUPFAM; SSF56502; gp120 core; 2.
DR   SUPFAM; SSF58069; Virus ectodomain; 1.
PE   3: Inferred from homology;
KW   AIDS; Apoptosis; Clathrin-mediated endocytosis of virus by host;
KW   Cleavage on pair of basic residues; Coiled coil; Disulfide bond;
KW   Fusion of virus membrane with host endosomal membrane;
KW   Fusion of virus membrane with host membrane; Glycoprotein;
KW   Host cell membrane; Host endosome; Host membrane; Host-virus interaction;
KW   Lipoprotein; Membrane; Palmitate; Signal; Transmembrane;
KW   Transmembrane helix; Viral attachment to host cell; Viral envelope protein;
KW   Viral immunoevasion; Viral penetration into host cytoplasm; Virion;
KW   Virus endocytosis by host; Virus entry into host cell.
FT   SIGNAL          1..31
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CHAIN           32..856
FT                   /note="Envelope glycoprotein gp160"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000239480"
FT   CHAIN           32..511
FT                   /note="Surface protein gp120"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000038400"
FT   CHAIN           512..856
FT                   /note="Transmembrane protein gp41"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT                   /id="PRO_0000038401"
FT   TOPO_DOM        32..684
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   TRANSMEM        685..705
FT                   /note="Helical"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   TOPO_DOM        706..856
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          130..152
FT                   /note="V1"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          153..197
FT                   /note="V2"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          297..330
FT                   /note="V3"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          365..375
FT                   /note="CD4-binding loop"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          386..418
FT                   /note="V4"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          461..471
FT                   /note="V5"
FT   REGION          463..471
FT                   /note="V5"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          512..532
FT                   /note="Fusion peptide"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          574..592
FT                   /note="Immunosuppression"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          662..683
FT                   /note="MPER; binding to GalCer"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   REGION          720..742
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COILED          633..667
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   MOTIF           712..715
FT                   /note="YXXL motif; contains endocytosis signal"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   MOTIF           855..856
FT                   /note="Di-leucine internalization motif"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   COMPBIAS        722..742
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   SITE            511..512
FT                   /note="Cleavage; by host furin"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   LIPID           764
FT                   /note="S-palmitoyl cysteine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        87
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        132
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        138
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        152
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        156
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        183
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        198
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        242
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        263
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        277
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        294
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        302
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        332
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        339
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        355
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        364
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        387
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        393
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        398
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        402
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        411
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        448
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        461
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        462
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        465
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        611
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        616
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   CARBOHYD        637
FT                   /note="N-linked (GlcNAc...) asparagine; by host"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        53..73
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        118..206
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        125..197
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        130..153
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        219..248
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        229..240
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        297..331
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        379..445
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        386..418
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
FT   DISULFID        598..604
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04083"
SQ   SEQUENCE   856 AA;  96909 MW;  8396E3F8BBBD174E CRC64;
     MKVKGIQGNW QNWWKWGTLI LGLVIICSAA ENLWVTVYYG VPVWKDAETT LFCASDAKAY
     DTEKHNVWAT HACVPTDPNP QELSLGNVTE KFDMWKNNMV EQMHEDVISL WDQSLKPCVK
     LTPLCVTLSC HNITIKDNNT NVDTEMKEEI KNCSYNMTTE LRDKQRKIYS LFYRLDIVPI
     GGNSSNGDSS KYRLINCNTS AITQACPKVS FEPIPIHYCA PAGFAILKCR DEEFEGKGPC
     RNVSTVQCTH GIRPVVSTQL LLNGSLAEGE VRIRSENFTD NAKIIIVQLV KPVNITCMRP
     NNNTRKSISI GPGRAFFATG DIIGDIRQAH CNVSRTEWND TLSKVAAQLR KHFVNTSTDI
     IFANSSGGDV EITTHSFNCG GEFFYCNTSG LFNGTWLNGT SNNTWKIDTV NDTIILPCRI
     KQIVNMWQRV GQAMYAPPIK GVIKCVSNIT GILLTRDGVG NNTSNETFRP GGGDMRDNWR
     SELYKYKVVK IEPLGVAPTK AKRRVVAREK RAIGMGAFFL GFLGAAGSTM GAASITLTVQ
     ARRLLSGIVQ QQNNLLRAIE AQQHLLKLTV WGIKQLQARI LAVERYLKDQ QLLGIWGCSG
     KIICPTNVPW NSSWSNKSQS DIWDKMTWLE WDKEVSNYTQ VIYNLIEESQ TQQEINERDL
     LALDKWANLW NWFDISNWLW YIKIFIMIVG GLIGLRIVFA VLSIINRVRQ GYSPLSFQTL
     THHQREPDRP ERIEEGGGEQ DRDRSIRLVS GFLPLAWDDL RSLCLFCYHR LRDCALIAAR
     IVETLIRRGW ETLKYLGNLV IYWGQELKNS AINLLDTVAI AVADWTDRVI EVVQRAGRAF
     LNIPRRIRQG LERALL
//
