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"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms 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 --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 //