ID CASC3_HUMAN Reviewed; 703 AA. AC O15234; A8K8R0; DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot. DT 14-AUG-2001, sequence version 2. DT 18-SEP-2019, entry version 182. DE RecName: Full=Protein CASC3; DE AltName: Full=Cancer susceptibility candidate gene 3 protein; DE AltName: Full=Metastatic lymph node gene 51 protein {ECO:0000303|PubMed:12080473}; DE Short=MLN 51; DE AltName: Full=Protein barentsz; DE Short=Btz; GN Name=CASC3; Synonyms=MLN51 {ECO:0000303|PubMed:12080473}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Mammary carcinoma; RX PubMed=7490069; DOI=10.1006/geno.1995.1163; RA Tomasetto C.L., Regnier C.H., Moog-Lutz C., Mattei M.-G., RA Chenard M.-P., Lidereau R., Basset P., Rio M.-C.; RT "Identification of four novel human genes amplified and overexpressed RT in breast carcinoma and localized to the q11-q21.3 region of RT chromosome 17."; RL Genomics 28:367-376(1995). RN [2] RP SEQUENCE REVISION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND RP PHOSPHORYLATION. RC TISSUE=Mammary carcinoma; RX PubMed=12080473; DOI=10.1038/sj.onc.1205611; RA Degot S.F., Regnier C.H., Wendling C., Chenard M.-P., Rio M.-C., RA Tomasetto C.L.; RT "Metastatic lymph node 51, a novel nucleo-cytoplasmic protein RT overexpressed in breast cancer."; RL Oncogene 21:4422-4434(2002). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Testis; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16625196; DOI=10.1038/nature04689; RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., RA Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., RA Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., RA Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., RA Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., RA Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., RA Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., RA Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.; RT "DNA sequence of human chromosome 17 and analysis of rearrangement in RT the human lineage."; RL Nature 440:1045-1049(2006). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Duodenum, and Skin; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] RP OVEREXPRESSION IN GASTRIC CANCERS. RX PubMed=11980659; RA Varis A., Wolf M., Monni O., Vakkari M.-L., Kokkola A., Moskaluk C., RA Frierson H.F. Jr., Powell S.M., Knuutila S., Kallioniemi A., RA El-Rifai W.; RT "Targets of gene amplification and overexpression at 17q in gastric RT cancer."; RL Cancer Res. 62:2625-2629(2002). RN [7] RP INTERACTION WITH MAGOH; NXF1 AND RBM8A, RNA-BINDING, AND SUBCELLULAR RP LOCATION. RX PubMed=15166247; DOI=10.1074/jbc.m402754200; RA Degot S., Le Hir H., Alpy F., Kedinger V., Stoll I., Wendling C., RA Seraphin B., Rio M.-C., Tomasetto C.; RT "Association of the breast cancer protein MLN51 with the exon junction RT complex via its speckle localizer and RNA binding module."; RL J. Biol. Chem. 279:33702-33715(2004). RN [8] RP IDENTIFICATION IN THE CORE EXON JUNCTION COMPLEX, INTERACTION WITH RP EIF4A3, MUTAGENESIS OF TYR-181; 184-ARG-LYS-185; PHE-188; TRP-218; RP 220-HIS-ASP-221 AND 240-TYR-GLY-241, SUBCELLULAR LOCATION, AND RP RNA-BINDING. RX PubMed=16170325; DOI=10.1038/nsmb990; RA Ballut L., Marchadier B., Baguet A., Tomasetto C., Seraphin B., RA Le Hir H.; RT "The exon junction core complex is locked onto RNA by inhibition of RT eIF4AIII ATPase activity."; RL Nat. Struct. Mol. Biol. 12:861-869(2005). RN [9] RP IDENTIFICATION IN THE CORE EXON JUNCTION COMPLEX, IDENTIFICATION IN A RP MRNA SPLICING-DEPENDENT EXON JUNCTION COMPLEX, AND IDENTIFICATION BY RP MASS SPECTROMETRY. RX PubMed=16314458; DOI=10.1261/rna.2155905; RA Tange T.O., Shibuya T., Jurica M.S., Moore M.J.; RT "Biochemical analysis of the EJC reveals two new factors and a stable RT tetrameric protein core."; RL RNA 11:1869-1883(2005). RN [10] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-363 AND SER-373, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026; RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., RA Mann M.; RT "Global, in vivo, and site-specific phosphorylation dynamics in RT signaling networks."; RL Cell 127:635-648(2006). RN [11] RP FUNCTION IN STRESS RESPONSE, AND SUBCELLULAR LOCATION. RX PubMed=17652158; DOI=10.1242/jcs.009225; RA Baguet A., Degot S., Cougot N., Bertrand E., Chenard M.P., RA Wendling C., Kessler P., Le Hir H., Rio M.C., Tomasetto C.; RT "The exon-junction-complex-component metastatic lymph node 51 RT functions in stress-granule assembly."; RL J. Cell Sci. 120:2774-2784(2007). RN [12] RP FUNCTION IN EIF4A3 ATPASE AND RNA-HELICASE ACTIVITY. RX PubMed=17375189; DOI=10.1371/journal.pone.0000303; RA Noble C.G., Song H.; RT "MLN51 stimulates the RNA-helicase activity of eIF4AIII."; RL PLoS ONE 2:E303-E303(2007). RN [13] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-148 AND SER-477, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [14] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., RA Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in RT a refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [15] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-148, AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200; RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., RA Mann M., Daub H.; RT "Large-scale proteomics analysis of the human kinome."; RL Mol. Cell. Proteomics 8:1751-1764(2009). RN [16] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [17] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [18] RP ADP-RIBOSYLATION, AND UBIQUITINATION. RX PubMed=21478859; DOI=10.1038/ncb2222; RA Zhang Y., Liu S., Mickanin C., Feng Y., Charlat O., Michaud G.A., RA Schirle M., Shi X., Hild M., Bauer A., Myer V.E., Finan P.M., RA Porter J.A., Huang S.M., Cong F.; RT "RNF146 is a poly(ADP-ribose)-directed E3 ligase that regulates axin RT degradation and Wnt signalling."; RL Nat. Cell Biol. 13:623-629(2011). RN [19] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-117; SER-148; SER-265; RP SER-363 AND SER-373, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE RP SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., RA Blagoev B.; RT "System-wide temporal characterization of the proteome and RT phosphoproteome of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [20] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-117; SER-148; SER-265 RP AND SER-363, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [21] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-117; SER-148 AND RP THR-357, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., RA Wang L., Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human RT liver phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [22] RP X-RAY CRYSTALLOGRAPHY (2.21 ANGSTROMS) OF 137-286 IN THE EJC COMPLEX RP WITH EIF4A3; MAGOH; RBM8A AND AMP-PNP. RX PubMed=16923391; DOI=10.1016/j.cell.2006.08.006; RA Bono F., Ebert J., Lorentzen E., Conti E.; RT "The crystal structure of the exon junction complex reveals how it RT maintains a stable grip on mRNA."; RL Cell 126:713-725(2006). RN [23] RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 170-246 IN THE EJC COMPLEX RP WITH EIF4A3; MAGOH; RBM8A AND ADP-NP. RX PubMed=16931718; DOI=10.1126/science.1131981; RA Andersen C.B., Ballut L., Johansen J.S., Chamieh H., Nielsen K.H., RA Oliveira C.L., Pedersen J.S., Seraphin B., Le Hir H., Andersen G.R.; RT "Structure of the exon junction core complex with a trapped DEAD-box RT ATPase bound to RNA."; RL Science 313:1968-1972(2006). RN [24] RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 138-283 IN THE EJC COMPLEX RP WITH EIF4A3; MAGOH; RBM8A AND TRANSITION STATE ANALOG ADP-ALF3. RX PubMed=19033377; DOI=10.1261/rna.1283109; RA Nielsen K.H., Chamieh H., Andersen C.B., Fredslund F., Hamborg K., RA Le Hir H., Andersen G.R.; RT "Mechanism of ATP turnover inhibition in the EJC."; RL RNA 15:67-75(2009). RN [25] {ECO:0000244|PDB:2XB2} RP X-RAY CRYSTALLOGRAPHY (3.40 ANGSTROMS) OF 137-286 IN THE EJC COMPLEX RP WITH EIF4A3; MAGOH; RBM8A; UPF3B; UPF2 AND RNA, AND IDENTIFICATION IN RP THE EJC COMPLEX WITH UPF3A. RX PubMed=20479275; DOI=10.1073/pnas.1000993107; RA Buchwald G., Ebert J., Basquin C., Sauliere J., Jayachandran U., RA Bono F., Le Hir H., Conti E.; RT "Insights into the recruitment of the NMD machinery from the crystal RT structure of a core EJC-UPF3b complex."; RL Proc. Natl. Acad. Sci. U.S.A. 107:10050-10055(2010). RN [26] {ECO:0000244|PDB:5XJC} RP STRUCTURE BY ELECTRON MICROSCOPY (3.60 ANGSTROMS), FUNCTION, RP SUBCELLULAR LOCATION, AND SUBUNIT. RX PubMed=28502770; DOI=10.1016/j.cell.2017.04.033; RA Zhang X., Yan C., Hang J., Finci L.I., Lei J., Shi Y.; RT "An Atomic Structure of the Human Spliceosome."; RL Cell 169:918-929(2017). RN [27] {ECO:0000244|PDB:5YZG} RP STRUCTURE BY ELECTRON MICROSCOPY (4.10 ANGSTROMS), FUNCTION, RP SUBCELLULAR LOCATION, AND SUBUNIT. RX PubMed=29301961; DOI=10.1126/science.aar6401; RA Zhan X., Yan C., Zhang X., Lei J., Shi Y.; RT "Structure of a human catalytic step I spliceosome."; RL Science 359:537-545(2018). CC -!- FUNCTION: Required for pre-mRNA splicing as component of the CC spliceosome (PubMed:28502770, PubMed:29301961). Core component of CC the splicing-dependent multiprotein exon junction complex (EJC) CC deposited at splice junctions on mRNAs. The EJC is a dynamic CC structure consisting of core proteins and several peripheral CC nuclear and cytoplasmic associated factors that join the complex CC only transiently either during EJC assembly or during subsequent CC mRNA metabolism. The EJC marks the position of the exon-exon CC junction in the mature mRNA for the gene expression machinery and CC the core components remain bound to spliced mRNAs throughout all CC stages of mRNA metabolism thereby influencing downstream processes CC including nuclear mRNA export, subcellular mRNA localization, CC translation efficiency and nonsense-mediated mRNA decay (NMD). CC Stimulates the ATPase and RNA-helicase activities of EIF4A3. Plays CC a role in the stress response by participating in cytoplasmic CC stress granules assembly and by favoring cell recovery following CC stress. Component of the dendritic ribonucleoprotein particles CC (RNPs) in hippocampal neurons. May play a role in mRNA transport. CC Binds spliced mRNA in sequence-independent manner, 20-24 CC nucleotides upstream of mRNA exon-exon junctions. Binds poly(G) CC and poly(U) RNA homopolymer. {ECO:0000269|PubMed:17375189, CC ECO:0000269|PubMed:17652158, ECO:0000269|PubMed:28502770, CC ECO:0000269|PubMed:29301961}. CC -!- SUBUNIT: Identified in the spliceosome C complex (PubMed:28502770, CC PubMed:29301961). Component of the mRNA splicing-dependent exon CC junction complex (EJC), which contains at least CASC3, EIF4A3, CC MAGOH, NXF1 and RBM8A/Y14 (PubMed:15166247, PubMed:16170325, CC PubMed:16314458, PubMed:16923391, PubMed:16931718, CC PubMed:19033377, PubMed:20479275). Identified in a complex CC composed of the EJC core, UPF3B and UPF2. The EJC core can also CC interact with UPF3A (in vitro) (PubMed:20479275). Forms CC homooligomers (By similarity). Interacts with STAU in an RNA- CC dependent manner (By similarity). {ECO:0000250|UniProtKB:Q8K3X0, CC ECO:0000269|PubMed:15166247, ECO:0000269|PubMed:16170325, CC ECO:0000269|PubMed:16314458, ECO:0000269|PubMed:16923391, CC ECO:0000269|PubMed:16931718, ECO:0000269|PubMed:19033377, CC ECO:0000269|PubMed:20479275, ECO:0000269|PubMed:28502770, CC ECO:0000269|PubMed:29301961}. CC -!- INTERACTION: CC P38919:EIF4A3; NbExp=30; IntAct=EBI-299118, EBI-299104; CC P61326:MAGOH; NbExp=23; IntAct=EBI-299118, EBI-299134; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:12080473}. CC Cytoplasm, perinuclear region {ECO:0000250|UniProtKB:Q8K3W3}. CC Nucleus {ECO:0000269|PubMed:12080473, ECO:0000269|PubMed:28502770, CC ECO:0000269|PubMed:29301961}. Nucleus speckle CC {ECO:0000269|PubMed:16170325}. Cytoplasm, Stress granule CC {ECO:0000269|PubMed:17652158}. Cytoplasm, Cytoplasmic CC ribonucleoprotein granule {ECO:0000250|UniProtKB:Q8K3X0}. Cell CC projection, dendrite {ECO:0000250|UniProtKB:Q8K3X0}. Note=Shuttles CC between the nucleus and the cytoplasm in a XPO1/CRM1-dependent CC manner. Transported to the cytoplasm as part of the exon junction CC complex (EJC) bound to mRNA (PubMed:15166247). In nuclear CC speckles, colocalizes with MAGOH. Under stress conditions, CC colocalizes with FMR1 and TIA1, but not MAGOH and RBM8A EJC core CC factors, in cytoplasmic stress granules (PubMed:17652158). In the CC dendrites of hippocampal neurons, localizes to dendritic CC ribonucleoprotein granules (By similarity). CC {ECO:0000250|UniProtKB:Q8K3X0, ECO:0000269|PubMed:15166247, CC ECO:0000269|PubMed:17652158}. CC -!- TISSUE SPECIFICITY: Widely expressed. Overexpressed in breast CC cancers and metastasis, as well as in gastric cancers. CC {ECO:0000269|PubMed:12080473}. CC -!- DOMAIN: The coiled coil domain may be involved in oligomerization. CC -!- PTM: ADP-ribosylated by tankyrase TNKS and TNKS2. Poly-ADP- CC ribosylated protein is recognized by RNF146, followed by CC ubiquitination. {ECO:0000269|PubMed:21478859}. CC -!- PTM: Ubiquitinated by RNF146 when poly-ADP-ribosylated, leading to CC its degradation. {ECO:0000269|PubMed:21478859}. CC -!- SIMILARITY: Belongs to the CASC3 family. {ECO:0000305}. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology CC and Haematology; CC URL="http://atlasgeneticsoncology.org/Genes/MLN51ID241.html"; 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; X80199; CAC27699.1; -; mRNA. DR EMBL; AK292425; BAF85114.1; -; mRNA. DR EMBL; AC068669; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC044656; AAH44656.1; -; mRNA. DR EMBL; BC050526; AAH50526.1; -; mRNA. DR CCDS; CCDS11362.1; -. DR RefSeq; NP_031385.2; NM_007359.4. DR RefSeq; XP_005257220.1; XM_005257163.1. DR PDB; 2HYI; X-ray; 2.30 A; D/J=170-246. DR PDB; 2J0Q; X-ray; 3.20 A; I/T=137-286. DR PDB; 2J0S; X-ray; 2.21 A; T=137-286. DR PDB; 2J0U; X-ray; 3.00 A; T=137-250. DR PDB; 2XB2; X-ray; 3.40 A; S/T=137-286. DR PDB; 3EX7; X-ray; 2.30 A; D/I=138-283. DR PDB; 5XJC; EM; 3.60 A; x=1-703. DR PDB; 5YZG; EM; 4.10 A; x=1-703. DR PDB; 6ICZ; EM; 3.00 A; x=1-703. DR PDBsum; 2HYI; -. DR PDBsum; 2J0Q; -. DR PDBsum; 2J0S; -. DR PDBsum; 2J0U; -. DR PDBsum; 2XB2; -. DR PDBsum; 3EX7; -. DR PDBsum; 5XJC; -. DR PDBsum; 5YZG; -. DR PDBsum; 6ICZ; -. DR SMR; O15234; -. DR BioGrid; 116475; 61. DR ComplexPortal; CPX-1941; Exon junction core complex, MAGOH variant. DR ComplexPortal; CPX-682; Exon junction core complex, MAGOHB variant. DR CORUM; O15234; -. DR DIP; DIP-33288N; -. DR ELM; O15234; -. DR IntAct; O15234; 50. DR MINT; O15234; -. DR STRING; 9606.ENSP00000264645; -. DR TCDB; 3.A.18.1.1; the nuclear mrna exporter (mrna-e) family. DR iPTMnet; O15234; -. DR PhosphoSitePlus; O15234; -. DR BioMuta; CASC3; -. DR EPD; O15234; -. DR jPOST; O15234; -. DR MassIVE; O15234; -. DR MaxQB; O15234; -. DR PaxDb; O15234; -. DR PeptideAtlas; O15234; -. DR PRIDE; O15234; -. DR ProteomicsDB; 48528; -. DR TopDownProteomics; O15234; -. DR Ensembl; ENST00000264645; ENSP00000264645; ENSG00000108349. DR GeneID; 22794; -. DR KEGG; hsa:22794; -. DR UCSC; uc002hue.4; human. DR CTD; 22794; -. DR DisGeNET; 22794; -. DR GeneCards; CASC3; -. DR HGNC; HGNC:17040; CASC3. DR HPA; HPA024592; -. DR HPA; HPA050262; -. DR MIM; 606504; gene. DR neXtProt; NX_O15234; -. DR OpenTargets; ENSG00000108349; -. DR PharmGKB; PA134948596; -. DR eggNOG; KOG4264; Eukaryota. DR eggNOG; ENOG410ZW5Y; LUCA. DR GeneTree; ENSGT00390000006930; -. DR HOGENOM; HOG000069997; -. DR InParanoid; O15234; -. DR KO; K14323; -. DR OMA; ERPNKSH; -. DR OrthoDB; 486761at2759; -. DR PhylomeDB; O15234; -. DR TreeFam; TF329663; -. DR Reactome; R-HSA-159236; Transport of Mature mRNA derived from an Intron-Containing Transcript. DR Reactome; R-HSA-72163; mRNA Splicing - Major Pathway. DR Reactome; R-HSA-72187; mRNA 3'-end processing. DR Reactome; R-HSA-73856; RNA Polymerase II Transcription Termination. DR Reactome; R-HSA-9010553; Regulation of expression of SLITs and ROBOs. DR Reactome; R-HSA-975957; Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC). DR ChiTaRS; CASC3; human. DR EvolutionaryTrace; O15234; -. DR GeneWiki; CASC3; -. DR GenomeRNAi; 22794; -. DR Pharos; O15234; -. DR PMAP-CutDB; O15234; -. DR PRO; PR:O15234; -. DR Proteomes; UP000005640; Chromosome 17. DR Bgee; ENSG00000108349; Expressed in 233 organ(s), highest expression level in middle frontal gyrus. DR ExpressionAtlas; O15234; baseline and differential. DR Genevisible; O15234; HS. DR GO; GO:0010494; C:cytoplasmic stress granule; IEA:UniProtKB-SubCell. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0030425; C:dendrite; IEA:UniProtKB-SubCell. DR GO; GO:0035145; C:exon-exon junction complex; IDA:UniProtKB. DR GO; GO:0031965; C:nuclear membrane; IDA:HPA. DR GO; GO:0016607; C:nuclear speck; IEA:UniProtKB-SubCell. DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell. DR GO; GO:0071006; C:U2-type catalytic step 1 spliceosome; IDA:UniProtKB. DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB. DR GO; GO:0042802; F:identical protein binding; IDA:MGI. DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB. DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:UniProtKB. DR GO; GO:0008298; P:intracellular mRNA localization; IEA:Ensembl. DR GO; GO:0031124; P:mRNA 3'-end processing; TAS:Reactome. DR GO; GO:0006406; P:mRNA export from nucleus; TAS:Reactome. DR GO; GO:0000398; P:mRNA splicing, via spliceosome; IDA:UniProtKB. DR GO; GO:0000184; P:nuclear-transcribed mRNA catabolic process, nonsense-mediated decay; TAS:Reactome. DR GO; GO:0006417; P:regulation of translation; IEA:UniProtKB-KW. DR GO; GO:0006405; P:RNA export from nucleus; TAS:Reactome. DR InterPro; IPR018545; Btz_dom. DR InterPro; IPR028544; CASC3. DR PANTHER; PTHR13434; PTHR13434; 1. DR Pfam; PF09405; Btz; 1. DR SMART; SM01044; Btz; 1. PE 1: Evidence at protein level; KW 3D-structure; ADP-ribosylation; Cell projection; Coiled coil; KW Complete proteome; Cytoplasm; mRNA processing; mRNA splicing; KW mRNA transport; Nonsense-mediated mRNA decay; Nucleus; Phosphoprotein; KW Reference proteome; RNA-binding; Spliceosome; Stress response; KW Translation regulation; Transport; Ubl conjugation. FT CHAIN 1 703 Protein CASC3. FT /FTId=PRO_0000089324. FT REGION 137 283 Necessary for RNA-binding, interaction FT with MAGOH and localization in nucleus FT speckles. {ECO:0000269|PubMed:15166247}. FT REGION 137 283 Sufficient to form the EJC. FT REGION 377 703 Necessary for localization in cytoplasmic FT stress granules. FT COILED 95 131 {ECO:0000255}. FT MOTIF 204 210 Nuclear localization signal 1. FT {ECO:0000255}. FT MOTIF 254 262 Nuclear localization signal 2. FT {ECO:0000255}. FT MOTIF 462 466 Nuclear export signal. FT COMPBIAS 41 46 Poly-Gly. FT COMPBIAS 392 395 Poly-Pro. FT COMPBIAS 425 428 Poly-Pro. FT COMPBIAS 643 648 Poly-Pro. FT COMPBIAS 692 695 Poly-Pro. FT MOD_RES 35 35 Phosphoserine. FT {ECO:0000250|UniProtKB:Q8K3W3}. FT MOD_RES 117 117 Phosphoserine. FT {ECO:0000244|PubMed:21406692, FT ECO:0000244|PubMed:23186163, FT ECO:0000244|PubMed:24275569}. FT MOD_RES 148 148 Phosphoserine. FT {ECO:0000244|PubMed:18669648, FT ECO:0000244|PubMed:19369195, FT ECO:0000244|PubMed:21406692, FT ECO:0000244|PubMed:23186163, FT ECO:0000244|PubMed:24275569}. FT MOD_RES 265 265 Phosphoserine. FT {ECO:0000244|PubMed:21406692, FT ECO:0000244|PubMed:23186163}. FT MOD_RES 357 357 Phosphothreonine. FT {ECO:0000244|PubMed:24275569}. FT MOD_RES 363 363 Phosphoserine. FT {ECO:0000244|PubMed:17081983, FT ECO:0000244|PubMed:21406692, FT ECO:0000244|PubMed:23186163}. FT MOD_RES 373 373 Phosphoserine. FT {ECO:0000244|PubMed:17081983, FT ECO:0000244|PubMed:21406692}. FT MOD_RES 477 477 Phosphoserine. FT {ECO:0000244|PubMed:18669648}. FT MUTAGEN 181 181 Y->A: Does not affect EJC formation. FT {ECO:0000269|PubMed:16170325}. FT MUTAGEN 184 185 RK->AA: Does not affect EJC formation. FT {ECO:0000269|PubMed:16170325}. FT MUTAGEN 188 188 F->A: Does not affect EJC formation. FT {ECO:0000269|PubMed:16170325}. FT MUTAGEN 218 218 W->A: Abolishes interaction with EIF4A3, FT EJC formation and localization in nucleus FT speckles. {ECO:0000269|PubMed:16170325}. FT MUTAGEN 220 221 HD->AA: Abolishes interaction with FT EIF4A3, EJC formation and localization in FT nucleus speckles. FT {ECO:0000269|PubMed:16170325}. FT MUTAGEN 240 241 YG->AA: Abolishes interaction with FT EIF4A3, EJC formation and localization in FT nucleus speckles. FT {ECO:0000269|PubMed:16170325}. FT HELIX 172 174 {ECO:0000244|PDB:2J0S}. FT HELIX 226 228 {ECO:0000244|PDB:2J0S}. FT HELIX 233 240 {ECO:0000244|PDB:2HYI}. FT TURN 244 246 {ECO:0000244|PDB:3EX7}. SQ SEQUENCE 703 AA; 76278 MW; 642A4C01C8DD3BE0 CRC64; MADRRRQRAS QDTEDEESGA SGSDSGGSPL RGGGSCSGSA GGGGSGSLPS QRGGRTGALH LRRVESGGAK SAEESECESE DGIEGDAVLS DYESAEDSEG EEGEYSEEEN SKVELKSEAN DAVNSSTKEE KGEEKPDTKS TVTGERQSGD GQESTEPVEN KVGKKGPKHL DDDEDRKNPA YIPRKGLFFE HDLRGQTQEE EVRPKGRQRK LWKDEGRWEH DKFREDEQAP KSRQELIALY GYDIRSAHNP DDIKPRRIRK PRYGSPPQRD PNWNGERLNK SHRHQGLGGT LPPRTFINRN AAGTGRMSAP RNYSRSGGFK EGRAGFRPVE AGGQHGGRSG ETVKHEISYR SRRLEQTSVR DPSPEADAPV LGSPEKEEAA SEPPAAAPDA APPPPDRPIE KKSYSRARRT RTKVGDAVKL AEEVPPPPEG LIPAPPVPET TPTPPTKTGT WEAPVDSSTS GLEQDVAQLN IAEQNWSPGQ PSFLQPRELR GMPNHIHMGA GPPPQFNRME EMGVQGGRAK RYSSQRQRPV PEPPAPPVHI SIMEGHYYDP LQFQGPIYTH GDSPAPLPPQ GMLVQPGMNL PHPGLHPHQT PAPLPNPGLY PPPVSMSPGQ PPPQQLLAPT YFSAPGVMNF GNPSYPYAPG ALPPPPPPHL YPNTQAPSQV YGGVTYYNPA QQQVQPKPSP PRRTPQPVTI KPPPPEVVSR GSS //