ID TS101_HUMAN Reviewed; 390 AA. AC Q99816; Q9BUM5; DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot. DT 01-AUG-1998, sequence version 2. DT 27-MAR-2024, entry version 241. DE RecName: Full=Tumor susceptibility gene 101 protein; DE AltName: Full=ESCRT-I complex subunit TSG101; GN Name=TSG101; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND RETRACTED PAPER. RC TISSUE=Placenta; RX PubMed=9019400; DOI=10.1016/s0092-8674(00)81866-8; RA Li L., Li X., Francke U., Cohen S.N.; RT "The TSG101 tumor susceptibility gene is located in chromosome 11 band p15 RT and is mutated in human breast cancer."; RL Cell 88:143-154(1997). RN [2] RP ERRATUM OF PUBMED:9019400, AND RETRACTION NOTICE OF PUBMED:9019400. RX PubMed=9867424; DOI=10.1016/s0092-8674(00)89342-3; RA Li L., Francke U., Cohen S.N.; RL Cell 93:661-661(1998). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Eye; 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 project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [4] RP ALTERNATIVE SPLICING (ISOFORM 2). RX PubMed=9366528; DOI=10.1038/sj.onc.1201591; RA Gayther S.A., Barski P., Batley S.J., Li L., de Foy K.A., Cohen S.N., RA Ponder B.A., Caldas C.; RT "Aberrant splicing of the TSG101 and FHIT genes occurs frequently in RT multiple malignancies and in normal tissues and mimics alterations RT previously described in tumours."; RL Oncogene 15:2119-2126(1997). RN [5] RP ALTERNATIVE SPLICING. RX PubMed=9242438; RA Lee M.P., Feinberg A.P.; RT "Aberrant splicing but not mutations of TSG101 in human breast cancer."; RL Cancer Res. 57:3131-3134(1997). RN [6] RP ALTERNATIVE SPLICING. RX PubMed=9840940; DOI=10.1038/sj.onc.1202529; RA Wagner K.-U., Dierisseau P., Rucker E.B. III, Robinson G.W., RA Hennighausen L.; RT "Genomic architecture and transcriptional activation of the mouse and human RT tumor susceptibility gene TSG101: common types of shorter transcripts are RT true alternative splice variants."; RL Oncogene 17:2761-2770(1998). RN [7] RP INTERACTION WITH DMAP1. RX PubMed=10888872; DOI=10.1038/77023; RA Rountree M.R., Bachman K.E., Baylin S.B.; RT "DNMT1 binds HDAC2 and a new co-repressor, DMAP1, to form a complex at RT replication foci."; RL Nat. Genet. 25:269-277(2000). RN [8] RP INTERACTION WITH HIV-1 P6 (MICROBIAL INFECTION) AND UBIQUITIN. RX PubMed=11595185; DOI=10.1016/s0092-8674(01)00506-2; RA Garrus J.E., von Schwedler U.K., Pornillos O.W., Morham S.G., Zavitz K.H., RA Wang H.E., Wettstein D.A., Stray K.M., Cote M., Rich R.L., Myszka D.G., RA Sundquist W.I.; RT "Tsg101 and the vacuolar protein sorting pathway are essential for HIV-1 RT budding."; RL Cell 107:55-65(2001). RN [9] RP INTERACTION WITH HIV-1 P6 (MICROBIAL INFECTION). RX PubMed=11427703; DOI=10.1073/pnas.131059198; RA VerPlank L., Bouamr F., LaGrassa T.J., Agresta B., Kikonyogo A., Leis J., RA Carter C.A.; RT "Tsg101, a homologue of ubiquitin-conjugating (E2) enzymes, binds the L RT domain in HIV type 1 Pr55(Gag)."; RL Proc. Natl. Acad. Sci. U.S.A. 98:7724-7729(2001). RN [10] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=11916981; DOI=10.1083/jcb.200112080; RA Bishop N., Horman A., Woodman P.; RT "Mammalian class E vps proteins recognize ubiquitin and act in the removal RT of endosomal protein-ubiquitin conjugates."; RL J. Cell Biol. 157:91-101(2002). RN [11] RP SELF-ASSOCIATION, INTERACTION WITH PDCD6IP; VPS28; SNF8 AND VPS36, AND RP MUTAGENESIS OF MET-95. RX PubMed=14505570; DOI=10.1016/s0092-8674(03)00714-1; RA von Schwedler U.K., Stuchell M., Mueller B., Ward D.M., Chung H.-Y., RA Morita E., Wang H.E., Davis T., He G.P., Cimbora D.M., Scott A., RA Kraeusslich H.-G., Kaplan J., Morham S.G., Sundquist W.I.; RT "The protein network of HIV budding."; RL Cell 114:701-713(2003). RN [12] RP INTERACTION WITH HIV-1 GAG (MICROBIAL INFECTION) AND HGS, AND RP SELF-ASSOCIATION. RX PubMed=12900394; DOI=10.1083/jcb.200302138; RA Pornillos O., Higginson D.S., Stray K.M., Fisher R.D., Garrus J.E., RA Payne M., He G.P., Wang H.E., Morham S.G., Sundquist W.I.; RT "HIV Gag mimics the Tsg101-recruiting activity of the human Hrs protein."; RL J. Cell Biol. 162:425-434(2003). RN [13] RP INTERACTION WITH EBOLA VIRUS VP40 (MICROBIAL INFECTION). RX PubMed=12559917; DOI=10.1016/s0022-2836(02)01406-7; RA Timmins J., Schoehn G., Ricard-Blum S., Scianimanico S., Vernet T., RA Ruigrok R.W., Weissenhorn W.; RT "Ebola virus matrix protein VP40 interaction with human cellular factors RT Tsg101 and Nedd4."; RL J. Mol. Biol. 326:493-502(2003). RN [14] RP INTERACTION WITH HTLV-1 GAG (MICROBIAL INFECTION). RX PubMed=14581525; DOI=10.1128/jvi.77.22.11882-11895.2003; RA Bouamr F., Melillo J.A., Wang M.Q., Nagashima K., de Los Santos M., RA Rein A., Goff S.P.; RT "PPPYVEPTAP motif is the late domain of human T-cell leukemia virus type 1 RT Gag and mediates its functional interaction with cellular proteins Nedd4 RT and Tsg101."; RL J. Virol. 77:11882-11895(2003). RN [15] RP MUTAGENESIS OF ASN-45 AND MET-95. RX PubMed=12802020; DOI=10.1073/pnas.0932599100; RA Lu Q., Hope L.W., Brasch M., Reinhard C., Cohen S.N.; RT "TSG101 interaction with HRS mediates endosomal trafficking and receptor RT down-regulation."; RL Proc. Natl. Acad. Sci. U.S.A. 100:7626-7631(2003). RN [16] RP SELF-ASSOCIATION, AND INTERACTION WITH PDCD6IP AND EIAV P9 (MICROBIAL RP INFECTION). RX PubMed=14519844; DOI=10.1073/pnas.2133846100; RA Martin-Serrano J., Yarovoy A., Perez-Caballero D., Bieniasz P.D.; RT "Divergent retroviral late-budding domains recruit vacuolar protein sorting RT factors by using alternative adaptor proteins."; RL Proc. Natl. Acad. Sci. U.S.A. 100:12414-12419(2003). RN [17] RP ERRATUM OF PUBMED:14519844. RA Martin-Serrano J., Yarovoy A., Perez-Caballero D., Bieniasz P.D.; RL Proc. Natl. Acad. Sci. U.S.A. 100:152845-152845(2003). RN [18] RP UBIQUITINATION BY LRSAM1. RX PubMed=15256501; DOI=10.1101/gad.294904; RA Amit I., Yakir L., Katz M., Zwang Y., Marmor M.D., Citri A., Shtiegman K., RA Alroy I., Tuvia S., Reiss Y., Roubini E., Cohen M., Wides R., Bacharach E., RA Schubert U., Yarden Y.; RT "Tal, a Tsg101-specific E3 ubiquitin ligase, regulates receptor endocytosis RT and retrovirus budding."; RL Genes Dev. 18:1737-1752(2004). RN [19] RP INTERACTION WITH VPS37A AND VPS37B, AND MUTAGENESIS OF MET-95. RX PubMed=15218037; DOI=10.1074/jbc.m405226200; RA Stuchell M.D., Garrus J.E., Mueller B., Stray K.M., Ghaffarian S., RA McKinnon R., Kraeusslich H.-G., Morham S.G., Sundquist W.I.; RT "The human endosomal sorting complex required for transport (ESCRT-I) and RT its role in HIV-1 budding."; RL J. Biol. Chem. 279:36059-36071(2004). RN [20] RP INTERACTION WITH GGA1. RX PubMed=15143060; DOI=10.1074/jbc.m402183200; RA Mattera R., Puertollano R., Smith W.J., Bonifacino J.S.; RT "The trihelical bundle subdomain of the GGA proteins interacts with RT multiple partners through overlapping but distinct sites."; RL J. Biol. Chem. 279:31409-31418(2004). RN [21] RP INTERACTION WITH GGA3. RX PubMed=15039775; DOI=10.1038/ncb1106; RA Puertollano R., Bonifacino J.S.; RT "Interactions of GGA3 with the ubiquitin sorting machinery."; RL Nat. Cell Biol. 6:244-251(2004). RN [22] RP INTERACTION WITH VPS37C, AND MUTAGENESIS OF 368-ARG--PHE-371. RX PubMed=15509564; DOI=10.1074/jbc.m410384200; RA Eastman S.W., Martin-Serrano J., Chung W., Zang T., Bieniasz P.D.; RT "Identification of human VPS37C, a component of endosomal sorting complex RT required for transport-I important for viral budding."; RL J. Biol. Chem. 280:628-636(2005). RN [23] RP INTERACTION WITH HUMAN SPUMARETROVIRUS GAG (MICROBIAL INFECTION). RX PubMed=15858022; DOI=10.1128/jvi.79.10.6392-6399.2005; RA Patton G.S., Morris S.A., Chung W., Bieniasz P.D., McClure M.O.; RT "Identification of domains in gag important for prototypic foamy virus RT egress."; RL J. Virol. 79:6392-6399(2005). RN [24] RP INTERACTION WITH LASSA VIRUS RING FINGER PROTEIN Z (MICROBIAL INFECTION). RX PubMed=16571837; DOI=10.1128/jvi.80.8.4191-4195.2006; RA Urata S., Noda T., Kawaoka Y., Yokosawa H., Yasuda J.; RT "Cellular factors required for Lassa virus budding."; RL J. Virol. 80:4191-4195(2006). RN [25] RP INTERACTION WITH VPS28; VPS37A; VPS37B; VPS37C; VPS37D; MVB12A AND MVB12B, RP AND RECONSTITUTION OF THE ESCRT-I COMPLEX. RX PubMed=18005716; DOI=10.1016/j.chom.2007.06.003; RA Morita E., Sandrin V., Alam S.L., Eckert D.M., Gygi S.P., Sundquist W.I.; RT "Identification of human MVB12 proteins as ESCRT-I subunits that function RT in HIV budding."; RL Cell Host Microbe 2:41-53(2007). RN [26] RP FUNCTION IN CYTOKINESIS, SUBCELLULAR LOCATION, INTERACTION WITH CEP55; RP CD2AP; IQGAP1 AND ROCK1, AND MUTAGENESIS OF 158-PRO--ASN-160. RX PubMed=17853893; DOI=10.1038/sj.emboj.7601850; RA Morita E., Sandrin V., Chung H.Y., Morham S.G., Gygi S.P., Rodesch C.K., RA Sundquist W.I.; RT "Human ESCRT and ALIX proteins interact with proteins of the midbody and RT function in cytokinesis."; RL EMBO J. 26:4215-4227(2007). RN [27] RP INTERACTION WITH MGRN1, UBIQUITINATION BY MGRN1, SUBCELLULAR LOCATION, AND RP MUTAGENESIS OF ASN-45 AND MET-95. RX PubMed=17229889; DOI=10.1091/mbc.e06-09-0787; RA Kim B.Y., Olzmann J.A., Barsh G.S., Chin L.S., Li L.; RT "Spongiform neurodegeneration-associated E3 ligase Mahogunin ubiquitylates RT TSG101 and regulates endosomal trafficking."; RL Mol. Biol. Cell 18:1129-1142(2007). RN [28] RP FUNCTION IN CYTOKINESIS, FUNCTION IN HIV-1 BUDDING, SUBCELLULAR LOCATION, RP SELF-ASSOCIATION, INTERACTION WITH CEP55; HSG; VPS28; VPS37A; VPS37B; RP VPS37C; VPS37D; PDCD6IP; LRSAM1; HIV-1 GAG AND EBOLA VIRUS VP40, AND RP MUTAGENESIS OF 158-PRO--SER-162. RX PubMed=17556548; DOI=10.1126/science.1143422; RA Carlton J.G., Martin-Serrano J.; RT "Parallels between cytokinesis and retroviral budding: a role for the ESCRT RT machinery."; RL Science 316:1908-1912(2007). RN [29] RP INTERACTION WITH PDCD6. RX PubMed=18256029; DOI=10.1074/jbc.m800717200; RA Shibata H., Suzuki H., Kakiuchi T., Inuzuka T., Yoshida H., Mizuno T., RA Maki M.; RT "Identification of Alix-type and non-Alix-type ALG-2-binding sites in human RT phospholipid scramblase 3: differential binding to an alternatively spliced RT isoform and amino acid-substituted mutants."; RL J. Biol. Chem. 283:9623-9632(2008). RN [30] RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [31] RP INTERACTION WITH PDCD6IP. RX PubMed=19520058; DOI=10.1016/j.bbrc.2009.06.015; RA Okumura M., Ichioka F., Kobayashi R., Suzuki H., Yoshida H., Shibata H., RA Maki M.; RT "Penta-EF-hand protein ALG-2 functions as a Ca2+-dependent adaptor that RT bridges Alix and TSG101."; RL Biochem. Biophys. Res. Commun. 386:237-241(2009). RN [32] RP INTERACTION WITH MGRN1, AND UBIQUITINATION BY MGRN1. RX PubMed=19703557; DOI=10.1016/j.bbadis.2009.08.009; RA Jiao J., Sun K., Walker W.P., Bagher P., Cota C.D., Gunn T.M.; RT "Abnormal regulation of TSG101 in mice with spongiform neurodegeneration."; RL Biochim. Biophys. Acta 1792:1027-1035(2009). RN [33] 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., Buerckstuemmer T., RA 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 [34] RP FUNCTION, SUBUNIT, AND IDENTIFICATION IN AN ESCRT-I COMPLEX WITH UBAP1. RX PubMed=21757351; DOI=10.1016/j.cub.2011.06.028; RA Stefani F., Zhang L., Taylor S., Donovan J., Rollinson S., Doyotte A., RA Brownhill K., Bennion J., Pickering-Brown S., Woodman P.; RT "UBAP1 is a component of an endosome-specific ESCRT-I complex that is RT essential for MVB sorting."; RL Curr. Biol. 21:1245-1250(2011). RN [35] RP INTERACTION WITH HEPATITIS E VIRUS PROTEIN ORF3. RX PubMed=21068219; DOI=10.1099/vir.0.025791-0; RA Nagashima S., Takahashi M., Jirintai S., Tanaka T., Yamada K., RA Nishizawa T., Okamoto H.; RT "A PSAP motif in the ORF3 protein of hepatitis E virus is necessary for RT virion release from infected cells."; RL J. Gen. Virol. 92:269-278(2011). RN [36] RP INTERACTION WITH ARRDC1. RX PubMed=21191027; DOI=10.1128/jvi.02045-10; RA Rauch S., Martin-Serrano J.; RT "Multiple interactions between the ESCRT machinery and arrestin-related RT proteins: implications for PPXY-dependent budding."; RL J. Virol. 85:3546-3556(2011). RN [37] RP INTERACTION WITH LITAF, AND SUBCELLULAR LOCATION. RX PubMed=23166352; DOI=10.1083/jcb.201204137; RA Lee S.M., Chin L.S., Li L.; RT "Charcot-Marie-Tooth disease-linked protein SIMPLE functions with the ESCRT RT machinery in endosomal trafficking."; RL J. Cell Biol. 199:799-816(2012). RN [38] RP FUNCTION. RX PubMed=22660413; DOI=10.1038/ncb2502; RA Baietti M.F., Zhang Z., Mortier E., Melchior A., Degeest G., Geeraerts A., RA Ivarsson Y., Depoortere F., Coomans C., Vermeiren E., Zimmermann P., RA David G.; RT "Syndecan-syntenin-ALIX regulates the biogenesis of exosomes."; RL Nat. Cell Biol. 14:677-685(2012). RN [39] RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RX PubMed=22814378; DOI=10.1073/pnas.1210303109; RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N-terminal RT acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). RN [40] RP FUNCTION, INTERACTION WITH ARRDC1, AND MUTAGENESIS OF MET-95. RX PubMed=22315426; DOI=10.1073/pnas.1200448109; RA Nabhan J.F., Hu R., Oh R.S., Cohen S.N., Lu Q.; RT "Formation and release of arrestin domain-containing protein 1-mediated RT microvesicles (ARMMs) at plasma membrane by recruitment of TSG101 RT protein."; RL Proc. Natl. Acad. Sci. U.S.A. 109:4146-4151(2012). RN [41] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-220, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE 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 [42] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [43] RP STRUCTURE BY NMR OF 1-145, INTERACTION WITH HIV-1 P6 (MICROBIAL INFECTION) RP AND UBIQUITIN, AND MUTAGENESIS OF VAL-43; ASN-45; ASP-46; TYR-63; PHE-88; RP VAL-89; MET-95 AND VAL-141. RX PubMed=12006492; DOI=10.1093/emboj/21.10.2397; RA Pornillos O.W., Alam S.L., Rich R.L., Myszka D.G., Davis D.R., RA Sundquist W.I.; RT "Structure and functional interactions of the Tsg101 UEV domain."; RL EMBO J. 21:2397-2406(2002). RN [44] RP STRUCTURE BY NMR OF 1-145. RX PubMed=12379843; DOI=10.1038/nsb856; RA Pornillos O., Alam S.L., Davis D.R., Sundquist W.I.; RT "Structure of the Tsg101 UEV domain in complex with the PTAP motif of the RT HIV-1 p6 protein."; RL Nat. Struct. Biol. 9:812-817(2002). RN [45] RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 1-145 IN COMPLEX WITH UBIQUITIN. RX PubMed=15053872; DOI=10.1016/s1097-2765(04)00129-7; RA Sundquist W.I., Schubert H.L., Kelly B.N., Hill G.C., Holton J.M., RA Hill C.P.; RT "Ubiquitin recognition by the human TSG101 protein."; RL Mol. Cell 13:783-789(2004). RN [46] RP X-RAY CRYSTALLOGRAPHY (2.26 ANGSTROMS) OF 1-145. RX PubMed=16552148; DOI=10.1107/s0907444906005221; RA Palencia A., Martinez J.C., Mateo P.L., Luque I., Camara-Artigas A.; RT "Structure of human TSG101 UEV domain."; RL Acta Crystallogr. D 62:458-464(2006). RN [47] RP X-RAY CRYSTALLOGRAPHY (1.4 ANGSTROMS) OF 2-145 IN COMPLEX WITH HIV-1 GAG P6 RP PEPTIDE (MICROBIAL INFECTION), FUNCTION, AND SUBUNIT. RX PubMed=21070952; DOI=10.1016/j.str.2010.08.010; RA Im Y.J., Kuo L., Ren X., Burgos P.V., Zhao X.Z., Liu F., Burke T.R. Jr., RA Bonifacino J.S., Freed E.O., Hurley J.H.; RT "Crystallographic and functional analysis of the ESCRT-I /HIV-1 Gag PTAP RT interaction."; RL Structure 18:1536-1547(2010). RN [48] RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 2-145 IN COMPLEX WITH HIV-1 GAG P6 RP PEPTIDE (MICROBIAL INFECTION), AND SUBUNIT. RX PubMed=21643473; DOI=10.1021/ml1002579; RA Kim S.E., Liu F., Im Y.J., Stephen A.G., Fivash M.J., Waheed A.A., RA Freed E.O., Fisher R.J., Hurley J.H., Burke T.R. Jr.; RT "Elucidation of new binding interactions with the tumor susceptibility gene RT 101 (Tsg101) protein using modified HIV-1 Gag-p6 derived peptide ligands."; RL ACS Med. Chem. Lett. 2:337-341(2011). CC -!- FUNCTION: Component of the ESCRT-I complex, a regulator of vesicular CC trafficking process. Binds to ubiquitinated cargo proteins and is CC required for the sorting of endocytic ubiquitinated cargos into CC multivesicular bodies (MVBs). Mediates the association between the CC ESCRT-0 and ESCRT-I complex. Required for completion of cytokinesis; CC the function requires CEP55. May be involved in cell growth and CC differentiation. Acts as a negative growth regulator. Involved in the CC budding of many viruses through an interaction with viral proteins that CC contain a late-budding motif P-[ST]-A-P. This interaction is essential CC for viral particle budding of numerous retroviruses. Required for the CC exosomal release of SDCBP, CD63 and syndecan (PubMed:22660413). It may CC also play a role in the extracellular release of microvesicles that CC differ from the exosomes (PubMed:22315426). CC {ECO:0000269|PubMed:11916981, ECO:0000269|PubMed:17556548, CC ECO:0000269|PubMed:17853893, ECO:0000269|PubMed:21070952, CC ECO:0000269|PubMed:21757351, ECO:0000269|PubMed:22315426, CC ECO:0000269|PubMed:22660413}. CC -!- SUBUNIT: Component of the ESCRT-I complex (endosomal sorting complex CC required for transport I) which consists of TSG101, VPS28, a VPS37 CC protein (VPS37A to -D) and MVB12A or MVB12B in a 1:1:1:1 stoichiometry CC (PubMed:18005716). Interacts with VPS37A, VPS37B and VPS37C CC (PubMed:15218037, PubMed:15509564). Interacts with DMAP1 CC (PubMed:10888872). Interacts with ubiquitin (PubMed:11595185). CC Interacts with stathmin, GMCL and AATF (By similarity). Component of an CC ESCRT-I complex (endosomal sorting complex required for transport I) CC which consists of TSG101, VPS28, VPS37A and UBAP1 in a 1:1:1:1 CC stoichiometry (PubMed:21757351). Interacts with HGS; the interaction CC mediates the association with the ESCRT-0 complex. Interacts with GGA1 CC and GGA3 (PubMed:15143060, PubMed:15039775). Interacts (via UEV domain) CC with PDCD6IP/AIP1 (PubMed:14505570, PubMed:14519844). Interacts with CC VPS28, SNF8 and VPS36 (PubMed:14505570). Self-associates CC (PubMed:14505570, PubMed:14519844). Interacts with MVB12A; the CC association appears to be mediated by the TSG101-VPS37 binary CC subcomplex. Interacts with VPS37D. Interacts with LRSAM1. Interacts CC with CEP55; the interaction is required for cytokinesis but not for CC viral budding (PubMed:17853893). Interacts with PDCD6 CC (PubMed:18256029). Interacts with LITAF (PubMed:23166352). Interacts CC with MGRN1 (PubMed:17229889). Interacts with ARRDC1; recruits TSG101 to CC the plasma membrane (PubMed:21191027, PubMed:22315426). {ECO:0000250, CC ECO:0000250|UniProtKB:Q6IRE4, ECO:0000269|PubMed:10888872, CC ECO:0000269|PubMed:14505570, ECO:0000269|PubMed:15039775, CC ECO:0000269|PubMed:15053872, ECO:0000269|PubMed:15143060, CC ECO:0000269|PubMed:15218037, ECO:0000269|PubMed:15509564, CC ECO:0000269|PubMed:15858022, ECO:0000269|PubMed:17229889, CC ECO:0000269|PubMed:17556548, ECO:0000269|PubMed:17853893, CC ECO:0000269|PubMed:18005716, ECO:0000269|PubMed:18256029, CC ECO:0000269|PubMed:19520058, ECO:0000269|PubMed:19703557, CC ECO:0000269|PubMed:21191027, ECO:0000269|PubMed:21757351, CC ECO:0000269|PubMed:22315426, ECO:0000269|PubMed:23166352}. CC -!- SUBUNIT: (Microbial infection) Interacts with HIV-1 p6. CC {ECO:0000269|PubMed:11427703, ECO:0000269|PubMed:11595185, CC ECO:0000269|PubMed:12900394, ECO:0000269|PubMed:21070952, CC ECO:0000269|PubMed:21643473}. CC -!- SUBUNIT: (Microbial infection) Interacts with human spumavirus Gag. CC {ECO:0000269|PubMed:15858022}. CC -!- SUBUNIT: (Microbial infection) Interacts with HTLV-1 Gag. CC {ECO:0000269|PubMed:14581525}. CC -!- SUBUNIT: (Microbial infection) Interacts with Ebola virus VP40. CC {ECO:0000269|PubMed:12559917}. CC -!- SUBUNIT: (Microbial infection) Interacts with EIAV p9; the interaction CC has been shown in vitro. {ECO:0000269|PubMed:14519844}. CC -!- SUBUNIT: (Microbial infection) Interacts with Lassa virus protein Z. CC {ECO:0000269|PubMed:16571837}. CC -!- SUBUNIT: (Microbial infection) Interacts with hepatitis E virus protein CC ORF3. {ECO:0000269|PubMed:21068219}. CC -!- INTERACTION: CC Q99816; Q96IF1: AJUBA; NbExp=4; IntAct=EBI-346882, EBI-949782; CC Q99816; O95429: BAG4; NbExp=3; IntAct=EBI-346882, EBI-2949658; CC Q99816; Q9ULD4-2: BRPF3; NbExp=3; IntAct=EBI-346882, EBI-23662416; CC Q99816; Q8TC20-4: CAGE1; NbExp=3; IntAct=EBI-346882, EBI-11522698; CC Q99816; Q9Y3M2: CBY1; NbExp=3; IntAct=EBI-346882, EBI-947308; CC Q99816; A6NC98: CCDC88B; NbExp=3; IntAct=EBI-346882, EBI-347573; CC Q99816; Q8TD31-3: CCHCR1; NbExp=3; IntAct=EBI-346882, EBI-10175300; CC Q99816; Q9Y5K6: CD2AP; NbExp=2; IntAct=EBI-346882, EBI-298152; CC Q99816; Q53EZ4: CEP55; NbExp=24; IntAct=EBI-346882, EBI-747776; CC Q99816; Q96MT8-3: CEP63; NbExp=3; IntAct=EBI-346882, EBI-11522539; CC Q99816; Q9UER7: DAXX; NbExp=4; IntAct=EBI-346882, EBI-77321; CC Q99816; Q9BQ89: FAM110A; NbExp=3; IntAct=EBI-346882, EBI-1752811; CC Q99816; Q8IZU0: FAM9B; NbExp=3; IntAct=EBI-346882, EBI-10175124; CC Q99816; P10070: GLI2; NbExp=2; IntAct=EBI-346882, EBI-10821567; CC Q99816; Q8NBJ4: GOLM1; NbExp=3; IntAct=EBI-346882, EBI-712073; CC Q99816; Q96CS2: HAUS1; NbExp=6; IntAct=EBI-346882, EBI-2514791; CC Q99816; O14964: HGS; NbExp=5; IntAct=EBI-346882, EBI-740220; CC Q99816; Q96JZ2: HSH2D; NbExp=3; IntAct=EBI-346882, EBI-3919324; CC Q99816; Q0VD86: INCA1; NbExp=3; IntAct=EBI-346882, EBI-6509505; CC Q99816; P46940: IQGAP1; NbExp=5; IntAct=EBI-346882, EBI-297509; CC Q99816; P28290: ITPRID2; NbExp=2; IntAct=EBI-346882, EBI-722905; CC Q99816; Q86T90: KIAA1328; NbExp=3; IntAct=EBI-346882, EBI-3437878; CC Q99816; Q9BVG8: KIFC3; NbExp=3; IntAct=EBI-346882, EBI-2125614; CC Q99816; A1A4E9: KRT13; NbExp=3; IntAct=EBI-346882, EBI-10171552; CC Q99816; P08779: KRT16; NbExp=3; IntAct=EBI-346882, EBI-356410; CC Q99816; P05783: KRT18; NbExp=4; IntAct=EBI-346882, EBI-297888; CC Q99816; Q15323: KRT31; NbExp=6; IntAct=EBI-346882, EBI-948001; CC Q99816; O76011: KRT34; NbExp=5; IntAct=EBI-346882, EBI-1047093; CC Q99816; Q92764: KRT35; NbExp=3; IntAct=EBI-346882, EBI-1058674; CC Q99816; O95678: KRT75; NbExp=3; IntAct=EBI-346882, EBI-2949715; CC Q99816; P80188: LCN2; NbExp=3; IntAct=EBI-346882, EBI-11911016; CC Q99816; Q96PV6: LENG8; NbExp=3; IntAct=EBI-346882, EBI-739546; CC Q99816; Q99732: LITAF; NbExp=3; IntAct=EBI-346882, EBI-725647; CC Q99816; Q8TBB1: LNX1; NbExp=3; IntAct=EBI-346882, EBI-739832; CC Q99816; Q6UWE0: LRSAM1; NbExp=8; IntAct=EBI-346882, EBI-720984; CC Q99816; O60291: MGRN1; NbExp=5; IntAct=EBI-346882, EBI-2129851; CC Q99816; Q8WU39: MZB1; NbExp=3; IntAct=EBI-346882, EBI-7212043; CC Q99816; Q8WUM4: PDCD6IP; NbExp=2; IntAct=EBI-346882, EBI-310624; CC Q99816; Q9NR12: PDLIM7; NbExp=10; IntAct=EBI-346882, EBI-350517; CC Q99816; Q96KN3: PKNOX2; NbExp=3; IntAct=EBI-346882, EBI-2692890; CC Q99816; Q96KQ4: PPP1R13B; NbExp=3; IntAct=EBI-346882, EBI-1105153; CC Q99816; Q96M27: PRRC1; NbExp=2; IntAct=EBI-346882, EBI-2560879; CC Q99816; Q9H3S7: PTPN23; NbExp=2; IntAct=EBI-346882, EBI-724478; CC Q99816; Q13464: ROCK1; NbExp=4; IntAct=EBI-346882, EBI-876651; CC Q99816; Q6ZMJ2-2: SCARA5; NbExp=3; IntAct=EBI-346882, EBI-12823227; CC Q99816; O95295: SNAPIN; NbExp=3; IntAct=EBI-346882, EBI-296723; CC Q99816; Q8N0S2: SYCE1; NbExp=6; IntAct=EBI-346882, EBI-6872807; CC Q99816; Q86VP1: TAX1BP1; NbExp=6; IntAct=EBI-346882, EBI-529518; CC Q99816; Q9UBB9: TFIP11; NbExp=3; IntAct=EBI-346882, EBI-1105213; CC Q99816; Q15025: TNIP1; NbExp=3; IntAct=EBI-346882, EBI-357849; CC Q99816; O75674: TOM1L1; NbExp=2; IntAct=EBI-346882, EBI-712991; CC Q99816; Q9BYV2: TRIM54; NbExp=3; IntAct=EBI-346882, EBI-2130429; CC Q99816; Q8N7C3: TRIML2; NbExp=3; IntAct=EBI-346882, EBI-11059915; CC Q99816; Q8N6Y0: USHBP1; NbExp=3; IntAct=EBI-346882, EBI-739895; CC Q99816; Q9UK41: VPS28; NbExp=10; IntAct=EBI-346882, EBI-727424; CC Q99816; Q9UK41-2: VPS28; NbExp=6; IntAct=EBI-346882, EBI-12146727; CC Q99816; Q8NEZ2: VPS37A; NbExp=6; IntAct=EBI-346882, EBI-2850578; CC Q99816; Q8NEZ2-2: VPS37A; NbExp=5; IntAct=EBI-346882, EBI-10270911; CC Q99816; Q9H9H4: VPS37B; NbExp=3; IntAct=EBI-346882, EBI-4400866; CC Q99816; A5D8V6: VPS37C; NbExp=6; IntAct=EBI-346882, EBI-2559305; CC Q99816; O95229: ZWINT; NbExp=3; IntAct=EBI-346882, EBI-1001132; CC Q99816; P18095: gag; Xeno; NbExp=11; IntAct=EBI-346882, EBI-40205277; CC Q99816; Q99LI8: Hgs; Xeno; NbExp=3; IntAct=EBI-346882, EBI-2119135; CC Q99816-1; O14964: HGS; NbExp=2; IntAct=EBI-15891993, EBI-740220; CC Q99816-1; PRO_0000038598 [P04591]: gag; Xeno; NbExp=3; IntAct=EBI-15891993, EBI-10634977; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:17853893}. Early CC endosome membrane {ECO:0000269|PubMed:23166352}; Peripheral membrane CC protein {ECO:0000305|PubMed:23166352}; Cytoplasmic side CC {ECO:0000305|PubMed:23166352}. Late endosome membrane CC {ECO:0000269|PubMed:11916981, ECO:0000269|PubMed:17229889}; Peripheral CC membrane protein. Cytoplasm, cytoskeleton, microtubule organizing CC center, centrosome {ECO:0000269|PubMed:17853893}. Midbody, Midbody ring CC {ECO:0000269|PubMed:17556548, ECO:0000269|PubMed:17853893}. Nucleus CC {ECO:0000269|PubMed:17229889}. Note=Mainly cytoplasmic. Membrane- CC associated when active and soluble when inactive. Nuclear localization CC is cell cycle-dependent. Interaction with CEP55 is required for CC localization to the midbody during cytokinesis. CC {ECO:0000269|PubMed:17556548, ECO:0000269|PubMed:17853893}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Comment=Additional isoforms seem to exist. Several shorter isoforms CC are detected in primary breast cancers and other tumors.; CC Name=1; CC IsoId=Q99816-1; Sequence=Displayed; CC Name=2; CC IsoId=Q99816-2; Sequence=VSP_004440; CC -!- TISSUE SPECIFICITY: Heart, brain, placenta, lung, liver, skeletal, CC kidney and pancreas. CC -!- DOMAIN: The UEV domain is required for the interaction of the complex CC with ubiquitin. It also mediates the interaction with PTAP/PSAP motifs CC of HIV-1 P6 protein and human spumaretrovirus Gag protein. CC -!- DOMAIN: The coiled coil domain may interact with stathmin. CC -!- DOMAIN: The UEV domain binds ubiquitin and P-[ST]-A-P peptide motif CC independently. CC -!- PTM: Monoubiquitinated at multiple sites by LRSAM1 and by MGRN1. CC Ubiquitination inactivates it, possibly by regulating its shuttling CC between an active membrane-bound protein and an inactive soluble form. CC Ubiquitination by MGRN1 requires the presence of UBE2D1. CC {ECO:0000269|PubMed:15256501, ECO:0000269|PubMed:17229889, CC ECO:0000269|PubMed:19703557}. CC -!- MISCELLANEOUS: [Isoform 2]: Detected in normal as well as cancer CC tissues. {ECO:0000305}. CC -!- SIMILARITY: Belongs to the ubiquitin-conjugating enzyme family. UEV CC subfamily. {ECO:0000305}. 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; U82130; AAC52083.1; -; mRNA. DR EMBL; BC002487; AAH02487.1; -; mRNA. DR CCDS; CCDS7842.1; -. [Q99816-1] DR RefSeq; NP_006283.1; NM_006292.3. [Q99816-1] DR PDB; 1KPP; NMR; -; A=1-145. DR PDB; 1KPQ; NMR; -; A=1-145. DR PDB; 1M4P; NMR; -; A=1-145. DR PDB; 1M4Q; NMR; -; A=1-145. DR PDB; 1S1Q; X-ray; 2.00 A; A/C=1-145. DR PDB; 2F0R; X-ray; 2.26 A; A/B=1-145. DR PDB; 3IV1; X-ray; 2.50 A; A/B/C/D/E/F/G/H=229-304. DR PDB; 3OBQ; X-ray; 1.40 A; A=2-145. DR PDB; 3OBS; X-ray; 1.50 A; A=2-145. DR PDB; 3OBU; X-ray; 1.60 A; A=2-145. DR PDB; 3OBX; X-ray; 1.60 A; A=2-145. DR PDB; 3P9G; X-ray; 1.80 A; A=2-145. DR PDB; 3P9H; X-ray; 1.80 A; A=2-145. DR PDB; 4EJE; X-ray; 2.20 A; A/B=1-145. DR PDB; 4YC1; X-ray; 2.00 A; A/B/C=1-145. DR PDB; 4ZNY; X-ray; 2.40 A; A=4-145. DR PDB; 5VKG; NMR; -; A=2-145. DR PDB; 6UD0; NMR; -; C=1-145. DR PDB; 6VME; X-ray; 2.19 A; B/F/G/H/I/J=308-388. DR PDB; 7NLC; X-ray; 1.40 A; A=1-145. DR PDB; 7ZLX; X-ray; 2.25 A; A/B/C/D/E/F/G/H/I/J/K/L=1-145. DR PDBsum; 1KPP; -. DR PDBsum; 1KPQ; -. DR PDBsum; 1M4P; -. DR PDBsum; 1M4Q; -. DR PDBsum; 1S1Q; -. DR PDBsum; 2F0R; -. DR PDBsum; 3IV1; -. DR PDBsum; 3OBQ; -. DR PDBsum; 3OBS; -. DR PDBsum; 3OBU; -. DR PDBsum; 3OBX; -. DR PDBsum; 3P9G; -. DR PDBsum; 3P9H; -. DR PDBsum; 4EJE; -. DR PDBsum; 4YC1; -. DR PDBsum; 4ZNY; -. DR PDBsum; 5VKG; -. DR PDBsum; 6UD0; -. DR PDBsum; 6VME; -. DR PDBsum; 7NLC; -. DR PDBsum; 7ZLX; -. DR AlphaFoldDB; Q99816; -. DR SMR; Q99816; -. DR BioGRID; 113102; 289. DR ComplexPortal; CPX-2505; ESCRT-I complex, VPS37B-MVB12A variant. DR ComplexPortal; CPX-7146; ESCRT-I complex, VPS37A-MVB12B variant. DR ComplexPortal; CPX-7147; ESCRT-I complex, VPS37C-MVB12A variant. DR ComplexPortal; CPX-7148; ESCRT-I complex, VPS37D-MVB12A variant. DR ComplexPortal; CPX-7162; ESCRT-I complex, VPS37A-MVB12A variant. DR ComplexPortal; CPX-7164; ESCRT-I complex, VPS37B-MVB12B variant. DR ComplexPortal; CPX-7166; ESCRT-I complex, VPS37C-MVB12B variant. DR ComplexPortal; CPX-7167; ESCRT-I complex, VPS37D-MVB12B variant. DR ComplexPortal; CPX-7181; ESCRT-I complex, VPS37A-UBAP1 variant. DR ComplexPortal; CPX-7201; ESCRT-I complex, VPS37B-UBAP1 variant. DR ComplexPortal; CPX-7202; ESCRT-I complex, VPS37C-UBAP1 variant. DR ComplexPortal; CPX-7203; ESCRT-I complex, VPS37D-UBAP1 variant. DR CORUM; Q99816; -. DR DIP; DIP-31809N; -. DR ELM; Q99816; -. DR IntAct; Q99816; 175. DR MINT; Q99816; -. DR STRING; 9606.ENSP00000251968; -. DR BindingDB; Q99816; -. DR ChEMBL; CHEMBL6157; -. DR MoonDB; Q99816; Curated. DR GlyGen; Q99816; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q99816; -. DR PhosphoSitePlus; Q99816; -. DR SwissPalm; Q99816; -. DR BioMuta; TSG101; -. DR DMDM; 9789790; -. DR EPD; Q99816; -. DR jPOST; Q99816; -. DR MassIVE; Q99816; -. DR MaxQB; Q99816; -. DR PaxDb; 9606-ENSP00000251968; -. DR PeptideAtlas; Q99816; -. DR ProteomicsDB; 78490; -. [Q99816-1] DR ProteomicsDB; 78491; -. [Q99816-2] DR Pumba; Q99816; -. DR Antibodypedia; 1752; 584 antibodies from 40 providers. DR DNASU; 7251; -. DR Ensembl; ENST00000251968.4; ENSP00000251968.3; ENSG00000074319.13. [Q99816-1] DR GeneID; 7251; -. DR KEGG; hsa:7251; -. DR MANE-Select; ENST00000251968.4; ENSP00000251968.3; NM_006292.4; NP_006283.1. DR UCSC; uc001mor.4; human. [Q99816-1] DR AGR; HGNC:15971; -. DR CTD; 7251; -. DR DisGeNET; 7251; -. DR GeneCards; TSG101; -. DR HGNC; HGNC:15971; TSG101. DR HPA; ENSG00000074319; Low tissue specificity. DR MIM; 601387; gene. DR neXtProt; NX_Q99816; -. DR OpenTargets; ENSG00000074319; -. DR PharmGKB; PA38068; -. DR VEuPathDB; HostDB:ENSG00000074319; -. DR eggNOG; KOG2391; Eukaryota. DR GeneTree; ENSGT00940000153903; -. DR HOGENOM; CLU_017548_1_1_1; -. DR InParanoid; Q99816; -. DR OMA; GTVYKFP; -. DR OrthoDB; 37962at2759; -. DR PhylomeDB; Q99816; -. DR TreeFam; TF312917; -. DR PathwayCommons; Q99816; -. DR Reactome; R-HSA-162588; Budding and maturation of HIV virion. DR Reactome; R-HSA-174490; Membrane binding and targetting of GAG proteins. DR Reactome; R-HSA-917729; Endosomal Sorting Complex Required For Transport (ESCRT). DR Reactome; R-HSA-9610379; HCMV Late Events. DR Reactome; R-HSA-9615710; Late endosomal microautophagy. DR SignaLink; Q99816; -. DR SIGNOR; Q99816; -. DR BioGRID-ORCS; 7251; 755 hits in 1175 CRISPR screens. DR ChiTaRS; TSG101; human. DR EvolutionaryTrace; Q99816; -. DR GeneWiki; TSG101; -. DR GenomeRNAi; 7251; -. DR Pharos; Q99816; Tbio. DR PRO; PR:Q99816; -. DR Proteomes; UP000005640; Chromosome 11. DR RNAct; Q99816; Protein. DR Bgee; ENSG00000074319; Expressed in oocyte and 210 other cell types or tissues. DR ExpressionAtlas; Q99816; baseline and differential. DR GO; GO:0005813; C:centrosome; IEA:UniProtKB-SubCell. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0005769; C:early endosome; IDA:UniProtKB. DR GO; GO:0031901; C:early endosome membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005768; C:endosome; IDA:UniProtKB. DR GO; GO:0010008; C:endosome membrane; TAS:Reactome. DR GO; GO:0000813; C:ESCRT I complex; IDA:UniProtKB. DR GO; GO:0070062; C:extracellular exosome; IDA:UniProtKB. DR GO; GO:0090543; C:Flemming body; IEA:UniProtKB-SubCell. DR GO; GO:0005770; C:late endosome; IMP:BHF-UCL. DR GO; GO:0031902; C:late endosome membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005771; C:multivesicular body; TAS:HGNC-UCL. DR GO; GO:0005730; C:nucleolus; IDA:HPA. DR GO; GO:0005886; C:plasma membrane; IDA:HPA. DR GO; GO:0048306; F:calcium-dependent protein binding; IPI:UniProtKB. DR GO; GO:0003677; F:DNA binding; TAS:ProtInc. DR GO; GO:0042803; F:protein homodimerization activity; IPI:UniProtKB. DR GO; GO:0044877; F:protein-containing complex binding; IDA:UniProtKB. DR GO; GO:0003714; F:transcription corepressor activity; TAS:ProtInc. DR GO; GO:0043130; F:ubiquitin binding; IDA:UniProtKB. DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:UniProtKB. DR GO; GO:0046790; F:virion binding; IDA:UniProtKB. DR GO; GO:0097352; P:autophagosome maturation; TAS:ParkinsonsUK-UCL. DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW. DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW. DR GO; GO:0008333; P:endosome to lysosome transport; IBA:GO_Central. DR GO; GO:1990182; P:exosomal secretion; IEA:Ensembl. DR GO; GO:0006858; P:extracellular transport; IMP:UniProtKB. DR GO; GO:0030216; P:keratinocyte differentiation; IEA:Ensembl. DR GO; GO:0016236; P:macroautophagy; TAS:ParkinsonsUK-UCL. DR GO; GO:0090148; P:membrane fission; NAS:ComplexPortal. DR GO; GO:0036258; P:multivesicular body assembly; TAS:ParkinsonsUK-UCL. DR GO; GO:0008285; P:negative regulation of cell population proliferation; IEA:Ensembl. DR GO; GO:0042059; P:negative regulation of epidermal growth factor receptor signaling pathway; IMP:ParkinsonsUK-UCL. DR GO; GO:0007175; P:negative regulation of epidermal growth factor-activated receptor activity; IMP:UniProtKB. DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IEA:Ensembl. DR GO; GO:1903543; P:positive regulation of exosomal secretion; IMP:UniProtKB. DR GO; GO:2000397; P:positive regulation of ubiquitin-dependent endocytosis; IEA:Ensembl. DR GO; GO:1903774; P:positive regulation of viral budding via host ESCRT complex; IMP:UniProtKB. DR GO; GO:0036211; P:protein modification process; IEA:InterPro. DR GO; GO:0043328; P:protein transport to vacuole involved in ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway; NAS:ComplexPortal. DR GO; GO:0051726; P:regulation of cell cycle; IEA:Ensembl. DR GO; GO:0001558; P:regulation of cell growth; IEA:Ensembl. DR GO; GO:1903551; P:regulation of extracellular exosome assembly; IMP:UniProtKB. DR GO; GO:0043405; P:regulation of MAP kinase activity; IMP:UniProtKB. DR GO; GO:0043162; P:ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway; IDA:HGNC-UCL. DR GO; GO:0046755; P:viral budding; IMP:UniProtKB. DR GO; GO:0039702; P:viral budding via host ESCRT complex; TAS:ParkinsonsUK-UCL. DR GO; GO:0019076; P:viral release from host cell; IMP:UniProtKB. DR Gene3D; 6.10.140.820; -; 1. DR Gene3D; 6.10.250.370; -; 1. DR Gene3D; 3.10.110.10; Ubiquitin Conjugating Enzyme; 1. DR InterPro; IPR037202; ESCRT_assembly_dom. DR InterPro; IPR017916; SB_dom. DR InterPro; IPR016135; UBQ-conjugating_enzyme/RWD. DR InterPro; IPR008883; UEV_N. DR PANTHER; PTHR23306:SF17; TUMOR SUSCEPTIBILITY GENE 101 PROTEIN; 1. DR PANTHER; PTHR23306; TUMOR SUSCEPTIBILITY GENE 101 PROTEIN-RELATED; 1. DR Pfam; PF05743; UEV; 1. DR Pfam; PF09454; Vps23_core; 1. DR SMART; SM00212; UBCc; 1. DR SUPFAM; SSF140111; Endosomal sorting complex assembly domain; 1. DR SUPFAM; SSF54495; UBC-like; 1. DR PROSITE; PS51312; SB; 1. DR PROSITE; PS51322; UEV; 1. DR Genevisible; Q99816; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Cell cycle; Cell division; KW Coiled coil; Cytoplasm; Cytoskeleton; Endosome; Growth regulation; KW Host-virus interaction; Membrane; Nucleus; Phosphoprotein; KW Protein transport; Reference proteome; Transport; Ubl conjugation. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0007744|PubMed:19413330, FT ECO:0007744|PubMed:22814378" FT CHAIN 2..390 FT /note="Tumor susceptibility gene 101 protein" FT /id="PRO_0000082606" FT DOMAIN 2..145 FT /note="UEV" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00652" FT DOMAIN 322..390 FT /note="SB" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00644" FT REGION 158..162 FT /note="Interaction with CEP55" FT REGION 198..220 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COILED 235..316 FT /evidence="ECO:0000255" FT MOTIF 320..323 FT /note="PTAP motif" FT COMPBIAS 199..220 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 2 FT /note="N-acetylalanine" FT /evidence="ECO:0007744|PubMed:19413330, FT ECO:0007744|PubMed:22814378" FT MOD_RES 220 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:23186163" FT VAR_SEQ 15..119 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000305" FT /id="VSP_004440" FT VARIANT 167 FT /note="M -> I (in dbSNP:rs34385327)" FT /id="VAR_034572" FT MUTAGEN 43 FT /note="V->A: Reduces interaction with ubiquitin; inhibits FT down-regulation of EGFR." FT /evidence="ECO:0000269|PubMed:12006492" FT MUTAGEN 45 FT /note="N->A: Reduces interaction with ubiquitin. No effect FT on MGRN1-binding." FT /evidence="ECO:0000269|PubMed:12006492, FT ECO:0000269|PubMed:12802020, ECO:0000269|PubMed:17229889" FT MUTAGEN 46 FT /note="D->A: Reduces interaction with ubiquitin." FT /evidence="ECO:0000269|PubMed:12006492" FT MUTAGEN 63 FT /note="Y->A: Reduces interaction with HIV-1 p6; impairs FT HIV-1 budding." FT /evidence="ECO:0000269|PubMed:12006492" FT MUTAGEN 88 FT /note="F->A: Reduces interaction with ubiquitin; no effect FT on in interaction with HIV-1 p6." FT /evidence="ECO:0000269|PubMed:12006492" FT MUTAGEN 89 FT /note="V->A: No change in interaction with p6; no effect on FT HIV-1 budding." FT /evidence="ECO:0000269|PubMed:12006492" FT MUTAGEN 95 FT /note="M->A: Reduces interaction with VPS37B and HIV-1 p6; FT abolishes interaction with PDCD6IP; impairs HIV-1 budding; FT inhibits down-regulation of EGFR. Abolishes MGRN1-binding. FT Loss of interaction with ARRDC1." FT /evidence="ECO:0000269|PubMed:12006492, FT ECO:0000269|PubMed:12802020, ECO:0000269|PubMed:14505570, FT ECO:0000269|PubMed:15218037, ECO:0000269|PubMed:17229889, FT ECO:0000269|PubMed:22315426" FT MUTAGEN 141 FT /note="V->A: Reduces interaction with HIV-1 p6." FT /evidence="ECO:0000269|PubMed:12006492" FT MUTAGEN 158..162 FT /note="Missing: Abolishes interaction with CEP55 and FT midbody localization; no effect on interaction with ESCRT-I FT proteins, PDCD6IP and viral proteins." FT /evidence="ECO:0000269|PubMed:17556548" FT MUTAGEN 158..160 FT /note="PPN->AAA: Abolishes interaction with CEP55." FT /evidence="ECO:0000269|PubMed:17853893" FT MUTAGEN 368..371 FT /note="RKQF->AAAA: Loss of interaction with VPS28. No FT effect on interaction with VPS37C." FT /evidence="ECO:0000269|PubMed:15509564" FT CONFLICT 343 FT /note="F -> L (in Ref. 3; AAH02487)" FT /evidence="ECO:0000305" FT HELIX 5..11 FT /evidence="ECO:0007829|PDB:7NLC" FT TURN 12..14 FT /evidence="ECO:0007829|PDB:7NLC" FT HELIX 18..29 FT /evidence="ECO:0007829|PDB:7NLC" FT STRAND 35..43 FT /evidence="ECO:0007829|PDB:7NLC" FT STRAND 45..47 FT /evidence="ECO:0007829|PDB:4ZNY" FT STRAND 49..63 FT /evidence="ECO:0007829|PDB:7NLC" FT STRAND 66..75 FT /evidence="ECO:0007829|PDB:7NLC" FT TURN 78..81 FT /evidence="ECO:0007829|PDB:7NLC" FT STRAND 86..89 FT /evidence="ECO:0007829|PDB:7NLC" FT STRAND 95..97 FT /evidence="ECO:0007829|PDB:7NLC" FT STRAND 100..103 FT /evidence="ECO:0007829|PDB:1S1Q" FT STRAND 107..109 FT /evidence="ECO:0007829|PDB:1KPP" FT HELIX 112..115 FT /evidence="ECO:0007829|PDB:7NLC" FT TURN 119..121 FT /evidence="ECO:0007829|PDB:7NLC" FT HELIX 124..137 FT /evidence="ECO:0007829|PDB:7NLC" FT STRAND 140..143 FT /evidence="ECO:0007829|PDB:7NLC" FT HELIX 230..299 FT /evidence="ECO:0007829|PDB:3IV1" FT HELIX 314..316 FT /evidence="ECO:0007829|PDB:6VME" FT STRAND 317..322 FT /evidence="ECO:0007829|PDB:6VME" FT HELIX 323..350 FT /evidence="ECO:0007829|PDB:6VME" FT HELIX 356..383 FT /evidence="ECO:0007829|PDB:6VME" SQ SEQUENCE 390 AA; 43944 MW; ADD6912FC22DF162 CRC64; MAVSESQLKK MVSKYKYRDL TVRETVNVIT LYKDLKPVLD SYVFNDGSSR ELMNLTGTIP VPYRGNTYNI PICLWLLDTY PYNPPICFVK PTSSMTIKTG KHVDANGKIY LPYLHEWKHP QSDLLGLIQV MIVVFGDEPP VFSRPISASY PPYQATGPPN TSYMPGMPGG ISPYPSGYPP NPSGYPGCPY PPGGPYPATT SSQYPSQPPV TTVGPSRDGT ISEDTIRASL ISAVSDKLRW RMKEEMDRAQ AELNALKRTE EDLKKGHQKL EEMVTRLDQE VAEVDKNIEL LKKKDEELSS ALEKMENQSE NNDIDEVIIP TAPLYKQILN LYAEENAIED TIFYLGEALR RGVIDLDVFL KHVRLLSRKQ FQLRALMQKA RKTAGLSDLY //