ID HGS_HUMAN Reviewed; 777 AA. AC O14964; Q9NR36; DT 19-JUL-2005, integrated into UniProtKB/Swiss-Prot. DT 01-JAN-1998, sequence version 1. DT 24-JAN-2024, entry version 207. DE RecName: Full=Hepatocyte growth factor-regulated tyrosine kinase substrate; DE AltName: Full=Hrs {ECO:0000303|PubMed:9407053}; DE AltName: Full=Protein pp110; GN Name=HGS; Synonyms=HRS; 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), TISSUE SPECIFICITY, AND INTERACTION RP WITH STAM. RX PubMed=9407053; DOI=10.1074/jbc.272.52.32785; RA Asao H., Sasaki Y., Arita T., Tanaka N., Endo K., Kasai H., Takeshita T., RA Endo Y., Fujita T., Sugamura K.; RT "Hrs is associated with STAM, a signal-transducing adaptor molecule. Its RT suppressive effect on cytokine-induced cell growth."; RL J. Biol. Chem. 272:32785-32791(1997). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY. RC TISSUE=Placenta; RX PubMed=9630564; DOI=10.1016/s0378-1119(98)00184-x; RA Lu L., Komada M., Kitamura N.; RT "Human Hrs, a tyrosine kinase substrate in growth factor-stimulated cells: RT cDNA cloning and mapping of the gene to chromosome 17."; RL Gene 213:125-132(1998). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), DOMAIN, INTERACTION WITH NF2, AND RP SUBCELLULAR LOCATION. RC TISSUE=Brain; RX PubMed=10861283; DOI=10.1093/hmg/9.11.1567; RA Scoles D.R., Huynh D.P., Chen M.S., Burke S.P., Gutmann D.H., Pulst S.-M.; RT "The neurofibromatosis 2 tumor suppressor protein interacts with hepatocyte RT growth factor-regulated tyrosine kinase substrate."; RL Hum. Mol. Genet. 9:1567-1574(2000). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."; RL Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=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 project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] RP SUBCELLULAR LOCATION. RX PubMed=9252367; DOI=10.1074/jbc.272.33.20538; RA Komada M., Masaki R., Yamamoto A., Kitamura N.; RT "Hrs, a tyrosine kinase substrate with a conserved double zinc finger RT domain, is localized to the cytoplasmic surface of early endosomes."; RL J. Biol. Chem. 272:20538-20544(1997). RN [7] RP UBIQUITINATION BY ITCH. RX PubMed=14602072; DOI=10.1016/s1534-5807(03)00321-6; RA Marchese A., Raiborg C., Santini F., Keen J.H., Stenmark H., Benovic J.L.; RT "The E3 ubiquitin ligase AIP4 mediates ubiquitination and sorting of the G RT protein-coupled receptor CXCR4."; RL Dev. Cell 5:709-722(2003). RN [8] RP INTERACTION WITH STAM; STAM2 AND EPS15, AND IDENTIFICATION IN A COMPLEX RP WITH STAM2 AND EPS15. RX PubMed=12551915; DOI=10.1074/jbc.m210843200; RA Bache K.G., Raiborg C., Mehlum A., Stenmark H.; RT "STAM and Hrs are subunits of a multivalent ubiquitin-binding complex on RT early endosomes."; RL J. Biol. Chem. 278:12513-12521(2003). RN [9] RP INTERACTION WITH HIV-1 GAG AND HGS, AND 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 [10] RP INTERACTION WITH VPS37C. 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 [11] RP SUBCELLULAR LOCATION. RX PubMed=16159959; DOI=10.1242/jcs.02571; RA Regan-Klapisz E., Sorokina I., Voortman J., de Keizer P., Roovers R.C., RA Verheesen P., Urbe S., Fallon L., Fon E.A., Verkleij A., Benmerah A., RA van Bergen en Henegouwen P.M.; RT "Ubiquilin recruits Eps15 into ubiquitin-rich cytoplasmic aggregates via a RT UIM-UBL interaction."; RL J. Cell Sci. 118:4437-4450(2005). RN [12] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-216, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=15592455; DOI=10.1038/nbt1046; RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., RA Zha X.-M., Polakiewicz R.D., Comb M.J.; RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer cells."; RL Nat. Biotechnol. 23:94-101(2005). RN [13] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=16964243; DOI=10.1038/nbt1240; RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.; RT "A probability-based approach for high-throughput protein phosphorylation RT analysis and site localization."; RL Nat. Biotechnol. 24:1285-1292(2006). RN [14] RP INTERACTION WITH TRAK1. RX PubMed=18675823; DOI=10.1016/j.jmb.2008.07.045; RA Webber E., Li L., Chin L.S.; RT "Hypertonia-associated protein Trak1 is a novel regulator of endosome-to- RT lysosome trafficking."; RL J. Mol. Biol. 382:638-651(2008). RN [15] RP IDENTIFICATION IN THE CART COMPLEX. RX PubMed=15772161; DOI=10.1091/mbc.e04-11-1014; RA Yan Q., Sun W., Kujala P., Lotfi Y., Vida T.A., Bean A.J.; RT "CART: an Hrs/actinin-4/BERP/myosin V protein complex required for RT efficient receptor recycling."; RL Mol. Biol. Cell 16:2470-2482(2005). RN [16] 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 [17] 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., 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 [18] RP DOMAIN FYVE-TYPE ZINC-FINGER. RX PubMed=19296456; DOI=10.1002/prot.22392; RA He J., Vora M., Haney R.M., Filonov G.S., Musselman C.A., Burd C.G., RA Kutateladze A.G., Verkhusha V.V., Stahelin R.V., Kutateladze T.G.; RT "Membrane insertion of the FYVE domain is modulated by pH."; RL Proteins 76:852-860(2009). RN [19] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-207, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19608861; DOI=10.1126/science.1175371; RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., RA Olsen J.V., Mann M.; RT "Lysine acetylation targets protein complexes and co-regulates major RT cellular functions."; RL Science 325:834-840(2009). RN [20] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [21] 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 [22] RP IDENTIFICATION IN A COMPLEX WITH STAM AND 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 [23] RP IDENTIFICATION IN A COMPLEX WITH ARRDC4 AND AVPR2. RX PubMed=23236378; DOI=10.1371/journal.pone.0050557; RA Shea F.F., Rowell J.L., Li Y., Chang T.H., Alvarez C.E.; RT "Mammalian alpha arrestins link activated seven transmembrane receptors to RT Nedd4 family e3 ubiquitin ligases and interact with beta arrestins."; RL PLoS ONE 7:E50557-E50557(2012). RN [24] RP INTERACTION WITH ARRDC3. RX PubMed=23208550; DOI=10.1038/embor.2012.187; RA Han S.O., Kommaddi R.P., Shenoy S.K.; RT "Distinct roles for beta-arrestin2 and arrestin-domain-containing proteins RT in beta2 adrenergic receptor trafficking."; RL EMBO Rep. 14:164-171(2013). RN [25] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE 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., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [26] RP INTERACTION WITH DTX3L, IDENTIFICATION IN A COMPLEX WITH DTX3L; STAM AND RP ITCH, SUBCELLULAR LOCATION, AND UBIQUITINATION. RX PubMed=24790097; DOI=10.1091/mbc.e13-10-0612; RA Holleman J., Marchese A.; RT "The ubiquitin ligase deltex-3l regulates endosomal sorting of the G RT protein-coupled receptor CXCR4."; RL Mol. Biol. Cell 25:1892-1904(2014). RN [27] RP INTERACTION WITH LAPTM4B, AND UBIQUITINATION. RX PubMed=25588945; DOI=10.15252/embj.201489425; RA Tan X., Sun Y., Thapa N., Liao Y., Hedman A.C., Anderson R.A.; RT "LAPTM4B is a PtdIns(4,5)P2 effector that regulates EGFR signaling, RT lysosomal sorting, and degradation."; RL EMBO J. 34:475-490(2015). RN [28] RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 257-277 IN COMPLEX WITH UBIQUITIN, RP AND MUTAGENESIS OF ALA-266 AND ALA-268. RX PubMed=16462748; DOI=10.1038/nsmb1051; RA Hirano S., Kawasaki M., Ura H., Kato R., Raiborg C., Stenmark H., RA Wakatsuki S.; RT "Double-sided ubiquitin binding of Hrs-UIM in endosomal protein sorting."; RL Nat. Struct. Mol. Biol. 13:272-277(2006). RN [29] RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 404-501 IN COMPLEX WITH STAM, AND RP INTERACTION WITH STAM. RX PubMed=19278655; DOI=10.1016/j.str.2009.01.012; RA Ren X., Kloer D.P., Kim Y.C., Ghirlando R., Saidi L.F., Hummer G., RA Hurley J.H.; RT "Hybrid structural model of the complete human ESCRT-0 complex."; RL Structure 17:406-416(2009). RN [30] RP X-RAY CRYSTALLOGRAPHY (1.40 ANGSTROMS) OF 346-354 IN COMPLEX WITH TSG101, RP AND INTERACTION WITH TSG101. 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 [31] RP VARIANT [LARGE SCALE ANALYSIS] SER-7. RX PubMed=18987736; DOI=10.1038/nature07485; RA Ley T.J., Mardis E.R., Ding L., Fulton B., McLellan M.D., Chen K., RA Dooling D., Dunford-Shore B.H., McGrath S., Hickenbotham M., Cook L., RA Abbott R., Larson D.E., Koboldt D.C., Pohl C., Smith S., Hawkins A., RA Abbott S., Locke D., Hillier L.W., Miner T., Fulton L., Magrini V., RA Wylie T., Glasscock J., Conyers J., Sander N., Shi X., Osborne J.R., RA Minx P., Gordon D., Chinwalla A., Zhao Y., Ries R.E., Payton J.E., RA Westervelt P., Tomasson M.H., Watson M., Baty J., Ivanovich J., Heath S., RA Shannon W.D., Nagarajan R., Walter M.J., Link D.C., Graubert T.A., RA DiPersio J.F., Wilson R.K.; RT "DNA sequencing of a cytogenetically normal acute myeloid leukaemia RT genome."; RL Nature 456:66-72(2008). CC -!- FUNCTION: Involved in intracellular signal transduction mediated by CC cytokines and growth factors. When associated with STAM, it suppresses CC DNA signaling upon stimulation by IL-2 and GM-CSF. Could be a direct CC effector of PI3-kinase in vesicular pathway via early endosomes and may CC regulate trafficking to early and late endosomes by recruiting CC clathrin. May concentrate ubiquitinated receptors within clathrin- CC coated regions. Involved in down-regulation of receptor tyrosine kinase CC via multivesicular body (MVBs) when complexed with STAM (ESCRT-0 CC complex). The ESCRT-0 complex binds ubiquitin and acts as a sorting CC machinery that recognizes ubiquitinated receptors and transfers them to CC further sequential lysosomal sorting/trafficking processes. May CC contribute to the efficient recruitment of SMADs to the activin CC receptor complex. Involved in receptor recycling via its association CC with the CART complex, a multiprotein complex required for efficient CC transferrin receptor recycling but not for EGFR degradation. CC -!- SUBUNIT: Component of the ESCRT-0 complex composed of STAM or STAM2 and CC HGS. Part of a complex at least composed of HSG, STAM2 (or probably CC STAM) and EPS15 (PubMed:12551915). Interacts with STAM CC (PubMed:9407053). Interacts with STAM2 (By similarity). Interacts with CC EPS15; the interaction is direct, calcium-dependent and inhibited by CC SNAP25 (By similarity). Identified in a complex with STAM and LITAF CC (PubMed:23166352). Found in a complex with STAM and E3 ligase ITCH and CC DTX3L (PubMed:24790097). Interacts with E3 ligase DTX3L; the CC interaction brings together STAM and HSG, promotes their recruitment to CC early endosomes and decreases STAM and HGS ubiquitination by ITCH CC (PubMed:24790097). Interacts with NF2; the interaction is direct CC (PubMed:10861283). Interacts with ubiquitin; the interaction is direct CC (By similarity). Interacts with VPS37C (PubMed:15509564). Interacts CC with SMAD1, SMAD2 and SMAD3 (By similarity). Interacts with TSG101; the CC interaction mediates the association with the ESCRT-I complex CC (PubMed:21070952). Interacts with SNAP25; the interaction is direct and CC decreases with addition of increasing concentrations of free calcium CC (By similarity). Interacts with SNX1; the interaction is direct (By CC similarity). Component of a 550 kDa membrane complex at least composed CC of HGS and SNX1 but excluding EGFR (By similarity). Interacts with CC TRAK1 (PubMed:18675823). Interacts with TRAK2 (By similarity). CC Component of the CART complex, at least composed of ACTN4, HGS/HRS, CC MYO5B and TRIM3 (PubMed:15772161). Interacts (via UIM domain) with CC UBQLN1 (via ubiquitin-like domain) (By similarity). Interacts with CC ARRDC3 (PubMed:23208550). Identified in a complex containing at least CC ARRDC4, AVPR2 and HGS (PubMed:23236378). Interacts with LAPTM4B; CC promotes HGS ubiquitination (PubMed:25588945). CC {ECO:0000250|UniProtKB:Q99LI8, ECO:0000250|UniProtKB:Q9JJ50, CC ECO:0000269|PubMed:10861283, ECO:0000269|PubMed:12551915, CC ECO:0000269|PubMed:12900394, ECO:0000269|PubMed:15509564, CC ECO:0000269|PubMed:15772161, ECO:0000269|PubMed:16462748, CC ECO:0000269|PubMed:18675823, ECO:0000269|PubMed:19278655, CC ECO:0000269|PubMed:21070952, ECO:0000269|PubMed:23166352, CC ECO:0000269|PubMed:23208550, ECO:0000269|PubMed:23236378, CC ECO:0000269|PubMed:24790097, ECO:0000269|PubMed:25588945, CC ECO:0000269|PubMed:9407053}. CC -!- INTERACTION: CC O14964; Q9NYB9: ABI2; NbExp=5; IntAct=EBI-740220, EBI-743598; CC O14964; Q8WXI4-2: ACOT11; NbExp=3; IntAct=EBI-740220, EBI-17721098; CC O14964; Q08043: ACTN3; NbExp=3; IntAct=EBI-740220, EBI-2880652; CC O14964; P18825: ADRA2C; NbExp=3; IntAct=EBI-740220, EBI-12015266; CC O14964; Q9ULX6: AKAP8L; NbExp=3; IntAct=EBI-740220, EBI-357530; CC O14964; Q3KP44: ANKRD55; NbExp=3; IntAct=EBI-740220, EBI-14493093; CC O14964; Q9BQD7: ANTKMT; NbExp=3; IntAct=EBI-740220, EBI-713602; CC O14964; P53365: ARFIP2; NbExp=3; IntAct=EBI-740220, EBI-638194; CC O14964; Q9H6L4: ARMC7; NbExp=3; IntAct=EBI-740220, EBI-742909; CC O14964; Q8WXK4-2: ASB12; NbExp=3; IntAct=EBI-740220, EBI-18394052; CC O14964; Q86V38: ATN1; NbExp=3; IntAct=EBI-740220, EBI-11954292; CC O14964; Q96PG8: BBC3; NbExp=3; IntAct=EBI-740220, EBI-17289784; CC O14964; O75934: BCAS2; NbExp=4; IntAct=EBI-740220, EBI-1050106; CC O14964; Q13515: BFSP2; NbExp=3; IntAct=EBI-740220, EBI-10229433; CC O14964; Q6AI39: BICRAL; NbExp=3; IntAct=EBI-740220, EBI-1012434; CC O14964; P78537: BLOC1S1; NbExp=3; IntAct=EBI-740220, EBI-348630; CC O14964; Q96GS4: BORCS6; NbExp=3; IntAct=EBI-740220, EBI-10193358; CC O14964; Q6P1W5: C1orf94; NbExp=3; IntAct=EBI-740220, EBI-946029; CC O14964; Q96LM9: C20orf173; NbExp=3; IntAct=EBI-740220, EBI-12851858; CC O14964; Q3SXR2: C3orf36; NbExp=3; IntAct=EBI-740220, EBI-18036948; CC O14964; Q8IW40: CCDC103; NbExp=4; IntAct=EBI-740220, EBI-10261970; CC O14964; A0A1B0GWI1: CCDC196; NbExp=3; IntAct=EBI-740220, EBI-10181422; CC O14964; P30281: CCND3; NbExp=3; IntAct=EBI-740220, EBI-375013; CC O14964; Q01850: CDR2; NbExp=6; IntAct=EBI-740220, EBI-1181367; CC O14964; P40199: CEACAM6; NbExp=3; IntAct=EBI-740220, EBI-4314501; CC O14964; Q53EZ4: CEP55; NbExp=5; IntAct=EBI-740220, EBI-747776; CC O14964; Q8IYX8-2: CEP57L1; NbExp=3; IntAct=EBI-740220, EBI-10181988; CC O14964; Q96MT8-3: CEP63; NbExp=6; IntAct=EBI-740220, EBI-11522539; CC O14964; Q76N32-2: CEP68; NbExp=3; IntAct=EBI-740220, EBI-11975967; CC O14964; Q9H5F2: CFAP68; NbExp=3; IntAct=EBI-740220, EBI-718615; CC O14964; Q6J272: CIMIP2A; NbExp=3; IntAct=EBI-740220, EBI-12811067; CC O14964; Q96MW5: COG8; NbExp=3; IntAct=EBI-740220, EBI-720875; CC O14964; O43186: CRX; NbExp=6; IntAct=EBI-740220, EBI-748171; CC O14964; P33240: CSTF2; NbExp=6; IntAct=EBI-740220, EBI-711360; CC O14964; Q9H0L4: CSTF2T; NbExp=3; IntAct=EBI-740220, EBI-747012; CC O14964; Q9P2B4: CTTNBP2NL; NbExp=3; IntAct=EBI-740220, EBI-1774273; CC O14964; Q6BCY4-2: CYB5R2; NbExp=3; IntAct=EBI-740220, EBI-12102608; CC O14964; Q15038: DAZAP2; NbExp=9; IntAct=EBI-740220, EBI-724310; CC O14964; Q9H410: DSN1; NbExp=3; IntAct=EBI-740220, EBI-1001144; CC O14964; Q86UW9: DTX2; NbExp=3; IntAct=EBI-740220, EBI-740376; CC O14964; Q8WWB3: DYDC1; NbExp=3; IntAct=EBI-740220, EBI-740680; CC O14964; Q5JST6: EFHC2; NbExp=3; IntAct=EBI-740220, EBI-2349927; CC O14964; Q9UHF1: EGFL7; NbExp=3; IntAct=EBI-740220, EBI-949532; CC O14964; O00303: EIF3F; NbExp=3; IntAct=EBI-740220, EBI-711990; CC O14964; Q86VI1: EXOC3L1; NbExp=3; IntAct=EBI-740220, EBI-2813180; CC O14964; O00471: EXOC5; NbExp=3; IntAct=EBI-740220, EBI-949824; CC O14964; Q9UPT5: EXOC7; NbExp=4; IntAct=EBI-740220, EBI-720048; CC O14964; O00167-2: EYA2; NbExp=3; IntAct=EBI-740220, EBI-12807776; CC O14964; Q92567-2: FAM168A; NbExp=8; IntAct=EBI-740220, EBI-11978259; CC O14964; Q8N0U4: FAM185A; NbExp=3; IntAct=EBI-740220, EBI-12842420; CC O14964; B7ZLH0: FAM22F; NbExp=3; IntAct=EBI-740220, EBI-10220102; CC O14964; A0A0S2Z4A7: FANCG; NbExp=3; IntAct=EBI-740220, EBI-16433879; CC O14964; P35555: FBN1; NbExp=3; IntAct=EBI-740220, EBI-2505934; CC O14964; O94868-3: FCHSD2; NbExp=3; IntAct=EBI-740220, EBI-11958845; CC O14964; Q5HY92: FIGN; NbExp=3; IntAct=EBI-740220, EBI-12297985; CC O14964; Q9BVV2: FNDC11; NbExp=3; IntAct=EBI-740220, EBI-744935; CC O14964; Q9NU39: FOXD4L1; NbExp=3; IntAct=EBI-740220, EBI-11320806; CC O14964; Q12951-2: FOXI1; NbExp=3; IntAct=EBI-740220, EBI-12018822; CC O14964; A1L4K1: FSD2; NbExp=3; IntAct=EBI-740220, EBI-5661036; CC O14964; O95954: FTCD; NbExp=3; IntAct=EBI-740220, EBI-10192648; CC O14964; O43716: GATC; NbExp=3; IntAct=EBI-740220, EBI-6929453; CC O14964; Q08379: GOLGA2; NbExp=3; IntAct=EBI-740220, EBI-618309; CC O14964; A6NEM1: GOLGA6L9; NbExp=3; IntAct=EBI-740220, EBI-5916454; CC O14964; Q2TAP0: GOLGA7B; NbExp=3; IntAct=EBI-740220, EBI-13310443; CC O14964; O95843: GUCA1C; NbExp=3; IntAct=EBI-740220, EBI-23668738; CC O14964; P54257: HAP1; NbExp=3; IntAct=EBI-740220, EBI-712814; CC O14964; Q96CS2: HAUS1; NbExp=3; IntAct=EBI-740220, EBI-2514791; CC O14964; P52272: HNRNPM; NbExp=3; IntAct=EBI-740220, EBI-486809; CC O14964; Q9ULV5-2: HSF4; NbExp=3; IntAct=EBI-740220, EBI-12056251; CC O14964; Q96LI6: HSFY2; NbExp=3; IntAct=EBI-740220, EBI-3957665; CC O14964; Q8NDH6-2: ICA1L; NbExp=3; IntAct=EBI-740220, EBI-12141931; CC O14964; P05015: IFNA16; NbExp=3; IntAct=EBI-740220, EBI-7055360; CC O14964; Q96LB3-2: IFT74; NbExp=3; IntAct=EBI-740220, EBI-12066130; CC O14964; Q8WYH8: ING5; NbExp=6; IntAct=EBI-740220, EBI-488533; CC O14964; Q96HW7: INTS4; NbExp=4; IntAct=EBI-740220, EBI-5663129; CC O14964; Q96HW7-2: INTS4; NbExp=3; IntAct=EBI-740220, EBI-16438029; CC O14964; Q8TEX9: IPO4; NbExp=5; IntAct=EBI-740220, EBI-395967; CC O14964; Q96AA8: JAKMIP2; NbExp=3; IntAct=EBI-740220, EBI-752007; CC O14964; P0C870: JMJD7; NbExp=3; IntAct=EBI-740220, EBI-9090173; CC O14964; Q2KHM9: KIAA0753; NbExp=3; IntAct=EBI-740220, EBI-2805604; CC O14964; Q8IV33: KIAA0825; NbExp=3; IntAct=EBI-740220, EBI-17702098; CC O14964; O43474: KLF4; NbExp=3; IntAct=EBI-740220, EBI-7232405; CC O14964; P13646: KRT13; NbExp=6; IntAct=EBI-740220, EBI-1223876; CC O14964; P02533: KRT14; NbExp=3; IntAct=EBI-740220, EBI-702178; CC O14964; P19012: KRT15; NbExp=6; IntAct=EBI-740220, EBI-739566; CC O14964; P08779: KRT16; NbExp=3; IntAct=EBI-740220, EBI-356410; CC O14964; P05783: KRT18; NbExp=7; IntAct=EBI-740220, EBI-297888; CC O14964; P08727: KRT19; NbExp=4; IntAct=EBI-740220, EBI-742756; CC O14964; Q2M2I5: KRT24; NbExp=3; IntAct=EBI-740220, EBI-2952736; CC O14964; Q7Z3Z0: KRT25; NbExp=3; IntAct=EBI-740220, EBI-11980019; CC O14964; Q7Z3Y9: KRT26; NbExp=5; IntAct=EBI-740220, EBI-12084444; CC O14964; Q7Z3Y8: KRT27; NbExp=3; IntAct=EBI-740220, EBI-3044087; CC O14964; P12035: KRT3; NbExp=3; IntAct=EBI-740220, EBI-2430095; CC O14964; Q15323: KRT31; NbExp=6; IntAct=EBI-740220, EBI-948001; CC O14964; Q14525: KRT33B; NbExp=6; IntAct=EBI-740220, EBI-1049638; CC O14964; O76011: KRT34; NbExp=3; IntAct=EBI-740220, EBI-1047093; CC O14964; Q92764: KRT35; NbExp=3; IntAct=EBI-740220, EBI-1058674; CC O14964; O76013-2: KRT36; NbExp=3; IntAct=EBI-740220, EBI-11958506; CC O14964; O76014: KRT37; NbExp=3; IntAct=EBI-740220, EBI-1045716; CC O14964; O76015: KRT38; NbExp=6; IntAct=EBI-740220, EBI-1047263; CC O14964; Q6A163: KRT39; NbExp=3; IntAct=EBI-740220, EBI-11958242; CC O14964; Q6A162: KRT40; NbExp=6; IntAct=EBI-740220, EBI-10171697; CC O14964; P02538: KRT6A; NbExp=6; IntAct=EBI-740220, EBI-702198; CC O14964; O95678: KRT75; NbExp=3; IntAct=EBI-740220, EBI-2949715; CC O14964; Q01546: KRT76; NbExp=3; IntAct=EBI-740220, EBI-2952745; CC O14964; Q9NSB4: KRT82; NbExp=3; IntAct=EBI-740220, EBI-1045341; CC O14964; O43790: KRT86; NbExp=3; IntAct=EBI-740220, EBI-9996498; CC O14964; Q3LI72: KRTAP19-5; NbExp=3; IntAct=EBI-740220, EBI-1048945; CC O14964; Q6PEX3: KRTAP26-1; NbExp=3; IntAct=EBI-740220, EBI-3957672; CC O14964; Q8IUC3: KRTAP7-1; NbExp=3; IntAct=EBI-740220, EBI-18394498; CC O14964; Q14847-2: LASP1; NbExp=3; IntAct=EBI-740220, EBI-9088686; CC O14964; O95751: LDOC1; NbExp=10; IntAct=EBI-740220, EBI-740738; CC O14964; Q99732: LITAF; NbExp=8; IntAct=EBI-740220, EBI-725647; CC O14964; P25800: LMO1; NbExp=3; IntAct=EBI-740220, EBI-8639312; CC O14964; P61968: LMO4; NbExp=3; IntAct=EBI-740220, EBI-2798728; CC O14964; Q9BV99: LRRC61; NbExp=3; IntAct=EBI-740220, EBI-2350424; CC O14964; Q96LR2: LURAP1; NbExp=4; IntAct=EBI-740220, EBI-741355; CC O14964; O15481: MAGEB4; NbExp=3; IntAct=EBI-740220, EBI-751857; CC O14964; Q9Y5V3: MAGED1; NbExp=6; IntAct=EBI-740220, EBI-716006; CC O14964; Q8NDC0: MAPK1IP1L; NbExp=6; IntAct=EBI-740220, EBI-741424; CC O14964; Q13503: MED21; NbExp=3; IntAct=EBI-740220, EBI-394678; CC O14964; Q15528-2: MED22; NbExp=3; IntAct=EBI-740220, EBI-12954271; CC O14964; Q71SY5: MED25; NbExp=3; IntAct=EBI-740220, EBI-394558; CC O14964; Q96HR3: MED30; NbExp=5; IntAct=EBI-740220, EBI-394659; CC O14964; Q9NPJ6: MED4; NbExp=3; IntAct=EBI-740220, EBI-394607; CC O14964; O43513: MED7; NbExp=4; IntAct=EBI-740220, EBI-394632; CC O14964; Q99687-3: MEIS3; NbExp=3; IntAct=EBI-740220, EBI-18582591; CC O14964; Q8N6F8: METTL27; NbExp=3; IntAct=EBI-740220, EBI-8487781; CC O14964; A9UHW6: MIF4GD; NbExp=5; IntAct=EBI-740220, EBI-373498; CC O14964; A9UHW6-2: MIF4GD; NbExp=6; IntAct=EBI-740220, EBI-9118295; CC O14964; Q13064: MKRN3; NbExp=3; IntAct=EBI-740220, EBI-2340269; CC O14964; Q96HT8: MRFAP1L1; NbExp=6; IntAct=EBI-740220, EBI-748896; CC O14964; Q6IA69: NADSYN1; NbExp=3; IntAct=EBI-740220, EBI-748610; CC O14964; O14777: NDC80; NbExp=6; IntAct=EBI-740220, EBI-715849; CC O14964; O96000: NDUFB10; NbExp=3; IntAct=EBI-740220, EBI-1246371; CC O14964; I6L9F6: NEFL; NbExp=3; IntAct=EBI-740220, EBI-10178578; CC O14964; P35240-4: NF2; NbExp=4; IntAct=EBI-740220, EBI-1014514; CC O14964; Q13952-2: NFYC; NbExp=3; IntAct=EBI-740220, EBI-11956831; CC O14964; Q13287: NMI; NbExp=10; IntAct=EBI-740220, EBI-372942; CC O14964; Q7Z3B4: NUP54; NbExp=7; IntAct=EBI-740220, EBI-741048; CC O14964; P37198: NUP62; NbExp=3; IntAct=EBI-740220, EBI-347978; CC O14964; Q96M63: ODAD1; NbExp=9; IntAct=EBI-740220, EBI-10173858; CC O14964; A1E959: ODAM; NbExp=3; IntAct=EBI-740220, EBI-5774125; CC O14964; O43482: OIP5; NbExp=3; IntAct=EBI-740220, EBI-536879; CC O14964; Q7Z4N8: P4HA3; NbExp=6; IntAct=EBI-740220, EBI-10181968; CC O14964; Q02548: PAX5; NbExp=3; IntAct=EBI-740220, EBI-296331; CC O14964; P26367: PAX6; NbExp=3; IntAct=EBI-740220, EBI-747278; CC O14964; Q9UBV8: PEF1; NbExp=3; IntAct=EBI-740220, EBI-724639; CC O14964; Q96KN3: PKNOX2; NbExp=3; IntAct=EBI-740220, EBI-2692890; CC O14964; O15496: PLA2G10; NbExp=3; IntAct=EBI-740220, EBI-726466; CC O14964; Q9HDD0: PLAAT1; NbExp=3; IntAct=EBI-740220, EBI-12387058; CC O14964; P51178: PLCD1; NbExp=3; IntAct=EBI-740220, EBI-4405387; CC O14964; Q96CS7: PLEKHB2; NbExp=3; IntAct=EBI-740220, EBI-373552; CC O14964; Q7Z3K3: POGZ; NbExp=6; IntAct=EBI-740220, EBI-1389308; CC O14964; Q16633: POU2AF1; NbExp=5; IntAct=EBI-740220, EBI-943588; CC O14964; P78424: POU6F2; NbExp=3; IntAct=EBI-740220, EBI-12029004; CC O14964; Q9Y5P8: PPP2R3B; NbExp=3; IntAct=EBI-740220, EBI-2479826; CC O14964; P85299-2: PRR5; NbExp=3; IntAct=EBI-740220, EBI-12944296; CC O14964; A5LHX3: PSMB11; NbExp=3; IntAct=EBI-740220, EBI-19951687; CC O14964; P28070: PSMB4; NbExp=3; IntAct=EBI-740220, EBI-603350; CC O14964; Q9H2L5: RASSF4; NbExp=3; IntAct=EBI-740220, EBI-2933362; CC O14964; P35250-2: RFC2; NbExp=3; IntAct=EBI-740220, EBI-12936957; CC O14964; Q8HWS3: RFX6; NbExp=3; IntAct=EBI-740220, EBI-746118; CC O14964; P78317: RNF4; NbExp=3; IntAct=EBI-740220, EBI-2340927; CC O14964; Q96P16-3: RPRD1A; NbExp=3; IntAct=EBI-740220, EBI-12840198; CC O14964; Q2I0M5: RSPO4; NbExp=3; IntAct=EBI-740220, EBI-12821217; CC O14964; Q01196-8: RUNX1; NbExp=3; IntAct=EBI-740220, EBI-12001422; CC O14964; Q5SSQ6-2: SAPCD1; NbExp=3; IntAct=EBI-740220, EBI-13072754; CC O14964; Q7Z5V6-2: SAXO4; NbExp=6; IntAct=EBI-740220, EBI-12000762; CC O14964; P09683: SCT; NbExp=3; IntAct=EBI-740220, EBI-12844598; CC O14964; P20132: SDS; NbExp=3; IntAct=EBI-740220, EBI-17859611; CC O14964; Q9UGK8: SERGEF; NbExp=3; IntAct=EBI-740220, EBI-465368; CC O14964; Q9UJW9: SERTAD3; NbExp=3; IntAct=EBI-740220, EBI-748621; CC O14964; Q12824-2: SMARCB1; NbExp=3; IntAct=EBI-740220, EBI-358436; CC O14964; Q9UNH6: SNX7; NbExp=3; IntAct=EBI-740220, EBI-751422; CC O14964; O60504: SORBS3; NbExp=3; IntAct=EBI-740220, EBI-741237; CC O14964; Q7Z6I5: SPATA12; NbExp=3; IntAct=EBI-740220, EBI-10696971; CC O14964; Q9HBM1: SPC25; NbExp=3; IntAct=EBI-740220, EBI-999909; CC O14964; Q8WWL2-2: SPIRE2; NbExp=3; IntAct=EBI-740220, EBI-10963872; CC O14964; Q8NCR6: SPMIP6; NbExp=3; IntAct=EBI-740220, EBI-10269322; CC O14964; O75177-5: SS18L1; NbExp=3; IntAct=EBI-740220, EBI-12035119; CC O14964; Q92783: STAM; NbExp=4; IntAct=EBI-740220, EBI-752333; CC O14964; Q92783-1: STAM; NbExp=5; IntAct=EBI-740220, EBI-15763634; CC O14964; Q92783-2: STAM; NbExp=3; IntAct=EBI-740220, EBI-12025738; CC O14964; Q86UX6: STK32C; NbExp=3; IntAct=EBI-740220, EBI-1050045; CC O14964; Q9NZ72: STMN3; NbExp=3; IntAct=EBI-740220, EBI-725557; CC O14964; O75558: STX11; NbExp=3; IntAct=EBI-740220, EBI-714135; CC O14964; P63165: SUMO1; NbExp=3; IntAct=EBI-740220, EBI-80140; CC O14964; O75478: TADA2A; NbExp=4; IntAct=EBI-740220, EBI-742268; CC O14964; O75478-2: TADA2A; NbExp=3; IntAct=EBI-740220, EBI-16433586; CC O14964; O60806: TBX19; NbExp=3; IntAct=EBI-740220, EBI-12096770; CC O14964; Q8N4U5: TCP11L2; NbExp=3; IntAct=EBI-740220, EBI-11897462; CC O14964; Q969V4: TEKT1; NbExp=6; IntAct=EBI-740220, EBI-10180409; CC O14964; Q96M29: TEKT5; NbExp=3; IntAct=EBI-740220, EBI-10239812; CC O14964; Q92734: TFG; NbExp=3; IntAct=EBI-740220, EBI-357061; CC O14964; Q9Y5J6: TIMM10B; NbExp=3; IntAct=EBI-740220, EBI-1200382; CC O14964; Q08117-2: TLE5; NbExp=8; IntAct=EBI-740220, EBI-11741437; CC O14964; Q12888: TP53BP1; NbExp=3; IntAct=EBI-740220, EBI-396540; CC O14964; Q13077: TRAF1; NbExp=3; IntAct=EBI-740220, EBI-359224; CC O14964; Q9BUZ4: TRAF4; NbExp=6; IntAct=EBI-740220, EBI-3650647; CC O14964; Q9UDY6-2: TRIM10; NbExp=3; IntAct=EBI-740220, EBI-11981577; CC O14964; Q9Y577: TRIM17; NbExp=6; IntAct=EBI-740220, EBI-743894; CC O14964; P36406: TRIM23; NbExp=3; IntAct=EBI-740220, EBI-740098; CC O14964; P14373: TRIM27; NbExp=3; IntAct=EBI-740220, EBI-719493; CC O14964; Q9BYV2: TRIM54; NbExp=3; IntAct=EBI-740220, EBI-2130429; CC O14964; Q86WT6-2: TRIM69; NbExp=6; IntAct=EBI-740220, EBI-11525489; CC O14964; Q86UV6-2: TRIM74; NbExp=5; IntAct=EBI-740220, EBI-10259086; CC O14964; Q8N7C3: TRIML2; NbExp=3; IntAct=EBI-740220, EBI-11059915; CC O14964; Q99816: TSG101; NbExp=5; IntAct=EBI-740220, EBI-346882; CC O14964; Q99816-1: TSG101; NbExp=2; IntAct=EBI-740220, EBI-15891993; CC O14964; Q5T6F2: UBAP2; NbExp=3; IntAct=EBI-740220, EBI-2514383; CC O14964; Q7KZS0: UBE2I; NbExp=5; IntAct=EBI-740220, EBI-10180829; CC O14964; Q9UHD9: UBQLN2; NbExp=3; IntAct=EBI-740220, EBI-947187; CC O14964; Q8IYU4: UBQLNL; NbExp=3; IntAct=EBI-740220, EBI-12295223; CC O14964; Q5T124-6: UBXN11; NbExp=3; IntAct=EBI-740220, EBI-11524408; CC O14964; Q8N6Y0: USHBP1; NbExp=4; IntAct=EBI-740220, EBI-739895; CC O14964; Q70EL1-9: USP54; NbExp=3; IntAct=EBI-740220, EBI-11975223; CC O14964; A8MV65-2: VGLL3; NbExp=3; IntAct=EBI-740220, EBI-11957216; CC O14964; Q9H9H4: VPS37B; NbExp=6; IntAct=EBI-740220, EBI-4400866; CC O14964; A5D8V6: VPS37C; NbExp=3; IntAct=EBI-740220, EBI-2559305; CC O14964; Q8N1B4: VPS52; NbExp=3; IntAct=EBI-740220, EBI-2799833; CC O14964; Q2NKJ9: ZNF430; NbExp=3; IntAct=EBI-740220, EBI-12298837; CC O14964; M0R160: ZNF44; NbExp=3; IntAct=EBI-740220, EBI-12945254; CC O14964; A0A1U9X8X8; NbExp=3; IntAct=EBI-740220, EBI-17234977; CC O14964; Q7TLC7: ORF14; Xeno; NbExp=2; IntAct=EBI-740220, EBI-25488942; CC O14964; Q6NRD3: sh3rf1; Xeno; NbExp=3; IntAct=EBI-740220, EBI-7734031; CC O14964; P03410: tax; Xeno; NbExp=4; IntAct=EBI-740220, EBI-9676218; CC O14964; P14079: tax; Xeno; NbExp=4; IntAct=EBI-740220, EBI-9675698; CC O14964; P0CG53: UBB; Xeno; NbExp=7; IntAct=EBI-740220, EBI-5333021; CC O14964; P62990: UBC; Xeno; NbExp=2; IntAct=EBI-740220, EBI-413053; CC O14964-1; P35240-1: NF2; NbExp=3; IntAct=EBI-21239519, EBI-1014500; CC O14964-2; P35240-3: NF2; NbExp=5; IntAct=EBI-21581128, EBI-1014509; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q9JJ50}. Early CC endosome membrane {ECO:0000269|PubMed:23166352, CC ECO:0000269|PubMed:24790097}; Peripheral membrane protein CC {ECO:0000305|PubMed:23166352, ECO:0000305|PubMed:24790097}; Cytoplasmic CC side {ECO:0000305|PubMed:23166352, ECO:0000305|PubMed:24790097}. CC Endosome, multivesicular body membrane {ECO:0000250|UniProtKB:Q9JJ50}; CC Peripheral membrane protein {ECO:0000250|UniProtKB:Q9JJ50}. CC Note=Colocalizes with UBQLN1 in ubiquitin-rich cytoplasmic aggregates CC that are not endocytic compartments. {ECO:0000269|PubMed:16159959}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; Synonyms=HRSi1; CC IsoId=O14964-1; Sequence=Displayed; CC Name=2; Synonyms=HRSi2; CC IsoId=O14964-2; Sequence=VSP_036172; CC -!- TISSUE SPECIFICITY: Ubiquitous expression in adult and fetal tissues CC with higher expression in testis and peripheral blood leukocytes. CC {ECO:0000269|PubMed:9407053, ECO:0000269|PubMed:9630564}. CC -!- DOMAIN: Has a double-sided UIM that can bind 2 ubiquitin molecules, one CC on each side of the helix. CC -!- DOMAIN: The FYVE-type zinc finger domain mediates interactions with CC phosphatidylinositol 3-phosphate in membranes of early endosomes and CC penetrates bilayers. The FYVE domain insertion into PtdIns(3)P-enriched CC membranes is substantially increased in acidic conditions. CC -!- PTM: Phosphorylated on Tyr-334. A minor site of phosphorylation on Tyr- CC 329 is detected (By similarity). Phosphorylation occurs in response to CC EGF, IL-2, GM-CSF and HGF. {ECO:0000250|UniProtKB:Q99LI8}. CC -!- PTM: Ubiquitinated (PubMed:25588945). Ubiquitinated by ITCH CC (PubMed:14602072, PubMed:24790097). {ECO:0000269|PubMed:14602072, CC ECO:0000269|PubMed:24790097, ECO:0000269|PubMed:25588945}. CC -!- MISCELLANEOUS: [Isoform 2]: Dubious isoform produced through aberrant CC splice sites. {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; U43895; AAC51929.1; -; mRNA. DR EMBL; D84064; BAA23366.1; -; mRNA. DR EMBL; AF260566; AAF82361.1; -; mRNA. DR EMBL; BT009754; AAP88756.1; -; mRNA. DR EMBL; BC003565; AAH03565.1; -; mRNA. DR CCDS; CCDS11784.1; -. [O14964-1] DR RefSeq; NP_004703.1; NM_004712.4. [O14964-1] DR PDB; 2D3G; X-ray; 1.70 A; P=257-277. DR PDB; 3F1I; X-ray; 2.30 A; H=404-501. DR PDB; 3OBQ; X-ray; 1.40 A; B=346-354. DR PDB; 3ZYQ; X-ray; 1.48 A; A=1-225. DR PDB; 4AVX; X-ray; 1.68 A; A=1-225. DR PDBsum; 2D3G; -. DR PDBsum; 3F1I; -. DR PDBsum; 3OBQ; -. DR PDBsum; 3ZYQ; -. DR PDBsum; 4AVX; -. DR AlphaFoldDB; O14964; -. DR SMR; O14964; -. DR BioGRID; 114593; 528. DR ComplexPortal; CPX-2825; ESCRT-0 complex, STAM variant. DR ComplexPortal; CPX-7143; ESCRT-0 complex, STAM2 variant. DR CORUM; O14964; -. DR DIP; DIP-29050N; -. DR ELM; O14964; -. DR IntAct; O14964; 316. DR MINT; O14964; -. DR STRING; 9606.ENSP00000331201; -. DR DrugBank; DB04272; Citric acid. DR GlyCosmos; O14964; 4 sites, 1 glycan. DR GlyGen; O14964; 8 sites, 1 O-linked glycan (8 sites). DR iPTMnet; O14964; -. DR MetOSite; O14964; -. DR PhosphoSitePlus; O14964; -. DR BioMuta; HGS; -. DR EPD; O14964; -. DR jPOST; O14964; -. DR MassIVE; O14964; -. DR MaxQB; O14964; -. DR PaxDb; 9606-ENSP00000331201; -. DR PeptideAtlas; O14964; -. DR ProteomicsDB; 48337; -. [O14964-1] DR ProteomicsDB; 48338; -. [O14964-2] DR Pumba; O14964; -. DR Antibodypedia; 1403; 647 antibodies from 40 providers. DR DNASU; 9146; -. DR Ensembl; ENST00000329138.9; ENSP00000331201.4; ENSG00000185359.14. [O14964-1] DR Ensembl; ENST00000676546.1; ENSP00000504106.1; ENSG00000185359.14. [O14964-1] DR GeneID; 9146; -. DR KEGG; hsa:9146; -. DR MANE-Select; ENST00000329138.9; ENSP00000331201.4; NM_004712.5; NP_004703.1. DR UCSC; uc002kbg.4; human. [O14964-1] DR AGR; HGNC:4897; -. DR CTD; 9146; -. DR DisGeNET; 9146; -. DR GeneCards; HGS; -. DR HGNC; HGNC:4897; HGS. DR HPA; ENSG00000185359; Low tissue specificity. DR MIM; 604375; gene. DR neXtProt; NX_O14964; -. DR OpenTargets; ENSG00000185359; -. DR PharmGKB; PA29271; -. DR VEuPathDB; HostDB:ENSG00000185359; -. DR eggNOG; KOG1818; Eukaryota. DR GeneTree; ENSGT00940000158297; -. DR HOGENOM; CLU_013062_1_0_1; -. DR InParanoid; O14964; -. DR OMA; DQQCSAK; -. DR OrthoDB; 922060at2759; -. DR PhylomeDB; O14964; -. DR TreeFam; TF314470; -. DR PathwayCommons; O14964; -. DR Reactome; R-HSA-182971; EGFR downregulation. DR Reactome; R-HSA-432720; Lysosome Vesicle Biogenesis. DR Reactome; R-HSA-5689880; Ub-specific processing proteases. DR Reactome; R-HSA-6807004; Negative regulation of MET activity. DR Reactome; R-HSA-8856825; Cargo recognition for clathrin-mediated endocytosis. DR Reactome; R-HSA-8856828; Clathrin-mediated endocytosis. DR Reactome; R-HSA-8875360; InlB-mediated entry of Listeria monocytogenes into host cell. DR Reactome; R-HSA-9013420; RHOU GTPase cycle. DR Reactome; R-HSA-917729; Endosomal Sorting Complex Required For Transport (ESCRT). DR Reactome; R-HSA-9635644; Inhibition of membrane repair. DR Reactome; R-HSA-9636383; Prevention of phagosomal-lysosomal fusion. DR Reactome; R-HSA-9706019; RHOBTB3 ATPase cycle. DR SignaLink; O14964; -. DR SIGNOR; O14964; -. DR BioGRID-ORCS; 9146; 532 hits in 1169 CRISPR screens. DR ChiTaRS; HGS; human. DR EvolutionaryTrace; O14964; -. DR GeneWiki; HGS_(gene); -. DR GenomeRNAi; 9146; -. DR Pharos; O14964; Tbio. DR PRO; PR:O14964; -. DR Proteomes; UP000005640; Chromosome 17. DR RNAct; O14964; Protein. DR Bgee; ENSG00000185359; Expressed in right uterine tube and 204 other cell types or tissues. DR ExpressionAtlas; O14964; baseline and differential. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0005769; C:early endosome; IDA:HGNC-UCL. DR GO; GO:0031901; C:early endosome membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005768; C:endosome; IDA:HGNC-UCL. DR GO; GO:0033565; C:ESCRT-0 complex; IDA:UniProtKB. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0005764; C:lysosome; IDA:HPA. DR GO; GO:0032585; C:multivesicular body membrane; IEA:UniProtKB-SubCell. DR GO; GO:0097013; C:phagocytic vesicle lumen; TAS:Reactome. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0035091; F:phosphatidylinositol binding; IEA:InterPro. DR GO; GO:0019904; F:protein domain specific binding; IPI:UniProtKB. DR GO; GO:0043130; F:ubiquitin binding; IBA:GO_Central. DR GO; GO:0044389; F:ubiquitin-like protein ligase binding; IPI:UniProtKB. DR GO; GO:0032456; P:endocytic recycling; IBA:GO_Central. DR GO; GO:0016197; P:endosomal transport; NAS:UniProtKB. DR GO; GO:0016236; P:macroautophagy; TAS:ParkinsonsUK-UCL. DR GO; GO:0090148; P:membrane fission; NAS:ComplexPortal. DR GO; GO:0010324; P:membrane invagination; IMP:UniProtKB. DR GO; GO:0036258; P:multivesicular body assembly; TAS:ParkinsonsUK-UCL. DR GO; GO:0016525; P:negative regulation of angiogenesis; IMP:BHF-UCL. DR GO; GO:0008285; P:negative regulation of cell population proliferation; TAS:ProtInc. DR GO; GO:0010642; P:negative regulation of platelet-derived growth factor receptor signaling pathway; IMP:BHF-UCL. DR GO; GO:0046426; P:negative regulation of receptor signaling pathway via JAK-STAT; IDA:HGNC-UCL. DR GO; GO:0030948; P:negative regulation of vascular endothelial growth factor receptor signaling pathway; IMP:BHF-UCL. DR GO; GO:1903543; P:positive regulation of exosomal secretion; IMP:UniProtKB. DR GO; GO:0010628; P:positive regulation of gene expression; IMP:UniProtKB. DR GO; GO:0072657; P:protein localization to membrane; IMP:UniProtKB. DR GO; GO:0006622; P:protein targeting to lysosome; IMP:UniProtKB. 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:0031623; P:receptor internalization; IBA:GO_Central. DR GO; GO:0043405; P:regulation of MAP kinase activity; IMP:UniProtKB. DR GO; GO:0042176; P:regulation of protein catabolic process; TAS:HGNC-UCL. DR GO; GO:0007165; P:signal transduction; TAS:ProtInc. DR CDD; cd15720; FYVE_Hrs; 1. DR CDD; cd21387; GAT_Hrs; 1. DR CDD; cd03569; VHS_Hrs; 1. DR Gene3D; 1.20.5.1940; -; 1. DR Gene3D; 1.25.40.90; -; 1. DR Gene3D; 3.30.40.10; Zinc/RING finger domain, C3HC4 (zinc finger); 1. DR InterPro; IPR008942; ENTH_VHS. DR InterPro; IPR017073; HGS/VPS27. DR InterPro; IPR024641; HRS_helical. DR InterPro; IPR003903; UIM_dom. DR InterPro; IPR002014; VHS_dom. DR InterPro; IPR000306; Znf_FYVE. DR InterPro; IPR017455; Znf_FYVE-rel. DR InterPro; IPR011011; Znf_FYVE_PHD. DR InterPro; IPR013083; Znf_RING/FYVE/PHD. DR PANTHER; PTHR46275; HEPATOCYTE GROWTH FACTOR-REGULATED TYROSINE KINASE SUBSTRATE; 1. DR PANTHER; PTHR46275:SF1; HEPATOCYTE GROWTH FACTOR-REGULATED TYROSINE KINASE SUBSTRATE; 1. DR Pfam; PF01363; FYVE; 1. DR Pfam; PF12210; Hrs_helical; 1. DR Pfam; PF00790; VHS; 1. DR PIRSF; PIRSF036956; Hrs_Vps27; 1. DR SMART; SM00064; FYVE; 1. DR SMART; SM00288; VHS; 1. DR SUPFAM; SSF48464; ENTH/VHS domain; 1. DR SUPFAM; SSF57903; FYVE/PHD zinc finger; 1. DR PROSITE; PS50330; UIM; 1. DR PROSITE; PS50179; VHS; 1. DR PROSITE; PS50178; ZF_FYVE; 1. DR Genevisible; O14964; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Cytoplasm; Endosome; KW Membrane; Metal-binding; Phosphoprotein; Protein transport; KW Reference proteome; Transport; Ubl conjugation; Zinc; Zinc-finger. FT CHAIN 1..777 FT /note="Hepatocyte growth factor-regulated tyrosine kinase FT substrate" FT /id="PRO_0000098708" FT DOMAIN 15..143 FT /note="VHS" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00218" FT DOMAIN 258..277 FT /note="UIM" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00213" FT ZN_FING 160..220 FT /note="FYVE-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091" FT REGION 223..319 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 225..543 FT /note="Interaction with SNX1" FT /evidence="ECO:0000250" FT REGION 338..407 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 445..543 FT /note="Interaction with SNAP25 and TRAK2" FT /evidence="ECO:0000250" FT REGION 454..572 FT /note="Interaction with STAM" FT /evidence="ECO:0000250|UniProtKB:Q99LI8" FT REGION 480..777 FT /note="Interaction with NF2" FT /evidence="ECO:0000269|PubMed:10861283" FT REGION 718..777 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 223..252 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 285..316 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 718..746 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 761..777 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 166 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091" FT BINDING 169 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091" FT BINDING 182 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091" FT BINDING 185 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091" FT BINDING 190 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091" FT BINDING 193 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091" FT BINDING 212 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091" FT BINDING 215 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091" FT MOD_RES 207 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 216 FT /note="Phosphotyrosine" FT /evidence="ECO:0007744|PubMed:15592455" FT MOD_RES 308 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:Q99LI8" FT MOD_RES 329 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:Q99LI8" FT MOD_RES 334 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:Q99LI8" FT MOD_RES 551 FT /note="N6-succinyllysine" FT /evidence="ECO:0000250|UniProtKB:Q99LI8" FT VAR_SEQ 518..604 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:10861283" FT /id="VSP_036172" FT VARIANT 7 FT /note="T -> S (in dbSNP:rs753682847)" FT /evidence="ECO:0000269|PubMed:18987736" FT /id="VAR_054154" FT VARIANT 400 FT /note="E -> D (in dbSNP:rs34868130)" FT /id="VAR_052981" FT VARIANT 733 FT /note="A -> S (in dbSNP:rs56058441)" FT /id="VAR_061991" FT MUTAGEN 266 FT /note="A->Q: Strongly reduced ubiquitin-binding. Reduced FT degradation of ubiquitinated EGFR." FT /evidence="ECO:0000269|PubMed:16462748" FT MUTAGEN 268 FT /note="A->Q: Strongly reduced ubiquitin-binding. Reduced FT degradation of ubiquitinated EGFR." FT /evidence="ECO:0000269|PubMed:16462748" FT CONFLICT 236 FT /note="E -> D (in Ref. 3; AAF82361)" FT /evidence="ECO:0000305" FT HELIX 7..15 FT /evidence="ECO:0007829|PDB:3ZYQ" FT HELIX 25..36 FT /evidence="ECO:0007829|PDB:3ZYQ" FT HELIX 42..53 FT /evidence="ECO:0007829|PDB:3ZYQ" FT HELIX 58..75 FT /evidence="ECO:0007829|PDB:3ZYQ" FT HELIX 77..83 FT /evidence="ECO:0007829|PDB:3ZYQ" FT HELIX 86..98 FT /evidence="ECO:0007829|PDB:3ZYQ" FT HELIX 102..118 FT /evidence="ECO:0007829|PDB:3ZYQ" FT TURN 119..121 FT /evidence="ECO:0007829|PDB:3ZYQ" FT HELIX 123..125 FT /evidence="ECO:0007829|PDB:3ZYQ" FT HELIX 126..138 FT /evidence="ECO:0007829|PDB:3ZYQ" FT HELIX 147..150 FT /evidence="ECO:0007829|PDB:3ZYQ" FT TURN 167..169 FT /evidence="ECO:0007829|PDB:3ZYQ" FT TURN 183..185 FT /evidence="ECO:0007829|PDB:3ZYQ" FT TURN 191..193 FT /evidence="ECO:0007829|PDB:3ZYQ" FT STRAND 196..200 FT /evidence="ECO:0007829|PDB:3ZYQ" FT HELIX 201..203 FT /evidence="ECO:0007829|PDB:3ZYQ" FT STRAND 205..211 FT /evidence="ECO:0007829|PDB:3ZYQ" FT HELIX 213..219 FT /evidence="ECO:0007829|PDB:3ZYQ" FT HELIX 258..273 FT /evidence="ECO:0007829|PDB:2D3G" FT HELIX 405..428 FT /evidence="ECO:0007829|PDB:3F1I" FT HELIX 433..435 FT /evidence="ECO:0007829|PDB:3F1I" FT HELIX 437..499 FT /evidence="ECO:0007829|PDB:3F1I" SQ SEQUENCE 777 AA; 86192 MW; DD64167A19DCF030 CRC64; MGRGSGTFER LLDKATSQLL LETDWESILQ ICDLIRQGDT QAKYAVNSIK KKVNDKNPHV ALYALEVMES VVKNCGQTVH DEVANKQTME ELKDLLKRQV EVNVRNKILY LIQAWAHAFR NEPKYKVVQD TYQIMKVEGH VFPEFKESDA MFAAERAPDW VDAEECHRCR VQFGVMTRKH HCRACGQIFC GKCSSKYSTI PKFGIEKEVR VCEPCYEQLN RKAEGKATST TELPPEYLTS PLSQQSQLPP KRDETALQEE EELQLALALS QSEAEEKERL RQKSTYTSYP KAEPMPSASS APPASSLYSS PVNSSAPLAE DIDPELARYL NRNYWEKKQE EARKSPTPSA PVPLTEPAAQ PGEGHAAPTN VVENPLPETD SQPIPPSGGP FSEPQFHNGE SEESHEQFLK ALQNAVTTFV NRMKSNHMRG RSITNDSAVL SLFQSINGMH PQLLELLNQL DERRLYYEGL QDKLAQIRDA RGALSALREE HREKLRRAAE EAERQRQIQL AQKLEIMRQK KQEYLEVQRQ LAIQRLQEQE KERQMRLEQQ KQTVQMRAQM PAFPLPYAQL QAMPAAGGVL YQPSGPASFP STFSPAGSVE GSPMHGVYMS QPAPAAGPYP SMPSTAADPS MVSAYMYPAG ATGAQAAPQA QAGPTASPAY SSYQPTPTAG YQNVASQAPQ SLPAISQPPQ SSTMGYMGSQ SVSMGYQPYN MQNLMTTLPS QDASLPPQQP YIAGQQPMYQ QMAPSGGPPQ QQPPVAQQPQ AQGPPAQGSE AQLISFD //