HGS_HUMAN
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 03-AUG-2022, entry version 199.
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 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; Q9H5F2: C11orf1; NbExp=3; IntAct=EBI-740220, EBI-718615;
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; 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; Q6J272: FAM166A; NbExp=3; IntAct=EBI-740220, EBI-12811067;
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; Q7Z5V6-2: PPP1R32; NbExp=6; IntAct=EBI-740220, EBI-12000762;
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; 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; Q8NCR6: SMRP1; NbExp=3; IntAct=EBI-740220, EBI-10269322;
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; 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}.
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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; 487.
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; 289.
DR MINT; O14964; -.
DR STRING; 9606.ENSP00000331201; -.
DR DrugBank; DB04272; Citric acid.
DR GlyGen; O14964; 4 sites, 1 O-linked glycan (4 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; O14964; -.
DR PeptideAtlas; O14964; -.
DR PRIDE; O14964; -.
DR ProteomicsDB; 48337; -. [O14964-1]
DR ProteomicsDB; 48338; -. [O14964-2]
DR Antibodypedia; 1403; 563 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 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; PHSSCYS; -.
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; 511 hits in 1092 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 202 other tissues.
DR ExpressionAtlas; O14964; baseline and differential.
DR Genevisible; O14964; HS.
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; IC: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; IC: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 Gene3D; 1.25.40.90; -; 1.
DR Gene3D; 3.30.40.10; -; 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; PTHR46275; 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; SSF48464; 1.
DR SUPFAM; SSF57903; SSF57903; 1.
DR PROSITE; PS50330; UIM; 1.
DR PROSITE; PS50179; VHS; 1.
DR PROSITE; PS50178; ZF_FYVE; 1.
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
