HGS_MOUSE
ID HGS_MOUSE Reviewed; 775 AA.
AC Q99LI8; Q61691; Q8BQW3;
DT 19-JUL-2005, integrated into UniProtKB/Swiss-Prot.
DT 19-JUL-2005, sequence version 2.
DT 03-AUG-2022, entry version 167.
DE RecName: Full=Hepatocyte growth factor-regulated tyrosine kinase substrate;
GN Name=Hgs; Synonyms=Hrs;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=7565774; DOI=10.1128/mcb.15.11.6213;
RA Komada M., Kitamura N.;
RT "Growth factor-induced tyrosine phosphorylation of Hrs, a novel 115-
RT kilodalton protein with a structurally-conserved putative zinc finger
RT domain.";
RL Mol. Cell. Biol. 15:6213-6221(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Corpora quadrigemina;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Mammary tumor;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP INTERACTION WITH STAM, AND DOMAIN.
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 [5]
RP TISSUE SPECIFICITY.
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 [6]
RP DISRUPTION PHENOTYPE.
RX PubMed=10364163; DOI=10.1101/gad.13.11.1475;
RA Komada M., Soriano P.;
RT "Hrs, a FYVE finger protein localized to early endosomes, is implicated in
RT vesicular traffic and required for ventral folding morphogenesis.";
RL Genes Dev. 13:1475-1485(1999).
RN [7]
RP INTERACTION WITH STAM2, AND SUBCELLULAR LOCATION.
RX PubMed=10651905; DOI=10.1046/j.1365-2443.2000.00303.x;
RA Takata H., Kato M., Denda K., Kitamura N.;
RT "A hrs binding protein having a Src homology 3 domain is involved in
RT intracellular degradation of growth factors and their receptors.";
RL Genes Cells 5:57-69(2000).
RN [8]
RP INTERACTION WITH SMAD1; SMAD2 AND SMAD3, DISRUPTION PHENOTYPE, AND
RP FUNCTION.
RX PubMed=11094085; DOI=10.1128/mcb.20.24.9346-9355.2000;
RA Miura S., Takeshita T., Asao H., Kimura Y., Murata K., Sasaki Y., Hanai J.,
RA Beppu H., Tsukazaki T., Wrana J.L., Miyazono K., Sugamura K.;
RT "Hgs (Hrs), a FYVE domain protein, is involved in Smad signaling through
RT cooperation with SARA.";
RL Mol. Cell. Biol. 20:9346-9355(2000).
RN [9]
RP MUTAGENESIS OF ARG-183 AND CYS-215, AND SUBCELLULAR LOCATION.
RX PubMed=11493665; DOI=10.1242/jcs.114.12.2255;
RA Raiborg C., Bremnes B., Mehlum A., Gillooly D.J., D'Arrigo A., Stang E.,
RA Stenmark H.;
RT "FYVE and coiled-coil domains determine the specific localisation of Hrs to
RT early endosomes.";
RL J. Cell Sci. 114:2255-2263(2001).
RN [10]
RP INTERACTION WITH UBIQUITIN, AND MUTAGENESIS OF SER-270.
RX PubMed=11988743; DOI=10.1038/ncb791;
RA Raiborg C., Bache K.G., Gillooly D.J., Madshus I.H., Stang E., Stenmark H.;
RT "Hrs sorts ubiquitinated proteins into clathrin-coated microdomains of
RT early endosomes.";
RL Nat. Cell Biol. 4:394-398(2002).
RN [11]
RP PHOSPHORYLATION AT TYR-329 AND TYR-334, IDENTIFICATION BY MASS
RP SPECTROMETRY, MUTAGENESIS OF LEU-269; SER-270; TYR-329 AND TYR-334, AND
RP SUBCELLULAR LOCATION.
RX PubMed=12953068; DOI=10.1242/jcs.00723;
RA Urbe S., Sachse M., Row P.E., Preisinger C., Barr F.A., Strous G.,
RA Klumperman J., Clague M.J.;
RT "The UIM domain of Hrs couples receptor sorting to vesicle formation.";
RL J. Cell Sci. 116:4169-4179(2003).
RN [12]
RP INTERACTION WITH TSG101.
RX PubMed=12802020; DOI=10.1073/pnas.0932599100;
RA Lu Q., Hope L.W., Brasch M., Reinhard C., Cohen S.N.;
RT "TSG101 interaction with HRS mediates endosomal trafficking and receptor
RT down-regulation.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:7626-7631(2003).
RN [13]
RP INTERACTION WITH UBQLN1.
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 [14]
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 [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-308, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Mast cell;
RX PubMed=17947660; DOI=10.4049/jimmunol.179.9.5864;
RA Cao L., Yu K., Banh C., Nguyen V., Ritz A., Raphael B.J., Kawakami Y.,
RA Kawakami T., Salomon A.R.;
RT "Quantitative time-resolved phosphoproteomic analysis of mast cell
RT signaling.";
RL J. Immunol. 179:5864-5876(2007).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-216, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=18034455; DOI=10.1021/pr0701254;
RA Ballif B.A., Carey G.R., Sunyaev S.R., Gygi S.P.;
RT "Large-scale identification and evolution indexing of tyrosine
RT phosphorylation sites from murine brain.";
RL J. Proteome Res. 7:311-318(2008).
RN [17]
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 [18]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Kidney, Liver, Lung, Pancreas, Spleen,
RC and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [19]
RP SUCCINYLATION [LARGE SCALE ANALYSIS] AT LYS-549, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic fibroblast;
RX PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
RA Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y.,
RA Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
RT "SIRT5-mediated lysine desuccinylation impacts diverse metabolic
RT pathways.";
RL Mol. Cell 50:919-930(2013).
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 {ECO:0000269|PubMed:11094085}.
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 (By similarity). Interacts with STAM (PubMed:9407053,
CC PubMed:19278655). Interacts with STAM2 (PubMed:10651905). Interacts
CC with EPS15; the interaction is direct, calcium-dependent and inhibited
CC by SNAP25 (By similarity). Identified in a complex with STAM and LITAF
CC (By similarity). Found in a complex with STAM and E3 ligase ITCH and
CC DTX3L (By similarity). Interacts with E3 ligase DTX3L; the interaction
CC brings together STAM and HSG, promotes their recruitment to early
CC endosomes and decreases STAM and HGS ubiquitination by ITCH (By
CC similarity). Interacts with NF2; the interaction is direct (By
CC similarity). Interacts with ubiquitin; the interaction is direct
CC (PubMed:11988743). Interacts with VPS37C (By similarity). Interacts
CC with SMAD1, SMAD2 and SMAD3 (PubMed:11094085). Interacts with TSG101;
CC the interaction mediates the association with the ESCRT-I complex
CC (PubMed:12802020). 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 (By similarity). Interacts with TRAK2 (By similarity). Component
CC of the CART complex, at least composed of ACTN4, HGS/HRS, MYO5B and
CC TRIM3 (By similarity). Interacts with ARRDC3 (By similarity).
CC Identified in a complex containing at least ARRDC4, AVPR2 and HGS (By
CC similarity). Interacts (via UIM domain) with UBQLN1 (via ubiquitin-like
CC domain) (PubMed:16159959). Interacts with LAPTM4B; promotes HGS
CC ubiquitination (By similarity). {ECO:0000250|UniProtKB:O14964,
CC ECO:0000250|UniProtKB:Q9JJ50, ECO:0000269|PubMed:10651905,
CC ECO:0000269|PubMed:11094085, ECO:0000269|PubMed:11988743,
CC ECO:0000269|PubMed:12802020, ECO:0000269|PubMed:16159959,
CC ECO:0000269|PubMed:19278655, ECO:0000269|PubMed:9407053}.
CC -!- INTERACTION:
CC Q99LI8; Q99LI8: Hgs; NbExp=2; IntAct=EBI-2119135, EBI-2119135;
CC Q99LI8; P15209: Ntrk2; NbExp=2; IntAct=EBI-2119135, EBI-309647;
CC Q99LI8; O88689-1: Pcdha4; NbExp=2; IntAct=EBI-2119135, EBI-15880299;
CC Q99LI8; Q92783-1: STAM; Xeno; NbExp=4; IntAct=EBI-2119135, EBI-15763634;
CC Q99LI8; Q99816: TSG101; Xeno; NbExp=3; IntAct=EBI-2119135, EBI-346882;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Early endosome membrane; Peripheral
CC membrane protein; Cytoplasmic side. Endosome, multivesicular body
CC membrane; Peripheral membrane protein. Note=Colocalizes with UBQLN1 in
CC ubiquitin-rich cytoplasmic aggregates that are not endocytic
CC compartments. {ECO:0000250|UniProtKB:O14964}.
CC -!- TISSUE SPECIFICITY: Ubiquitous expression in adult and fetal tissues
CC with higher expression in testis. {ECO:0000269|PubMed:7565774,
CC 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. {ECO:0000250}.
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 (By
CC similarity). {ECO:0000250}.
CC -!- PTM: Phosphorylated on Tyr-334. This phosphorylation occurs in response
CC to EGF. A minor site of phosphorylation on Tyr-329 is detected. Protein
CC phosphorylation may also be triggered in response to IL-2, GM-CSF and
CC HGF. {ECO:0000269|PubMed:12953068}.
CC -!- PTM: Ubiquitinated by ITCH. {ECO:0000250|UniProtKB:O14964}.
CC -!- DISRUPTION PHENOTYPE: Mice show a defect in ventral folding
CC morphogenesis, exhibiting two bilateral heart tubes and absence of
CC foregut, and died around embryonic day 11. Significantly enlarged
CC endosomes were also detected in cells of the endoderm.
CC {ECO:0000269|PubMed:10364163, ECO:0000269|PubMed:11094085}.
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DR EMBL; D50050; BAA08768.1; -; mRNA.
DR EMBL; AK046299; BAC32676.1; -; mRNA.
DR EMBL; BC003239; AAH03239.1; -; mRNA.
DR CCDS; CCDS88297.1; -.
DR PIR; I49759; I49759.
DR RefSeq; NP_001152800.1; NM_001159328.1.
DR RefSeq; NP_032270.3; NM_008244.3.
DR AlphaFoldDB; Q99LI8; -.
DR SMR; Q99LI8; -.
DR BioGRID; 200296; 31.
DR CORUM; Q99LI8; -.
DR DIP; DIP-29102N; -.
DR IntAct; Q99LI8; 12.
DR MINT; Q99LI8; -.
DR STRING; 10090.ENSMUSP00000026900; -.
DR iPTMnet; Q99LI8; -.
DR PhosphoSitePlus; Q99LI8; -.
DR EPD; Q99LI8; -.
DR MaxQB; Q99LI8; -.
DR PaxDb; Q99LI8; -.
DR PRIDE; Q99LI8; -.
DR ProteomicsDB; 273105; -.
DR Antibodypedia; 1403; 563 antibodies from 40 providers.
DR DNASU; 15239; -.
DR Ensembl; ENSMUST00000106205; ENSMUSP00000101811; ENSMUSG00000025793.
DR GeneID; 15239; -.
DR KEGG; mmu:15239; -.
DR UCSC; uc007msx.2; mouse.
DR CTD; 9146; -.
DR MGI; MGI:104681; Hgs.
DR VEuPathDB; HostDB:ENSMUSG00000025793; -.
DR eggNOG; KOG1818; Eukaryota.
DR GeneTree; ENSGT00940000158297; -.
DR InParanoid; Q99LI8; -.
DR OrthoDB; 828765at2759; -.
DR Reactome; R-MMU-182971; EGFR downregulation.
DR Reactome; R-MMU-432720; Lysosome Vesicle Biogenesis.
DR Reactome; R-MMU-5689880; Ub-specific processing proteases.
DR Reactome; R-MMU-6807004; Negative regulation of MET activity.
DR Reactome; R-MMU-8856825; Cargo recognition for clathrin-mediated endocytosis.
DR Reactome; R-MMU-8856828; Clathrin-mediated endocytosis.
DR Reactome; R-MMU-9013420; RHOU GTPase cycle.
DR Reactome; R-MMU-917729; Endosomal Sorting Complex Required For Transport (ESCRT).
DR Reactome; R-MMU-9706019; RHOBTB3 ATPase cycle.
DR BioGRID-ORCS; 15239; 36 hits in 77 CRISPR screens.
DR ChiTaRS; Hgs; mouse.
DR PRO; PR:Q99LI8; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; Q99LI8; protein.
DR Bgee; ENSMUSG00000025793; Expressed in ileal epithelium and 243 other tissues.
DR ExpressionAtlas; Q99LI8; baseline and differential.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005769; C:early endosome; ISO:MGI.
DR GO; GO:0031901; C:early endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005768; C:endosome; ISO:MGI.
DR GO; GO:0033565; C:ESCRT-0 complex; ISO:MGI.
DR GO; GO:0005764; C:lysosome; ISO:MGI.
DR GO; GO:0016020; C:membrane; ISO:MGI.
DR GO; GO:0032585; C:multivesicular body membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0030141; C:secretory granule; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
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; ISO:MGI.
DR GO; GO:0043130; F:ubiquitin binding; IBA:GO_Central.
DR GO; GO:0140036; F:ubiquitin-dependent protein binding; IDA:UniProtKB.
DR GO; GO:0044389; F:ubiquitin-like protein ligase binding; ISO:MGI.
DR GO; GO:0032456; P:endocytic recycling; IBA:GO_Central.
DR GO; GO:0008333; P:endosome to lysosome transport; ISO:MGI.
DR GO; GO:0010324; P:membrane invagination; ISO:MGI.
DR GO; GO:0016525; P:negative regulation of angiogenesis; ISO:MGI.
DR GO; GO:0010642; P:negative regulation of platelet-derived growth factor receptor signaling pathway; ISO:MGI.
DR GO; GO:0046426; P:negative regulation of receptor signaling pathway via JAK-STAT; ISO:MGI.
DR GO; GO:0030948; P:negative regulation of vascular endothelial growth factor receptor signaling pathway; ISO:MGI.
DR GO; GO:1903543; P:positive regulation of exosomal secretion; ISO:MGI.
DR GO; GO:0010628; P:positive regulation of gene expression; ISO:MGI.
DR GO; GO:0072657; P:protein localization to membrane; ISO:MGI.
DR GO; GO:0006622; P:protein targeting to lysosome; ISO:MGI.
DR GO; GO:0031623; P:receptor internalization; IBA:GO_Central.
DR GO; GO:0043405; P:regulation of MAP kinase activity; ISO:MGI.
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 Acetylation; Cytoplasm; Endosome; Membrane; Metal-binding; Phosphoprotein;
KW Protein transport; Reference proteome; Transport; Ubl conjugation; Zinc;
KW Zinc-finger.
FT CHAIN 1..775
FT /note="Hepatocyte growth factor-regulated tyrosine kinase
FT substrate"
FT /id="PRO_0000098709"
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..541
FT /note="Interaction with SNX1"
FT /evidence="ECO:0000250"
FT REGION 338..405
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 443..541
FT /note="Interaction with SNAP25 and TRAK2"
FT /evidence="ECO:0000250"
FT REGION 452..570
FT /note="Interaction with STAM"
FT /evidence="ECO:0000269|PubMed:9407053"
FT REGION 478..775
FT /note="Interaction with NF2"
FT /evidence="ECO:0000250"
FT REGION 640..690
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 719..775
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 272..286
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 302..316
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 381..396
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 647..690
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 719..744
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 745..759
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 760..775
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:0000250|UniProtKB:O14964"
FT MOD_RES 216
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:15592455,
FT ECO:0007744|PubMed:18034455"
FT MOD_RES 308
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:17947660"
FT MOD_RES 329
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:12953068"
FT MOD_RES 334
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:12953068"
FT MOD_RES 549
FT /note="N6-succinyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MUTAGEN 183
FT /note="R->A: 100-fold loss of affinity for PIP3 and
FT accumulation in the cytosol."
FT /evidence="ECO:0000269|PubMed:11493665"
FT MUTAGEN 215
FT /note="C->S: Accumulation in proteinaceous aggregates
FT devoid of membranes and no interaction with PI3P."
FT /evidence="ECO:0000269|PubMed:11493665"
FT MUTAGEN 269
FT /note="L->A: Loss of protein phosphorylation at Y-329 and
FT Y-334; when associated with A-270."
FT /evidence="ECO:0000269|PubMed:12953068"
FT MUTAGEN 270
FT /note="S->A: Loss of protein phosphorylation at Y-329 and
FT Y-334; when associated with A-269."
FT /evidence="ECO:0000269|PubMed:11988743,
FT ECO:0000269|PubMed:12953068"
FT MUTAGEN 270
FT /note="S->E: No interaction with ubiquitin."
FT /evidence="ECO:0000269|PubMed:11988743,
FT ECO:0000269|PubMed:12953068"
FT MUTAGEN 329
FT /note="Y->F: No change in the phosphorylation level. Loss
FT of protein phosphorylation; when associated with F-334."
FT /evidence="ECO:0000269|PubMed:12953068"
FT MUTAGEN 334
FT /note="Y->F: No change in the phosphorylation level. Loss
FT of protein phosphorylation; when associated with F-329."
FT /evidence="ECO:0000269|PubMed:12953068"
FT CONFLICT 23
FT /note="T -> S (in Ref. 3; AAH03239)"
FT /evidence="ECO:0000305"
FT CONFLICT 584
FT /note="P -> S (in Ref. 2; BAC32676)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 775 AA; 86015 MW; 0E68BF5AB514865B CRC64;
MGRGSGTFER LLDKATSQLL LETDWESILQ ICDLIRQGDT QAKYAVNSIK KKVNDKNPHV
ALYALEVMES VVKNCGQTVH DEVANKQTME ELKELLKRQV EVNVRNKILY LIQAWAHAFR
NEPKYKVVQD TYQIMKVEGH VFPEFKESDA MFAAERAPDW VDAEECHRCR VQFGVVTRKH
HCRACGQIFC GKCSSKYSTI PKFGIEKEVR VCEPCYEQLN KKAEGKASST TELPPEYLTS
PLSQQSQLPP KRDETALQEE EELQLALALS QSEAEEKERM RQKTTYTAHP KAEPTPLASS
APPAGSLYSS PVNSSAPLAE DIDPELARYL NRNYWEKKQE EARKSPTPSA PVPLTEPAAQ
PGEGHTAPNS MAEAPLPETD SQPITPCSGP FSEYQNGESE ESHEQFLKAL QNAVSTFVNR
MKSNHMRGRS ITNDSAVLSL FQSINTMHPQ LLELLNQLDE RRLYYEGLQD KLAQIRDARG
ALSALREEHR EKLRRAAEEA ERQRQIQLAQ KLEIMRQKKQ EYLEVQRQLA IQRLQEQEKE
RQMRLEQQKQ TVQMRAQMPA FPLPYAQLQA MPTAGGVLYQ PSGPTSFPAT FSPAGSVEGS
PMHGVYMSQP APATGPYPSM PGTTADPSMV SAYMYPTGAP GAQAAPQAQA GPTTSPAYSS
YQPTPTPGYQ SVASQAPQSL PAISQPPQTS NIGYMGSQPM SMGYQPYNMQ NLMTALPGQD
ASLPAQQPYI PGQQPLYQQM APSTGPPQQQ PPVAQPAPTQ GPPAQGSEAQ LISFD
