ID A0A3Q2I4L2_HORSE Unreviewed; 817 AA.
AC A0A3Q2I4L2;
DT 10-APR-2019, integrated into UniProtKB/TrEMBL.
DT 13-SEP-2023, sequence version 2.
DT 27-MAR-2024, entry version 22.
DE RecName: Full=Hepatocyte growth factor-regulated tyrosine kinase substrate {ECO:0000256|ARBA:ARBA00015450, ECO:0000256|PIRNR:PIRNR036956};
GN Name=HGS {ECO:0000313|Ensembl:ENSECAP00000040569.2,
GN ECO:0000313|VGNC:VGNC:18770};
OS Equus caballus (Horse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Perissodactyla; Equidae; Equus.
OX NCBI_TaxID=9796 {ECO:0000313|Ensembl:ENSECAP00000040569.2, ECO:0000313|Proteomes:UP000002281};
RN [1] {ECO:0000313|Ensembl:ENSECAP00000040569.2, ECO:0000313|Proteomes:UP000002281}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Thoroughbred {ECO:0000313|Ensembl:ENSECAP00000040569.2,
RC ECO:0000313|Proteomes:UP000002281};
RX PubMed=19892987; DOI=10.1126/science.1178158;
RG Broad Institute Genome Sequencing Platform;
RG Broad Institute Whole Genome Assembly Team;
RA Wade C.M., Giulotto E., Sigurdsson S., Zoli M., Gnerre S., Imsland F.,
RA Lear T.L., Adelson D.L., Bailey E., Bellone R.R., Bloecker H., Distl O.,
RA Edgar R.C., Garber M., Leeb T., Mauceli E., MacLeod J.N., Penedo M.C.T.,
RA Raison J.M., Sharpe T., Vogel J., Andersson L., Antczak D.F., Biagi T.,
RA Binns M.M., Chowdhary B.P., Coleman S.J., Della Valle G., Fryc S.,
RA Guerin G., Hasegawa T., Hill E.W., Jurka J., Kiialainen A., Lindgren G.,
RA Liu J., Magnani E., Mickelson J.R., Murray J., Nergadze S.G., Onofrio R.,
RA Pedroni S., Piras M.F., Raudsepp T., Rocchi M., Roeed K.H., Ryder O.A.,
RA Searle S., Skow L., Swinburne J.E., Syvaenen A.C., Tozaki T., Valberg S.J.,
RA Vaudin M., White J.R., Zody M.C., Lander E.S., Lindblad-Toh K.;
RT "Genome sequence, comparative analysis, and population genetics of the
RT domestic horse.";
RL Science 326:865-867(2009).
RN [2] {ECO:0000313|Ensembl:ENSECAP00000040569.2}
RP IDENTIFICATION.
RC STRAIN=Thoroughbred {ECO:0000313|Ensembl:ENSECAP00000040569.2};
RG Ensembl;
RL Submitted (NOV-2023) to UniProtKB.
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:0000256|PIRNR:PIRNR036956}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000256|PIRNR:PIRNR036956}. Early
CC endosome membrane {ECO:0000256|ARBA:ARBA00004469,
CC ECO:0000256|PIRNR:PIRNR036956}; Peripheral membrane protein
CC {ECO:0000256|ARBA:ARBA00004469, ECO:0000256|PIRNR:PIRNR036956};
CC Cytoplasmic side {ECO:0000256|ARBA:ARBA00004469,
CC ECO:0000256|PIRNR:PIRNR036956}. Endosome, multivesicular body membrane
CC {ECO:0000256|PIRNR:PIRNR036956}; Peripheral membrane protein
CC {ECO:0000256|PIRNR:PIRNR036956}.
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 AlphaFoldDB; A0A3Q2I4L2; -.
DR Ensembl; ENSECAT00000033813.2; ENSECAP00000040569.2; ENSECAG00000010874.4.
DR VGNC; VGNC:18770; HGS.
DR GeneTree; ENSGT00940000158297; -.
DR Proteomes; UP000002281; Chromosome 11.
DR Bgee; ENSECAG00000010874; Expressed in synovial membrane of synovial joint and 23 other cell types or tissues.
DR ExpressionAtlas; A0A3Q2I4L2; baseline.
DR GO; GO:0031901; C:early endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0032585; C:multivesicular body membrane; IEA:UniProtKB-SubCell.
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; IEA:UniProtKB-UniRule.
DR GO; GO:0043130; F:ubiquitin binding; IEA:InterPro.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
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.
PE 4: Predicted;
KW Coiled coil {ECO:0000256|SAM:Coils};
KW Cytoplasm {ECO:0000256|PIRNR:PIRNR036956};
KW Endosome {ECO:0000256|PIRNR:PIRNR036956};
KW Membrane {ECO:0000256|PIRNR:PIRNR036956};
KW Metal-binding {ECO:0000256|ARBA:ARBA00022723};
KW Protein transport {ECO:0000256|PIRNR:PIRNR036956};
KW Reference proteome {ECO:0000313|Proteomes:UP000002281};
KW Transport {ECO:0000256|PIRNR:PIRNR036956};
KW Zinc {ECO:0000256|ARBA:ARBA00022833};
KW Zinc-finger {ECO:0000256|ARBA:ARBA00022771, ECO:0000256|PROSITE-
KW ProRule:PRU00091}.
FT DOMAIN 15..143
FT /note="VHS"
FT /evidence="ECO:0000259|PROSITE:PS50179"
FT DOMAIN 160..220
FT /note="FYVE-type"
FT /evidence="ECO:0000259|PROSITE:PS50178"
FT REGION 223..320
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 337..404
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 643..686
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 766..817
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 469..552
FT /evidence="ECO:0000256|SAM:Coils"
FT COMPBIAS 233..252
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 299..316
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 375..404
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 655..686
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 783..817
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 817 AA; 90373 MW; 88F4F4A33853F3AD CRC64;
MGRGSGTFER LLDKATSQLL LETDWESILQ ICDLIRQGDT QAKYAVSSIK KKVNDKNPHV
ALYALEVMES VVKNCGQTVH DEVANKQTME ELKELLKRQV EVNVRNKILY LIQAWAHAFR
NEPKYKVVQD TYQIMKVEGH VFPEFKESDA MFAAERAPDW VDAEECHRCR VQFGVVTRKH
HCRACGQIFC GKCSSKYSTI PKFGIEKEVR VCEPCYEQLN KKAEGKASAT TELPPEYLTS
PLSQQSQLPP KRDETALQEE EELQLALALS QSEAEEKERM RQKSAYTAYP KAEPTPVASS
APPASSLYSS PVNSSAPLAE DMDPELARYL NRNYWEKKQE EARKSPTPSA PVPLTEPAAQ
PGEGHTAPAS VVETPLPETD SQSMTPSSGP FSEQYQNGES EESHAQFLKA LQNAVTTFVN
RMKSNHVRGR SITNDSAVLS LFQSINSMHP QLLELLNQLD ERRLYYEGLQ DKLAQIRDAR
GALSALREEH REKLRRAAEE AERQRQIQLA QKLEIMRQKK QEYLEVQRQL AIQRLQEQEK
ERQMRLEQQK QTIQMRAQMP AFSLPYAQLQ AMPAAGGVLY QPSGPTSFPS TFSPAGSVEG
SPMHTVYMSQ PAPAASGPYP SMPGAGADPS MVSAYIYPAG ASGAQAAPQG PAGPTASPAY
SSYQPTPTQG YQNVASQAPQ SLPAISQPPQ SGTMGYMGSQ SVSMGYQPYS MQNLMTTLPS
QDAPLPPPQQ PYISGQQPMY QQDPVTRPLP DSITIQANAV GGVPRLARAQ DAASLPAPHG
RRGTRAPVEE EPKGKAARGQ RKLPALDDRG RRGRRGP
//
