HGS_BOVIN
ID HGS_BOVIN Reviewed; 777 AA.
AC Q0V8S0; Q2NKZ6;
DT 06-FEB-2007, integrated into UniProtKB/Swiss-Prot.
DT 05-SEP-2006, sequence version 1.
DT 03-AUG-2022, entry version 118.
DE RecName: Full=Hepatocyte growth factor-regulated tyrosine kinase substrate;
GN Name=HGS;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=16305752; DOI=10.1186/1471-2164-6-166;
RA Harhay G.P., Sonstegard T.S., Keele J.W., Heaton M.P., Clawson M.L.,
RA Snelling W.M., Wiedmann R.T., Van Tassell C.P., Smith T.P.L.;
RT "Characterization of 954 bovine full-CDS cDNA sequences.";
RL BMC Genomics 6:166-166(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Crossbred X Angus; TISSUE=Liver;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (DEC-2005) to the EMBL/GenBank/DDBJ databases.
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 (By
CC similarity). {ECO:0000250}.
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. Interacts with STAM. Interacts with STAM2. Interacts
CC with EPS15; the interaction is direct, calcium-dependent and inhibited
CC by SNAP25. Identified in a complex with STAM and LITAF. Found in a
CC complex with STAM and E3 ligase ITCH and DTX3L. Interacts with E3
CC ligase DTX3L; the interaction brings together STAM and HSG, promotes
CC their recruitment to early endosomes and decreases STAM and HGS
CC ubiquitination by ITCH. Interacts with NF2; the interaction is direct.
CC Interacts with ubiquitin; the interaction is direct. Interacts with
CC VPS37C. Interacts with SMAD1, SMAD2 and SMAD3. Interacts with TSG101;
CC the interaction mediates the association with the ESCRT-I complex.
CC Interacts with SNAP25; the interaction is direct and decreases with
CC addition of increasing concentrations of free calcium. Interacts with
CC SNX1; the interaction is direct. Component of a 550 kDa membrane
CC complex at least composed of HGS and SNX1 but excluding EGFR. Interacts
CC with TRAK1. Interacts with TRAK2. Component of the CART complex, at
CC least composed of ACTN4, HGS/HRS, MYO5B and TRIM3. Interacts (via UIM
CC domain) with UBQLN1 (via ubiquitin-like domain). Interacts with ARRDC3.
CC Identified in a complex containing at least ARRDC4, AVPR2 and HGS.
CC Interacts with LAPTM4B; promotes HGS ubiquitination (By similarity).
CC {ECO:0000250|UniProtKB:O14964, ECO:0000250|UniProtKB:Q99LI8,
CC ECO:0000250|UniProtKB:Q9JJ50}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q9JJ50}. Early
CC endosome membrane {ECO:0000250|UniProtKB:Q9JJ50}; Peripheral membrane
CC protein {ECO:0000250|UniProtKB:Q9JJ50}; Cytoplasmic side
CC {ECO:0000250|UniProtKB:Q9JJ50}. Endosome, multivesicular body membrane
CC {ECO:0000250|UniProtKB:Q9JJ50}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:Q9JJ50}. Note=Colocalizes with UBQLN1 in
CC ubiquitin-rich cytoplasmic aggregates that are not endocytic
CC compartments. {ECO:0000250|UniProtKB:O14964}.
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. 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 by ITCH. {ECO:0000250|UniProtKB:O14964}.
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DR EMBL; BT026148; ABG66987.1; -; mRNA.
DR EMBL; BC111313; AAI11314.1; -; mRNA.
DR RefSeq; NP_001039554.1; NM_001046089.1.
DR RefSeq; XP_005221090.1; XM_005221033.3.
DR AlphaFoldDB; Q0V8S0; -.
DR SMR; Q0V8S0; -.
DR STRING; 9913.ENSBTAP00000000527; -.
DR PaxDb; Q0V8S0; -.
DR PeptideAtlas; Q0V8S0; -.
DR PRIDE; Q0V8S0; -.
DR Ensembl; ENSBTAT00000000527; ENSBTAP00000000527; ENSBTAG00000000411.
DR GeneID; 511582; -.
DR KEGG; bta:511582; -.
DR CTD; 9146; -.
DR VEuPathDB; HostDB:ENSBTAG00000000411; -.
DR VGNC; VGNC:29836; HGS.
DR eggNOG; KOG1818; Eukaryota.
DR GeneTree; ENSGT00940000158297; -.
DR HOGENOM; CLU_013062_1_0_1; -.
DR InParanoid; Q0V8S0; -.
DR OMA; PHSSCYS; -.
DR OrthoDB; 828765at2759; -.
DR TreeFam; TF314470; -.
DR Proteomes; UP000009136; Chromosome 19.
DR Bgee; ENSBTAG00000000411; Expressed in retina and 105 other tissues.
DR ExpressionAtlas; Q0V8S0; baseline and differential.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0005769; C:early endosome; IBA:GO_Central.
DR GO; GO:0031901; C:early endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0033565; C:ESCRT-0 complex; IEA:Ensembl.
DR GO; GO:0005764; C:lysosome; IEA:Ensembl.
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:Ensembl.
DR GO; GO:0043130; F:ubiquitin binding; IBA:GO_Central.
DR GO; GO:0044389; F:ubiquitin-like protein ligase binding; IEA:Ensembl.
DR GO; GO:0032456; P:endocytic recycling; IBA:GO_Central.
DR GO; GO:0010324; P:membrane invagination; IEA:Ensembl.
DR GO; GO:0016525; P:negative regulation of angiogenesis; IEA:Ensembl.
DR GO; GO:0010642; P:negative regulation of platelet-derived growth factor receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0046426; P:negative regulation of receptor signaling pathway via JAK-STAT; IEA:Ensembl.
DR GO; GO:0030948; P:negative regulation of vascular endothelial growth factor receptor signaling pathway; IEA:Ensembl.
DR GO; GO:1903543; P:positive regulation of exosomal secretion; IEA:Ensembl.
DR GO; GO:0010628; P:positive regulation of gene expression; IEA:Ensembl.
DR GO; GO:0072657; P:protein localization to membrane; IEA:Ensembl.
DR GO; GO:0006622; P:protein targeting to lysosome; IEA:Ensembl.
DR GO; GO:0031623; P:receptor internalization; IBA:GO_Central.
DR GO; GO:0043405; P:regulation of MAP kinase activity; IEA:Ensembl.
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 2: Evidence at transcript level;
KW Acetylation; Cytoplasm; Endosome; Membrane; Metal-binding; Phosphoprotein;
KW Protein transport; Reference proteome; Transport; Ubl conjugation; Zinc;
KW Zinc-finger.
FT CHAIN 1..777
FT /note="Hepatocyte growth factor-regulated tyrosine kinase
FT substrate"
FT /id="PRO_0000274196"
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..370
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:0000250|UniProtKB:Q99LI8"
FT REGION 478..777
FT /note="Interaction with NF2"
FT /evidence="ECO:0000250"
FT REGION 645..698
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 712..777
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
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 649..698
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 747..761
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 762..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:0000250|UniProtKB:O14964"
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 549
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q99LI8"
FT CONFLICT 321
FT /note="D -> E (in Ref. 2; AAI11314)"
FT /evidence="ECO:0000305"
FT CONFLICT 392
FT /note="Missing (in Ref. 2; AAI11314)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 777 AA; 85786 MW; 13DD0CE832AD56B4 CRC64;
MGRGSGTFER LLDKATSQLL LETDWESILQ ICDLIRQGDT QAKYAVSSIK KKVNDKNPHV
ALYALEVMES VVKNCGQTVH DEVANKQTME ELKDLLKRQV EVNVRNKILY LIQAWAHAFR
NEPKYKVVQD TYQIMKVEGH VFPEFKESDA MFAAERAPDW VDAEECHRCR VQFGVMTRKH
HCRACGQIFC GKCSSKYSTI PKFGIEKEVR VCEPCFEQLN KKAEGKAAST TELPPEYLTS
PLSQQSQLPP KRDETALQEE EELQLALALS QSEAEEKERM RQKSAYTAYP KAEPTPVASS
APPASSLYSS PVNSSAPLAE DIDPELARYL NRNYWEKKQE EARKSPTPSA PVPLTEPTAQ
PGEGHAIPAN VETSLPETDP QAVTAAGAAF SEQYQNGESE ESHAQFLKAL QNAVTTFVNR
MKSNHVRGRS ITNDSAVLSL FQSINTMHPQ LLELLNQLDE RRLYYEGLQD KLAQIRDARG
ALSALREEHR EKLRRAAEEA ERQRQIQLAQ KLEIMRQKKQ EYLEVQRQLA IQRLQEQEKE
RQMRLEQQKQ TIQMRAQMPA FSLPYAQLQA MPAAGGVLYQ PSGPASFAGT FSPAGSVEGS
PMHTMYMSQP APAASGPYPS MPAAAADPSM VSAYMYPAGA AGAQAAAQGP AGPTTSPAYS
SYQPTPTQGY QTVASQAPQS LPAISQPPQS GTMGYMGSQS VSMGYQPYSM QNLMPTLPGQ
DAPLPPPQQP YISGQQPVYQ QMAPSSGPPQ QQPPVAQQPP AQGPPAQGSE AQLISFD
