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-APR-2013, entry version 63.
DE RecName: Full=Hepatocyte growth factor-regulated tyrosine kinase substrate;
GN Name=HGS;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Laurasiatheria; Cetartiodactyla; Ruminantia;
OC Pecora; Bovidae; 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
CC by cytokines and growth factors. When associated with STAM it
CC suppresses DNA signaling upon stimulation by IL-2 and GM-CSF.
CC Could be a direct effector of PI3-kinase in vesicular pathway via
CC early endosomes and may regulate trafficking to early and late
CC endosomes by recruiting clathrin. May concentrate ubiquitinated
CC receptors within clathrin-coated regions. Involved in down-
CC regulation of receptor tyrosine kinase via multivesicular body
CC (MVBs) when complexed with STAM (ESCRT-0 complex). The ESCRT-0
CC complex binds ubiquitin and acts as sorting machinery that
CC recognizes ubiquitinated receptors and transfers them to further
CC sequential lysosomal sorting/trafficking processes. May contribute
CC to the efficient recruitment of SMADs to the activin receptor
CC complex. Involved in receptor recycling via its association with
CC the CART complex, a multiprotein complex required for efficient
CC transferrin receptor recycling but not for EGFR degradation (By
CC similarity).
CC -!- SUBUNIT: Component of the ESCRT-0 complex composed of STAM or
CC STAM2 and HGS. Part of a complex at least composed of HSG, STAM2
CC (or probably STAM) and EPS15. Interacts with STAM. Interacts with
CC STAM2. Interacts with EPS15; the interaction is direct, calcium-
CC dependent and inhibited by SNAP25. Interacts with NF2; the
CC interaction is direct. Interacts with ubiquitin; the interaction
CC is direct. Interacts with VPS37C. Interacts with SMAD1, SMAD2 and
CC SMAD3. Interacts with TSG101. Interacts with SNAP25; the
CC interaction is direct and decreases with addition of increasing
CC concentrations of free calcium. Interacts with SNX1; the
CC interaction is direct. Component of a 550 kDa membrane complex at
CC least composed of HGS and SNX1 but excluding EGFR. Component of
CC the CART complex, at least composed of ACTN4, HGS/HRS, MYO5B and
CC TRIM3. Interacts with TRAK2 (By similarity).
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Early endosome membrane;
CC Peripheral membrane protein; Cytoplasmic side (By similarity).
CC Endosome, multivesicular body membrane; Peripheral membrane
CC protein (By similarity).
CC -!- DOMAIN: Has a double-sided UIM that can bind 2 ubiquitin
CC molecules, one on each side of the helix (By similarity).
CC -!- DOMAIN: The FYVE-type zinc finger domain mediates interactions
CC with phosphatidylinositol 3-phosphate in membranes of early
CC endosomes and penetrates bilayers. The FYVE domain insertion into
CC PtdIns(3)P-enriched membranes is substantially increased in acidic
CC conditions (By similarity).
CC -!- PTM: Phosphorylated on Tyr-334. A minor site of phosphorylation on
CC Tyr-329 is detected (By similarity). Phosphorylation occurs in
CC response to EGF, IL-2, GM-CSF and HGF.
CC -!- SIMILARITY: Contains 1 FYVE-type zinc finger.
CC -!- SIMILARITY: Contains 1 UIM (ubiquitin-interacting motif) repeat.
CC -!- SIMILARITY: Contains 1 VHS domain.
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DR EMBL; BT026148; ABG66987.1; -; mRNA.
DR EMBL; BC111313; AAI11314.1; -; mRNA.
DR IPI; IPI00697763; -.
DR RefSeq; NP_001039554.1; NM_001046089.1.
DR UniGene; Bt.6724; -.
DR ProteinModelPortal; Q0V8S0; -.
DR SMR; Q0V8S0; 6-221.
DR STRING; 9913.ENSBTAP00000000527; -.
DR PaxDb; Q0V8S0; -.
DR PRIDE; Q0V8S0; -.
DR Ensembl; ENSBTAT00000000527; ENSBTAP00000000527; ENSBTAG00000000411.
DR GeneID; 511582; -.
DR KEGG; bta:511582; -.
DR CTD; 9146; -.
DR eggNOG; NOG257212; -.
DR GeneTree; ENSGT00670000098022; -.
DR HOGENOM; HOG000044175; -.
DR HOVERGEN; HBG062917; -.
DR InParanoid; Q0V8S0; -.
DR KO; K12182; -.
DR OMA; QEYLEMQ; -.
DR OrthoDB; EOG4H463C; -.
DR NextBio; 20869998; -.
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:0006886; P:intracellular protein transport; IEA:InterPro.
DR GO; GO:0046426; P:negative regulation of JAK-STAT cascade; IEA:Compara.
DR Gene3D; 1.25.40.90; -; 1.
DR Gene3D; 3.30.40.10; -; 1.
DR InterPro; IPR008942; ENTH_VHS.
DR InterPro; IPR024641; HRS_helical.
DR InterPro; IPR017073; Ubi-bd_Hrs_VPS27.
DR InterPro; IPR003903; Ubiquitin-int_motif.
DR InterPro; IPR002014; VHS.
DR InterPro; IPR018205; VHS_subgr.
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 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; SM00726; UIM; 1.
DR SMART; SM00288; VHS; 1.
DR SUPFAM; SSF48464; ENTH_VHS; 1.
DR SUPFAM; SSF57903; FYVE_PHD_ZnF; 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; Complete proteome; Cytoplasm; Endosome; Membrane;
KW Metal-binding; Phosphoprotein; Protein transport; Reference proteome;
KW Transport; Zinc; Zinc-finger.
FT CHAIN 1 777 Hepatocyte growth factor-regulated
FT tyrosine kinase substrate.
FT /FTId=PRO_0000274196.
FT DOMAIN 15 143 VHS.
FT REPEAT 258 277 UIM.
FT ZN_FING 160 220 FYVE-type.
FT REGION 225 541 Interaction with SNX1 (By similarity).
FT REGION 443 541 Interaction with SNAP25 and TRAK2 (By
FT similarity).
FT REGION 452 570 Interaction with STAM1 (By similarity).
FT REGION 478 777 Interaction with NF2 (By similarity).
FT COMPBIAS 503 772 Gln-rich.
FT MOD_RES 207 207 N6-acetyllysine (By similarity).
FT MOD_RES 308 308 Phosphotyrosine (By similarity).
FT MOD_RES 329 329 Phosphotyrosine (By similarity).
FT MOD_RES 334 334 Phosphotyrosine (By similarity).
FT CONFLICT 321 321 D -> E (in Ref. 2; AAI11314).
FT CONFLICT 392 392 Missing (in Ref. 2; AAI11314).
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
//
