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Protein

Hepatocyte growth factor-regulated tyrosine kinase substrate

Gene

Hgs

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Involved in intracellular signal transduction mediated by cytokines and growth factors. When associated with STAM, it suppresses DNA signaling upon stimulation by IL-2 and GM-CSF. Could be a direct effector of PI3-kinase in vesicular pathway via early endosomes and may regulate trafficking to early and late endosomes by recruiting clathrin. May concentrate ubiquitinated receptors within clathrin-coated regions. Involved in down-regulation of receptor tyrosine kinase via multivesicular body (MVBs) when complexed with STAM (ESCRT-0 complex). The ESCRT-0 complex binds ubiquitin and acts as sorting machinery that recognizes ubiquitinated receptors and transfers them to further sequential lysosomal sorting/trafficking processes. Involved in receptor recycling via its association with the CART complex, a multiprotein complex required for efficient transferrin receptor recycling but not for EGFR degradation (By similarity). May contribute to the efficient recruitment of SMADs to the activin receptor complex.By similarity

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri160 – 220FYVE-typePROSITE-ProRule annotationAdd BLAST61

GO - Molecular functioni

  • metal ion binding Source: UniProtKB-KW
  • protein domain specific binding Source: RGD

GO - Biological processi

  • endosome to lysosome transport Source: RGD
  • intracellular protein transport Source: InterPro
Complete GO annotation...

Keywords - Biological processi

Protein transport, Transport

Keywords - Ligandi

Metal-binding, Zinc

Names & Taxonomyi

Protein namesi
Recommended name:
Hepatocyte growth factor-regulated tyrosine kinase substrate
Alternative name(s):
SNAP-25-interacting protein Hrs-2
Gene namesi
Name:Hgs
Synonyms:Hrs, Hrs2
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi69225. Hgs.

Subcellular locationi

  • Cytoplasm 1 Publication
  • Early endosome membrane 1 Publication; Peripheral membrane protein 1 Publication; Cytoplasmic side 1 Publication
  • Endosomemultivesicular body membrane 1 Publication; Peripheral membrane protein 1 Publication

  • Note: Colocalizes with UBQLN1 in ubiquitin-rich cytoplasmic aggregates that are not endocytic compartments.By similarity

GO - Cellular componenti

  • cytosol Source: RGD
  • early endosome membrane Source: UniProtKB-SubCell
  • membrane Source: RGD
  • multivesicular body membrane Source: UniProtKB-SubCell
  • secretory granule Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Endosome, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000987101 – 776Hepatocyte growth factor-regulated tyrosine kinase substrateAdd BLAST776

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei207N6-acetyllysineBy similarity1
Modified residuei216PhosphotyrosineBy similarity1
Modified residuei308PhosphotyrosineBy similarity1
Modified residuei329PhosphotyrosineBy similarity1
Modified residuei334PhosphotyrosineBy similarity1
Modified residuei550N6-succinyllysineBy similarity1

Post-translational modificationi

Phosphorylated on Tyr-334. This phosphorylation occurs in response to EGF. A minor site of phosphorylation on Tyr-329 is detected. Protein phosphorylation may also be triggered in response to IL-2, GM-CSF and HGF (By similarity).By similarity
Ubiquitinated by ITCH.By similarity

Keywords - PTMi

Acetylation, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ9JJ50.
PRIDEiQ9JJ50.

PTM databases

iPTMnetiQ9JJ50.
PhosphoSitePlusiQ9JJ50.

Expressioni

Tissue specificityi

Ubiquitously expressed.3 Publications

Gene expression databases

BgeeiENSRNOG00000036696.
GenevisibleiQ9JJ50. RN.

Interactioni

Subunit structurei

Component of the ESCRT-0 complex composed of STAM or STAM2 and HGS. Part of a complex at least composed of HSG, STAM2 (or probably STAM) and EPS15. Interacts with STAM. Interacts with STAM2. Interacts with EPS15; the interaction is direct, calcium-dependent and inhibited by SNAP25. Interacts with NF2; the interaction is direct. Interacts with ubiquitin; the interaction is direct. Interacts with VPS37C. Interacts with SMAD1, SMAD2 and SMAD3. Interacts with TSG101; the interaction mediates the association with the ESCRT-I complex. Component of the CART complex, at least composed of ACTN4, HGS/HRS, MYO5B and TRIM3 (By similarity). Interacts with SNAP25; the interaction is direct and decreases with addition of increasing concentrations of free calcium (PubMed:9039916, PubMed:10825299). Interacts with SNX1; the interaction is direct (PubMed:11110793). Component of a 550 kDa membrane complex at least composed of HGS and SNX1 but excluding EGFR. Interacts with TRAK2 (PubMed:17062640). Interacts with TRAK1 (By similarity). Interacts (via UIM domain) with UBQLN1 (via ubiquitin-like domain) (By similarity). Interacts with ARRDC3. Identified in a complex containing at least ARRDC4, V2R and HGS (By similarity).By similarity5 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Hap1P542565EBI-7092491,EBI-994539
Hap1P54256-25EBI-7092491,EBI-994554

GO - Molecular functioni

  • protein domain specific binding Source: RGD

Protein-protein interaction databases

BioGridi248562. 7 interactors.
IntActiQ9JJ50. 1 interactor.
MINTiMINT-107197.
STRINGi10116.ENSRNOP00000051849.

Structurei

3D structure databases

ProteinModelPortaliQ9JJ50.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini15 – 143VHSPROSITE-ProRule annotationAdd BLAST129
Domaini258 – 277UIMPROSITE-ProRule annotationAdd BLAST20

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni225 – 542Interaction with SNX11 PublicationAdd BLAST318
Regioni444 – 542Interaction with SNAP25 and TRAK21 PublicationAdd BLAST99
Regioni453 – 571Interaction with STAMBy similarityAdd BLAST119
Regioni479 – 776Interaction with NF2By similarityAdd BLAST298

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi504 – 559Gln-richAdd BLAST56
Compositional biasi560 – 764Pro-richAdd BLAST205

Domaini

Has a double-sided UIM that can bind 2 ubiquitin molecules, one on each side of the helix.By similarity
The FYVE-type zinc finger domain mediates interactions with phosphatidylinositol 3-phosphate in membranes of early endosomes and penetrates bilayers. The FYVE domain insertion into PtdIns3P-enriched membranes is substantially increased in acidic conditions (By similarity).By similarity

Sequence similaritiesi

Contains 1 FYVE-type zinc finger.PROSITE-ProRule annotation
Contains 1 UIM (ubiquitin-interacting motif) domain.PROSITE-ProRule annotation
Contains 1 VHS domain.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri160 – 220FYVE-typePROSITE-ProRule annotationAdd BLAST61

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG1818. Eukaryota.
ENOG410XNRF. LUCA.
HOVERGENiHBG062917.
InParanoidiQ9JJ50.
KOiK12182.
OrthoDBiEOG091G06JJ.
PhylomeDBiQ9JJ50.

Family and domain databases

Gene3Di1.25.40.90. 1 hit.
3.30.40.10. 1 hit.
InterProiIPR008942. ENTH_VHS.
IPR024641. HRS_helical.
IPR017073. Ubi-bd_Hrs_VPS27.
IPR003903. UIM_dom.
IPR002014. VHS_dom.
IPR000306. Znf_FYVE.
IPR017455. Znf_FYVE-rel.
IPR011011. Znf_FYVE_PHD.
IPR013083. Znf_RING/FYVE/PHD.
[Graphical view]
PfamiPF01363. FYVE. 1 hit.
PF12210. Hrs_helical. 1 hit.
PF00790. VHS. 1 hit.
[Graphical view]
PIRSFiPIRSF036956. Hrs_Vps27. 1 hit.
SMARTiSM00064. FYVE. 1 hit.
SM00288. VHS. 1 hit.
[Graphical view]
SUPFAMiSSF48464. SSF48464. 1 hit.
SSF57903. SSF57903. 1 hit.
PROSITEiPS50330. UIM. 1 hit.
PS50179. VHS. 1 hit.
PS50178. ZF_FYVE. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9JJ50-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MGRGSGTFER LLDKATSQLL LETDWESILQ ICDLIRQGDT QAKYAVNSIK
60 70 80 90 100
KKVNDKNPHV ALYALEVMES VVKNCGQTVH DEVANKQTME ELKELLKRQV
110 120 130 140 150
EVNVRNKILY LIQAWAHAFR NEPKYKVVQD TYQIMKVEGH VFPEFKESDA
160 170 180 190 200
MFAAERAPDW VDAEECHRCR VQFGVVTRKH HCRACGQIFC GKCSSKYSTI
210 220 230 240 250
PKFGIEKEVR VCEPCYEQLN KKAEGKAAST TELPPEYLTS PLSQQSQLPP
260 270 280 290 300
KRDETALQEE EELQLALALS QSEAEEKERM RQKSTYTAHP KSEPAPLASS
310 320 330 340 350
APPAGSLYSS PVNSSAPLAE DIDPELARYL NRNYWEKKQE EARKSPTPSA
360 370 380 390 400
PVPLTEPAAQ PGEGHTAPNS MVEAPLPETD SQPITSCSGP FSEQYQNGES
410 420 430 440 450
EESHEQFLKA LQNAVSTFVN RMKSNHMRGR SITNDSAVLS LFQSINSTHP
460 470 480 490 500
QLLELLNRLD ERRLYYEGLQ DKLAQIRDAR GALSALREEH REKLRRAAEE
510 520 530 540 550
AERQRQIQLA QKLEIMRQKK QEYLEVQRQL AIQRLQEQEK ERQMRLEQQK
560 570 580 590 600
QTVQMRAQMP AFPLPYAQLQ AMPTAGGVLY QPSGPTSFPG TFSPAGSVEG
610 620 630 640 650
SPMHGVYMSQ PAPATGPYPS MPGTTADPSM VSAYMYPAGA PGAQAAPQAQ
660 670 680 690 700
AGPTTNPAYS SYQPTPTPGY QNVASQAPQS LPAISQPPQT SNIGYMGSQP
710 720 730 740 750
MSMGYQPYNM QNLMTTLPGQ DASLPAQQPY ITGQQPMYQQ MAPSTGPPQQ
760 770
QPPVAQPPPT QGPPAQGNET QLISFD
Length:776
Mass (Da):86,246
Last modified:October 1, 2000 - v1
Checksum:iFD61BEC121F37E67
GO
Isoform 2 (identifier: Q9JJ50-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     671-675: Missing.

Show »
Length:771
Mass (Da):85,747
Checksum:i626D111BE89783CB
GO

Sequence cautioni

The sequence AAB49681 differs from that shown. Reason: Frameshift at positions 256, 270, 480, 487, 503, 573, 597, 614, 640, 646, 649, 653, 658, 733, 748 and 754.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti394Missing in AAB49681 (PubMed:9039916).Curated1
Sequence conflicti398G → A in AAH83561 (PubMed:15489334).Curated1
Sequence conflicti561A → V in AAH83561 (PubMed:15489334).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_014852671 – 675Missing in isoform 2. 2 Publications5

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U87863 mRNA. Translation: AAB49681.1. Frameshift.
AB002811 mRNA. Translation: BAD08342.1.
AF036344 mRNA. Translation: AAF76251.1.
BC083561 mRNA. Translation: AAH83561.1.
RefSeqiNP_062260.2. NM_019387.2. [Q9JJ50-2]
UniGeneiRn.21.

Genome annotation databases

GeneIDi56084.
KEGGirno:56084.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U87863 mRNA. Translation: AAB49681.1. Frameshift.
AB002811 mRNA. Translation: BAD08342.1.
AF036344 mRNA. Translation: AAF76251.1.
BC083561 mRNA. Translation: AAH83561.1.
RefSeqiNP_062260.2. NM_019387.2. [Q9JJ50-2]
UniGeneiRn.21.

3D structure databases

ProteinModelPortaliQ9JJ50.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi248562. 7 interactors.
IntActiQ9JJ50. 1 interactor.
MINTiMINT-107197.
STRINGi10116.ENSRNOP00000051849.

PTM databases

iPTMnetiQ9JJ50.
PhosphoSitePlusiQ9JJ50.

Proteomic databases

PaxDbiQ9JJ50.
PRIDEiQ9JJ50.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi56084.
KEGGirno:56084.

Organism-specific databases

CTDi9146.
RGDi69225. Hgs.

Phylogenomic databases

eggNOGiKOG1818. Eukaryota.
ENOG410XNRF. LUCA.
HOVERGENiHBG062917.
InParanoidiQ9JJ50.
KOiK12182.
OrthoDBiEOG091G06JJ.
PhylomeDBiQ9JJ50.

Miscellaneous databases

PROiQ9JJ50.

Gene expression databases

BgeeiENSRNOG00000036696.
GenevisibleiQ9JJ50. RN.

Family and domain databases

Gene3Di1.25.40.90. 1 hit.
3.30.40.10. 1 hit.
InterProiIPR008942. ENTH_VHS.
IPR024641. HRS_helical.
IPR017073. Ubi-bd_Hrs_VPS27.
IPR003903. UIM_dom.
IPR002014. VHS_dom.
IPR000306. Znf_FYVE.
IPR017455. Znf_FYVE-rel.
IPR011011. Znf_FYVE_PHD.
IPR013083. Znf_RING/FYVE/PHD.
[Graphical view]
PfamiPF01363. FYVE. 1 hit.
PF12210. Hrs_helical. 1 hit.
PF00790. VHS. 1 hit.
[Graphical view]
PIRSFiPIRSF036956. Hrs_Vps27. 1 hit.
SMARTiSM00064. FYVE. 1 hit.
SM00288. VHS. 1 hit.
[Graphical view]
SUPFAMiSSF48464. SSF48464. 1 hit.
SSF57903. SSF57903. 1 hit.
PROSITEiPS50330. UIM. 1 hit.
PS50179. VHS. 1 hit.
PS50178. ZF_FYVE. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiHGS_RAT
AccessioniPrimary (citable) accession number: Q9JJ50
Secondary accession number(s): P97847, Q5XIV8, Q76N76
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 19, 2005
Last sequence update: October 1, 2000
Last modified: November 2, 2016
This is version 125 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.