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Protein

Hepatocyte growth factor-regulated tyrosine kinase substrate

Gene

Hgs

Organism
Mus musculus (Mouse)
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. May contribute to the efficient recruitment of SMADs to the activin receptor complex. 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.1 Publication

Regions

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

GO - Molecular functioni

  • identical protein binding Source: IntAct
  • metal ion binding Source: UniProtKB-KW
  • protein domain specific binding Source: MGI
  • ubiquitin-dependent protein binding Source: UniProtKB
  • ubiquitin-like protein ligase binding Source: MGI

GO - Biological processi

Keywordsi

Biological processProtein transport, Transport
LigandMetal-binding, Zinc

Names & Taxonomyi

Protein namesi
Recommended name:
Hepatocyte growth factor-regulated tyrosine kinase substrate
Gene namesi
Name:Hgs
Synonyms:Hrs
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Unplaced

Organism-specific databases

MGIiMGI:104681. Hgs.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Endosome, Membrane

Pathology & Biotechi

Disruption phenotypei

Mice show a defect in ventral folding morphogenesis, exhibiting two bilateral heart tubes and absence of foregut, and died around embryonic day 11. Significantly enlarged endosomes were also detected in cells of the endoderm.2 Publications

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi183R → A: 100-fold loss of affinity for PIP3 and accumulation in the cytosol. 1 Publication1
Mutagenesisi215C → S: Accumulation in proteinaceous aggregates devoid of membranes and no interaction with PI3P. 1 Publication1
Mutagenesisi269L → A: Loss of protein phosphorylation at Y-329 and Y-334; when associated with A-270. 1 Publication1
Mutagenesisi270S → A: Loss of protein phosphorylation at Y-329 and Y-334; when associated with A-269. 2 Publications1
Mutagenesisi270S → E: No interaction with ubiquitin. 2 Publications1
Mutagenesisi329Y → F: No change in the phosphorylation level. Loss of protein phosphorylation; when associated with F-334. 1 Publication1
Mutagenesisi334Y → F: No change in the phosphorylation level. Loss of protein phosphorylation; when associated with F-329. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000987091 – 775Hepatocyte growth factor-regulated tyrosine kinase substrateAdd BLAST775

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei207N6-acetyllysineBy similarity1
Modified residuei216PhosphotyrosineCombined sources1
Modified residuei308PhosphotyrosineCombined sources1
Modified residuei329Phosphotyrosine1 Publication1
Modified residuei334Phosphotyrosine1 Publication1
Modified residuei549N6-succinyllysineCombined sources1

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.1 Publication
Ubiquitinated by ITCH.By similarity

Keywords - PTMi

Acetylation, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ99LI8.
MaxQBiQ99LI8.
PaxDbiQ99LI8.
PRIDEiQ99LI8.

PTM databases

iPTMnetiQ99LI8.
PhosphoSitePlusiQ99LI8.

Expressioni

Tissue specificityi

Ubiquitous expression in adult and fetal tissues with higher expression in testis.2 Publications

Gene expression databases

CleanExiMM_HGS.

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 (By similarity). Interacts with STAM (PubMed:9407053, PubMed:19278655). Interacts with STAM2 (PubMed:10651905). Interacts with EPS15; the interaction is direct, calcium-dependent and inhibited by SNAP25 (By similarity). Identified in a complex with STAM and LITAF (By similarity). Found in a complex with STAM and E3 ligase ITCH and DTX3L (By similarity). Interacts with E3 ligase DTX3L; the interaction brings together STAM and HSG, promotes their recruitment to early endosomes and decreases STAM and HGS ubiquitination by ITCH (By similarity). Interacts with NF2; the interaction is direct (By similarity). Interacts with ubiquitin; the interaction is direct (PubMed:11988743). Interacts with VPS37C (By similarity). Interacts with SMAD1, SMAD2 and SMAD3 (PubMed:11094085). Interacts with TSG101; the interaction mediates the association with the ESCRT-I complex (PubMed:12802020). Interacts with SNAP25; the interaction is direct and decreases with addition of increasing concentrations of free calcium (By similarity). Interacts with SNX1; the interaction is direct (By similarity). Component of a 550 kDa membrane complex at least composed of HGS and SNX1 but excluding EGFR (By similarity). Interacts with TRAK1 (By similarity). Interacts with TRAK2 (By similarity). Component of the CART complex, at least composed of ACTN4, HGS/HRS, MYO5B and TRIM3 (By similarity). Interacts with ARRDC3 (By similarity). Identified in a complex containing at least ARRDC4, AVPR2 and HGS (By similarity). Interacts (via UIM domain) with UBQLN1 (via ubiquitin-like domain) (PubMed:16159959). Interacts with LAPTM4B; promotes HGS ubiquitination (By similarity).By similarity7 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • identical protein binding Source: IntAct
  • protein domain specific binding Source: MGI
  • ubiquitin-dependent protein binding Source: UniProtKB
  • ubiquitin-like protein ligase binding Source: MGI

Protein-protein interaction databases

BioGridi200296. 7 interactors.
CORUMiQ99LI8.
DIPiDIP-29102N.
IntActiQ99LI8. 12 interactors.
MINTiMINT-267768.
STRINGi10090.ENSMUSP00000026900.

Structurei

3D structure databases

ProteinModelPortaliQ99LI8.
SMRiQ99LI8.
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 – 541Interaction with SNX1By similarityAdd BLAST317
Regioni443 – 541Interaction with SNAP25 and TRAK2By similarityAdd BLAST99
Regioni452 – 570Interaction with STAM1 PublicationAdd BLAST119
Regioni478 – 775Interaction with NF2By similarityAdd BLAST298

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi503 – 558Gln-richAdd BLAST56
Compositional biasi559 – 763Pro-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

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.
InParanoidiQ99LI8.
KOiK12182.

Family and domain databases

Gene3Di1.25.40.90. 1 hit.
3.30.40.10. 1 hit.
InterProiView protein in InterPro
IPR008942. 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.
PfamiView protein in Pfam
PF01363. FYVE. 1 hit.
PF12210. Hrs_helical. 1 hit.
PF00790. VHS. 1 hit.
PIRSFiPIRSF036956. Hrs_Vps27. 1 hit.
SMARTiView protein in SMART
SM00064. FYVE. 1 hit.
SM00288. VHS. 1 hit.
SUPFAMiSSF48464. SSF48464. 1 hit.
SSF57903. SSF57903. 1 hit.
PROSITEiView protein in PROSITE
PS50330. UIM. 1 hit.
PS50179. VHS. 1 hit.
PS50178. ZF_FYVE. 1 hit.

Sequencei

Sequence statusi: Complete.

Q99LI8-1 [UniParc]FASTAAdd to basket

« 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 KKAEGKASST TELPPEYLTS PLSQQSQLPP
260 270 280 290 300
KRDETALQEE EELQLALALS QSEAEEKERM RQKTTYTAHP KAEPTPLASS
310 320 330 340 350
APPAGSLYSS PVNSSAPLAE DIDPELARYL NRNYWEKKQE EARKSPTPSA
360 370 380 390 400
PVPLTEPAAQ PGEGHTAPNS MAEAPLPETD SQPITPCSGP FSEYQNGESE
410 420 430 440 450
ESHEQFLKAL QNAVSTFVNR MKSNHMRGRS ITNDSAVLSL FQSINTMHPQ
460 470 480 490 500
LLELLNQLDE RRLYYEGLQD KLAQIRDARG ALSALREEHR EKLRRAAEEA
510 520 530 540 550
ERQRQIQLAQ KLEIMRQKKQ EYLEVQRQLA IQRLQEQEKE RQMRLEQQKQ
560 570 580 590 600
TVQMRAQMPA FPLPYAQLQA MPTAGGVLYQ PSGPTSFPAT FSPAGSVEGS
610 620 630 640 650
PMHGVYMSQP APATGPYPSM PGTTADPSMV SAYMYPTGAP GAQAAPQAQA
660 670 680 690 700
GPTTSPAYSS YQPTPTPGYQ SVASQAPQSL PAISQPPQTS NIGYMGSQPM
710 720 730 740 750
SMGYQPYNMQ NLMTALPGQD ASLPAQQPYI PGQQPLYQQM APSTGPPQQQ
760 770
PPVAQPAPTQ GPPAQGSEAQ LISFD
Length:775
Mass (Da):86,015
Last modified:July 19, 2005 - v2
Checksum:i0E68BF5AB514865B
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti23T → S in AAH03239 (PubMed:15489334).Curated1
Sequence conflicti584P → S in BAC32676 (PubMed:16141072).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D50050 mRNA. Translation: BAA08768.1.
AK046299 mRNA. Translation: BAC32676.1.
BC003239 mRNA. Translation: AAH03239.1.
PIRiI49759.
RefSeqiNP_001152800.1. NM_001159328.1.
NP_032270.3. NM_008244.3.
UniGeneiMm.7919.

Genome annotation databases

GeneIDi15239.
KEGGimmu:15239.
UCSCiuc007msx.2. mouse.

Similar proteinsi

Entry informationi

Entry nameiHGS_MOUSE
AccessioniPrimary (citable) accession number: Q99LI8
Secondary accession number(s): Q61691, Q8BQW3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 19, 2005
Last sequence update: July 19, 2005
Last modified: November 22, 2017
This is version 143 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot