UniProtKB - Q99LI8 (HGS_MOUSE)
Hepatocyte growth factor-regulated tyrosine kinase substrate
Hgs
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 PublicationSites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Metal bindingi | 166 | Zinc 1PROSITE-ProRule annotation | 1 | |
Metal bindingi | 169 | Zinc 1PROSITE-ProRule annotation | 1 | |
Metal bindingi | 182 | Zinc 2PROSITE-ProRule annotation | 1 | |
Metal bindingi | 185 | Zinc 2PROSITE-ProRule annotation | 1 | |
Metal bindingi | 190 | Zinc 1PROSITE-ProRule annotation | 1 | |
Metal bindingi | 193 | Zinc 1PROSITE-ProRule annotation | 1 | |
Metal bindingi | 212 | Zinc 2PROSITE-ProRule annotation | 1 | |
Metal bindingi | 215 | Zinc 2PROSITE-ProRule annotation | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Zinc fingeri | 160 – 220 | FYVE-typePROSITE-ProRule annotationAdd BLAST | 61 |
GO - Molecular functioni
- identical protein binding Source: IntAct
- metal ion binding Source: UniProtKB-KW
- phosphatidylinositol binding Source: InterPro
- protein domain specific binding Source: MGI
- ubiquitin binding Source: InterPro
- ubiquitin-dependent protein binding Source: UniProtKB
- ubiquitin-like protein ligase binding Source: MGI
GO - Biological processi
- endosome to lysosome transport Source: MGI
- membrane invagination Source: MGI
- negative regulation of angiogenesis Source: MGI
- negative regulation of platelet-derived growth factor receptor signaling pathway Source: MGI
- negative regulation of receptor signaling pathway via JAK-STAT Source: MGI
- negative regulation of vascular endothelial growth factor receptor signaling pathway Source: MGI
- positive regulation of exosomal secretion Source: MGI
- positive regulation of gene expression Source: MGI
- protein localization to membrane Source: MGI
- protein targeting to lysosome Source: MGI
- regulation of MAP kinase activity Source: MGI
Keywordsi
Biological process | Protein transport, Transport |
Ligand | Metal-binding, Zinc |
Enzyme and pathway databases
Reactomei | R-MMU-182971, EGFR downregulation R-MMU-432720, Lysosome Vesicle Biogenesis R-MMU-5689880, Ub-specific processing proteases R-MMU-6807004, Negative regulation of MET activity R-MMU-8856825, Cargo recognition for clathrin-mediated endocytosis R-MMU-8856828, Clathrin-mediated endocytosis R-MMU-9013420, RHOU GTPase cycle R-MMU-917729, Endosomal Sorting Complex Required For Transport (ESCRT) R-MMU-9706019, RHOBTB3 ATPase cycle |
Names & Taxonomyi
Protein namesi | Recommended name: Hepatocyte growth factor-regulated tyrosine kinase substrate |
Gene namesi | Name:Hgs Synonyms:Hrs |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:104681, Hgs |
VEuPathDBi | HostDB:ENSMUSG00000025793 |
Subcellular locationi
Cytoplasm and Cytosol
Endosome
Note: Colocalizes with UBQLN1 in ubiquitin-rich cytoplasmic aggregates that are not endocytic compartments.By similarity
Cytosol
- cytosol Source: MGI
Endosome
- early endosome Source: MGI
- early endosome membrane Source: UniProtKB-SubCell
- endosome Source: MGI
- ESCRT-0 complex Source: MGI
- multivesicular body membrane Source: UniProtKB-SubCell
Lysosome
- lysosome Source: MGI
Other locations
- cytoplasm Source: MGI
- intracellular membrane-bounded organelle Source: MGI
- membrane Source: MGI
- secretory granule Source: MGI
Keywords - Cellular componenti
Cytoplasm, Endosome, MembranePathology & Biotechi
Disruption phenotypei
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 183 | R → A: 100-fold loss of affinity for PIP3 and accumulation in the cytosol. 1 Publication | 1 | |
Mutagenesisi | 215 | C → S: Accumulation in proteinaceous aggregates devoid of membranes and no interaction with PI3P. 1 Publication | 1 | |
Mutagenesisi | 269 | L → A: Loss of protein phosphorylation at Y-329 and Y-334; when associated with A-270. 1 Publication | 1 | |
Mutagenesisi | 270 | S → A: Loss of protein phosphorylation at Y-329 and Y-334; when associated with A-269. 2 Publications | 1 | |
Mutagenesisi | 270 | S → E: No interaction with ubiquitin. 2 Publications | 1 | |
Mutagenesisi | 329 | Y → F: No change in the phosphorylation level. Loss of protein phosphorylation; when associated with F-334. 1 Publication | 1 | |
Mutagenesisi | 334 | Y → F: No change in the phosphorylation level. Loss of protein phosphorylation; when associated with F-329. 1 Publication | 1 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000098709 | 1 – 775 | Hepatocyte growth factor-regulated tyrosine kinase substrateAdd BLAST | 775 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 207 | N6-acetyllysineBy similarity | 1 | |
Modified residuei | 216 | PhosphotyrosineCombined sources | 1 | |
Modified residuei | 308 | PhosphotyrosineCombined sources | 1 | |
Modified residuei | 329 | Phosphotyrosine1 Publication | 1 | |
Modified residuei | 334 | Phosphotyrosine1 Publication | 1 | |
Modified residuei | 549 | N6-succinyllysineCombined sources | 1 |
Post-translational modificationi
Keywords - PTMi
Acetylation, Phosphoprotein, Ubl conjugationProteomic databases
EPDi | Q99LI8 |
MaxQBi | Q99LI8 |
PaxDbi | Q99LI8 |
PRIDEi | Q99LI8 |
ProteomicsDBi | 273105 |
PTM databases
iPTMneti | Q99LI8 |
PhosphoSitePlusi | Q99LI8 |
Expressioni
Tissue specificityi
Gene expression databases
ExpressionAtlasi | Q99LI8, baseline and differential |
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 PublicationsBinary interactionsi
Q99LI8
GO - Molecular functioni
- identical protein binding Source: IntAct
- protein domain specific binding Source: MGI
- ubiquitin binding Source: InterPro
- ubiquitin-dependent protein binding Source: UniProtKB
- ubiquitin-like protein ligase binding Source: MGI
Protein-protein interaction databases
BioGRIDi | 200296, 31 interactors |
CORUMi | Q99LI8 |
DIPi | DIP-29102N |
IntActi | Q99LI8, 12 interactors |
MINTi | Q99LI8 |
STRINGi | 10090.ENSMUSP00000026900 |
Miscellaneous databases
RNActi | Q99LI8, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 15 – 143 | VHSPROSITE-ProRule annotationAdd BLAST | 129 | |
Domaini | 258 – 277 | UIMPROSITE-ProRule annotationAdd BLAST | 20 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 223 – 319 | DisorderedSequence analysisAdd BLAST | 97 | |
Regioni | 225 – 541 | Interaction with SNX1By similarityAdd BLAST | 317 | |
Regioni | 338 – 405 | DisorderedSequence analysisAdd BLAST | 68 | |
Regioni | 443 – 541 | Interaction with SNAP25 and TRAK2By similarityAdd BLAST | 99 | |
Regioni | 452 – 570 | Interaction with STAM1 PublicationAdd BLAST | 119 | |
Regioni | 478 – 775 | Interaction with NF2By similarityAdd BLAST | 298 | |
Regioni | 640 – 690 | DisorderedSequence analysisAdd BLAST | 51 | |
Regioni | 719 – 775 | DisorderedSequence analysisAdd BLAST | 57 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 223 – 252 | Polar residuesSequence analysisAdd BLAST | 30 | |
Compositional biasi | 272 – 286 | Basic and acidic residuesSequence analysisAdd BLAST | 15 | |
Compositional biasi | 302 – 316 | Polar residuesSequence analysisAdd BLAST | 15 | |
Compositional biasi | 381 – 396 | Polar residuesSequence analysisAdd BLAST | 16 | |
Compositional biasi | 647 – 690 | Polar residuesSequence analysisAdd BLAST | 44 | |
Compositional biasi | 719 – 744 | Polar residuesSequence analysisAdd BLAST | 26 | |
Compositional biasi | 745 – 759 | Pro residuesSequence analysisAdd BLAST | 15 | |
Compositional biasi | 760 – 775 | Polar residuesSequence analysisAdd BLAST | 16 |
Domaini
Zinc finger
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Zinc fingeri | 160 – 220 | FYVE-typePROSITE-ProRule annotationAdd BLAST | 61 |
Keywords - Domaini
Zinc-fingerPhylogenomic databases
eggNOGi | KOG1818, Eukaryota |
GeneTreei | ENSGT00940000158297 |
InParanoidi | Q99LI8 |
OrthoDBi | 828765at2759 |
Family and domain databases
Gene3Di | 1.25.40.90, 1 hit 3.30.40.10, 1 hit |
InterProi | View 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 |
Pfami | View protein in Pfam PF01363, FYVE, 1 hit PF12210, Hrs_helical, 1 hit PF00790, VHS, 1 hit |
PIRSFi | PIRSF036956, Hrs_Vps27, 1 hit |
SMARTi | View protein in SMART SM00064, FYVE, 1 hit SM00288, VHS, 1 hit |
SUPFAMi | SSF48464, SSF48464, 1 hit SSF57903, SSF57903, 1 hit |
PROSITEi | View protein in PROSITE PS50330, UIM, 1 hit PS50179, VHS, 1 hit PS50178, ZF_FYVE, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
This entry has 1 described isoform and 3 potential isoforms that are computationally mapped.Show allAlign All
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
Computationally mapped potential isoform sequencesi
There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketQ3UMA3 | Q3UMA3_MOUSE | Hepatocyte growth factor-regulated ... | Hgs | 776 | Annotation score: | ||
B1ATY9 | B1ATY9_MOUSE | Hepatocyte growth factor-regulated ... | Hgs | 245 | Annotation score: | ||
F6VV02 | F6VV02_MOUSE | Hepatocyte growth factor-regulated ... | Hgs | 294 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 23 | T → S in AAH03239 (PubMed:15489334).Curated | 1 | |
Sequence conflicti | 584 | P → S in BAC32676 (PubMed:16141072).Curated | 1 |
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 |
CCDSi | CCDS88297.1 |
PIRi | I49759 |
RefSeqi | NP_001152800.1, NM_001159328.1 NP_032270.3, NM_008244.3 |
Genome annotation databases
Ensembli | ENSMUST00000106205; ENSMUSP00000101811; ENSMUSG00000025793 |
GeneIDi | 15239 |
KEGGi | mmu:15239 |
UCSCi | uc007msx.2, mouse |
Similar proteinsi
Cross-referencesi
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 |
CCDSi | CCDS88297.1 |
PIRi | I49759 |
RefSeqi | NP_001152800.1, NM_001159328.1 NP_032270.3, NM_008244.3 |
3D structure databases
SMRi | Q99LI8 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 200296, 31 interactors |
CORUMi | Q99LI8 |
DIPi | DIP-29102N |
IntActi | Q99LI8, 12 interactors |
MINTi | Q99LI8 |
STRINGi | 10090.ENSMUSP00000026900 |
PTM databases
iPTMneti | Q99LI8 |
PhosphoSitePlusi | Q99LI8 |
Proteomic databases
EPDi | Q99LI8 |
MaxQBi | Q99LI8 |
PaxDbi | Q99LI8 |
PRIDEi | Q99LI8 |
ProteomicsDBi | 273105 |
Protocols and materials databases
Antibodypediai | 1403, 548 antibodies from 40 providers |
DNASUi | 15239 |
Genome annotation databases
Ensembli | ENSMUST00000106205; ENSMUSP00000101811; ENSMUSG00000025793 |
GeneIDi | 15239 |
KEGGi | mmu:15239 |
UCSCi | uc007msx.2, mouse |
Organism-specific databases
CTDi | 9146 |
MGIi | MGI:104681, Hgs |
VEuPathDBi | HostDB:ENSMUSG00000025793 |
Phylogenomic databases
eggNOGi | KOG1818, Eukaryota |
GeneTreei | ENSGT00940000158297 |
InParanoidi | Q99LI8 |
OrthoDBi | 828765at2759 |
Enzyme and pathway databases
Reactomei | R-MMU-182971, EGFR downregulation R-MMU-432720, Lysosome Vesicle Biogenesis R-MMU-5689880, Ub-specific processing proteases R-MMU-6807004, Negative regulation of MET activity R-MMU-8856825, Cargo recognition for clathrin-mediated endocytosis R-MMU-8856828, Clathrin-mediated endocytosis R-MMU-9013420, RHOU GTPase cycle R-MMU-917729, Endosomal Sorting Complex Required For Transport (ESCRT) R-MMU-9706019, RHOBTB3 ATPase cycle |
Miscellaneous databases
BioGRID-ORCSi | 15239, 31 hits in 69 CRISPR screens |
ChiTaRSi | Hgs, mouse |
PROi | PR:Q99LI8 |
RNActi | Q99LI8, protein |
SOURCEi | Search... |
Gene expression databases
ExpressionAtlasi | Q99LI8, baseline and differential |
Family and domain databases
Gene3Di | 1.25.40.90, 1 hit 3.30.40.10, 1 hit |
InterProi | View 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 |
Pfami | View protein in Pfam PF01363, FYVE, 1 hit PF12210, Hrs_helical, 1 hit PF00790, VHS, 1 hit |
PIRSFi | PIRSF036956, Hrs_Vps27, 1 hit |
SMARTi | View protein in SMART SM00064, FYVE, 1 hit SM00288, VHS, 1 hit |
SUPFAMi | SSF48464, SSF48464, 1 hit SSF57903, SSF57903, 1 hit |
PROSITEi | View protein in PROSITE PS50330, UIM, 1 hit PS50179, VHS, 1 hit PS50178, ZF_FYVE, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | HGS_MOUSE | |
Accessioni | Q99LI8Primary (citable) accession number: Q99LI8 Secondary accession number(s): Q61691, Q8BQW3 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | July 19, 2005 |
Last sequence update: | July 19, 2005 | |
Last modified: | February 23, 2022 | |
This is version 165 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot