HGS hepatocyte growth factor-regulated tyrosine kinase substrate [Homo sapiens (human)] - Gene

Summary

Official Symbol: HGSprovided by HGNC
Official Full Name: hepatocyte growth factor-regulated tyrosine kinase substrateprovided by HGNC
Primary source: HGNC:HGNC:4897
See related: Ensembl:ENSG00000185359 MIM:604375; AllianceGenome:HGNC:4897
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: HRS
Summary: The protein encoded by this gene regulates endosomal sorting and plays a critical role in the recycling and degradation of membrane receptors. The encoded protein sorts monoubiquitinated membrane proteins into the multivesicular body, targeting these proteins for lysosome-dependent degradation. [provided by RefSeq, Dec 2010]
Expression: Ubiquitous expression in testis (RPKM 20.7), bone marrow (RPKM 16.1) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 17q25.3

Exon count:: 22

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	17	NC_000017.11 (81684011..81702121)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	17	NC_060941.1 (82600905..82619025)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	17	NC_000017.10 (79651041..79669151)

Chromosome 17 - NC_000017.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

HRS Regulates Small Extracellular Vesicle PD-L1 Secretion and Is Associated with Anti-PD-1 Treatment Efficacy.
Title: HRS Regulates Small Extracellular Vesicle PD-L1 Secretion and Is Associated with Anti-PD-1 Treatment Efficacy.
Hepatocyte growth factor-regulated tyrosine kinase substrate is essential for endothelial cell polarity and cerebrovascular stability.
Title: Hepatocyte growth factor-regulated tyrosine kinase substrate is essential for endothelial cell polarity and cerebrovascular stability.
Epstein-Barr Virus LMP1 Promotes Syntenin-1- and Hrs-Induced Extracellular Vesicle Formation for Its Own Secretion To Increase Cell Proliferation and Migration.
Title: Epstein-Barr Virus LMP1 Promotes Syntenin-1- and Hrs-Induced Extracellular Vesicle Formation for Its Own Secretion To Increase Cell Proliferation and Migration.
Study provides in vivo evidence that Beclin 1 suppresses tumor proliferation by regulating the endocytic trafficking and degradation of the EGFR and transferrin (TFR1) receptors. Beclin 1 promoted endosomal recruitment of hepatocyte growth factor tyrosine kinase substrate (HRS), which was necessary for sorting surface receptors to intraluminal vesicles for signal silencing and lysosomal degradation.
Title: Beclin 1 Promotes Endosome Recruitment of Hepatocyte Growth Factor Tyrosine Kinase Substrate to Suppress Tumor Proliferation.
The ESCRT-0 protein HRS interacts with the HTLV-II antisense protein APH-2 and suppresses viral replication. [APH-2]
Title: The ESCRT-0 Protein HRS Interacts with the Human T Cell Leukemia Virus Type 2 Antisense Protein APH-2 and Suppresses Viral Replication.
Post-traumatic stress disorder (PTSD) is associated with differential methylation, measured in blood, within HGS and NRG1 across three civilian cohorts.
Title: Epigenetic meta-analysis across three civilian cohorts identifies NRG1 and HGS as blood-based biomarkers for post-traumatic stress disorder.
Degradation of CLR-RAMP2 was sensitive to overexpression of hepatocyte growth factor-regulated tyrosine kinase substrate (HRS), but not to HRS knockdown, whereas CLRDelta9KR-RAMP2 degradation was unaffected. Overexpression, but not knockdown of HRS, promoted hyperubiquitination of CLR under basal conditions. These results propose a role for ubiquitin and HRS in the regulation of AM-induced degradation of CLR-RAMP2.
Title: The Role of Ubiquitination and Hepatocyte Growth Factor-Regulated Tyrosine Kinase Substrate in the Degradation of the Adrenomedullin Type I Receptor.
Results demonstrate the existence of crosstalk between beta-catenin signaling and HGS in two different types of cancer (hepatoblastoma and colorectal).
Title: A kinome siRNA screen identifies HGS as a potential target for liver cancers with oncogenic mutations in CTNNB1.
detailed analysis of the subcellular localization and functional significance of Hrs in macropinocytosis-mediated entry of Kaposi's Sarcoma-Associated Herpesvirus
Title: ESCRT-0 Component Hrs Promotes Macropinocytosis of Kaposi's Sarcoma-Associated Herpesvirus in Human Dermal Microvascular Endothelial Cells.
ESCRT-0 protein hepatocyte growth factor-regulated tyrosine kinase substrate (Hrs) is targeted to endosomes independently of signal-transducing adaptor molecule (STAM) and the complex formation with STAM promotes its endosomal dissociation.
Title: ESCRT-0 protein hepatocyte growth factor-regulated tyrosine kinase substrate (Hrs) is targeted to endosomes independently of signal-transducing adaptor molecule (STAM) and the complex formation with STAM promotes its endosomal dissociation.

Submit: New GeneRIF Correction See all GeneRIFs (43)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
Digital quantification of human eye color highlights genetic association of three new loci. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Replication interactions

Interaction	Pubs
Knockdown of hepatocyte growth factor-regulated tyrosine kinase substrate (HGS) by siRNA inhibits HIV-1 replication in HeLa-derived TZM-bl cells	PubMed

Protein interactions

Protein	Gene	Interaction	Pubs
Nef	nef	HIV-1 Nef co-localizes with CXCR4, AIP4, NEDD4, CD63/LAMP-1-positive vesicles, and HRS/VPS27-positive ESCRT-0 structures in HeLa cells	PubMed
Pr55(Gag)	gag	Overexpression of the C-terminal fragment of HRS (residues 391-777) or HRS mutants lacking either the N-terminal FYVE domain (residues 215-290) or the PSAP (residues 348-351) motif efficiently inhibit HIV-1 Gag particle production	PubMed
Vpu	vpu	Vpu interacts with HGS (HRS) via the HGS double-ubiquitin interaction motif, indicating this motif is the direct binding site for Vpu or ubiquitination of cargo mediates Vpu/HGS interaction or by factors associated in the degradation pathway	PubMed
	vpu	Physiological levels of Vpu requires the core ESCRT pathway (TSG1010 and UBAP1) and HGA (HRS) for Vpu-mediated BST-2 (tetherin) degradation but does NOT require these proteins for counteraction of BST2 (tetherin's) physical antiviral activity	PubMed
	vpu	HRS, an ESCRT-0 complex component, is required for the Vpu-induced downregulation of BST-2, indicating that Vpu-induced BST-2 degradation involves the ESCRT/MVB pathway	PubMed
	vpu	HRS interacts with both HIV-1 Vpu and tetherin by co-precipitation analysis	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D11S2921 (e-PCR)
- UniSTS:152074

G35510 (e-PCR)
- UniSTS:44150

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables phosphatidylinositol binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein domain specific binding	IPI Inferred from Physical Interaction more info	PubMed
enables ubiquitin binding	IBA Inferred from Biological aspect of Ancestor more info
enables ubiquitin-like protein ligase binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in endocytic recycling	IBA Inferred from Biological aspect of Ancestor more info
involved_in endosomal transport	NAS Non-traceable Author Statement more info	PubMed
involved_in macroautophagy	TAS Traceable Author Statement more info	PubMed
involved_in membrane fission	NAS Non-traceable Author Statement more info	PubMed
involved_in membrane invagination	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in multivesicular body assembly	NAS Non-traceable Author Statement more info	PubMed
involved_in multivesicular body assembly	TAS Traceable Author Statement more info	PubMed
involved_in negative regulation of angiogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of cell population proliferation	TAS Traceable Author Statement more info	PubMed
involved_in negative regulation of platelet-derived growth factor receptor signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of receptor signaling pathway via JAK-STAT	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of vascular endothelial growth factor receptor signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of exosomal secretion	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of gene expression	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in protein localization to membrane	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in protein targeting to lysosome	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in protein transport to vacuole involved in ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway	NAS Non-traceable Author Statement more info	PubMed
involved_in receptor internalization	IBA Inferred from Biological aspect of Ancestor more info
involved_in regulation of MAP kinase activity	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of protein catabolic process	TAS Traceable Author Statement more info	PubMed
involved_in signal transduction	TAS Traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
part_of ESCRT-0 complex	IDA Inferred from Direct Assay more info	PubMed
part_of ESCRT-0 complex	IPI Inferred from Physical Interaction more info	PubMed
part_of ESCRT-0 complex	ISS Inferred from Sequence or Structural Similarity more info
part_of ESCRT-0 complex	TAS Traceable Author Statement more info	PubMed
located_in cytosol	IDA Inferred from Direct Assay more info
located_in cytosol	TAS Traceable Author Statement more info
is_active_in early endosome	IBA Inferred from Biological aspect of Ancestor more info
located_in early endosome	IDA Inferred from Direct Assay more info	PubMed
located_in early endosome membrane	IEA Inferred from Electronic Annotation more info
located_in endosome	IDA Inferred from Direct Assay more info	PubMed
located_in extracellular exosome	HDA more info	PubMed
located_in lysosome	IDA Inferred from Direct Assay more info
located_in multivesicular body membrane	IEA Inferred from Electronic Annotation more info
located_in phagocytic vesicle lumen	TAS Traceable Author Statement more info

General protein information

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Preferred Names: hepatocyte growth factor-regulated tyrosine kinase substrate

Names: human growth factor-regulated tyrosine kinase substrate; protein pp110

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_004712.5 → NP_004703.1 hepatocyte growth factor-regulated tyrosine kinase substrate

See identical proteins and their annotated locations for NP_004703.1

Status: REVIEWED

Source sequence(s)

AI365104, BC003565

Consensus CDS

CCDS11784.1

UniProtKB/Swiss-Prot

O14964, Q9NR36

UniProtKB/TrEMBL

A0A0S2Z4R4, A0A7I2V307

Related

ENSP00000331201.4, ENST00000329138.9

Conserved Domains (6) summary

cd03569
Location:4 → 145

VHS_Hrs_Vps27p; VHS domain family, Hrs and Vps27p subfamily; composed of Hrs (Hepatocyte growth factor-regulated tyrosine kinase substrate) and its yeast homolog Vps27p (vacuolar protein sorting). The VHS domain, an essential part of Hrs/Vps27p, has a superhelical ...

cd15720
Location:159 → 219

FYVE_Hrs; FYVE domain found in hepatocyte growth factor (HGF)-regulated tyrosine kinase substrate (Hrs) and similar proteins

pfam07223
Location:519 → 746

DUF1421; Protein of unknown function (DUF1421)

pfam12210
Location:407 → 501

Hrs_helical; Hepatocyte growth factor-regulated tyrosine kinase substrate

cd16269
Location:531 → 542

GBP_C; coiled coil [structural motif]

cl20817
Location:486 → 560

GBP_C; Guanylate-binding protein, C-terminal domain