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

Gene ID: 9146, updated on 17-Feb-2017
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; Vega:OTTHUMG00000178109
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]
Orthologs
Location:
17q25.3
Exon count:
23
Annotation release Status Assembly Chr Location
108 current GRCh38.p7 (GCF_000001405.33) 17 NC_000017.11 (81683932..81702121)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 17 NC_000017.10 (79650962..79669151)

Chromosome 17 - NC_000017.11Genomic Context describing neighboring genes Neighboring gene coiled-coil domain containing 137 Neighboring gene ADP ribosylation factor like GTPase 16 Neighboring gene microRNA 6786 Neighboring gene mitochondrial ribosomal protein L12 Neighboring gene solute carrier family 25 member 10

  • Project title: 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 Jun 15 11:32:44 2016

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

NHGRI GWAS Catalog

Description
Digital quantification of human eye color highlights genetic association of three new loci.
NHGRI GWA Catalog

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

  • CXCR4-mediated signaling events, organism-specific biosystem (from Pathway Interaction Database)
    CXCR4-mediated signaling events, organism-specific biosystem
    CXCR4-mediated signaling events
  • Cargo recognition for clathrin-mediated endocytosis, organism-specific biosystem (from REACTOME)
    Cargo recognition for clathrin-mediated endocytosis, organism-specific biosystemRecruitment of plasma membrane-localized cargo into clathrin-coated endocytic vesicles is mediated by interaction with a variety of clathrin-interacting proteins collectively called CLASPs (clathrin-...
  • Clathrin derived vesicle budding, organism-specific biosystem (from REACTOME)
    Clathrin derived vesicle budding, organism-specific biosystemThere at least two classes of clathrin coated vesicles in cells, one predominantly Golgi-associated, involved in budding from the trans-Golgi network and the other at the plasma membrane. Here the cl...
  • Clathrin-mediated endocytosis, organism-specific biosystem (from REACTOME)
    Clathrin-mediated endocytosis, organism-specific biosystemClathrin-mediated endocytosis (CME) is one of a number of process that control the uptake of material from the plasma membrane, and leads to the formation of clathrin-coated vesicles (Pearse et al, 1...
  • Deubiquitination, organism-specific biosystem (from REACTOME)
    Deubiquitination, organism-specific biosystemUbiquitination, the modification of proteins by the covalent attachment of ubiquitin (Ub), is a key regulatory mechanism for many many cellular processes, including protein degradation by the 26S pro...
  • Disease, organism-specific biosystem (from REACTOME)
    Disease, organism-specific biosystemBiological processes are captured in Reactome by identifying the molecules (DNA, RNA, protein, small molecules) involved in them and describing the details of their interactions. From this molecular ...
  • EGF/EGFR Signaling Pathway, organism-specific biosystem (from WikiPathways)
    EGF/EGFR Signaling Pathway, organism-specific biosystemEpidermal growth factor receptor (EGFR) also known as ErbB1/HER1 is a member of the ErbB family of receptor tyrosine kinases which also includes ErbB2 (Neu, HER2), ErbB3 (HER3) and ErbB4 (HER4). Sev...
  • EGFR downregulation, organism-specific biosystem (from REACTOME)
    EGFR downregulation, organism-specific biosystemRegulation of receptor tyrosine kinase (RTK) activity is implicated in the control of almost all cellular functions. One of the best understood RTKs is epidermal growth factor receptor (EGFR). Growth...
  • ESCRT-0 complex, organism-specific biosystem (from KEGG)
    ESCRT-0 complex, organism-specific biosystemStructural complex; Genetic information processing; Protein processing
  • ESCRT-0 complex, conserved biosystem (from KEGG)
    ESCRT-0 complex, conserved biosystemStructural complex; Genetic information processing; Protein processing
  • Endocytosis, organism-specific biosystem (from KEGG)
    Endocytosis, organism-specific biosystemEndocytosis is a mechanism for cells to remove ligands, nutrients, and plasma membrane (PM) proteins, and lipids from the cell surface, bringing them into the cell interior. Transmembrane proteins en...
  • Endocytosis, conserved biosystem (from KEGG)
    Endocytosis, conserved biosystemEndocytosis is a mechanism for cells to remove ligands, nutrients, and plasma membrane (PM) proteins, and lipids from the cell surface, bringing them into the cell interior. Transmembrane proteins en...
  • Endosomal Sorting Complex Required For Transport (ESCRT), organism-specific biosystem (from REACTOME)
    Endosomal Sorting Complex Required For Transport (ESCRT), organism-specific biosystemMany plasma membrane proteins are in a constant flux throughout the internal trafficking pathways of the cell. Some receptors are continuously internalized into recycling endosomes and returned to th...
  • Infectious disease, organism-specific biosystem (from REACTOME)
    Infectious disease, organism-specific biosystem
    Infectious disease
  • InlB-mediated entry of Listeria monocytogenes into host cell, organism-specific biosystem (from REACTOME)
    InlB-mediated entry of Listeria monocytogenes into host cell, organism-specific biosystemInlB, a cell wall protein of Listeria monocytogenes, binds MET receptor, acting as an HGF agonist (Shen et al. 2000, Veiga and Cossart 2005). Listeria monocytogenes InlB proteins dimerize through the...
  • Internalization of ErbB1, organism-specific biosystem (from Pathway Interaction Database)
    Internalization of ErbB1, organism-specific biosystem
    Internalization of ErbB1
  • Listeria monocytogenes entry into host cells, organism-specific biosystem (from REACTOME)
    Listeria monocytogenes entry into host cells, organism-specific biosystemListeria monocytogenes is a short, gram-positive, nonspore-forming motile rod. Serotypes 1/2a, 1/2b and 4b make up more than 95% of isolates from humans, with serotype 4b causing most of the food-bor...
  • Lysosome Vesicle Biogenesis, organism-specific biosystem (from REACTOME)
    Lysosome Vesicle Biogenesis, organism-specific biosystemProteins that have been synthesized, processed and sorted eventually reach the final steps of the secretory pathway. This pathway is responsible not only for proteins that are secreted from the cell ...
  • Membrane Trafficking, organism-specific biosystem (from REACTOME)
    Membrane Trafficking, organism-specific biosystemThe secretory membrane system allows a cell to regulate delivery of newly synthesized proteins, carbohydrates, and lipids to the cell surface, a necessity for growth and homeostasis. The system is ma...
  • Metabolism of proteins, organism-specific biosystem (from REACTOME)
    Metabolism of proteins, organism-specific biosystemProtein metabolism comprises the pathways of translation, post-translational modification and protein folding.
  • Negative regulation of MET activity, organism-specific biosystem (from REACTOME)
    Negative regulation of MET activity, organism-specific biosystemSignaling by MET receptor is negatively regulated mainly by MET receptor dephosphorylation or MET receptor degradation. Protein tyrosine phosphatase PTPRJ dephosphorylates MET tyrosine residue Y1349,...
  • Phagosome, organism-specific biosystem (from KEGG)
    Phagosome, organism-specific biosystemPhagocytosis is the process of taking in relatively large particles by a cell, and is a central mechanism in the tissue remodeling, inflammation, and defense against infectious agents. A phagosome is...
  • Phagosome, conserved biosystem (from KEGG)
    Phagosome, conserved biosystemPhagocytosis is the process of taking in relatively large particles by a cell, and is a central mechanism in the tissue remodeling, inflammation, and defense against infectious agents. A phagosome is...
  • Post-translational protein modification, organism-specific biosystem (from REACTOME)
    Post-translational protein modification, organism-specific biosystemAfter translation, many newly formed proteins undergo further covalent modifications that alter their functional properties and that are essentially irreversible under physiological conditions in the...
  • Signal Transduction, organism-specific biosystem (from REACTOME)
    Signal Transduction, organism-specific biosystemSignal transduction is a process in which extracellular signals elicit changes in cell state and activity. Transmembrane receptors sense changes in the cellular environment by binding ligands, such a...
  • Signaling by EGFR, organism-specific biosystem (from REACTOME)
    Signaling by EGFR, organism-specific biosystemThe epidermal growth factor receptor (EGFR) is one member of the ERBB family of transmembrane glycoprotein tyrosine receptor kinases (RTK). Binding of EGFR to its ligands induces conformational chang...
  • Signaling by MET, organism-specific biosystem (from REACTOME)
    Signaling by MET, organism-specific biosystemMET is a receptor tyrosine kinase (RTK) (Cooper et al. 1984, Park et al. 1984) activated by binding to its ligand, Hepatocyte growth factor/Scatter factor (HGF/SF) (Bottaro et al. 1991, Naldini et al...
  • Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met), organism-specific biosystem (from Pathway Interaction Database)
    Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met), organism-specific biosystem
    Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met)
  • TGF-beta Signaling Pathway, organism-specific biosystem (from WikiPathways)
    TGF-beta Signaling Pathway, organism-specific biosystemThe signal transduction mechanisms underlying the pathophysiological activities of transforming growth factor-? (TGF-?) have been extensively studied since its discovery nearly 30 years ago. TGF-? li...
  • Ub-specific processing proteases, organism-specific biosystem (from REACTOME)
    Ub-specific processing proteases, organism-specific biosystemUb-specific processing proteases (USPs) are the largest of the DUB families with more than 50 members in humans. The USP catalytic domain varies considerably in size and consists of six conserved mo...
  • Vesicle-mediated transport, organism-specific biosystem (from REACTOME)
    Vesicle-mediated transport, organism-specific biosystemThe transit of proteins and other cargo through the cell requires a cellular transport process in which transported substances are moved in membrane-bounded vesicles. Transported substances are enclo...
  • trans-Golgi Network Vesicle Budding, organism-specific biosystem (from REACTOME)
    trans-Golgi Network Vesicle Budding, organism-specific biosystemAfter passing through the Golgi complex, secretory cargo is packaged into post-Golgi transport intermediates (post-Golgi), which translocate plus-end directed along microtubules to the plasma membran...
Products Interactant Other Gene Complex Source Pubs Description

Markers

Homology

Clone Names

  • FLJ11421, FLJ39878

Gene Ontology Provided by GOA

Function Evidence Code Pubs
metal ion binding IEA
Inferred from Electronic Annotation
more info
 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein domain specific binding IPI
Inferred from Physical Interaction
more info
PubMed 
Process Evidence Code Pubs
endosomal transport NAS
Non-traceable Author Statement
more info
PubMed 
endosomal transport TAS
Traceable Author Statement
more info
 
macroautophagy TAS
Traceable Author Statement
more info
PubMed 
membrane invagination IMP
Inferred from Mutant Phenotype
more info
PubMed 
membrane organization TAS
Traceable Author Statement
more info
 
multivesicular body assembly TAS
Traceable Author Statement
more info
PubMed 
negative regulation of JAK-STAT cascade IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of cell proliferation TAS
Traceable Author Statement
more info
PubMed 
negative regulation of epidermal growth factor receptor signaling pathway TAS
Traceable Author Statement
more info
 
positive regulation of exosomal secretion IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of gene expression IMP
Inferred from Mutant Phenotype
more info
PubMed 
protein deubiquitination TAS
Traceable Author Statement
more info
 
protein localization to membrane IMP
Inferred from Mutant Phenotype
more info
PubMed 
protein targeting to lysosome IMP
Inferred from Mutant Phenotype
more info
PubMed 
regulation of MAP kinase activity IMP
Inferred from Mutant Phenotype
more info
PubMed 
regulation of protein catabolic process TAS
Traceable Author Statement
more info
PubMed 
signal transduction TAS
Traceable Author Statement
more info
PubMed 
Component Evidence Code Pubs
ESCRT-0 complex TAS
Traceable Author Statement
more info
PubMed 
cytosol IDA
Inferred from Direct Assay
more info
 
cytosol TAS
Traceable Author Statement
more info
 
early endosome IDA
Inferred from Direct Assay
more info
PubMed 
early endosome membrane IEA
Inferred from Electronic Annotation
more info
 
endosome IDA
Inferred from Direct Assay
more info
PubMed 
extracellular exosome IDA
Inferred from Direct Assay
more info
PubMed 
intracellular membrane-bounded organelle IDA
Inferred from Direct Assay
more info
 
lysosome IDA
Inferred from Direct Assay
more info
 
multivesicular body membrane IEA
Inferred from Electronic Annotation
more info
 
Preferred Names
hepatocyte growth factor-regulated tyrosine kinase substrate
Names
human growth factor-regulated tyrosine kinase substrate
protein pp110

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)

  1. NM_004712.4NP_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, DR001213
    Consensus CDS
    CCDS11784.1
    UniProtKB/Swiss-Prot
    O14964
    UniProtKB/TrEMBL
    A0A0S2Z4R4
    Related
    ENSP00000331201, OTTHUMP00000258518, ENST00000329138, OTTHUMT00000440541
    Conserved Domains (6) summary
    cd03569
    Location:4145
    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:159219
    FYVE_Hrs; FYVE domain found in hepatocyte growth factor (HGF)-regulated tyrosine kinase substrate (Hrs) and similar proteins
    pfam07223
    Location:519746
    DUF1421; Protein of unknown function (DUF1421)
    pfam12210
    Location:407501
    Hrs_helical; Hepatocyte growth factor-regulated tyrosine kinase substrate
    cd16269
    Location:531542
    GBP_C; coiled coil [structural motif]
    cl20817
    Location:486560
    GBP_C; Guanylate-binding protein, C-terminal domain

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 108 details...Open this link in a new tab

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p7 Primary Assembly

Genomic

  1. NC_000017.11 Reference GRCh38.p7 Primary Assembly

    Range
    81683932..81702121
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_011525463.2XP_011523765.1  hepatocyte growth factor-regulated tyrosine kinase substrate isoform X1

    Conserved Domains (6) summary
    cd03569
    Location:4145
    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:159219
    FYVE_Hrs; FYVE domain found in hepatocyte growth factor (HGF)-regulated tyrosine kinase substrate (Hrs) and similar proteins
    pfam07223
    Location:519749
    DUF1421; Protein of unknown function (DUF1421)
    pfam12210
    Location:407501
    Hrs_helical; Hepatocyte growth factor-regulated tyrosine kinase substrate
    cd16269
    Location:531542
    GBP_C; coiled coil [structural motif]
    cl20817
    Location:486560
    GBP_C; Guanylate-binding protein, C-terminal domain
  2. XM_017025298.1XP_016880787.1  hepatocyte growth factor-regulated tyrosine kinase substrate isoform X3

    Conserved Domains (4) summary
    pfam12210
    Location:232326
    Hrs_helical; Hepatocyte growth factor-regulated tyrosine kinase substrate
    cd16269
    Location:356367
    GBP_C; coiled coil [structural motif]
    cl20817
    Location:311385
    GBP_C; Guanylate-binding protein, C-terminal domain
    cl22851
    Location:144
    PHD_SF; PHD finger superfamily
  3. XM_017025297.1XP_016880786.1  hepatocyte growth factor-regulated tyrosine kinase substrate isoform X2

    Conserved Domains (6) summary
    cd03569
    Location:4136
    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:150210
    FYVE_Hrs; FYVE domain found in hepatocyte growth factor (HGF)-regulated tyrosine kinase substrate (Hrs) and similar proteins
    pfam07223
    Location:510737
    DUF1421; Protein of unknown function (DUF1421)
    pfam12210
    Location:398492
    Hrs_helical; Hepatocyte growth factor-regulated tyrosine kinase substrate
    cd16269
    Location:522533
    GBP_C; coiled coil [structural motif]
    cl20817
    Location:477551
    GBP_C; Guanylate-binding protein, C-terminal domain

Alternate CHM1_1.1

Genomic

  1. NC_018928.2 Alternate CHM1_1.1

    Range
    79737183..79755370
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
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