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HGS Gene(Protein Coding)

Hepatocyte Growth Factor-Regulated Tyrosine Kinase Substrate

GCID:
GC17P081683
GIFtS:
63
Genes Participants
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Aliases for HGS Gene

Aliases for HGS Gene

  • Hepatocyte Growth Factor-Regulated Tyrosine Kinase Substrate 2 3 5
  • Protein Pp110 3 4
  • HRS 3 4
  • Human Growth Factor-Regulated Tyrosine Kinase Substrate 3

External Ids for HGS Gene

Previous GeneCards Identifiers for HGS Gene

  • GC17U990142
  • GC17P080211
  • GC17P080346
  • GC17P077261
  • GC17P079651
  • GC17P075097

Summaries for HGS Gene

Entrez Gene Summary for HGS Gene

  • 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]

GeneCards Summary for HGS Gene

HGS (Hepatocyte Growth Factor-Regulated Tyrosine Kinase Substrate) is a Protein Coding gene. Diseases associated with HGS include Hypertonia. Among its related pathways are Clathrin derived vesicle budding and HIV Life Cycle. GO annotations related to this gene include protein domain specific binding. An important paralog of this gene is WDFY2.

UniProtKB/Swiss-Prot for HGS Gene

  • 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.

Gene Wiki entry for HGS Gene

No data available for CIViC summary , Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for HGS Gene

Genomics for HGS Gene

Products:

  1. Regulatory Element

Regulatory Elements for HGS Gene


Enhancers around HGS on UCSC Golden Path with GeneCards custom track

Promoters for HGS Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters
ENSR00000099462 574 1801 PKNOX1 ARNT ARID4B SIN3A DMAP1 ZNF2 SLC30A9 ZNF143 FOS SP3

Transcription factor binding sites by QIAGEN in the HGS gene promoter:

Genomic Location for HGS Gene

Chromosome:
17
Start:
81,683,326 bp from pter
End:
81,703,138 bp from pter
Size:
19,813 bases
Orientation:
Plus strand

Genomic View for HGS Gene

Genes around HGS on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
HGS Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for HGS Gene
GeneLoc Logo Genomic Neighborhood • Exon Structure • Gene Density

RefSeq DNA sequence for HGS Gene

Proteins for HGS Gene

Products:

  1. Antibody
  2. Protein
  3. Assay

  • Protein details for HGS Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    O14964-HGS_HUMAN
    Recommended name:
    Hepatocyte growth factor-regulated tyrosine kinase substrate
    Protein Accession:
    O14964
    Secondary Accessions:
    • Q9NR36

    Protein attributes for HGS Gene

    Size:
    777 amino acids
    Molecular mass:
    86192 Da
    Quaternary structure:
    • Interacts with TRAK1. Interacts with TRAK2 (By similarity). Interacts with TRAK1. 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. Interacts with SNAP25; the interaction is direct and decreases with addition of increasing concentrations of free calcium. Interacts with SNX1; the interaction is direct. Component of a 550 kDa membrane complex at least composed of HGS and SNX1 but excluding EGFR. Component of the CART complex, at least composed of ACTN4, HGS/HRS, MYO5B and TRIM3. Interacts (via UIM domain) with UBQLN1 (via ubiquitin-like domain) (By similarity). Interacts with ARRDC3 (PubMed:23208550). Identified in a complex containing at least ARRDC4, V2R and HGS (PubMed:23236378).

    Three dimensional structures from OCA and Proteopedia for HGS Gene

    Alternative splice isoforms for HGS Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for HGS Gene

Protein Expression for HGS Gene

See protein expression from ProteomicsDB, MOPED, PaxDb, and MaxQB

Post-translational modifications for HGS Gene

  • Phosphorylated on Tyr-334. A minor site of phosphorylation on Tyr-329 is detected (By similarity). Phosphorylation occurs in response to EGF, IL-2, GM-CSF and HGF.
  • Ubiquitinated by ITCH.
  • Ubiquitination at posLast=8686, posLast=9393, isoforms=297, posLast=126126, posLast=136136, isoforms=2192, isoforms=2202, posLast=207207, isoforms=2251, isoforms=2473, posLast=513513, and posLast=551551
  • Modification sites at PhosphoSitePlus

Other Protein References for HGS Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for HGS Gene

Domains & Families for HGS Gene

Gene Families for HGS Gene

HGNC:

Protein Domains for HGS Gene

InterPro:
Blocks:
ProtoNet:

Suggested Antigen Peptide Sequences for HGS Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

O14964

UniProtKB/Swiss-Prot:

HGS_HUMAN :
  • Has a double-sided UIM that can bind 2 ubiquitin molecules, one on each side of the helix.
Domain:
  • Has a double-sided UIM that can bind 2 ubiquitin molecules, one on each side of the helix.
  • 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 PtdIns(3)P-enriched membranes is substantially increased in acidic conditions.
genes like me logo Genes that share domains with HGS: view

Function for HGS Gene

Products:

  1. Animal Model
  2. CRISPR
  3. miRNA
  4. Inhibitory RNA
  5. Clone
  6. Cell Line
  7. Flow Cytometry

Molecular function for HGS Gene

GENATLAS Biochemistry:
hepatocyte growth factor-regulated tyrosine kinase substrate,inhibiting the cytokine cell growth function induced by STAM
UniProtKB/Swiss-Prot Function:
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.

Gene Ontology (GO) - Molecular Function for HGS Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005515 protein binding IPI 10861283
GO:0016301 kinase activity IEA --
GO:0019904 protein domain specific binding IPI 11984006
GO:0046872 metal ion binding IEA --
genes like me logo Genes that share ontologies with HGS: view
genes like me logo Genes that share phenotypes with HGS: view

Animal Models for HGS Gene

MGI Knock Outs for HGS:

Animal Model Products

CRISPR Products

Inhibitory RNA Products

Flow Cytometry Products

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for HGS Gene

Localization for HGS Gene

Subcellular locations from UniProtKB/Swiss-Prot for HGS Gene

Cytoplasm. Early endosome membrane; Peripheral membrane protein; Cytoplasmic side. Endosome, multivesicular body membrane; Peripheral membrane protein. Note=Colocalizes with UBQLN1 in ubiquitin-rich cytoplasmic aggregates that are not endocytic compartments. {ECO:0000269 PubMed:16159959}.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for HGS gene
Compartment Confidence
extracellular 5
cytosol 5
lysosome 5
endosome 5
plasma membrane 2
nucleus 2
golgi apparatus 2
mitochondrion 1

Gene Ontology (GO) - Cellular Components for HGS Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005622 intracellular IEA --
GO:0005737 cytoplasm IEA --
GO:0005764 lysosome IDA --
GO:0005768 endosome IDA 15611048
GO:0005769 early endosome IDA 10861283
genes like me logo Genes that share ontologies with HGS: view

Pathways & Interactions for HGS Gene

genes like me logo Genes that share pathways with HGS: view

SIGNOR curated interactions for HGS Gene

Activates:
Is activated by:

Gene Ontology (GO) - Biological Process for HGS Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006622 protein targeting to lysosome IMP 18767904
GO:0006810 transport IEA --
GO:0006886 intracellular protein transport IEA --
GO:0007165 signal transduction TAS 9407053
GO:0008285 negative regulation of cell proliferation TAS 9407053
genes like me logo Genes that share ontologies with HGS: view

Drugs & Compounds for HGS Gene

Products:

  1. Drug

(7) Drugs for HGS Gene - From: DrugBank and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Citric Acid Vet_approved Nutra Agonist, Activator, Target 1160

(7) Additional Compounds for HGS Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with HGS: view

Transcripts for HGS Gene

Products:

  1. CRISPR
  2. miRNA
  3. Inhibitory RNA
  4. Clone
  5. Flow Cytometry

mRNA/cDNA for HGS Gene

(4) REFSEQ mRNAs :
(7) Additional mRNA sequences :
(715) Selected AceView cDNA sequences:
(17) Ensembl transcripts including schematic representations, and UCSC links where relevant :

Unigene Clusters for HGS Gene

Hepatocyte growth factor-regulated tyrosine kinase substrate:
Representative Sequences:

CRISPR Products

Inhibitory RNA Products

Flow Cytometry Products

Alternative Splicing Database (ASD) splice patterns (SP) for HGS Gene

ExUns: 1 ^ 2a · 2b ^ 3 ^ 4a · 4b ^ 5 ^ 6a · 6b ^ 7a · 7b ^ 8a · 8b ^ 9 ^ 10 ^ 11a · 11b ^ 12 ^ 13a · 13b ^ 14 ^ 15 ^ 16a · 16b ^ 17 ^ 18a ·
SP1: - - - - -
SP2: - - - - -
SP3: - - - -
SP4: -
SP5: - - -
SP6: -
SP7:
SP8:
SP9:
SP10:
SP11:

ExUns: 18b · 18c ^ 19 ^ 20a · 20b · 20c ^ 21a · 21b ^ 22 ^ 23 ^ 24a · 24b · 24c · 24d
SP1:
SP2: - - -
SP3:
SP4:
SP5:
SP6:
SP7: -
SP8:
SP9:
SP10: -
SP11:

Relevant External Links for HGS Gene

GeneLoc Exon Structure for
HGS
ECgene alternative splicing isoforms for
HGS

Expression for HGS Gene

Products:

  1. Primer

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for HGS Gene

mRNA expression in normal human tissues for HGS Gene
mRNA expression by BioGPS for HGS GenemRNA expression by GTEx for HGS Gene

Protein differential expression in normal tissues from HIPED for HGS Gene

This gene is overexpressed in Heart (7.8).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MaxQB, and MOPED for HGS Gene



Protein tissue co-expression partners for HGS Gene

- Elite partner

NURSA nuclear receptor signaling pathways regulating expression of HGS Gene:

HGS

SOURCE GeneReport for Unigene cluster for HGS Gene:

Hs.661056

mRNA Expression by UniProt/SwissProt for HGS Gene:

O14964-HGS_HUMAN
Tissue specificity: Ubiquitous expression in adult and fetal tissues with higher expression in testis and peripheral blood leukocytes.

Evidence on tissue expression from TISSUES for HGS Gene

  • Skin(4.7)
  • Nervous system(4.7)
  • Liver(4.4)
  • Muscle(2.6)
  • Blood(2.2)
  • Eye(2.1)
  • Heart(2.1)
  • Intestine(2.1)
  • Kidney(2.1)
genes like me logo Genes that share expression patterns with HGS: view

Primer Products

No data available for mRNA differential expression in normal tissues and Phenotype-based relationships between genes and organs from Gene ORGANizer for HGS Gene

Orthologs for HGS Gene

This gene was present in the common ancestor of animals and fungi.

Orthologs for HGS Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
 Mammalia HGS 34 35
  • 98.96 (n)
oppossum
(Monodelphis domestica)
 Mammalia HGS 35
  • 89 (a)
 OneToOne
dog
(Canis familiaris)
 Mammalia HGS 34 35
  • 88.06 (n)
cow
(Bos Taurus)
 Mammalia HGS 34 35
  • 87.77 (n)
mouse
(Mus musculus)
 Mammalia Hgs 34 16 35
  • 86.98 (n)
rat
(Rattus norvegicus)
 Mammalia Hgs 34
  • 86.81 (n)
platypus
(Ornithorhynchus anatinus)
 Mammalia -- 35
  • 42 (a)
 ManyToMany
chicken
(Gallus gallus)
 Aves HGS 34 35
  • 79.29 (n)
lizard
(Anolis carolinensis)
 Reptilia HGS 35
  • 82 (a)
 OneToOne
tropical clawed frog
(Silurana tropicalis)
 Amphibia hgs 34
  • 73.61 (n)
African clawed frog
(Xenopus laevis)
 Amphibia MGC68804 34
zebrafish
(Danio rerio)
 Actinopterygii hgs 34 35
  • 78.62 (n)
wufi34f05 34
African malaria mosquito
(Anopheles gambiae)
 Insecta AgaP_AGAP008887 34
  • 61.05 (n)
fruit fly
(Drosophila melanogaster)
 Insecta Hrs 36 34 35
  • 58.71 (n)
worm
(Caenorhabditis elegans)
 Secernentea hgrs-1 34 35
  • 46.77 (n)
baker's yeast
(Saccharomyces cerevisiae)
 Saccharomycetes VPS27 35 37
  • 18 (a)
 OneToMany
sea squirt
(Ciona savignyi)
 Ascidiacea -- 35
  • 46 (a)
 OneToOne
Species where no ortholog for HGS was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for HGS Gene

ENSEMBL:
Gene Tree for HGS (if available)
TreeFam:
Gene Tree for HGS (if available)

Paralogs for HGS Gene

Paralogs for HGS Gene

(3) SIMAP similar genes for HGS Gene using alignment to 8 proteins:

genes like me logo Genes that share paralogs with HGS: view

Variants for HGS Gene

Sequence variations from dbSNP and Humsavar for HGS Gene

SNP ID Clin Chr 17 pos Sequence Context AA Info Type
rs863223352 Likely pathogenic 81,683,794(-) GAGCC(G/T)CGGCG nc-transcript-variant, upstream-variant-2KB, reference, missense, utr-variant-5-prime
rs1000299525 -- 81,700,930(+) CCTCC(C/T)CCTCC intron-variant
rs1000633808 -- 81,699,617(+) GACAG(A/G)GTTTT intron-variant
rs1000782977 -- 81,697,574(+) GACGG(C/G)GTCTG intron-variant
rs1000835485 -- 81,697,421(+) TGTCC(C/T)AAGAG intron-variant

Structural Variations from Database of Genomic Variants (DGV) for HGS Gene

Variant ID Type Subtype PubMed ID
esv26223 CNV gain+loss 19812545
nsv1113896 CNV deletion 24896259
nsv428351 CNV gain 18775914
nsv470620 CNV loss 18288195
nsv828128 CNV loss 20364138
nsv952390 CNV deletion 24416366

Variation tolerance for HGS Gene

Residual Variation Intolerance Score: 6.52% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 3.24; 52.60% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for HGS Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
HGS

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for HGS Gene

Disorders for HGS Gene

MalaCards: The human disease database

(1) MalaCards diseases for HGS Gene - From: GeneCards

Disorder Aliases PubMed IDs
hypertonia
- elite association - COSMIC cancer census association via MalaCards
Search HGS in MalaCards View complete list of genes associated with diseases

Relevant External Links for HGS

Genetic Association Database (GAD)
HGS
Human Genome Epidemiology (HuGE) Navigator
HGS
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
HGS
genes like me logo Genes that share disorders with HGS: view

No data available for UniProtKB/Swiss-Prot and Genatlas for HGS Gene

Publications for HGS Gene

  1. Human Hrs, a tyrosine kinase substrate in growth factor-stimulated cells: cDNA cloning and mapping of the gene to chromosome 17. (PMID: 9630564) Lu L. … Kitamura N. (Gene 1998) 2 3 4 22 64
  2. Hrs is associated with STAM, a signal-transducing adaptor molecule. Its suppressive effect on cytokine-induced cell growth. (PMID: 9407053) Asao H. … Sugamura K. (J. Biol. Chem. 1997) 2 3 4 22 64
  3. STAM and Hrs are subunits of a multivalent ubiquitin-binding complex on early endosomes. (PMID: 12551915) Bache K.G. … Stenmark H. (J. Biol. Chem. 2003) 3 4 22 64
  4. HIV Gag mimics the Tsg101-recruiting activity of the human Hrs protein. (PMID: 12900394) Pornillos O. … Sundquist W.I. (J. Cell Biol. 2003) 3 4 22 64
  5. The E3 ubiquitin ligase AIP4 mediates ubiquitination and sorting of the G protein-coupled receptor CXCR4. (PMID: 14602072) Marchese A. … Benovic J.L. (Dev. Cell 2003) 3 4 22 64

Products for HGS Gene

  • Addgene plasmids for HGS

Sources for HGS Gene

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