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Aliases for IRS4 Gene

Aliases for IRS4 Gene

  • Insulin Receptor Substrate 4 2 3 5
  • 160 KDa Phosphotyrosine Protein 3 4
  • Phosphoprotein Of 160 KDa 3 4
  • PY160 3 4
  • IRS-4 3 4
  • Pp160 3 4

External Ids for IRS4 Gene

Previous GeneCards Identifiers for IRS4 Gene

  • GC0XM103383
  • GC0XM105051
  • GC0XM106008
  • GC0XM106747
  • GC0XM106171
  • GC0XM107781
  • GC0XM107862
  • GC0XM107975
  • GC0XM097599

Summaries for IRS4 Gene

Entrez Gene Summary for IRS4 Gene

  • IRS4 encodes the insulin receptor substrate 4, a cytoplasmic protein that contains many potential tyrosine and serine/threonine phosphorylation sites. Tyrosine-phosphorylated IRS4 protein has been shown to associate with cytoplasmic signalling molecules that contain SH2 domains. The IRS4 protein is phosphorylated by the insulin receptor tyrosine kinase upon receptor stimulation.. [provided by RefSeq, Jul 2008]

GeneCards Summary for IRS4 Gene

IRS4 (Insulin Receptor Substrate 4) is a Protein Coding gene. Diseases associated with IRS4 include Exostosis and Boutonneuse Fever. Among its related pathways are ERK Signaling and TGF-Beta Pathway. GO annotations related to this gene include signal transducer activity and insulin receptor binding. An important paralog of this gene is IRS1.

UniProtKB/Swiss-Prot for IRS4 Gene

  • Acts as an interface between multiple growth factor receptors possessing tyrosine kinase activity, such as insulin receptor, IGF1R and FGFR1, and a complex network of intracellular signaling molecules containing SH2 domains. Involved in the IGF1R mitogenic signaling pathway. Promotes the AKT1 signaling pathway and BAD phosphorylation during insulin stimulation without activation of RPS6KB1 or the inhibition of apoptosis. Interaction with GRB2 enhances insulin-stimulated mitogen-activated protein kinase activity. May be involved in nonreceptor tyrosine kinase signaling in myoblasts. Plays a pivotal role in the proliferation/differentiation of hepatoblastoma cell through EPHB2 activation upon IGF1 stimulation. May play a role in the signal transduction in response to insulin and to a lesser extent in response to IL4 and GH on mitogenesis. Plays a role in growth, reproduction and glucose homeostasis. May act as negative regulators of the IGF1 signaling pathway by suppressing the function of IRS1 and IRS2.

Gene Wiki entry for IRS4 Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for IRS4 Gene

Genomics for IRS4 Gene

Regulatory Elements for IRS4 Gene

Enhancers for IRS4 Gene
GeneHancer Identifier Score Enhancer Sources TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Other Gene Targets for Enhancer

Enhancers around IRS4 on UCSC Golden Path with GeneCards custom track

Genomic Location for IRS4 Gene

Chromosome:
X
Start:
108,719,949 bp from pter
End:
108,736,584 bp from pter
Size:
16,636 bases
Orientation:
Minus strand

Genomic View for IRS4 Gene

Genes around IRS4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
IRS4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for IRS4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for IRS4 Gene

Proteins for IRS4 Gene

  • Protein details for IRS4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    O14654-IRS4_HUMAN
    Recommended name:
    Insulin receptor substrate 4
    Protein Accession:
    O14654

    Protein attributes for IRS4 Gene

    Size:
    1257 amino acids
    Molecular mass:
    133768 Da
    Quaternary structure:
    • Interacts with SOCS6 in response to stimulatiom with either insulin or IGF1 (By similarity). Interacts with CRK and CRKL. Interaction with CRK is stronger than with CRKL. Interacts with CRK via the phosphorylated YXXM motifs. Interacts with GRB2 and PIK3R1. Interacts with PLC-gamma, SHC1, PTK6, PPP4C and NISCH.

neXtProt entry for IRS4 Gene

Proteomics data for IRS4 Gene at MOPED

Post-translational modifications for IRS4 Gene

  • Phosphorylated on tyrosine residues in response to both insulin and IGF1 signaling. Phosphorylated on Tyr-921 in response to FGF2 signaling. Phosphorylation of Tyr-921 is required for GRB2, phospholipase C-gamma and phosphatidylinositol 3-kinase interaction.
  • Ubiquitination at Lys 240, Lys 618, Lys 803, Lys 835, Lys 843, and Lys 928
  • Modification sites at PhosphoSitePlus

Other Protein References for IRS4 Gene

ENSEMBL proteins:
REFSEQ proteins:

Antibody Products

  • Abcam antibodies for IRS4

No data available for DME Specific Peptides for IRS4 Gene

Domains & Families for IRS4 Gene

Protein Domains for IRS4 Gene

Suggested Antigen Peptide Sequences for IRS4 Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

O14654

UniProtKB/Swiss-Prot:

IRS4_HUMAN :
  • Contains 1 IRS-type PTB domain.
Domain:
  • Contains 1 IRS-type PTB domain.
  • Contains 1 PH domain.
genes like me logo Genes that share domains with IRS4: view

No data available for Gene Families for IRS4 Gene

Function for IRS4 Gene

Molecular function for IRS4 Gene

UniProtKB/Swiss-Prot Function:
Acts as an interface between multiple growth factor receptors possessing tyrosine kinase activity, such as insulin receptor, IGF1R and FGFR1, and a complex network of intracellular signaling molecules containing SH2 domains. Involved in the IGF1R mitogenic signaling pathway. Promotes the AKT1 signaling pathway and BAD phosphorylation during insulin stimulation without activation of RPS6KB1 or the inhibition of apoptosis. Interaction with GRB2 enhances insulin-stimulated mitogen-activated protein kinase activity. May be involved in nonreceptor tyrosine kinase signaling in myoblasts. Plays a pivotal role in the proliferation/differentiation of hepatoblastoma cell through EPHB2 activation upon IGF1 stimulation. May play a role in the signal transduction in response to insulin and to a lesser extent in response to IL4 and GH on mitogenesis. Plays a role in growth, reproduction and glucose homeostasis. May act as negative regulators of the IGF1 signaling pathway by suppressing the function of IRS1 and IRS2.
UniProtKB/Swiss-Prot Induction:
Down-regulated by PPP4C in a phosphatase activity-dependent manner.

Gene Ontology (GO) - Molecular Function for IRS4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005515 protein binding IEA,IPI 11316748
genes like me logo Genes that share ontologies with IRS4: view
genes like me logo Genes that share phenotypes with IRS4: view

Animal Model Products

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Animal Models , Transcription Factor Targets and HOMER Transcription for IRS4 Gene

Localization for IRS4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for IRS4 Gene

Cell membrane; Peripheral membrane protein; Cytoplasmic side.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for IRS4 Gene COMPARTMENTS Subcellular localization image for IRS4 gene
Compartment Confidence
plasma membrane 5
cytosol 4
endoplasmic reticulum 2
extracellular 2
golgi apparatus 1
lysosome 1
nucleus 1
vacuole 1

No data available for Gene Ontology (GO) - Cellular Components for IRS4 Gene

Pathways & Interactions for IRS4 Gene

genes like me logo Genes that share pathways with IRS4: view

SIGNOR curated interactions for IRS4 Gene

Is activated by:

Gene Ontology (GO) - Biological Process for IRS4 Gene

None

Drugs & Compounds for IRS4 Gene

(1) Drugs for IRS4 Gene - From: Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials

(3) Additional Compounds for IRS4 Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with IRS4: view

Transcripts for IRS4 Gene

mRNA/cDNA for IRS4 Gene

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

Unigene Clusters for IRS4 Gene

Insulin receptor substrate 4:
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for IRS4 Gene

No ASD Table

Relevant External Links for IRS4 Gene

GeneLoc Exon Structure for
IRS4
ECgene alternative splicing isoforms for
IRS4

Expression for IRS4 Gene

mRNA expression in normal human tissues for IRS4 Gene

Protein differential expression in normal tissues from HIPED for IRS4 Gene

This gene is overexpressed in Pancreatic juice (51.6) and Heart (17.4).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MOPED, and MaxQB for IRS4 Gene



SOURCE GeneReport for Unigene cluster for IRS4 Gene Hs.460872

mRNA Expression by UniProt/SwissProt for IRS4 Gene

O14654-IRS4_HUMAN
Tissue specificity: Expressed in myoblasts. Expressed in liver and hepatocellular carcinoma.
genes like me logo Genes that share expression patterns with IRS4: view

Protein tissue co-expression partners for IRS4 Gene

Primer Products

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery and mRNA differential expression in normal tissues for IRS4 Gene

Orthologs for IRS4 Gene

This gene was present in the common ancestor of animals.

Orthologs for IRS4 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia IRS4 35
  • 99.01 (n)
  • 98.39 (a)
cow
(Bos Taurus)
Mammalia IRS4 36
  • 81 (a)
OneToOne
dog
(Canis familiaris)
Mammalia IRS4 36
  • 79 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia IRS4 36
  • 30 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Irs4 36
  • 72 (a)
OneToOne
chicken
(Gallus gallus)
Aves IRS4 36
  • 28 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia IRS4 36
  • 32 (a)
OneToOne
zebrafish
(Danio rerio)
Actinopterygii IRS4 (1 of 2) 36
  • 27 (a)
OneToMany
irs4a 36
  • 25 (a)
OneToMany
fruit fly
(Drosophila melanogaster)
Insecta chico 37
  • 32 (a)
chico 36
  • 18 (a)
OneToMany
sea squirt
(Ciona savignyi)
Ascidiacea -- 36
  • 33 (a)
OneToMany
Species with no ortholog for IRS4:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • 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)
  • platypus (Ornithorhynchus anatinus)
  • rainbow trout (Oncorhynchus mykiss)
  • rat (Rattus norvegicus)
  • 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)
  • tropical clawed frog (Silurana tropicalis)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for IRS4 Gene

ENSEMBL:
Gene Tree for IRS4 (if available)
TreeFam:
Gene Tree for IRS4 (if available)

Paralogs for IRS4 Gene

Paralogs for IRS4 Gene

genes like me logo Genes that share paralogs with IRS4: view

Variants for IRS4 Gene

Sequence variations from dbSNP and Humsavar for IRS4 Gene

SNP ID Clin Chr 0X pos Sequence Context AA Info Type
VAR_038042 A colorectal cancer sample
VAR_038043 A colorectal cancer sample
VAR_038044 A colorectal cancer sample
VAR_051078 -
VAR_051079 -

Structural Variations from Database of Genomic Variants (DGV) for IRS4 Gene

Variant ID Type Subtype PubMed ID
nsv519041 CNV Gain 19592680

Variation tolerance for IRS4 Gene

Residual Variation Intolerance Score: 34.6% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 5.18; 69.64% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for IRS4 Gene

Human Gene Mutation Database (HGMD)
IRS4

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for IRS4 Gene

Disorders for IRS4 Gene

MalaCards: The human disease database

(3) MalaCards diseases for IRS4 Gene - From: DISEASES and GeneCards

Disorder Aliases PubMed IDs
exostosis
  • bone spur
boutonneuse fever
  • south african tick-bite fever
cribriform carcinoma
  • ductal carcinoma, cribriform type
- elite association - COSMIC cancer census association via MalaCards
Search IRS4 in MalaCards View complete list of genes associated with diseases

Relevant External Links for IRS4

Genetic Association Database (GAD)
IRS4
Human Genome Epidemiology (HuGE) Navigator
IRS4
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
IRS4
genes like me logo Genes that share disorders with IRS4: view

No data available for UniProtKB/Swiss-Prot and Genatlas for IRS4 Gene

Publications for IRS4 Gene

  1. Characterization of insulin receptor substrate 4 in human embryonic kidney 293 cells. (PMID: 9553137) Fantin V.R. … Lavan B.E. (J. Biol. Chem. 1998) 2 3 4 23 67
  2. A novel 160-kDa phosphotyrosine protein in insulin-treated embryonic kidney cells is a new member of the insulin receptor substrate family. (PMID: 9261155) Lavan B.E. … Lienhard G.E. (J. Biol. Chem. 1997) 2 3 23
  3. Adenovirus 5 E1A is responsible for increased expression of insulin receptor substrate 4 in established adenovirus 5-transformed cell lines and interacts with IRS components activating the PI3 kinase/Akt signalling pathway. (PMID: 19029952) Shimwell N.J. … Grand R.J. (Oncogene 2009) 3 23
  4. Insulin receptor substrate 4 couples the leptin receptor to multiple signaling pathways. (PMID: 18165436) Wauman J. … Tavernier J. (Mol. Endocrinol. 2008) 3 23
  5. Role of insulin receptor substrate-4 in IGF-I-stimulated HEPG2 proliferation. (PMID: 17408801) Cuevas E.P. … Guijarro L.G. (J. Hepatol. 2007) 3 23

Products for IRS4 Gene

Sources for IRS4 Gene

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