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    IRS4 insulin receptor substrate 4 [ Homo sapiens ]

    Gene ID: 8471, updated on 12-May-2012
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    Summary

    Official Symbol
    IRS4provided by HGNC
    Official Full Name
    insulin receptor substrate 4provided by HGNC
    Primary source
    HGNC:6128
    See related
    Ensembl:ENSG00000133124; HPRD:04620; MIM:603510; Vega:OTTHUMG00000022181
    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
    IRS-4; PY160
    Summary
    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]
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    Genomic context

    Location :
    Xq22.3
    Sequence :
    Chromosome: X; NC_000023.10 (107975727..107979607, complement)
    See IRS4 in Epigenomics, MapViewer

    Chromosome X - NC_000023.10Genomic Context describing neighboring genes Neighboring gene collagen, type IV, alpha 6 Neighboring gene collagen, type IV, alpha 5 Neighboring gene glyceraldehyde-3-phosphate dehydrogenase-like Neighboring gene guanylate cyclase 2F, retinal

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    Genomic regions, transcripts, and products

    Go to nucleotideGraphics FASTA GenBank

    Go to reference sequence details
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    Bibliography

    Related articles in PubMed

    1. Association between body mass index and insulin receptor substrate-4 (IRS-4) gene polymorphisms in patients with schizophrenia. Melkersson K, et al. Neuro Endocrinol Lett, 2011. PMID 22167131.
    2. Ankyrin repeat and SOCS box containing protein 4 (Asb-4) colocalizes with insulin receptor substrate 4 (IRS4) in the hypothalamic neurons and mediates IRS4 degradation. Li JY, et al. BMC Neurosci, 2011 Sep 28. PMID 21955513.
    3. A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles. Wagner SA, et al. Mol Cell Proteomics, 2011 Oct. PMID 21890473.
    4. Acetylation regulates gluconeogenesis by promoting PEPCK1 degradation via recruiting the UBR5 ubiquitin ligase. Jiang W, et al. Mol Cell, 2011 Jul 8. PMID 21726808.
    5. The insulin receptor substrate 4 gene (IRS4) is mutated in paediatric T-cell acute lymphoblastic leukaemia. Karrman K, et al. Br J Haematol, 2011 Nov. PMID 21517825.

    See all (40) citations in PubMed

    See citations in PubMed for homologs of this gene provided by HomoloGene

    GeneRIFs: Gene References Into Functions What's a GeneRIF?

    1. This study clearly demonstrates associations between body mass index and IRS-4 variants in schizophrenia patients, but not in healthy controls, pointing to a possible involvement of IRS-4 in the control of body weight in schizophrenia.
      Title: Association between body mass index and insulin receptor substrate-4 (IRS-4) gene polymorphisms in patients with schizophrenia.
    2. Study for the first time identified IRS4 mutations in T-ALL.
      Title: The insulin receptor substrate 4 gene (IRS4) is mutated in paediatric T-cell acute lymphoblastic leukaemia.
    3. IRS-4 gene is not of importance for aetiology of the vast majority of schizophrenia cases, but a single patient with schizophrenia and a mutation in IRS-4 points to that the insulin signalling system is of interest in the search for schizophrenia genes
      Title: The insulin receptor substrate-4 (IRS-4) gene and schizophrenia: no evidence for a main genetic factor, however one report of a single schizophrenia patient with a mutation.
    4. The t(X;6) in subungual exostosis results in transcriptional deregulation of the gene for insulin receptor substrate 4.
      Title: The t(X;6) in subungual exostosis results in transcriptional deregulation of the gene for insulin receptor substrate 4.
    5. Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
      Title: Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study.
    6. Observational study of gene-disease association, gene-gene interaction, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
      Title: Insulin-like growth factor axis gene polymorphisms and clinical outcomes in pancreatic cancer.
    7. Transgenic rat gene WDR6 interacts with insulin receptor substrate 4 (IRS-4) in the rat brain and may participate in signaling and regulation of feeding behavior and longevity in the brain.
      Title: Identification and characterization of an insulin receptor substrate 4-interacting protein in rat brain: implications for longevity.
    8. 53BP2S interacts and modulates the insulin signals mediated by insulin receptor substrates.
      Title: 53BP2S, interacting with insulin receptor substrates, modulates insulin signaling.
    9. The association and altered regulation of IRS proteins by Ad5E1A contribute to the adenovirus-transformed phenotype and modulates viral infection in an Akt-dependent manner.
      Title: 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.
    10. Observational study of gene-disease association. (HuGE Navigator)
      Title: Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.
    Submit: New GeneRIF Correction See all (19)
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    Phenotypes

    Review eQTL and phenotype association data in this region using PheGenI

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    Interactions

    Products Interactant Other Gene Complex Source Pubs Description
    Insulin receptor substrate 4 P46108 CRK    HPRD  PubMed  
    Insulin receptor substrate 4 P46109 CRKL    HPRD  PubMed  
    Insulin receptor substrate 4 P62993 GRB2    HPRD  PubMed  
    Insulin receptor substrate 4 P08069 IGF1R    HPRD  PubMed  
    Insulin receptor substrate 4 Insulin receptor substrate 4 IRS4    HPRD  PubMed  
    Insulin receptor substrate 4 P48039 MTNR1A    HPRD  PubMed  
    Insulin receptor substrate 4 P49286 MTNR1B    HPRD  PubMed  
    Insulin receptor substrate 4 Nischarin NISCH    HPRD  PubMed  
    Insulin receptor substrate 4 P42336 PIK3CA    HPRD  PubMed  
    Insulin receptor substrate 4 P27986 PIK3R1    HPRD  PubMed  
    Insulin receptor substrate 4 Q05513 PRKCZ    HPRD  PubMed  
    Insulin receptor substrate 4 Q06124 PTPN11    HPRD  PubMed  
    Insulin receptor substrate 4 P29350 PTPN6    HPRD  PubMed  
    Insulin receptor substrate 4 O14544 SOCS6    HPRD  PubMed  
    Insulin receptor substrate 4 O14512 SOCS7    HPRD  PubMed  
    Insulin receptor substrate 4 P61981 YWHAG    HPRD  PubMed  
    BioGRID:114048 BioGRID:106739 ALK    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:114048 BioGRID:211144 Asb4    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:114048 BioGRID:107788 CRK    BioGRID  PubMed Affinity Capture-Western; Reconstituted Complex 
    BioGRID:114048 BioGRID:107789 CRKL    BioGRID  PubMed Reconstituted Complex 
    BioGRID:114048 BioGRID:109142 GRB2    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:114048 BioGRID:115331 HDAC5    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:114048 BioGRID:109552 HSP90AA1    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:114048 BioGRID:109540 HSPA4    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:114048 BioGRID:110694 MYC    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:114048 BioGRID:116358 NISCH    BioGRID  PubMed Affinity Capture-MS; Affinity Capture-Western 
    BioGRID:114048 BioGRID:111136 PCK1    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:114048 BioGRID:111308 PIK3CA    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:114048 BioGRID:111700 PTEN    BioGRID  PubMed Affinity Capture-MS; Affinity Capture-Western 
    BioGRID:114048 BioGRID:114719 SOCS6    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:114048 BioGRID:112872 TERF1    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:114048 BioGRID:112873 TERF2    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:114048 BioGRID:113164 UBC    BioGRID  PubMed Affinity Capture-MS 
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    General gene information

    Markers

    Genotypes

    Homology

    Pathways from BioSystems

    • Adipocytokine signaling pathway, organism-specific biosystem (from KEGG)
      Adipocytokine signaling pathway, organism-specific biosystemIncreased adipocyte volume and number are positively correlated with leptin production, and negatively correlated with production of adiponectin. Leptin is an important regulator of energy intake and...
    • Adipocytokine signaling pathway, conserved biosystem (from KEGG)
      Adipocytokine signaling pathway, conserved biosystemIncreased adipocyte volume and number are positively correlated with leptin production, and negatively correlated with production of adiponectin. Leptin is an important regulator of energy intake and...
    • Adipogenesis, organism-specific biosystem (from WikiPathways)
      Adipogenesis, organism-specific biosystemThe different classess of factors involved in adipogenesis are shown. Adipogenesis is the process by which fat cells differentiate from predadipocytes to adipocytes (fat cells). Adipose tissue, compo...
    • Aldosterone-regulated sodium reabsorption, organism-specific biosystem (from KEGG)
      Aldosterone-regulated sodium reabsorption, organism-specific biosystemSodium transport across the tight epithelia of Na+ reabsorbing tissues such as the distal part of the kidney nephron and colon is the major factor determining total-body Na+ levels, and thus, long-te...
    • Aldosterone-regulated sodium reabsorption, conserved biosystem (from KEGG)
      Aldosterone-regulated sodium reabsorption, conserved biosystemSodium transport across the tight epithelia of Na+ reabsorbing tissues such as the distal part of the kidney nephron and colon is the major factor determining total-body Na+ levels, and thus, long-te...
    • Insulin Signaling, organism-specific biosystem (from WikiPathways)
      Insulin Signaling, organism-specific biosystem
      Insulin Signaling
    • Insulin signaling pathway, organism-specific biosystem (from KEGG)
      Insulin signaling pathway, organism-specific biosystemInsulin binding to its receptor results in the tyrosine phosphorylation of insulin receptor substrates (IRS) by the insulin receptor tyrosine kinase (INSR). This allows association of IRSs with the r...
    • Insulin signaling pathway, conserved biosystem (from KEGG)
      Insulin signaling pathway, conserved biosystemInsulin binding to its receptor results in the tyrosine phosphorylation of insulin receptor substrates (IRS) by the insulin receptor tyrosine kinase (INSR). This allows association of IRSs with the r...
    • Neurotrophin signaling pathway, organism-specific biosystem (from KEGG)
      Neurotrophin signaling pathway, organism-specific biosystemNeurotrophins are a family of trophic factors involved in differentiation and survival of neural cells. The neurotrophin family consists of nerve growth factor (NGF), brain derived neurotrophic facto...
    • Neurotrophin signaling pathway, conserved biosystem (from KEGG)
      Neurotrophin signaling pathway, conserved biosystemNeurotrophins are a family of trophic factors involved in differentiation and survival of neural cells. The neurotrophin family consists of nerve growth factor (NGF), brain derived neurotrophic facto...
    • Type II diabetes mellitus, organism-specific biosystem (from KEGG)
      Type II diabetes mellitus, organism-specific biosystemInsulin resistance is strongly associated with type II diabetes. "Diabetogenic" factors including FFA, TNFalpha and cellular stress induce insulin resistance through inhibition of IRS1 functions. Ser...
    • Type II diabetes mellitus, conserved biosystem (from KEGG)
      Type II diabetes mellitus, conserved biosystemInsulin resistance is strongly associated with type II diabetes. "Diabetogenic" factors including FFA, TNFalpha and cellular stress induce insulin resistance through inhibition of IRS1 functions. Ser...

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    SH3/SH2 adaptor activity TAS
    Traceable Author Statement
    more info
    		 PubMed 
    insulin receptor binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    signal transducer activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    Process Evidence Code Pubs
    signal transduction TAS
    Traceable Author Statement
    more info
    		 PubMed 
    Component Evidence Code Pubs
    plasma membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
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    General protein information

    Preferred Names
    insulin receptor substrate 4
    Names
    insulin receptor substrate 4
    pp160
    phosphoprotein of 160 kDa
    160 kDa phosphotyrosine protein
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    NCBI Reference Sequences (RefSeq)

    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.

    Genomic

    1. NG_013239.1 RefSeqGene

      Range
      5001..8881
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_003604.2 → NP_003595.1  insulin receptor substrate 4

      Status: REVIEWED

      Source sequence(s)
      AF007567
      Consensus CDS
      CCDS14544.1
      UniProtKB/Swiss-Prot
      O14654
      Related
      ENSP00000361202, OTTHUMP00000023837, ENST00000372129, OTTHUMT00000057879
      Conserved Domains (2) summary
      cd01204
      Location:231 – 331
      Blast Score: 452
      IRS_PTB; Insulin receptor substrate (IRS) Phosphotyrosine-binding domain(PTB)
      cl00273
      Location:78 – 197
      Blast Score: 359
      PH-like; Pleckstrin homology-like domain

    RefSeqs of Annotated Genomes: Build 37.3

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

    Reference GRCh37.p5 Primary Assembly

    Genomic

    1. NC_000023.10 Reference GRCh37.p5 Primary Assembly

      Range
      107975727..107979607, complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate HuRef

    Genomic

    1. AC_000155.1 Alternate HuRef

      Range
      97599533..97603519, complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
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    Related Sequences

    Nucleotide Protein
    Heading Accession and Version
    genomic AL035425.13 CAB90290.1
    genomic CH471120.2 EAX02682.1
    mRNA AF007567.1 AAC51738.1
    other-genetic BC156188.1 AAI56189.1
    other-genetic BC156977.1 AAI56978.1
    Protein Accession Links
    GenPept Link UniProtKB Link
    O14654.1 GenPept UniProtKB/Swiss-Prot:O14654
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    Additional Links

    Additional Links

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

    Chemical Information
    Molecular Biology Databases
    Research Materials
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      Supplemental Content

      Table of contents

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