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    IRS1 insulin receptor substrate 1 [ Homo sapiens (human) ]

    Gene ID: 3667, updated on 19-May-2024

    Summary

    Official Symbol
    IRS1provided by HGNC
    Official Full Name
    insulin receptor substrate 1provided by HGNC
    Primary source
    HGNC:HGNC:6125
    See related
    Ensembl:ENSG00000169047 MIM:147545; AllianceGenome:HGNC:6125
    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
    HIRS-1
    Summary
    This gene encodes a protein which is phosphorylated by insulin receptor tyrosine kinase. Mutations in this gene are associated with type II diabetes and susceptibility to insulin resistance. [provided by RefSeq, Nov 2009]
    Expression
    Broad expression in thyroid (RPKM 15.0), endometrium (RPKM 12.3) and 22 other tissues See more
    Orthologs
    NEW
    Try the new Gene table
    Try the new Transcript table

    Genomic context

    See IRS1 in Genome Data Viewer
    Location:
    2q36.3
    Exon count:
    4
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 2 NC_000002.12 (226731312..226799820, complement)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 2 NC_060926.1 (227214139..227282678, complement)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 2 NC_000002.11 (227596028..227664536, complement)

    Chromosome 2 - NC_000002.12Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105373915 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr2:227342641-227343191 Neighboring gene NANOG hESC enhancer GRCh37_chr2:227348646-227349147 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:227513913-227514828 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:227514829-227515742 Neighboring gene MPRA-validated peak4063 silencer Neighboring gene MPRA-validated peak4064 silencer Neighboring gene MPRA-validated peak4065 silencer Neighboring gene Sharpr-MPRA regulatory region 3334 Neighboring gene microRNA 5702 Neighboring gene MPRA-validated peak4066 silencer Neighboring gene Sharpr-MPRA regulatory region 11623 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12389 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:227661675-227662624 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12390 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12391 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12392 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12393 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr2:227677874-227678445 Neighboring gene Sharpr-MPRA regulatory region 3963 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12394 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 17195 Neighboring gene rhomboid domain containing 1 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12395 Neighboring gene MPRA-validated peak4067 silencer Neighboring gene small nucleolar RNA SNORA48 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 17196 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr2:227859794-227860993 Neighboring gene collagen type IV alpha 4 chain Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:227929821-227930408 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:228028248-228029149 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12397 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:228050272-228050810 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr2:228055439-228056638 Neighboring gene collagen type IV alpha 3 chain Neighboring gene MFF divergent transcript

    Genomic regions, transcripts, and products

    Expression

    • 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 Apr 4 07:08:55 2018

    Bibliography

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?

    Phenotypes

    Associated conditions

    Description Tests
    Type 2 diabetes mellitus
    MedGen: C0011860 OMIM: 125853 GeneReviews: WFS1 Spectrum Disorder
    Compare labs

    EBI GWAS Catalog

    Description
    A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance.
    EBI GWAS Catalog
    Biological, clinical and population relevance of 95 loci for blood lipids.
    EBI GWAS Catalog
    Discovery and refinement of loci associated with lipid levels.
    EBI GWAS Catalog
    Genetic variant near IRS1 is associated with type 2 diabetes, insulin resistance and hyperinsulinemia.
    EBI GWAS Catalog
    Genetic variation near IRS1 associates with reduced adiposity and an impaired metabolic profile.
    EBI GWAS Catalog
    Genome-wide association for abdominal subcutaneous and visceral adipose reveals a novel locus for visceral fat in women.
    EBI GWAS Catalog
    Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility.
    EBI GWAS Catalog
    Novel loci for adiponectin levels and their influence on type 2 diabetes and metabolic traits: a multi-ethnic meta-analysis of 45,891 individuals.
    EBI GWAS Catalog
    Sex-stratified genome-wide association studies including 270,000 individuals show sexual dimorphism in genetic loci for anthropometric traits.
    EBI GWAS Catalog
    Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis.
    EBI GWAS Catalog

    Pathways from PubChem

    Interactions

    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

    Markers

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables SH2 domain binding ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    enables insulin receptor binding IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    enables insulin receptor binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables insulin-like growth factor receptor binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables phosphatidylinositol 3-kinase binding IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    enables phosphatidylinositol 3-kinase binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables phosphatidylinositol 3-kinase binding ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    enables phosphotyrosine residue binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables protein kinase C binding ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    enables signaling adaptor activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables signaling receptor complex adaptor activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables transmembrane receptor protein tyrosine kinase adaptor activity ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    Process Evidence Code Pubs
    involved_in cellular response to fatty acid ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in cellular response to insulin stimulus IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in cytokine-mediated signaling pathway IGI
    Inferred from Genetic Interaction
    more info
    PubMed 
    involved_in glucose homeostasis TAS
    Traceable Author Statement
    more info
    PubMed 
    involved_in insulin receptor signaling pathway IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    involved_in insulin receptor signaling pathway IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in insulin receptor signaling pathway IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in insulin receptor signaling pathway IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    involved_in insulin-like growth factor receptor signaling pathway IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    involved_in negative regulation of insulin receptor signaling pathway ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in negative regulation of insulin secretion IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in phosphatidylinositol 3-kinase/protein kinase B signal transduction IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in positive regulation of cell population proliferation NAS
    Non-traceable Author Statement
    more info
    PubMed 
    involved_in positive regulation of fatty acid beta-oxidation IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in positive regulation of glucose import IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in positive regulation of glucose import IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in positive regulation of glucose metabolic process IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in positive regulation of glycogen biosynthetic process IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in positive regulation of glycogen biosynthetic process NAS
    Non-traceable Author Statement
    more info
    PubMed 
    involved_in positive regulation of insulin receptor signaling pathway IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in positive regulation of insulin receptor signaling pathway ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in response to insulin IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in signal transduction TAS
    Traceable Author Statement
    more info
    PubMed 
    Component Evidence Code Pubs
    located_in caveola IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in cytoplasm ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    is_active_in cytosol IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
     
    located_in cytosol TAS
    Traceable Author Statement
    more info
     
    part_of insulin receptor complex ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    located_in intracellular membrane-bounded organelle ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    located_in nucleoplasm IDA
    Inferred from Direct Assay
    more info
     
    located_in nucleus ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    is_active_in plasma membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    located_in plasma membrane IDA
    Inferred from Direct Assay
    more info
     
    located_in plasma membrane TAS
    Traceable Author Statement
    more info
     

    General protein information

    Preferred Names
    insulin receptor substrate 1

    NCBI Reference Sequences (RefSeq)

    NEW Try the new Transcript table

    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_015830.1 RefSeqGene

      Range
      3971..72479
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_005544.3NP_005535.1  insulin receptor substrate 1

      See identical proteins and their annotated locations for NP_005535.1

      Status: REVIEWED

      Source sequence(s)
      AC010735, BC053895
      Consensus CDS
      CCDS2463.1
      UniProtKB/Swiss-Prot
      P35568
      Related
      ENSP00000304895.4, ENST00000305123.6
      Conserved Domains (2) summary
      cd01204
      Location:160263
      PTB_IRS; Insulin receptor substrate phosphotyrosine-binding domain (PTBi)
      cd01257
      Location:11118
      PH_IRS; Insulin receptor substrate (IRS) pleckstrin homology (PH) domain

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000002.12 Reference GRCh38.p14 Primary Assembly

      Range
      226731312..226799820 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047444224.1XP_047300180.1  insulin receptor substrate 1 isoform X1

      UniProtKB/Swiss-Prot
      P35568
    2. XM_047444223.1XP_047300179.1  insulin receptor substrate 1 isoform X1

      UniProtKB/Swiss-Prot
      P35568

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060926.1 Alternate T2T-CHM13v2.0

      Range
      227214139..227282678 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054341875.1XP_054197850.1  insulin receptor substrate 1 isoform X1

      UniProtKB/Swiss-Prot
      P35568