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Aliases for IRS1 Gene

Aliases for IRS1 Gene

  • Insulin Receptor Substrate 1 2 3
  • IRS-1 3 4
  • HIRS-1 3

External Ids for IRS1 Gene

Previous GeneCards Identifiers for IRS1 Gene

  • GC02M225622
  • GC02M226321
  • GC02M227563
  • GC02M227802
  • GC02M227425
  • GC02M227308
  • GC02M219439

Summaries for IRS1 Gene

Entrez Gene Summary for IRS1 Gene

  • 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]

GeneCards Summary for IRS1 Gene

IRS1 (Insulin Receptor Substrate 1) is a Protein Coding gene. Diseases associated with IRS1 include leprechaunism and diabetes mellitus, noninsulin-dependent. Among its related pathways are PI3K-Akt signaling pathway and PI-3K cascade. GO annotations related to this gene include phospholipid binding and protein kinase C binding. An important paralog of this gene is IRS4.

UniProtKB/Swiss-Prot for IRS1 Gene

  • May mediate the control of various cellular processes by insulin. When phosphorylated by the insulin receptor binds specifically to various cellular proteins containing SH2 domains such as phosphatidylinositol 3-kinase p85 subunit or GRB2. Activates phosphatidylinositol 3-kinase when bound to the regulatory p85 subunit (By similarity).

Gene Wiki entry for IRS1 Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for IRS1 Gene

Genomics for IRS1 Gene

Regulatory Elements for IRS1 Gene

Epigenetics Products

  • DNA Methylation CpG Assay Predesigned for Pyrosequencing in human,mouse,rat

Genomic Location for IRS1 Gene

226,731,317 bp from pter
226,799,829 bp from pter
68,513 bases
Minus strand

Genomic View for IRS1 Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for IRS1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for IRS1 Gene

Proteins for IRS1 Gene

  • Protein details for IRS1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Recommended name:
    Insulin receptor substrate 1
    Protein Accession:
    Secondary Accessions:

    Protein attributes for IRS1 Gene

    1242 amino acids
    Molecular mass:
    131591 Da
    Quaternary structure:
    • Interacts with UBTF and PIK3CA (By similarity). Interacts (via phosphorylated YXXM motifs) with PIK3R1 (By similarity). Interacts with ROCK1 and FER (By similarity). Interacts (via PH domain) with PHIP (By similarity). Interacts with GRB2 (By similarity). Interacts with SOCS7. Interacts (via IRS-type PTB domain) with IGF1R and INSR (via the tyrosine-phosphorylated NPXY motif). Interacts with ALK. Interacts with EIF2AK2/PKR (By similarity).

    Three dimensional structures from OCA and Proteopedia for IRS1 Gene

neXtProt entry for IRS1 Gene

Proteomics data for IRS1 Gene at MOPED

Post-translational modifications for IRS1 Gene

  • Serine phosphorylation of IRS1 is a mechanism for insulin resistance. Ser-312 phosphorylation inhibits insulin action through disruption of IRS1 interaction with the insulin receptor (By similarity). Phosphorylation of Tyr-896 is required for GRB2-binding (By similarity). Phosphorylated by ALK. Phosphorylated at Ser-270, Ser-307, Ser-636 and Ser-1101 by RPS6KB1; phosphorylation induces accelerated degradation of IRS1.
  • Ubiquitinated by the Cul7-RING(FBXW8) complex in a mTOR-dependent manner, leading to its degradation: the Cul7-RING(FBXW8) complex recognizes and binds IRS1 previously phosphorylated by S6 kinase (RPS6KB1 or RPS6KB2).
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for IRS1 Gene

ENSEMBL proteins:
Reactome Protein details:
REFSEQ proteins:

No data available for DME Specific Peptides for IRS1 Gene

Domains for IRS1 Gene

Gene Families for IRS1 Gene

Suggested Antigen Peptide Sequences for IRS1 Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry



  • Contains 1 IRS-type PTB domain.
  • Contains 1 IRS-type PTB domain.
  • Contains 1 PH domain.
genes like me logo Genes that share domains with IRS1: view

Function for IRS1 Gene

Molecular function for IRS1 Gene

GENATLAS Biochemistry:
insulin receptor,substrate 1,overexpressed in skeletal muscle,and adipocytes (polymorphism associated to susceptibility to NIDDM),located in the low density microsome fraction,tyrosine phosphorylated in response to insulin stimulation,interacting with several proteins containing SH2 domains,such as PIKRs,GRB2
UniProtKB/Swiss-Prot Function:
May mediate the control of various cellular processes by insulin. When phosphorylated by the insulin receptor binds specifically to various cellular proteins containing SH2 domains such as phosphatidylinositol 3-kinase p85 subunit or GRB2. Activates phosphatidylinositol 3-kinase when bound to the regulatory p85 subunit (By similarity).

Gene Ontology (GO) - Molecular Function for IRS1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004871 signal transducer activity IEA --
GO:0005068 transmembrane receptor protein tyrosine kinase adaptor activity ISS --
GO:0005080 protein kinase C binding ISS --
GO:0005158 insulin receptor binding IPI 7493946
GO:0005159 insulin-like growth factor receptor binding IPI 7541045
genes like me logo Genes that share ontologies with IRS1: view
genes like me logo Genes that share phenotypes with IRS1: view

Animal Models for IRS1 Gene

MGI Knock Outs for IRS1:

Animal Model Products

miRNA Products

Inhibitory RNA Products

  • Predesigned siRNA for gene silencing in human,mouse,rat for IRS1

In Situ Assay Products

Flow Cytometry Products

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for IRS1 Gene

Localization for IRS1 Gene

Subcellular locations from

Jensen Localization Image for IRS1 Gene COMPARTMENTS Subcellular localization image for IRS1 gene
Compartment Confidence
cytosol 4
nucleus 4
plasma membrane 4
cytoskeleton 2
endoplasmic reticulum 2
extracellular 2
mitochondrion 2
peroxisome 2

Gene Ontology (GO) - Cellular Components for IRS1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus ISS --
GO:0005737 cytoplasm ISS --
GO:0005829 cytosol TAS --
GO:0005886 plasma membrane TAS --
GO:0005899 insulin receptor complex ISS --
genes like me logo Genes that share ontologies with IRS1: view

No data available for Subcellular locations from UniProtKB/Swiss-Prot for IRS1 Gene

Pathways for IRS1 Gene

SuperPathways for IRS1 Gene

Superpath Contained pathways
1 PI-3K cascade
2 Signaling by FGFR
3 Insulin receptor signalling cascade
4 IL-9 Signaling Pathways
5 Translation Insulin regulation of translation
genes like me logo Genes that share pathways with IRS1: view

PCR Array Products

Gene Ontology (GO) - Biological Process for IRS1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0002053 positive regulation of mesenchymal cell proliferation IEA --
GO:0007165 signal transduction TAS 1311924
GO:0007173 epidermal growth factor receptor signaling pathway TAS --
GO:0008284 positive regulation of cell proliferation NAS 17925406
GO:0008286 insulin receptor signaling pathway TAS --
genes like me logo Genes that share ontologies with IRS1: view

Drugs for IRS1 Gene

(1) Drugbank Compounds for IRS1 Gene

Compound Status Synonyms Cas Number PubChem ID Type Actions PubMed IDs
24871491 Target experimental

(87) Novoseek inferred chemical compound relationships for IRS1 Gene

Compound -log(P) Hits PubMed IDs
phosphatidylinositol 90.7 203
tyrosine 87.3 270
glucose 78.9 155
phosphotyrosine 77.5 53
glycogen 76.2 72
genes like me logo Genes that share compounds with IRS1: view

Transcripts for IRS1 Gene

mRNA/cDNA for IRS1 Gene

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

Unigene Clusters for IRS1 Gene

Insulin receptor substrate 1:
Representative Sequences:

miRNA Products

Inhibitory RNA Products

  • Predesigned siRNA for gene silencing in human,mouse,rat for IRS1

Flow Cytometry Products

Alternative Splicing Database (ASD) splice patterns (SP) for IRS1 Gene

No ASD Table

Relevant External Links for IRS1 Gene

GeneLoc Exon Structure for
ECgene alternative splicing isoforms for

Expression for IRS1 Gene

mRNA expression in normal human tissues for IRS1 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues for IRS1 Gene

This gene is overexpressed in Brain (66.1).

Integrated Proteomics: protein expression from ProteomicsDB, PaxDb, MOPED, and MaxQB for IRS1 Gene

SOURCE GeneReport for Unigene cluster for IRS1 Gene Hs.471508

genes like me logo Genes that share expressions with IRS1: view

Primer Products

In Situ Assay Products

No data available for mRNA differential expression in normal tissues , mRNA Expression by UniProt/SwissProt and Expression partners for IRS1 Gene

Orthologs for IRS1 Gene

This gene was present in the common ancestor of animals.

Orthologs for IRS1 Gene

Organism Taxonomy Gene Similarity Type Details
(Bos Taurus)
Mammalia IRS1 35
  • 88.74 (n)
  • 91.01 (a)
IRS1 36
  • 90 (a)
(Canis familiaris)
Mammalia IRS1 35
  • 88.97 (n)
  • 91.76 (a)
IRS1 36
  • 87 (a)
(Mus musculus)
Mammalia Irs1 35
  • 85.37 (n)
  • 89.17 (a)
Irs1 16
Irs1 36
  • 88 (a)
(Pan troglodytes)
Mammalia IRS1 35
  • 99.19 (n)
  • 98.87 (a)
IRS1 36
  • 99 (a)
(Rattus norvegicus)
Mammalia Irs1 35
  • 84.97 (n)
  • 89.1 (a)
(Monodelphis domestica)
Mammalia IRS1 36
  • 74 (a)
(Gallus gallus)
Aves IRS1 35
  • 74.2 (n)
  • 79.78 (a)
IRS1 36
  • 74 (a)
(Anolis carolinensis)
Reptilia IRS1 36
  • 63 (a)
tropical clawed frog
(Silurana tropicalis)
Amphibia LOC100495320 35
  • 62.74 (n)
  • 69.99 (a)
African clawed frog
(Xenopus laevis)
Amphibia Xl.957 35
(Danio rerio)
Actinopterygii irs1 35
  • 61.99 (n)
  • 65.38 (a)
irs1 36
  • 59 (a)
fruit fly
(Drosophila melanogaster)
Insecta chico 36
  • 21 (a)
sea squirt
(Ciona savignyi)
Ascidiacea -- 36
  • 38 (a)
Species with no ortholog for IRS1:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • 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)
  • 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)
  • worm (Caenorhabditis elegans)

Evolution for IRS1 Gene

Gene Tree for IRS1 (if available)
Gene Tree for IRS1 (if available)

Paralogs for IRS1 Gene

Paralogs for IRS1 Gene

(1) SIMAP similar genes for IRS1 Gene using alignment to 4 proteins:

genes like me logo Genes that share paralogs with IRS1: view

Variants for IRS1 Gene

Polymorphic Variants from UniProtKB/Swiss-Prot for IRS1 Gene

The Arg-971 polymorphism impairs the ability of insulin to stimulate glucose transport, glucose transporter translocation, and glycogen synthesis by affecting the PI3K/AKT1/GSK3 signaling pathway. The polymorphism at Arg-971 may contribute to the in vivo insulin resistance observed in carriers of this variant. Arg-971 could contribute to the risk for atherosclerotic cardiovascular diseases associated with non-insulin-dependent diabetes mellitus (NIDDM) by producing a cluster of insulin resistance-related metabolic abnormalities. In insulin-stimulated human endothelial cells from carriers of the Arg-971 polymorphism, genetic impairment of the IRS1/PI3K/PDPK1/AKT1 insulin signaling cascade results in impaired insulin-stimulated nitric oxide (NO) release and suggested that this may be a mechanism through which the Arg-971 polymorphism contributes to the genetic predisposition to develop endothelial dysfunction and cardiovascular disease. The Arg-971 polymorphism not only reduces phosphorylation of the substrate but allows IRS1 to act as an inhibitor of PI3K, producing global insulin resistance

Sequence variations from dbSNP and Humsavar for IRS1 Gene

SNP ID Clin Chr 02 pos Sequence Context AA Info Type MAF
rs10203 -- 226,793,170(+) CAATT(C/T)TCTTC intron-variant
rs15625 -- 226,736,165(-) AGGAC(C/T)TCATA utr-variant-3-prime
rs919423 -- 226,755,850(+) TAATC(C/T)AACAG intron-variant
rs1025333 -- 226,780,809(+) TTTTT(A/T)AAATA intron-variant
rs1078533 -- 226,765,871(+) TTACA(A/C)TAGGG intron-variant

Structural Variations from Database of Genomic Variants (DGV) for IRS1 Gene

Variant ID Type Subtype PubMed ID
nsv3190 CNV Loss 18451855
nsv875921 CNV Loss 21882294
nsv821910 CNV Gain 20364138

Relevant External Links for IRS1 Gene

HapMap Linkage Disequilibrium report
Human Gene Mutation Database (HGMD)

Disorders for IRS1 Gene

(1) OMIM Diseases for IRS1 Gene (147545)


  • Diabetes mellitus, non-insulin-dependent (NIDDM) [MIM:125853]: A multifactorial disorder of glucose homeostasis caused by a lack of sensitivity to the bodys own insulin. Affected individuals usually have an obese body habitus and manifestations of a metabolic syndrome characterized by diabetes, insulin resistance, hypertension and hypertriglyceridemia. The disease results in long-term complications that affect the eyes, kidneys, nerves, and blood vessels. {ECO:0000269 PubMed:10206679, ECO:0000269 PubMed:12843189, ECO:0000269 PubMed:8723689}. Note=The gene represented in this entry may be involved in disease pathogenesis.

(4) University of Copenhagen DISEASES for IRS1 Gene

(64) Novoseek inferred disease relationships for IRS1 Gene

Disease -log(P) Hits PubMed IDs
insulin resistance 89.1 152
insulin sensitivity 79.2 33
niddm 67.8 91
hyperinsulinemia 64.6 19
obesity 61.5 44

Relevant External Links for IRS1

Genetic Association Database (GAD)
Human Genome Epidemiology (HuGE) Navigator
genes like me logo Genes that share disorders with IRS1: view

No data available for Genatlas for IRS1 Gene

Publications for IRS1 Gene

  1. A novel T608R missense mutation in insulin receptor substrate-1 identified in a subject with type 2 diabetes impairs metabolic insulin signaling. (PMID: 12679424) Esposito D.L. … Cama A. (J. Clin. Endocrinol. Metab. 2003) 3 4 23 48
  2. The Arg(972) variant in insulin receptor substrate-1 is associated with an atherogenic profile in offspring of type 2 diabetic patients. (PMID: 12843189) Marini M.A. … Sesti G. (J. Clin. Endocrinol. Metab. 2003) 3 4 23 48
  3. Aminoacid polymorphisms of insulin receptor substrate-1 in non- insulin-dependent diabetes mellitus. (PMID: 8104271) Almind K. … Pedersen O. (Lancet 1993) 3 4 23 48
  4. Association of Gly972Arg polymorphism of IRS1 gene with type 2 diabetes mellitus in lean participants of a national health survey in Mexico: a candidate gene study. (PMID: 19716569) Burguete-Garcia A.I. … Velasco-MondragA^n E. (Metab. Clin. Exp. 2010) 3 23 48
  5. [Effect of the Gly972Arg, SNP43 and Prol2Ala polymorphisms of the genes IRS1, CAPN10 and PPARG2 on secondary failure to sulphonylurea and metformin in patients with type 2 diabetes in YucatA!n, MAcxico]. (PMID: 19418728) GarcA-a-Escalante M.G. … Laviada-Molina H. (Invest Clin 2009) 3 23 48

Products for IRS1 Gene

  • Addgene plasmids for IRS1

Sources for IRS1 Gene

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