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    IRS1 insulin receptor substrate 1 [ Homo sapiens ]

    Gene ID: 3667, updated on 19-May-2012
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    Summary

    Official Symbol
    IRS1provided by HGNC
    Official Full Name
    insulin receptor substrate 1provided by HGNC
    Primary source
    HGNC:6125
    See related
    Ensembl:ENSG00000169047; HPRD:00943; MIM:147545; Vega:OTTHUMG00000133179
    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]
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    Genomic context

    Location :
    2q36
    Sequence :
    Chromosome: 2; NC_000002.11 (227596033..227663506, complement)
    See IRS1 in Epigenomics, MapViewer

    Chromosome 2 - NC_000002.11Genomic Context describing neighboring genes Neighboring gene dedicator of cytokinesis 10 Neighboring gene microRNA 4439 Neighboring gene neuronal tyrosine-phosphorylated phosphoinositide-3-kinase adaptor 2 Neighboring gene rhomboid domain containing 1 Neighboring gene collagen, type IV, alpha 4

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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. Antiangiogenic activity of aganirsen in nonhuman primate and rodent models of retinal neovascular disease after topical administration. Cloutier F, et al. Invest Ophthalmol Vis Sci, 2012. PMID 22323484.
    2. Global IRS-1 phosphorylation analysis in insulin resistance. Langlais P, et al. Diabetologia, 2011 Nov. PMID 21850561.
    3. Genetic variation near IRS1 associates with reduced adiposity and an impaired metabolic profile. Kilpeläinen TO, et al. Nat Genet, 2011 Jun 26. PMID 21706003.
    4. Impact of insulin receptor substrate-1 genotypes on platelet reactivity and cardiovascular outcomes in patients with type 2 diabetes mellitus and coronary artery disease. Angiolillo DJ, et al. J Am Coll Cardiol, 2011 Jun 28. PMID 21700086.
    5. The associations between G972R polymorphism of the IRS-1 gene, insulin resistance, salt sensitivity and non-dipper hypertension. Dziwura J, et al. Hypertens Res, 2011 Oct. PMID 21677657.

    See all (368) 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. Retinal delivery after topical administration was confirmed, and retinal expression of IRS-1 was demonstrated to be elevated in patients with subretinal neovascularization and AMD.
      Title: Antiangiogenic activity of aganirsen in nonhuman primate and rodent models of retinal neovascular disease after topical administration.
    2. rs1801278 GA of IRS-1 carriers had lower risk of metabolic syndrome, especially among smokers.
      Title: The rs1801278 G>A polymorphism of IRS-1 is associated with metabolic syndrome in healthy nondiabetic men. Modulation by cigarette smoking status.
    3. Data suggest that IRS-1 in skeletal muscle (i.e., vastus lateralis) of patients with either type 2 diabetes or obesity undergoes both hyper- and hypo-Ser/Thr phosphorylation of IRS-1 in response to insulin infusion.
      Title: Global IRS-1 phosphorylation analysis in insulin resistance.
    4. The G972R polymorphism of the IRS-1 gene is associated with insulin resistance, salt sensitivity and non-dipper hypertension.
      Title: The associations between G972R polymorphism of the IRS-1 gene, insulin resistance, salt sensitivity and non-dipper hypertension.
    5. G972R polymorphism associated with gestational diabetes in Greek women
      Title: Gestational diabetes mellitus shares polymorphisms of genes associated with insulin resistance and type 2 diabetes in the Greek population.
    6. genetic association studies in population in south India: No associations were found between IRS1 gene variants Gly972Arg (rs1801278) or Ala513Pro (rs1801276) and type 2 diabetes; no associations were found based on age of onset of diabetes/obesity.
      Title: Association study of IRS1 gene polymorphisms with type 2 diabetes in south Indians.
    7. Genetic variation near IRS1 associates with reduced adiposity and an impaired metabolic profile.
      Title: Genetic variation near IRS1 associates with reduced adiposity and an impaired metabolic profile.
    8. The down-regulation of PTEN and IRS1 is a critical event leading to the HCV genotype 3a-induced formation of large lipid droplets in hepatocytes.
      Title: Down-regulation of phosphatase and tensin homolog by hepatitis C virus core 3a in hepatocytes triggers the formation of large lipid droplets.
    9. this is the first evidence that IRS-1 is involved in the molecular pathway leading to lymphangiogenesis
      Title: Blockade of insulin receptor substrate-1 inhibits corneal lymphangiogenesis.
    10. knockdown of IRS1 is capable of inducing the downregulation of Akt/mTOR and MAPK pathways and further decreasing proliferation, and clonogenicity and induces to cell cycle delay at G0/G1 phase in BCR-ABL cells
      Title: Knockdown of insulin receptor substrate 1 reduces proliferation and downregulates Akt/mTOR and MAPK pathways in K562 cells.
    Submit: New GeneRIF Correction See all (172)
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    Phenotypes

    Review eQTL and phenotype association data in this region using PheGenI

    Coronary artery disease, susceptibility to

    Diabetes mellitus, noninsulin-dependent

    Genetic variant near IRS1 is associated with type 2 diabetes, insulin resistance and hyperinsulinemia.

    Genetic variation near IRS1 associates with reduced adiposity and an impaired metabolic profile.

    Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis.

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    Interactions

    Products Interactant Other Gene Complex Source Pubs Description
    NP_005535.1 NP_000866.1 IGF1R    BIND  PubMed IGFIR interacts with IRS-1. 
    NP_005535.1 NP_000866.1 IGF1R    BIND  PubMed IRS-1 interacts with IGF-IR. This interaction was modeled on a demonstrated interaction between rat IRS-1 and human IGF-IR. 
    NP_005535.1 NP_000199.1 INSR    BIND  PubMed IRS-1 interacts with IR. This interaction was modeled on a demonstrated interaction between rat IRS-1 and human IR. 
    NP_005535.1 NP_000199.1 INSR    BIND  PubMed Insulin Receptor Substrate-1 Binds to the Insulin Receptor. This interaction is modeled on demonstrated interaction between human IR and rat IRS-1 
    NP_005535.1 NP_005018.1 PIK3R2    BIND  PubMed IRS-1 interacts with p85-beta. This interaction was modeled based on a demonstrated interaction between IRS-1 from an unspecified species and p85-beta from an unknown species. 
    NP_005535.1 NP_892113.1 SHC1    BIND  PubMed Direct interaction between IRS-1 and SHC. This interaction was modeled on a demonstrated interaction between rat IRS-1 and human SHC 
    NP_005535.1 NP_006752.1 YWHAE    BIND  PubMed IRS-1 interacts with 14-3-3-epsilon isoform. This interaction was modeled on a demonstrated interaction between human IRS-1 and mouse 14-3-3-epsilon isoform. 
    NP_005535.1 1IRS|B     BIND  PubMed Interaction between IL-4R Phosphopeptide (PDB ID: 1IRS_B) and IRS-1 (PDB ID: 1IRS_A). 
    P35568 P31749 AKT1    HPRD  PubMed  
    P35568 Q9UM73 ALK    HPRD  PubMed  
    P35568 Q92572 AP3S1    HPRD  PubMed  
    P35568 O14983 ATP2A1    HPRD  PubMed  
    P35568 P16615 ATP2A2    HPRD  PubMed  
    P35568 Q93084 ATP2A3    HPRD  PubMed  
    P35568 Q07817 BCL2L1    HPRD  PubMed  
    P35568 P11274 BCR    HPRD  PubMed  
    P35568 Q03135 CAV1    HPRD  PubMed  
    P35568 P12830 CDH1    HPRD  PubMed  
    P35568 O15111 CHUK    HPRD  PubMed  
    P35568 P46108 CRK    HPRD  PubMed  
    P35568 P68400 CSNK2A1    HPRD  PubMed  
    P35568 P67870 CSNK2B    HPRD  PubMed  
    P35568 P16591 FER    HPRD  PubMed  
    P35568 P07332 FES    HPRD  PubMed  
    P35568 P06241 FYN    HPRD  PubMed  
    P35568 P10912 GHR    HPRD  PubMed  
    P35568 Q14449 GRB14    HPRD  PubMed  
    P35568 P62993 GRB2    HPRD  PubMed  
    P35568 P08069 IGF1R    HPRD  PubMed  
    P35568 O14920 IKBKB    HPRD  PubMed  
    P35568 P24394 IL4R    HPRD  PubMed  
    P35568 P06213 INSR    HPRD  PubMed  
    P35568 P35568 IRS1    HPRD  PubMed  
    P35568 P23458 JAK1    HPRD  PubMed  
    P35568 O60674 JAK2    HPRD  PubMed  
    P35568 P52333 JAK3    HPRD  PubMed  
    P35568 P28482 MAPK1    HPRD  PubMed  
    P35568 P45983 MAPK8    HPRD  PubMed  
    P35568 P45984 MAPK9    HPRD  PubMed  
    P35568 P42345 MTOR    HPRD  PubMed  
    P35568 P06748 NPM1    HPRD  PubMed  
    P35568 P04629 NTRK1    HPRD  PubMed  
    P35568 O15530 PDPK1    HPRD  PubMed  
    P35568 Pleckstrin homology domain interacting protein PHIP    HPRD  PubMed  
    P35568 P27986 PIK3R1    HPRD  PubMed  
    P35568 O00459 PIK3R2    HPRD  PubMed  
    P35568 Q92569 PIK3R3    HPRD  PubMed  
    P35568 Q05655 PRKCD    HPRD  PubMed  
    P35568 P05129 PRKCG    HPRD  PubMed  
    P35568 Q04759 PRKCQ    HPRD  PubMed  
    P35568 Q05513 PRKCZ    HPRD  PubMed  
    P35568 Q05397 PTK2    HPRD  PubMed  
    P35568 P18031 PTPN1    HPRD  PubMed  
    P35568 Q06124 PTPN11    HPRD  PubMed  
    P35568 P08575 PTPRC    HPRD  PubMed  
    P35568 P10586 PTPRF    HPRD  PubMed  
    P35568 Q06609 RAD51    HPRD  PubMed  
    P35568 Q13464 ROCK1    HPRD  PubMed  
    P35568 Raptor RPTOR    HPRD  PubMed  
    P35568 P29353 SHC1    HPRD  PubMed  
    P35568 Q9H0K1 SIK2    HPRD  PubMed  
    P35568 O15524 SOCS1    HPRD  PubMed  
    P35568 O14543 SOCS3    HPRD  PubMed  
    P35568 P50607 TUB    HPRD  PubMed  
    P35568 P29597 TYK2    HPRD  PubMed  
    P35568 P17480 UBTF    HPRD  PubMed  
    P35568 P31946 YWHAB    HPRD  PubMed  
    P35568 P62258 YWHAE    HPRD  PubMed  
    P35568 P61981 YWHAG    HPRD  PubMed  
    P35568 P63104 YWHAZ    HPRD  PubMed  
    BioGRID:109874 BioGRID:106710 AKT1    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:109874 BioGRID:106739 ALK    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:109874 BioGRID:107590 AP3S1    BioGRID  PubMed Reconstituted Complex 
    BioGRID:109874 BioGRID:107068 BCL2    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:109874 BioGRID:107070 BCL2L1    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:109874 BioGRID:107315 CBL    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:109874 BioGRID:107316 CBLB    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:109874 BioGRID:107569 CHUK    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:109874 BioGRID:108403 ESR1    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:109874 BioGRID:109144 GRB10    BioGRID  PubMed Reconstituted Complex 
    BioGRID:109874 BioGRID:109142 GRB2    BioGRID  PubMed Affinity Capture-Western; Reconstituted Complex 
    BioGRID:109874 BioGRID:109316 HDAC2    BioGRID  PubMed Affinity Capture-Western; Reconstituted Complex; Two-hybrid 
    BioGRID:109874 BioGRID:109701 IGF1R    BioGRID  PubMed Affinity Capture-Western; Two-hybrid 
    BioGRID:109874 BioGRID:109767 IKBKB    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:109874 BioGRID:109854 INSR    BioGRID  PubMed Two-hybrid 
    BioGRID:109874 BioGRID:114209 IRS2    BioGRID  PubMed Co-fractionation 
    BioGRID:109874 BioGRID:109919 JAK1    BioGRID  PubMed Affinity Capture-Western; Biochemical Activity 
    BioGRID:109874 BioGRID:109920 JAK2    BioGRID  PubMed Affinity Capture-Western; Biochemical Activity 
    BioGRID:109874 BioGRID:109921 JAK3    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:109874 BioGRID:115900 KHDRBS1    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:109874 BioGRID:111585 MAPK8    BioGRID  PubMed Affinity Capture-Western; Reconstituted Complex; Two-hybrid 
    BioGRID:109874 BioGRID:108757 MTOR    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:109874 BioGRID:114020 NCK2    BioGRID  PubMed Reconstituted Complex 
    BioGRID:109874 BioGRID:110811 NEDD4    BioGRID  PubMed Reconstituted Complex 
    BioGRID:109874 BioGRID:116358 NISCH    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:109874 BioGRID:111308 PIK3CA    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:109874 BioGRID:111313 PIK3R1    BioGRID  PubMed Affinity Capture-Western; Far Western 
    BioGRID:109874 BioGRID:114075 PIK3R3    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:109874 BioGRID:111566 PRKCD    BioGRID  PubMed Affinity Capture-Western; Biochemical Activity 
    BioGRID:109874 BioGRID:111719 PTK2    BioGRID  PubMed Affinity Capture-Western; Two-hybrid 
    BioGRID:109874 BioGRID:111736 PTPN1    BioGRID  PubMed Affinity Capture-Western; Reconstituted Complex 
    BioGRID:109874 BioGRID:111745 PTPN11    BioGRID  PubMed Affinity Capture-Western; Reconstituted Complex 
    BioGRID:109874 BioGRID:109072 SFN    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:109874 BioGRID:112361 SHC1    BioGRID  PubMed Reconstituted Complex 
    BioGRID:109874 BioGRID:114203 SOCS1    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:109874 BioGRID:113164 UBC    BioGRID  PubMed Affinity Capture-MS; Affinity Capture-Western 
    BioGRID:109874 BioGRID:113190 UBTF    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:109874 BioGRID:113361 YWHAB    BioGRID  PubMed Reconstituted Complex 
    BioGRID:109874 BioGRID:113363 YWHAE    BioGRID  PubMed Reconstituted Complex; Two-hybrid 
    BioGRID:109874 BioGRID:113365 YWHAH    BioGRID  PubMed Affinity Capture-Western 
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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...
    • Alpha6-Beta4 Integrin Signaling Pathway, organism-specific biosystem (from WikiPathways)
      Alpha6-Beta4 Integrin Signaling Pathway, organism-specific biosystem"Integrins are cell surface heterodimeric protein complex consisting of one alpha and one beta chain. Integrins act as cell adhesion molecules as well as participate in cellular signaling. The ligand...
    • Cytokine Signaling in Immune system, organism-specific biosystem (from REACTOME)
      Cytokine Signaling in Immune system, organism-specific biosystemCytokines are small proteins that regulate and mediate immunity, inflammation, and hematopoiesis. They are secreted in response to immune stimuli, and usually act briefly, locally, at very low concen...
    • EPO Receptor Signaling, organism-specific biosystem (from WikiPathways)
      EPO Receptor Signaling, organism-specific biosystemThe erythropoietin receptor is a 66 kDa peptide and is a member of the cytokine receptor family. The receptor is tyrosine phosphorylated upon binding by erythropoietin and associates with and activat...
    • Growth hormone receptor signaling, organism-specific biosystem (from REACTOME)
      Growth hormone receptor signaling, organism-specific biosystemGrowth hormone (Somatotropin or GH) is a key factor in determining lean body mass, stimulating the growth and metabolism of muscle, bone and cartilage cells, while reducing body fat. It has many othe...
    • IGF1 pathway, organism-specific biosystem (from Pathway Interaction Database)
      IGF1 pathway, organism-specific biosystem
      IGF1 pathway
    • IL-2 Signaling Pathway, organism-specific biosystem (from WikiPathways)
      IL-2 Signaling Pathway, organism-specific biosystemInterleukin-2 belongs to a family of cytokines, which includes IL-4, IL-7, IL-9, IL-15 and IL-21. IL-2 signals through a receptor complex consisting of IL-2 specific IL-2 receptor alpha (CD25), IL-2 ...
    • IL-4 signaling Pathway, organism-specific biosystem (from WikiPathways)
      IL-4 signaling Pathway, organism-specific biosystemInterleukin-4 belongs to the IL-2 family of cytokines, which includes IL-2, IL-7, IL-9, IL-15 and IL-21. It signals through 2 different receptor complexes; Receptor complex 1 comprises of IL-4 recept...
    • IL-7 Signaling Pathway, organism-specific biosystem (from WikiPathways)
      IL-7 Signaling Pathway, organism-specific biosystemInterleukin-7 belongs to a family of cytokines, which includes IL-2, IL-4, IL-9, IL-15 and IL-21. It signals through a receptor complex consisting of IL-7 receptor alpha chain (IL7RA) and a common ga...
    • IL-9 Signaling Pathway, organism-specific biosystem (from WikiPathways)
      IL-9 Signaling Pathway, organism-specific biosystemInterleukin-9 belongs to a family of cytokines, which includes IL-2, IL-4, IL-7, IL-15 and IL-21. It signals through a receptor complex consisting of an IL-9 receptor (IL9R) and a common gamma chain ...
    • IL2-mediated signaling events, organism-specific biosystem (from Pathway Interaction Database)
      IL2-mediated signaling events, organism-specific biosystem
      IL2-mediated signaling events
    • IL4-mediated signaling events, organism-specific biosystem (from Pathway Interaction Database)
      IL4-mediated signaling events, organism-specific biosystem
      IL4-mediated signaling events
    • IRS activation, organism-specific biosystem (from REACTOME)
      IRS activation, organism-specific biosystemUsing receptor mutagenesis studies it is known that IRS1 via its PTB domain binds to the insulin receptor at the juxtamembrane region at tyrosine 972. The interaction is further stabilized by the PH ...
    • IRS-mediated signalling, organism-specific biosystem (from REACTOME)
      IRS-mediated signalling, organism-specific biosystemRelease of phospho-IRS from the insulin receptor triggers a cascade of signalling events via PI3K, SOS, RAF and the MAP kinases.
    • IRS-related events, organism-specific biosystem (from REACTOME)
      IRS-related events, organism-specific biosystemIRS is one of the mediators of insulin signalling events. It is activated by phosphorylation and triggers a cascade of events involving PI3K, SOS, RAF and the MAP kinases. The proteins mentioned unde...
    • Id Signaling Pathway, organism-specific biosystem (from WikiPathways)
      Id Signaling Pathway, organism-specific biosystemInhibitor of DNA binding (ID) proteins are members of the helix-loop-helix (HLH) family of proteins which lack a DNA binding domain themselves but bind to other family members inhibiting their DNA bi...
    • Immune System, organism-specific biosystem (from REACTOME)
      Immune System, organism-specific biosystemHumans are exposed to millions of potential pathogens daily, through contact, ingestion, and inhalation. Our ability to avoid infection depends on the adaptive immune system and during the first crit...
    • Insulin Pathway, organism-specific biosystem (from Pathway Interaction Database)
      Insulin Pathway, organism-specific biosystem
      Insulin Pathway
    • Insulin Signaling, organism-specific biosystem (from WikiPathways)
      Insulin Signaling, organism-specific biosystem
      Insulin Signaling
    • Insulin receptor signalling cascade, organism-specific biosystem (from REACTOME)
      Insulin receptor signalling cascade, organism-specific biosystemAutophosphorylation of the insulin receptor triggers a series of signalling events, mediated by SHC or IRS, and resulting in activation of the Ras/RAF and MAP kinase cascades. A second effect of the ...
    • 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...
    • Integrins in angiogenesis, organism-specific biosystem (from Pathway Interaction Database)
      Integrins in angiogenesis, organism-specific biosystem
      Integrins in angiogenesis
    • NGF signalling via TRKA from the plasma membrane, organism-specific biosystem (from REACTOME)
      NGF signalling via TRKA from the plasma membrane, organism-specific biosystemTrk receptors signal from the plasma membrane and from intracellular membranes, particularly from early endosomes. Signalling from the plasma membrane is fast but transient; signalling from endosomes...
    • 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...
    • PI3K Cascade, organism-specific biosystem (from REACTOME)
      PI3K Cascade, organism-specific biosystem
      PI3K Cascade
    • PI3K/AKT activation, organism-specific biosystem (from REACTOME)
      PI3K/AKT activation, organism-specific biosystemPI3K/AKT signalling is a major regulator of neuron survival. It blocks cell death by both impinging on the cytoplasmic cell death machinery and by regulating the expression of genes involved in cell...
    • S1P2 pathway, organism-specific biosystem (from Pathway Interaction Database)
      S1P2 pathway, organism-specific biosystem
      S1P2 pathway
    • SOS-mediated signalling, organism-specific biosystem (from REACTOME)
      SOS-mediated signalling, organism-specific biosystemSOS is recruited to the plasma membrane and mediates activation of Ras.
    • Signal Transduction, organism-specific biosystem (from REACTOME)
      Signal Transduction, organism-specific biosystemSignal transduction is a process in which extracellular signals elicit changes in cell state and activity. Transmembrane receptors sense changes in the cellular environment by binding ligands, such a...
    • Signal attenuation, organism-specific biosystem (from REACTOME)
      Signal attenuation, organism-specific biosystemNow with the complete receptor-ligand dissociation and subsequent degradation of insulin in the endosomal lumen, the endosomally associated protein tyrosine phosphatases (PTPs) complete the receptor ...
    • Signaling by Insulin receptor, organism-specific biosystem (from REACTOME)
      Signaling by Insulin receptor, organism-specific biosystemInsulin binding to its receptor results in receptor autophosphorylation on tyrosine residues and the tyrosine phosphorylation of insulin receptor substrates (e.g. IRS and Shc) by the insulin receptor...
    • Signaling events mediated by PTP1B, organism-specific biosystem (from Pathway Interaction Database)
      Signaling events mediated by PTP1B, organism-specific biosystem
      Signaling events mediated by PTP1B
    • Signaling events regulated by Ret tyrosine kinase, organism-specific biosystem (from Pathway Interaction Database)
      Signaling events regulated by Ret tyrosine kinase, organism-specific biosystem
      Signaling events regulated by Ret tyrosine kinase
    • Signalling by NGF, organism-specific biosystem (from REACTOME)
      Signalling by NGF, organism-specific biosystemNeurotrophins (NGF, BDNF, NT-3, NT-4/5) play pivotal roles in survival, differentiation, and plasticity of neurons in the peripheral and central nervous system. They are produced, and secreted in mi...
    • 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...
    • mTOR signaling pathway, organism-specific biosystem (from Pathway Interaction Database)
      mTOR signaling pathway, organism-specific biosystem
      mTOR signaling pathway

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    SH2 domain binding ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    insulin receptor binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    insulin-like growth factor receptor binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    insulin-like growth factor-activated receptor activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    phosphatidylinositol 3-kinase binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    phosphatidylinositol 3-kinase binding ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    phosphatidylinositol-4,5-bisphosphate 3-kinase activity TAS
    Traceable Author Statement
    more info
    		  
    protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    protein kinase C binding ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    signal transducer activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    transmembrane receptor protein tyrosine kinase adaptor activity ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    Process Evidence Code Pubs
    JAK-STAT cascade involved in growth hormone signaling pathway TAS
    Traceable Author Statement
    more info
    		  
    cellular response to insulin stimulus IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    glucose homeostasis TAS
    Traceable Author Statement
    more info
    		 PubMed 
    insulin receptor signaling pathway IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    insulin receptor signaling pathway IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    insulin receptor signaling pathway IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    insulin receptor signaling pathway TAS
    Traceable Author Statement
    more info
    		  
    insulin-like growth factor receptor signaling pathway IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    lipid catabolic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    mammary gland development IEA
    Inferred from Electronic Annotation
    more info
    		  
    negative regulation of insulin receptor signaling pathway ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    negative regulation of insulin secretion IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    negative regulation of somatostatin secretion IEA
    Inferred from Electronic Annotation
    more info
    		  
    nerve growth factor receptor signaling pathway TAS
    Traceable Author Statement
    more info
    		  
    phosphatidylinositol 3-kinase cascade IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    phosphatidylinositol-mediated signaling TAS
    Traceable Author Statement
    more info
    		  
    positive regulation of cell migration IEA
    Inferred from Electronic Annotation
    more info
    		  
    positive regulation of cell proliferation NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    positive regulation of fatty acid beta-oxidation IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    positive regulation of glucagon secretion IEA
    Inferred from Electronic Annotation
    more info
    		  
    positive regulation of glucose import IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    positive regulation of glucose metabolic process IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    positive regulation of glycogen biosynthetic process IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    positive regulation of glycogen biosynthetic process NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    positive regulation of insulin receptor signaling pathway ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    positive regulation of mesenchymal cell proliferation IEA
    Inferred from Electronic Annotation
    more info
    		  
    positive regulation of phosphatidylinositol 3-kinase activity ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    positive regulation of phosphorylation IEA
    Inferred from Electronic Annotation
    more info
    		  
    protein heterooligomerization IEA
    Inferred from Electronic Annotation
    more info
    		  
    protein kinase B signaling cascade IEA
    Inferred from Electronic Annotation
    more info
    		  
    protein localization to nucleus IEA
    Inferred from Electronic Annotation
    more info
    		  
    regulation of gene expression IEA
    Inferred from Electronic Annotation
    more info
    		  
    response to insulin stimulus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    response to peptide hormone stimulus ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    signal transduction TAS
    Traceable Author Statement
    more info
    		 PubMed 
    transmembrane receptor protein tyrosine kinase signaling pathway ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    Component Evidence Code Pubs
    caveola IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    cytoplasm ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    cytosol TAS
    Traceable Author Statement
    more info
    		  
    insulin receptor complex ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    microsome ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    nucleus ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    plasma membrane TAS
    Traceable Author Statement
    more info
    		  
    Help top of page

    General protein information

    Preferred Names
    insulin receptor substrate 1
    Names
    insulin receptor substrate 1
    IRS-1
    Help top of page

    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_015830.1 RefSeqGene

      Range
      5001..72474
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_005544.2 → NP_005535.1  insulin receptor substrate 1

      Status: REVIEWED

      Source sequence(s)
      AC010735, AW469017, BC053895
      Consensus CDS
      CCDS2463.1
      UniProtKB/Swiss-Prot
      P35568
      Related
      ENSP00000304895, OTTHUMP00000164234, ENST00000305123, OTTHUMT00000256886
      Conserved Domains (2) summary
      cd01204
      Location:160 – 263
      Blast Score: 538
      IRS_PTB; Insulin receptor substrate (IRS) Phosphotyrosine-binding domain(PTB)
      cd01257
      Location:12 – 113
      Blast Score: 497
      PH_IRS; Insulin receptor substrate (IRS) pleckstrin homology (PH) 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_000002.11 Reference GRCh37.p5 Primary Assembly

      Range
      227596033..227663506, complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate HuRef

    Genomic

    1. AC_000134.1 Alternate HuRef

      Range
      219439592..219507082, complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Help top of page

    Related Sequences

    Nucleotide Protein
    Heading Accession and Version
    genomic AC010735.11 (11070..79338) None
    genomic CH471063.1 EAW70838.1
      EAW70839.1
    genomic HC477893.1 CBL64020.1
    genomic S85963.1 AAB21608.1
    mRNA AW469017.1 None
    mRNA BC053895.1 AAH53895.1
    mRNA S62539.1 AAB27175.1
    other-genetic EU831611.1 ACE87211.1
    other-genetic EU831698.1 ACE86532.1
    Protein Accession Links
    GenPept Link UniProtKB Link
    P35568.1 GenPept UniProtKB/Swiss-Prot:P35568
    Help top of page

    Additional Links

    Gene LinkOut

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

    Chemical Information
    Medical
    Molecular Biology Databases
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