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IRS1 Gene

protein-coding   GIFtS: 69
GCID: GC02M227563

Insulin Receptor Substrate 1

  See related diseases
at  

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
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Aliases
Insulin Receptor Substrate 11 2
IRS-12 3
HIRS-12

External Ids:    HGNC: 61251   Entrez Gene: 36672   Ensembl: ENSG000001690477   OMIM: 1475455   UniProtKB: P355683   

Export aliases for IRS1 gene to outside databases

Previous GC identifers: GC02M225622 GC02M226321 GC02M227802 GC02M227425 GC02M227308 GC02M219439


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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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 lipoatrophic diabetes, and insulin resistance. GO annotations related to this gene include protein kinase C binding and phospholipid binding. An important paralog of this gene is IRS2.

UniProtKB/Swiss-Prot: IRS1_HUMAN, P35568
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 Wiki entry for IRS1 Gene


(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence:
NC_000002.12  NT_005403.18  NC_018913.2  
Regulatory elements:
   Regulatory transcription factor binding sites in the IRS1 gene promoter:
         c-Fos   CREB   AP-1   ATF-2   deltaCREB   STAT3   c-Jun   c-Ets-1   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmidIRS1 promoter sequence
   Search Chromatin IP Primers for IRS1

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat IRS1


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 2q36   Ensembl cytogenetic band:  2q36.3   HGNC cytogenetic band: 2q36

IRS1 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
IRS1 gene location

GeneLoc information about chromosome 2         GeneLoc Exon Structure

GeneLoc location for GC02M227563:  view genomic region     (about GC identifiers)

Start:
227,596,033 bp from pter      End:
227,664,475 bp from pter
Size:
68,443 bases      Orientation:
minus strand

(According to 1UniProtKB, HORDE, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Cloud-Clone Corp.,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Cloud-Clone Corp., Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, Cloud-Clone Corp, and/or others.)
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UniProtKB/Swiss-Prot: IRS1_HUMAN, P35568 (See protein sequence)
Recommended Name: Insulin receptor substrate 1  
Size: 1242 amino acids; 131591 Da
Subunit: 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)
4 PDB 3D structures from and Proteopedia for IRS1:
1IRS (3D)        1K3A (3D)        1QQG (3D)        2Z8C (3D)    

Explore the universe of human proteins at neXtProt for IRS1: NX_P35568

Explore proteomics data for IRS1 at MOPED

Post-translational modifications: 

  • 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 IRS11
  • Modification sites at neXtProt
  • Modification sites at PhosphoSitePlus

  • See IRS1 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins: NP_005535.1  
    ENSEMBL proteins: 
     ENSP00000304895  
    Reactome Protein details: P35568

    IRS1 Human Recombinant Protein Products:

    EMD Millipore Purified and/or Recombinant IRS1 Protein
    Browse R&D Systems for human recombinant proteins
    Browse recombinant and purified proteins available from Enzo Life Sciences
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    OriGene Protein Over-expression Lysate for IRS1
    OriGene Custom MassSpec
    OriGene Custom Protein Services for IRS1
    GenScript Custom Purified and Recombinant Proteins Services for IRS1
    Novus Biologicals IRS1 Protein
    Novus Biologicals IRS1 Lysate
    Browse Sino Biological Recombinant Proteins
    Browse Sino Biological Cell Lysates
    Browse ProSpec Recombinant Proteins
    Cloud-Clone Corp. Proteins for IRS1

    IRS1 Antibody Products:

    EMD Millipore Mono- and Polyclonal Antibodies for the study of IRS1
    R&D Systems Antibodies for IRS1
    Cell Signaling Technology (CST) Antibodies for IRS1 
    OriGene Antibodies for IRS1
    OriGene Custom Antibody Services for IRS1
    Novus Biologicals IRS1 Antibodies
    Abcam antibodies for IRS1
    Cloud-Clone Corp. Antibodies for IRS1
    ThermoFisher Antibodies for IRS1
    LSBio Antibodies in human, mouse, rat for IRS1

    IRS1 Assay Products:

    EMD Millipore Kits and Assays for the Analysis of IRS1
    OriGene Custom Assay Services for IRS1
    Browse R&D Systems for biochemical assays
    GenScript Custom Assay Services for IRS1
    Cell Signaling Technology (CST) Sandwich ELISA Kits for IRS1
    Browse Enzo Life Sciences for kits & assays
    Cloud-Clone Corp. ELISAs for IRS1
    Cloud-Clone Corp. CLIAs for IRS1


    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    HGNC Gene Families:
    PLEKH: Pleckstrin homology (PH) domain containing

    3 InterPro protein domains:
     IPR002404 Insln_rcpt_S1
     IPR001849 Pleckstrin_homology
     IPR011993 PH_like_dom

    Graphical View of Domain Structure for InterPro Entry P35568

    ProtoNet protein and cluster: P35568

    2 Blocks protein domains:
    IPB001849 Pleckstrin-like
    IPB002404 Insulin receptor substrate-1 PTB domain signature


    UniProtKB/Swiss-Prot: IRS1_HUMAN, P35568
    Similarity: Contains 1 IRS-type PTB domain
    Similarity: Contains 1 PH domain


    IRS1 for domains           About GeneDecksing


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
    transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Molecular Function:

         UniProtKB/Swiss-Prot Summary: IRS1_HUMAN, P35568
    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)

         Genatlas biochemistry entry for IRS1:
    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

         Gene Ontology (GO): Selected molecular function terms (see all 9):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0004871signal transducer activity IEA--
    GO:0005068transmembrane receptor protein tyrosine kinase adaptor activity ISS--
    GO:0005080protein kinase C binding ISS--
    GO:0005158insulin receptor binding IPI7493946
    GO:0005159insulin-like growth factor receptor binding IPI7541045
         
    IRS1 for ontologies           About GeneDecksing


    Phenotypes:
         5 GenomeRNAi human phenotypes for IRS1:
     Decreased Salmonella enterica   Decreased focal adhesion (FA)   Decreased nuclei size in G2M  Increased cell death HMECs cel 
     Increased gamma-H2AX phosphory 

         14 MGI mutant phenotypes (inferred from 8 alleles(MGI details for Irs1):
     adipose tissue  cardiovascular system  cellular  endocrine/exocrine gland  growth/size/body 
     hearing/vestibular/ear  hematopoietic system  homeostasis/metabolism  immune system  limbs/digits/tail 
     liver/biliary system  mortality/aging  muscle  skeleton 

    IRS1 for phenotypes           About GeneDecksing

    Animal Models:
         MGI mouse knock-outs for IRS1: Irs1tm1Tka Irs1tm1Jos

       inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for IRS1
       inGenious Targeting Laboratory: Contact us about creating complex and humanized mouse models for IRS1

       genOway customized KO model: permanent, tissue-specific or time-controlled inactivation for IRS1
       genOway customized Knockin model: humanization, point mutation, expression monitoring, etc. for IRS1

    miRNA
    Products:
        
    miRTarBase miRNAs that target IRS1:
    hsa-mir-126-3p (MIRT004355), hsa-mir-148a-3p (MIRT006859), hsa-mir-152-3p (MIRT006860), hsa-mir-145-5p (MIRT000731), hsa-mir-7-5p (MIRT003807)

    Block miRNA regulation of human, mouse, rat IRS1 using miScript Target Protectors
    Selected qRT-PCR Assays for microRNAs that regulate IRS1 (see all 119):
    hsa-miR-576-3p hsa-miR-548j hsa-miR-26a-2* hsa-miR-15a hsa-miR-128 hsa-miR-30d hsa-miR-550a* hsa-miR-30a
    SwitchGear 3'UTR luciferase reporter plasmidIRS1 3' UTR sequence
    Inhib. RNA
    Products:
        
    OriGene RNAi products in human, mouse, rat for IRS1
    Predesigned siRNA for gene silencing in human, mouse, rat IRS1

    Gene Editing
    Products:
    DNA2.0 Custom Protein Engineering Service for IRS1

    Clone
    Products:
         
    OriGene clones in human, mouse for IRS1 (see all 7)
    OriGene ORF clones in mouse, rat for IRS1
    OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
    GenScript: all cDNA clones in your preferred vector: IRS1 (NM_005544)
    Browse Sino Biological Human cDNA Clones
    DNA2.0 Custom Codon Optimized Gene Synthesis Service for IRS1
    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat IRS1

    Cell Line
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    GenScript Custom overexpressing Cell Line Services for IRS1
    Browse ESI BIO Cell Lines and PureStem Progenitors for IRS1 
    In Situ Assay
    Products:
       

     
    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for IRS1


    (According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    cytosol4
    nucleus4
    plasma membrane4
    cytoskeleton2
    endoplasmic reticulum2
    extracellular2
    mitochondrion2
    peroxisome2

    Gene Ontology (GO): Selected cellular component terms (see all 7):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005634nucleus ISS--
    GO:0005737cytoplasm ISS--
    GO:0005829cytosol TAS--
    GO:0005886plasma membrane TAS--
    GO:0005899insulin receptor complex ISS--

    IRS1 for ontologies           About GeneDecksing


    (SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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    SuperPaths for IRS1 About   (see all 63)  
    See pathways by source

    SuperPathSelected contained pathways About (see all per SuperPath)
    1IL-9 Signaling Pathways
    IL-9 Signaling Pathways0.90
    IL-4 Signaling Pathways0.84
    IL-7 Signaling Pathways0.90
    IL-9 Signaling Pathway0.42
    IL-21 Signaling Pathways0.90
    Immune response IL 9 signaling pathway0.42
    Common Cytokine Receptor Gamma-Chain Family Signaling Pathways0.90
    IL-7 Signaling Pathway0.40
    2Development IGF 1 receptor signaling
    Development IGF RI signaling0.49
    Development IGF 1 receptor signaling0.48
    Signal transduction AKT signaling0.49
    Immune response IL 4 signaling pathway0.39
    3Type II diabetes mellitus
    Type II diabetes mellitus0.38
    Type II diabetes mellitus0.35
    Anti-diabetic Drug Potassium Channel Inhibitors Pathway, Pharmacodynamics0.38
    4Translation Insulin regulation of translation
    Translation Insulin regulation of translation0.59
    Transcription PPAR Pathway0.34
    Regulation of lipid metabolism Insulin signaling generic cascades0.59
    Development Growth hormone signaling via PI3K AKT and MAPK cascades0.34
    Transcription Receptor mediated HIF regulation0.51
    mTOR signaling pathway0.34
    Translation Regulation activity of EIF20.47
    Insulin signaling pathway0.32
    5Prolactin Signaling Pathway
    Development Prolactin receptor signaling0.39
    Leptin signaling pathway0.35
    Prolactin Signaling Pathway0.39

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways

    Selected R&D Systems Pathways for IRS1 (see all 8)
        IL-21 Signaling Pathways
    IL-2 Signaling Pathways
    IL-4 Signaling Pathways
    Adipocytokines & Insulin Signaling
    IL-7 Signaling Pathways

    Selected Downloadable PowerPoint Slides of GeneGlobe Pathway Central Maps for IRS1 (see all 19)
        IL-4 Pathway
    Molecular Mechanisms of Cancer
    Interferon Pathway
    JNK Pathway
    mTOR Pathway

    2 Cell Signaling Technology (CST) Pathways for IRS1
        Tyrosine Kinases / Adaptors
    Glucose / Energy Metabolism

    Selected GeneGo (Thomson Reuters) Pathways for IRS1 (see all 22)
        Apoptosis and survival Caspase cascade
    Signal transduction AKT signaling
    Immune response IL-9 signaling pathway
    Transcription PPAR Pathway
    Translation Insulin regulation of translation

    Selected BioSystems Pathways for IRS1 (see all 27)
        Adipogenesis
    Insulin Signaling
    DNA damage response (only ATM dependent)
    EPO Receptor Signaling
    Integrated Breast Cancer Pathway

    Selected Reactome Pathways for IRS1 (see all 10)
        PI3K Cascade
    PI3K/AKT activation
    Signal attenuation
    SOS-mediated signalling
    Constitutive PI3K/AKT Signaling in Cancer

    1 PharmGKB Pathway for IRS1
        Anti-diabetic Drug Potassium Channel Inhibitors Pathway, Pharmacodynamics

    Selected Kegg Pathways  (Kegg details for IRS1) (see all 10):
        FoxO signaling pathway
    mTOR signaling pathway
    PI3K-Akt signaling pathway
    Neurotrophin signaling pathway
    Insulin signaling pathway


    IRS1 for pathways           About GeneDecksing

        Pathway & Disease-focused RT2 Profiler PCR Arrays including IRS1 (see all 10): 
              mTOR Signaling in human mouse rat
              Insulin Signaling Pathway in human mouse rat
              Liver Cancer in human mouse rat
              Diabetes in human mouse rat
              Adipogenesis in human mouse rat

    Interactions:

        GeneGlobe Interaction Network for IRS1

    STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

    Selected Interacting proteins for IRS1 (P355681, 2, 3 ENSP000003048954) via UniProtKB, MINT, STRING, and/or I2D (see all 212)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    PIK3R1P279861, 2, 3, ENSP000002743354EBI-517592,EBI-79464 MINT-8036617 MINT-8028908 MINT-8036602 MINT-8033089 MINT-8036587 MINT-8033340 MINT-8036572 MINT-8028923 MINT-8033074 MINT-68735 I2D: score=10 STRING: ENSP00000274335
    PTPN11Q061241, 2, 3, ENSP000003409444EBI-517592,EBI-297779 MINT-8035069 MINT-8032601 MINT-8037305 I2D: score=5 STRING: ENSP00000340944
    ERBB2P046261, 2, 3, ENSP000002695714EBI-517592,EBI-641062 MINT-74553 MINT-74552 I2D: score=2 STRING: ENSP00000269571
    YWHAEP622582, 3, ENSP000002643354MINT-16662 MINT-8005105 MINT-8005168 MINT-8005150 MINT-16661 MINT-8005175 I2D: score=7 STRING: ENSP00000264335
    SFNP319472, 3, ENSP000003409894MINT-3975430 I2D: score=2 STRING: ENSP00000340989
    About this table

    Gene Ontology (GO): Selected biological process terms (see all 32):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0002053positive regulation of mesenchymal cell proliferation IEA--
    GO:0007165signal transduction TAS1311924
    GO:0007173epidermal growth factor receptor signaling pathway TAS--
    GO:0008284positive regulation of cell proliferation NAS17925406
    GO:0008286insulin receptor signaling pathway TAS--

    IRS1 for ontologies           About GeneDecksing



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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    Browse Small Molecules at EMD Millipore
       Browse drugs & compounds from Enzo Life Sciences
      Browse compounds at ApexBio 

    Browse Tocris compounds for IRS1

    1 DrugBank Compound for IRS1    About this table
    CompoundSynonyms CAS #TypeActionsPubMed Ids
    [4-({5-(AMINOCARBONYL)-4-[(3-METHYLPHENYL)AMINO]PYRIMIDIN-2-YL}AMINO)PHENYL]ACETIC ACID-- --target--10592235

    Selected Novoseek inferred chemical compound relationships for IRS1 gene (see all 87)    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    phosphatidylinositol 90.7 672 8385139 (7), 1332046 (6), 9242642 (5), 1380456 (5) (see all 99)
    tyrosine 87.3 1172 1334490 (5), 7592659 (5), 15130378 (5), 15240096 (5) (see all 99)
    glucose 78.9 352 15001544 (5), 16556765 (5), 15581362 (4), 10764799 (4) (see all 99)
    phosphotyrosine 77.5 75 7520748 (3), 8383963 (3), 9312143 (3), 14668342 (3) (see all 42)
    glycogen 76.2 93 8037748 (3), 17279354 (2), 10416561 (2), 11325523 (2) (see all 61)
    wortmannin 75 32 8660383 (4), 8649395 (2), 8674815 (2), 9761740 (2) (see all 22)
    serine 72.9 441 12351658 (6), 7818531 (5), 14556646 (5), 10488146 (5) (see all 99)
    ag 1024 70.2 6 17454144 (1), 18762365 (1), 14767998 (1)
    rapamycin 68.6 92 17908691 (4), 18264722 (4), 10847581 (4), 11438661 (3) (see all 39)
    2-deoxyglucose 67.2 13 7507665 (1), 8960823 (1), 11438661 (1), 16269459 (1) (see all 11)



    IRS1 for compounds           About GeneDecksing



    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
    Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, and/or QIAGEN )
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    REFSEQ mRNAs for IRS1 gene: 
    NM_005544.2  

    Unigene Cluster for IRS1:

    Insulin receptor substrate 1
    Hs.471508  [show with all ESTs]
    Unigene Representative Sequence: NM_005544
    2 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000305123(uc002voh.4) ENST00000498335
    miRNA
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    Block miRNA regulation of human, mouse, rat IRS1 using miScript Target Protectors
    Selected qRT-PCR Assays for microRNAs that regulate IRS1 (see all 119):
    hsa-miR-576-3p hsa-miR-548j hsa-miR-26a-2* hsa-miR-15a hsa-miR-128 hsa-miR-30d hsa-miR-550a* hsa-miR-30a
    SwitchGear 3'UTR luciferase reporter plasmidIRS1 3' UTR sequence
    Inhib. RNA
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    Predesigned siRNA for gene silencing in human, mouse, rat IRS1
    Clone
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    OriGene clones in human, mouse for IRS1 (see all 7)
    OriGene ORF clones in mouse, rat for IRS1
    OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
    GenScript: all cDNA clones in your preferred vector: IRS1 (NM_005544)
    DNA2.0 Custom Codon Optimized Gene Synthesis Service for IRS1
    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat IRS1
    Primer
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    OriGene qPCR primer pairs and template standards for IRS1
    OriGene qSTAR qPCR primer pairs in human, mouse for IRS1
    Pre-validated RT2 qPCR Primer Assay in human, mouse, rat IRS1
      QuantiTect SYBR Green Assays in human, mouse, rat IRS1
      QuantiFast Probe-based Assays in human, mouse, rat IRS1

    Additional mRNA sequence: 

    BC053895.1 S62539.1 

    6 DOTS entries:

    DT.112047  DT.40220008  DT.447217  DT.40112397  DT.100716681  DT.97786529 

    Selected AceView cDNA sequences (see all 115):

    AI358832 AL043318 CB053406 AA860695 N34594 BQ433020 BG207239 AL039246 
    AI580782 AA694085 BM982252 NM_005544 CA425762 BG187732 AI681976 CB306477 
    S62539 AI160216 BU154427 D17048 BQ771873 AI752714 AA069842 BU541406 

    GeneLoc Exon Structure


    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
    About This Section

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    IRS1 expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: TATTGTAAAC
    IRS1 Expression
    About this image


    IRS1 expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database
     selected tissues (see all 3) fully expand
     
     Blood (Cardiovascular System)    fully expand to see all 3 entries
             Mature B-Cells Peripheral Blood
     
     Thymus (Hematopoietic System)
             Double Positive Thymocytes Thymus
     
     Thyroid (Endocrine System)
    IRS1 Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    IRS1 Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.471508
        Pathway & Disease-focused RT2 Profiler PCR Arrays including IRS1 (see all 10): 
              mTOR Signaling in human mouse rat
              Insulin Signaling Pathway in human mouse rat
              Liver Cancer in human mouse rat
              Diabetes in human mouse rat
              Adipogenesis in human mouse rat

    Primer
    Products:
    OriGene qPCR primer pairs and template standards for IRS1
    OriGene qSTAR qPCR primer pairs in human, mouse for IRS1
    Pre-validated RT2 qPCR Primer Assay in human, mouse, rat IRS1
    QuantiTect SYBR Green Assays in human, mouse, rat IRS1
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    In Situ
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    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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    This gene was present in the common ancestor of animals.

    Orthologs for IRS1 gene from Selected species (see all 13)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Irs11 , 5 insulin receptor substrate 11, 5 85.37(n)1
    89.17(a)1
      1 (42.00 cM)5
    163671  NM_010570.41  NP_034700.21 
     822331015 
    chicken
    (Gallus gallus)
    Aves IRS11 insulin receptor substrate 1 74.2(n)
    79.78(a)
      101749888  XM_004951101.1  XP_004951158.1 
    lizard
    (Anolis carolinensis)
    Reptilia IRS16
    insulin receptor substrate 1
    63(a)
    1 ↔ 1
    3(23742830-23746420)
    African clawed frog
    (Xenopus laevis)
    Amphibia Xl.9572 Xenopus laevis insulin receptor substrate-1-like protein more 78.78(n)    U27842.1 
    zebrafish
    (Danio rerio)
    Actinopterygii irs11 insulin receptor substrate 1 61.99(n)
    65.38(a)
      559281  XM_005157774.1  XP_005157831.1 
    fruit fly
    (Drosophila melanogaster)
    Insecta chico6
    chico
    21(a)
    1 → many
    2L(10242512-10247078)


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

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for IRS1 gene
    IRS22  IRS42  
    1 SIMAP similar gene for IRS1 using alignment to 4 protein entries:     IRS1_HUMAN (see all proteins):
    IRS2

    IRS1 for paralogs           About GeneDecksing



    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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    Polymorphic Variants from UniProtKB/Swiss-Prot
    IRS1_HUMAN, P35568: 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


    Selected SNPs for IRS1 (see all 1403)    About this table    
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 2 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    VAR_0053034
    Diabetes mellitus, non-insulin-dependent (NIDDM)4--see VAR_0053032 C Y mis40--------
    VAR_0053024
    Diabetes mellitus, non-insulin-dependent (NIDDM)4--see VAR_0053022 S Y mis40--------
    rs1048936421,2
    Cpathogenic1227032835(-) CCACAC/G/TGGATG 2 T R mis10--------
    rs18012781,2,,4
    C,F,Hother1227031747(-) CTCCCA/C/G/
            
    GGGCT
    2 R G mis1 ese319EA MN NA CA NS WA EU 9510
    rs1384350651,2
    C--219459551(+) CGGGT-/ATTTTT 1 -- int10--------
    rs343199591,2
    C--219489040(+) AGATTACAA/-  
            
    ACAGT
    1 -- int11Minor allele frequency- -:0.50CSA 2
    rs721748281,2
    C--219489042(+) GATTA-/ACAA  
            
    CAGTC
    1 -- int10--------
    rs30547951,2
    C--219489043(+) TTACA-/AACA  
            
    GTCTT
    1 -- int10--------
    rs2021091791,2
    --219494936(+) AAAAA-/ACAAAAA 1 -- int10--------
    rs2003409761,2
    C--219495078(+) AGTCT-/AAAAAAA 1 -- int10--------

    HapMap Linkage Disequilibrium report for IRS1 (227596033 - 227664475 bp)

    Structural Variations
         Database of Genomic Variants (DGV) 3 variations for IRS1:    About this table    
    Variant IDTypeSubtypePubMed ID
    nsv875921CNV Loss21882294
    nsv3190CNV Loss18451855
    nsv821910CNV Gain20364138

    Human Gene Mutation Database (HGMD): IRS1
    Selected Site Specific Mutation Identification with PCR Assays for IRS1 (see all 8):
    Cosmic IdAA Change
    39670p.Y47C
    35437p.R1140H
    48440p.V154L
    87724p.P679L
    48441p.E147D
    SeqTarget long-range PCR primers for resequencing IRS1
    DNA2.0 Custom Variant and Variant Library Synthesis for IRS1

    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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    OMIM gene information: 147545   
    OMIM disorders: 125853  
    UniProtKB/Swiss-Prot: IRS1_HUMAN, P35568
  • Diabetes mellitus, non-insulin-dependent (NIDDM) [MIM:125853]: A multifactorial disorder of glucose
    homeostasis caused by a lack of sensitivity to the body's 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. Note=The gene represented in this entry may be involved in disease
    pathogenesis

  • Selected diseases for IRS1 (see all 86):    
    About MalaCards
    lipoatrophic diabetes    insulin resistance    coronary artery disease    carbohydrate metabolic disorder
    type 2 diabetes mellitus    diabetes mellitus, noninsulin-dependent    polycystic ovary syndrome    ossification of the posterior longitudinal ligament of the spine
    silver-russell syndrome    gestational diabetes    estrogen-receptor negative breast cancer    familial combined hyperlipidemia
    21-hydroxylase deficiency    hyperinsulinism    precocious puberty    diabetes mellitus
    hyperandrogenism    hypertriglyceridemia    tuberous sclerosis    glucose intolerance

    4 diseases from the University of Copenhagen DISEASES database for IRS1:
    Diabetes mellitus     Hyperglycemia     Hyperinsulinism     Polycystic ovary syndrome

    IRS1 for disorders           About GeneDecksing

    Selected Novoseek inferred disease relationships for IRS1 gene (see all 64)    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    insulin resistance 89.1 293 16896943 (4), 12176670 (4), 12358865 (3), 15634339 (3) (see all 99)
    insulin sensitivity 79.2 40 19801385 (2), 15356080 (2), 10591678 (2), 10707551 (1) (see all 30)
    niddm 67.8 159 8739921 (6), 8104271 (5), 9032113 (5), 11038788 (4) (see all 44)
    hyperinsulinemia 64.6 25 10480621 (2), 10416561 (1), 15855318 (1), 17416760 (1) (see all 18)
    obesity 61.5 65 11317670 (4), 15636429 (3), 9812905 (3), 8960833 (3) (see all 28)
    polycystic ovary syndrome 58 32 15705377 (3), 15130378 (3), 11522686 (2), 15474880 (2) (see all 13)
    hyperglycemia 49.8 6 15855318 (1), 8617880 (1), 20207740 (1), 17184177 (1) (see all 5)
    syndrome x 42.2 2 10842657 (1)
    breast cancer 41.9 114 19261680 (5), 16882697 (5), 15917419 (5), 16151579 (4) (see all 46)
    diabetes gestational 41 10 10973656 (3), 17631765 (2), 17046546 (2), 11832353 (1)

    Genetic Association Database (GAD): IRS1
    Human Genome Epidemiology (HuGE) Navigator: IRS1 (138 documents)

    Export disorders for IRS1 gene to outside databases

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
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    PubMed articles for IRS1 gene, integrated from 10 sources (see all 1396):
    (articles sorted by number of sources associating them with IRS1)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. A novel T608R missense mutation in insulin receptor substrate-1 identified in a subject with type 2 diabetes impairs metabolic insulin signaling. (PubMed id 12679424)1, 2, 4, 9 Esposito D.L....Cama A. (J. Clin. Endocrinol. Metab. 2003)
    2. The Arg(972) variant in insulin receptor substrate-1 is associated with an atherogenic profile in offspring of type 2 diabetic patients. (PubMed id 12843189)1, 2, 4, 9 Marini M.A.... Sesti G. (J. Clin. Endocrinol. Metab. 2003)
    3. Aminoacid polymorphisms of insulin receptor substrate-1 in non- insulin-dependent diabetes mellitus. (PubMed id 8104271)1, 2, 4, 9 Almind K....Pedersen O. (Lancet 1993)
    4. Distinct modes of interaction of SHC and insulin receptor substrate-1 with the insulin receptor NPEY region via non-SH2 domains. (PubMed id 7559478)1, 2, 9 He W.... Gustafson T.A. (J. Biol. Chem. 1995)
    5. S6K directly phosphorylates IRS-1 on Ser-270 to promote insulin resistance in response to TNF-(alpha) signaling through IKK2. (PubMed id 18952604)1, 2, 9 Zhang J.... Ye J. (J. Biol. Chem. 2008)
    6. Human insulin receptor substrate-1 (IRS-1) polymorphism G972R causes IRS-1 to associate with the insulin receptor and inhibit receptor autophosphorylation. (PubMed id 15590636)1, 2, 9 McGettrick A.J.... Kahn C.R. (J. Biol. Chem. 2005)
    7. The role of insulin receptor substrate-1 gene (IRS1) in type 2 diabetes in Pima Indians. (PubMed id 14633864)1, 4, 9 Kovacs P....Baier L.J. (Diabetes 2003)
    8. The G972R variant of the insulin receptor substrate-1 (IRS-1) gene, body fat distribution and insulin-resistance. (PubMed id 11317670)1, 4, 9 Baroni M.G....Di Mario U. (Diabetologia 2001)
    9. The insulin-like growth factor-1 pathway mediator genes: SHC1 Met300Val shows a protective effect in breast cancer. (PubMed id 15308584)1, 4, 9 Wagner K....FAPrsti A. (Carcinogenesis 2004)
    10. No association of the G972S polymorphism of the insulin receptor substrate-1 gene with polycystic ovary syndrome in lean PCOS women with biochemical hyperandrogenemia. (PubMed id 20012307)1, 4, 9 Marioli D.J....Georgopoulos N.A. (Arch. Gynecol. Obstet. 2010)

    (in PubMed, OMIM, and NCBI Bookshelf)
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     ANDOR
    Aliases
    Disorders
    Free Text  

      Query String
    PubMed
    OMIM
    NCBI Bookshelf
      (Note: In FireFox, select the above section and copy using Ctrl-C)

    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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    Entrez Gene: 3667 HGNC: 6125 AceView: IRS1 Ensembl:ENSG00000169047 euGenes: HUgn3667
    ECgene: IRS1 Kegg: 3667 H-InvDB: IRS1

    (According to HUGE)
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      --

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
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    NameDescription
    PharmGKB entry for IRS1 Pharmacogenomics, SNPs, Pathways
    ATLAS Chromosomes in Cancer entry for IRS1 Genetics and Cytogenetics in Oncology and Haematology

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
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    Patent Information for IRS1 gene:
    Search GeneIP for patents involving IRS1

    GeneCards and IP:
    Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



    (Antibodies, recombinant proteins, and assays from EMD Millipore, R&D Systems, OriGene, QIAGEN, GenScript, Cell Signaling Technology, Novus Biologicals, Sino Biological, Enzo Life Sciences, Abcam, ProSpec, Cloud-Clone Corp., Thermo Fisher Scientific, LSBio, Gene Editing from DNA2.0. Clones from OriGene, GenScript, Sino Biological, DNA2.0, SwitchGear Genomics, Vector BioLabs, Cell lines from GenScript, and ESI BIO, PCR Arrays from QIAGEN, Drugs and/or compounds from EMD Millipore, Tocris Bioscience, Enzo Life Sciences, and/or ApexBio, In Situ Hybridization Assays from
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