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] See more...

Aliases for IRS1 Gene

Aliases for IRS1 Gene

  • Insulin Receptor Substrate 1 2 3 4 5
  • 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 Diabetes Mellitus, Noninsulin-Dependent and Rare Diabetes Mellitus Type 2. Among its related pathways are RET signaling and Downstream signaling events of B Cell Receptor (BCR). Gene Ontology (GO) annotations related to this gene include protein kinase binding and protein kinase C binding. An important paralog of this gene is IRS2.

UniProtKB/Swiss-Prot Summary 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

Additional gene information for IRS1 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for IRS1 Gene

Genomics for IRS1 Gene

GeneHancer (GH) Regulatory Elements for IRS1 Gene

Promoters and enhancers for IRS1 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH02J226788 Promoter/Enhancer 2.5 EPDnew FANTOM5 Ensembl ENCODE CraniofacialAtlas dbSUPER 502.3 +4.3 4253 13.8 EP300 FOXK2 ZBTB40 CTCF TCF12 MYC POLR2G USF1 SP1 NCOR1 RHBDD1 IRS1 ENSG00000261379 5MWI_A-105 ENSG00000272622 HSALNG0022707
GH02J226834 Promoter/Enhancer 2.2 EPDnew Ensembl ENCODE CraniofacialAtlas dbSUPER 10.8 -37.6 -37611 6.7 ZBTB40 EP300 SIN3A NRF1 MYC TCF12 USF1 POLR2G PHF8 PHB2 RHBDD1 lnc-COL4A3-4 lnc-IRS1-6 IRS1 piR-30521
GH02J226423 Enhancer 1.4 FANTOM5 ENCODE CraniofacialAtlas dbSUPER 15.7 +373.0 372998 7.3 EP300 TCF12 NCOR1 JUND FOS ZBTB25 TEAD1 ZBTB26 CTCF FOXA2 IRS1 HSALNG0022696 lnc-IRS1-1
GH02J226771 Enhancer 1.5 Ensembl ENCODE CraniofacialAtlas dbSUPER 11.9 +27.1 27140 3.6 SP1 EP300 TCF7 AFF1 TRIM28 RELA HES1 MEF2C RUNX1 CTBP1 IRS1 5MWI_A-105 HSALNG0022707
GH02J226981 Enhancer 1.6 FANTOM5 Ensembl ENCODE CraniofacialAtlas dbSUPER 11.1 -183.5 -183542 5.4 EP300 CTCF SP1 TCF7 REST RAD21 TRIM22 TEAD1 SMC3 ZSCAN9 lnc-COL4A4-1 IRS1 RHBDD1 COL4A3 lnc-IRS1-3 lnc-COL4A4-2 COL4A4
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around IRS1 on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for IRS1

Top Transcription factor binding sites by QIAGEN in the IRS1 gene promoter:
  • AP-1
  • ATF-2
  • c-Ets-1
  • c-Fos
  • c-Jun
  • CREB
  • deltaCREB
  • STAT3

Genomic Locations for IRS1 Gene

Genomic Locations for IRS1 Gene
chr2:226,731,317-226,799,759
(GRCh38/hg38)
Size:
68,443 bases
Orientation:
Minus strand
chr2:227,596,033-227,664,475
(GRCh37/hg19)
Size:
68,443 bases
Orientation:
Minus strand

Genomic View for IRS1 Gene

Genes around IRS1 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
IRS1 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
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:
    P35568-IRS1_HUMAN
    Recommended name:
    Insulin receptor substrate 1
    Protein Accession:
    P35568

    Protein attributes for IRS1 Gene

    Size:
    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 (PubMed:16127460). Interacts (via IRS-type PTB domain) with IGF1R and INSR (via the tyrosine-phosphorylated NPXY motif) (PubMed:7541045, PubMed:7559478, PubMed:7537849). Interacts with ALK (PubMed:15226403, PubMed:16878150). Interacts with EIF2AK2/PKR (By similarity). Interacts with GKAP1 (By similarity). Interacts with DGKZ in the absence of insulin; insulin stimulation decreases this interaction (By similarity). Found in a ternary complex with DGKZ and PIP5K1A in the absence of insulin stimulation (By similarity).

    Three dimensional structures from OCA and Proteopedia for IRS1 Gene

neXtProt entry for IRS1 Gene

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. Phosphorylated on tyrosine residues in response to insulin (By similarity).
  • 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:
REFSEQ proteins:

Antibody Products

  • Abcam antibodies for IRS1

No data available for DME Specific Peptides for IRS1 Gene

Domains & Families for IRS1 Gene

Gene Families for IRS1 Gene

HGNC:
Human Protein Atlas (HPA):
  • Disease related genes
  • Plasma proteins
  • Predicted intracellular proteins

Protein Domains for IRS1 Gene

Blocks:
  • Pleckstrin-like
  • Insulin receptor substrate-1 PTB domain signature
InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for IRS1 Gene

GenScript: Design optimal peptide antigens:
  • Insulin receptor substrate 1 (IRS1_HUMAN)
genes like me logo Genes that share domains with IRS1: view

No data available for Graphical View of Domain Structure and UniProtKB/Swiss-Prot for IRS1 Gene

Function for IRS1 Gene

Molecular function for IRS1 Gene

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).
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

Phenotypes From GWAS Catalog for IRS1 Gene

Gene Ontology (GO) - Molecular Function for IRS1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001784 phosphotyrosine residue binding IPI 20624904
GO:0005068 transmembrane receptor protein tyrosine kinase adaptor activity TAS,ISS --
GO:0005070 SH3/SH2 adaptor activity IDA 7493946
GO:0005080 protein kinase C binding ISS --
GO:0005158 insulin receptor binding IPI 7493946
genes like me logo Genes that share ontologies with IRS1: view
genes like me logo Genes that share phenotypes with IRS1: view

Human Phenotype Ontology for IRS1 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for IRS1 Gene

MGI Knock Outs for IRS1:

Animal Model Products

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for IRS1

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

Localization for IRS1 Gene

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for IRS1 gene
Compartment Confidence
plasma membrane 5
nucleus 5
cytosol 5
extracellular 3
mitochondrion 3
endoplasmic reticulum 3
cytoskeleton 2
peroxisome 2
endosome 2
lysosome 2
golgi apparatus 2

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cytosol (3)
  • Nucleoplasm (3)
  • Plasma membrane (3)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for IRS1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus ISS,IDA --
GO:0005654 nucleoplasm IDA --
GO:0005737 cytoplasm ISS,TAS --
GO:0005829 cytosol TAS --
GO:0005886 plasma membrane TAS,IBA --
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 & Interactions for IRS1 Gene

PathCards logo

SuperPathways for IRS1 Gene

SuperPathway Contained pathways
1 RET signaling
2 Regulation of lipid metabolism Insulin signaling-generic cascades
.59
.59
.51
.47
.44
.34
3 Common Cytokine Receptor Gamma-Chain Family Signaling Pathways
.42
4 GAB1 signalosome
5 IL-2 Pathway
.54
.49
.35
.34
genes like me logo Genes that share pathways with IRS1: view