This gene encodes the insulin receptor substrate 2, a cytoplasmic signaling molecule that mediates effects of insulin, insulin-like growth factor 1, and other cytokines by acting as a molecular adaptor between diverse receptor tyrosine kinases and downstream effectors. The product of this gene is phosphorylated by the insulin receptor tyrosine kinase upon receptor stimulation, ... See more...

Aliases for IRS2 Gene

Aliases for IRS2 Gene

  • Insulin Receptor Substrate 2 2 3 4 5
  • IRS-2 3 4

External Ids for IRS2 Gene

Previous GeneCards Identifiers for IRS2 Gene

  • GC13M108766
  • GC13M104793
  • GC13M109242
  • GC13M108132
  • GC13M108104
  • GC13M109204
  • GC13M110406
  • GC13M091005

Summaries for IRS2 Gene

Entrez Gene Summary for IRS2 Gene

  • This gene encodes the insulin receptor substrate 2, a cytoplasmic signaling molecule that mediates effects of insulin, insulin-like growth factor 1, and other cytokines by acting as a molecular adaptor between diverse receptor tyrosine kinases and downstream effectors. The product of this gene is phosphorylated by the insulin receptor tyrosine kinase upon receptor stimulation, as well as by an interleukin 4 receptor-associated kinase in response to IL4 treatment. [provided by RefSeq, Jul 2008]

CIViC Summary for IRS2 Gene

GeneCards Summary for IRS2 Gene

IRS2 (Insulin Receptor Substrate 2) is a Protein Coding gene. Diseases associated with IRS2 include Diabetes Mellitus, Noninsulin-Dependent and Fatty Liver Disease. 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 domain specific binding. An important paralog of this gene is IRS1.

UniProtKB/Swiss-Prot Summary for IRS2 Gene

  • May mediate the control of various cellular processes by insulin.

Gene Wiki entry for IRS2 Gene

Additional gene information for IRS2 Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for IRS2 Gene

Genomics for IRS2 Gene

GeneHancer (GH) Regulatory Elements for IRS2 Gene

Promoters and enhancers for IRS2 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
GH13J109777 Promoter/Enhancer 2.4 EPDnew FANTOM5 Ensembl ENCODE CraniofacialAtlas dbSUPER 511.9 +4.0 4022 13.1 HNRNPK EP300 CTCF ZSCAN5C NRF1 USF1 SP1 GTF2E2 JUND PHF8 IRS2 ENSG00000275741 lnc-COL4A1-5
GH13J109381 Enhancer 1.2 FANTOM5 Ensembl ENCODE 19.4 +393.5 393482 24.2 JUND FOS EP300 MXI1 FOXA2 NR2F2 DEK GATA3 SMARCC2 SMARCA4 IRS2 piR-33614-081 lnc-IRS2-1 LINC00399 LOC105370359
GH13J110136 Promoter/Enhancer 1.7 FANTOM5 ENCODE CraniofacialAtlas dbSUPER 9.8 -351.1 -351079 3.1 CTCF USF1 JUND FOS ZIC2 POLR2A ZBTB11 ZBTB26 HES1 RELA ENSG00000287575 RAB20 IRS2 LOC101927712
GH13J109153 Enhancer 1.5 FANTOM5 Ensembl ENCODE dbSUPER 11 +628.2 628164 10 CTCF SIN3A SP1 JUND FOS TEAD4 EP300 REST RELA MEF2C IRS2 MYO16-AS1 MYO16 LOC105370356
GH13J109704 Enhancer 1.1 FANTOM5 ENCODE 13.5 +80.6 80585 3.8 TCF12 GTF2E2 ZIC2 POLR2A AFF1 TRIM28 TOE1 CTBP1 EP300 MYC LINC00676 IRS2 piR-60973 lnc-MYO16-8 LOC105370359 ENSG00000285534
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around IRS2 on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for IRS2

Top Transcription factor binding sites by QIAGEN in the IRS2 gene promoter:
  • AP-1
  • ATF-2
  • c-Jun
  • C/EBPalpha
  • E2F
  • NRSF form 1
  • NRSF form 2

Genomic Locations for IRS2 Gene

Genomic Locations for IRS2 Gene
chr13:109,752,695-109,786,583
(GRCh38/hg38)
Size:
33,889 bases
Orientation:
Minus strand
chr13:110,406,184-110,438,915
(GRCh37/hg19)
Size:
32,732 bases
Orientation:
Minus strand

Genomic View for IRS2 Gene

Genes around IRS2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
IRS2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for IRS2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for IRS2 Gene

Proteins for IRS2 Gene

  • Protein details for IRS2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9Y4H2-IRS2_HUMAN
    Recommended name:
    Insulin receptor substrate 2
    Protein Accession:
    Q9Y4H2
    Secondary Accessions:
    • Q96RR2
    • Q9BZG0
    • Q9Y6I5

    Protein attributes for IRS2 Gene

    Size:
    1338 amino acids
    Molecular mass:
    137334 Da
    Quaternary structure:
    • Interacts with PHIP.

    Three dimensional structures from OCA and Proteopedia for IRS2 Gene

neXtProt entry for IRS2 Gene

Post-translational modifications for IRS2 Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for IRS2 Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for IRS2 Gene

Domains & Families for IRS2 Gene

Gene Families for IRS2 Gene

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

Protein Domains for IRS2 Gene

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

Suggested Antigen Peptide Sequences for IRS2 Gene

GenScript: Design optimal peptide antigens:
  • Insulin receptor substrate 2 (IRS2_HUMAN)
  • Insulin receptor substrate-2 (Q8TF73_HUMAN)
  • Insulin receptor substrate 2 insertion mutant (Q96RG4_HUMAN)
  • Insulin receptor substrate 2 insertion mutant (Q96RG5_HUMAN)
  • Insulin receptor substrate-2 (Q9UP29_HUMAN)
genes like me logo Genes that share domains with IRS2: view

No data available for Graphical View of Domain Structure and UniProtKB/Swiss-Prot for IRS2 Gene

Function for IRS2 Gene

Molecular function for IRS2 Gene

UniProtKB/Swiss-Prot Function:
May mediate the control of various cellular processes by insulin.
GENATLAS Biochemistry:
insulin receptor substrate 2,pleiotropes mediator of insulin coordinating Igf-1 receptor-mediated beta cell development and peripheral insertion signaling,interacting with several proteins containing SH2 domains,such as PIKRs,GRB2,unlikely to be involved in NIDDM

Phenotypes From GWAS Catalog for IRS2 Gene

Gene Ontology (GO) - Molecular Function for IRS2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005158 insulin receptor binding IBA 21873635
GO:0005515 protein binding IPI 15161933
GO:0019901 protein kinase binding IEA --
GO:0019903 protein phosphatase binding IEA --
GO:0019904 protein domain specific binding IEA --
genes like me logo Genes that share ontologies with IRS2: view
genes like me logo Genes that share phenotypes with IRS2: view

Human Phenotype Ontology for IRS2 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for IRS2 Gene

MGI Knock Outs for IRS2:

Animal Model Products

CRISPR Products

Clone Products

  • Addgene plasmids for IRS2

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for IRS2 Gene

Localization for IRS2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for IRS2 Gene

Cytoplasm, cytosol.

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 IRS2 gene
Compartment Confidence
cytosol 5
plasma membrane 4
nucleus 4
extracellular 2
cytoskeleton 2
mitochondrion 2
peroxisome 2
endoplasmic reticulum 2
lysosome 2
endosome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cytosol (3)
  • Aggresome (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for IRS2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005623 cell IEA --
GO:0005737 cytoplasm IEA --
GO:0005829 cytosol TAS --
GO:0005886 plasma membrane IEA,TAS --
GO:0032991 protein-containing complex IEA --
genes like me logo Genes that share ontologies with IRS2: view

Pathways & Interactions for IRS2 Gene

PathCards logo

SuperPathways for IRS2 Gene

SuperPathway Contained pathways
1 RET signaling
2 Common Cytokine Receptor Gamma-Chain Family Signaling Pathways
.42
.38
.36
3 Regulation of lipid metabolism Insulin signaling-generic cascades
.59
.59
.51
.47
.34
4 GAB1 signalosome
5 Type I Interferon Signaling Pathways
.33
genes like me logo Genes that share pathways with IRS2: view

Pathways by source for IRS2 Gene

12 GeneGo (Thomson Reuters) pathways for IRS2 Gene
  • Development EGFR signaling via PIP3
  • Development Growth hormone signaling via PI3K/AKT and MAPK cascades
  • Development IGF-1 receptor signaling
  • Development Thrombopoietin-regulated cell processes
  • Development_Leptin signaling via PI3K-dependent pathway
10 Qiagen pathways for IRS2 Gene
  • AMPK Enzyme Complex Pathway
  • GDNF-Family Ligands and Receptor Interactions
  • IGF1R Signaling
  • IL-4 Pathway
  • IL-9 Pathway
1 Cell Signaling Technology pathway for IRS2 Gene

SIGNOR curated interactions for IRS2 Gene

Activates:
Is activated by:
Is inactivated by:

Gene Ontology (GO) - Biological Process for IRS2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000165 MAPK cascade TAS --
GO:0002053 positive regulation of mesenchymal cell proliferation IEA --
GO:0002903 negative regulation of B cell apoptotic process IEA,ISS --
GO:0006006 glucose metabolic process TAS 9495343
GO:0007165 signal transduction TAS 7675087
genes like me logo Genes that share ontologies with IRS2: view

Drugs & Compounds for IRS2 Gene

(24) Drugs for IRS2 Gene - From: Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials

(15) Additional Compounds for IRS2 Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with IRS2: view

Transcripts for IRS2 Gene

mRNA/cDNA for IRS2 Gene

1 REFSEQ mRNAs :
10 NCBI additional mRNA sequence :
1 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Clone Products

  • Addgene plasmids for IRS2

Alternative Splicing Database (ASD) splice patterns (SP) for IRS2 Gene

No ASD Table

Relevant External Links for IRS2 Gene

GeneLoc Exon Structure for
IRS2

Expression for IRS2 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for IRS2 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for IRS2 Gene

This gene is overexpressed in Brain (27.8) and Cerebrospinal fluid (22.2).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for IRS2 Gene



Transcriptomic regulation report from SPP (The Signaling Pathways Project) for IRS2

SOURCE GeneReport for Unigene cluster for IRS2 Gene:

Hs.442344

Evidence on tissue expression from TISSUES for IRS2 Gene

  • Liver(4.7)
  • Blood(4.5)
  • Nervous system(3.5)
  • Muscle(3.1)
  • Pancreas(3)
  • Heart(2.3)
  • Intestine(2.1)
  • Kidney(2)
genes like me logo Genes that share expression patterns with IRS2: view

No data available for mRNA differential expression in normal tissues , Protein tissue co-expression partners , mRNA Expression by UniProt/SwissProt and Phenotype-based relationships between genes and organs from Gene ORGANizer for IRS2 Gene

Orthologs for IRS2 Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for IRS2 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia IRS2 31 30
  • 97.69 (n)
OneToOne
dog
(Canis familiaris)
Mammalia IRS2 31 30
  • 87.38 (n)
OneToOne
cow
(Bos Taurus)
Mammalia IRS2 31 30
  • 84.79 (n)
OneToOne
rat
(Rattus norvegicus)
Mammalia Irs2 30
  • 81.48 (n)
mouse
(Mus musculus)
Mammalia Irs2 17 31 30
  • 80.8 (n)
oppossum
(Monodelphis domestica)
Mammalia IRS2 31
  • 73 (a)
OneToOne
chicken
(Gallus gallus)
Aves IRS2 31 30
  • 74.39 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia -- 31
  • 44 (a)
ManyToMany
tropical clawed frog
(Silurana tropicalis)
Amphibia LOC100498409 30
  • 57.07 (n)
African clawed frog
(Xenopus laevis)
Amphibia Xl.694 30
zebrafish
(Danio rerio)
Actinopterygii irs2 30
  • 61.73 (n)
IRS2 31
  • 53 (a)
OneToOne
zgc56306 30
fruit fly
(Drosophila melanogaster)
Insecta chico 31
  • 19 (a)
OneToMany
rice
(Oryza sativa)
Liliopsida Os.5303 30
sea squirt
(Ciona savignyi)
Ascidiacea -- 31
  • 36 (a)
OneToMany
Species where no ortholog for IRS2 was found in the sources mined by GeneCards:
  • 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 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 IRS2 Gene

ENSEMBL:
Gene Tree for IRS2 (if available)
TreeFam:
Gene Tree for IRS2 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for IRS2: view image

Paralogs for IRS2 Gene

Paralogs for IRS2 Gene

(2) SIMAP similar genes for IRS2 Gene using alignment to 6 proteins:

  • IRS2_HUMAN
  • L0R5B5_HUMAN
  • L8ECA6_HUMAN
  • Q96RG4_HUMAN
  • Q96RG5_HUMAN
  • Q9UP29_HUMAN
genes like me logo Genes that share paralogs with IRS2: view

Variants for IRS2 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for IRS2 Gene

SNP ID Clinical significance and condition Chr 13 pos Variation AA Info Type
rs137852740 Risk Factor: DIABETES, TYPE II, SUSCEPTIBILITY TO 109,784,115(-) G/C MISSENSE_VARIANT
rs1805097 Risk Factor: DIABETES, TYPE II, SUSCEPTIBILITY TO. - 109,782,884(-) C/Tp.Gly1057Asp MISSENSE_VARIANT
rs201499247 - p.Gly882Ala
rs35223808 - p.His789Tyr
rs35927012 - p.Val999Met

Additional dbSNP identifiers (rs#s) for IRS2 Gene

Structural Variations from Database of Genomic Variants (DGV) for IRS2 Gene

Variant ID Type Subtype PubMed ID
dgv3385n54 CNV loss 21841781
dgv3386n54 CNV gain+loss 21841781
dgv3387n54 CNV gain 21841781
dgv3388n54 CNV gain 21841781
dgv3389n54 CNV gain+loss 21841781
dgv348n67 CNV gain 20364138
dgv349n67 CNV gain 20364138
esv2157648 CNV deletion 18987734
esv22887 CNV loss 19812545
esv2500078 CNV deletion 19546169
esv2658062 CNV deletion 23128226
esv2660355 CNV deletion 23128226
esv2747995 CNV deletion 23290073
esv2747997 CNV deletion 23290073
esv29023 CNV gain+loss 19812545
esv3403446 CNV duplication 20981092
esv3582827 CNV gain 25503493
nsv1044855 CNV gain 25217958
nsv1071125 CNV deletion 25765185
nsv1126353 CNV deletion 24896259
nsv1131065 CNV deletion 24896259
nsv1136175 CNV deletion 24896259
nsv512337 CNV loss 21212237
nsv526943 CNV loss 19592680
nsv563072 CNV loss 21841781
nsv563076 CNV loss 21841781
nsv563088 CNV loss 21841781
nsv563094 CNV loss 21841781
nsv818995 CNV gain 17921354
nsv821265 CNV deletion 20802225
nsv826791 CNV loss 20364138
nsv826796 CNV gain 20364138
nsv9108 CNV gain+loss 18304495
nsv951919 CNV deletion 24416366

Variation tolerance for IRS2 Gene

Gene Damage Index Score: 6.02; 75.02% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for IRS2 Gene

Human Gene Mutation Database (HGMD)
IRS2
SNPedia medical, phenotypic, and genealogical associations of SNPs for
IRS2

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for IRS2 Gene

Disorders for IRS2 Gene

MalaCards: The human disease database

(19) MalaCards diseases for IRS2 Gene - From: OMIM, ClinVar, GTR, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
diabetes mellitus, noninsulin-dependent
  • niddm
fatty liver disease
  • steatosis of liver
polycystic ovary syndrome
  • pco
gestational diabetes
  • gdm
ascaris lumbricoides infection
  • ascaris lumbricoides infection, susceptibility to
- elite association - COSMIC cancer census association via MalaCards
Search IRS2 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for IRS2

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with IRS2: view

No data available for UniProtKB/Swiss-Prot and Genatlas for IRS2 Gene

Publications for IRS2 Gene

  1. Complex haplotypes of IRS2 gene are associated with severe obesity and reveal heterogeneity in the effect of Gly1057Asp mutation. (PMID: 12687350) Lautier C … Grigorescu F (Human genetics 2003) 3 4 23 41 54
  2. The IRS2 Gly1057Asp variant is associated with human longevity. (PMID: 19887537) Barbieri M … Paolisso G (The journals of gerontology. Series A, Biological sciences and medical sciences 2010) 3 23 41 54
  3. Insulin receptor substrate-2 gene polymorphism: is it associated with endometrial cancer? (PMID: 20184486) Cayan F … Dilek S (Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology 2010) 3 23 41 54
  4. Association of the FTO gene with obesity and the metabolic syndrome is independent of the IRS-2 gene in the female population of Southern France. (PMID: 19818665) Attaoua R … Grigorescu F (Diabetes & metabolism 2009) 3 23 41 54
  5. The G1057D polymorphism of IRS-2 gene is not associated with type 2 diabetes and obese patients among ethnic groups in Tunisian population. (PMID: 19332049) Ouederni TB … Benammar-Elgaaied A (Clinical biochemistry 2009) 3 23 41 54

Products for IRS2 Gene

Sources for IRS2 Gene