IRS1

Gene Information
 
Gene Symbol
IRS1
 
Aliases
HIRS-1
 
Entrez Gene ID
 
Gene Name
Insulin receptor substrate 1
 
Chromosomal Location
2q36.3
 
HGNC ID
 
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]
 
RefSeq DNA
 
RefSeq mRNA
  e!Ensembl
Gene
Transcript  
Protein

SNPs

SNP Id
Upstream Sequence
SNP
Downstream Sequence Functional Significance References
rs1801278
27264388

Gene Ontology (GO)

GO ID Ontology Function Evidence Reference
GO:0007165 Biological process Signal transduction TAS 1311924
GO:0008284 Biological process Positive regulation of cell proliferation NAS 17925406
GO:0008286 Biological process Insulin receptor signaling pathway IBA 21873635
GO:0008286 Biological process Insulin receptor signaling pathway IDA 16516141
GO:0008286 Biological process Insulin receptor signaling pathway IMP 16814735
Protein Information
 
Protein Name
Insulin receptor substrate 1, IRS-1
 
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
 
Refseq Proteins
 
UniProt
 
PDB
 
Pfam
Pfam Accession Pfam ID
PF02174 IRS
PF00169 PH
Pathways
 
KEGG
 
Reactome
 

cGMP-PKG signaling pathway
FoxO signaling pathway
Autophagy - animal
mTOR signaling pathway
PI3K-Akt signaling pathway
AMPK signaling pathway
Longevity regulating pathway
Longevity regulating pathway - multiple species
Neurotrophin signaling pathway
Insulin signaling pathway
Adipocytokine signaling pathway
Regulation of lipolysis in adipocytes
Type II diabetes mellitus
Insulin resistance
Non-alcoholic fatty liver disease (NAFLD)
Aldosterone-regulated sodium reabsorption
MicroRNAs in cancer

 

PI3K Cascade
IRS-mediated signalling
SOS-mediated signalling
PIP3 activates AKT signaling
Interleukin-7 signaling
PI3K/AKT activation
Constitutive Signaling by Aberrant PI3K in Cancer
IRS-related events triggered by IGF1R
RAF/MAP kinase cascade
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
IRS activation
Signal attenuation

Interactions
 
STRING MINT IntAct
ENSP00000302665 P05019 P05019
    View interactions
     

Associated Diseases

Disease groupDisease NameReferences
Cardiovascular Diseases
Coronary heart disease
Arteriosclerosis
Endocrine System Diseases
Diabetes Mellitus
PCOS
Neoplasms
Prostate cancer
References
 
 
PubMed ID Associated gene/s Associated condition Genetic Mutation Diagnostic Criteria Association with PCOS Ethnicity Conclusion
IRS-2 and IRS-4 
 
 
Women with PCOS were identified based on a history of oligo/amenorrhoea, hirsutism, and typical morphological appearance of polycystic ovaries 
Related 
11 women with PCOS and 10 regularly cycling control women 
This data demonstrates cell-specific alterations in IRS protein concentrations in theca cells from polycystic ovaries that are consistent with an exaggerated amplification of the insulin signal and which may play an important role in ovarian hyperandrogenism and thecal hyperplasia. 
CYP21 
 
G972R variant 
Inclusion criteria were evidence of ovulatory dysfunction in conjunction with hirsutism and/or hyperandrogenemia, as well as exclusion of other disorders, such as nonclassic 21-hydroxylase-deficient adrenal hyperplasia (NCAH), Cushing's syndrome, hyperpr 
Related 
PCOS (n = 114) and healthy controls (n = 95) 
This IRS1 variant and CYP21 mutations seem to play a limited role in the development of PCOS 
IRS-2 
 
 
PCOS was defined by oligo-ovulation, clinical and/or biochemical hyperandrogenism and exclusion of hyperprolactinaemia (serum prolactin <24 g/l), non-classic congenital adrenal hyperplasia [adrenocorticotrophic hormone (ACTH)-stimulated 17-hydroxyprogest 
Related 
Spanish PCOS (n = 103) women compared with a control group (n = 48) of healthy women 
The Gly972Arg in IRS-1 and Gly1057Asp in IRS-2 polymorphisms influence glucose homeostasis in premenopausal women, but are not associated with PCOS. 
ERK1/2 and MEK1/2 
 
 
Women with PCOS had six or fewer menses per year and elevated total testosterone and/or nonsex hormonebinding globulinbound testosterone levels 
Related 
Women with PCOS (n = 20) and control (n=15) 
ERK1/2 activation inhibits association of IRS-1 with p85 via IRS-1 Ser312 phosphorylation, 
 
 
variant in gene 
 
Related 
65 women with PCOS and 27 age-matched healthy women 
The IRS-1 Gly972Arg has the highest frequency reported world-wide for PCOS women. This variant is associated with insulin resistance and higher fasting insulin in PCOS women. 

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