IRS1

Gene Information
 
Gene Symbol
IRS1
 
Aliases
HIRS-1
 
Entrez Gene ID
 
Gene Name
Insulin receptor substrate 1
 
Chromosomal Location
2q36
 
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)
 
GeneCards ID
 
UniGene
 
RefSeq DNA
 
RefSeq mRNA
  e!Ensembl
Gene
Transcript  
Protein

Gene Ontology (GO)

GO ID Ontology Definition Evidence Reference
GO:0007165 Biological process Signal transduction TAS 1311924
GO:0008284 Biological process Positive regulation of cell proliferation NAS 17925406
GO:0010907 Biological process Positive regulation of glucose metabolic process IMP 16814735
GO:0014065 Biological process Phosphatidylinositol 3-kinase cascade IDA 7782332
GO:0032000 Biological process Positive regulation of fatty acid beta-oxidation IMP 16814735
Protein Information
 
Protein Name
Insulin receptor substrate 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 (By similarity)
 
Refseq Proteins
 
UniProt
 
PDB
 
InterPro
 
Pfam
Pfam Accession Pfam ID
PF00169 PH PH domain
PF02174 IRS PTB domain (IRS-1 type)
 
KEGG
 
OMIM
 
Phenotype MIM ID
 
Interactions

Associated Diseases

Diseases References
Atherosclerosis 12890697, 10480621
Cancer (carcinoma) 20179297, 17030605, 16882697, 8645156, 11102895
Coronary heart disease 12910680
Diabetes gestational 10973656, 17631765, 17046546, 11832353
Diabetes mellitus 11038788, 8636384, 7673430, 19140314, 8723689, 9398740, 10591678, 18585970, 9218152, 10206679, 7989470
   
References
 
Primary:

Prevalence of CYP21 mutations and IRS1 variant among women with polycystic ovary syndrome and adrenal androgen excess.

Witchel Selma F, Kahsar-Miller Melissa, Aston Christopher E, White Carlie, Azziz Ricardo
Department of Pediatrics, Children's Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, PA 15213, USA. selma.witchel@chp.edu
Fertil Steril. 2005 Feb;83(2):371-5.
 
Supporting Literature:
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, hyperp 
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 µg/l), non-classic congenital adrenal hyperplasia [adrenocorticotrophic hormone (ACTH)-stimulated 17-hydroxyproges 
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 non–sex hormone–binding globulin–bound 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. 

Unreviewed Literature:

PubMed / PMC ID
Title Type of study
26179926
Potent therapeutic effects of Shouwu Jiangqi Decoction () on polycystic ovary syndrome with insulin resistance in rats. 
Animal study 
25310961, PMC4203877
Association of Gly972Arg variant of insulin receptor subtrate-1 and Gly1057Asp variant of insulin receptor subtrate-2 with polycystic ovary syndrome in the Chinese population. 
Clinical study 
25064406
Association of abdominal obesity, insulin resistance, and oxidative stress in adipose tissue in women with polycystic ovary syndrome. 
Clinical study 
24842895
Lifestyle intervention up-regulates gene and protein levels of molecules involved in insulin signaling in the endometrium of overweight/obese women with polycystic ovary syndrome. 
Clinical study 
24672951
[Effect of Bushen Huatan Recipe on the Akt signal pathway in polycystic ovarian syndrome model rats with insulin resistance: an experimental research]. 
Animal study 

 

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