GenAge entry for IRS1 (Homo sapiens)

Gene name (HAGRID: 32)

HGNC symbol: IRS1
Aliases: HIRS-1
Common name: insulin receptor substrate 1

Potential relevance to the human ageing process

Main reason for selection: Entry selected based on evidence directly linking the gene product to ageing in a non-mammalian animal model
Description: IRS1 and IRS2 mediate many of the cellular actions of insulin (INS). Results from model organisms suggest IRS1 is involved in the IGF1/GH1 axis that could regulate ageing. In Drosophila, loss of chico, an insulin receptor substrate, extends lifespan [188]. Median lifespan was extended 18% in knockout mice from both sexes and 32% in females. Female animals displayed signs of resistance to ageing markers in skin, bone, immune system, and motor dysfunction, in spite of mild, lifelong insulin resistance. Heterozygous animals had normal lifespans [1924]. IRS1 may also be involved in the extended lifespan of some mouse strains [292]. In humans, mutations in IRS1 have been associated with diabetes [1658] and atherosclerosis [1657]. While it appears that IRS1 plays a role in some human age-related pathologies, its exact impact on the human ageing process is unknown.

Cytogenetic information

Cytogenetic band: 2q36
Location: 226,731,317 bp to 226,798,790 bp
Orientation: Minus strand

Display region using the UCSC Genome Browser (GRCh38/hg38)

Protein information

Gene Ontology

Process:

GO:0000165; MAPK cascade
GO:0007165; signal transduction
GO:0008284; positive regulation of cell proliferation
GO:0008286; insulin receptor signaling pathway
GO:0010907; positive regulation of glucose metabolic process
GO:0014065; phosphatidylinositol 3-kinase signaling
GO:0014066; regulation of phosphatidylinositol 3-kinase signaling
GO:0032000; positive regulation of fatty acid beta-oxidation
GO:0032868; response to insulin
GO:0032869; cellular response to insulin stimulus
GO:0036092; phosphatidylinositol-3-phosphate biosynthetic process

And 14 more GO terms

Cellular component:

GO:0005634; nucleus
GO:0005737; cytoplasm
GO:0005829; cytosol
GO:0005886; plasma membrane
GO:0005899; insulin receptor complex
GO:0005901; caveola
GO:0043231; intracellular membrane-bounded organelle

Function:

GO:0004871; signal transducer activity
GO:0005068; transmembrane receptor protein tyrosine kinase adaptor activity
GO:0005080; protein kinase C binding
GO:0005088; Ras guanyl-nucleotide exchange factor activity
GO:0005158; insulin receptor binding
GO:0005159; insulin-like growth factor receptor binding
GO:0005515; protein binding
GO:0016303; 1-phosphatidylinositol-3-kinase activity
GO:0042169; SH2 domain binding
GO:0043548; phosphatidylinositol 3-kinase binding
GO:0046934; phosphatidylinositol-4,5-bisphosphate 3-kinase activity

And 1 more GO terms

Show all GO terms

Protein interactions and network

Protein-protein interacting partners in GenAge: IGF1R, PTPN11, PTPN1, IRS2, AKT1, PIK3CB, EGFR, ERBB2, INSR, PRKCD, PLCG2, BCL2, GRB2, APP, SIRT1, MAPK8, PTK2, PIK3R1, HDAC2, JAK2, ESR1, MTOR, PIK3CA, IKBKB
STRING interaction network

Retrieve sequences for IRS1

ORF: ORF
CDS: CDS

Homologs in model organisms

Danio rerio: irs1
Mus musculus: Irs1
Rattus norvegicus: Irs1

In other databases

GenAge model organism genes

A homolog of this gene for Mus musculus is present as Irs1

LongevityMap

This gene is present as IRS1

Selected references

[2192] Jing et al. (2011) "Sirtuin-3 (Sirt3) regulates skeletal muscle metabolism and insulin signaling via altered mitochondrial oxidation and reactive oxygen species production." Proc. Natl. Acad. Sci. U.S.A. 108(35):14608-14613 (PubMed)
[1997] Kilpeläinen et al. (2011) "Genetic variation near IRS1 associates with reduced adiposity and an impaired metabolic profile." Nat. Genet. 43(8):753-760 (PubMed)
[1996] Rung et al. (2009) "Genetic variant near IRS1 is associated with type 2 diabetes, insulin resistance and hyperinsulinemia." Nat. Genet. 41(10):1110-1115 (PubMed)
[1924] Selman et al. (2008) "Evidence for lifespan extension and delayed age-related biomarkers in insulin receptor substrate 1 null mice." FASEB J. 22(3):807-818 (PubMed)
[3391] Foukas et al. (2006) "Critical role for the p110alpha phosphoinositide-3-OH kinase in growth and metabolic regulation." Nature 441(7091):366-370 (PubMed)
[1608] Masternak et al. (2006) "Caloric restriction and growth hormone receptor knockout: effects on expression of genes involved in insulin action in the heart." Exp. Gerontol. 41(4):417-429 (PubMed)
[1485] Kurosu et al. (2005) "Suppression of aging in mice by the hormone Klotho." Science 309(5742):1829-1833 (PubMed)
[1349] van Heemst et al. (2005) "Reduced insulin/IGF-1 signalling and human longevity." Aging Cell 4(2):79-85 (PubMed)
[1334] Papaconstantinou et al. (2005) "Hepatic gene and protein expression of primary components of the IGF-I axis in long lived Snell dwarf mice." Mech. Ageing Dev. 126(6-7):692-704 (PubMed)
[1318] Martin and Hall (2005) "The expanding TOR signaling network." Curr. Opin. Cell Biol. 17(2):158-166 (PubMed)
Show all references (13 more)