GenAge entry for IRS2 (Homo sapiens)

Gene name (HAGRID: 34)

HGNC symbol: IRS2
Aliases
Common name: insulin receptor substrate 2

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: IRS2 and IRS1 mediate many of the cellular actions of insulin (INS). Results from model organisms suggest IRS2 is involved in the IGF1/GH1 axis that appears to influence ageing in model organisms. In Drosophila, loss of chico, an insulin receptor substrate, extends lifespan [188]. IRS2 brain-specific knockout mice were overweight, hyperinsulinemic, glucose intolerant, yet more active and lived up to 18% longer [1919]. In another experiment, however, IRS2 knockout mice were reported to have a shorter median lifespan. Heterozygous animals had normal lifespans [1924]. IRS2 may also be involved in the extended lifespan of other mouse strains [292]. In humans, mutations in IRS2 have been associated with diabetes [1659]. IRS2 likely plays a role in some human age-related pathologies, but its exact impact on the human ageing process is unknown.

Cytogenetic information

Cytogenetic band: 13q34
Location: 109,753,837 bp to 109,786,567 bp
Orientation: Minus strand

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

Protein information

Gene Ontology

Process:

GO:0000165; MAPK cascade
GO:0002053; positive regulation of mesenchymal cell proliferation
GO:0002903; negative regulation of B cell apoptotic process
GO:0006006; glucose metabolic process
GO:0007165; signal transduction
GO:0007420; brain development
GO:0008283; cell proliferation
GO:0008284; positive regulation of cell proliferation
GO:0008286; insulin receptor signaling pathway
GO:0009749; response to glucose
GO:0010748; negative regulation of plasma membrane long-chain fatty acid transport
GO:0010907; positive regulation of glucose metabolic process
GO:0014066; regulation of phosphatidylinositol 3-kinase signaling
GO:0019216; regulation of lipid metabolic process
GO:0030335; positive regulation of cell migration
GO:0030879; mammary gland development
GO:0030890; positive regulation of B cell proliferation
GO:0032000; positive regulation of fatty acid beta-oxidation
GO:0032024; positive regulation of insulin secretion
GO:0032869; cellular response to insulin stimulus
GO:0033673; negative regulation of kinase activity
GO:0036092; phosphatidylinositol-3-phosphate biosynthetic process
GO:0043547; positive regulation of GTPase activity
GO:0045725; positive regulation of glycogen biosynthetic process
GO:0046326; positive regulation of glucose import
GO:0046854; phosphatidylinositol phosphorylation
GO:0048015; phosphatidylinositol-mediated signaling
GO:0055088; lipid homeostasis
GO:0071333; cellular response to glucose stimulus

Cellular component:

GO:0005829; cytosol
GO:0005886; plasma membrane
GO:0043234; protein complex

Function:

GO:0004871; signal transducer activity
GO:0005088; Ras guanyl-nucleotide exchange factor activity
GO:0005158; insulin receptor binding
GO:0005515; protein binding
GO:0016303; 1-phosphatidylinositol-3-kinase activity
GO:0019901; protein kinase binding
GO:0019903; protein phosphatase binding
GO:0019904; protein domain specific binding
GO:0043548; phosphatidylinositol 3-kinase binding
GO:0046934; phosphatidylinositol-4,5-bisphosphate 3-kinase activity
GO:0071889; 14-3-3 protein binding

Hide GO terms

Protein interactions and network

Protein-protein interacting partners in GenAge: PTPN11, IRS1, MYC, EGFR, INSR, EPOR, BCL2, GRB2, SIRT1, YWHAZ, PIK3R1, ESR1, PIK3CA
STRING interaction network

Retrieve sequences for IRS2

ORF: ORF
CDS: CDS

Homologs in model organisms

Danio rerio: zgc:56306
Mus musculus: Irs2
Rattus norvegicus: Irs2

In other databases

GenAge model organism genes

A homolog of this gene for Mus musculus is present as Irs2

GenDR gene expression

A homolog of this gene for Mus musculus is present as Irs2

LongevityMap

This gene is present as IRS2