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
GO:0042593; glucose homeostasis
GO:0043434; response to peptide hormone
GO:0043547; positive regulation of GTPase activity
GO:0043552; positive regulation of phosphatidylinositol 3-kinase activity
GO:0045725; positive regulation of glycogen biosynthetic process
GO:0046326; positive regulation of glucose import
GO:0046627; negative regulation of insulin receptor signaling pathway
GO:0046628; positive regulation of insulin receptor signaling pathway
GO:0046676; negative regulation of insulin secretion
GO:0046854; phosphatidylinositol phosphorylation
GO:0048009; insulin-like growth factor receptor signaling pathway
GO:0048015; phosphatidylinositol-mediated signaling
GO:2001275; positive regulation of glucose import in response to insulin stimulus

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

Hide 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