GenAge entry for IGF1R (Homo sapiens)

Gene name (HAGRID: 0015)

HGNC symbol: IGF1R
Aliases: JTK13; CD221; IGFIR; MGC18216; IGFR
Common name: insulin-like growth factor 1 receptor

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: The receptor for IGF1, IGF1R mediates the activation of the IGF1-stimulated signalling cascade. Evidence from model organisms, including results from flies [0187] and roundworms [0239], relates IGF1R homologues to ageing, most likely as part of the GH1/IGF1 axis. Mice heterozygous for IGF1R live 26% longer, though it is unclear whether they age slower. Null mutants are not viable [0018]. The IGF1/GH1 axis appears to impact on ageing in model organisms, including rodents, and so IGF1R may affect human ageing. In humans, IGF1R has been implicated with growth retardation [0186], and genotype combinations in the human IGF1R and PIK3CB genes have been related to plasma IGF1 levels and longevity [0141].

Cytogenetic information

Cytogenetic band: 15q26.3
Location: 97,010,287 bp to 97,319,034 bp
Orientation: Plus strand

Display region using the UCSC Genome Browser

Protein information

Gene Ontology

Process:

GO:0006468; protein amino acid phosphorylation
GO:0007420; brain development
GO:0009887; organ morphogenesis
GO:0030238; male sex determination

Function:

GO:0000166; nucleotide binding
GO:0004713; protein tyrosine kinase activity
GO:0004872; receptor activity
GO:0005524; ATP binding
GO:0016740; transferase activity

Cellular component:

GO:0016020; membrane

Protein interactions and network

Protein-protein interacting partners in GenAge: SHC1, PTPN11, IGF1, IGF2, INS, IRS1, PTPN1, IRS2, IGFBP3, YWHAZ, PIK3R1, SOCS2
IDG: Display interactions using the IGD
STRING interaction network

Retrieve sequences for IGF1R

ORF: ORF
CDS: CDS

Homologues in model organisms

Bos taurus: IGF1R_BOVI
Caenorhabditis elegans: daf-2
Danio rerio: igf1ra
Danio rerio: igf1rb
Drosophila melanogaster: InR
Mus musculus: Igf1r
Pan troglodytes: IGF1R
Rattus norvegicus: Igf1r

In other databases

GenDR

This gene is present in the GenDR gene manipulations database for Caenorhabditis elegans.

GenAge

This gene has the homolog daf-2 in GenAge for Caenorhabditis elegans
This gene has the homolog Igf1r in GenAge for Mus musculus
This gene has the homolog InR in GenAge for Drosophila melanogaster

AnAge

This species has an entry in AnAge

Selected references

[1960] Bokov et al. (2011) Does reduced IGF-1R signaling in Igf1r+/- mice alter aging?, PubMed
[2041] Kappeler et al. (2008) Brain IGF-1 receptors control mammalian growth and lifespan through a neuroendocrine mechanism., PubMed
[2119] Li et al. (2008) Age-related differences in insulin-like growth factor-1 receptor signaling regulates Akt/FOXO3a and ERK/Fos pathways in vascular smooth muscle cells., PubMed
[1908] Suh et al. (2008) Functionally significant insulin-like growth factor I receptor mutations in centenarians, PubMed
[1775] Baugh and Sternberg (2006) DAF-16/FOXO regulates transcription of cki-1/Cip/Kip and repression of lin-4 during C. elegans L1 arrest, 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, PubMed
[1485] Kurosu et al. (2005) Suppression of aging in mice by the hormone Klotho, PubMed
[1783] Yang et al. (2005) Activated IGF-1R inhibits hyperglycemia-induced DNA damage and promotes DNA repair by homologous recombination, PubMed
[1347] Bartke (2005) Role of the growth hormone/insulin-like growth factor system in mammalian aging, 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, PubMed
[1266] Franceschi et al. (2005) Genes involved in immune response/inflammation, IGF1/insulin pathway and response to oxidative stress play a major role in the genetics of human longevity: the lesson of centenarians, PubMed
[1241] de Magalhaes et al. (2005) The influence of genes on the aging process of mice: a statistical assessment of the genetics of aging, PubMed
[1268] Holzenberger et al. (2004) IGF-1 signaling and aging, PubMed
[1261] Wessells et al. (2004) Insulin regulation of heart function in aging fruit flies, PubMed
[1306] Shahrabani-Gargir et al. (2004) Ataxia-telangiectasia mutated gene controls insulin-like growth factor I receptor gene expression in a deoxyribonucleic acid damage response pathway via mechanisms involving zinc-finger transcription factors Sp1 and WT1, PubMed
[1157] Mobbs (2004) Not wisely but too well: aging as a cost of neuroendocrine activity, PubMed
[1271] Holzenberger (2004) The GH/IGF-I axis and longevity, PubMed
[1119] Martin and Friedman (2004) Ticking fast or ticking slow, through shc must you go?, PubMed
[1107] Quarrie and Riabowol (2004) Murine models of life span extension, PubMed
[1146] Maier et al. (2004) Modulation of mammalian life span by the short isoform of p53, PubMed
[1151] Dupont and Holzenberger (2003) Biology of insulin-like growth factors in development, PubMed
[0899] Liang et al. (2003) Genetic mouse models of extended lifespan, PubMed
[0966] Abuzzahab et al. (2003) IGF-I receptor mutations resulting in intrauterine and postnatal growth retardation, PubMed
[0964] Nef et al. (2003) Testis determination requires insulin receptor family function in mice, PubMed
[0141] Bonafe et al. (2003) Polymorphic variants of insulin-like growth factor I (IGF-I) receptor and phosphoinositide 3-kinase genes affect IGF-I plasma levels and human longevity: cues for an evolutionarily conserved mechanism of life span control, PubMed
[0018] Holzenberger et al. (2003) IGF-1 receptor regulates lifespan and resistance to oxidative stress in mice, PubMed
[0187] Tatar et al. (2001) A mutant Drosophila insulin receptor homolog that extends life-span and impairs neuroendocrine function, PubMed
[1591] Peretz et al. (2001) ATM-dependent expression of the insulin-like growth factor-I receptor in a pathway regulating radiation response, PubMed
[1109] Lupu et al. (2001) Roles of growth hormone and insulin-like growth factor 1 in mouse postnatal growth, PubMed
[0189] Wolkow et al. (2000) Regulation of C. elegans life-span by insulinlike signaling in the nervous system, PubMed
[0425] Gil et al. (1999) Regulation of the insulin-like developmental pathway of Caenorhabditis elegans by a homolog of the PTEN tumor suppressor gene, PubMed
[0948] Paradis and Ruvkun (1998) Caenorhabditis elegans Akt/PKB transduces insulin receptor-like signals from AGE-1 PI3 kinase to the DAF-16 transcription factor, PubMed
[0241] Baker et al. (1993) Role of insulin-like growth factors in embryonic and postnatal growth, PubMed
[0965] Liu et al. (1993) Mice carrying null mutations of the genes encoding insulin-like growth factor I (Igf-1) and type 1 IGF receptor (Igf1r), PubMed
[0239] Kenyon et al. (1993) A C. elegans mutant that lives twice as long as wild type, PubMed
[0186] Roback et al. (1991) An infant with deletion of the distal long arm of chromosome 15 (q26.1----qter) and loss of insulin-like growth factor 1 receptor gene, PubMed