IRS2

Insulin receptor substrate 2 is a protein that in humans is encoded by the IRS2 gene.[5]

IRS2
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesIRS2, IRS-2, insulin receptor substrate 2
External IDsOMIM: 600797 MGI: 109334 HomoloGene: 2778 GeneCards: IRS2
Gene location (Human)
Chr.Chromosome 13 (human)[1]
Band13q34Start109,752,695 bp[1]
End109,786,583 bp[1]
RNA expression pattern


More reference expression data
Orthologs
SpeciesHumanMouse
Entrez

8660

384783

Ensembl

ENSG00000185950

ENSMUSG00000038894

UniProt

Q9Y4H2

P81122

RefSeq (mRNA)

NM_003749

NM_001081212

RefSeq (protein)

NP_003740

NP_001074681

Location (UCSC)Chr 13: 109.75 – 109.79 MbChr 8: 10.98 – 11.01 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Function

This gene encodes the insulin receptor substrate 2, a cytoplasmic signaling molecule that mediates effects of insulin, insulin-like growth factor 1, and other cytokines by acting as a molecular adaptor between diverse receptor tyrosine kinases and downstream effectors. The product of this gene is phosphorylated by the insulin receptor tyrosine kinase upon receptor stimulation, as well as by an interleukin 4 receptor-associated kinase in response to IL4 treatment.[6]

Mice lacking IRS2 have a diabetic phenotype[7] as well as a 40% reduction in brain mass.[8]

Interactions

IRS2 has been shown to interact with:

References

  1. GRCh38: Ensembl release 89: ENSG00000185950 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000038894 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. Ogihara T, Isobe T, Ichimura T, Taoka M, Funaki M, Sakoda H, Onishi Y, Inukai K, Anai M, Fukushima Y, Kikuchi M, Yazaki Y, Oka Y, Asano T (Oct 1997). "14-3-3 protein binds to insulin receptor substrate-1, one of the binding sites of which is in the phosphotyrosine binding domain". J Biol Chem. 272 (40): 25267–74. doi:10.1074/jbc.272.40.25267. PMID 9312143.
  6. "Entrez Gene: IRS2 insulin receptor substrate 2".
  7. Lin X, Taguchi A, Park S, Kushner JA, Li F, Li Y, White MF (October 2004). "Dysregulation of insulin receptor substrate 2 in beta cells and brain causes obesity and diabetes". J. Clin. Invest. 114 (7): 908–16. doi:10.1172/JCI22217. PMC 518668. PMID 15467829.
  8. Schubert M, Brazil DP, Burks DJ, Kushner JA, Ye J, Flint CL, Farhang-Fallah J, Dikkes P, Warot XM, Rio C, Corfas G, White MF (August 2003). "Insulin receptor substrate-2 deficiency impairs brain growth and promotes tau phosphorylation". J. Neurosci. 23 (18): 7084–92. doi:10.1523/JNEUROSCI.23-18-07084.2003. PMC 6740672. PMID 12904469.
  9. Sozzani P, Hasan L, Séguélas MH, Caput D, Ferrara P, Pipy B, Cambon C (March 1998). "IL-13 induces tyrosine phosphorylation of phospholipase C gamma-1 following IRS-2 association in human monocytes: relationship with the inhibitory effect of IL-13 on ROI production". Biochem. Biophys. Res. Commun. 244 (3): 665–70. doi:10.1006/bbrc.1998.8314. PMID 9535722.
  10. Rui L, Yuan M, Frantz D, Shoelson S, White MF (November 2002). "SOCS-1 and SOCS-3 block insulin signaling by ubiquitin-mediated degradation of IRS1 and IRS2". J. Biol. Chem. 277 (44): 42394–8. doi:10.1074/jbc.C200444200. PMID 12228220.
  11. Argetsinger LS, Norstedt G, Billestrup N, White MF, Carter-Su C (November 1996). "Growth hormone, interferon-gamma, and leukemia inhibitory factor utilize insulin receptor substrate-2 in intracellular signaling". J. Biol. Chem. 271 (46): 29415–21. doi:10.1074/jbc.271.46.29415. PMID 8910607.
  12. Verdier F, Chrétien S, Billat C, Gisselbrecht S, Lacombe C, Mayeux P (October 1997). "Erythropoietin induces the tyrosine phosphorylation of insulin receptor substrate-2. An alternate pathway for erythropoietin-induced phosphatidylinositol 3-kinase activation". J. Biol. Chem. 272 (42): 26173–8. doi:10.1074/jbc.272.42.26173. PMID 9334184.
  13. Kim B, Cheng HL, Margolis B, Feldman EL (December 1998). "Insulin receptor substrate 2 and Shc play different roles in insulin-like growth factor I signaling". J. Biol. Chem. 273 (51): 34543–50. doi:10.1074/jbc.273.51.34543. PMID 9852124.
  14. Hamer I, Foti M, Emkey R, Cordier-Bussat M, Philippe J, De Meyts P, Maeder C, Kahn CR, Carpentier JL (May 2002). "An arginine to cysteine(252) mutation in insulin receptors from a patient with severe insulin resistance inhibits receptor internalisation but preserves signalling events". Diabetologia. 45 (5): 657–67. doi:10.1007/s00125-002-0798-5. PMID 12107746.

Further reading

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