IRS2

Last updated
IRS2
Protein IRS2 PDB 3FQW.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases IRS2 , IRS-2, insulin receptor substrate 2
External IDs OMIM: 600797; MGI: 109334; HomoloGene: 2778; GeneCards: IRS2; OMA:IRS2 - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_003749

NM_001081212

RefSeq (protein)

NP_003740

NP_001074681

Location (UCSC) Chr 13: 109.75 – 109.79 Mb Chr 8: 11.03 – 11.06 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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

Contents

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. 1 2 3 GRCh38: Ensembl release 89: ENSG00000185950 Ensembl, May 2017
  2. 1 2 3 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