This gene encodes a nonadrenergic imidazoline-1 receptor protein that localizes to the cytosol and anchors to the inner layer of the plasma membrane. The orthologous mouse protein has been shown to influence cytoskeletal organization and cell migration by binding to alpha-5-beta-1 integrin. In humans, this protein has been shown to bind to the adapter insulin receptor substrate 4 (IRS4) to mediate translocation of alpha-5 integrin from the cell membrane to endosomes. In human cardiac tissue, this gene was found to affect cell growth and death while in neural tissue it affected neuronal growth and differentiation.[3]
Clinical significance
Expression of this protein was reduced in human breast cancers while its overexpression reduced tumor growth and metastasis; possibly by limiting the expression of alpha-5 integrin.[3]
↑ 1.01.1Sano H, Liu SC, Lane WS, Piletz JE, Lienhard GE (May 2002). "Insulin receptor substrate 4 associates with the protein IRAS". J Biol Chem. 277 (22): 19439–47. doi:10.1074/jbc.M111838200. PMID11912194.
↑Piletz JE, Ivanov TR, Sharp JD, Ernsberger P, Chang CH, Pickard RT, Gold G, Roth B, Zhu H, Jones JC, Baldwin J, Reis DJ (Jul 2000). "Imidazoline receptor antisera-selected (IRAS) cDNA: cloning and characterization". DNA Cell Biol. 19 (6): 319–29. doi:10.1089/10445490050043290. PMID10882231.
Ivanov TR, Jones JC, Dontenwill M, et al. (1999). "Characterization of a partial cDNA clone detected by imidazoline receptor-selective antisera". J. Auton. Nerv. Syst. 72 (2–3): 98–110. doi:10.1016/S0165-1838(98)00094-0. PMID9851558.
Nagase T, Ishikawa K, Suyama M, et al. (1999). "Prediction of the coding sequences of unidentified human genes. XIII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro". DNA Res. 6 (1): 63–70. doi:10.1093/dnares/6.1.63. PMID10231032.
El-Ayoubi R, Gutkowska J, Regunathan S, Mukaddam-Daher S (2002). "Imidazoline receptors in the heart: characterization, distribution, and regulation". J. Cardiovasc. Pharmacol. 39 (6): 875–83. doi:10.1097/00005344-200206000-00013. PMID12021582.
Edwards L, Ernsberger P (2003). "The I(1)-imidazoline receptor in PC12 pheochromocytoma cells reverses NGF-induced ERK activation and induces MKP-2 phosphatase". Brain Res. 980 (1): 71–9. doi:10.1016/S0006-8993(03)02893-2. PMID12865160.
Dontenwill M, Pascal G, Piletz JE, et al. (2004). "IRAS, the human homologue of Nischarin, prolongs survival of transfected PC12 cells". Cell Death Differ. 10 (8): 933–5. doi:10.1038/sj.cdd.4401275. PMID12868002.
Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID14702039.
Dontenwill M, Piletz JE, Chen M, et al. (2004). "IRAS is an anti-apoptotic protein". Ann. N. Y. Acad. Sci. 1009: 400–12. doi:10.1196/annals.1304.054. PMID15028619.
Piletz JE, Deleersnijder W, Roth BL, et al. (2004). "IRAS splice variants". Ann. N. Y. Acad. Sci. 1009: 419–26. doi:10.1196/annals.1304.056. PMID15028621.
Chen MJ, Zhu HE, Piletz JE (2004). "Intracellular effect of imidazoline receptor on alpha(2A)-noradrenergic receptor". Ann. N. Y. Acad. Sci. 1009: 427–38. doi:10.1196/annals.1304.057. PMID15028622.
Zhu H, Hayes J, Chen M, et al. (2004). "Relationship between platelet imidazoline receptor-binding peptides and candidate imidazoline-1 receptor, IRAS". Ann. N. Y. Acad. Sci. 1009: 439–46. doi:10.1196/annals.1304.058. PMID15028623.
Lim KP, Hong W (2005). "Human Nischarin/imidazoline receptor antisera-selected protein is targeted to the endosomes by a combined action of a PX domain and a coiled-coil region". J. Biol. Chem. 279 (52): 54770–82. doi:10.1074/jbc.M411315200. PMID15475348.
Li F, Wu N, Su RB, et al. (2006). "Involvement of phosphatidylcholine-selective phospholipase C in activation of mitogen-activated protein kinase pathways in imidazoline receptor antisera-selected protein". J. Cell. Biochem. 98 (6): 1615–28. doi:10.1002/jcb.20806. PMID16598778.
