NISCH

Function

This gene encodes a nonadrenergic imidazoline-1 receptor protein that localizes to the inner layer of the plasma membrane as well as early and recycling endosome membranes. It is a scaffold protein related to Sorting nexins and it regulates protein cargo traffic. 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.[5][6]

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.[5]

Interactions

NISCH has been shown to interact with IRS4,[3] Integrin alpha 5,[7] and small GTPases Rac1, Rab4a, Rab9a, Rab14 and Rab38 in GTP-bound form.[8] NISCH also interacts with phospholipid PI(3)P via its PX domain.[9]

See also

References
  1. GRCh38: Ensembl release 89: ENSG00000010322 - Ensembl, May 2017
  2. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  3. Sano H, Liu SC, Lane WS, Piletz JE, Lienhard GE (May 2002). "Insulin receptor substrate 4 associates with the protein IRAS". The Journal of Biological Chemistry. 277 (22): 19439–47. doi:10.1074/jbc.M111838200. PMID 11912194.
  4. Piletz JE, Ivanov TR, Sharp JD, Ernsberger P, Chang CH, Pickard RT, et al. (June 2000). "Imidazoline receptor antisera-selected (IRAS) cDNA: cloning and characterization". DNA and Cell Biology. 19 (6): 319–29. doi:10.1089/10445490050043290. PMID 10882231.
  5. "Entrez Gene: NISCH nischarin".
  6. Maziveyi M, Alahari SK (October 2015). "Breast Cancer Tumor Suppressors: A Special Emphasis on Novel Protein Nischarin". Cancer Research. 75 (20): 4252–9. doi:10.1158/0008-5472.CAN-15-1395. PMID 26392073.
  7. Alahari SK, Lee JW, Juliano RL (December 2000). "Nischarin, a novel protein that interacts with the integrin alpha5 subunit and inhibits cell migration". The Journal of Cell Biology. 151 (6): 1141–54. doi:10.1083/jcb.151.6.1141. PMC 2190593. PMID 11121431.
  8. Kuijl C, Pilli M, Alahari SK, Janssen H, Khoo PS, Ervin KE, et al. (March 2013). "Rac and Rab GTPases dual effector Nischarin regulates vesicle maturation to facilitate survival of intracellular bacteria". The EMBO Journal. 32 (5): 713–27. doi:10.1038/emboj.2013.10. PMC 3590985. PMID 23386062.
  9. Lim KP, Hong W (December 2004). "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". The Journal of Biological Chemistry. 279 (52): 54770–82. doi:10.1074/jbc.m411315200. PMID 15475348.

Further reading
  • Ivanov TR, Jones JC, Dontenwill M, Bousquet P, Piletz JE (October 1998). "Characterization of a partial cDNA clone detected by imidazoline receptor-selective antisera". Journal of the Autonomic Nervous System. 72 (2–3): 98–110. doi:10.1016/S0165-1838(98)00094-0. PMID 9851558.
  • Nagase T, Ishikawa K, Suyama M, Kikuno R, Hirosawa M, Miyajima N, et al. (February 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 Research. 6 (1): 63–70. doi:10.1093/dnares/6.1.63. PMID 10231032.
  • El-Ayoubi R, Gutkowska J, Regunathan S, Mukaddam-Daher S (June 2002). "Imidazoline receptors in the heart: characterization, distribution, and regulation". Journal of Cardiovascular Pharmacology. 39 (6): 875–83. doi:10.1097/00005344-200206000-00013. PMID 12021582.
  • Edwards L, Ernsberger P (August 2003). "The I(1)-imidazoline receptor in PC12 pheochromocytoma cells reverses NGF-induced ERK activation and induces MKP-2 phosphatase". Brain Research. 980 (1): 71–9. doi:10.1016/S0006-8993(03)02893-2. PMID 12865160.
  • Dontenwill M, Pascal G, Piletz JE, Chen M, Baldwin J, Rondé P, et al. (August 2003). "IRAS, the human homologue of Nischarin, prolongs survival of transfected PC12 cells". Cell Death and Differentiation. 10 (8): 933–5. doi:10.1038/sj.cdd.4401275. PMID 12868002.
  • Dontenwill M, Piletz JE, Chen M, Baldwin J, Pascal G, Ronde P, et al. (December 2003). "IRAS is an anti-apoptotic protein". Annals of the New York Academy of Sciences. 1009 (1): 400–12. Bibcode:2003NYASA1009..400D. doi:10.1196/annals.1304.054. PMID 15028619.
  • Piletz JE, Deleersnijder W, Roth BL, Ernsberger P, Zhu H, Ziegler D (December 2003). "IRAS splice variants". Annals of the New York Academy of Sciences. 1009 (1): 419–26. Bibcode:2003NYASA1009..419P. doi:10.1196/annals.1304.056. PMID 15028621.
  • Chen MJ, Zhu HE, Piletz JE (December 2003). "Intracellular effect of imidazoline receptor on alpha(2A)-noradrenergic receptor". Annals of the New York Academy of Sciences. 1009: 427–38. doi:10.1196/annals.1304.057. PMID 15028622.
  • Zhu H, Hayes J, Chen M, Baldwin J, Piletz JE (December 2003). "Relationship between platelet imidazoline receptor-binding peptides and candidate imidazoline-1 receptor, IRAS". Annals of the New York Academy of Sciences. 1009 (1): 439–46. Bibcode:2003NYASA1009..439Z. doi:10.1196/annals.1304.058. PMID 15028623.
  • Lim KP, Hong W (December 2004). "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". The Journal of Biological Chemistry. 279 (52): 54770–82. doi:10.1074/jbc.M411315200. PMID 15475348.
  • Li F, Wu N, Su RB, Zheng JQ, Xu B, Lu XQ, et al. (August 2006). "Involvement of phosphatidylcholine-selective phospholipase C in activation of mitogen-activated protein kinase pathways in imidazoline receptor antisera-selected protein". Journal of Cellular Biochemistry. 98 (6): 1615–28. doi:10.1002/jcb.20806. PMID 16598778.

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