NISCH explained

Nischarin is a protein that in humans is encoded by the NISCH gene.^{[1] [2] [3] [4]}

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.^[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]

Interactions

NISCH has been shown to interact with IRS4, Integrin alpha 5,^[5] and small GTPases Rac1, Rab4a, Rab9a, Rab14 and Rab38 in GTP-bound form.^[6] NISCH also interacts with phospholipid PI(3)P via its PX domain.^[7]

See also

• Imidazoline receptor

Further reading

• Ivanov TR, Jones JC, Dontenwill M, Bousquet P, Piletz JE . Characterization of a partial cDNA clone detected by imidazoline receptor-selective antisera . Journal of the Autonomic Nervous System . 72 . 2–3 . 98–110 . October 1998 . 9851558 . 10.1016/S0165-1838(98)00094-0 .
• Nagase T, Ishikawa K, Suyama M, Kikuno R, Hirosawa M, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O . 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 . February 1999 . 10231032 . 10.1093/dnares/6.1.63 . free .
• El-Ayoubi R, Gutkowska J, Regunathan S, Mukaddam-Daher S . Imidazoline receptors in the heart: characterization, distribution, and regulation . Journal of Cardiovascular Pharmacology . 39 . 6 . 875–83 . June 2002 . 12021582 . 10.1097/00005344-200206000-00013 . 40681466 . free .
• Edwards L, Ernsberger P . 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 . August 2003 . 12865160 . 10.1016/S0006-8993(03)02893-2 . 37607140 .
• Dontenwill M, Pascal G, Piletz JE, Chen M, Baldwin J, Rondé P, Dupuy L, Urosevic D, Greney H, Takeda K, Bousquet P . IRAS, the human homologue of Nischarin, prolongs survival of transfected PC12 cells . Cell Death and Differentiation . 10 . 8 . 933–5 . August 2003 . 12868002 . 10.1038/sj.cdd.4401275 . free .
• Dontenwill M, Piletz JE, Chen M, Baldwin J, Pascal G, Ronde P, Dupuy L, Greney H, Takeda K, Bousquetd P . IRAS is an anti-apoptotic protein . Annals of the New York Academy of Sciences . 1009 . 1. 400–12 . December 2003 . 15028619 . 10.1196/annals.1304.054 . 2003NYASA1009..400D . 36921298 .
• Bryan Roth . Piletz JE, Deleersnijder W, Roth BL, Ernsberger P, Zhu H, Ziegler D . IRAS splice variants . Annals of the New York Academy of Sciences . 1009 . 1. 419–26 . December 2003 . 15028621 . 10.1196/annals.1304.056 . 2003NYASA1009..419P . 23908934 .
• Chen MJ, Zhu HE, Piletz JE . Intracellular effect of imidazoline receptor on alpha(2A)-noradrenergic receptor . Annals of the New York Academy of Sciences . 1009 . 427–38 . December 2003 . 1 . 15028622 . 10.1196/annals.1304.057 . 2003NYASA1009..427C . 84144730 .
• Zhu H, Hayes J, Chen M, Baldwin J, Piletz JE . 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 . December 2003 . 15028623 . 10.1196/annals.1304.058 . 2003NYASA1009..439Z . 21454607 .
• Lim KP, Hong W . 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 . December 2004 . 15475348 . 10.1074/jbc.M411315200 . free .
• Li F, Wu N, Su RB, Zheng JQ, Xu B, Lu XQ, Cong B, Li J . 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 . August 2006 . 16598778 . 10.1002/jcb.20806 . 29347951 .

Notes and References

1. Sano H, Liu SC, Lane WS, Piletz JE, Lienhard GE . Insulin receptor substrate 4 associates with the protein IRAS . The Journal of Biological Chemistry . 277 . 22 . 19439–47 . May 2002 . 11912194 . 10.1074/jbc.M111838200 . free .
2. Piletz JE, Ivanov TR, Sharp JD, Ernsberger P, Chang CH, Pickard RT, Gold G, Roth B, Zhu H, Jones JC, Baldwin J, Reis DJ . Imidazoline receptor antisera-selected (IRAS) cDNA: cloning and characterization . DNA and Cell Biology . 19 . 6 . 319–29 . June 2000 . 10882231 . 10.1089/10445490050043290 .
3. Web site: Entrez Gene: NISCH nischarin.
4. Maziveyi M, Alahari SK . Breast Cancer Tumor Suppressors: A Special Emphasis on Novel Protein Nischarin . Cancer Research . 75 . 20 . 4252–9 . October 2015 . 26392073 . 10.1158/0008-5472.CAN-15-1395 . free .
5. Alahari SK, Lee JW, Juliano RL . Nischarin, a novel protein that interacts with the integrin alpha5 subunit and inhibits cell migration . The Journal of Cell Biology . 151 . 6 . 1141–54 . December 2000 . 11121431 . 10.1083/jcb.151.6.1141 . 2190593 . free .
6. Kuijl C, Pilli M, Alahari SK, Janssen H, Khoo PS, Ervin KE, Calero M, Jonnalagadda S, Scheller RH, Neefjes J, Junutula JR . Rac and Rab GTPases dual effector Nischarin regulates vesicle maturation to facilitate survival of intracellular bacteria . The EMBO Journal . 32 . 5 . 713–27 . March 2013 . 23386062 . 3590985 . 10.1038/emboj.2013.10 .
7. Lim KP, Hong W . 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 . December 2004 . 15475348 . 10.1074/jbc.m411315200 . free .