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

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

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