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Gene Review

NISCH  -  nischarin

Homo sapiens

Synonyms: I-1, I-1 receptor candidate protein, I1R, I1R candidate protein, IR1, ...
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Disease relevance of NISCH


Psychiatry related information on NISCH

  • This study suggests that IRAS mediates agmatine's high affinity effects on cellular morphine dependence and may play a role in opioid dependence [2].

High impact information on NISCH

  • Our data further show that PKA targets protein phosphatase-1 (PP1) through the phosphorylation of a regulatory protein inhibitor-1 (I-1) to promote growth cone attraction [3].
  • IRAS, the human homologue of Nischarin, prolongs survival of transfected PC12 cells [4].
  • Interaction of human IRAS with alpha(5) integrin is not affected by the NH(2)-terminal extension, and overexpression of IRAS could cause a redistribution of surface alpha(5) integrin to intracellular endosomal structures [5].
  • The mouse homologue, previously identified as Nischarin, has been shown to interact with the alpha(5) subunit of integrin and inhibit cell migration (Alahari, S. K., Lee J. W., and Juliano R. L. (2000) J. Cell Biol. 51, 1141-1154) [5].
  • The PX domain of IRAS is essential for association with phosphatidylinositol 3-phosphate-enriched endosomal membranes [5].

Chemical compound and disease context of NISCH


Biological context of NISCH

  • However, hIRAS expression led to prolonged cell survival against known apoptotic stimuli: serum starvation or thapsigargin or staurosporine treatments [6].
  • In a host-cell-specific manner, transfection of IRAS cDNA into Chinese hamster ovary cells led to high-affinity I1 binding sites by criteria of nanomolar affinity for moxonidine and rilmenidine [7].
  • RESULTS: On average, IRAS participants consumed 0.8 servings of whole grains/d. Whole-grain intake was significantly associated with S(I) (beta = 0.082, P = 0.0005) and insulin (beta = -0.0646, P = 0.019) after adjustment for demographics, total energy intake and expenditure, smoking, and family history of diabetes [8].
  • Western blots with polyclonal anti-IRAS showed reduced IRAS expression in the major 85-kDa band relative to an actin reference, paralleling the reduction in binding site density [1].
  • Equally important, the Nischarin ODNs eliminated the production of MAPK(p42/44), a recognized signal transduction product generated by I1-receptor activation in differentiated PC12 cells [9].

Anatomical context of NISCH

  • 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 [5].
  • Focus was on antiserum(227-241), corresponding to amino acids No. 227 to 241 in IRAS, because this antiserum was found uniquely able to immunoprecipitate non-denatured 85-kD and 170-kD forms of IRAS from a human megakaryoblastoma cell line (MEG01), a model of platelet-producing cells [10].
  • When stably transfected into PC12 cells, hIRAS localizes to the cytosol as a 167 kDa immunoreactive protein [6].
  • The effect of Nischarin on Rac induced migration and invasion by breast and colon epithelial cell lines has been determined [11].
  • Nischarin, a cytosolic protein that binds the alpha5beta1 integrin, plays an important role in fibroblast migration, and in regulation of the actin cytoskeleton [11].

Associations of NISCH with chemical compounds

  • After irreversible blockade of alpha2-adrenergic receptors, binding was inhibited by the selective I1-agonist, moxonidine, and the I1-antagonist, efaroxan, in a concentration-dependent (10-12 to 10-5 M) manner [12].
  • The respective phenylalanine 312 of AT ties the alpha-helix hI1 to the molecule, thus stabilizing the tertiary structure [13].
  • Single-dish maps of SO, CH3OH, and SiO show pronounced wing emission to the west of the IRAS source, which interferometer observations reveal to be a compact region of outflow activity [14].
  • CS emission as redshifted and blueshifted velocities reveals a bipolar outflow oriented with a position angle of 45 degrees, while SiO emission appears to be tracing a fast shock interaction region at the CS red-lobe peak, 14" west and 8" south of the IRAS source [14].
  • It can be demonstrated that a methylene (-CH2-) substructure, as in cycloalkanes, is the likely carrier of the 6.9 microns band emission of dust that has recently been formed around IRAS 22272+5433, NGC 7027, and CPD -56 8032 [15].

Regulatory relationships of NISCH

  • On the other hand, overexpression of IRAS enhanced IRS-4-dependent insulin stimulation of the extracellularly regulated kinase [16].
  • In addition, Nischarin failed to inhibit migration induced by MEK1, a downstream effector in the Ras-Raf-MEK-Erk signaling cascade [11].

Other interactions of NISCH


Analytical, diagnostic and therapeutic context of NISCH

  • Immunoblotting also revealed increased expression of membranous alpha(2A)AR by IRAS [17].
  • The reversible self-assembly of a series of bipolar amphiphiles, alpha,omega-bis(3- or 4-amidinophenoxy)alkanes (chain length n = 5-12), on mercaptoalkanoic acid-functionalized gold surfaces (chain length n = 10, 11, 14, 15) has been studied by in-situ ellipsometry, IR reflection absorption spectroscopy (IRAS), and atomic force microscopy (AFM) [18].
  • Accuracy of IRAS GT interferometer and potential acuity meter prediction of visual acuity after phacoemulsification: prospective comparative study [19].
  • DESIGN AND SUBJECTS: Cross-sectional analysis of the IRAS (Insulin Resistance Atherosclerosis Study), a large (n=1559) tri-ethnic population (non-Hispanic whites, African-Americans and Mexican-Americans) across different states of glucose tolerance [20].
  • IRAS (infrared reflection-absorption spectroscopy) and STM (scanning tunneling microscopy) experiments revealed that single-component monolayers of II, III, and IV are essentially disordered, an important property that prevents excited photoluminescent molecules from self-quenching in the organic layers of an OLED device [21].


  1. Identification of IRAS/Nischarin as an I(1)-imidazoline receptor in PC12 rat pheochromocytoma cells. Sun, Z., Chang, C.H., Ernsberger, P. J. Neurochem. (2007) [Pubmed]
  2. IRAS, a candidate for I1-imidazoline receptor, mediates inhibitory effect of agmatine on cellular morphine dependence. Wu, N., Su, R.B., Xu, B., Lu, X.Q., Liu, Y., Zheng, J.Q., Piletz, J.E., Li, J., Qin, B.Y. Biochem. Pharmacol. (2005) [Pubmed]
  3. Spatial targeting of type II protein kinase A to filopodia mediates the regulation of growth cone guidance by cAMP. Han, J., Han, L., Tiwari, P., Wen, Z., Zheng, J.Q. J. Cell Biol. (2007) [Pubmed]
  4. IRAS, the human homologue of Nischarin, prolongs survival of transfected PC12 cells. Dontenwill, M., Pascal, G., Piletz, J.E., Chen, M., Baldwin, J., Rondé, P., Dupuy, L., Urosevic, D., Greney, H., Takeda, K., Bousquet, P. Cell Death Differ. (2003) [Pubmed]
  5. 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. Lim, K.P., Hong, W. J. Biol. Chem. (2004) [Pubmed]
  6. IRAS is an anti-apoptotic protein. Dontenwill, M., Piletz, J.E., Chen, M., Baldwin, J., Pascal, G., Ronde, P., Dupuy, L., Greney, H., Takeda, K., Bousquetd, P. Ann. N. Y. Acad. Sci. (2003) [Pubmed]
  7. Imidazoline receptor antisera-selected (IRAS) cDNA: cloning and characterization. Piletz, J.E., Ivanov, T.R., Sharp, J.D., Ernsberger, P., Chang, C.H., Pickard, R.T., Gold, G., Roth, B., Zhu, H., Jones, J.C., Baldwin, J., Reis, D.J. DNA Cell Biol. (2000) [Pubmed]
  8. Whole-grain intake and insulin sensitivity: the Insulin Resistance Atherosclerosis Study. Liese, A.D., Roach, A.K., Sparks, K.C., Marquart, L., D'Agostino, R.B., Mayer-Davis, E.J. Am. J. Clin. Nutr. (2003) [Pubmed]
  9. Nischarin as a functional imidazoline (I1) receptor. Zhang, J., Abdel-Rahman, A.A. FEBS Lett. (2006) [Pubmed]
  10. Relationship between platelet imidazoline receptor-binding peptides and candidate imidazoline-1 receptor, IRAS. Zhu, H., Hayes, J., Chen, M., Baldwin, J., Piletz, J.E. Ann. N. Y. Acad. Sci. (2003) [Pubmed]
  11. Nischarin inhibits Rac induced migration and invasion of epithelial cells by affecting signaling cascades involving PAK. Alahari, S.K. Exp. Cell Res. (2003) [Pubmed]
  12. Imidazoline receptors in the heart: characterization, distribution, and regulation. El-Ayoubi, R., Gutkowska, J., Regunathan, S., Mukaddam-Daher, S. J. Cardiovasc. Pharmacol. (2002) [Pubmed]
  13. Molecular and structural characterization of the heat-resistant thyroxine-binding globulin-Chicago. Janssen, O.E., Chen, B., Büttner, C., Refetoff, S., Scriba, P.C. J. Biol. Chem. (1995) [Pubmed]
  14. The circumstellar environment of IRAS 05338-0624. McMullin, J.P., Mundy, L.G., Blake, G.A. Astrophys. J. (1994) [Pubmed]
  15. Laboratory investigation of the contribution of complex aromatic/aliphatic polycyclic hybrid molecular structures to interstellar ultraviolet extinction and infrared emission. Arnoult, K.M., Wdowiak, T.J., Beegle, L.W. Astrophys. J. (2000) [Pubmed]
  16. Insulin receptor substrate 4 associates with the protein IRAS. Sano, H., Liu, S.C., Lane, W.S., Piletz, J.E., Lienhard, G.E. J. Biol. Chem. (2002) [Pubmed]
  17. Intracellular effect of imidazoline receptor on alpha(2A)-noradrenergic receptor. Chen, M.J., Zhu, H.E., Piletz, J.E. Ann. N. Y. Acad. Sci. (2003) [Pubmed]
  18. Odd-even chain length-dependent order in pH-switchable self-assembled layers. Auer, F., Nelles, G., Sellergren, B. Chemistry (Weinheim an der Bergstrasse, Germany) (2004) [Pubmed]
  19. Accuracy of IRAS GT interferometer and potential acuity meter prediction of visual acuity after phacoemulsification: prospective comparative study. Le Sage, C., Bazalgette, C., Arnaud, B., Schmitt-Bernard, C.F. Journal of cataract and refractive surgery. (2002) [Pubmed]
  20. The relation of body fat mass and distribution to markers of chronic inflammation. Festa, A., D'Agostino, R., Williams, K., Karter, A.J., Mayer-Davis, E.J., Tracy, R.P., Haffner, S.M. Int. J. Obes. Relat. Metab. Disord. (2001) [Pubmed]
  21. Monolayer structures of highly photoluminescent furan oligoaryls: an approach to improve packing crystallinity of dithiolated aromatics. Lin, S.Y., Chen, I.W., Chen, C.H., Lee, C.F., Chou, C.M., Luh, T.Y. The journal of physical chemistry. B, Condensed matter, materials, surfaces, interfaces & biophysical. (2005) [Pubmed]
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