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Gene Review

NF2  -  neurofibromin 2 (merlin)

Homo sapiens

Synonyms: ACN, BANF, Merlin, Moesin-ezrin-radixin-like protein, Neurofibromin-2, ...
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Disease relevance of NF2


Psychiatry related information on NF2

  • A single high i.v. dose of SCH 58500 (1.1 x 10(12) pfu/kg) was associated with lethargy, soft feces, a ruffled-hair coat, and death within 1 h postdose [6].
  • These findings extend to the behavioural parameters the protective effects of SCH 58261 in the QA model of Huntington's disease [7].
  • The effects of SCH 72788 suggest that M2 receptor antagonists may be useful for treating the cognitive decline observed in AD and other dementias [8].

High impact information on NF2


Chemical compound and disease context of NF2


Biological context of NF2


Anatomical context of NF2

  • Interaction between NF2 protein and the actin-containing cytoskeleton was indicated by partial colocalization, by cytochalasin B-induced coclustering, and by retention of NF2 protein in the detergent-insoluble fraction [18].
  • Both transfected and endogenous NF2 protein localized underneath the plasma membrane in a pattern typical of an ERM protein [18].
  • The cells contained restructured membrane extensions and blebs, and CHO cells expressing NF2 protein were more elongated than control transfectants [18].
  • In COS-1 transfectants, NF2 protein typically codistributed with ezrin but, in cells with poorly developed actin cytoskeleton, it replaced ezrin in filopodia and ruffling edges [18].
  • Merlin is also expressed in reactive astrocytes and in the astrocytes of NF2-associated glial hamartomas [19].

Associations of NF2 with chemical compounds


Physical interactions of NF2


Co-localisations of NF2

  • NF2 protein colocalized with CD44, which in transfected cells accumulated into restructured cell membrane protrusions [18].

Regulatory relationships of NF2


Other interactions of NF2


Analytical, diagnostic and therapeutic context of NF2


  1. A novel moesin-, ezrin-, radixin-like gene is a candidate for the neurofibromatosis 2 tumor suppressor. Trofatter, J.A., MacCollin, M.M., Rutter, J.L., Murrell, J.R., Duyao, M.P., Parry, D.M., Eldridge, R., Kley, N., Menon, A.G., Pulaski, K. Cell (1993) [Pubmed]
  2. Neurofibromatosis 2 tumour suppressor schwannomin interacts with betaII-spectrin. Scoles, D.R., Huynh, D.P., Morcos, P.A., Coulsell, E.R., Robinson, N.G., Tamanoi, F., Pulst, S.M. Nat. Genet. (1998) [Pubmed]
  3. Mixed-lineage kinase 3 regulates B-Raf through maintenance of the B-Raf/Raf-1 complex and inhibition by the NF2 tumor suppressor protein. Chadee, D.N., Xu, D., Hung, G., Andalibi, A., Lim, D.J., Luo, Z., Gutmann, D.H., Kyriakis, J.M. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  4. Cyclic AMP-dependent protein kinase phosphorylates merlin at serine 518 independently of p21-activated kinase and promotes merlin-ezrin heterodimerization. Alfthan, K., Heiska, L., Grönholm, M., Renkema, G.H., Carpén, O. J. Biol. Chem. (2004) [Pubmed]
  5. The tumor suppressor merlin interacts with microtubules and modulates Schwann cell microtubule cytoskeleton. Muranen, T., Grönholm, M., Lampin, A., Lallemand, D., Zhao, F., Giovannini, M., Carpén, O. Hum. Mol. Genet. (2007) [Pubmed]
  6. Rodent nonclinical safety evaluation studies of SCH 58500, an adenoviral vector for the p53 gene. Morrissey, R.E., Horvath, C., Snyder, E.A., Patrick, J., MacDonald, J.S. Toxicol. Sci. (2002) [Pubmed]
  7. Adenosine A(2A) receptor blockade before striatal excitotoxic lesions prevents long term behavioural disturbances in the quinolinic rat model of Huntington's disease. Scattoni, M.L., Valanzano, A., Pezzola, A., March, Z.D., Fusco, F.R., Popoli, P., Calamandrei, G. Behav. Brain Res. (2007) [Pubmed]
  8. Facilitation of acetylcholine release and improvement in cognition by a selective M2 muscarinic antagonist, SCH 72788. Lachowicz, J.E., Duffy, R.A., Ruperto, V., Kozlowski, J., Zhou, G., Clader, J., Billard, W., Binch, H., Crosby, G., Cohen-Williams, M., Strader, C.D., Coffin, V. Life Sci. (2001) [Pubmed]
  9. Delineation of a Fat tumor suppressor pathway. Cho, E., Feng, Y., Rauskolb, C., Maitra, S., Fehon, R., Irvine, K.D. Nat. Genet. (2006) [Pubmed]
  10. Paxillin binds schwannomin and regulates its density-dependent localization and effect on cell morphology. Fernandez-Valle, C., Tang, Y., Ricard, J., Rodenas-Ruano, A., Taylor, A., Hackler, E., Biggerstaff, J., Iacovelli, J. Nat. Genet. (2002) [Pubmed]
  11. NHE-RF, a merlin-interacting protein, is primarily expressed in luminal epithelia, proliferative endometrium, and estrogen receptor-positive breast carcinomas. Stemmer-Rachamimov, A.O., Wiederhold, T., Nielsen, G.P., James, M., Pinney-Michalowski, D., Roy, J.E., Cohen, W.A., Ramesh, V., Louis, D.N. Am. J. Pathol. (2001) [Pubmed]
  12. Quinidine impairs proliferation of neurofibromatosis type 2-deficient human malignant mesothelioma cells. Utermark, T., Alekov, A., Lerche, H., Abramowski, V., Giovannini, M., Hanemann, C.O. Cancer (2003) [Pubmed]
  13. Effects of the antiestrogen EM-800 (SCH 57050) and cyclophosphamide alone and in combination on growth of human ZR-75-1 breast cancer xenografts in nude mice. Gutman, M., Couillard, S., Labrie, F., Candas, B., Labrie, C. Cancer Res. (1999) [Pubmed]
  14. Bronchial hyperreactivity to histamine and methacholine in asthmatic children after inhalation of SCH 1000 and chlorpheniramine maleate. Woenne, R., Kattan, M., Orange, R.P., Levison, H. J. Allergy Clin. Immunol. (1978) [Pubmed]
  15. Comparison of aerosolized atropine sulfate and SCH 1000 on exercise-induced bronchospasm in children. Borut, T.C., Tashkin, D.P., Fischer, T.J., Katz, R., Rachelefsky, G., Siegel, S.C., Lee, E., Harper, C. J. Allergy Clin. Immunol. (1977) [Pubmed]
  16. Nucleocytoplasmic transfer of the NF2 tumor suppressor protein merlin is regulated by exon 2 and a CRM1-dependent nuclear export signal in exon 15. Kressel, M., Schmucker, B. Hum. Mol. Genet. (2002) [Pubmed]
  17. Serine 518 phosphorylation modulates merlin intramolecular association and binding to critical effectors important for NF2 growth suppression. Rong, R., Surace, E.I., Haipek, C.A., Gutmann, D.H., Ye, K. Oncogene (2004) [Pubmed]
  18. Neurofibromatosis 2 tumor suppressor protein colocalizes with ezrin and CD44 and associates with actin-containing cytoskeleton. Sainio, M., Zhao, F., Heiska, L., Turunen, O., den Bakker, M., Zwarthoff, E., Lutchman, M., Rouleau, G.A., Jääskeläinen, J., Vaheri, A., Carpén, O. J. Cell. Sci. (1997) [Pubmed]
  19. Expression of NF2-encoded merlin and related ERM family proteins in the human central nervous system. Stemmer-Rachamimov, A.O., Gonzalez-Agosti, C., Xu, L., Burwick, J.A., Beauchamp, R., Pinney, D., Louis, D.N., Ramesh, V. J. Neuropathol. Exp. Neurol. (1997) [Pubmed]
  20. Merlin, a tumor suppressor, interacts with transactivation-responsive RNA-binding protein and inhibits its oncogenic activity. Lee, J.Y., Kim, H., Ryu, C.H., Kim, J.Y., Choi, B.H., Lim, Y., Huh, P.W., Kim, Y.H., Lee, K.H., Jun, T.Y., Rha, H.K., Kang, J.K., Choi, C.R. J. Biol. Chem. (2004) [Pubmed]
  21. Phosphorylation of the NF2 tumor suppressor in Schwann cells is mediated by Cdc42-Pak and requires paxillin binding. Thaxton, C., Lopera, J., Bott, M., Baldwin, M.E., Kalidas, P., Fernandez-Valle, C. Mol. Cell. Neurosci. (2007) [Pubmed]
  22. Characterization of mammalian neurofilament triplet proteins. Subunit stoichiometry and morphology of native and reconstituted filaments. Scott, D., Smith, K.E., O'Brien, B.J., Angelides, K.J. J. Biol. Chem. (1985) [Pubmed]
  23. Neurofibromatosis 2 (NF2) tumor suppressor schwannomin and its interacting protein HRS regulate STAT signaling. Scoles, D.R., Nguyen, V.D., Qin, Y., Sun, C.X., Morrison, H., Gutmann, D.H., Pulst, S.M. Hum. Mol. Genet. (2002) [Pubmed]
  24. Homotypic and heterotypic interaction of the neurofibromatosis 2 tumor suppressor protein merlin and the ERM protein ezrin. Grönholm, M., Sainio, M., Zhao, F., Heiska, L., Vaheri, A., Carpén, O. J. Cell. Sci. (1999) [Pubmed]
  25. Hierarchy of merlin and ezrin N- and C-terminal domain interactions in homo- and heterotypic associations and their relationship to binding of scaffolding proteins EBP50 and E3KARP. Nguyen, R., Reczek, D., Bretscher, A. J. Biol. Chem. (2001) [Pubmed]
  26. Overexpression of the NF2 gene inhibits schwannoma cell proliferation through promoting PDGFR degradation. Fraenzer, J.T., Pan, H., Minimo, L., Smith, G.M., Knauer, D., Hung, G. Int. J. Oncol. (2003) [Pubmed]
  27. Cell cycle-dependent nucleocytoplasmic shuttling of the neurofibromatosis 2 tumour suppressor merlin. Muranen, T., Grönholm, M., Renkema, G.H., Carpén, O. Oncogene (2005) [Pubmed]
  28. A clue to the therapy of neurofibromatosis type 2: NF2/merlin is a PAK1 inhibitor. Hirokawa, Y., Tikoo, A., Huynh, J., Utermark, T., Hanemann, C.O., Giovannini, M., Xiao, G.H., Testa, J.R., Wood, J., Maruta, H. Cancer journal (Sudbury, Mass.) (2004) [Pubmed]
  29. Merlin facilitates ubiquitination and degradation of transactivation-responsive RNA-binding protein. Lee, J.Y., Moon, H.J., Lee, W.K., Chun, H.J., Han, C.W., Jeon, Y.W., Lim, Y., Kim, Y.H., Yao, T.P., Lee, K.H., Jun, T.Y., Rha, H.K., Kang, J.K. Oncogene (2006) [Pubmed]
  30. Loss of DAL-1, a protein 4.1-related tumor suppressor, is an important early event in the pathogenesis of meningiomas. Gutmann, D.H., Donahoe, J., Perry, A., Lemke, N., Gorse, K., Kittiniyom, K., Rempel, S.A., Gutierrez, J.A., Newsham, I.F. Hum. Mol. Genet. (2000) [Pubmed]
  31. The motor protein kinesin-1 links neurofibromin and merlin in a common cellular pathway of neurofibromatosis. Hakimi, M.A., Speicher, D.W., Shiekhattar, R. J. Biol. Chem. (2002) [Pubmed]
  32. Magicin, a novel cytoskeletal protein associates with the NF2 tumor suppressor merlin and Grb2. Wiederhold, T., Lee, M.F., James, M., Neujahr, R., Smith, N., Murthy, A., Hartwig, J., Gusella, J.F., Ramesh, V. Oncogene (2004) [Pubmed]
  33. Expression of neurofibromatosis 2 transcript and gene product during mouse fetal development. Huynh, D.P., Tran, T.M., Nechiporuk, T., Pulst, S.M. Cell Growth Differ. (1996) [Pubmed]
  34. The merlin tumor suppressor localizes preferentially in membrane ruffles. Gonzalez-Agosti, C., Xu, L., Pinney, D., Beauchamp, R., Hobbs, W., Gusella, J., Ramesh, V. Oncogene (1996) [Pubmed]
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