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Gene Review

Nf2  -  neurofibromatosis 2

Mus musculus

Synonyms: Merlin, Moesin-ezrin-radixin-like protein, Neurofibromin-2, Nf-2, Schwannomin, ...
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Disease relevance of Nf2


High impact information on Nf2

  • Merlin colocalizes and interacts with adherens junction (AJ) components in confluent wild-type cells, suggesting that the lack of AJs and contact-dependent growth arrest in Nf2(-/-) cells directly results from the absence of merlin at sites of cell:cell contact [1].
  • Mutation of the Neurofibromatosis 2 (NF2) tumor suppressor gene leads to cancer development in humans and mice [1].
  • We show that, beginning at four months of age, thirty percent of mice with arachnoidal cell Cre-mediated excision of Nf2 exon 2 developed a range of meningioma subtypes histologically similar to the human tumors [5].
  • The neurofibromatosis-2 (NF2) gene encodes merlin, an ezrin-radixin-moesin-(ERM)-related protein that functions as a tumor suppressor [6].
  • At high cell density, merlin becomes hypo-phosphorylated and inhibits cell growth in response to hyaluronate (HA), a mucopolysaccharide that surrounds cells [6].

Chemical compound and disease context of Nf2


Biological context of Nf2


Anatomical context of Nf2


Associations of Nf2 with chemical compounds


Physical interactions of Nf2

  • Moreover, it was shown that merlin interacted with endogenous growth factor receptor bound 2 (Grb2) protein and inhibited its expression [17].

Enzymatic interactions of Nf2


Regulatory relationships of Nf2


Other interactions of Nf2


Analytical, diagnostic and therapeutic context of Nf2


  1. NF2 deficiency promotes tumorigenesis and metastasis by destabilizing adherens junctions. Lallemand, D., Curto, M., Saotome, I., Giovannini, M., McClatchey, A.I. Genes Dev. (2003) [Pubmed]
  2. Erbin regulates mitogen-activated protein (MAP) kinase activation and MAP kinase-dependent interactions between Merlin and adherens junction protein complexes in Schwann cells. Rangwala, R., Banine, F., Borg, J.P., Sherman, L.S. J. Biol. Chem. (2005) [Pubmed]
  3. Conditional biallelic Nf2 mutation in the mouse promotes manifestations of human neurofibromatosis type 2. Giovannini, M., Robanus-Maandag, E., van der Valk, M., Niwa-Kawakita, M., Abramowski, V., Goutebroze, L., Woodruff, J.M., Berns, A., Thomas, G. Genes Dev. (2000) [Pubmed]
  4. A mouse model recapitulating molecular features of human mesothelioma. Altomare, D.A., Vaslet, C.A., Skele, K.L., De Rienzo, A., Devarajan, K., Jhanwar, S.C., McClatchey, A.I., Kane, A.B., Testa, J.R. Cancer Res. (2005) [Pubmed]
  5. Nf2 gene inactivation in arachnoidal cells is rate-limiting for meningioma development in the mouse. Kalamarides, M., Niwa-Kawakita, M., Leblois, H., Abramowski, V., Perricaudet, M., Janin, A., Thomas, G., Gutmann, D.H., Giovannini, M. Genes Dev. (2002) [Pubmed]
  6. The NF2 tumor suppressor gene product, merlin, mediates contact inhibition of growth through interactions with CD44. Morrison, H., Sherman, L.S., Legg, J., Banine, F., Isacke, C., Haipek, C.A., Gutmann, D.H., Ponta, H., Herrlich, P. Genes Dev. (2001) [Pubmed]
  7. 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]
  8. Merlin phosphorylation by p21-activated kinase 2 and effects of phosphorylation on merlin localization. Kissil, J.L., Johnson, K.C., Eckman, M.S., Jacks, T. J. Biol. Chem. (2002) [Pubmed]
  9. Expression of schwannomin in lens and Schwann cells. Claudio, J.O., Veneziale, R.W., Menko, A.S., Rouleau, G.A. Neuroreport (1997) [Pubmed]
  10. The Nf2 tumor suppressor gene product is essential for extraembryonic development immediately prior to gastrulation. McClatchey, A.I., Saotome, I., Ramesh, V., Gusella, J.F., Jacks, T. Genes Dev. (1997) [Pubmed]
  11. Inhibition of ras-mediated activator protein 1 activity and cell growth by merlin. Kim, H., Lim, J.Y., Kim, Y.H., Kim, H., Park, S.H., Lee, K.H., Han, H., Jeun, S.S., Lee, J.H., Rha, H.K. Mol. Cells (2002) [Pubmed]
  12. Mutant products of the NF2 tumor suppressor gene are degraded by the ubiquitin-proteasome pathway. Gautreau, A., Manent, J., Fievet, B., Louvard, D., Giovannini, M., Arpin, M. J. Biol. Chem. (2002) [Pubmed]
  13. Association of Caspr/paranodin with tumour suppressor schwannomin/merlin and beta1 integrin in the central nervous system. Denisenko-Nehrbass, N., Goutebroze, L., Galvez, T., Bonnon, C., Stankoff, B., Ezan, P., Giovannini, M., Faivre-Sarrailh, C., Girault, J.A. J. Neurochem. (2003) [Pubmed]
  14. The neurofibromatosis type 2 gene product, schwannomin, suppresses growth of NIH 3T3 cells. Lutchman, M., Rouleau, G.A. Cancer Res. (1995) [Pubmed]
  15. Structural basis for neurofibromatosis type 2. Crystal structure of the merlin FERM domain. Shimizu, T., Seto, A., Maita, N., Hamada, K., Tsukita, S., Tsukita, S., Hakoshima, T. J. Biol. Chem. (2002) [Pubmed]
  16. Inhibition of NF-kappaB activation by merlin. Kim, J.Y., Kim, H., Jeun, S.S., Rha, S.J., Kim, Y.H., Ko, Y.J., Won, J., Lee, K.H., Rha, H.K., Wang, Y.P. Biochem. Biophys. Res. Commun. (2002) [Pubmed]
  17. Merlin inhibits growth hormone-regulated Raf-ERKs pathways by binding to Grb2 protein. Lim, J.Y., Kim, H., Jeun, S.S., Kang, S.G., Lee, K.J. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
  18. Regulation of the Neurofibromatosis 2 gene promoter expression during embryonic development. Akhmametyeva, E.M., Mihaylova, M.M., Luo, H., Kharzai, S., Welling, D.B., Chang, L.S. Dev. Dyn. (2006) [Pubmed]
  19. Merlin suppresses the SRE-dependent transcription by inhibiting the activation of Ras-ERK pathway. Lim, J.Y., Kim, H., Kim, Y.H., Kim, S.W., Huh, P.W., Lee, K.H., Jeun, S.S., Rha, H.K., Kang, J.K. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  20. Widespread but cell type-specific expression of the mouse neurofibromatosis type 2 gene. Claudio, J.O., Lutchman, M., Rouleau, G.A. Neuroreport (1995) [Pubmed]
  21. Molecular cloning and characterization of alternatively spliced transcripts of the mouse neurofibromatosis 2 gene. Hara, T., Bianchi, A.B., Seizinger, B.R., Kley, N. Cancer Res. (1994) [Pubmed]
  22. Treatment of schwannomas with an oncolytic recombinant herpes simplex virus in murine models of neurofibromatosis type 2. Messerli, S.M., Prabhakar, S., Tang, Y., Mahmood, U., Weissleder, R., Bronson, R., Martuza, R., Rabkin, S., Breakefield, X.O. Hum. Gene Ther. (2006) [Pubmed]
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