Human merlin is coded by the geneNF2 inchromosome 22.Mouse merlin gene is located on chromosome 11[7] andrat merlin gene on chromosome 17.Fruit fly merlin gene (symbolMer) is located on chromosome 1 and shares 58% similarity to its humanhomologue.Other merlin-like genes are known from a wide range of animals, and the derivation of merlin is thought to be in earlymetazoa. Merlin is a member of the ERM family of proteins including ezrin, moesin, and radixin, which are in theprotein 4.1 superfamily of proteins. Merlin is also known asschwannomin, a name derived from the most common type of tumor in the NF2 patient phenotype, theschwannoma.
Vertebrate merlin is a 70 kDa protein. There are 10 knownisoforms of human merlin molecule (the full molecule being 595amino acids in length). The two most common of these are also found in the mouse and are calledtype 1 andtype 2, differing by the absence or presence ofexon 16 or 17, respectively). All the known varieties have a conservedN-terminal part, which contains aFERM domain (a domain found in most cytoskeletal-membrane organizing proteins). The FERM domain is followed by analpha-helical domain and ahydrophilic tail.[8][9] Merlin candimerize with itself and heterodimerize with other ERM family proteins.
Work inDrosophila identified Merlin as an upstream regulator of theHippo tumor suppressor pathway,[14] a function that is conserved in mammals.[15] The Hippo pathway is a well conserved signalling pathway that coordinately regulates cell proliferation and apoptosis.[16]
Mutations of the NF2 gene cause a human autosomal dominant disease called neurofibromatosis type 2. It is characterized by the development of tumors of the nervous system, most commonly of bilateralvestibular schwannomas (also called acoustic neuromas). NF2 belongs to thetumor suppressor group of genes.[17]
^"Human PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
^Rouleau GA, Merel P, Lutchman M, Sanson M, Zucman J, Marineau C, Hoang-Xuan K, Demczuk S, Desmaze C, Plougastel B (1993). "Alteration in a new gene encoding a putative membrane-organizing protein causes neuro-fibromatosis type 2".Nature.363 (6429):515–21.Bibcode:1993Natur.363..515R.doi:10.1038/363515a0.PMID8379998.S2CID24532924.
^Haase VH, Trofatter JA, MacCollin M, Tarttelin E, Gusella JF, Ramesh V (1994). "The murine NF2 homologue encodes a highly conserved merlin protein with alternative forms".Hum. Mol. Genet.3 (3):407–11.doi:10.1093/hmg/3.3.407.PMID8012352.
^Hamaratoglu F, Willecke M, Kango-Singh M, et al. (2006). "The tumour-suppressor genes NF2/Merlin and Expanded act through Hippo signalling to regulate cell proliferation and apoptosis".Nature Cell Biology.8 (1):27–36.doi:10.1038/ncb1339.PMID16341207.S2CID15468669.
^Grönholm M, Sainio M, Zhao F, Heiska L, Vaheri A, Carpén O (March 1999). "Homotypic and heterotypic interaction of the neurofibromatosis 2 tumor suppressor protein merlin and the ERM protein ezrin".J. Cell Sci.112 (6):895–904.doi:10.1242/jcs.112.6.895.PMID10036239.
