Human merlin is coded by the gene NF2 in Chromosome 22. Mouse merlin gene is located on chromosome 11 and rat merlin gene on chromosome 17. Fruit fly merlin gene (symbol Mer) is located on chromosome 1 and shares 58% similarity to its human homologue. Other merlin-like genes are known from a wide range of animals, and the derivation of merlin is thought to be in early metazoa. Merlin is a member of the ERM family of proteins including ezrin, moesin, and radixin, which are in the protein 4.1 superfamily of proteins. Merlin is also known as schwannomin, a name derived from the most common type of tumor in the NF2 patient phenotype, the schwannoma.
Vertebrate merlin is a 70-kDa protein. There are 10 known isoforms of human merlin molecule (the full molecule being 595 amino acids in length). The two most common these are also found in the mouse and are called type 1 and type 2, differing by the absence or presence of exon 16 or 17, respectively). All the known varieties have a conserved N-terminal part, which contains a FERM domain (a domain found in most cytoskeletal-membrane organizing proteins). The FERM domain is followed by an alpha-helical domain and a hydrophilic tail. Merlin can dimerize with itself and heterodimerize with other ERM family proteins.
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 bilateral vestibular schwannomas (also called acoustic neuromas). NF2 belongs to the tumor suppressor group of genes.
^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". Nature363 (6429): 515–21. doi:10.1038/363515a0. PMID8379998.
^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.
^Shimizu T, Seto A, Maita N, Hamada K, Tsukita S, Tsukita S, Hakoshima T (2002). "Structural basis for neurofibromatosis type 2. Crystal structure of the merlin FERM domain". J. Biol. Chem.277 (12): 10332–6. doi:10.1074/jbc.M109979200. PMID11756419.
^McClatchey AI, Giovannini M (2005). "Membrane organization and tumorigenesis--the NF2 tumor suppressor, Merlin". Genes Dev.19 (19): 2265–77. doi:10.1101/gad.1335605. PMID16204178.
^Alfthan K, Heiska L, Grönholm M, Renkema GH, Carpén O (2004). "Cyclic AMP-dependent protein kinase phosphorylates merlin at serine 518 independently of p21-activated kinase and promotes merlin-ezrin heterodimerization". J. Biol. Chem.279 (18): 18559–66. doi:10.1074/jbc.M313916200. PMID14981079.
^Scoles DR, Yong WH, Qin Y, Wawrowsky K, Pulst SM (2006). "Schwannomin inhibits tumorigenesis through direct interaction with the eukaryotic initiation factor subunit c (eIF3c)". Hum. Mol. Genet.15 (7): 1059–70. doi:10.1093/hmg/ddl021. PMID16497727.
^Gutmann, D H; Haipek C A; Burke S P; Sun C X; Scoles D R; Pulst S M (April 2001). "The NF2 interactor, hepatocyte growth factor-regulated tyrosine kinase substrate (HRS), associates with merlin in the "open" conformation and suppresses cell growth and motility". Hum. Mol. Genet. (England) 10 (8): 825–34. doi:10.1093/hmg/10.8.825. ISSN0964-6906. PMID11285248.
^Scoles, D R; Huynh D P; Chen M S; Burke S P; Gutmann D H; Pulst S M (July 2000). "The neurofibromatosis 2 tumor suppressor protein interacts with hepatocyte growth factor-regulated tyrosine kinase substrate". Hum. Mol. Genet. (ENGLAND) 9 (11): 1567–74. doi:10.1093/hmg/9.11.1567. ISSN0964-6906. PMID10861283.
^ abcdHuang, J; Chen J (July 2008). "VprBP targets Merlin to the Roc1-Cul4A-DDB1 E3 ligase complex for degradation". Oncogene (England) 27 (29): 4056–64. doi:10.1038/onc.2008.44. PMID18332868.
^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. (ENGLAND) 112 (6): 895–904. ISSN0021-9533. PMID10036239.
^Jannatipour, M; Dion P; Khan S; Jindal H; Fan X; Laganière J; Chishti A H; Rouleau G A (August 2001). "Schwannomin isoform-1 interacts with syntenin via PDZ domains". J. Biol. Chem. (United States) 276 (35): 33093–100. doi:10.1074/jbc.M105792200. ISSN0021-9258. PMID11432873.
^Wiederhold, Thorsten; Lee Ming-Fen; James Marianne; Neujahr Ralph; Smith Nicole; Murthy Anita; Hartwig John; Gusella James F; Ramesh Vijaya (November 2004). "Magicin, a novel cytoskeletal protein associates with the NF2 tumor suppressor merlin and Grb2". Oncogene (England) 23 (54): 8815–25. doi:10.1038/sj.onc.1208110. ISSN0950-9232. PMID15467741.