Merlin (protein)

Merlin (also called Neurofibromin 2 or schwannomin) is a is_associated_with::cytoskeletal is_associated_with::protein. In humans, it is a tumor suppressor protein involved in is_associated_with::Neurofibromatosis type II. Sequence data reveal its similarity to the is_associated_with::ERM protein family.

The name "merlin" is an is_associated_with::acronym for "is_associated_with::Moesin-is_associated_with::Ezrin-is_associated_with::Radixin-Like Protein".

Gene
Human merlin is coded by the gene NF2 in is_associated_with::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 is_associated_with::homologue. Other merlin-like genes are known from a wide range of animals, and the derivation of merlin is thought to be in early is_associated_with::metazoa. Merlin is a member of the ERM family of proteins including ezrin, moesin, and radixin, which are in the is_associated_with::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 is_associated_with::schwannoma.

Structure
Vertebrate merlin is a 70-kDa protein. There are 10 known is_associated_with::isoforms of human merlin molecule (the full molecule being 595 is_associated_with::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 is_associated_with::exon 16 or 17, respectively). All the known varieties have a conserved is_associated_with::N-terminal part, which contains a is_associated_with::FERM domain (a domain found in most cytoskeletal-membrane organizing proteins). The FERM domain is followed by an alpha-helical domain and a is_associated_with::hydrophilic tail. Merlin can dimerize with itself and heterodimerize with other ERM family proteins.

Function
Merlin is a membrane-cytoskeleton scaffolding protein, i.e. linking is_associated_with::actin filaments to cell membrane or membrane is_associated_with::glycoproteins. Human merlin is predominantly found in is_associated_with::nervous tissue, but also in several other is_associated_with::fetal tissues, and is mainly located in is_associated_with::adherens junctions. Its tumor suppressor properties are probably associated with contact-mediated growth inhibition. Drosophila merlin is expressed in embryonic is_associated_with::hindgut, is_associated_with::salivary glands, and is_associated_with::imaginal discs, and has apparently a slightly different role than in vertebrates.

The is_associated_with::phosphorylation of is_associated_with::serine 518 is known to alter the functional state of merlin. The signaling pathway of merlin is proposed to include several salient cell growth controlling molecules, including eIF3c, is_associated_with::CD44, is_associated_with::protein kinase A, and is_associated_with::p21 activated kinases.

is_associated_with::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 is_associated_with::tumor suppressor group of genes.

Interactions
Merlin (protein) has been shown to interact with:


 * is_associated_with::CUL4A,
 * is_associated_with::DDB1,
 * EZR,
 * HGS,
 * is_associated_with::MED28,
 * is_associated_with::RIT1,
 * is_associated_with::SDCBP,
 * is_associated_with::SPTBN1, and
 * is_associated_with::VPRBP.