Merlin (protein)

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Merlin
Merlin
Neurofibromin 2 according to PDB  1H4R

Existing structural data : 1h4r , 1isn

Properties of human protein
Mass / length primary structure 595 amino acids; 69.7 kDa
Isoforms 10
Identifier
Gene name NF2
External IDs
Occurrence
Parent taxon Bilateria (bilateral animals)
Orthologue
human mouse
Entrez 4771 18016
Ensemble ENSG00000186575 ENSMUSG00000009073
UniProt P35240 Q3TIW4
Refseq (mRNA) NM_000268 NM_010898
Refseq (protein) NP_000259 NP_035028
Gene locus Chr 22: 28.33 - 28.42 Mb Chr 11: 4.67 - 4.75 Mb
PubMed search 4771 18016

Merlin , also known as neurofibromin 2 or schwannomin , is a protein found in the cytoskeleton . In humans, it is a tumor suppressor protein that is involved in the development of type 2 neurofibromatosis . Sequence analyzes have shown the protein's similarity to the ezrin-radexin-moesin protein family . The name Merlin is an acronym for Moesin-Ezrin-Radixin-Like Protein and has nothing to do with the literary figure of the same name, the magician Merlin .

gene

The NF-2 gene on chromosome 22 codes for human merlin . The house mouse merlin gene is located on chromosome 11 of the mouse and the merlin gene of the brown rat is located on the rat chromosome 17. The Drosophila merlin gene (symbol Mer ) is found on chromosome 1 and has a 58 percent rate Sequence similarity to its human homolog. Other merlin-like genes are known from many animals, and the origin of the merlin is believed to have occurred at the time of the metazoa . Merlin is a member of the ERM protein family, which includes Ezrin, Moesin, and Radixin. These belong to the Protein 4.1 superfamily of proteins. Merlin is also called Schwannomin. This is a name for the most common tumor in NF2 patients, schwannoma .

structure

The vertebrate merlin is a 70 kDa protein. There are ten known isoforms of the human merlin molecule. The complete molecule is 595 amino acids long . The two most common isoforms are also found in the mouse, are called type 1 and type 2 and differ in the absence or presence of the respective exons 16 or 17. All known variants have a highly conserved N-terminal part, the so-called FERM domain, which is found in many proteins that connect the cytoskeleton to the cell membrane. The FERM domain is followed by an α-helix with a hydrophilic part. Merlin can form dimers with itself and heterodimers with other members of the ERM family.

function

Merlin is a membrane - cytoskeletal folding protein. This means that it connects actin filaments with the cell membrane or with membrane glycoproteins . The human merlin occurs mainly in nerve tissue and some fetal tissues, and is found mainly in the area of ​​the adherens junctions . Its tumor suppressor properties are possibly linked to contact-mediated growth inhibition. The Drosophila merlin is mainly expressed in the embryonic hindgut , salivary glands, and imaginal discs and obviously has a slightly different function than the vertebrate merlin.

A phosphorylation of serine number 518 changes the function of Merlin. The merlin-dependent signal pathway probably includes some mechanisms that regulate cell division, such as eIF3c, CD44 , protein kinase A and the p21-activated kinases .

Mutations in the NF2 gene cause an autosomal dominant disease in humans, neurofibromatosis type 2 . This condition is characterized by the development of tumors of the nervous system, primarily bilateral vestibular schwannomas (also called acoustic neuromas). NF2 is one of the tumor suppressor genes .

Individual evidence

  1. ↑ Rouleau GA, Merel P, Lutchman M, Sanson M, Zucman J, Marineau C, Hoang-Xuan K, Demczuk S, Desmaze C, Plougastel B: Alteration in a new gene encoding a putative membrane-organizing protein causes neuro-fibromatosis type 2 . In: Nature . 363, No. 6429, 1993, pp. 515-21. doi : 10.1038 / 363515a0 . PMID 8379998 .
  2. ↑ Golovnina K, Blinov A, Akhmametyeva EM, Omelyanchuk LV, Chang LS: Evolution and origin of merlin, the product of the Neurofibromatosis type 2 (NF2) tumor suppressor gene . In: BMC Evol. Biol . 5, 2005, p. 69. doi : 10.1186 / 1471-2148-5-69 . PMID 16324214 .
  3. ↑ Haase VH, Trofatter YES, MacCollin M, Tarttelin E, Gusella JF, Ramesh V: The murine homologue NF2 Encodes a highly conserved protein merlin with alternative forms . In: Hum. Mol. Genet. . 3, No. 3, 1994, pp. 407-11. doi : 10.1093 / hmg / 3.3.407 . PMID 8012352 .
  4. ↑ Shimizu T, Seto A, Maita N, Hamada K, Tsukita S, Tsukita S, Hakoshima T: Structural basis for neurofibromatosis type 2. Crystal structure of the merlin FERM domain . In: J. Biol. Chem. . 277, No. 12, 2002, pp. 10332-6. doi : 10.1074 / jbc.M109979200 . PMID 11756419 .
  5. ^ McClatchey AI, Giovannini M: Membrane organization and tumorigenesis - the NF2 tumor suppressor, Merlin . In: Genes Dev. . 19, No. 19, 2005, pp. 2265-77. doi : 10.1101 / gad.1335605 . PMID 16204178 .
  6. ↑ den Bakker MA, Vissers KJ, Molijn AC, Kros JM, Zwarthoff EC, van der Kwast TH: Expression of the neurofibromatosis type 2 gene in human tissues Archived from the original on May 18, 2008. Info: The archive link was automatically inserted and still Not checked. Please check the original and archive link according to the instructions and then remove this notice. In: J. Histochem. Cytochem. . 47, No. 11, 1999, pp. 1471-80. PMID 10544220 . Retrieved February 24, 2008. @1@ 2Template: Webachiv / IABot / www.jhc.org
  7. ↑ LaJeunesse DR, McCartney BM, Fehon RG: Structural analysis of Drosophila merlin reveals functional domains important for growth control and subcellular localization . In: J. Cell Biol. . 141, No. 7, 1998, pp. 1589-99. doi : 10.1083 / jcb.141.7.1589 . PMID 9647651 .
  8. ↑ Alfthan K, Heiska L, Grönholm M, Renkema GH, Carpén O: Cyclic AMP-dependent protein kinase phosphorylates merlin at serine 518 independently of p21-activated kinase and promotes merlin-ezrin heterodimerization . In: J. Biol. Chem. . 279, No. 18, 2004, pp. 18559-66. doi : 10.1074 / jbc.M313916200 . PMID 14981079 .
  9. ↑ Scoles DR, Yong WH, Qin Y, Wawrowsky K, Pulst SM: Schwannomin inhibits tumorigenesis through direct interaction with the eukaryotic initiation factor subunit c (eIF3c) . In: Hum. Mol. Genet. . 15, No. 7, 2006, pp. 1059-70. doi : 10.1093 / hmg / ddl021 . PMID 16497727 .

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