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Merlin (protein)
open-in-new
<h2 id="gene">Gene</h2> <p><a href="/facts/Homo_sapiens/rlcTENsr">Human</a> merlin is coded by the gene <i>NF2</i> in <a href="/facts/Chromosome_22/s2e5G3LQ">chromosome 22</a>. <a href="/facts/Mus_musculus/A1fj6LQ2">Mouse</a> merlin gene is located on chromosome 11<a class="footnote-ref" id="fnref:3" href="#fn:3"><sup>3</sup></a> and <a href="/facts/Rattus_norvegicus/6KzSs2qg">rat</a> merlin gene on chromosome 17. <a href="/facts/Drosophila_melanogaster/KtnHVCcB">Fruit fly</a> merlin gene (symbol <i>Mer</i>) is located on chromosome 1 and shares 58% similarity to its human <a href="/facts/Homology_(biology)/muctKlyT">homologue</a>. Other merlin-like genes are known from a wide range of animals, and the derivation of merlin is thought to be in early <a href="/facts/Metazoa/4b8J33nd">metazoa</a>. Merlin is a member of the ERM family of proteins including ezrin, moesin, and radixin, which are in the <a href="/facts/Protein_4.1/LbY36lo9">protein 4.1</a> superfamily of proteins. Merlin is also known as <i>schwannomin</i>, a name derived from the most common type of tumor in the NF2 patient phenotype, the <a href="/facts/Schwannoma/P9s7AUa1">schwannoma</a>. </p> <h2 id="structure">Structure</h2> <p>Vertebrate merlin is a 70 <a href="/facts/Kilodalton/IMATU3vf">kDa</a> protein. There are 10 known <a href="/facts/Isoform/oWmzfg4l">isoforms</a> of human merlin molecule (the full molecule being 595 <a href="/facts/Amino_acid/WDxYwBny">amino acids</a> in length). The two most common of these are also found in the mouse and are called <i>type 1</i> and <i>type 2</i>, differing by the absence or presence of <a href="/facts/Exon/8KWJtLuN">exon</a> 16 or 17, respectively). All the known varieties have a conserved <a href="/facts/N-terminal/yKYpuaBJ">N-terminal</a> part, which contains a <a href="/facts/FERM_domain/NG1htjf5">FERM domain</a> (a domain found in most cytoskeletal-membrane organizing proteins). The FERM domain is followed by an <a href="/facts/Alpha_helix/7CESPIYJ">alpha-helical</a> domain and a <a href="/facts/Hydrophilic/k8p95WYu">hydrophilic</a> tail.<a class="footnote-ref" id="fnref:4" href="#fn:4"><sup>4</sup></a><a class="footnote-ref" id="fnref:5" href="#fn:5"><sup>5</sup></a> Merlin can <a href="/facts/Protein_dimer/c8LwFJPG">dimerize</a> with itself and heterodimerize with other ERM family proteins. </p> <h2 id="function">Function</h2> <p>Merlin is a <a href="/facts/Cell_membrane/vAXSD0DT">membrane</a>-cytoskeleton scaffolding protein, i.e. linking <a href="/facts/Actin/Hu3qIUL9">actin</a> filaments to cell membrane or membrane <a href="/facts/Glycoprotein/bKPzzW7m">glycoproteins</a>.<a class="footnote-ref" id="fnref:6" href="#fn:6"><sup>6</sup></a> Human merlin is predominantly found in <a href="/facts/Nervous_tissue/YY7qG0WD">nervous tissue</a>, but also in several other <a href="/facts/Fetal/evocHd0Y">fetal</a> tissues, and is mainly located in <a href="/facts/Adherens_junction/CNFe2Qaj">adherens junctions</a>.<a class="footnote-ref" id="fnref:7" href="#fn:7"><sup>7</sup></a> Its tumor suppressor properties are probably associated with <a href="/facts/Contact_inhibition/2cfQFBPL">contact-mediated growth inhibition</a>. <i>Drosophila</i> merlin is expressed in embryonic <a href="/facts/Hindgut/6xLpD3Lg">hindgut</a>, <a href="/facts/Salivary_gland/VtteDtH0">salivary glands</a>, and <a href="/facts/Imaginal_disc/vYFkuA04">imaginal discs</a>, and has apparently a slightly different role than in vertebrates.<a class="footnote-ref" id="fnref:8" href="#fn:8"><sup>8</sup></a> </p><p>The <a href="/facts/Phosphorylation/LXUEEeIL">phosphorylation</a> of <a href="/facts/Serine/4duVl30B">serine</a> 518 is known to alter the functional state of merlin.<a class="footnote-ref" id="fnref:9" href="#fn:9"><sup>9</sup></a> The signaling pathway of merlin is proposed to include several salient cell growth controlling molecules, including eIF3c, <a href="/facts/CD44/A0hN9LtL">CD44</a>, <a href="/facts/Protein_kinase_A/kaKoYfbp">protein kinase A</a>, and <a href="/facts/P21_activated_kinase/IoVkSGRy">p21 activated kinases</a>. </p><p>Work in <i>Drosophila</i> identified Merlin as an upstream regulator of the <a href="/facts/Hippo_tumor_suppressor_pathway/4Xs0NBPk">Hippo tumor suppressor pathway</a>,<a class="footnote-ref" id="fnref:10" href="#fn:10"><sup>10</sup></a> a function that is conserved in mammals.<a class="footnote-ref" id="fnref:11" href="#fn:11"><sup>11</sup></a> The Hippo pathway is a well conserved signalling pathway that coordinately regulates cell proliferation and apoptosis.<a class="footnote-ref" id="fnref:12" href="#fn:12"><sup>12</sup></a> </p><p><a href="/facts/Mutation/Ee4NnWbY">Mutations</a> 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 <a href="/facts/Vestibular_schwannoma/w6eusFYb">vestibular schwannomas</a> (also called acoustic neuromas). NF2 belongs to the <a href="/facts/Tumor_suppressor/Awte4S51">tumor suppressor</a> group of genes.<a class="footnote-ref" id="fnref:13" href="#fn:13"><sup>13</sup></a> </p> <h2 id="interactions">Interactions</h2> <p>Merlin (protein) has been shown to <a href="/facts/Protein-protein_interaction/etvm9Wmg">interact</a> with: </p> <ul><li><a href="/facts/CUL4A/UBNDf9up">CUL4A</a>,<a class="footnote-ref" id="fnref:14" href="#fn:14"><sup>14</sup></a></li> <li><a href="/facts/DDB1/7qAH9LBY">DDB1</a>,<a class="footnote-ref" id="fnref:15" href="#fn:15"><sup>15</sup></a></li> <li><a href="/facts/Ezrin/AGRXyzLQ">EZR</a>,<a class="footnote-ref" id="fnref:16" href="#fn:16"><sup>16</sup></a></li> <li><a href="/facts/HGS_(gene)/E3J4EKkS">HGS</a>,<a class="footnote-ref" id="fnref:17" href="#fn:17"><sup>17</sup></a><a class="footnote-ref" id="fnref:18" href="#fn:18"><sup>18</sup></a></li> <li><a href="/facts/MED28/XdtuEfUd">MED28</a>,<a class="footnote-ref" id="fnref:19" href="#fn:19"><sup>19</sup></a></li> <li><a href="/facts/RIT1/M3Q666oJ">RIT1</a>,<a class="footnote-ref" id="fnref:20" href="#fn:20"><sup>20</sup></a></li> <li><a href="/facts/SDCBP/1FPY3ccc">SDCBP</a>,<a class="footnote-ref" id="fnref:21" href="#fn:21"><sup>21</sup></a></li> <li><a href="/facts/SPTBN1/Lk5SfuCX">SPTBN1</a>,<a class="footnote-ref" id="fnref:22" href="#fn:22"><sup>22</sup></a> and</li> <li><a href="/facts/VPRBP/mtU6rhvX">VPRBP</a>.<a class="footnote-ref" id="fnref:23" href="#fn:23"><sup>23</sup></a></li></ul> <h2 id="external-links">External links</h2> <ul><li><a href="https://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=nf2">GeneReviews/NCBI/NIH/UW entry on Neurofibromatosis 2</a></li> <li><a href="https://web.archive.org/web/19990921040820/http://flybase.bio.indiana.edu/.bin/fbidq.html?FBgn0013951">FlyBase synopsis of gene Mer</a></li></ul> <h2 id="references">References</h2> <ol> <li id="fn:1"><p>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. PMID 8379998. S2CID 24532924. <a href="/wiki/Bibcode_(identifier)" target="_blank">/wiki/Bibcode_(identifier)</a> <a href="#fnref:1" class="footnote-back-ref">↩</a></p></li> <li id="fn:2"><p>Golovnina K, Blinov A, Akhmametyeva EM, Omelyanchuk LV, Chang LS (2005). "Evolution and origin of merlin, the product of the Neurofibromatosis type 2 (NF2) tumor-suppressor gene". BMC Evol. Biol. 5 (1): 69. Bibcode:2005BMCEE...5...69G. doi:10.1186/1471-2148-5-69. PMC 1315344. PMID 16324214. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1315344" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1315344</a> <a href="#fnref:2" class="footnote-back-ref">↩</a></p></li> <li id="fn:3"><p>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. PMID 8012352. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:3" class="footnote-back-ref">↩</a></p></li> <li id="fn:4"><p>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. PMID 11756419. <a href="https://doi.org/10.1074%2Fjbc.M109979200" target="_blank">https://doi.org/10.1074%2Fjbc.M109979200</a> <a href="#fnref:4" class="footnote-back-ref">↩</a></p></li> <li id="fn:5"><p>Ali Khajeh J, Ju JH, Atchiba M (2014). "Molecular conformation of the full-length tumor suppressor NF2/Merlin--a small-angle neutron scattering study". Journal of Molecular Biology. 426 (15): 2755–68. doi:10.1016/j.jmb.2014.05.011. PMC 4407695. PMID 24882693. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4407695" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4407695</a> <a href="#fnref:5" class="footnote-back-ref">↩</a></p></li> <li id="fn:6"><p>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. PMID 16204178. <a href="https://doi.org/10.1101%2Fgad.1335605" target="_blank">https://doi.org/10.1101%2Fgad.1335605</a> <a href="#fnref:6" class="footnote-back-ref">↩</a></p></li> <li id="fn:7"><p>den Bakker MA, Vissers KJ, Molijn AC, Kros JM, Zwarthoff EC, van der Kwast TH (1999). "Expression of the neurofibromatosis type 2 gene in human tissues". J. Histochem. Cytochem. 47 (11): 1471–80. doi:10.1177/002215549904701113. PMID 10544220. <a href="https://doi.org/10.1177%2F002215549904701113" target="_blank">https://doi.org/10.1177%2F002215549904701113</a> <a href="#fnref:7" class="footnote-back-ref">↩</a></p></li> <li id="fn:8"><p>LaJeunesse DR, McCartney BM, Fehon RG (1998). "Structural Analysis of Drosophila Merlin Reveals Functional Domains Important for Growth Control and Subcellular Localization". J. Cell Biol. 141 (7): 1589–99. doi:10.1083/jcb.141.7.1589. PMC 2133006. PMID 9647651. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2133006" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2133006</a> <a href="#fnref:8" class="footnote-back-ref">↩</a></p></li> <li id="fn:9"><p>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. PMID 14981079. <a href="https://doi.org/10.1074%2Fjbc.M313916200" target="_blank">https://doi.org/10.1074%2Fjbc.M313916200</a> <a href="#fnref:9" class="footnote-back-ref">↩</a></p></li> <li id="fn:10"><p>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. PMID 16341207. S2CID 15468669. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:10" class="footnote-back-ref">↩</a></p></li> <li id="fn:11"><p>Zhang N, Bai H, David KK, Dong J, Zheng Y, Cai J, Giovannini M, Liu P, Anders RA, Pan D (2010). "The Merlin/NF2 tumor suppressor functions through the YAP oncoprotein to regulate tissue homeostasis in mammals". Developmental Cell. 19 (1): 27–38. doi:10.1016/j.devcel.2010.06.015. PMC 2925178. PMID 20643348. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2925178" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2925178</a> <a href="#fnref:11" class="footnote-back-ref">↩</a></p></li> <li id="fn:12"><p>Pan D (October 2010). "The hippo signaling pathway in development and cancer". Developmental Cell. 19 (4): 491–505. doi:10.1016/j.devcel.2010.09.011. PMC 3124840. PMID 20951342. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3124840" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3124840</a> <a href="#fnref:12" class="footnote-back-ref">↩</a></p></li> <li id="fn:13"><p>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. PMID 16497727. <a href="https://doi.org/10.1093%2Fhmg%2Fddl021" target="_blank">https://doi.org/10.1093%2Fhmg%2Fddl021</a> <a href="#fnref:13" class="footnote-back-ref">↩</a></p></li> <li id="fn:14"><p>Huang J, Chen J (July 2008). "VprBP targets Merlin to the Roc1-Cul4A-DDB1 E3 ligase complex for degradation". Oncogene. 27 (29): 4056–64. doi:10.1038/onc.2008.44. PMID 18332868. S2CID 23628888. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:14" class="footnote-back-ref">↩</a></p></li> <li id="fn:15"><p>Huang J, Chen J (July 2008). "VprBP targets Merlin to the Roc1-Cul4A-DDB1 E3 ligase complex for degradation". Oncogene. 27 (29): 4056–64. doi:10.1038/onc.2008.44. PMID 18332868. S2CID 23628888. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:15" class="footnote-back-ref">↩</a></p></li> <li id="fn:16"><p>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. PMID 10036239. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:16" class="footnote-back-ref">↩</a></p></li> <li id="fn:17"><p>Gutmann DH, Haipek CA, Burke SP, Sun CX, Scoles DR, Pulst SM (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. 10 (8): 825–34. doi:10.1093/hmg/10.8.825. PMID 11285248. <a href="https://doi.org/10.1093%2Fhmg%2F10.8.825" target="_blank">https://doi.org/10.1093%2Fhmg%2F10.8.825</a> <a href="#fnref:17" class="footnote-back-ref">↩</a></p></li> <li id="fn:18"><p>Scoles DR, Huynh DP, Chen MS, Burke SP, Gutmann DH, Pulst SM (July 2000). "The neurofibromatosis 2 tumor suppressor protein interacts with hepatocyte growth factor-regulated tyrosine kinase substrate". Hum. Mol. Genet. 9 (11): 1567–74. doi:10.1093/hmg/9.11.1567. PMID 10861283. <a href="https://doi.org/10.1093%2Fhmg%2F9.11.1567" target="_blank">https://doi.org/10.1093%2Fhmg%2F9.11.1567</a> <a href="#fnref:18" class="footnote-back-ref">↩</a></p></li> <li id="fn:19"><p>Wiederhold T, Lee MF, James M, Neujahr R, Smith N, Murthy A, Hartwig J, Gusella JF, Ramesh V (November 2004). "Magicin, a novel cytoskeletal protein associates with the NF2 tumor suppressor merlin and Grb2". Oncogene. 23 (54): 8815–25. doi:10.1038/sj.onc.1208110. PMID 15467741. <a href="https://doi.org/10.1038%2Fsj.onc.1208110" target="_blank">https://doi.org/10.1038%2Fsj.onc.1208110</a> <a href="#fnref:19" class="footnote-back-ref">↩</a></p></li> <li id="fn:20"><p>Huang J, Chen J (July 2008). "VprBP targets Merlin to the Roc1-Cul4A-DDB1 E3 ligase complex for degradation". Oncogene. 27 (29): 4056–64. doi:10.1038/onc.2008.44. PMID 18332868. S2CID 23628888. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:20" class="footnote-back-ref">↩</a></p></li> <li id="fn:21"><p>Jannatipour M, Dion P, Khan S, Jindal H, Fan X, Laganière J, Chishti AH, Rouleau GA (August 2001). "Schwannomin isoform-1 interacts with syntenin via PDZ domains". J. Biol. Chem. 276 (35): 33093–100. doi:10.1074/jbc.M105792200. PMID 11432873. <a href="https://doi.org/10.1074%2Fjbc.M105792200" target="_blank">https://doi.org/10.1074%2Fjbc.M105792200</a> <a href="#fnref:21" class="footnote-back-ref">↩</a></p></li> <li id="fn:22"><p>Neill GW, Crompton MR (September 2001). "Binding of the merlin-I product of the neurofibromatosis type 2 tumour suppressor gene to a novel site in beta-fodrin is regulated by association between merlin domains". Biochem. J. 358 (Pt 3): 727–35. doi:10.1042/0264-6021:3580727. PMC 1222106. PMID 11535133. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1222106" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1222106</a> <a href="#fnref:22" class="footnote-back-ref">↩</a></p></li> <li id="fn:23"><p>Huang J, Chen J (July 2008). "VprBP targets Merlin to the Roc1-Cul4A-DDB1 E3 ligase complex for degradation". Oncogene. 27 (29): 4056–64. doi:10.1038/onc.2008.44. PMID 18332868. S2CID 23628888. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:23" class="footnote-back-ref">↩</a></p></li> </ol>