MERL_HUMAN
ID MERL_HUMAN Reviewed; 595 AA.
AC P35240; O95683; Q8WUJ2; Q969N0; Q969Q3; Q96T30; Q96T31; Q96T32; Q96T33;
AC Q9BTW3; Q9UNG9; Q9UNH3; Q9UNH4;
DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1994, sequence version 1.
DT 03-AUG-2022, entry version 241.
DE RecName: Full=Merlin;
DE AltName: Full=Moesin-ezrin-radixin-like protein;
DE AltName: Full=Neurofibromin-2;
DE AltName: Full=Schwannomerlin;
DE AltName: Full=Schwannomin;
GN Name=NF2; Synonyms=SCH;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=8453669; DOI=10.1016/0092-8674(93)90406-g;
RA Trofatter J.A., Maccollin M.M., Rutter J.L., Murrell J.R., Duyao M.P.,
RA Parry D.N., Eldridge R., Kley N., Menon A.G., Pulaski K., Haase V.H.,
RA Ambrose C.M., Munroe D., Bove C., Haines J.L., Martuza R.L.,
RA Macdonald M.E., Seizinger B.R., Short M.P., Buckler A.J., Gusella J.F.;
RT "A novel moesin-, ezrin-, radixin-like gene is a candidate for the
RT neurofibromatosis 2 tumor suppressor.";
RL Cell 72:791-800(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=8379998; DOI=10.1038/363515a0;
RA Rouleau G.A., Merel P., Lutchman M., Sanson M., Zucman J., Marineau C.,
RA Hoang-Xuan K., Demczuk S., Desmaze C., Plougastel B., Pulst S., Lenoir G.,
RA Bijlsma E., Fashold R., Dumanski J.P., de Jong P., Parry D., Eldrige R.,
RA Aurias A., Delattre O., Thomas G.;
RT "Alteration in a new gene encoding a putative membrane-organizing protein
RT causes neuro-fibromatosis type 2.";
RL Nature 363:515-521(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 1 AND 2).
RX PubMed=9817927; DOI=10.1093/hmg/7.13.2095;
RA Zucman-Rossi J., Legoix P., Der Sarjussian H., Cheret G., Sor F.,
RA Bernardi A., Cazes L., Giraud S., Lenoir G., Thomas G.;
RT "NF2 gene in neurofibromatosis type 2 patients.";
RL Hum. Mol. Genet. 7:2095-2101(1998).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 7; 9 AND 10), AND SUBCELLULAR
RP LOCATION.
RX PubMed=10401006; DOI=10.1093/hmg/8.8.1561;
RA Schmucker B., Tang Y., Kressel M.;
RT "Novel alternatively spliced isoforms of the neurofibromatosis type 2 tumor
RT suppressor are targeted to the nucleus and cytoplasmic granules.";
RL Hum. Mol. Genet. 8:1561-1570(1999).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 3; 4; 5; 6 AND 8).
RX PubMed=11827459; DOI=10.1006/geno.2001.6672;
RA Chang L.-S., Akhmametyeva E.M., Wu Y., Zhu L., Welling D.B.;
RT "Multiple transcription initiation sites, alternative splicing, and
RT differential polyadenylation contribute to the complexity of human
RT neurofibromatosis 2 transcripts.";
RL Genomics 79:63-76(2002).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=15461802; DOI=10.1186/gb-2004-5-10-r84;
RA Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A.,
RA Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J.,
RA Beare D.M., Dunham I.;
RT "A genome annotation-driven approach to cloning the human ORFeome.";
RL Genome Biol. 5:R84.1-R84.11(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 4).
RC TISSUE=Lung, and Skin;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP REVIEW.
RA Marineau C., Merel P., Rouleau G.A., Thomas G.;
RT "The gene of neurofibromatosis type 2.";
RL Medecine/Sciences 11:35-42(1995).
RN [9]
RP INTERACTION WITH SLC9A3R1.
RX PubMed=9430655; DOI=10.1074/jbc.273.3.1273;
RA Murthy A., Gonzalez-Agosti C., Cordero E., Pinney D., Candia C.,
RA Solomon F., Gusella J., Ramesh V.;
RT "NHE-RF, a regulatory cofactor for Na(+)-H+ exchange, is a common
RT interactor for merlin and ERM (MERM) proteins.";
RL J. Biol. Chem. 273:1273-1276(1998).
RN [10]
RP INTERACTION WITH HGS.
RX PubMed=10861283; DOI=10.1093/hmg/9.11.1567;
RA Scoles D.R., Huynh D.P., Chen M.S., Burke S.P., Gutmann D.H., Pulst S.-M.;
RT "The neurofibromatosis 2 tumor suppressor protein interacts with hepatocyte
RT growth factor-regulated tyrosine kinase substrate.";
RL Hum. Mol. Genet. 9:1567-1574(2000).
RN [11]
RP INTERACTION WITH SCHIP1, CHARACTERIZATION OF VARIANTS NF2 PHE-119 DEL, AND
RP CHARACTERIZATION OF VARIANT MET-219.
RC TISSUE=Brain;
RX PubMed=10669747; DOI=10.1128/mcb.20.5.1699-1712.2000;
RA Goutebroze L., Brault E., Muchardt C., Camonis J., Thomas G.;
RT "Cloning and characterization of SCHIP-1, a novel protein interacting
RT specifically with spliced isoforms and naturally occurring mutant NF2
RT proteins.";
RL Mol. Cell. Biol. 20:1699-1712(2000).
RN [12]
RP INVOLVEMENT IN MESOM.
RX PubMed=12136076; DOI=10.1212/wnl.59.2.290;
RA Baser M.E., De Rienzo A., Altomare D., Balsara B.R., Hedrick N.M.,
RA Gutmann D.H., Pitts L.H., Jackler R.K., Testa J.R.;
RT "Neurofibromatosis 2 and malignant mesothelioma.";
RL Neurology 59:290-291(2002).
RN [13]
RP INTERACTION WITH SGSM3.
RX PubMed=15541357; DOI=10.1016/j.bbrc.2004.10.095;
RA Lee I.K., Kim K.-S., Kim H., Lee J.Y., Ryu C.H., Chun H.J., Lee K.-U.,
RA Lim Y., Kim Y.H., Huh P.-W., Lee K.-H., Han S.-I., Jun T.-Y., Rha H.K.;
RT "MAP, a protein interacting with a tumor suppressor, merlin, through the
RT run domain.";
RL Biochem. Biophys. Res. Commun. 325:774-783(2004).
RN [14]
RP INTERACTION WITH AGAP2, AND MUTAGENESIS OF LEU-64.
RX PubMed=15598747; DOI=10.1073/pnas.0405971102;
RA Rong R., Tang X., Gutmann D.H., Ye K.;
RT "Neurofibromatosis 2 (NF2) tumor suppressor merlin inhibits
RT phosphatidylinositol 3-kinase through binding to PIKE-L.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:18200-18205(2004).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-518, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [16]
RP INTERACTION WITH DCAF1, AND UBIQUITINATION.
RX PubMed=18332868; DOI=10.1038/onc.2008.44;
RA Huang J., Chen J.;
RT "VprBP targets Merlin to the Roc1-Cul4A-DDB1 E3 ligase complex for
RT degradation.";
RL Oncogene 27:4056-4064(2008).
RN [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [18]
RP INTERACTION WITH MPP1, AND SUBCELLULAR LOCATION.
RX PubMed=19144871; DOI=10.3181/0809-rm-275;
RA Seo P.-S., Quinn B.J., Khan A.A., Zeng L., Takoudis C.G., Hanada T.,
RA Bolis A., Bolino A., Chishti A.H.;
RT "Identification of erythrocyte p55/MPP1 as a binding partner of NF2 tumor
RT suppressor protein/Merlin.";
RL Exp. Biol. Med. 234:255-262(2009).
RN [19]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH DCAF1 AND THE
RP CUL4A-RBX1-DDB1-VPRBP/DCAF1 E3 UBIQUITIN-PROTEIN LIGASE COMPLEX,
RP PHOSPHORYLATION, MUTAGENESIS OF LEU-64 AND SER-518, CHARACTERIZATION OF
RP VARIANT ARG-46, AND CHARACTERIZATION OF VARIANTS NF2 SER-62 AND PRO-141.
RX PubMed=20178741; DOI=10.1016/j.cell.2010.01.029;
RA Li W., You L., Cooper J., Schiavon G., Pepe-Caprio A., Zhou L., Ishii R.,
RA Giovannini M., Hanemann C.O., Long S.B., Erdjument-Bromage H., Zhou P.,
RA Tempst P., Giancotti F.G.;
RT "Merlin/NF2 suppresses tumorigenesis by inhibiting the E3 ubiquitin ligase
RT CRL4(DCAF1) in the nucleus.";
RL Cell 140:477-490(2010).
RN [20]
RP FUNCTION.
RX PubMed=20159598; DOI=10.1016/j.devcel.2009.12.012;
RA Yu J., Zheng Y., Dong J., Klusza S., Deng W.-M., Pan D.;
RT "Kibra functions as a tumor suppressor protein that regulates Hippo
RT signaling in conjunction with Merlin and Expanded.";
RL Dev. Cell 18:288-299(2010).
RN [21]
RP INTERACTION WITH WWC1.
RX PubMed=20159599; DOI=10.1016/j.devcel.2009.12.011;
RA Genevet A., Wehr M.C., Brain R., Thompson B.J., Tapon N.;
RT "Kibra Is a regulator of the Salvador/Warts/Hippo signaling network.";
RL Dev. Cell 18:300-308(2010).
RN [22]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [23]
RP FUNCTION, INTERACTION WITH NOP53, AND PHOSPHORYLATION.
RX PubMed=21167305; DOI=10.1016/j.biocel.2010.12.011;
RA Chen H., Mei L., Zhou L., Zhang X., Guo C., Li J., Wang H., Zhu Y.,
RA Zheng Y., Huang L.;
RT "Moesin-ezrin-radixin-like protein (merlin) mediates protein interacting
RT with the carboxyl terminus-1 (PICT-1)-induced growth inhibition of
RT glioblastoma cells in the nucleus.";
RL Int. J. Biochem. Cell Biol. 43:545-555(2011).
RN [24]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-13, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [25]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 1-313.
RX PubMed=11856822; DOI=10.1107/s0907444901021175;
RA Kang B.S., Cooper D.R., Devedjiev Y., Derewenda U., Derewenda Z.S.;
RT "The structure of the FERM domain of merlin, the neurofibromatosis type 2
RT gene product.";
RL Acta Crystallogr. D 58:381-391(2002).
RN [26]
RP VARIANT NF2 TYR-220.
RX PubMed=8230593; DOI=10.1001/jama.270.19.2316;
RA Maccollin M.M., Mohney T., Trofatter J.A., Wertelecki W., Ramesh V.,
RA Gusella J.F.;
RT "DNA diagnosis of neurofibromatosis 2. Altered coding sequence of the
RT merlin tumor suppressor in an extended pedigree.";
RL JAMA 270:2316-2320(1993).
RN [27]
RP VARIANT NF2 PHE-96 DEL.
RX PubMed=7913580;
RA Maccollin M.M., Ramesh V., Jacoby L.B., Louis D.N., Rubio M.-P.,
RA Pulaski K., Trofatter J.A., Short M.P., Bove C., Eldridge R., Parry D.M.,
RA Gusella J.F.;
RT "Mutational analysis of patients with neurofibromatosis 2.";
RL Am. J. Hum. Genet. 55:314-320(1994).
RN [28]
RP VARIANT ARG-46.
RX PubMed=8004107; DOI=10.1093/hmg/3.2.347;
RA Irving R.M., Moffat D.A., Hardy D.G., Barton D.E., Xuereb J.H., Maher E.R.;
RT "Somatic NF2 gene mutations in familial and non-familial vestibular
RT schwannoma.";
RL Hum. Mol. Genet. 3:347-350(1994).
RN [29]
RP VARIANTS MET-219 AND CYS-418.
RX PubMed=8012353; DOI=10.1093/hmg/3.3.413;
RA Jacoby L.B., Maccollin M.M., Louis D.N., Mohney T., Rubio M.-P.,
RA Pulaski K., Trofatter J.A., Kley N., Seizinger B.R., Ramesh V.,
RA Gusella J.F.;
RT "Exon scanning for mutation of the NF2 gene in schwannomas.";
RL Hum. Mol. Genet. 3:413-419(1994).
RN [30]
RP VARIANTS NF2 SER-62; GLY-106 AND MET-352.
RX PubMed=8081368; DOI=10.1093/hmg/3.5.813;
RA Bourn D., Carter S.A., Mason S., Gareth D., Evans R., Strachan T.;
RT "Germline mutations in the neurofibromatosis type 2 tumour suppressor
RT gene.";
RL Hum. Mol. Genet. 3:813-816(1994).
RN [31]
RP VARIANTS GLU-79 AND HIS-351.
RX PubMed=7951231; DOI=10.1093/hmg/3.6.885;
RA Sainz J., Huynh D.P., Figueroa K., Ragge N.K., Baser M.E., Pulst S.M.;
RT "Mutations of the neurofibromatosis type 2 gene and lack of the gene
RT product in vestibular schwannomas.";
RL Hum. Mol. Genet. 3:885-891(1994).
RN [32]
RP VARIANTS PHE-273 AND ILE-364.
RX PubMed=8162073; DOI=10.1038/ng0294-185;
RA Bianchi A.B., Hara T., Ramesh V., Gao J., Klein Szanto A.J., Morin F.,
RA Menon A.G., Trofatter J.A., Gusella J.F., Seizinger B.R., Kley N.;
RT "Mutations in transcript isoforms of the neurofibromatosis 2 gene in
RT multiple human tumour types.";
RL Nat. Genet. 6:185-192(1994).
RN [33]
RP VARIANTS NF2 PHE-119 DEL; GLU-413 AND PRO-535.
RX PubMed=7759081; DOI=10.1007/bf00223872;
RA Bourn D., Evans G., Mason S., Tekes S., Trueman L., Strachan T.;
RT "Eleven novel mutations in the NF2 tumour suppressor gene.";
RL Hum. Genet. 95:572-574(1995).
RN [34]
RP VARIANT NF2 PRO-535.
RX PubMed=7666400; DOI=10.1136/jmg.32.6.470;
RA Evans D.G.R., Bourn D., Wallace A., Ramsden R.T., Mitchell J.D.,
RA Strachan T.;
RT "Diagnostic issues in a family with late onset type 2 neurofibromatosis.";
RL J. Med. Genet. 32:470-474(1995).
RN [35]
RP VARIANT NF2 PRO-538.
RX PubMed=8566958; DOI=10.1007/bf02265270;
RA Kluwe L., Mautner V.-F.;
RT "A missense mutation in the NF2 gene results in moderate and mild clinical
RT phenotypes of neurofibromatosis type 2.";
RL Hum. Genet. 97:224-227(1996).
RN [36]
RP VARIANTS PHE-96 DEL; ILE-117; PHE-119 DEL; 122-VAL--GLU-129 DEL AND
RP PHE-339.
RX PubMed=8655144; DOI=10.1007/bf02281874;
RA de Vitis L.R., Tedde A., Vitelli F., Ammannati F., Mennonna P., Bigozzi U.,
RA Montali E., Papi L.;
RT "Screening for mutations in the neurofibromatosis type 2 (NF2) gene in
RT sporadic meningiomas.";
RL Hum. Genet. 97:632-637(1996).
RN [37]
RP VARIANTS NF2 CYS-197 AND HIS-539.
RX PubMed=8698340; DOI=10.1007/s004390050188;
RA Welling D.B., Guida M., Goll F., Pearl D.K., Glasscock M.E., Pappas D.G.,
RA Linthicum F.H., Rogers D., Prior T.W.;
RT "Mutational spectrum in the neurofibromatosis type 2 gene in sporadic and
RT familial schwannomas.";
RL Hum. Genet. 98:189-193(1996).
RN [38]
RP VARIANTS NF2 SER-62; VAL-77; GLY-106; MET-352; GLU-413 AND PRO-535.
RX PubMed=9643284; DOI=10.1136/jmg.35.6.450;
RA Evans D.G.R., Trueman L., Wallace A., Collins S., Strachan T.;
RT "Genotype/phenotype correlations in type 2 neurofibromatosis (NF2):
RT evidence for more severe disease associated with truncating mutations.";
RL J. Med. Genet. 35:450-455(1998).
RN [39]
RP ERRATUM OF PUBMED:9643284.
RA Evans D.G., Trueman L., Wallace A., Collins S., Strachan T.;
RL J. Med. Genet. 36:87-87(1999).
RN [40]
RP VARIANT NF2 ARG-234.
RX PubMed=10090912; DOI=10.1086/302338;
RA Baser M.E., Kluwe L., Mautner V.-F.;
RT "Germ-line NF2 mutations and disease severity in neurofibromatosis type 2
RT patients with retinal abnormalities.";
RL Am. J. Hum. Genet. 64:1230-1233(1999).
RN [41]
RP VARIANTS NF2 SER-62; THR-533 AND MET-579.
RX PubMed=10790209;
RX DOI=10.1002/(sici)1098-1004(200005)15:5<474::aid-humu9>3.0.co;2-7;
RA Faudoa R., Xue Z., Lee F., Baser M.E., Hung G.;
RT "Detection of novel NF2 mutations by an RNA mismatch cleavage method.";
RL Hum. Mutat. 15:474-478(2000).
RN [42]
RP VARIANT NF2 PRO-141.
RX PubMed=12709270; DOI=10.1016/s1472-6483(10)61809-3;
RA Verlinsky Y., Rechitsky S., Verlinsky O., Chistokhina A., Sharapova T.,
RA Masciangelo C., Levy M., Kaplan B., Lederer K., Kuliev A.;
RT "Preimplantation diagnosis for neurofibromatosis.";
RL Reprod. BioMed. Online 4:218-222(2002).
RN [43]
RP VARIANT [LARGE SCALE ANALYSIS] LYS-463.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
RN [44]
RP INVOLVEMENT IN SWNTS1.
RX PubMed=18072270; DOI=10.1002/humu.20679;
RA Sestini R., Bacci C., Provenzano A., Genuardi M., Papi L.;
RT "Evidence of a four-hit mechanism involving SMARCB1 and NF2 in
RT schwannomatosis-associated schwannomas.";
RL Hum. Mutat. 29:227-231(2008).
RN [45]
RP VARIANT NF2 ARG-133.
RX PubMed=20445339; DOI=10.3343/kjlm.2010.30.2.190;
RA Seong M.W., Yeo I.K., Cho S.I., Park C.K., Kim S.K., Paek S.H., Kim D.G.,
RA Jung H.W., Park H., Kim S.Y., Kim J.Y., Park S.S.;
RT "Molecular characterization of the NF2 gene in Korean patients with
RT neurofibromatosis type 2: a report of four novel mutations.";
RL Korean J. Lab. Med. 30:190-194(2010).
CC -!- FUNCTION: Probable regulator of the Hippo/SWH (Sav/Wts/Hpo) signaling
CC pathway, a signaling pathway that plays a pivotal role in tumor
CC suppression by restricting proliferation and promoting apoptosis. Along
CC with WWC1 can synergistically induce the phosphorylation of LATS1 and
CC LATS2 and can probably function in the regulation of the Hippo/SWH
CC (Sav/Wts/Hpo) signaling pathway. May act as a membrane stabilizing
CC protein. May inhibit PI3 kinase by binding to AGAP2 and impairing its
CC stimulating activity. Suppresses cell proliferation and tumorigenesis
CC by inhibiting the CUL4A-RBX1-DDB1-VprBP/DCAF1 E3 ubiquitin-protein
CC ligase complex. {ECO:0000269|PubMed:20159598,
CC ECO:0000269|PubMed:20178741, ECO:0000269|PubMed:21167305}.
CC -!- SUBUNIT: Interacts with SLC9A3R1, HGS and AGAP2. Interacts with LAYN
CC (By similarity). Interacts with SGSM3. Interacts (via FERM domain) with
CC MPP1. Interacts with WWC1. Interacts with the CUL4A-RBX1-DDB1-
CC VprBP/DCAF1 E3 ubiquitin-protein ligase complex. The unphosphorylated
CC form interacts (via FERM domain) with VPRBP/DCAF1. Interacts (via FERM
CC domain) with NOP53; the interaction is direct (PubMed:21167305).
CC Interacts with SCHIP1; the interaction is direct (PubMed:10669747).
CC {ECO:0000250, ECO:0000269|PubMed:10669747, ECO:0000269|PubMed:10861283,
CC ECO:0000269|PubMed:15541357, ECO:0000269|PubMed:15598747,
CC ECO:0000269|PubMed:18332868, ECO:0000269|PubMed:19144871,
CC ECO:0000269|PubMed:20159599, ECO:0000269|PubMed:20178741,
CC ECO:0000269|PubMed:21167305, ECO:0000269|PubMed:9430655}.
CC -!- INTERACTION:
CC P35240; Q6H8Q1-8: ABLIM2; NbExp=3; IntAct=EBI-1014472, EBI-16436655;
CC P35240; Q4VCS5: AMOT; NbExp=9; IntAct=EBI-1014472, EBI-2511319;
CC P35240; Q4VCS5-1: AMOT; NbExp=2; IntAct=EBI-1014472, EBI-3903812;
CC P35240; Q4VCS5-2: AMOT; NbExp=6; IntAct=EBI-1014472, EBI-3891843;
CC P35240; Q8WXF7: ATL1; NbExp=3; IntAct=EBI-1014472, EBI-2410266;
CC P35240; Q9UNS2: COPS3; NbExp=3; IntAct=EBI-1014472, EBI-350590;
CC P35240; Q5TAQ9-2: DCAF8; NbExp=3; IntAct=EBI-1014472, EBI-25842815;
CC P35240; O75530-2: EED; NbExp=3; IntAct=EBI-1014472, EBI-11132357;
CC P35240; Q8IZU1: FAM9A; NbExp=3; IntAct=EBI-1014472, EBI-8468186;
CC P35240; Q9BZE4: GTPBP4; NbExp=9; IntAct=EBI-1014472, EBI-1056249;
CC P35240; O60341: KDM1A; NbExp=4; IntAct=EBI-1014472, EBI-710124;
CC P35240; Q14525: KRT33B; NbExp=3; IntAct=EBI-1014472, EBI-1049638;
CC P35240; O95835: LATS1; NbExp=4; IntAct=EBI-1014472, EBI-444209;
CC P35240; Q8TBB1: LNX1; NbExp=3; IntAct=EBI-1014472, EBI-739832;
CC P35240; Q16584: MAP3K11; NbExp=4; IntAct=EBI-1014472, EBI-49961;
CC P35240; Q9H204: MED28; NbExp=4; IntAct=EBI-1014472, EBI-514199;
CC P35240; O76041: NEBL; NbExp=3; IntAct=EBI-1014472, EBI-2880203;
CC P35240; Q6X4W1-6: NSMF; NbExp=3; IntAct=EBI-1014472, EBI-25842707;
CC P35240; Q8NI35: PATJ; NbExp=2; IntAct=EBI-1014472, EBI-724390;
CC P35240; O75925: PIAS1; NbExp=3; IntAct=EBI-1014472, EBI-629434;
CC P35240; Q8WWB5: PIH1D2; NbExp=3; IntAct=EBI-1014472, EBI-10232538;
CC P35240; Q6ZR37: PLEKHG7; NbExp=3; IntAct=EBI-1014472, EBI-12891828;
CC P35240; Q6ZNE9: RUFY4; NbExp=3; IntAct=EBI-1014472, EBI-10181525;
CC P35240; Q9BY12-3: SCAPER; NbExp=3; IntAct=EBI-1014472, EBI-25837959;
CC P35240; Q13573: SNW1; NbExp=3; IntAct=EBI-1014472, EBI-632715;
CC P35240; Q9UNE7: STUB1; NbExp=3; IntAct=EBI-1014472, EBI-357085;
CC P35240; P54274-2: TERF1; NbExp=3; IntAct=EBI-1014472, EBI-711018;
CC P35240; Q96KP6: TNIP3; NbExp=3; IntAct=EBI-1014472, EBI-2509913;
CC P35240; Q86WT6-2: TRIM69; NbExp=3; IntAct=EBI-1014472, EBI-11525489;
CC P35240; Q99598: TSNAX; NbExp=3; IntAct=EBI-1014472, EBI-742638;
CC P35240; Q5VYS8-5: TUT7; NbExp=3; IntAct=EBI-1014472, EBI-9088812;
CC P35240; Q8NEZ2: VPS37A; NbExp=3; IntAct=EBI-1014472, EBI-2850578;
CC P35240; Q15776: ZKSCAN8; NbExp=3; IntAct=EBI-1014472, EBI-2602314;
CC P35240; P17024: ZNF20; NbExp=3; IntAct=EBI-1014472, EBI-717634;
CC P35240; Q9C0F3: ZNF436; NbExp=3; IntAct=EBI-1014472, EBI-8489702;
CC P35240; Q6ZNH5: ZNF497; NbExp=3; IntAct=EBI-1014472, EBI-10486136;
CC P35240; Q7Z3I7: ZNF572; NbExp=3; IntAct=EBI-1014472, EBI-10172590;
CC P35240; Q10728: Ppp1r12a; Xeno; NbExp=2; IntAct=EBI-1014472, EBI-918263;
CC P35240; P0DPB4: Schip1; Xeno; NbExp=2; IntAct=EBI-1014472, EBI-1397475;
CC P35240-1; O14964-1: HGS; NbExp=3; IntAct=EBI-1014500, EBI-21239519;
CC P35240-1; Q9H204: MED28; NbExp=2; IntAct=EBI-1014500, EBI-514199;
CC P35240-1; O14745: SLC9A3R1; NbExp=4; IntAct=EBI-1014500, EBI-349787;
CC P35240-1; E2RJV1: AMOT; Xeno; NbExp=2; IntAct=EBI-1014500, EBI-16145865;
CC P35240-1; F1PFK4: PARD3; Xeno; NbExp=2; IntAct=EBI-1014500, EBI-16145946;
CC P35240-3; O14964-2: HGS; NbExp=5; IntAct=EBI-1014509, EBI-21581128;
CC P35240-3; Q01082: SPTBN1; NbExp=4; IntAct=EBI-1014509, EBI-351561;
CC P35240-4; A2BDD9: AMOT; NbExp=3; IntAct=EBI-1014514, EBI-17286414;
CC P35240-4; Q9Y2J4: AMOTL2; NbExp=3; IntAct=EBI-1014514, EBI-746752;
CC P35240-4; Q96DX5-3: ASB9; NbExp=3; IntAct=EBI-1014514, EBI-25843552;
CC P35240-4; Q5H9J7: BEX5; NbExp=3; IntAct=EBI-1014514, EBI-10243741;
CC P35240-4; Q13895: BYSL; NbExp=3; IntAct=EBI-1014514, EBI-358049;
CC P35240-4; Q13191: CBLB; NbExp=3; IntAct=EBI-1014514, EBI-744027;
CC P35240-4; P48730-2: CSNK1D; NbExp=3; IntAct=EBI-1014514, EBI-9087876;
CC P35240-4; O00303: EIF3F; NbExp=3; IntAct=EBI-1014514, EBI-711990;
CC P35240-4; P50402: EMD; NbExp=3; IntAct=EBI-1014514, EBI-489887;
CC P35240-4; Q9Y6C2-2: EMILIN1; NbExp=3; IntAct=EBI-1014514, EBI-11748557;
CC P35240-4; Q8IZU1: FAM9A; NbExp=3; IntAct=EBI-1014514, EBI-8468186;
CC P35240-4; O14964: HGS; NbExp=4; IntAct=EBI-1014514, EBI-740220;
CC P35240-4; Q8N594: MPND; NbExp=3; IntAct=EBI-1014514, EBI-2512452;
CC P35240-4; O15381-5: NVL; NbExp=3; IntAct=EBI-1014514, EBI-18577082;
CC P35240-4; Q96FW1: OTUB1; NbExp=3; IntAct=EBI-1014514, EBI-1058491;
CC P35240-4; Q6GQQ9-2: OTUD7B; NbExp=3; IntAct=EBI-1014514, EBI-25830200;
CC P35240-4; O75925: PIAS1; NbExp=3; IntAct=EBI-1014514, EBI-629434;
CC P35240-4; Q8WVD3: RNF138; NbExp=3; IntAct=EBI-1014514, EBI-749039;
CC P35240-4; Q96D59: RNF183; NbExp=3; IntAct=EBI-1014514, EBI-743938;
CC P35240-4; Q8N488: RYBP; NbExp=3; IntAct=EBI-1014514, EBI-752324;
CC P35240-4; P60896: SEM1; NbExp=3; IntAct=EBI-1014514, EBI-79819;
CC P35240-4; Q8NHS9: SPATA22; NbExp=3; IntAct=EBI-1014514, EBI-7067260;
CC P35240-4; Q8N3L3: TXLNB; NbExp=3; IntAct=EBI-1014514, EBI-6116822;
CC P35240-4; P40337-2: VHL; NbExp=3; IntAct=EBI-1014514, EBI-12157263;
CC P35240-4; Q8NEZ2: VPS37A; NbExp=3; IntAct=EBI-1014514, EBI-2850578;
CC P35240-4; P58304: VSX2; NbExp=3; IntAct=EBI-1014514, EBI-6427899;
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Cell projection, filopodium
CC membrane; Peripheral membrane protein; Cytoplasmic side. Cell
CC projection, ruffle membrane; Peripheral membrane protein; Cytoplasmic
CC side. Nucleus. Note=In a fibroblastic cell line, isoform 1 is found
CC homogeneously distributed over the entire cell, with a particularly
CC strong staining in ruffling membranes and filopodia. Colocalizes with
CC MPP1 in non-myelin-forming Schwann cells. Binds with DCAF1 in the
CC nucleus. The intramolecular association of the FERM domain with the C-
CC terminal tail promotes nuclear accumulation. The unphosphorylated form
CC accumulates predominantly in the nucleus while the phosphorylated form
CC is largely confined to the non-nuclear fractions.
CC -!- SUBCELLULAR LOCATION: [Isoform 7]: Cytoplasm, perinuclear region.
CC Cytoplasmic granule. Note=Observed in cytoplasmic granules concentrated
CC in a perinuclear location. Isoform 7 is absent from ruffling membranes
CC and filopodia.
CC -!- SUBCELLULAR LOCATION: [Isoform 9]: Cytoplasm, perinuclear region.
CC Cytoplasmic granule. Note=Observed in cytoplasmic granules concentrated
CC in a perinuclear location. Isoform 9 is absent from ruffling membranes
CC and filopodia.
CC -!- SUBCELLULAR LOCATION: [Isoform 10]: Nucleus. Cell projection,
CC filopodium membrane; Peripheral membrane protein; Cytoplasmic side.
CC Cell projection, ruffle membrane; Peripheral membrane protein;
CC Cytoplasmic side. Cytoplasm, perinuclear region. Cytoplasmic granule.
CC Cytoplasm, cytoskeleton. Note=In a fibroblastic cell line, isoform 10
CC is found homogeneously distributed over the entire cell, with a
CC particularly strong staining in ruffling membranes and filopodia.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=10;
CC Name=1; Synonyms=I;
CC IsoId=P35240-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P35240-2; Sequence=VSP_000492;
CC Name=3; Synonyms=II;
CC IsoId=P35240-3; Sequence=VSP_007050, VSP_007051;
CC Name=4; Synonyms=delE2/3;
CC IsoId=P35240-4; Sequence=VSP_007041, VSP_007050, VSP_007051;
CC Name=5; Synonyms=delE3;
CC IsoId=P35240-5; Sequence=VSP_007042, VSP_007050, VSP_007051;
CC Name=6; Synonyms=delE2;
CC IsoId=P35240-6; Sequence=VSP_007040, VSP_007050, VSP_007051;
CC Name=7; Synonyms=MER150;
CC IsoId=P35240-7; Sequence=VSP_007045, VSP_007046;
CC Name=8;
CC IsoId=P35240-8; Sequence=VSP_007048, VSP_007050, VSP_007051;
CC Name=9; Synonyms=MER162;
CC IsoId=P35240-9; Sequence=VSP_007044;
CC Name=10; Synonyms=MER151;
CC IsoId=P35240-10; Sequence=VSP_007041, VSP_007043, VSP_007047,
CC VSP_007049;
CC -!- TISSUE SPECIFICITY: Widely expressed. Isoform 1 and isoform 3 are
CC predominant. Isoform 4, isoform 5 and isoform 6 are expressed
CC moderately. Isoform 8 is found at low frequency. Isoform 7, isoform 9
CC and isoform 10 are not expressed in adult tissues, with the exception
CC of adult retina expressing isoform 10. Isoform 9 is faintly expressed
CC in fetal brain, heart, lung, skeletal muscle and spleen. Fetal thymus
CC expresses isoforms 1, 7, 9 and 10 at similar levels.
CC -!- PTM: Phosphorylation of Ser-518 inhibits nuclear localization by
CC disrupting the intramolecular association of the FERM domain with the
CC C-terminal tail (PubMed:20178741). The dephosphorylation of Ser-518
CC favors the interaction with NOP53 (PubMed:21167305).
CC {ECO:0000269|PubMed:20178741, ECO:0000269|PubMed:21167305}.
CC -!- PTM: Ubiquitinated by the CUL4A-RBX1-DDB1-DCAF1/VprBP E3 ubiquitin-
CC protein ligase complex for ubiquitination and subsequent proteasome-
CC dependent degradation. {ECO:0000269|PubMed:18332868}.
CC -!- DISEASE: Neurofibromatosis 2 (NF2) [MIM:101000]: Genetic disorder
CC characterized by bilateral vestibular schwannomas (formerly called
CC acoustic neuromas), schwannomas of other cranial and peripheral nerves,
CC meningiomas, and ependymomas. It is inherited in an autosomal dominant
CC fashion with full penetrance. Affected individuals generally develop
CC symptoms of eighth-nerve dysfunction in early adulthood, including
CC deafness and balance disorder. Although the tumors of NF2 are
CC histologically benign, their anatomic location makes management
CC difficult, and patients suffer great morbidity and mortality.
CC {ECO:0000269|PubMed:10090912, ECO:0000269|PubMed:10669747,
CC ECO:0000269|PubMed:10790209, ECO:0000269|PubMed:12709270,
CC ECO:0000269|PubMed:20178741, ECO:0000269|PubMed:20445339,
CC ECO:0000269|PubMed:7666400, ECO:0000269|PubMed:7759081,
CC ECO:0000269|PubMed:7913580, ECO:0000269|PubMed:8081368,
CC ECO:0000269|PubMed:8230593, ECO:0000269|PubMed:8566958,
CC ECO:0000269|PubMed:8698340, ECO:0000269|PubMed:9643284}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Schwannomatosis 1 (SWNTS1) [MIM:162091]: A cancer syndrome in
CC which patients develop multiple non-vestibular schwannomas, benign
CC neoplasms that arise from Schwann cells of the cranial, peripheral, and
CC autonomic nerves. {ECO:0000269|PubMed:18072270}. Note=The disease is
CC caused by variants affecting the gene represented in this entry.
CC -!- DISEASE: Mesothelioma, malignant (MESOM) [MIM:156240]: An aggressive
CC neoplasm of the serosal lining of the chest. It appears as broad sheets
CC of cells, with some regions containing spindle-shaped, sarcoma-like
CC cells and other regions showing adenomatous patterns. Pleural
CC mesotheliomas have been linked to exposure to asbestos.
CC {ECO:0000269|PubMed:12136076}. Note=The disease may be caused by
CC variants affecting the gene represented in this entry.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="https://atlasgeneticsoncology.org/gene/117/nf2-(neurofibromatosis-type-2)";
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DR EMBL; L11353; AAA36212.1; -; mRNA.
DR EMBL; X72655; CAA51220.1; -; Genomic_DNA.
DR EMBL; X72656; CAA51220.1; JOINED; Genomic_DNA.
DR EMBL; X72657; CAA51220.1; JOINED; Genomic_DNA.
DR EMBL; X72658; CAA51220.1; JOINED; Genomic_DNA.
DR EMBL; X72659; CAA51220.1; JOINED; Genomic_DNA.
DR EMBL; X72660; CAA51220.1; JOINED; Genomic_DNA.
DR EMBL; X72661; CAA51220.1; JOINED; Genomic_DNA.
DR EMBL; X72662; CAA51220.1; JOINED; Genomic_DNA.
DR EMBL; X72663; CAA51220.1; JOINED; Genomic_DNA.
DR EMBL; X72664; CAA51220.1; JOINED; Genomic_DNA.
DR EMBL; X72665; CAA51220.1; JOINED; Genomic_DNA.
DR EMBL; X72666; CAA51220.1; JOINED; Genomic_DNA.
DR EMBL; X72667; CAA51220.1; JOINED; Genomic_DNA.
DR EMBL; X72668; CAA51220.1; JOINED; Genomic_DNA.
DR EMBL; X72669; CAA51220.1; JOINED; Genomic_DNA.
DR EMBL; X72670; CAA51220.1; JOINED; Genomic_DNA.
DR EMBL; Z22664; CAA80377.1; -; mRNA.
DR EMBL; Y18000; CAA76992.1; -; Genomic_DNA.
DR EMBL; Y18000; CAA76993.1; -; Genomic_DNA.
DR EMBL; AF122827; AAD48752.1; -; mRNA.
DR EMBL; AF122828; AAD48753.1; -; mRNA.
DR EMBL; AF123570; AAD48754.1; -; mRNA.
DR EMBL; AF369657; AAK54160.1; -; mRNA.
DR EMBL; AF369658; AAK54161.1; -; mRNA.
DR EMBL; AF369661; AAK54162.1; -; mRNA.
DR EMBL; AF369662; AAK54163.1; -; mRNA.
DR EMBL; AF369663; AAK54164.1; -; mRNA.
DR EMBL; AF369664; AAK54165.1; -; mRNA.
DR EMBL; AF369665; AAK54166.1; -; mRNA.
DR EMBL; AF369700; AAK54195.1; -; mRNA.
DR EMBL; AF369701; AAK54196.1; -; mRNA.
DR EMBL; CR456530; CAG30416.1; -; mRNA.
DR EMBL; BC003112; AAH03112.2; -; mRNA.
DR EMBL; BC020257; AAH20257.1; -; mRNA.
DR CCDS; CCDS13861.1; -. [P35240-1]
DR CCDS; CCDS13862.1; -. [P35240-3]
DR CCDS; CCDS13863.1; -. [P35240-6]
DR CCDS; CCDS13864.1; -. [P35240-5]
DR CCDS; CCDS13865.1; -. [P35240-4]
DR CCDS; CCDS54516.1; -. [P35240-9]
DR PIR; S33809; S33809.
DR RefSeq; NP_000259.1; NM_000268.3. [P35240-1]
DR RefSeq; NP_057502.2; NM_016418.5. [P35240-3]
DR RefSeq; NP_861546.1; NM_181825.2. [P35240-3]
DR RefSeq; NP_861966.1; NM_181828.2. [P35240-6]
DR RefSeq; NP_861967.1; NM_181829.2. [P35240-5]
DR RefSeq; NP_861968.1; NM_181830.2. [P35240-4]
DR RefSeq; NP_861969.1; NM_181831.2. [P35240-4]
DR RefSeq; NP_861970.1; NM_181832.2. [P35240-3]
DR RefSeq; NP_861971.1; NM_181833.2. [P35240-9]
DR PDB; 1H4R; X-ray; 1.80 A; A/B=1-313.
DR PDB; 3U8Z; X-ray; 2.64 A; A/B/C/D=18-312.
DR PDB; 4ZRI; X-ray; 2.70 A; A/B=1-320.
DR PDB; 4ZRJ; X-ray; 2.30 A; A=1-320, B=506-595.
DR PDB; 6CDS; X-ray; 2.62 A; A/B=1-339.
DR PDB; 7LWH; X-ray; 1.61 A; A=1-339.
DR PDBsum; 1H4R; -.
DR PDBsum; 3U8Z; -.
DR PDBsum; 4ZRI; -.
DR PDBsum; 4ZRJ; -.
DR PDBsum; 6CDS; -.
DR PDBsum; 7LWH; -.
DR AlphaFoldDB; P35240; -.
DR SMR; P35240; -.
DR BioGRID; 110844; 325.
DR CORUM; P35240; -.
DR DIP; DIP-35389N; -.
DR ELM; P35240; -.
DR IntAct; P35240; 135.
DR MINT; P35240; -.
DR STRING; 9606.ENSP00000344666; -.
DR CarbonylDB; P35240; -.
DR iPTMnet; P35240; -.
DR PhosphoSitePlus; P35240; -.
DR BioMuta; NF2; -.
DR DMDM; 462594; -.
DR CPTAC; CPTAC-1739; -.
DR EPD; P35240; -.
DR jPOST; P35240; -.
DR MassIVE; P35240; -.
DR MaxQB; P35240; -.
DR PaxDb; P35240; -.
DR PeptideAtlas; P35240; -.
DR PRIDE; P35240; -.
DR ProteomicsDB; 54999; -. [P35240-1]
DR ProteomicsDB; 55000; -. [P35240-10]
DR ProteomicsDB; 55001; -. [P35240-2]
DR ProteomicsDB; 55002; -. [P35240-3]
DR ProteomicsDB; 55003; -. [P35240-4]
DR ProteomicsDB; 55004; -. [P35240-5]
DR ProteomicsDB; 55005; -. [P35240-6]
DR ProteomicsDB; 55006; -. [P35240-7]
DR ProteomicsDB; 55007; -. [P35240-8]
DR ProteomicsDB; 55008; -. [P35240-9]
DR Antibodypedia; 319; 683 antibodies from 44 providers.
DR DNASU; 4771; -.
DR Ensembl; ENST00000334961.11; ENSP00000335652.7; ENSG00000186575.19. [P35240-4]
DR Ensembl; ENST00000338641.10; ENSP00000344666.5; ENSG00000186575.19. [P35240-1]
DR Ensembl; ENST00000353887.8; ENSP00000340626.4; ENSG00000186575.19. [P35240-4]
DR Ensembl; ENST00000361452.8; ENSP00000354897.4; ENSG00000186575.19. [P35240-5]
DR Ensembl; ENST00000361676.8; ENSP00000355183.4; ENSG00000186575.19. [P35240-6]
DR Ensembl; ENST00000397789.3; ENSP00000380891.3; ENSG00000186575.19. [P35240-3]
DR Ensembl; ENST00000403435.5; ENSP00000384029.1; ENSG00000186575.19. [P35240-8]
DR Ensembl; ENST00000403999.7; ENSP00000384797.3; ENSG00000186575.19. [P35240-3]
DR Ensembl; ENST00000413209.6; ENSP00000409921.2; ENSG00000186575.19. [P35240-9]
DR Ensembl; ENST00000432151.5; ENSP00000395885.1; ENSG00000186575.19. [P35240-10]
DR Ensembl; ENST00000672461.1; ENSP00000500919.1; ENSG00000186575.19. [P35240-3]
DR Ensembl; ENST00000672896.1; ENSP00000500117.1; ENSG00000186575.19. [P35240-3]
DR GeneID; 4771; -.
DR KEGG; hsa:4771; -.
DR MANE-Select; ENST00000338641.10; ENSP00000344666.5; NM_000268.4; NP_000259.1.
DR UCSC; uc003afy.5; human. [P35240-1]
DR CTD; 4771; -.
DR DisGeNET; 4771; -.
DR GeneCards; NF2; -.
DR GeneReviews; NF2; -.
DR HGNC; HGNC:7773; NF2.
DR HPA; ENSG00000186575; Low tissue specificity.
DR MalaCards; NF2; -.
DR MIM; 101000; phenotype.
DR MIM; 156240; phenotype.
DR MIM; 162091; phenotype.
DR MIM; 607379; gene.
DR neXtProt; NX_P35240; -.
DR OpenTargets; ENSG00000186575; -.
DR Orphanet; 2495; Meningioma.
DR Orphanet; 637; Neurofibromatosis type 2.
DR Orphanet; 93921; Schwannomatosis.
DR PharmGKB; PA31580; -.
DR VEuPathDB; HostDB:ENSG00000186575; -.
DR eggNOG; KOG3529; Eukaryota.
DR GeneTree; ENSGT01020000230354; -.
DR HOGENOM; CLU_136855_0_0_1; -.
DR InParanoid; P35240; -.
DR OMA; KERVDYW; -.
DR PhylomeDB; P35240; -.
DR TreeFam; TF313935; -.
DR PathwayCommons; P35240; -.
DR Reactome; R-HSA-2029482; Regulation of actin dynamics for phagocytic cup formation.
DR Reactome; R-HSA-5627123; RHO GTPases activate PAKs.
DR SignaLink; P35240; -.
DR SIGNOR; P35240; -.
DR BioGRID-ORCS; 4771; 69 hits in 1113 CRISPR screens.
DR ChiTaRS; NF2; human.
DR EvolutionaryTrace; P35240; -.
DR GeneWiki; Merlin_(protein); -.
DR GenomeRNAi; 4771; -.
DR Pharos; P35240; Tbio.
DR PRO; PR:P35240; -.
DR Proteomes; UP000005640; Chromosome 22.
DR RNAct; P35240; protein.
DR Bgee; ENSG00000186575; Expressed in endometrium epithelium and 203 other tissues.
DR ExpressionAtlas; P35240; baseline and differential.
DR Genevisible; P35240; HS.
DR GO; GO:0005912; C:adherens junction; IBA:GO_Central.
DR GO; GO:0045177; C:apical part of cell; IBA:GO_Central.
DR GO; GO:0044297; C:cell body; IEA:Ensembl.
DR GO; GO:0032154; C:cleavage furrow; IEA:Ensembl.
DR GO; GO:0030864; C:cortical actin cytoskeleton; IEA:Ensembl.
DR GO; GO:0005737; C:cytoplasm; IDA:HGNC-UCL.
DR GO; GO:0005856; C:cytoskeleton; TAS:ProtInc.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005769; C:early endosome; IDA:HGNC-UCL.
DR GO; GO:0031527; C:filopodium membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0030027; C:lamellipodium; IEA:Ensembl.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0043005; C:neuron projection; IEA:Ensembl.
DR GO; GO:0005730; C:nucleolus; IDA:HGNC-UCL.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:HGNC-UCL.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0032587; C:ruffle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0003779; F:actin binding; IEA:InterPro.
DR GO; GO:0005178; F:integrin binding; IBA:GO_Central.
DR GO; GO:0030036; P:actin cytoskeleton organization; IMP:HGNC-UCL.
DR GO; GO:0045216; P:cell-cell junction organization; IEA:Ensembl.
DR GO; GO:0007398; P:ectoderm development; IEA:Ensembl.
DR GO; GO:0021766; P:hippocampus development; IEA:Ensembl.
DR GO; GO:0070306; P:lens fiber cell differentiation; IEA:Ensembl.
DR GO; GO:0000165; P:MAPK cascade; IEA:Ensembl.
DR GO; GO:0001707; P:mesoderm formation; IEA:Ensembl.
DR GO; GO:0030336; P:negative regulation of cell migration; TAS:HGNC-UCL.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IDA:UniProtKB.
DR GO; GO:0022408; P:negative regulation of cell-cell adhesion; IDA:HGNC-UCL.
DR GO; GO:0001953; P:negative regulation of cell-matrix adhesion; TAS:HGNC-UCL.
DR GO; GO:0043409; P:negative regulation of MAPK cascade; IEA:Ensembl.
DR GO; GO:0033689; P:negative regulation of osteoblast proliferation; IEA:Ensembl.
DR GO; GO:0006469; P:negative regulation of protein kinase activity; IEA:Ensembl.
DR GO; GO:0046426; P:negative regulation of receptor signaling pathway via JAK-STAT; IDA:HGNC-UCL.
DR GO; GO:0010626; P:negative regulation of Schwann cell proliferation; IEA:Ensembl.
DR GO; GO:0042532; P:negative regulation of tyrosine phosphorylation of STAT protein; IDA:HGNC-UCL.
DR GO; GO:0042475; P:odontogenesis of dentin-containing tooth; IEA:Ensembl.
DR GO; GO:0033687; P:osteoblast proliferation; IEA:Ensembl.
DR GO; GO:0045597; P:positive regulation of cell differentiation; IEA:Ensembl.
DR GO; GO:0051496; P:positive regulation of stress fiber assembly; IMP:HGNC-UCL.
DR GO; GO:0042981; P:regulation of apoptotic process; IMP:UniProtKB.
DR GO; GO:0051726; P:regulation of cell cycle; IMP:UniProtKB.
DR GO; GO:0014013; P:regulation of gliogenesis; IBA:GO_Central.
DR GO; GO:0035330; P:regulation of hippo signaling; IMP:UniProtKB.
DR GO; GO:2000177; P:regulation of neural precursor cell proliferation; IEA:Ensembl.
DR GO; GO:1900180; P:regulation of protein localization to nucleus; IEA:Ensembl.
DR GO; GO:0031647; P:regulation of protein stability; IEA:Ensembl.
DR GO; GO:0072091; P:regulation of stem cell proliferation; IEA:Ensembl.
DR GO; GO:0014010; P:Schwann cell proliferation; IMP:HGNC-UCL.
DR CDD; cd14473; FERM_B-lobe; 1.
DR CDD; cd13194; FERM_C_ERM; 1.
DR Gene3D; 1.20.80.10; -; 1.
DR Gene3D; 2.30.29.30; -; 1.
DR Gene3D; 6.10.360.10; -; 1.
DR InterPro; IPR019749; Band_41_domain.
DR InterPro; IPR011174; ERM.
DR InterPro; IPR041789; ERM_FERM_C.
DR InterPro; IPR000798; Ez/rad/moesin-like.
DR InterPro; IPR014352; FERM/acyl-CoA-bd_prot_sf.
DR InterPro; IPR035963; FERM_2.
DR InterPro; IPR019748; FERM_central.
DR InterPro; IPR019747; FERM_CS.
DR InterPro; IPR000299; FERM_domain.
DR InterPro; IPR018979; FERM_N.
DR InterPro; IPR018980; FERM_PH-like_C.
DR InterPro; IPR008954; Moesin_tail_sf.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR029071; Ubiquitin-like_domsf.
DR PANTHER; PTHR23281; PTHR23281; 1.
DR Pfam; PF09380; FERM_C; 1.
DR Pfam; PF00373; FERM_M; 1.
DR Pfam; PF09379; FERM_N; 1.
DR PIRSF; PIRSF002305; ERM; 1.
DR PRINTS; PR00935; BAND41.
DR PRINTS; PR00661; ERMFAMILY.
DR SMART; SM00295; B41; 1.
DR SMART; SM01196; FERM_C; 1.
DR SUPFAM; SSF47031; SSF47031; 1.
DR SUPFAM; SSF48678; SSF48678; 1.
DR SUPFAM; SSF54236; SSF54236; 1.
DR PROSITE; PS00660; FERM_1; 1.
DR PROSITE; PS00661; FERM_2; 1.
DR PROSITE; PS50057; FERM_3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell membrane; Cell projection;
KW Cytoplasm; Cytoskeleton; Deafness; Disease variant; Membrane; Nucleus;
KW Phosphoprotein; Reference proteome; Tumor suppressor; Ubl conjugation.
FT CHAIN 1..595
FT /note="Merlin"
FT /id="PRO_0000219412"
FT DOMAIN 22..311
FT /note="FERM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00084"
FT MOD_RES 13
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 518
FT /note="Phosphoserine; by PAK"
FT /evidence="ECO:0007744|PubMed:17081983"
FT VAR_SEQ 39..121
FT /note="Missing (in isoform 4 and isoform 10)"
FT /evidence="ECO:0000303|PubMed:10401006,
FT ECO:0000303|PubMed:11827459, ECO:0000303|PubMed:15489334"
FT /id="VSP_007041"
FT VAR_SEQ 39..80
FT /note="Missing (in isoform 6)"
FT /evidence="ECO:0000303|PubMed:11827459"
FT /id="VSP_007040"
FT VAR_SEQ 81..121
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:11827459"
FT /id="VSP_007042"
FT VAR_SEQ 150..579
FT /note="Missing (in isoform 9)"
FT /evidence="ECO:0000303|PubMed:10401006"
FT /id="VSP_007044"
FT VAR_SEQ 150..225
FT /note="Missing (in isoform 10)"
FT /evidence="ECO:0000303|PubMed:10401006"
FT /id="VSP_007043"
FT VAR_SEQ 259
FT /note="N -> R (in isoform 7)"
FT /evidence="ECO:0000303|PubMed:10401006"
FT /id="VSP_007045"
FT VAR_SEQ 260..595
FT /note="Missing (in isoform 7)"
FT /evidence="ECO:0000303|PubMed:10401006"
FT /id="VSP_007046"
FT VAR_SEQ 334..379
FT /note="MERQRLAREKQMREEAERTRDELERRLLQMKEEATMANEALMRSEE -> GQ
FT RGRSAEAGPAGSTRGGAKSQAEAPGDCHQAHVPAHEPNSSTVAS (in isoform
FT 10)"
FT /evidence="ECO:0000303|PubMed:10401006"
FT /id="VSP_007047"
FT VAR_SEQ 335..363
FT /note="Missing (in isoform 8)"
FT /evidence="ECO:0000303|PubMed:11827459"
FT /id="VSP_007048"
FT VAR_SEQ 380..595
FT /note="Missing (in isoform 10)"
FT /evidence="ECO:0000303|PubMed:10401006"
FT /id="VSP_007049"
FT VAR_SEQ 580..595
FT /note="LTLQSAKSRVAFFEEL -> SSPRQKTYLHLSPQSRLFPGTLYVVMLYVVMV
FT LPSVILTRA (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_000492"
FT VAR_SEQ 580..590
FT /note="LTLQSAKSRVA -> PQAQGRRPICI (in isoform 3, isoform 4,
FT isoform 5, isoform 6 and isoform 8)"
FT /evidence="ECO:0000303|PubMed:11827459,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_007050"
FT VAR_SEQ 591..595
FT /note="Missing (in isoform 3, isoform 4, isoform 5, isoform
FT 6 and isoform 8)"
FT /evidence="ECO:0000303|PubMed:11827459,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_007051"
FT VARIANT 46
FT /note="L -> R (in vestibular schwannoma; loss of ability to
FT interact with the CUL4A-RBX1-DDB1-VprBP/DCAF1 E3 ubiquitin-
FT protein ligase complex)"
FT /evidence="ECO:0000269|PubMed:20178741,
FT ECO:0000269|PubMed:8004107"
FT /id="VAR_000809"
FT VARIANT 62
FT /note="F -> S (in NF2; loss of ability to interact with the
FT CUL4A-RBX1-DDB1-VprBP/DCAF1 E3 ubiquitin-protein ligase
FT complex; dbSNP:rs121434261)"
FT /evidence="ECO:0000269|PubMed:10790209,
FT ECO:0000269|PubMed:20178741, ECO:0000269|PubMed:8081368,
FT ECO:0000269|PubMed:9643284"
FT /id="VAR_000810"
FT VARIANT 77
FT /note="M -> V (in NF2)"
FT /evidence="ECO:0000269|PubMed:9643284"
FT /id="VAR_043011"
FT VARIANT 79
FT /note="K -> E (in vestibular schwannoma)"
FT /evidence="ECO:0000269|PubMed:7951231"
FT /id="VAR_000811"
FT VARIANT 96
FT /note="Missing (in NF2; also found in sporadic meningioma)"
FT /evidence="ECO:0000269|PubMed:7913580,
FT ECO:0000269|PubMed:8655144"
FT /id="VAR_000812"
FT VARIANT 106
FT /note="E -> G (in NF2)"
FT /evidence="ECO:0000269|PubMed:8081368,
FT ECO:0000269|PubMed:9643284"
FT /id="VAR_000813"
FT VARIANT 117
FT /note="L -> I (in sporadic meningioma)"
FT /evidence="ECO:0000269|PubMed:8655144"
FT /id="VAR_000814"
FT VARIANT 119
FT /note="Missing (in sporadic meningioma; no effect on
FT interaction with SCHIP1)"
FT /evidence="ECO:0000269|PubMed:10669747,
FT ECO:0000269|PubMed:7759081, ECO:0000269|PubMed:8655144"
FT /id="VAR_000815"
FT VARIANT 122..129
FT /note="Missing (in sporadic meningioma)"
FT /evidence="ECO:0000269|PubMed:8655144"
FT /id="VAR_000816"
FT VARIANT 133
FT /note="C -> R (in NF2)"
FT /evidence="ECO:0000269|PubMed:20445339"
FT /id="VAR_065227"
FT VARIANT 141
FT /note="L -> P (in NF2; loss of ability to interact with the
FT CUL4A-RBX1-DDB1-VprBP/DCAF1 E3 ubiquitin-protein ligase
FT complex)"
FT /evidence="ECO:0000269|PubMed:12709270,
FT ECO:0000269|PubMed:20178741"
FT /id="VAR_043012"
FT VARIANT 197
FT /note="G -> C (in NF2)"
FT /evidence="ECO:0000269|PubMed:8698340"
FT /id="VAR_043013"
FT VARIANT 219
FT /note="V -> M (in vestibular schwannoma; changed
FT interaction with SCHIP1; dbSNP:rs1555994816)"
FT /evidence="ECO:0000269|PubMed:10669747,
FT ECO:0000269|PubMed:8012353"
FT /id="VAR_000817"
FT VARIANT 220
FT /note="N -> Y (in NF2; dbSNP:rs1601618646)"
FT /evidence="ECO:0000269|PubMed:8230593"
FT /id="VAR_000818"
FT VARIANT 234
FT /note="L -> R (in NF2; also found in retinal hamartoma;
FT severe)"
FT /evidence="ECO:0000269|PubMed:10090912"
FT /id="VAR_009123"
FT VARIANT 273
FT /note="I -> F (in breast ductal carcinoma)"
FT /evidence="ECO:0000269|PubMed:8162073"
FT /id="VAR_000819"
FT VARIANT 339
FT /note="L -> F (in sporadic meningioma)"
FT /evidence="ECO:0000269|PubMed:8655144"
FT /id="VAR_000820"
FT VARIANT 351
FT /note="R -> H (in dbSNP:rs771675702)"
FT /evidence="ECO:0000269|PubMed:7951231"
FT /id="VAR_029041"
FT VARIANT 352
FT /note="T -> M (in NF2; dbSNP:rs764441073)"
FT /evidence="ECO:0000269|PubMed:8081368,
FT ECO:0000269|PubMed:9643284"
FT /id="VAR_000821"
FT VARIANT 360
FT /note="L -> P (in NF2; dbSNP:rs74315492)"
FT /id="VAR_000822"
FT VARIANT 364
FT /note="K -> I (in melanoma)"
FT /evidence="ECO:0000269|PubMed:8162073"
FT /id="VAR_000823"
FT VARIANT 413
FT /note="K -> E (in NF2; dbSNP:rs766974263)"
FT /evidence="ECO:0000269|PubMed:7759081,
FT ECO:0000269|PubMed:9643284"
FT /id="VAR_043014"
FT VARIANT 418
FT /note="R -> C (in vestibular schwannoma;
FT dbSNP:rs765540111)"
FT /evidence="ECO:0000269|PubMed:8012353"
FT /id="VAR_000824"
FT VARIANT 463
FT /note="E -> K (in a breast cancer sample; somatic mutation;
FT dbSNP:rs74315503)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_035848"
FT VARIANT 533
FT /note="K -> T (in NF2)"
FT /evidence="ECO:0000269|PubMed:10790209"
FT /id="VAR_043015"
FT VARIANT 535
FT /note="L -> P (in NF2; late onset; dbSNP:rs74315493)"
FT /evidence="ECO:0000269|PubMed:7666400,
FT ECO:0000269|PubMed:7759081, ECO:0000269|PubMed:9643284"
FT /id="VAR_000825"
FT VARIANT 538
FT /note="Q -> P (in NF2; mild; dbSNP:rs74315494)"
FT /evidence="ECO:0000269|PubMed:8566958"
FT /id="VAR_000826"
FT VARIANT 539
FT /note="L -> H (in NF2)"
FT /evidence="ECO:0000269|PubMed:8698340"
FT /id="VAR_043016"
FT VARIANT 579
FT /note="K -> M (in NF2)"
FT /evidence="ECO:0000269|PubMed:10790209"
FT /id="VAR_043017"
FT MUTAGEN 64
FT /note="L->P: Abolishes binding to AGAP2 and interaction
FT with the CUL4A-RBX1-DDB1-VprBP/DCAF1 E3 ubiquitin-protein
FT ligase complex."
FT /evidence="ECO:0000269|PubMed:15598747,
FT ECO:0000269|PubMed:20178741"
FT MUTAGEN 518
FT /note="S->A: Loss of phosphorylation. Significant
FT accumulation in the nucleus and no effect on binding to
FT DCAF1."
FT /evidence="ECO:0000269|PubMed:20178741"
FT MUTAGEN 518
FT /note="S->D: No effect on phosphorylation. Defective
FT nuclear accumulation. Significant decrease in binding to
FT DCAF1 and in ability to inhibit cell proliferation."
FT /evidence="ECO:0000269|PubMed:20178741"
FT CONFLICT 77
FT /note="M -> I (in Ref. 7; AAH20257)"
FT /evidence="ECO:0000305"
FT CONFLICT 581
FT /note="T -> P (in Ref. 5; AAK54160/AAK54162)"
FT /evidence="ECO:0000305"
FT STRAND 24..27
FT /evidence="ECO:0007829|PDB:7LWH"
FT STRAND 32..35
FT /evidence="ECO:0007829|PDB:7LWH"
FT HELIX 43..54
FT /evidence="ECO:0007829|PDB:7LWH"
FT HELIX 59..61
FT /evidence="ECO:0007829|PDB:7LWH"
FT STRAND 62..70
FT /evidence="ECO:0007829|PDB:7LWH"
FT STRAND 72..74
FT /evidence="ECO:0007829|PDB:7LWH"
FT STRAND 77..80
FT /evidence="ECO:0007829|PDB:4ZRJ"
FT TURN 81..83
FT /evidence="ECO:0007829|PDB:7LWH"
FT STRAND 84..86
FT /evidence="ECO:0007829|PDB:4ZRJ"
FT STRAND 90..100
FT /evidence="ECO:0007829|PDB:7LWH"
FT HELIX 105..108
FT /evidence="ECO:0007829|PDB:7LWH"
FT HELIX 112..127
FT /evidence="ECO:0007829|PDB:7LWH"
FT HELIX 135..150
FT /evidence="ECO:0007829|PDB:7LWH"
FT TURN 155..157
FT /evidence="ECO:0007829|PDB:7LWH"
FT TURN 160..165
FT /evidence="ECO:0007829|PDB:7LWH"
FT HELIX 171..174
FT /evidence="ECO:0007829|PDB:7LWH"
FT HELIX 181..194
FT /evidence="ECO:0007829|PDB:7LWH"
FT TURN 195..197
FT /evidence="ECO:0007829|PDB:7LWH"
FT HELIX 200..211
FT /evidence="ECO:0007829|PDB:7LWH"
FT TURN 215..218
FT /evidence="ECO:0007829|PDB:7LWH"
FT STRAND 220..226
FT /evidence="ECO:0007829|PDB:7LWH"
FT STRAND 231..236
FT /evidence="ECO:0007829|PDB:7LWH"
FT STRAND 238..244
FT /evidence="ECO:0007829|PDB:7LWH"
FT STRAND 249..251
FT /evidence="ECO:0007829|PDB:7LWH"
FT STRAND 253..257
FT /evidence="ECO:0007829|PDB:7LWH"
FT HELIX 258..260
FT /evidence="ECO:0007829|PDB:7LWH"
FT STRAND 261..267
FT /evidence="ECO:0007829|PDB:7LWH"
FT STRAND 270..277
FT /evidence="ECO:0007829|PDB:7LWH"
FT STRAND 283..286
FT /evidence="ECO:0007829|PDB:7LWH"
FT HELIX 290..309
FT /evidence="ECO:0007829|PDB:7LWH"
FT HELIX 316..336
FT /evidence="ECO:0007829|PDB:7LWH"
FT HELIX 513..547
FT /evidence="ECO:0007829|PDB:4ZRJ"
FT HELIX 552..554
FT /evidence="ECO:0007829|PDB:4ZRJ"
FT HELIX 557..562
FT /evidence="ECO:0007829|PDB:4ZRJ"
FT HELIX 573..581
FT /evidence="ECO:0007829|PDB:4ZRJ"
FT HELIX 585..594
FT /evidence="ECO:0007829|PDB:4ZRJ"
SQ SEQUENCE 595 AA; 69690 MW; B1A1BF2BD5DA561C CRC64;
MAGAIASRMS FSSLKRKQPK TFTVRIVTMD AEMEFNCEMK WKGKDLFDLV CRTLGLRETW
FFGLQYTIKD TVAWLKMDKK VLDHDVSKEE PVTFHFLAKF YPENAEEELV QEITQHLFFL
QVKKQILDEK IYCPPEASVL LASYAVQAKY GDYDPSVHKR GFLAQEELLP KRVINLYQMT
PEMWEERITA WYAEHRGRAR DEAEMEYLKI AQDLEMYGVN YFAIRNKKGT ELLLGVDALG
LHIYDPENRL TPKISFPWNE IRNISYSDKE FTIKPLDKKI DVFKFNSSKL RVNKLILQLC
IGNHDLFMRR RKADSLEVQQ MKAQAREEKA RKQMERQRLA REKQMREEAE RTRDELERRL
LQMKEEATMA NEALMRSEET ADLLAEKAQI TEEEAKLLAQ KAAEAEQEMQ RIKATAIRTE
EEKRLMEQKV LEAEVLALKM AEESERRAKE ADQLKQDLQE AREAERRAKQ KLLEIATKPT
YPPMNPIPAP LPPDIPSFNL IGDSLSFDFK DTDMKRLSME IEKEKVEYME KSKHLQEQLN
ELKTEIEALK LKERETALDI LHNENSDRGG SSKHNTIKKL TLQSAKSRVA FFEEL
