ID MECP2_HUMAN Reviewed; 486 AA. AC P51608; O15233; Q6QHH9; Q7Z384; DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-1996, sequence version 1. DT 27-MAR-2024, entry version 255. DE RecName: Full=Methyl-CpG-binding protein 2; DE Short=MeCp-2 protein; DE Short=MeCp2; GN Name=MECP2; 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 A). RX PubMed=9710633; DOI=10.1128/mcb.18.9.5492; RA Kudo S.; RT "Methyl-CpG-binding protein MeCP2 represses Sp1-activated transcription of RT the human leukosialin gene when the promoter is methylated."; RL Mol. Cell. Biol. 18:5492-5499(1998). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A). RX PubMed=8976388; DOI=10.1159/000134438; RA Vilain A., Apiou F., Vogt N., Dutrillaux B., Malfoy B.; RT "Assignment of the gene for methyl-CpG-binding protein 2 (MECP2) to human RT chromosome band Xq28 by in situ hybridization."; RL Cytogenet. Cell Genet. 74:293-294(1996). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A). RX PubMed=10369871; DOI=10.1093/hmg/8.7.1253; RA Coy J.F., Sedlacek Z., Baechner D., Delius H., Poustka A.; RT "A complex pattern of evolutionary conservation and alternative RT polyadenylation within the long 3'-untranslated region of the methyl-CpG- RT binding protein 2 gene (MeCP2) suggests a regulatory role in gene RT expression."; RL Hum. Mol. Genet. 8:1253-1262(1999). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A). RX PubMed=10723722; DOI=10.1007/s003350010035; RA Reichwald K., Thiesen J., Wiehe T., Weitzel J., Poustka W.A., Rosenthal A., RA Platzer M., Stratling W.H., Kioschis P.; RT "Comparative sequence analysis of the MECP2-locus in human and mouse RT reveals new transcribed regions."; RL Mamm. Genome 11:182-190(2000). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM B), AND INVOLVEMENT IN RTT. RX PubMed=15034579; DOI=10.1038/ng1327; RA Mnatzakanian G.N., Lohi H., Munteanu I., Alfred S.E., Yamada T., RA MacLeod P.J.M., Jones J.R., Scherer S.W., Schanen N.C., Friez M.J., RA Vincent J.B., Minassian B.A.; RT "A previously unidentified MECP2 open reading frame defines a new protein RT isoform relevant to Rett syndrome."; RL Nat. Genet. 36:339-341(2004). RN [6] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A). RC TISSUE=Placenta; RA Straetling W.H.; RL Submitted (APR-1997) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM B). RC TISSUE=Colon endothelium; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., RA Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15772651; DOI=10.1038/nature03440; RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., RA Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C., RA Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., RA Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., RA Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., RA Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., RA Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., RA Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., RA Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., RA Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., RA Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., RA Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., RA Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., RA Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., RA Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., RA Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., RA Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., RA Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., RA Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., RA Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., RA Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., RA Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., RA Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., RA Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., RA Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., RA Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., RA Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., RA Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., RA Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., RA Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., RA Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., RA Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., RA d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., RA Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., RA Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., RA Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., RA Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., RA Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., RA Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., RA Rogers J., Bentley D.R.; RT "The DNA sequence of the human X chromosome."; RL Nature 434:325-337(2005). RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM A). RC TISSUE=Placenta; 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 [10] RP NUCLEOTIDE SEQUENCE [MRNA] OF 10-486 (ISOFORM A). RC TISSUE=Skeletal muscle; RX PubMed=8672133; DOI=10.1007/s003359900157; RA D'Esposito M., Quaderi N.A., Ciccodicola A., Bruni P., Esposito T., RA D'Urso M., Brown S.D.M.; RT "Isolation, physical mapping, and Northern analysis of the X-linked human RT gene encoding methyl CpG-binding protein, MECP2."; RL Mamm. Genome 7:533-535(1996). RN [11] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 10-486 (ISOFORM A). RA Reichwald K., Bauer D., Brenner V., Drescher B., Coy J.F., Kioschis P., RA Korn B., Nyakatura G., Platzer M., Poustka A., Sandoval N., Rosenthal A.; RT "Genetic organization of human methyl-CpG-binding protein 2."; RL Submitted (DEC-1996) to the EMBL/GenBank/DDBJ databases. RN [12] RP IDENTIFICATION (ISOFORM B). RX PubMed=15034150; DOI=10.1093/nar/gkh349; RA Kriaucionis S., Bird A.; RT "The major form of MeCP2 has a novel N-terminus generated by alternative RT splicing."; RL Nucleic Acids Res. 32:1818-1823(2004). RN [13] RP REVIEW ON VARIANTS. RX PubMed=12872250; DOI=10.1002/humu.10243; RA Miltenberger-Miltenyi G., Laccone F.; RT "Mutations and polymorphisms in the human methyl CpG-binding protein RT MECP2."; RL Hum. Mutat. 22:107-115(2003). RN [14] RP INTERACTION WITH CDKL5. RX PubMed=15917271; DOI=10.1093/hmg/ddi198; RA Mari F., Azimonti S., Bertani I., Bolognese F., Colombo E., Caselli R., RA Scala E., Longo I., Grosso S., Pescucci C., Ariani F., Hayek G., RA Balestri P., Bergo A., Badaracco G., Zappella M., Broccoli V., Renieri A., RA Kilstrup-Nielsen C., Landsberger N.; RT "CDKL5 belongs to the same molecular pathway of MeCP2 and it is responsible RT for the early-onset seizure variant of Rett syndrome."; RL Hum. Mol. Genet. 14:1935-1946(2005). RN [15] RP IDENTIFICATION BY 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 IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=T-cell; RX PubMed=19367720; DOI=10.1021/pr800500r; RA Carrascal M., Ovelleiro D., Casas V., Gay M., Abian J.; RT "Phosphorylation analysis of primary human T lymphocytes using sequential RT IMAC and titanium oxide enrichment."; RL J. Proteome Res. 7:5167-5176(2008). RN [17] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-80; SER-116 AND SER-426, AND 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 IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [19] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-80, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [20] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-449, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19608861; DOI=10.1126/science.1175371; RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., RA Olsen J.V., Mann M.; RT "Lysine acetylation targets protein complexes and co-regulates major RT cellular functions."; RL Science 325:834-840(2009). RN [21] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-80 AND SER-216, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [22] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-80, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [23] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-80 AND SER-229, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; 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 [24] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-426, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [25] RP STRUCTURE BY NMR OF 77-166. RX PubMed=10518942; DOI=10.1006/jmbi.1999.3023; RA Wakefield R.I., Smith B.O., Nan X., Free A., Soteriou A., Uhrin D., RA Bird A.P., Barlow P.N.; RT "The solution structure of the domain from MeCP2 that binds to methylated RT DNA."; RL J. Mol. Biol. 291:1055-1065(1999). RN [26] RP VARIANTS RTT TRP-106; CYS-133; SER-155; MET-158 AND CYS-306, AND VARIANT RP LYS-397. RX PubMed=10577905; DOI=10.1086/302690; RA Wan M., Lee S.S.J., Zhang X., Houwink-Manville I., Song H.-R., Amir R.E., RA Budden S., Naidu S., Pereira J.L.P., Lo I.F.M., Zoghbi H.Y., Schanen N.C., RA Francke U.; RT "Rett syndrome and beyond: recurrent spontaneous and familial MECP2 RT mutations at CpG hotspots."; RL Am. J. Hum. Genet. 65:1520-1529(1999). RN [27] RP VARIANTS RTT TRP-106; CYS-133; SER-155 AND MET-158. RX PubMed=10508514; DOI=10.1038/13810; RA Amir R.E., Van den Veyver I.B., Wan M., Tran C.Q., Francke U., Zoghbi H.Y.; RT "Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl- RT CpG-binding protein 2."; RL Nat. Genet. 23:185-188(1999). RN [28] RP INVOLVEMENT IN MRXS13. RX PubMed=10986043; DOI=10.1086/303078; RA Meloni I., Bruttini M., Longo I., Mari F., Rizzolio F., D'Adamo P., RA Denvriendt K., Fryns J.-P., Toniolo D., Renieri A.; RT "A mutation in the Rett syndrome gene, MECP2, causes X-linked mental RT retardation and progressive spasticity in males."; RL Am. J. Hum. Genet. 67:982-985(2000). RN [29] RP VARIANTS RTT VAL-100; GLN-106; TRP-106; CYS-133; ARG-152; SER-155; MET-158; RP ARG-305; CYS-306 AND HIS-306, AND VARIANTS CYS-86; MET-203; PRO-287; RP ALA-291; LYS-397; ILE-412 AND THR-444. RX PubMed=11055898; DOI=10.1086/316913; RA Buyse I.M., Fang P., Hoon K.T., Amir R.E., Zoghbi H.Y., Roa B.B.; RT "Diagnostic testing for Rett syndrome by DHPLC and direct sequencing RT analysis of the MECP2 gene: identification of several novel mutations and RT polymorphisms."; RL Am. J. Hum. Genet. 67:1428-1436(2000). RN [30] RP VARIANT MRXS13 VAL-140, AND VARIANT MET-203. RX PubMed=11007980; DOI=10.1016/s0014-5793(00)01994-3; RA Orrico A., Lam C., Galli L., Dotti M.T., Hayek G., Tong S.F., Poon P.M., RA Zappella M., Federico A., Sorrentino V.; RT "MECP2 mutation in male patients with non-specific X-linked mental RT retardation."; RL FEBS Lett. 481:285-288(2000). RN [31] RP VARIANTS RTT LEU-101; HIS-101; THR-101; TRP-106; CYS-133; CYS-134; ARG-152; RP MET-158; ARG-225; LEU-302; CYS-306 AND HIS-306, AND VARIANTS LEU-229 AND RP THR-439. RX PubMed=10767337; DOI=10.1093/hmg/9.7.1119; RA Cheadle J.P., Gill H., Fleming N., Maynard J., Kerr A., Leonard H., RA Krawczak M., Cooper D.N., Lynch S., Thomas N., Hughes H., Hulten M., RA Ravine D., Sampson J.R., Clarke A.; RT "Long-read sequence analysis of the MECP2 gene in Rett syndrome patients: RT correlation of disease severity with mutation type and location."; RL Hum. Mol. Genet. 9:1119-1129(2000). RN [32] RP VARIANTS RTT GLN-106; MET-158; ARG-302; CYS-306 AND ALA-322. RX PubMed=10814719; DOI=10.1093/hmg/9.9.1377; RA Bienvenu T., Carrie A., de Roux N., Vinet M.-C., Jonveaux P., Couvert P., RA Villard L., Arzimanoglou A., Beldjord C., Fontes M., Tardieu M., Chelly J.; RT "MECP2 mutations account for most cases of typical forms of Rett RT syndrome."; RL Hum. Mol. Genet. 9:1377-1384(2000). RN [33] RP VARIANTS RTT MET-158; HIS-302 AND CYS-306, AND VARIANTS VAL-201; ALA-232; RP LEU-251 AND SER-376. RX PubMed=10944854; DOI=10.1007/s100380070032; RA Amano K., Nomura Y., Segawa M., Yamakawa K.; RT "Mutational analysis of the MECP2 gene in Japanese patients with Rett RT syndrome."; RL J. Hum. Genet. 45:231-236(2000). RN [34] RP VARIANTS RTT GLU-97; TRP-106; CYS-133; ILE-155; MET-158 AND CYS-306. RX PubMed=10745042; DOI=10.1136/jmg.37.4.250; RA Xiang F., Buervenich S., Nicolao P., Bailey M.E., Zhang Z., Anvret M.; RT "Mutation screening in Rett syndrome patients."; RL J. Med. Genet. 37:250-255(2000). RN [35] RP VARIANTS RTT TRP-106; PHE-124; CYS-133; CYS-134; ARG-152; MET-158 AND RP CYS-306. RX PubMed=10991688; DOI=10.1136/jmg.37.8.608; RA Obata K., Matsuishi T., Yamashita Y., Fukuda T., Kuwajima K., Horiuchi I., RA Nagamitsu S., Iwanaga R., Kimura A., Omori I., Endo S., Mori K., Kondo I.; RT "Mutation analysis of the methyl-CpG binding protein 2 gene (MECP2) in RT patients with Rett syndrome."; RL J. Med. Genet. 37:608-610(2000). RN [36] RP VARIANTS RTT ARG-101; TRP-106; MET-158 AND CYS-306, AND VARIANT LYS-397. RX PubMed=10991689; DOI=10.1136/jmg.37.8.610; RA Hampson K., Woods C.G., Latif F., Webb T.; RT "Mutations in the MECP2 gene in a cohort of girls with Rett syndrome."; RL J. Med. Genet. 37:610-612(2000). RN [37] RP VARIANT RTT HIS-133. RX PubMed=11706982; DOI=10.1002/ana.1272; RA Armstrong J., Poo P., Pineda M., Aibar E., Gean E., Catala V., Monros E.; RT "Classic Rett syndrome in a boy as a result of somatic mosaicism for a RT MECP2 mutation."; RL Ann. Neurol. 50:692-692(2001). RN [38] RP VARIANTS RTT ASP-120; CYS-133; MET-158 AND CYS-306. RX PubMed=11376998; DOI=10.1016/s0387-7604(01)00197-8; RA Inui K., Akagi M., Ono J., Tsukamoto H., Shimono K., Mano T., Imai K., RA Yamada M., Muramatsu T., Sakai N., Okada S.; RT "Mutational analysis of MECP2 in Japanese patients with atypical Rett RT syndrome."; RL Brain Dev. 23:212-215(2001). RN [39] RP VARIANTS RTT TRP-106; CYS-134; ARG-152; MET-158; ALA-302; CYS-306 AND RP ALA-322, AND VARIANTS VAL-201 AND LYS-397. RX PubMed=11738883; DOI=10.1016/s0387-7604(01)00342-4; RA Giunti L., Pelagatti S., Lazzerini V., Guarducci S., Lapi E., Coviello S., RA Cecconi A., Ombroni L., Andreucci E., Sani I., Brusaferri A., Lasagni A., RA Ricotti G., Giometto B., Nicolao P., Gasparini P., Granatiero M., RA Giovannucci Uzielli M.L.; RT "Spectrum and distribution of MECP2 mutations in 64 Italian Rett syndrome RT girls: tentative genotype/phenotype correlation."; RL Brain Dev. 23:S242-S245(2001). RN [40] RP VARIANTS MRXS13 GLY-137; VAL-140; TRP-167; GLU-284; LEU-399 AND GLN-453. RX PubMed=11309367; DOI=10.1093/hmg/10.9.941; RA Couvert P., Bienvenu T., Aquaviva C., Poirier K., Moraine C., Gendrot C., RA Verloes A., Andres C., Le Fevre A.C., Souville I., Steffann J., RA des Portes V., Ropers H.-H., Yntema H.G., Fryns J.-P., Briault S., RA Chelly J., Cherif B.; RT "MECP2 is highly mutated in X-linked mental retardation."; RL Hum. Mol. Genet. 10:941-946(2001). RN [41] RP VARIANTS RTT TRP-106; GLY-111; CYS-133; GLU-135; ARG-152; GLY-156; MET-158; RP ILE-210; ARG-302 AND CYS-306. RX PubMed=11241840; DOI=10.1002/humu.3; RA Laccone F., Huppke P., Hanefeld F., Meins M.; RT "Mutation spectrum in patients with Rett syndrome in the German population: RT evidence of hot spot regions."; RL Hum. Mutat. 17:183-190(2001). RN [42] RP VARIANT RTT ARG-101, AND INVOLVEMENT IN AS. RX PubMed=11283202; DOI=10.1136/jmg.38.4.224; RA Watson P., Black G., Ramsden S., Barrow M., Super M., Kerr B., RA Clayton-Smith J.; RT "Angelman syndrome phenotype associated with mutations in MECP2, a gene RT encoding a methyl CpG binding protein."; RL J. Med. Genet. 38:224-228(2001). RN [43] RP VARIANT ENS-MECP2 SER-428. RX PubMed=11238684; DOI=10.1136/jmg.38.3.171; RA Imessaoudene B., Bonnefont J.-P., Royer G., Cormier-Daire V., Lyonnet S., RA Lyon G., Munnich A., Amiel J.; RT "MECP2 mutation in non-fatal, non-progressive encephalopathy in a male."; RL J. Med. Genet. 38:171-174(2001). RN [44] RP VARIANTS RTT SER-101; TRP-106; CYS-133; CYS-134; ARG-152; ALA-158 AND RP MET-158. RX PubMed=11269512; DOI=10.1007/s001090000155; RA Vacca M., Filippini F., Budillon A., Rossi V., Mercadante G., Manzati E., RA Gualandi F., Bigoni S., Trabanelli C., Pini G., Calzolari E., Ferlini A., RA Meloni I., Hayek G., Zappella M., Renieri A., D'Urso M., D'Esposito M., RA MacDonald F., Kerr A., Dhanjal S., Hulten M.; RT "Mutation analysis of the MECP2 gene in British and Italian Rett syndrome RT females."; RL J. Mol. Med. 78:648-655(2001). RN [45] RP VARIANTS RTT TYR-97; TRP-106; HIS-133; CYS-133; ARG-152; MET-158; ARG-305; RP CYS-306 AND LEU-322, AND VARIANT MET-197. RX PubMed=11402105; DOI=10.1212/wnl.56.11.1486; RA Hoffbuhr K., Devaney J.M., LaFleur B., Sirianni N., Scacheri C., Giron J., RA Schuette J., Innis J., Marino M., Philippart M., Narayanan V., Umansky R., RA Kronn D., Hoffman E.P., Naidu S.; RT "MeCP2 mutations in children with and without the phenotype of Rett RT syndrome."; RL Neurology 56:1486-1495(2001). RN [46] RP VARIANT MRXS13 VAL-140. RX PubMed=11885030; DOI=10.1086/339553; RA Klauck S.M., Lindsay S., Beyer K.S., Splitt M., Burn J., Poustka A.; RT "A mutation hot spot for nonspecific X-linked mental retardation in the RT MECP2 gene causes the PPM-X syndrome."; RL Am. J. Hum. Genet. 70:1034-1037(2002). RN [47] RP VARIANTS PRO-359 AND LYS-397. RX PubMed=11896461; DOI=10.1038/sj.ejhg.5200761; RA Moncla A., Kpebe A., Missirian C., Mancini J., Villard L.; RT "Polymorphisms in the C-terminal domain of MECP2 in mentally handicapped RT boys: implications for genetic counselling."; RL Eur. J. Hum. Genet. 10:86-89(2002). RN [48] RP VARIANTS SER-196; SER-228; LYS-394 AND SER-480. RX PubMed=12111644; DOI=10.1038/sj.ejhg.5200836; RA Yntema H.G., Kleefstra T., Oudakker A.R., Romein T., de Vries B.B.A., RA Nillesen W., Sistermans E.A., Brunner H.G., Hamel B.C.J., van Bokhoven H.; RT "Low frequency of MECP2 mutations in mentally retarded males."; RL Eur. J. Hum. Genet. 10:487-490(2002). RN [49] RP VARIANTS VAL-181; SER-376; PRO-388 DEL AND LEU-402. RX PubMed=12384770; DOI=10.1007/s00439-002-0786-3; RA Beyer K.S., Blasi F., Bacchelli E., Klauck S.M., Maestrini E., Poustka A.; RT "Mutation analysis of the coding sequence of the MECP2 gene in infantile RT autism."; RL Hum. Genet. 111:305-309(2002). RN [50] RP VARIANT MRXS13 VAL-140. RX PubMed=12325019; DOI=10.1002/humu.10130; RA Winnepenninckx B., Errijgers V., Hayez-Delatte F., Reyniers E., Kooy R.F.; RT "Identification of a family with nonspecific mental retardation (MRX79) RT with the A140V mutation in the MECP2 gene: is there a need for routine RT screening?"; RL Hum. Mutat. 20:249-252(2002). RN [51] RP VARIANT MRXS13 VAL-140, VARIANT RTT TRP-344, VARIANTS MET-197; SER-376; RP LEU-399 AND SER-428, AND DISCUSSION OF PATHOGENIC ROLE. RX PubMed=12161600; DOI=10.1136/jmg.39.8.586; RA Laccone F., Zoll B., Huppke P., Hanefeld F., Pepinski W., Trappe R.; RT "MECP2 gene nucleotide changes and their pathogenicity in males: proceed RT with caution."; RL J. Med. Genet. 39:586-588(2002). RN [52] RP VARIANT MRXS13 VAL-140. RX PubMed=11805248; DOI=10.1212/wnl.58.2.226; RA Dotti M.T., Orrico A., De Stefano N., Battisti C., Sicurelli F., Severi S., RA Lam C.-W., Galli L., Sorrentino V., Federico A.; RT "A Rett syndrome MECP2 mutation that causes mental retardation in men."; RL Neurology 58:226-230(2002). RN [53] RP VARIANTS RTT CYS-133; MET-158; CYS-306 AND SER-388, AND VARIANT SER-376. RX PubMed=12567420; DOI=10.1002/ajmg.a.10898; RA Conforti F.L., Mazzei R., Magariello A., Patitucci A.L., Gabriele A.L., RA Muglia M., Quattrone A., Fiumara A., Pavone L., Barone R., Nistico R., RA Mangone L.; RT "Mutation analysis of the MECP2 gene in patients with Rett syndrome."; RL Am. J. Med. Genet. A 117:184-187(2003). RN [54] RP VARIANT RTT VAL-100. RX PubMed=12966522; DOI=10.1002/ajmg.a.20320; RA Hammer S., Dorrani N., Hartiala J., Stein S., Schanen N.C.; RT "Rett syndrome in a 47,XXX patient with a de novo MECP2 mutation."; RL Am. J. Med. Genet. A 122:223-226(2003). RN [55] RP VARIANTS RTT GLN-10; PRO-128; CYS-133; ARG-152; MET-158 AND CYS-306. RX PubMed=12966523; DOI=10.1002/ajmg.a.20321; RA Smeets E., Schollen E., Moog U., Matthijs G., Herbergs J., Smeets H., RA Curfs L., Schrander-Stumpel C., Fryns J.-P.; RT "Rett syndrome in adolescent and adult females: clinical and molecular RT genetic findings."; RL Am. J. Med. Genet. A 122:227-233(2003). RN [56] RP VARIANT MRXS13 LEU-225. RX PubMed=12615169; DOI=10.1016/s1090-3798(02)00134-4; RA Moog U., Smeets E.E.J., van Roozendaal K.E.P., Schoenmakers S., RA Herbergs J., Schoonbrood-Lenssen A.M.J., Schrander-Stumpel C.T.R.M.; RT "Neurodevelopmental disorders in males related to the gene causing Rett RT syndrome in females (MECP2)."; RL Eur. J. Paediatr. Neurol. 7:5-12(2003). RN [57] RP INVOLVEMENT IN AUTSX3. RX PubMed=12770674; DOI=10.1016/s0887-8994(02)00624-0; RA Carney R.M., Wolpert C.M., Ravan S.A., Shahbazian M., Ashley-Koch A., RA Cuccaro M.L., Vance J.M., Pericak-Vance M.A.; RT "Identification of MeCP2 mutations in a series of females with autistic RT disorder."; RL Pediatr. Neurol. 28:205-211(2003). RN [58] RP VARIANTS RTT ARG-100; VAL-100; TRP-106; CYS-133; ARG-152; ALA-158; MET-158; RP VAL-161; CYS-306 AND HIS-306. RX PubMed=15057977; DOI=10.1002/ajmg.a.20571; RA Schanen C., Houwink E.J.F., Dorrani N., Lane J., Everett R., Feng A., RA Cantor R.M., Percy A.; RT "Phenotypic manifestations of MECP2 mutations in classical and atypical RT Rett syndrome."; RL Am. J. Med. Genet. A 126:129-140(2004). RN [59] RP INVOLVEMENT IN MRXSL. RX PubMed=16080119; DOI=10.1086/444549; RA Van Esch H., Bauters M., Ignatius J., Jansen M., Raynaud M., Hollanders K., RA Lugtenberg D., Bienvenu T., Jensen L.R., Gecz J., Moraine C., Marynen P., RA Fryns J.-P., Froyen G.; RT "Duplication of the MECP2 region is a frequent cause of severe mental RT retardation and progressive neurological symptoms in males."; RL Am. J. Hum. Genet. 77:442-453(2005). RN [60] RP VARIANT MRXS13 SER-322. RX PubMed=16966553; DOI=10.1212/01.wnl.0000233990.87889.15; RA Ventura P., Galluzzi R., Bacca S.M., Giorda R., Massagli A.; RT "A novel familial MECP2 mutation in a young boy: clinical and molecular RT findings."; RL Neurology 67:867-868(2006). RN [61] RP CHARACTERIZATION OF VARIANT RTT CYS-133, AND CHARACTERIZATION OF VARIANT RP MRXS13 VAL-140. RX PubMed=17296936; DOI=10.1073/pnas.0608056104; RA Nan X., Hou J., Maclean A., Nasir J., Lafuente M.J., Shu X., RA Kriaucionis S., Bird A.; RT "Interaction between chromatin proteins MECP2 and ATRX is disrupted by RT mutations that cause inherited mental retardation."; RL Proc. Natl. Acad. Sci. U.S.A. 104:2709-2714(2007). RN [62] RP VARIANT RTT 270-ARG--SER-486 DEL. RX PubMed=23662938; DOI=10.1111/epi.12203; RA Kodera H., Kato M., Nord A.S., Walsh T., Lee M., Yamanaka G., Tohyama J., RA Nakamura K., Nakagawa E., Ikeda T., Ben-Zeev B., Lev D., Lerman-Sagie T., RA Straussberg R., Tanabe S., Ueda K., Amamoto M., Ohta S., Nonoda Y., RA Nishiyama K., Tsurusaki Y., Nakashima M., Miyake N., Hayasaka K., RA King M.C., Matsumoto N., Saitsu H.; RT "Targeted capture and sequencing for detection of mutations causing early RT onset epileptic encephalopathy."; RL Epilepsia 54:1262-1269(2013). RN [63] RP VARIANT RTT CYS-133. RX PubMed=25818041; DOI=10.1111/epi.12954; RA Mercimek-Mahmutoglu S., Patel J., Cordeiro D., Hewson S., Callen D., RA Donner E.J., Hahn C.D., Kannu P., Kobayashi J., Minassian B.A., Moharir M., RA Siriwardena K., Weiss S.K., Weksberg R., Snead O.C. III; RT "Diagnostic yield of genetic testing in epileptic encephalopathy in RT childhood."; RL Epilepsia 56:707-716(2015). RN [64] RP VARIANTS RTT 270-ARG--SER-486 DEL AND CYS-306. RX PubMed=26993267; DOI=10.1136/jmedgenet-2015-103263; RA Trump N., McTague A., Brittain H., Papandreou A., Meyer E., Ngoh A., RA Palmer R., Morrogh D., Boustred C., Hurst J.A., Jenkins L., Kurian M.A., RA Scott R.H.; RT "Improving diagnosis and broadening the phenotypes in early-onset seizure RT and severe developmental delay disorders through gene panel analysis."; RL J. Med. Genet. 53:310-317(2016). RN [65] RP VARIANT RTT TRP-344. RX PubMed=28709814; DOI=10.1016/j.braindev.2017.06.003; RA Liang J.S., Lin L.J., Yang M.T., Wang J.S., Lu J.F.; RT "The therapeutic implication of a novel SCN2A mutation associated early- RT onset epileptic encephalopathy with Rett-like features."; RL Brain Dev. 39:877-881(2017). RN [66] RP VARIANT RTT CYS-133, AND VARIANT ASN-305. RX PubMed=27864847; DOI=10.1002/humu.23149; RG Clinical Study Group; RA Parrini E., Marini C., Mei D., Galuppi A., Cellini E., Pucatti D., RA Chiti L., Rutigliano D., Bianchini C., Virdo S., De Vita D., Bigoni S., RA Barba C., Mari F., Montomoli M., Pisano T., Rosati A., Guerrini R.; RT "Diagnostic targeted resequencing in 349 patients with drug-resistant RT pediatric epilepsies identifies causative mutations in 30 different RT genes."; RL Hum. Mutat. 38:216-225(2017). RN [67] RP VARIANTS RTT ARG-305 AND CYS-306, CHARACTERIZATION OF VARIANTS RTT ARG-305 RP AND CYS-306, SUBCELLULAR LOCATION, AND INTERACTION WITH TBL1XR1 AND TBL1X. RX PubMed=28348241; DOI=10.1073/pnas.1700731114; RA Kruusvee V., Lyst M.J., Taylor C., Tarnauskaite Z., Bird A.P., Cook A.G.; RT "Structure of the MeCP2-TBLR1 complex reveals a molecular basis for Rett RT syndrome and related disorders."; RL Proc. Natl. Acad. Sci. U.S.A. 114:E3243-E3250(2017). CC -!- FUNCTION: Chromosomal protein that binds to methylated DNA. It can bind CC specifically to a single methyl-CpG pair. It is not influenced by CC sequences flanking the methyl-CpGs. Mediates transcriptional repression CC through interaction with histone deacetylase and the corepressor SIN3A. CC Binds both 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC)- CC containing DNA, with a preference for 5-methylcytosine (5mC). CC {ECO:0000250|UniProtKB:Q9Z2D6}. CC -!- SUBUNIT: Interacts with FNBP3 (By similarity). Interacts with CDKL5 CC (PubMed:15917271). Interacts with ATRX; MECP2 recruits ATRX to CC pericentric heterochromatin in neuronal cells (By similarity). CC Interacts with NCOR2 (By similarity). Interacts with TBL1XR1; bridges CC interaction between MECP2 and NCOR1 (PubMed:28348241). Interacts with CC TBL1X; recruits TBL1X to the heterochromatin foci (PubMed:28348241). CC {ECO:0000250|UniProtKB:Q9Z2D6, ECO:0000269|PubMed:15917271, CC ECO:0000269|PubMed:28348241}. CC -!- INTERACTION: CC P51608; Q6PCB6: ABHD17C; NbExp=3; IntAct=EBI-1189067, EBI-22011868; CC P51608; P63010-2: AP2B1; NbExp=3; IntAct=EBI-1189067, EBI-11529439; CC P51608; Q9Y575-3: ASB3; NbExp=3; IntAct=EBI-1189067, EBI-14199987; CC P51608; Q9UII2: ATP5IF1; NbExp=3; IntAct=EBI-1189067, EBI-718459; CC P51608; Q8WUW1: BRK1; NbExp=3; IntAct=EBI-1189067, EBI-2837444; CC P51608; Q9UNS2: COPS3; NbExp=3; IntAct=EBI-1189067, EBI-350590; CC P51608; P35222: CTNNB1; NbExp=3; IntAct=EBI-1189067, EBI-491549; CC P51608; Q7L576: CYFIP1; NbExp=3; IntAct=EBI-1189067, EBI-1048143; CC P51608; Q9UHI6: DDX20; NbExp=3; IntAct=EBI-1189067, EBI-347658; CC P51608; O75398: DEAF1; NbExp=3; IntAct=EBI-1189067, EBI-718185; CC P51608; Q99504: EYA3; NbExp=3; IntAct=EBI-1189067, EBI-9089567; CC P51608; Q6PIV2: FOXR1; NbExp=3; IntAct=EBI-1189067, EBI-10253815; CC P51608; Q9H2X6: HIPK2; NbExp=2; IntAct=EBI-1189067, EBI-348345; CC P51608; P04792: HSPB1; NbExp=3; IntAct=EBI-1189067, EBI-352682; CC P51608; P42858: HTT; NbExp=18; IntAct=EBI-1189067, EBI-466029; CC P51608; Q6DN90-2: IQSEC1; NbExp=3; IntAct=EBI-1189067, EBI-21911304; CC P51608; Q92993-2: KAT5; NbExp=3; IntAct=EBI-1189067, EBI-20795332; CC P51608; Q9Y2M5: KLHL20; NbExp=3; IntAct=EBI-1189067, EBI-714379; CC P51608; Q8IUC2: KRTAP8-1; NbExp=3; IntAct=EBI-1189067, EBI-10261141; CC P51608; P07948: LYN; NbExp=3; IntAct=EBI-1189067, EBI-79452; CC P51608; P61244: MAX; NbExp=2; IntAct=EBI-1189067, EBI-751711; CC P51608; Q8TDB4: MGARP; NbExp=3; IntAct=EBI-1189067, EBI-4397720; CC P51608; O43196-2: MSH5; NbExp=3; IntAct=EBI-1189067, EBI-25844576; CC P51608; Q99457: NAP1L3; NbExp=3; IntAct=EBI-1189067, EBI-8645631; CC P51608; P07196: NEFL; NbExp=3; IntAct=EBI-1189067, EBI-475646; CC P51608; Q96CV9: OPTN; NbExp=3; IntAct=EBI-1189067, EBI-748974; CC P51608; Q96FW1: OTUB1; NbExp=3; IntAct=EBI-1189067, EBI-1058491; CC P51608; Q6GQQ9-2: OTUD7B; NbExp=3; IntAct=EBI-1189067, EBI-25830200; CC P51608; O75925: PIAS1; NbExp=3; IntAct=EBI-1189067, EBI-629434; CC P51608; P60891: PRPS1; NbExp=3; IntAct=EBI-1189067, EBI-749195; CC P51608; P57729: RAB38; NbExp=3; IntAct=EBI-1189067, EBI-6552718; CC P51608; Q9NS23-4: RASSF1; NbExp=3; IntAct=EBI-1189067, EBI-438710; CC P51608; Q8WWW0-2: RASSF5; NbExp=3; IntAct=EBI-1189067, EBI-960502; CC P51608; Q9ULX5: RNF112; NbExp=3; IntAct=EBI-1189067, EBI-25829984; CC P51608; Q96D59: RNF183; NbExp=3; IntAct=EBI-1189067, EBI-743938; CC P51608; Q96ST3: SIN3A; NbExp=2; IntAct=EBI-1189067, EBI-347218; CC P51608; P51531: SMARCA2; NbExp=4; IntAct=EBI-1189067, EBI-679562; CC P51608; Q12824: SMARCB1; NbExp=3; IntAct=EBI-1189067, EBI-358419; CC P51608; Q16637-3: SMN2; NbExp=3; IntAct=EBI-1189067, EBI-395447; CC P51608; Q7Z6I5: SPATA12; NbExp=3; IntAct=EBI-1189067, EBI-10696971; CC P51608; O75558: STX11; NbExp=3; IntAct=EBI-1189067, EBI-714135; CC P51608; Q86WT6-2: TRIM69; NbExp=3; IntAct=EBI-1189067, EBI-11525489; CC P51608; Q86UV6-2: TRIM74; NbExp=3; IntAct=EBI-1189067, EBI-10259086; CC P51608; P10599: TXN; NbExp=3; IntAct=EBI-1189067, EBI-594644; CC P51608; O76024: WFS1; NbExp=3; IntAct=EBI-1189067, EBI-720609; CC P51608; Q9QZR5: Hipk2; Xeno; NbExp=3; IntAct=EBI-1189067, EBI-366905; CC P51608; Q60974: Ncor1; Xeno; NbExp=4; IntAct=EBI-1189067, EBI-349004; CC P51608; Q9WU42: Ncor2; Xeno; NbExp=4; IntAct=EBI-1189067, EBI-6673326; CC P51608; Q9QXE7: Tbl1x; Xeno; NbExp=3; IntAct=EBI-1189067, EBI-8821270; CC P51608; Q8BHJ5: Tbl1xr1; Xeno; NbExp=4; IntAct=EBI-1189067, EBI-1216384; CC P51608-1; O88508: Dnmt3a; Xeno; NbExp=10; IntAct=EBI-26687319, EBI-995154; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q9Z2D6}. CC Note=Colocalized with methyl-CpG in the genome. Colocalized with TBL1X CC to the heterochromatin foci. {ECO:0000269|PubMed:28348241}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=A; Synonyms=Beta; CC IsoId=P51608-1; Sequence=Displayed; CC Name=B; Synonyms=Alpha; CC IsoId=P51608-2; Sequence=VSP_022948; CC -!- TISSUE SPECIFICITY: Present in all adult somatic tissues tested. CC -!- PTM: Phosphorylated on Ser-423 in brain upon synaptic activity, which CC attenuates its repressor activity and seems to regulate dendritic CC growth and spine maturation. {ECO:0000250}. CC -!- DISEASE: Angelman syndrome (AS) [MIM:105830]: A neurodevelopmental CC disorder characterized by severe motor and intellectual retardation, CC ataxia, frequent jerky limb movements and flapping of the arms and CC hands, hypotonia, seizures, absence of speech, frequent smiling and CC episodes of paroxysmal laughter, open-mouthed expression revealing the CC tongue. {ECO:0000269|PubMed:11283202}. Note=The disease may be caused CC by variants affecting the gene represented in this entry. CC -!- DISEASE: Intellectual developmental disorder, X-linked, syndromic 13 CC (MRXS13) [MIM:300055]: A disorder characterized by significantly below CC average general intellectual functioning associated with impairments in CC adaptive behavior and manifested during the developmental period. CC MRXS13 patients manifest intellectual disability associated with other CC variable features such as spasticity, episodes of manic depressive CC psychosis, increased tone and macroorchidism. CC {ECO:0000269|PubMed:10986043, ECO:0000269|PubMed:11007980, CC ECO:0000269|PubMed:11309367, ECO:0000269|PubMed:11805248, CC ECO:0000269|PubMed:11885030, ECO:0000269|PubMed:12161600, CC ECO:0000269|PubMed:12325019, ECO:0000269|PubMed:12615169, CC ECO:0000269|PubMed:16966553, ECO:0000269|PubMed:17296936}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- DISEASE: Rett syndrome (RTT) [MIM:312750]: An X-linked dominant CC neurodevelopmental disorder, and one of the most common causes of CC intellectual disability in females. Patients appear to develop normally CC until 6 to 18 months of age, then gradually lose speech and purposeful CC hand movements, and develop microcephaly, seizures, autism, ataxia, CC intellectual disability and stereotypic hand movements. After initial CC regression, the condition stabilizes and patients usually survive into CC adulthood. {ECO:0000269|PubMed:10508514, ECO:0000269|PubMed:10577905, CC ECO:0000269|PubMed:10745042, ECO:0000269|PubMed:10767337, CC ECO:0000269|PubMed:10814719, ECO:0000269|PubMed:10944854, CC ECO:0000269|PubMed:10991688, ECO:0000269|PubMed:10991689, CC ECO:0000269|PubMed:11055898, ECO:0000269|PubMed:11241840, CC ECO:0000269|PubMed:11269512, ECO:0000269|PubMed:11283202, CC ECO:0000269|PubMed:11376998, ECO:0000269|PubMed:11402105, CC ECO:0000269|PubMed:11706982, ECO:0000269|PubMed:11738883, CC ECO:0000269|PubMed:12161600, ECO:0000269|PubMed:12567420, CC ECO:0000269|PubMed:12966522, ECO:0000269|PubMed:12966523, CC ECO:0000269|PubMed:15034579, ECO:0000269|PubMed:15057977, CC ECO:0000269|PubMed:17296936, ECO:0000269|PubMed:23662938, CC ECO:0000269|PubMed:25818041, ECO:0000269|PubMed:26993267, CC ECO:0000269|PubMed:27864847, ECO:0000269|PubMed:28348241, CC ECO:0000269|PubMed:28709814}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Autism, X-linked 3 (AUTSX3) [MIM:300496]: A complex CC multifactorial, pervasive developmental disorder characterized by CC impairments in reciprocal social interaction and communication, CC restricted and stereotyped patterns of interests and activities, and CC the presence of developmental abnormalities by 3 years of age. Most CC individuals with autism also manifest moderate intellectual disability. CC {ECO:0000269|PubMed:12770674}. Note=The disease may be caused by CC variants affecting the gene represented in this entry. CC -!- DISEASE: Encephalopathy, neonatal severe, due to MECP2 mutations (ENS- CC MECP2) [MIM:300673]: A neurodevelopmental disorder characterized by CC severe neonatal encephalopathy, developmental delay, intellectual CC disability, microcephaly, seizures. Additional features include CC respiratory insufficiency and central hypoventilation, gastroesophageal CC reflux, axial hypotonia, hyperreflexia and dyskinetic movements. CC {ECO:0000269|PubMed:11238684}. Note=The disease is caused by variants CC affecting the gene represented in this entry. The MECP2 gene is mutated CC in Rett syndrome, a severe neurodevelopmental disorder that almost CC always occurs in females. Although it was first thought that MECP2 CC mutations causing Rett syndrome were lethal in males, later reports CC identified a severe neonatal encephalopathy in surviving male sibs of CC patients with Rett syndrome. Additional reports have confirmed a severe CC phenotype in males with Rett syndrome-associated MECP2 mutations. CC -!- DISEASE: Intellectual developmental disorder, X-linked, syndromic, Lubs CC type (MRXSL) [MIM:300260]: A disorder characterized by significantly CC below average general intellectual functioning associated with CC impairments in adaptive behavior and manifested during the CC developmental period. MRXSL patients manifest intellectual disability CC associated with variable features. They include swallowing dysfunction CC and gastroesophageal reflux with secondary recurrent respiratory CC infections, hypotonia, mild myopathy and characteristic facies such as CC downslanting palpebral fissures, hypertelorism and a short nose with a CC low nasal bridge. {ECO:0000269|PubMed:16080119}. Note=The disease is CC caused by variants affecting the gene represented in this entry. CC Increased dosage of MECP2 due to gene duplication appears to be CC responsible for the intellectual disability phenotype. CC -!- MISCELLANEOUS: [Isoform B]: Ten times higher expression levels than CC isoform A in brain. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=CAD97991.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=RettBASE; Note=IRSA MECP2 variation database; CC URL="http://mecp2.chw.edu.au/"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; L37298; AAC32737.1; -; mRNA. DR EMBL; X99686; CAA68001.1; -; mRNA. DR EMBL; AJ132917; CAB46446.1; -; mRNA. DR EMBL; AF158180; AAF33023.1; -; mRNA. DR EMBL; Y12643; CAA73190.1; -; mRNA. DR EMBL; AY541280; AAS55455.1; -; mRNA. DR EMBL; BX538060; CAD97991.1; ALT_INIT; mRNA. DR EMBL; AF030876; AAC08757.1; -; Genomic_DNA. DR EMBL; BC011612; AAH11612.1; -; mRNA. DR EMBL; X89430; CAA61599.1; -; mRNA. DR EMBL; X94628; CAA64331.1; -; Genomic_DNA. DR CCDS; CCDS14741.1; -. [P51608-1] DR CCDS; CCDS48193.1; -. [P51608-2] DR RefSeq; NP_001104262.1; NM_001110792.1. [P51608-2] DR RefSeq; NP_001303266.1; NM_001316337.1. DR RefSeq; NP_004983.1; NM_004992.3. [P51608-1] DR PDB; 1QK9; NMR; -; A=77-166. DR PDB; 3C2I; X-ray; 2.50 A; A=77-167. DR PDB; 5BT2; X-ray; 2.20 A; A=77-167. DR PDB; 6C1Y; X-ray; 2.30 A; A/B=80-164. DR PDB; 6OGJ; X-ray; 1.80 A; A/B=77-166. DR PDB; 6OGK; X-ray; 1.65 A; A=77-167. DR PDB; 6YWW; X-ray; 2.10 A; A=77-161. DR PDB; 8AJR; NMR; -; A=89-181. DR PDB; 8ALQ; NMR; -; A=89-181. DR PDBsum; 1QK9; -. DR PDBsum; 3C2I; -. DR PDBsum; 5BT2; -. DR PDBsum; 6C1Y; -. DR PDBsum; 6OGJ; -. DR PDBsum; 6OGK; -. DR PDBsum; 6YWW; -. DR PDBsum; 8AJR; -. DR PDBsum; 8ALQ; -. DR AlphaFoldDB; P51608; -. DR BMRB; P51608; -. DR SMR; P51608; -. DR BioGRID; 110368; 260. DR CORUM; P51608; -. DR DIP; DIP-39983N; -. DR IntAct; P51608; 191. DR MINT; P51608; -. DR STRING; 9606.ENSP00000395535; -. DR BindingDB; P51608; -. DR ChEMBL; CHEMBL3638346; -. DR GlyCosmos; P51608; 2 sites, 1 glycan. DR GlyGen; P51608; 5 sites, 1 O-linked glycan (5 sites). DR iPTMnet; P51608; -. DR MetOSite; P51608; -. DR PhosphoSitePlus; P51608; -. DR BioMuta; MECP2; -. DR DMDM; 1708973; -. DR EPD; P51608; -. DR jPOST; P51608; -. DR MassIVE; P51608; -. DR MaxQB; P51608; -. DR PaxDb; 9606-ENSP00000395535; -. DR PeptideAtlas; P51608; -. DR ProteomicsDB; 56344; -. [P51608-1] DR ProteomicsDB; 56345; -. [P51608-2] DR Pumba; P51608; -. DR ABCD; P51608; 1 sequenced antibody. DR Antibodypedia; 394; 961 antibodies from 48 providers. DR DNASU; 4204; -. DR Ensembl; ENST00000303391.11; ENSP00000301948.6; ENSG00000169057.25. [P51608-1] DR Ensembl; ENST00000453960.7; ENSP00000395535.2; ENSG00000169057.25. [P51608-2] DR GeneID; 4204; -. DR KEGG; hsa:4204; -. DR MANE-Select; ENST00000453960.7; ENSP00000395535.2; NM_001110792.2; NP_001104262.1. [P51608-2] DR UCSC; uc004fjv.3; human. [P51608-1] DR AGR; HGNC:6990; -. DR CTD; 4204; -. DR DisGeNET; 4204; -. DR GeneCards; MECP2; -. DR GeneReviews; MECP2; -. DR HGNC; HGNC:6990; MECP2. DR HPA; ENSG00000169057; Low tissue specificity. DR MalaCards; MECP2; -. DR MIM; 105830; phenotype. DR MIM; 300005; gene. DR MIM; 300055; phenotype. DR MIM; 300260; phenotype. DR MIM; 300496; phenotype. DR MIM; 300673; phenotype. DR MIM; 312750; phenotype. DR neXtProt; NX_P51608; -. DR OpenTargets; ENSG00000169057; -. DR Orphanet; 3095; Atypical Rett syndrome. DR Orphanet; 106; NON RARE IN EUROPE: Autism. DR Orphanet; 1762; Proximal Xq28 duplication syndrome. DR Orphanet; 778; Rett syndrome. DR Orphanet; 209370; Severe neonatal-onset encephalopathy with microcephaly. DR Orphanet; 536; Systemic lupus erythematosus. DR Orphanet; 3077; X-linked intellectual disability-psychosis-macroorchidism syndrome. DR Orphanet; 777; X-linked non-syndromic intellectual disability. DR PharmGKB; PA30729; -. DR VEuPathDB; HostDB:ENSG00000169057; -. DR eggNOG; KOG4161; Eukaryota. DR GeneTree; ENSGT00530000063687; -. DR HOGENOM; CLU_045066_0_0_1; -. DR InParanoid; P51608; -. DR OMA; PYKHERK; -. DR OrthoDB; 5262043at2759; -. DR PhylomeDB; P51608; -. DR TreeFam; TF332974; -. DR PathwayCommons; P51608; -. DR Reactome; R-HSA-8986944; Transcriptional Regulation by MECP2. DR Reactome; R-HSA-9022534; Loss of MECP2 binding ability to 5hmC-DNA. DR Reactome; R-HSA-9022535; Loss of phosphorylation of MECP2 at T308. DR Reactome; R-HSA-9022537; Loss of MECP2 binding ability to the NCoR/SMRT complex. DR Reactome; R-HSA-9022538; Loss of MECP2 binding ability to 5mC-DNA. DR Reactome; R-HSA-9022692; Regulation of MECP2 expression and activity. DR Reactome; R-HSA-9022699; MECP2 regulates neuronal receptors and channels. DR Reactome; R-HSA-9022702; MECP2 regulates transcription of neuronal ligands. DR Reactome; R-HSA-9022707; MECP2 regulates transcription factors. DR Reactome; R-HSA-9022927; MECP2 regulates transcription of genes involved in GABA signaling. DR Reactome; R-HSA-9725371; Nuclear events stimulated by ALK signaling in cancer. DR SignaLink; P51608; -. DR SIGNOR; P51608; -. DR BioGRID-ORCS; 4204; 9 hits in 796 CRISPR screens. DR ChiTaRS; MECP2; human. DR EvolutionaryTrace; P51608; -. DR GeneWiki; MECP2; -. DR GenomeRNAi; 4204; -. DR Pharos; P51608; Tchem. DR PRO; PR:P51608; -. DR Proteomes; UP000005640; Chromosome X. DR RNAct; P51608; Protein. DR Bgee; ENSG00000169057; Expressed in paraflocculus and 186 other cell types or tissues. DR ExpressionAtlas; P51608; baseline and differential. DR GO; GO:0005813; C:centrosome; IMP:CAFA. DR GO; GO:0005829; C:cytosol; IEA:Ensembl. DR GO; GO:0005615; C:extracellular space; HDA:UniProtKB. DR GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl. DR GO; GO:0000792; C:heterochromatin; IDA:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0098794; C:postsynapse; IEA:GOC. DR GO; GO:0003682; F:chromatin binding; IBA:GO_Central. DR GO; GO:0031490; F:chromatin DNA binding; IEA:Ensembl. DR GO; GO:0003677; F:DNA binding; TAS:ProtInc. DR GO; GO:0010385; F:double-stranded methylated DNA binding; IMP:MGI. DR GO; GO:0000400; F:four-way junction DNA binding; IEA:Ensembl. DR GO; GO:0042826; F:histone deacetylase binding; IEA:Ensembl. DR GO; GO:0140566; F:histone reader activity; IEA:Ensembl. DR GO; GO:0042802; F:identical protein binding; IEA:Ensembl. DR GO; GO:0008327; F:methyl-CpG binding; IBA:GO_Central. DR GO; GO:0060090; F:molecular adaptor activity; EXP:DisProt. DR GO; GO:0140693; F:molecular condensate scaffold activity; IMP:DisProt. DR GO; GO:0003729; F:mRNA binding; IEA:Ensembl. DR GO; GO:0003676; F:nucleic acid binding; EXP:DisProt. DR GO; GO:1990841; F:promoter-specific chromatin binding; IEA:Ensembl. DR GO; GO:0019904; F:protein domain specific binding; IEA:Ensembl. DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB. DR GO; GO:0035197; F:siRNA binding; IEA:Ensembl. DR GO; GO:0003714; F:transcription corepressor activity; IDA:ARUK-UCL. DR GO; GO:0045322; F:unmethylated CpG binding; IEA:Ensembl. DR GO; GO:0008344; P:adult locomotory behavior; IEA:Ensembl. DR GO; GO:0001662; P:behavioral fear response; IEA:Ensembl. DR GO; GO:0006576; P:biogenic amine metabolic process; IEA:Ensembl. DR GO; GO:0032048; P:cardiolipin metabolic process; IEA:Ensembl. DR GO; GO:0050432; P:catecholamine secretion; IEA:Ensembl. DR GO; GO:0071317; P:cellular response to isoquinoline alkaloid; IEA:Ensembl. DR GO; GO:0035865; P:cellular response to potassium ion; IEA:Ensembl. DR GO; GO:0021549; P:cerebellum development; IEA:Ensembl. DR GO; GO:0021987; P:cerebral cortex development; IEA:Ensembl. DR GO; GO:0016358; P:dendrite development; IEA:Ensembl. DR GO; GO:0060079; P:excitatory postsynaptic potential; IEA:Ensembl. DR GO; GO:0010467; P:gene expression; IEA:Ensembl. DR GO; GO:0071514; P:genomic imprinting; IMP:MGI. DR GO; GO:0014009; P:glial cell proliferation; IEA:Ensembl. DR GO; GO:0008211; P:glucocorticoid metabolic process; IEA:Ensembl. DR GO; GO:0006541; P:glutamine metabolic process; IEA:Ensembl. DR GO; GO:0007507; P:heart development; IEA:Ensembl. DR GO; GO:0031507; P:heterochromatin formation; IEA:Ensembl. DR GO; GO:0021766; P:hippocampus development; IEA:Ensembl. DR GO; GO:0006020; P:inositol metabolic process; IEA:Ensembl. DR GO; GO:0007616; P:long-term memory; IEA:Ensembl. DR GO; GO:0060291; P:long-term synaptic potentiation; IEA:Ensembl. DR GO; GO:0048286; P:lung alveolus development; IEA:Ensembl. DR GO; GO:0016525; P:negative regulation of angiogenesis; IMP:BHF-UCL. DR GO; GO:0048712; P:negative regulation of astrocyte differentiation; IEA:Ensembl. DR GO; GO:0043537; P:negative regulation of blood vessel endothelial cell migration; IDA:BHF-UCL. DR GO; GO:1903860; P:negative regulation of dendrite extension; IEA:Ensembl. DR GO; GO:0061000; P:negative regulation of dendritic spine development; IEA:Ensembl. DR GO; GO:0045892; P:negative regulation of DNA-templated transcription; IDA:UniProtKB. DR GO; GO:0010629; P:negative regulation of gene expression; IDA:BHF-UCL. DR GO; GO:0090327; P:negative regulation of locomotion involved in locomotory behavior; IEA:Ensembl. DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IEA:Ensembl. DR GO; GO:2000635; P:negative regulation of primary miRNA processing; IEA:Ensembl. DR GO; GO:1903941; P:negative regulation of respiratory gaseous exchange; IEA:Ensembl. DR GO; GO:0051151; P:negative regulation of smooth muscle cell differentiation; IEA:Ensembl. DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IBA:GO_Central. DR GO; GO:0001976; P:nervous system process involved in regulation of systemic arterial blood pressure; IEA:Ensembl. DR GO; GO:0042551; P:neuron maturation; IEA:Ensembl. DR GO; GO:0007219; P:Notch signaling pathway; IEA:Ensembl. DR GO; GO:0021772; P:olfactory bulb development; IEA:Ensembl. DR GO; GO:0014003; P:oligodendrocyte development; IEA:Ensembl. DR GO; GO:0046470; P:phosphatidylcholine metabolic process; IEA:Ensembl. DR GO; GO:1901953; P:positive regulation of anterograde dense core granule transport; IEA:Ensembl. DR GO; GO:1905492; P:positive regulation of branching morphogenesis of a nerve; IEA:Ensembl. DR GO; GO:1903861; P:positive regulation of dendrite extension; IEA:Ensembl. DR GO; GO:0060999; P:positive regulation of dendritic spine development; IEA:Ensembl. DR GO; GO:1905643; P:positive regulation of DNA methylation; IDA:BHF-UCL. DR GO; GO:0060252; P:positive regulation of glial cell proliferation; IEA:Ensembl. DR GO; GO:0090063; P:positive regulation of microtubule nucleation; IMP:CAFA. DR GO; GO:1901956; P:positive regulation of retrograde dense core granule transport; IEA:Ensembl. DR GO; GO:0031915; P:positive regulation of synaptic plasticity; IEA:Ensembl. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IEA:Ensembl. DR GO; GO:0009791; P:post-embryonic development; IEA:Ensembl. DR GO; GO:0021740; P:principal sensory nucleus of trigeminal nerve development; IEA:Ensembl. DR GO; GO:0019230; P:proprioception; IEA:Ensembl. DR GO; GO:0008104; P:protein localization; IEA:Ensembl. DR GO; GO:0099611; P:regulation of action potential firing threshold; IEA:Ensembl. DR GO; GO:0051570; P:regulation of histone H3-K9 methylation; IEA:Ensembl. DR GO; GO:0002087; P:regulation of respiratory gaseous exchange by nervous system process; IEA:Ensembl. DR GO; GO:0050807; P:regulation of synapse organization; IEA:Ensembl. DR GO; GO:0007585; P:respiratory gaseous exchange by respiratory system; IEA:Ensembl. DR GO; GO:0042220; P:response to cocaine; IEA:Ensembl. DR GO; GO:0032355; P:response to estradiol; IEA:Ensembl. DR GO; GO:0001666; P:response to hypoxia; IEA:Ensembl. DR GO; GO:0010212; P:response to ionizing radiation; IEA:Ensembl. DR GO; GO:0010288; P:response to lead ion; IEA:Ensembl. DR GO; GO:0051707; P:response to other organism; IEA:Ensembl. DR GO; GO:0019233; P:sensory perception of pain; IEA:Ensembl. DR GO; GO:0035176; P:social behavior; IEA:Ensembl. DR GO; GO:0021510; P:spinal cord development; IEA:Ensembl. DR GO; GO:0001964; P:startle response; IEA:Ensembl. DR GO; GO:0021756; P:striatum development; IEA:Ensembl. DR GO; GO:0007416; P:synapse assembly; IEA:Ensembl. DR GO; GO:0021794; P:thalamus development; IEA:Ensembl. DR GO; GO:0099191; P:trans-synaptic signaling by BDNF; IEA:Ensembl. DR GO; GO:0021591; P:ventricular system development; IEA:Ensembl. DR GO; GO:0008542; P:visual learning; IEA:Ensembl. DR CDD; cd01396; MeCP2_MBD; 1. DR DisProt; DP00539; -. DR IDEAL; IID00717; -. DR InterPro; IPR016177; DNA-bd_dom_sf. DR InterPro; IPR017353; Me_CpG-bd_MeCP2. DR InterPro; IPR045138; MeCP2/MBD4. DR InterPro; IPR001739; Methyl_CpG_DNA-bd. DR PANTHER; PTHR15074; METHYL-CPG-BINDING PROTEIN; 1. DR PANTHER; PTHR15074:SF6; METHYL-CPG-BINDING PROTEIN 2; 1. DR Pfam; PF01429; MBD; 1. DR PIRSF; PIRSF038006; Methyl_CpG_bd_MeCP2; 1. DR SMART; SM00391; MBD; 1. DR SUPFAM; SSF54171; DNA-binding domain; 1. DR PROSITE; PS50982; MBD; 1. DR Genevisible; P51608; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Autism; KW Autism spectrum disorder; Chromosomal rearrangement; Disease variant; KW DNA-binding; Intellectual disability; Methylation; Nucleus; Phosphoprotein; KW Reference proteome; Repeat; Repressor; Transcription; KW Transcription regulation. FT CHAIN 1..486 FT /note="Methyl-CpG-binding protein 2" FT /id="PRO_0000096345" FT DOMAIN 90..162 FT /note="MBD" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00338" FT DNA_BIND 185..197 FT /note="A.T hook 1" FT DNA_BIND 265..277 FT /note="A.T hook 2" FT REGION 1..119 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 147..275 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 269..309 FT /note="Interaction with NCOR2" FT /evidence="ECO:0000250|UniProtKB:Q9Z2D6" FT REGION 285..309 FT /note="Interaction with TBL1XR1" FT /evidence="ECO:0000250|UniProtKB:Q9Z2D6" FT REGION 324..486 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 8..49 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 83..109 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 251..267 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 378..400 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 448..486 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 13 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q00566" FT MOD_RES 80 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163" FT MOD_RES 116 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 162 FT /note="Omega-N-methylarginine" FT /evidence="ECO:0000250|UniProtKB:Q9Z2D6" FT MOD_RES 216 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:20068231" FT MOD_RES 229 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 321 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:Q9Z2D6" FT MOD_RES 423 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9Z2D6" FT MOD_RES 426 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:24275569" FT MOD_RES 449 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT VAR_SEQ 1..9 FT /note="MVAGMLGLR -> MAAAAAAAPSGGGGGGEEERL (in isoform B)" FT /evidence="ECO:0000303|PubMed:15034579, FT ECO:0000303|PubMed:17974005" FT /id="VSP_022948" FT VARIANT 10 FT /note="E -> Q (in RTT; dbSNP:rs61754421)" FT /evidence="ECO:0000269|PubMed:12966523" FT /id="VAR_018180" FT VARIANT 86 FT /note="S -> C (in dbSNP:rs61754445)" FT /evidence="ECO:0000269|PubMed:11055898" FT /id="VAR_018181" FT VARIANT 97 FT /note="D -> E (in RTT; dbSNP:rs61754449)" FT /evidence="ECO:0000269|PubMed:10745042" FT /id="VAR_023552" FT VARIANT 97 FT /note="D -> Y (in RTT; dbSNP:rs61754448)" FT /evidence="ECO:0000269|PubMed:11402105" FT /id="VAR_018182" FT VARIANT 100 FT /note="L -> R (in RTT; dbSNP:rs61754451)" FT /evidence="ECO:0000269|PubMed:15057977" FT /id="VAR_023553" FT VARIANT 100 FT /note="L -> V (in RTT; dbSNP:rs28935168)" FT /evidence="ECO:0000269|PubMed:11055898, FT ECO:0000269|PubMed:12966522, ECO:0000269|PubMed:15057977" FT /id="VAR_017462" FT VARIANT 101 FT /note="P -> H (in RTT; dbSNP:rs61754453)" FT /evidence="ECO:0000269|PubMed:10767337" FT /id="VAR_018183" FT VARIANT 101 FT /note="P -> L (in RTT; dbSNP:rs61754453)" FT /evidence="ECO:0000269|PubMed:10767337" FT /id="VAR_018184" FT VARIANT 101 FT /note="P -> R (in RTT; also in a patient with Angelman FT syndrome and some typical RTT features; dbSNP:rs61754453)" FT /evidence="ECO:0000269|PubMed:10991689, FT ECO:0000269|PubMed:11283202" FT /id="VAR_010276" FT VARIANT 101 FT /note="P -> S (in RTT; dbSNP:rs61754452)" FT /evidence="ECO:0000269|PubMed:11269512" FT /id="VAR_023554" FT VARIANT 101 FT /note="P -> T (in RTT)" FT /evidence="ECO:0000269|PubMed:10767337" FT /id="VAR_018185" FT VARIANT 106 FT /note="R -> Q (in RTT; dbSNP:rs61754457)" FT /evidence="ECO:0000269|PubMed:10814719, FT ECO:0000269|PubMed:11055898" FT /id="VAR_018186" FT VARIANT 106 FT /note="R -> W (in RTT; dbSNP:rs28934907)" FT /evidence="ECO:0000269|PubMed:10508514, FT ECO:0000269|PubMed:10577905, ECO:0000269|PubMed:10745042, FT ECO:0000269|PubMed:10767337, ECO:0000269|PubMed:10991688, FT ECO:0000269|PubMed:10991689, ECO:0000269|PubMed:11055898, FT ECO:0000269|PubMed:11241840, ECO:0000269|PubMed:11269512, FT ECO:0000269|PubMed:11402105, ECO:0000269|PubMed:11738883, FT ECO:0000269|PubMed:15057977" FT /id="VAR_010272" FT VARIANT 111 FT /note="R -> G (in RTT; dbSNP:rs61754459)" FT /evidence="ECO:0000269|PubMed:11241840" FT /id="VAR_018187" FT VARIANT 120 FT /note="Y -> D (in RTT; dbSNP:rs267608454)" FT /evidence="ECO:0000269|PubMed:11376998" FT /id="VAR_023555" FT VARIANT 124 FT /note="L -> F (in RTT; dbSNP:rs61755763)" FT /evidence="ECO:0000269|PubMed:10991688" FT /id="VAR_010277" FT VARIANT 128 FT /note="Q -> P (in RTT; dbSNP:rs61748383)" FT /evidence="ECO:0000269|PubMed:12966523" FT /id="VAR_018188" FT VARIANT 133 FT /note="R -> C (in RTT; impairs interaction with ATRX and FT abolishes ATRX recruitment to heterochromatin; FT dbSNP:rs28934904)" FT /evidence="ECO:0000269|PubMed:10508514, FT ECO:0000269|PubMed:10577905, ECO:0000269|PubMed:10745042, FT ECO:0000269|PubMed:10767337, ECO:0000269|PubMed:10991688, FT ECO:0000269|PubMed:11055898, ECO:0000269|PubMed:11241840, FT ECO:0000269|PubMed:11269512, ECO:0000269|PubMed:11376998, FT ECO:0000269|PubMed:11402105, ECO:0000269|PubMed:12567420, FT ECO:0000269|PubMed:12966523, ECO:0000269|PubMed:15057977, FT ECO:0000269|PubMed:17296936, ECO:0000269|PubMed:25818041, FT ECO:0000269|PubMed:27864847" FT /id="VAR_010273" FT VARIANT 133 FT /note="R -> H (in RTT; dbSNP:rs61748389)" FT /evidence="ECO:0000269|PubMed:11402105, FT ECO:0000269|PubMed:11706982" FT /id="VAR_018189" FT VARIANT 134 FT /note="S -> C (in RTT; dbSNP:rs61748390)" FT /evidence="ECO:0000269|PubMed:10767337, FT ECO:0000269|PubMed:10991688, ECO:0000269|PubMed:11269512, FT ECO:0000269|PubMed:11738883" FT /id="VAR_010278" FT VARIANT 135 FT /note="K -> E (in RTT; dbSNP:rs61748391)" FT /evidence="ECO:0000269|PubMed:11241840" FT /id="VAR_018190" FT VARIANT 137 FT /note="E -> G (in MRXS13; dbSNP:rs61748392)" FT /evidence="ECO:0000269|PubMed:11309367" FT /id="VAR_017581" FT VARIANT 140 FT /note="A -> V (in MRXS13; impairs interaction with ATRX and FT abolishes ATRX recruitment to heterochromatin; FT dbSNP:rs28934908)" FT /evidence="ECO:0000269|PubMed:11007980, FT ECO:0000269|PubMed:11309367, ECO:0000269|PubMed:11805248, FT ECO:0000269|PubMed:11885030, ECO:0000269|PubMed:12161600, FT ECO:0000269|PubMed:12325019, ECO:0000269|PubMed:17296936" FT /id="VAR_010279" FT VARIANT 152 FT /note="P -> R (in RTT; dbSNP:rs61748404)" FT /evidence="ECO:0000269|PubMed:10767337, FT ECO:0000269|PubMed:10991688, ECO:0000269|PubMed:11055898, FT ECO:0000269|PubMed:11241840, ECO:0000269|PubMed:11269512, FT ECO:0000269|PubMed:11402105, ECO:0000269|PubMed:11738883, FT ECO:0000269|PubMed:12966523, ECO:0000269|PubMed:15057977" FT /id="VAR_010280" FT VARIANT 155 FT /note="F -> I (in RTT; dbSNP:rs61748406)" FT /evidence="ECO:0000269|PubMed:10745042" FT /id="VAR_023556" FT VARIANT 155 FT /note="F -> S (in RTT; dbSNP:rs28934905)" FT /evidence="ECO:0000269|PubMed:10508514, FT ECO:0000269|PubMed:10577905, ECO:0000269|PubMed:11055898" FT /id="VAR_010274" FT VARIANT 156 FT /note="D -> G (in RTT; dbSNP:rs61748407)" FT /evidence="ECO:0000269|PubMed:11241840" FT /id="VAR_018191" FT VARIANT 158 FT /note="T -> A (in RTT; dbSNP:rs61748411)" FT /evidence="ECO:0000269|PubMed:11269512, FT ECO:0000269|PubMed:15057977" FT /id="VAR_023557" FT VARIANT 158 FT /note="T -> M (in RTT; dbSNP:rs28934906)" FT /evidence="ECO:0000269|PubMed:10508514, FT ECO:0000269|PubMed:10577905, ECO:0000269|PubMed:10745042, FT ECO:0000269|PubMed:10767337, ECO:0000269|PubMed:10814719, FT ECO:0000269|PubMed:10944854, ECO:0000269|PubMed:10991688, FT ECO:0000269|PubMed:10991689, ECO:0000269|PubMed:11055898, FT ECO:0000269|PubMed:11241840, ECO:0000269|PubMed:11269512, FT ECO:0000269|PubMed:11376998, ECO:0000269|PubMed:11402105, FT ECO:0000269|PubMed:11738883, ECO:0000269|PubMed:12567420, FT ECO:0000269|PubMed:12966523, ECO:0000269|PubMed:15057977" FT /id="VAR_010275" FT VARIANT 161 FT /note="G -> V (in RTT; dbSNP:rs61748417)" FT /evidence="ECO:0000269|PubMed:15057977" FT /id="VAR_023558" FT VARIANT 167 FT /note="R -> W (in MRXS13; dbSNP:rs61748420)" FT /evidence="ECO:0000269|PubMed:11309367" FT /id="VAR_018192" FT VARIANT 181 FT /note="A -> V (in dbSNP:rs61749705)" FT /evidence="ECO:0000269|PubMed:12384770" FT /id="VAR_018193" FT VARIANT 196 FT /note="T -> S (in dbSNP:rs61749713)" FT /evidence="ECO:0000269|PubMed:12111644" FT /id="VAR_018194" FT VARIANT 197 FT /note="T -> M (in dbSNP:rs61749714)" FT /evidence="ECO:0000269|PubMed:11402105, FT ECO:0000269|PubMed:12161600" FT /id="VAR_018195" FT VARIANT 201 FT /note="A -> V (in dbSNP:rs61748381)" FT /evidence="ECO:0000269|PubMed:10944854, FT ECO:0000269|PubMed:11738883" FT /id="VAR_010281" FT VARIANT 203 FT /note="T -> M (in dbSNP:rs61749720)" FT /evidence="ECO:0000269|PubMed:11007980, FT ECO:0000269|PubMed:11055898" FT /id="VAR_018196" FT VARIANT 210 FT /note="K -> I (in RTT; dbSNP:rs61749730)" FT /evidence="ECO:0000269|PubMed:11241840" FT /id="VAR_018197" FT VARIANT 225 FT /note="P -> L (in MRXS13; dbSNP:rs61749715)" FT /evidence="ECO:0000269|PubMed:12615169" FT /id="VAR_037664" FT VARIANT 225 FT /note="P -> R (in RTT; dbSNP:rs61749715)" FT /evidence="ECO:0000269|PubMed:10767337" FT /id="VAR_018198" FT VARIANT 228 FT /note="T -> S (in dbSNP:rs61749738)" FT /evidence="ECO:0000269|PubMed:12111644" FT /id="VAR_018199" FT VARIANT 229 FT /note="S -> L (in dbSNP:rs61749739)" FT /evidence="ECO:0000269|PubMed:10767337" FT /id="VAR_018200" FT VARIANT 232 FT /note="G -> A (in dbSNP:rs61748422)" FT /evidence="ECO:0000269|PubMed:10944854" FT /id="VAR_018201" FT VARIANT 251 FT /note="P -> L (in dbSNP:rs61750229)" FT /evidence="ECO:0000269|PubMed:10944854" FT /id="VAR_018202" FT VARIANT 270..486 FT /note="Missing (in RTT)" FT /evidence="ECO:0000269|PubMed:23662938, FT ECO:0000269|PubMed:26993267" FT /id="VAR_078720" FT VARIANT 284 FT /note="K -> E (in MRXS13; dbSNP:rs61750255)" FT /evidence="ECO:0000269|PubMed:11309367" FT /id="VAR_018203" FT VARIANT 287 FT /note="A -> P (in dbSNP:rs61750257)" FT /evidence="ECO:0000269|PubMed:11055898" FT /id="VAR_018204" FT VARIANT 291 FT /note="S -> A (in dbSNP:rs61751360)" FT /evidence="ECO:0000269|PubMed:11055898" FT /id="VAR_018205" FT VARIANT 302 FT /note="P -> A (in RTT; dbSNP:rs61751373)" FT /evidence="ECO:0000269|PubMed:11738883" FT /id="VAR_018206" FT VARIANT 302 FT /note="P -> H (in RTT; dbSNP:rs61749723)" FT /evidence="ECO:0000269|PubMed:10944854" FT /id="VAR_018207" FT VARIANT 302 FT /note="P -> L (in RTT; dbSNP:rs61749723)" FT /evidence="ECO:0000269|PubMed:10767337" FT /id="VAR_018208" FT VARIANT 302 FT /note="P -> R (in RTT; dbSNP:rs61749723)" FT /evidence="ECO:0000269|PubMed:10814719, FT ECO:0000269|PubMed:11241840" FT /id="VAR_018209" FT VARIANT 305 FT /note="K -> N (found in a patient with drug-resistant FT epilepsy with intellectual disability, parkinsonism and FT other neurologic symptoms; likely pathogenic; FT dbSNP:rs1057519543)" FT /evidence="ECO:0000269|PubMed:27864847" FT /id="VAR_078221" FT VARIANT 305 FT /note="K -> R (in RTT; abolishes interaction with TBL1X; FT dbSNP:rs61751441)" FT /evidence="ECO:0000269|PubMed:11055898, FT ECO:0000269|PubMed:11402105, ECO:0000269|PubMed:28348241" FT /id="VAR_018210" FT VARIANT 306 FT /note="R -> C (in RTT; abolishes interaction with TBL1X and FT TBL1XR1; dbSNP:rs28935468)" FT /evidence="ECO:0000269|PubMed:10577905, FT ECO:0000269|PubMed:10745042, ECO:0000269|PubMed:10767337, FT ECO:0000269|PubMed:10814719, ECO:0000269|PubMed:10944854, FT ECO:0000269|PubMed:10991688, ECO:0000269|PubMed:10991689, FT ECO:0000269|PubMed:11055898, ECO:0000269|PubMed:11241840, FT ECO:0000269|PubMed:11376998, ECO:0000269|PubMed:11402105, FT ECO:0000269|PubMed:11738883, ECO:0000269|PubMed:12567420, FT ECO:0000269|PubMed:12966523, ECO:0000269|PubMed:15057977, FT ECO:0000269|PubMed:26993267, ECO:0000269|PubMed:28348241" FT /id="VAR_010282" FT VARIANT 306 FT /note="R -> H (in RTT; dbSNP:rs61751443)" FT /evidence="ECO:0000269|PubMed:10767337, FT ECO:0000269|PubMed:11055898, ECO:0000269|PubMed:15057977" FT /id="VAR_018211" FT VARIANT 322 FT /note="P -> A (in RTT; dbSNP:rs61751449)" FT /evidence="ECO:0000269|PubMed:10814719, FT ECO:0000269|PubMed:11738883" FT /id="VAR_018212" FT VARIANT 322 FT /note="P -> L (in RTT; dbSNP:rs61751450)" FT /evidence="ECO:0000269|PubMed:11402105" FT /id="VAR_018213" FT VARIANT 322 FT /note="P -> S (in MRXS13; dbSNP:rs61751449)" FT /evidence="ECO:0000269|PubMed:16966553" FT /id="VAR_037665" FT VARIANT 344 FT /note="R -> W (in RTT; dbSNP:rs61752361)" FT /evidence="ECO:0000269|PubMed:12161600, FT ECO:0000269|PubMed:28709814" FT /id="VAR_018214" FT VARIANT 359 FT /note="S -> P (in dbSNP:rs61752371)" FT /evidence="ECO:0000269|PubMed:11896461" FT /id="VAR_018215" FT VARIANT 376 FT /note="P -> S (in dbSNP:rs61752387)" FT /evidence="ECO:0000269|PubMed:10944854, FT ECO:0000269|PubMed:12161600, ECO:0000269|PubMed:12384770, FT ECO:0000269|PubMed:12567420" FT /id="VAR_018216" FT VARIANT 388 FT /note="P -> L (in dbSNP:rs61753006)" FT /id="VAR_023559" FT VARIANT 388 FT /note="P -> S (in RTT; uncertain significance; FT dbSNP:rs61753000)" FT /evidence="ECO:0000269|PubMed:12567420" FT /id="VAR_018218" FT VARIANT 388 FT /note="Missing" FT /evidence="ECO:0000269|PubMed:12384770" FT /id="VAR_018217" FT VARIANT 394 FT /note="E -> K (in dbSNP:rs63094662)" FT /evidence="ECO:0000269|PubMed:12111644" FT /id="VAR_018219" FT VARIANT 397 FT /note="E -> K (in dbSNP:rs56268439)" FT /evidence="ECO:0000269|PubMed:10577905, FT ECO:0000269|PubMed:10991689, ECO:0000269|PubMed:11055898, FT ECO:0000269|PubMed:11738883, ECO:0000269|PubMed:11896461" FT /id="VAR_010283" FT VARIANT 399 FT /note="P -> L (in MRXS13; uncertain significance; FT dbSNP:rs62915962)" FT /evidence="ECO:0000269|PubMed:11309367, FT ECO:0000269|PubMed:12161600" FT /id="VAR_018220" FT VARIANT 402 FT /note="P -> L (in dbSNP:rs61753014)" FT /evidence="ECO:0000269|PubMed:12384770" FT /id="VAR_018221" FT VARIANT 412 FT /note="V -> I (in dbSNP:rs61753966)" FT /evidence="ECO:0000269|PubMed:11055898" FT /id="VAR_018222" FT VARIANT 428 FT /note="G -> S (in ENS-MECP2; uncertain significance; FT dbSNP:rs61753971)" FT /evidence="ECO:0000269|PubMed:11238684, FT ECO:0000269|PubMed:12161600" FT /id="VAR_017463" FT VARIANT 439 FT /note="A -> T (in dbSNP:rs61753973)" FT /evidence="ECO:0000269|PubMed:10767337" FT /id="VAR_018223" FT VARIANT 444 FT /note="A -> T (in dbSNP:rs61753975)" FT /evidence="ECO:0000269|PubMed:11055898" FT /id="VAR_018224" FT VARIANT 453 FT /note="R -> Q (in MRXS13; dbSNP:rs61753980)" FT /evidence="ECO:0000269|PubMed:11309367" FT /id="VAR_018225" FT VARIANT 480 FT /note="P -> S (in dbSNP:rs267608636)" FT /evidence="ECO:0000269|PubMed:12111644" FT /id="VAR_018226" FT CONFLICT 72..75 FT /note="PAVP -> RLC (in Ref. 10; CAA61599)" FT /evidence="ECO:0000305" FT CONFLICT 290 FT /note="E -> G (in Ref. 2; CAA68001)" FT /evidence="ECO:0000305" FT CONFLICT 466 FT /note="M -> V (in Ref. 7; CAD97991)" FT /evidence="ECO:0000305" FT TURN 88..91 FT /evidence="ECO:0007829|PDB:6OGJ" FT STRAND 95..97 FT /evidence="ECO:0007829|PDB:1QK9" FT STRAND 100..103 FT /evidence="ECO:0007829|PDB:1QK9" FT STRAND 105..110 FT /evidence="ECO:0007829|PDB:6OGK" FT TURN 115..118 FT /evidence="ECO:0007829|PDB:6OGK" FT STRAND 120..125 FT /evidence="ECO:0007829|PDB:6OGK" FT TURN 127..129 FT /evidence="ECO:0007829|PDB:1QK9" FT STRAND 130..134 FT /evidence="ECO:0007829|PDB:1QK9" FT HELIX 135..144 FT /evidence="ECO:0007829|PDB:6OGK" FT HELIX 152..154 FT /evidence="ECO:0007829|PDB:6OGK" SQ SEQUENCE 486 AA; 52441 MW; EB6A33233AEDA566 CRC64; MVAGMLGLRE EKSEDQDLQG LKDKPLKFKK VKKDKKEEKE GKHEPVQPSA HHSAEPAEAG KAETSEGSGS APAVPEASAS PKQRRSIIRD RGPMYDDPTL PEGWTRKLKQ RKSGRSAGKY DVYLINPQGK AFRSKVELIA YFEKVGDTSL DPNDFDFTVT GRGSPSRREQ KPPKKPKSPK APGTGRGRGR PKGSGTTRPK AATSEGVQVK RVLEKSPGKL LVKMPFQTSP GGKAEGGGAT TSTQVMVIKR PGRKRKAEAD PQAIPKKRGR KPGSVVAAAA AEAKKKAVKE SSIRSVQETV LPIKKRKTRE TVSIEVKEVV KPLLVSTLGE KSGKGLKTCK SPGRKSKESS PKGRSSSASS PPKKEHHHHH HHSESPKAPV PLLPPLPPPP PEPESSEDPT SPPEPQDLSS SVCKEEKMPR GGSLESDGCP KEPAKTQPAV ATAATAAEKY KHRGEGERKD IVSSSMPRPN REEPVDSRTP VTERVS //