KMT2B_HUMAN
ID KMT2B_HUMAN Reviewed; 2715 AA.
AC Q9UMN6; O15022; O95836; Q96GP2; Q96IP3; Q9UK25; Q9Y668; Q9Y669;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 220.
DE RecName: Full=Histone-lysine N-methyltransferase 2B;
DE Short=Lysine N-methyltransferase 2B;
DE EC=2.1.1.364 {ECO:0000269|PubMed:25561738};
DE AltName: Full=Myeloid/lymphoid or mixed-lineage leukemia protein 4;
DE AltName: Full=Trithorax homolog 2;
DE AltName: Full=WW domain-binding protein 7;
DE Short=WBP-7;
GN Name=KMT2B; Synonyms=HRX2, KIAA0304, MLL2, MLL4, TRX2, WBP7;
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].
RA Angrand P.-O., Valvatne H., Jeanmougin F., Adamson A., van der Hoeven F.,
RA Olsen L., Tekotte H., Huang N., Poch O., Lamerdin J., Chambon P.,
RA Losson R., Stewart A., Aasland R.;
RT "Mammalian trithorax- and ASH1-like proteins: putative chromatin regulators
RT which contain PHD fingers and SET domains.";
RL Submitted (JUN-1998) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 111-2715.
RC TISSUE=Leukocyte, and Testis;
RX PubMed=10637508; DOI=10.1038/sj.onc.1203291;
RA Huntsman D.G., Chin S.-F., Muleris M., Batley S.J., Collins V.P.,
RA Wiedemann L.M., Aparicio S., Caldas C.;
RT "MLL2, the second human homolog of the Drosophila trithorax gene, maps to
RT 19q13.1 and is amplified in solid tumor cell lines.";
RL Oncogene 18:7975-7984(1999).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 301-2715.
RC TISSUE=Brain;
RX PubMed=9205841; DOI=10.1093/dnares/4.2.141;
RA Nagase T., Ishikawa K., Nakajima D., Ohira M., Seki N., Miyajima N.,
RA Tanaka A., Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. VII. The
RT complete sequences of 100 new cDNA clones from brain which can code for
RT large proteins in vitro.";
RL DNA Res. 4:141-150(1997).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1918-2715.
RC TISSUE=Brain, 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 [6]
RP PARTIAL NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Bone marrow, and Placenta;
RX PubMed=10409430; DOI=10.1006/geno.1999.5860;
RA FitzGerald K.T., Diaz M.O.;
RT "MLL2: a new mammalian member of the trx/MLL family of genes.";
RL Genomics 59:187-192(1999).
RN [7]
RP IDENTIFICATION IN THE MEN1-ASSOCIATED HISTONE METHYLTRANSFERASE COMPLEX,
RP AND INTERACTION OF THE COMPLEX WITH POLR2A AND POLR2B.
RX PubMed=14992727; DOI=10.1016/s1097-2765(04)00081-4;
RA Hughes C.M., Rozenblatt-Rosen O., Milne T.A., Copeland T.D., Levine S.S.,
RA Lee J.C., Hayes D.N., Shanmugam K.S., Bhattacharjee A., Biondi C.A.,
RA Kay G.F., Hayward N.K., Hess J.L., Meyerson M.;
RT "Menin associates with a trithorax family histone methyltransferase complex
RT and with the hoxc8 locus.";
RL Mol. Cell 13:587-597(2004).
RN [8]
RP INTERACTION WITH KDM6B.
RX PubMed=17825402; DOI=10.1016/j.cell.2007.08.019;
RA De Santa F., Totaro M.G., Prosperini E., Notarbartolo S., Testa G.,
RA Natoli G.;
RT "The histone H3 lysine-27 demethylase Jmjd3 links inflammation to
RT inhibition of polycomb-mediated gene silencing.";
RL Cell 130:1083-1094(2007).
RN [9]
RP FUNCTION, AND INTERACTION WITH NFE2.
RX PubMed=17707229; DOI=10.1016/j.molcel.2007.06.022;
RA Demers C., Chaturvedi C.-P., Ranish J.A., Juban G., Lai P., Morle F.,
RA Aebersold R., Dilworth F.J., Groudine M., Brand M.;
RT "Activator-mediated recruitment of the MLL2 methyltransferase complex to
RT the beta-globin locus.";
RL Mol. Cell 27:573-584(2007).
RN [10]
RP INTERACTION WITH WDR5.
RX PubMed=18840606; DOI=10.1074/jbc.m806900200;
RA Song J.J., Kingston R.E.;
RT "WDR5 interacts with mixed lineage leukemia (MLL) protein via the histone
RT H3-binding pocket.";
RL J. Biol. Chem. 283:35258-35264(2008).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-821; SER-844; SER-1032;
RP SER-1035 AND SER-1930, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP 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 [12]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [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 [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-2068 AND THR-2083, AND
RP IDENTIFICATION BY 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 [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-821, AND IDENTIFICATION BY
RP 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 [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-861, 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 [16]
RP INTERACTION WITH MEN1.
RX PubMed=22327296; DOI=10.1038/nature10806;
RA Huang J., Gurung B., Wan B., Matkar S., Veniaminova N.A., Wan K.,
RA Merchant J.L., Hua X., Lei M.;
RT "The same pocket in menin binds both MLL and JUND but has opposite effects
RT on transcription.";
RL Nature 482:542-546(2012).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-351; SER-821; SER-844;
RP SER-861; SER-936; SER-1092; SER-1095; SER-1936; THR-2083; SER-2288 AND
RP SER-2348, AND 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 [18]
RP IDENTIFICATION IN MLL4 COMPLEX, AND SUBCELLULAR LOCATION.
RX PubMed=23508102; DOI=10.1128/mcb.01742-12;
RA van Nuland R., Smits A.H., Pallaki P., Jansen P.W., Vermeulen M.,
RA Timmers H.T.;
RT "Quantitative dissection and stoichiometry determination of the human
RT SET1/MLL histone methyltransferase complexes.";
RL Mol. Cell. Biol. 33:2067-2077(2013).
RN [19]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=24081332; DOI=10.1128/mcb.01181-13;
RA Hu D., Gao X., Morgan M.A., Herz H.M., Smith E.R., Shilatifard A.;
RT "The MLL3/MLL4 branches of the COMPASS family function as major histone
RT H3K4 monomethylases at enhancers.";
RL Mol. Cell. Biol. 33:4745-4754(2013).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-861 AND THR-2083, AND
RP IDENTIFICATION BY 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 [21]
RP FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, AND MUTAGENESIS OF ASN-2652.
RX PubMed=25561738; DOI=10.1074/jbc.m114.627646;
RA Shinsky S.A., Monteith K.E., Viggiano S., Cosgrove M.S.;
RT "Biochemical reconstitution and phylogenetic comparison of human SET1
RT family core complexes involved in histone methylation.";
RL J. Biol. Chem. 290:6361-6375(2015).
RN [22]
RP INVOLVEMENT IN DYT28, AND VARIANTS DYT28 545-ARG--ASN-2715 DEL AND
RP 810-GLN--ASN-2715 DEL.
RX PubMed=27839873; DOI=10.1016/j.ajhg.2016.10.010;
RA Zech M., Boesch S., Maier E.M., Borggraefe I., Vill K., Laccone F.,
RA Pilshofer V., Ceballos-Baumann A., Alhaddad B., Berutti R., Poewe W.,
RA Haack T.B., Haslinger B., Strom T.M., Winkelmann J.;
RT "Haploinsufficiency of KMT2B, encoding the lysine-specific histone
RT methyltransferase 2B, results in early-onset generalized dystonia.";
RL Am. J. Hum. Genet. 99:1377-1387(2016).
RN [23]
RP INVOLVEMENT IN DYT28, TISSUE SPECIFICITY, AND VARIANTS DYT28
RP 564-ARG--ASN-2715 DEL; 1515-TYR--ASN-2715 DEL; ASP-1652; LEU-1662;
RP GLN-1705; CYS-1762; PRO-1781; TRP-2517 AND THR-2674.
RX PubMed=27992417; DOI=10.1038/ng.3740;
RG UK10K Consortium;
RG Deciphering Developmental Disorders Study;
RG NIHR BioResource Rare Diseases Consortium;
RA Meyer E., Carss K.J., Rankin J., Nichols J.M., Grozeva D., Joseph A.P.,
RA Mencacci N.E., Papandreou A., Ng J., Barral S., Ngoh A., Ben-Pazi H.,
RA Willemsen M.A., Arkadir D., Barnicoat A., Bergman H., Bhate S., Boys A.,
RA Darin N., Foulds N., Gutowski N., Hills A., Houlden H., Hurst J.A.,
RA Israel Z., Kaminska M., Limousin P., Lumsden D., McKee S., Misra S.,
RA Mohammed S.S., Nakou V., Nicolai J., Nilsson M., Pall H., Peall K.J.,
RA Peters G.B., Prabhakar P., Reuter M.S., Rump P., Segel R., Sinnema M.,
RA Smith M., Turnpenny P., White S.M., Wieczorek D., Wiethoff S., Wilson B.T.,
RA Winter G., Wragg C., Pope S., Heales S.J., Morrogh D., Pittman A.,
RA Carr L.J., Perez-Duenas B., Lin J.P., Reis A., Gahl W.A., Toro C.,
RA Bhatia K.P., Wood N.W., Kamsteeg E.J., Chong W.K., Gissen P., Topf M.,
RA Dale R.C., Chubb J.R., Raymond F.L., Kurian M.A.;
RT "Mutations in the histone methyltransferase gene KMT2B cause complex early-
RT onset dystonia.";
RL Nat. Genet. 49:223-237(2017).
RN [24]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-805 AND LYS-1136, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
RN [25] {ECO:0007744|PDB:4ERZ}
RP X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF 2504-2517 IN COMPLEX WITH WDR5,
RP INTERACTION WITH WDR5, AND MOTIF WIN.
RX PubMed=22665483; DOI=10.1074/jbc.m112.364125;
RA Dharmarajan V., Lee J.H., Patel A., Skalnik D.G., Cosgrove M.S.;
RT "Structural basis for WDR5 interaction (Win) motif recognition in human
RT SET1 family histone methyltransferases.";
RL J. Biol. Chem. 287:27275-27289(2012).
RN [26] {ECO:0007744|PDB:3UVM}
RP X-RAY CRYSTALLOGRAPHY (1.57 ANGSTROMS) OF 2508-2517 IN COMPLEX WITH WDR5,
RP INTERACTION WITH WDR5, AND MOTIF WIN.
RX PubMed=22266653; DOI=10.1093/nar/gkr1235;
RA Zhang P., Lee H., Brunzelle J.S., Couture J.F.;
RT "The plasticity of WDR5 peptide-binding cleft enables the binding of the
RT SET1 family of histone methyltransferases.";
RL Nucleic Acids Res. 40:4237-4246(2012).
RN [27] {ECO:0007744|PDB:4PZI}
RP X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS) OF 955-1020 IN COMPLEX WITH CPG DNA,
RP DOMAIN CXXC-TYPE ZINC-FINGER, AND ZINC-BINDING.
RX PubMed=29276034; DOI=10.1016/j.str.2017.11.022;
RA Xu C., Liu K., Lei M., Yang A., Li Y., Hughes T.R., Min J.;
RT "DNA Sequence Recognition of Human CXXC Domains and Their Structural
RT Determinants.";
RL Structure 26:85-95.e3(2018).
RN [28]
RP VARIANT ASN-215.
RX PubMed=30503518; DOI=10.1016/j.ajhg.2018.10.021;
RG Undiagnosed Diseases Network;
RA Ng B.G., Rosenfeld J.A., Emrick L., Jain M., Burrage L.C., Lee B.,
RA Craigen W.J., Bearden D.R., Graham B.H., Freeze H.H.;
RT "Pathogenic Variants in Fucokinase Cause a Congenital Disorder of
RT Glycosylation.";
RL Am. J. Hum. Genet. 103:1030-1037(2018).
CC -!- FUNCTION: Histone methyltransferase that catalyzes methyl group
CC transfer from S-adenosyl-L-methionine to the epsilon-amino group of
CC 'Lys-4' of histone H3 (H3K4) via a non-processive mechanism. Part of
CC chromatin remodeling machinery predominantly forms H3K4me1 and H3K4me2
CC methylation marks at active chromatin sites where transcription and DNA
CC repair take place (PubMed:25561738, PubMed:17707229). Likely plays a
CC redundant role with KMT2C in enriching H3K4me1 marks on primed and
CC active enhancer elements (PubMed:24081332). Plays a central role in
CC beta-globin locus transcription regulation by being recruited by NFE2
CC (PubMed:17707229). Plays an important role in controlling bulk H3K4me
CC during oocyte growth and preimplantation development (By similarity).
CC Required during the transcriptionally active period of oocyte growth
CC for the establishment and/or maintenance of bulk H3K4 trimethylation
CC (H3K4me3), global transcriptional silencing that preceeds resumption of
CC meiosis, oocyte survival and normal zygotic genome activation (By
CC similarity). {ECO:0000250|UniProtKB:O08550,
CC ECO:0000269|PubMed:17707229, ECO:0000269|PubMed:24081332,
CC ECO:0000269|PubMed:25561738}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-lysyl(4)-[histone H3] + S-adenosyl-L-methionine = H(+) +
CC N(6)-methyl-L-lysyl(4)-[histone H3] + S-adenosyl-L-homocysteine;
CC Xref=Rhea:RHEA:60264, Rhea:RHEA-COMP:15543, Rhea:RHEA-COMP:15547,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:29969, ChEBI:CHEBI:57856,
CC ChEBI:CHEBI:59789, ChEBI:CHEBI:61929; EC=2.1.1.364;
CC Evidence={ECO:0000269|PubMed:25561738};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60265;
CC Evidence={ECO:0000305|PubMed:24081332, ECO:0000305|PubMed:25561738};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=N(6)-methyl-L-lysyl(4)-[histone H3] + S-adenosyl-L-methionine
CC = H(+) + N(6),N(6)-dimethyl-L-lysyl(4)-[histone H3] + S-adenosyl-L-
CC homocysteine; Xref=Rhea:RHEA:60268, Rhea:RHEA-COMP:15540, Rhea:RHEA-
CC COMP:15543, ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789,
CC ChEBI:CHEBI:61929, ChEBI:CHEBI:61976;
CC Evidence={ECO:0000269|PubMed:25561738};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60269;
CC Evidence={ECO:0000305|PubMed:25561738};
CC -!- SUBUNIT: Component of the menin-associated histone methyltransferase
CC complex, at least composed of KMT2B/MLL4, ASH2L, RBBP5, WDR5, DPY30,
CC MEN1; the complex interacts with POLR2A and POLR2B via MEN1
CC (PubMed:14992727, PubMed:23508102). Interacts with NFE2
CC (PubMed:17707229). Interacts with KDM6B (PubMed:17825402). Interacts
CC (via WIN motif) with WDR5 (PubMed:22665483, PubMed:22266653,
CC PubMed:18840606). Interacts (via MBM motif) with MEN1
CC (PubMed:22327296). Forms a core complex with the evolutionary conserved
CC subcomplex WRAD composed of WDR5, RBBP5, ASH2L/ASH2 and DPY30 subunits;
CC WRAD differentially stimulates the methyltransferase activity
CC (PubMed:25561738). {ECO:0000269|PubMed:14992727,
CC ECO:0000269|PubMed:17707229, ECO:0000269|PubMed:17825402,
CC ECO:0000269|PubMed:18840606, ECO:0000269|PubMed:22266653,
CC ECO:0000269|PubMed:22327296, ECO:0000269|PubMed:22665483,
CC ECO:0000269|PubMed:23508102, ECO:0000269|PubMed:25561738}.
CC -!- INTERACTION:
CC Q9UMN6; Q9UBL3-3: ASH2L; NbExp=2; IntAct=EBI-765774, EBI-16130425;
CC Q9UMN6; P16333: NCK1; NbExp=2; IntAct=EBI-765774, EBI-389883;
CC Q9UMN6; Q14686: NCOA6; NbExp=5; IntAct=EBI-765774, EBI-78670;
CC Q9UMN6; P61964: WDR5; NbExp=7; IntAct=EBI-765774, EBI-540834;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:23508102}.
CC -!- TISSUE SPECIFICITY: Widely expressed. Highest levels in testis. Also
CC found in brain with higher expression in the cerebellum than in any
CC other region, bone marrow, heart, muscle, kidney, placenta, spleen,
CC thymus, prostate, ovary, intestine, colon, peripheral blood lymphocytes
CC and pancreas. Often amplified in pancreatic carcinomas.
CC {ECO:0000269|PubMed:27992417}.
CC -!- DOMAIN: The CXXC zinc finger mediates binding to DNA containing
CC unmethylated cytidine-phosphate-guanosine (CpG) dinucleotides.
CC {ECO:0000269|PubMed:29276034}.
CC -!- DISEASE: Dystonia 28, childhood-onset (DYT28) [MIM:617284]: A form of
CC dystonia, a disorder defined by the presence of sustained involuntary
CC muscle contraction, often leading to abnormal postures. DYT28 is an
CC autosomal dominant, progressive form characterized by onset in the
CC first decade of life and variable severity. Dystonia begins focally in
CC the lower limbs, resulting in gait difficulties, with later progression
CC to other body regions, including the upper limbs, neck, and orofacial
CC region. {ECO:0000269|PubMed:27839873, ECO:0000269|PubMed:27992417}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- SIMILARITY: Belongs to the class V-like SAM-binding methyltransferase
CC superfamily. Histone-lysine methyltransferase family. TRX/MLL
CC subfamily. {ECO:0000255|PROSITE-ProRule:PRU00190}.
CC -!- CAUTION: This protein was first named MLL2 by PubMed:10637508 and
CC PubMed:10409430. MLL2 corresponds to another protein located on
CC chromosome 12 (see AC O14686). Thus, KMT2B/MLL4 is often referred to as
CC MLL2 and vice versa in the literature. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAD26113.1; Type=Miscellaneous discrepancy; Note=Probably cloning artifact.; Evidence={ECO:0000305};
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DR EMBL; AJ007041; CAB45385.1; -; mRNA.
DR EMBL; AD000671; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AF186605; AAD56420.1; -; mRNA.
DR EMBL; AB002302; BAA20763.3; -; mRNA.
DR EMBL; BC009337; AAH09337.2; -; mRNA.
DR EMBL; BC007353; AAH07353.3; -; mRNA.
DR EMBL; AF104918; AAD17932.1; -; mRNA.
DR EMBL; AF105279; AAD26113.1; ALT_SEQ; mRNA.
DR EMBL; AF105280; AAD26112.1; -; mRNA.
DR CCDS; CCDS46055.1; -.
DR PDB; 3UVM; X-ray; 1.57 A; B=2508-2517.
DR PDB; 4ERZ; X-ray; 1.75 A; D/E/F=2504-2517.
DR PDB; 4PZI; X-ray; 2.15 A; A=955-1020.
DR PDB; 7BRE; X-ray; 2.80 A; B/E=2551-2715.
DR PDBsum; 3UVM; -.
DR PDBsum; 4ERZ; -.
DR PDBsum; 4PZI; -.
DR PDBsum; 7BRE; -.
DR SMR; Q9UMN6; -.
DR BioGRID; 115104; 104.
DR ComplexPortal; CPX-7062; Histone-lysine N-methyltransferase complex, KMT2B variant.
DR CORUM; Q9UMN6; -.
DR DIP; DIP-34598N; -.
DR ELM; Q9UMN6; -.
DR IntAct; Q9UMN6; 72.
DR MINT; Q9UMN6; -.
DR STRING; 9606.ENSP00000398837; -.
DR BindingDB; Q9UMN6; -.
DR ChEMBL; CHEMBL2189112; -.
DR iPTMnet; Q9UMN6; -.
DR PhosphoSitePlus; Q9UMN6; -.
DR BioMuta; KMT2B; -.
DR DMDM; 12643900; -.
DR EPD; Q9UMN6; -.
DR jPOST; Q9UMN6; -.
DR MassIVE; Q9UMN6; -.
DR MaxQB; Q9UMN6; -.
DR PaxDb; Q9UMN6; -.
DR PeptideAtlas; Q9UMN6; -.
DR PRIDE; Q9UMN6; -.
DR Antibodypedia; 70148; 191 antibodies from 32 providers.
DR DNASU; 9757; -.
DR Ensembl; ENST00000420124.4; ENSP00000398837.2; ENSG00000272333.8.
DR GeneID; 9757; -.
DR MANE-Select; ENST00000420124.4; ENSP00000398837.2; NM_014727.3; NP_055542.1.
DR UCSC; uc021usv.1; human.
DR CTD; 9757; -.
DR DisGeNET; 9757; -.
DR GeneCards; KMT2B; -.
DR GeneReviews; KMT2B; -.
DR HGNC; HGNC:15840; KMT2B.
DR HPA; ENSG00000272333; Low tissue specificity.
DR MalaCards; KMT2B; -.
DR MIM; 606834; gene.
DR MIM; 617284; phenotype.
DR neXtProt; NX_Q9UMN6; -.
DR OpenTargets; ENSG00000272333; -.
DR Orphanet; 589618; Dystonia 28.
DR VEuPathDB; HostDB:ENSG00000272333; -.
DR eggNOG; KOG1084; Eukaryota.
DR GeneTree; ENSGT00940000161496; -.
DR HOGENOM; CLU_000208_1_0_1; -.
DR InParanoid; Q9UMN6; -.
DR OMA; PRNRACE; -.
DR OrthoDB; 738155at2759; -.
DR PhylomeDB; Q9UMN6; -.
DR BioCyc; MetaCyc:HS02784-MON; -.
DR PathwayCommons; Q9UMN6; -.
DR Reactome; R-HSA-3214841; PKMTs methylate histone lysines.
DR Reactome; R-HSA-8936459; RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function.
DR SignaLink; Q9UMN6; -.
DR BioGRID-ORCS; 9757; 118 hits in 1014 CRISPR screens.
DR ChiTaRS; KMT2B; human.
DR GeneWiki; MLL4; -.
DR GenomeRNAi; 9757; -.
DR Pharos; Q9UMN6; Tbio.
DR PRO; PR:Q9UMN6; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q9UMN6; protein.
DR Bgee; ENSG00000272333; Expressed in right testis and 182 other tissues.
DR ExpressionAtlas; Q9UMN6; baseline and differential.
DR Genevisible; Q9UMN6; HS.
DR GO; GO:0035097; C:histone methyltransferase complex; IDA:MGI.
DR GO; GO:0044665; C:MLL1/2 complex; IPI:ComplexPortal.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0042800; F:histone methyltransferase activity (H3-K4 specific); IDA:MGI.
DR GO; GO:0045322; F:unmethylated CpG binding; IDA:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB.
DR GO; GO:0006325; P:chromatin organization; IEA:UniProtKB-KW.
DR GO; GO:0044648; P:histone H3-K4 dimethylation; IDA:CACAO.
DR GO; GO:0051568; P:histone H3-K4 methylation; IMP:UniProtKB.
DR GO; GO:0097692; P:histone H3-K4 monomethylation; IDA:CACAO.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IBA:GO_Central.
DR CDD; cd15694; ePHD_KMT2B; 1.
DR Gene3D; 1.20.920.10; -; 1.
DR Gene3D; 2.170.270.10; -; 1.
DR Gene3D; 3.30.40.10; -; 3.
DR IDEAL; IID00400; -.
DR InterPro; IPR036427; Bromodomain-like_sf.
DR InterPro; IPR034732; EPHD.
DR InterPro; IPR003889; FYrich_C.
DR InterPro; IPR003888; FYrich_N.
DR InterPro; IPR041959; KMT2B_ePHD.
DR InterPro; IPR016569; MeTrfase_trithorax.
DR InterPro; IPR003616; Post-SET_dom.
DR InterPro; IPR001214; SET_dom.
DR InterPro; IPR046341; SET_dom_sf.
DR InterPro; IPR002857; Znf_CXXC.
DR InterPro; IPR011011; Znf_FYVE_PHD.
DR InterPro; IPR001965; Znf_PHD.
DR InterPro; IPR019787; Znf_PHD-finger.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR Pfam; PF05965; FYRC; 1.
DR Pfam; PF05964; FYRN; 1.
DR Pfam; PF00628; PHD; 2.
DR Pfam; PF00856; SET; 1.
DR Pfam; PF02008; zf-CXXC; 1.
DR PIRSF; PIRSF010354; Methyltransferase_trithorax; 1.
DR SMART; SM00542; FYRC; 1.
DR SMART; SM00541; FYRN; 1.
DR SMART; SM00249; PHD; 4.
DR SMART; SM00508; PostSET; 1.
DR SMART; SM00317; SET; 1.
DR SUPFAM; SSF57903; SSF57903; 2.
DR SUPFAM; SSF82199; SSF82199; 1.
DR PROSITE; PS51805; EPHD; 1.
DR PROSITE; PS51543; FYRC; 1.
DR PROSITE; PS51542; FYRN; 1.
DR PROSITE; PS50868; POST_SET; 1.
DR PROSITE; PS50280; SET; 1.
DR PROSITE; PS51058; ZF_CXXC; 1.
DR PROSITE; PS01359; ZF_PHD_1; 3.
DR PROSITE; PS50016; ZF_PHD_2; 3.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Chromatin regulator; Disease variant;
KW DNA-binding; Dystonia; Isopeptide bond; Metal-binding; Methyltransferase;
KW Nucleus; Phosphoprotein; Reference proteome; Repeat;
KW S-adenosyl-L-methionine; Transcription; Transcription regulation;
KW Transferase; Ubl conjugation; Zinc; Zinc-finger.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:19413330"
FT CHAIN 2..2715
FT /note="Histone-lysine N-methyltransferase 2B"
FT /id="PRO_0000124881"
FT DOMAIN 1727..1783
FT /note="FYR N-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00875"
FT DOMAIN 2411..2492
FT /note="FYR C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00876"
FT DOMAIN 2575..2691
FT /note="SET"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00190"
FT DOMAIN 2699..2715
FT /note="Post-SET"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00155"
FT DNA_BIND 37..44
FT /note="A.T hook 1"
FT DNA_BIND 110..117
FT /note="A.T hook 2"
FT DNA_BIND 357..365
FT /note="A.T hook 3"
FT ZN_FING 959..1006
FT /note="CXXC-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509,
FT ECO:0000269|PubMed:29276034"
FT ZN_FING 1201..1252
FT /note="PHD-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00146"
FT ZN_FING 1249..1303
FT /note="PHD-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00146"
FT ZN_FING 1335..1396
FT /note="PHD-type 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00146"
FT ZN_FING 1578..1618
FT /note="C2HC pre-PHD-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01146"
FT ZN_FING 1639..1686
FT /note="PHD-type 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01146"
FT REGION 1..65
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 81..302
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 320..518
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 532..771
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 819..868
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 894..959
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1027..1132
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1146..1166
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1545..1567
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1806..1978
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2008..2093
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2118..2162
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2280..2412
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 17..36
FT /note="Menin-binding motif (MBM)"
FT /evidence="ECO:0000269|PubMed:22327296"
FT MOTIF 2508..2513
FT /note="WDR5 interaction motif (WIN)"
FT /evidence="ECO:0000269|PubMed:22266653,
FT ECO:0000269|PubMed:22665483"
FT COMPBIAS 81..95
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 145..159
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 374..396
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 398..455
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 541..555
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 556..596
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 616..640
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 670..689
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 726..750
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 751..770
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 839..857
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1059..1090
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1097..1124
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1903..1939
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1958..1973
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2021..2036
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2395..2412
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 966
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509,
FT ECO:0000269|PubMed:29276034, ECO:0007744|PDB:4PZI"
FT BINDING 969
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509,
FT ECO:0000269|PubMed:29276034, ECO:0007744|PDB:4PZI"
FT BINDING 972
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509,
FT ECO:0000269|PubMed:29276034, ECO:0007744|PDB:4PZI"
FT BINDING 978
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509,
FT ECO:0000269|PubMed:29276034, ECO:0007744|PDB:4PZI"
FT BINDING 981
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509,
FT ECO:0000269|PubMed:29276034, ECO:0007744|PDB:4PZI"
FT BINDING 984
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509,
FT ECO:0000269|PubMed:29276034, ECO:0007744|PDB:4PZI"
FT BINDING 1000
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509,
FT ECO:0000269|PubMed:29276034, ECO:0007744|PDB:4PZI"
FT BINDING 1005
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509,
FT ECO:0000269|PubMed:29276034, ECO:0007744|PDB:4PZI"
FT BINDING 2585
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00190"
FT BINDING 2587
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00190"
FT BINDING 2629
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00190"
FT BINDING 2652..2653
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q03164"
FT BINDING 2655
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q03164"
FT BINDING 2703
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q03164"
FT BINDING 2704
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00190"
FT BINDING 2705
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q03164"
FT BINDING 2710
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q03164"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0007744|PubMed:19413330"
FT MOD_RES 113
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O08550"
FT MOD_RES 114
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O08550"
FT MOD_RES 118
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O08550"
FT MOD_RES 351
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 821
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT MOD_RES 844
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 861
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 936
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1032
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 1035
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 1092
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1095
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1930
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 1936
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 2068
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 2083
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 2288
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 2348
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT CROSSLNK 805
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 1136
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT VARIANT 172
FT /note="T -> I (in dbSNP:rs60207923)"
FT /id="VAR_061913"
FT VARIANT 215
FT /note="T -> N"
FT /evidence="ECO:0000269|PubMed:30503518"
FT /id="VAR_081649"
FT VARIANT 545..2715
FT /note="Missing (in DYT28)"
FT /evidence="ECO:0000269|PubMed:27839873"
FT /id="VAR_080233"
FT VARIANT 564..2715
FT /note="Missing (in DYT28)"
FT /evidence="ECO:0000269|PubMed:27992417"
FT /id="VAR_080234"
FT VARIANT 587
FT /note="P -> R (in dbSNP:rs2242519)"
FT /id="VAR_046563"
FT VARIANT 754
FT /note="P -> L (in dbSNP:rs179686)"
FT /id="VAR_046564"
FT VARIANT 810..2715
FT /note="Missing (in DYT28)"
FT /evidence="ECO:0000269|PubMed:27839873"
FT /id="VAR_080235"
FT VARIANT 1097
FT /note="P -> L (in dbSNP:rs34014681)"
FT /id="VAR_046565"
FT VARIANT 1515..2715
FT /note="Missing (in DYT28)"
FT /evidence="ECO:0000269|PubMed:27992417"
FT /id="VAR_080236"
FT VARIANT 1652
FT /note="G -> D (in DYT28; unknown pathological significance;
FT dbSNP:rs1555731832)"
FT /evidence="ECO:0000269|PubMed:27992417"
FT /id="VAR_080237"
FT VARIANT 1662
FT /note="F -> L (in DYT28; unknown pathological significance;
FT dbSNP:rs372432644)"
FT /evidence="ECO:0000269|PubMed:27992417"
FT /id="VAR_080238"
FT VARIANT 1705
FT /note="R -> Q (in DYT28; unknown pathological significance;
FT dbSNP:rs1555731980)"
FT /evidence="ECO:0000269|PubMed:27992417"
FT /id="VAR_080239"
FT VARIANT 1762
FT /note="R -> C (in DYT28; unknown pathological significance;
FT dbSNP:rs1489232377)"
FT /evidence="ECO:0000269|PubMed:27992417"
FT /id="VAR_080240"
FT VARIANT 1781
FT /note="L -> P (in DYT28; unknown pathological significance;
FT dbSNP:rs1555732094)"
FT /evidence="ECO:0000269|PubMed:27992417"
FT /id="VAR_080241"
FT VARIANT 1829
FT /note="P -> L (in dbSNP:rs16970649)"
FT /id="VAR_052653"
FT VARIANT 2364
FT /note="D -> G (in dbSNP:rs231591)"
FT /id="VAR_052654"
FT VARIANT 2408
FT /note="K -> N (in dbSNP:rs36062432)"
FT /id="VAR_052655"
FT VARIANT 2517
FT /note="R -> W (in DYT28; unknown pathological significance;
FT dbSNP:rs1057519285)"
FT /evidence="ECO:0000269|PubMed:27992417"
FT /id="VAR_080242"
FT VARIANT 2674
FT /note="I -> T (in DYT28; unknown pathological significance;
FT dbSNP:rs1555735051)"
FT /evidence="ECO:0000269|PubMed:27992417"
FT /id="VAR_080243"
FT MUTAGEN 2652
FT /note="N->A: Abolishes interaction with S-adenosyl-L-
FT methionine."
FT /evidence="ECO:0000269|PubMed:25561738"
FT CONFLICT 834
FT /note="K -> E (in Ref. 6; AAD17932)"
FT /evidence="ECO:0000305"
FT CONFLICT 941
FT /note="S -> Y (in Ref. 6; AAD17932)"
FT /evidence="ECO:0000305"
FT CONFLICT 1317
FT /note="E -> Q (in Ref. 6; AAD17932)"
FT /evidence="ECO:0000305"
FT CONFLICT 1362
FT /note="H -> Y (in Ref. 6; AAD17932)"
FT /evidence="ECO:0000305"
FT CONFLICT 1438
FT /note="D -> N (in Ref. 6; AAD17932)"
FT /evidence="ECO:0000305"
FT CONFLICT 1918..1920
FT /note="PLA -> GTR (in Ref. 5; AAH09337)"
FT /evidence="ECO:0000305"
FT CONFLICT 2622
FT /note="D -> H (in Ref. 6; AAD26112)"
FT /evidence="ECO:0000305"
FT HELIX 970..973
FT /evidence="ECO:0007829|PDB:4PZI"
FT STRAND 979..981
FT /evidence="ECO:0007829|PDB:4PZI"
FT HELIX 982..985
FT /evidence="ECO:0007829|PDB:4PZI"
FT HELIX 988..990
FT /evidence="ECO:0007829|PDB:4PZI"
FT HELIX 1001..1003
FT /evidence="ECO:0007829|PDB:4PZI"
FT HELIX 1006..1015
FT /evidence="ECO:0007829|PDB:4PZI"
FT HELIX 2510..2512
FT /evidence="ECO:0007829|PDB:3UVM"
FT STRAND 2552..2554
FT /evidence="ECO:0007829|PDB:7BRE"
FT HELIX 2559..2566
FT /evidence="ECO:0007829|PDB:7BRE"
FT HELIX 2569..2576
FT /evidence="ECO:0007829|PDB:7BRE"
FT STRAND 2577..2581
FT /evidence="ECO:0007829|PDB:7BRE"
FT STRAND 2583..2593
FT /evidence="ECO:0007829|PDB:7BRE"
FT STRAND 2600..2603
FT /evidence="ECO:0007829|PDB:7BRE"
FT STRAND 2607..2610
FT /evidence="ECO:0007829|PDB:7BRE"
FT HELIX 2611..2613
FT /evidence="ECO:0007829|PDB:7BRE"
FT HELIX 2614..2624
FT /evidence="ECO:0007829|PDB:7BRE"
FT STRAND 2630..2632
FT /evidence="ECO:0007829|PDB:7BRE"
FT STRAND 2634..2640
FT /evidence="ECO:0007829|PDB:7BRE"
FT STRAND 2642..2645
FT /evidence="ECO:0007829|PDB:7BRE"
FT HELIX 2647..2650
FT /evidence="ECO:0007829|PDB:7BRE"
FT STRAND 2658..2666
FT /evidence="ECO:0007829|PDB:7BRE"
FT STRAND 2669..2678
FT /evidence="ECO:0007829|PDB:7BRE"
SQ SEQUENCE 2715 AA; 293515 MW; C0615B981BBEB7BF CRC64;
MAAAAGGGSC PGPGSARGRF PGRPRGAGGG GGRGGRGNGA ERVRVALRRG GGATGPGGAE
PGEDTALLRL LGLRRGLRRL RRLWAGPRVQ RGRGRGRGRG WGPSRGCVPE EESSDGESDE
EEFQGFHSDE DVAPSSLRSA LRSQRGRAPR GRGRKHKTTP LPPPRLADVA PTPPKTPARK
RGEEGTERMV QALTELLRRA QAPQAPRSRA CEPSTPRRSR GRPPGRPAGP CRRKQQAVVV
AEAAVTIPKP EPPPPVVPVK HQTGSWKCKE GPGPGPGTPR RGGQSSRGGR GGRGRGRGGG
LPFVIKFVSR AKKVKMGQLS LGLESGQGQG QHEESWQDVP QRRVGSGQGG SPCWKKQEQK
LDDEEEEKKE EEEKDKEGEE KEERAVAEEM MPAAEKEEAK LPPPPLTPPA PSPPPPLPPP
STSPPPPLCP PPPPPVSPPP LPSPPPPPAQ EEQEESPPPV VPATCSRKRG RPPLTPSQRA
EREAARAGPE GTSPPTPTPS TATGGPPEDS PTVAPKSTTF LKNIRQFIMP VVSARSSRVI
KTPRRFMDED PPKPPKVEVS PVLRPPITTS PPVPQEPAPV PSPPRAPTPP STPVPLPEKR
RSILREPTFR WTSLTRELPP PPPAPPPPPA PSPPPAPATS SRRPLLLRAP QFTPSEAHLK
IYESVLTPPP LGAPEAPEPE PPPADDSPAE PEPRAVGRTN HLSLPRFAPV VTTPVKAEVS
PHGAPALSNG PQTQAQLLQP LQALQTQLLP QALPPPQPQL QPPPSPQQMP PLEKARIAGV
GSLPLSGVEE KMFSLLKRAK VQLFKIDQQQ QQKVAASMPL SPGGQMEEVA GAVKQISDRG
PVRSEDESVE AKRERPSGPE SPVQGPRIKH VCRHAAVALG QARAMVPEDV PRLSALPLRD
RQDLATEDTS SASETESVPS RSRRGKVEAA GPGGESEPTG SGGTLAHTPR RSLPSHHGKK
MRMARCGHCR GCLRVQDCGS CVNCLDKPKF GGPNTKKQCC VYRKCDKIEA RKMERLAKKG
RTIVKTLLPW DSDESPEASP GPPGPRRGAG AGGPREEVVA HPGPEEQDSL LQRKSARRCV
KQRPSYDIFE DSDDSEPGGP PAPRRRTPRE NELPLPEPEE QSRPRKPTLQ PVLQLKARRR
LDKDALAPGP FASFPNGWTG KQKSPDGVHR VRVDFKEDCD LENVWLMGGL SVLTSVPGGP
PMVCLLCASK GLHELVFCQV CCDPFHPFCL EEAERPLPQH HDTWCCRRCK FCHVCGRKGR
GSKHLLECER CRHAYHPACL GPSYPTRATR KRRHWICSAC VRCKSCGATP GKNWDVEWSG
DYSLCPRCTQ LYEKGNYCPI CTRCYEDNDY ESKMMQCAQC DHWVHAKCEG LSDEDYEILS
GLPDSVLYTC GPCAGAAQPR WREALSGALQ GGLRQVLQGL LSSKVVGPLL LCTQCGPDGK
QLHPGPCGLQ AVSQRFEDGH YKSVHSFMED MVGILMRHSE EGETPDRRAG GQMKGLLLKL
LESAFGWFDA HDPKYWRRST RLPNGVLPNA VLPPSLDHVY AQWRQQEPET PESGQPPGDP
SAAFQGKDPA AFSHLEDPRQ CALCLKYGDA DSKEAGRLLY IGQNEWTHVN CAIWSAEVFE
ENDGSLKNVH AAVARGRQMR CELCLKPGAT VGCCLSSCLS NFHFMCARAS YCIFQDDKKV
FCQKHTDLLD GKEIVNPDGF DVLRRVYVDF EGINFKRKFL TGLEPDAINV LIGSIRIDSL
GTLSDLSDCE GRLFPIGYQC SRLYWSTVDA RRRCWYRCRI LEYRPWGPRE EPAHLEAAEE
NQTIVHSPAP SSEPPGGEDP PLDTDVLVPG APERHSPIQN LDPPLRPDSG SAPPPAPRSF
SGARIKVPNY SPSRRPLGGV SFGPLPSPGS PSSLTHHIPT VGDPDFPAPP RRSRRPSPLA
PRPPPSRWAS PPLKTSPQLR VPPPTSVVTA LTPTSGELAP PGPAPSPPPP EDLGPDFEDM
EVVSGLSAAD LDFAASLLGT EPFQEEIVAA GAMGSSHGGP GDSSEEESSP TSRYIHFPVT
VVSAPGLAPS ATPGAPRIEQ LDGVDDGTDS EAEAVQQPRG QGTPPSGPGV VRAGVLGAAG
DRARPPEDLP SEIVDFVLKN LGGPGDGGAG PREESLPPAP PLANGSQPSQ GLTASPADPT
RTFAWLPGAP GVRVLSLGPA PEPPKPATSK IILVNKLGQV FVKMAGEGEP VPPPVKQPPL
PPTISPTAPT SWTLPPGPLL GVLPVVGVVR PAPPPPPPPL TLVLSSGPAS PPRQAIRVKR
VSTFSGRSPP APPPYKAPRL DEDGEASEDT PQVPGLGSGG FSRVRMKTPT VRGVLDLDRP
GEPAGEESPG PLQERSPLLP LPEDGPPQVP DGPPDLLLES QWHHYSGEAS SSEEEPPSPD
DKENQAPKRT GPHLRFEISS EDGFSVEAES LEGAWRTLIE KVQEARGHAR LRHLSFSGMS
GARLLGIHHD AVIFLAEQLP GAQRCQHYKF RYHQQGEGQE EPPLNPHGAA RAEVYLRKCT
FDMFNFLASQ HRVLPEGATC DEEEDEVQLR STRRATSLEL PMAMRFRHLK KTSKEAVGVY
RSAIHGRGLF CKRNIDAGEM VIEYSGIVIR SVLTDKREKF YDGKGIGCYM FRMDDFDVVD
ATMHGNAARF INHSCEPNCF SRVIHVEGQK HIVIFALRRI LRGEELTYDY KFPIEDASNK
LPCNCGAKRC RRFLN
