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Database: UniProt
Entry: Q9UMN6
LinkDB: Q9UMN6
Original site: Q9UMN6 
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   10-APR-2019, entry version 199.
DE   RecName: Full=Histone-lysine N-methyltransferase 2B;
DE            Short=Lysine N-methyltransferase 2B;
DE            EC=2.1.1.43;
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;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA   Angrand P.-O., Valvatne H., Jeanmougin F., Adamson A.,
RA   van der Hoeven F., Olsen L., Tekotte H., Huang N., Poch O.,
RA   Lamerdin J., Chambon P., Losson R., Stewart A., Aasland R.;
RT   "Mammalian trithorax- and ASH1-like proteins: putative chromatin
RT   regulators 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.,
RA   Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M.,
RA   Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E.,
RA   Caenepeel S., Carrano A.V., Caoile C., Chan Y.M., Christensen M.,
RA   Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C.,
RA   Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M.,
RA   Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T.,
RA   Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H.,
RA   Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S.,
RA   Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J.,
RA   Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M.,
RA   Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J.,
RA   Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D.,
RA   Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A.,
RA   Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I.,
RA   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 (ISOFORM 1).
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
RT   to 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 (ISOFORM 1).
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.
RT   The complete sequences of 100 new cDNA clones from brain which can
RT   code for 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
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [6]
RP   PARTIAL NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
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
RP   COMPLEX, 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.,
RA   Levine S.S., Lee J.C., Hayes D.N., Shanmugam K.S., Bhattacharjee A.,
RA   Biondi C.A., Kay G.F., Hayward N.K., Hess J.L., Meyerson M.;
RT   "Menin associates with a trithorax family histone methyltransferase
RT   complex 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, ENZYME ACTIVITY, 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
RT   to the beta-globin locus.";
RL   Mol. Cell 27:573-584(2007).
RN   [10]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-821; SER-844; SER-1032;
RP   SER-1035 AND SER-1930, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE
RP   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   [11]
RP   ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP   METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS
RP   SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=19413330; DOI=10.1021/ac9004309;
RA   Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA   Mohammed S.;
RT   "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT   a refined SCX-based approach.";
RL   Anal. Chem. 81:4493-4501(2009).
RN   [12]
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   [13]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-821, AND IDENTIFICATION
RP   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.,
RA   Mann M.;
RT   "Quantitative phosphoproteomics reveals widespread full
RT   phosphorylation site occupancy during mitosis.";
RL   Sci. Signal. 3:RA3-RA3(2010).
RN   [14]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-861, AND IDENTIFICATION
RP   BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA   Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA   Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA   Blagoev B.;
RT   "System-wide temporal characterization of the proteome and
RT   phosphoproteome of human embryonic stem cell differentiation.";
RL   Sci. Signal. 4:RS3-RS3(2011).
RN   [15]
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
RP   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   [16]
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.,
RA   Wang L., Ye M., Zou H.;
RT   "An enzyme assisted RP-RPLC approach for in-depth analysis of human
RT   liver phosphoproteome.";
RL   J. Proteomics 96:253-262(2014).
RN   [17]
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   [18]
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.,
RA   Joseph A.P., Mencacci N.E., Papandreou A., Ng J., Barral S., Ngoh A.,
RA   Ben-Pazi H., Willemsen M.A., Arkadir D., Barnicoat A., Bergman H.,
RA   Bhate S., Boys A., Darin N., Foulds N., Gutowski N., Hills A.,
RA   Houlden H., Hurst J.A., Israel Z., Kaminska M., Limousin P.,
RA   Lumsden D., McKee S., Misra S., Mohammed S.S., Nakou V., Nicolai J.,
RA   Nilsson M., Pall H., Peall K.J., Peters G.B., Prabhakar P.,
RA   Reuter M.S., Rump P., Segel R., Sinnema M., Smith M., Turnpenny P.,
RA   White S.M., Wieczorek D., Wiethoff S., Wilson B.T., Winter G.,
RA   Wragg C., Pope S., Heales S.J., Morrogh D., Pittman A., Carr L.J.,
RA   Perez-Duenas B., Lin J.P., Reis A., Gahl W.A., Toro C., Bhatia K.P.,
RA   Wood N.W., Kamsteeg E.J., Chong W.K., Gissen P., Topf M., Dale R.C.,
RA   Chubb J.R., Raymond F.L., Kurian M.A.;
RT   "Mutations in the histone methyltransferase gene KMT2B cause complex
RT   early-onset dystonia.";
RL   Nat. Genet. 49:223-237(2017).
RN   [19]
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-
RT   modification with phosphorylation.";
RL   Nat. Struct. Mol. Biol. 24:325-336(2017).
CC   -!- FUNCTION: Histone methyltransferase. Methylates 'Lys-4' of histone
CC       H3. H3 'Lys-4' methylation represents a specific tag for
CC       epigenetic transcriptional activation. Plays a central role in
CC       beta-globin locus transcription regulation by being recruited by
CC       NFE2. Plays an important role in controlling bulk H3K4me during
CC       oocyte growth and preimplantation development. Required during the
CC       transcriptionally active period of oocyte growth for the
CC       establishment and/or maintenance of bulk H3K4 trimethylation
CC       (H3K4me3), global transcriptional silencing that preceeds
CC       resumption of meiosis, oocyte survival and normal zygotic genome
CC       activation. {ECO:0000269|PubMed:17707229}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=L-lysyl-[histone] + S-adenosyl-L-methionine = H(+) +
CC         N(6)-methyl-L-lysyl-[histone] + S-adenosyl-L-homocysteine;
CC         Xref=Rhea:RHEA:10024, Rhea:RHEA-COMP:9845, Rhea:RHEA-COMP:9846,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:29969, ChEBI:CHEBI:57856,
CC         ChEBI:CHEBI:59789, ChEBI:CHEBI:61929; EC=2.1.1.43;
CC         Evidence={ECO:0000269|PubMed:17707229};
CC   -!- SUBUNIT: Component of the menin-associated histone
CC       methyltransferase complex, at least composed of KMT2B/MLL4, ASH2L,
CC       RBBP5, WDR5, DPY30, MEN1; the complex interacts with POLR2A and
CC       POLR2B via MEN1. Interacts with NFE2. Interacts with KDM6B.
CC       {ECO:0000269|PubMed:14992727, ECO:0000269|PubMed:17707229,
CC       ECO:0000269|PubMed:17825402}.
CC   -!- INTERACTION:
CC       Q9UBL3-3:ASH2L; NbExp=2; IntAct=EBI-765774, EBI-16130425;
CC       P16333:NCK1; NbExp=2; IntAct=EBI-765774, EBI-389883;
CC       Q14686:NCOA6; NbExp=5; IntAct=EBI-765774, EBI-78670;
CC       P61964:WDR5; NbExp=5; IntAct=EBI-765774, EBI-540834;
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1; Synonyms=Long;
CC         IsoId=Q9UMN6-1; Sequence=Displayed;
CC       Name=2; Synonyms=Truncated;
CC         IsoId=Q9UMN6-2; Sequence=VSP_006668, VSP_006669;
CC   -!- TISSUE SPECIFICITY: Widely expressed. Highest levels in testis.
CC       Also found in brain with higher expression in the cerebellum than
CC       in any other region, bone marrow, heart, muscle, kidney, placenta,
CC       spleen, thymus, prostate, ovary, intestine, colon, peripheral
CC       blood lymphocytes and pancreas. Often amplified in pancreatic
CC       carcinomas. {ECO:0000269|PubMed:27992417}.
CC   -!- DISEASE: Dystonia 28, childhood-onset (DYT28) [MIM:617284]: A form
CC       of dystonia, a disorder defined by the presence of sustained
CC       involuntary muscle contraction, often leading to abnormal
CC       postures. DYT28 is an autosomal dominant, progressive form
CC       characterized by onset in the first decade of life and variable
CC       severity. Dystonia begins focally in the lower limbs, resulting in
CC       gait difficulties, with later progression to other body regions,
CC       including the upper limbs, neck, and orofacial region.
CC       {ECO:0000269|PubMed:27839873, ECO:0000269|PubMed:27992417}.
CC       Note=The disease is caused by mutations affecting the gene
CC       represented in this entry.
CC   -!- SIMILARITY: Belongs to the class V-like SAM-binding
CC       methyltransferase superfamily. Histone-lysine methyltransferase
CC       family. TRX/MLL 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
CC       to as MLL2 and vice versa in the literature. {ECO:0000305}.
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; -; mRNA.
DR   EMBL; AF105280; AAD26112.1; -; mRNA.
DR   CCDS; CCDS46055.1; -. [Q9UMN6-1]
DR   RefSeq; NP_055542.1; NM_014727.2. [Q9UMN6-1]
DR   UniGene; Hs.676457; -.
DR   UniGene; Hs.92236; -.
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   PDBsum; 3UVM; -.
DR   PDBsum; 4ERZ; -.
DR   PDBsum; 4PZI; -.
DR   ProteinModelPortal; Q9UMN6; -.
DR   SMR; Q9UMN6; -.
DR   BioGrid; 115104; 37.
DR   CORUM; Q9UMN6; -.
DR   DIP; DIP-34598N; -.
DR   ELM; Q9UMN6; -.
DR   IntAct; Q9UMN6; 49.
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   PaxDb; Q9UMN6; -.
DR   PeptideAtlas; Q9UMN6; -.
DR   PRIDE; Q9UMN6; -.
DR   ProteomicsDB; 85190; -.
DR   ProteomicsDB; 85191; -. [Q9UMN6-2]
DR   Ensembl; ENST00000420124; ENSP00000398837; ENSG00000272333. [Q9UMN6-1]
DR   GeneID; 9757; -.
DR   KEGG; hsa:9757; -.
DR   UCSC; uc021usv.1; human. [Q9UMN6-1]
DR   CTD; 9757; -.
DR   DisGeNET; 9757; -.
DR   EuPathDB; HostDB:ENSG00000272333.5; -.
DR   GeneCards; KMT2B; -.
DR   GeneReviews; KMT2B; -.
DR   HGNC; HGNC:15840; KMT2B.
DR   HPA; HPA006487; -.
DR   MalaCards; KMT2B; -.
DR   MIM; 606834; gene.
DR   MIM; 617284; phenotype.
DR   neXtProt; NX_Q9UMN6; -.
DR   OpenTargets; ENSG00000272333; -.
DR   eggNOG; KOG1084; Eukaryota.
DR   eggNOG; COG2940; LUCA.
DR   GeneTree; ENSGT00940000161496; -.
DR   HOVERGEN; HBG100043; -.
DR   InParanoid; Q9UMN6; -.
DR   KO; K14959; -.
DR   OMA; KRTGPHL; -.
DR   OrthoDB; 738155at2759; -.
DR   PhylomeDB; 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   ChiTaRS; KMT2B; human.
DR   GeneWiki; MLL4; -.
DR   GenomeRNAi; 9757; -.
DR   PRO; PR:Q9UMN6; -.
DR   Proteomes; UP000005640; Chromosome 19.
DR   Bgee; ENSG00000272333; Expressed in 212 organ(s), highest expression level in testis.
DR   Genevisible; Q9UMN6; HS.
DR   GO; GO:0035097; C:histone methyltransferase complex; IDA:MGI.
DR   GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR   GO; GO:0005634; C:nucleus; IDA:MGI.
DR   GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR   GO; GO:0003700; F:DNA-binding transcription factor activity; NAS:UniProtKB.
DR   GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB.
DR   GO; GO:0042800; F:histone methyltransferase activity (H3-K4 specific); IDA:MGI.
DR   GO; GO:0018024; F:histone-lysine N-methyltransferase activity; TAS:Reactome.
DR   GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR   GO; GO:0048096; P:chromatin-mediated maintenance of transcription; NAS:UniProtKB.
DR   GO; GO:0016458; P:gene silencing; IEA:Ensembl.
DR   GO; GO:0051568; P:histone H3-K4 methylation; IMP:UniProtKB.
DR   GO; GO:0080182; P:histone H3-K4 trimethylation; IEA:Ensembl.
DR   GO; GO:0007613; P:memory; IEA:Ensembl.
DR   GO; GO:0009994; P:oocyte differentiation; IEA:Ensembl.
DR   GO; GO:0001541; P:ovarian follicle development; IEA:Ensembl.
DR   GO; GO:0030728; P:ovulation; IEA:Ensembl.
DR   GO; GO:0051569; P:regulation of histone H3-K4 methylation; IEA:Ensembl.
DR   GO; GO:0045652; P:regulation of megakaryocyte differentiation; TAS:Reactome.
DR   Gene3D; 1.20.920.10; -; 1.
DR   Gene3D; 3.30.40.10; -; 3.
DR   InterPro; IPR036427; Bromodomain-like_sf.
DR   InterPro; IPR034732; EPHD.
DR   InterPro; IPR003889; FYrich_C.
DR   InterPro; IPR003888; FYrich_N.
DR   InterPro; IPR016569; MeTrfase_trithorax.
DR   InterPro; IPR003616; Post-SET_dom.
DR   InterPro; IPR001214; SET_dom.
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   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; Alternative splicing; Chromatin regulator;
KW   Complete proteome; Disease mutation; DNA-binding; Dystonia;
KW   Isopeptide bond; Metal-binding; Methyltransferase; Nucleus;
KW   Phosphoprotein; Polymorphism; Reference proteome; Repeat;
KW   S-adenosyl-L-methionine; Transcription; Transcription regulation;
KW   Transferase; Ubl conjugation; Zinc; Zinc-finger.
FT   INIT_MET      1      1       Removed. {ECO:0000244|PubMed:19413330}.
FT   CHAIN         2   2715       Histone-lysine N-methyltransferase 2B.
FT                                /FTId=PRO_0000124881.
FT   DOMAIN     1727   1783       FYR N-terminal. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00875}.
FT   DOMAIN     2411   2492       FYR C-terminal. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00876}.
FT   DOMAIN     2575   2691       SET. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00190}.
FT   DOMAIN     2699   2715       Post-SET. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00155}.
FT   DNA_BIND     37     44       A.T hook 1.
FT   DNA_BIND    110    117       A.T hook 2.
FT   DNA_BIND    357    365       A.T hook 3.
FT   ZN_FING     959   1006       CXXC-type. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00509}.
FT   ZN_FING    1201   1252       PHD-type 1. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00146}.
FT   ZN_FING    1249   1303       PHD-type 2. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00146}.
FT   ZN_FING    1335   1396       PHD-type 3. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00146}.
FT   ZN_FING    1578   1618       C2HC pre-PHD-type. {ECO:0000255|PROSITE-
FT                                ProRule:PRU01146}.
FT   ZN_FING    1639   1686       PHD-type 4. {ECO:0000255|PROSITE-
FT                                ProRule:PRU01146}.
FT   REGION     2652   2653       S-adenosyl-L-methionine binding.
FT                                {ECO:0000250}.
FT   COMPBIAS     26     37       Poly-Gly.
FT   COMPBIAS    248    255       Poly-Pro.
FT   COMPBIAS    362    398       Asp/Glu-rich (acidic).
FT   COMPBIAS    402    771       Pro-rich.
FT   COMPBIAS    808    812       Poly-Gln.
FT   COMPBIAS   1963   1970       Poly-Pro.
FT   COMPBIAS   2251   2259       Poly-Pro.
FT   METAL      2655   2655       Zinc. {ECO:0000250}.
FT   METAL      2703   2703       Zinc. {ECO:0000250}.
FT   METAL      2705   2705       Zinc. {ECO:0000250}.
FT   METAL      2710   2710       Zinc. {ECO:0000250}.
FT   BINDING    2585   2585       S-adenosyl-L-methionine.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00190}.
FT   BINDING    2587   2587       S-adenosyl-L-methionine.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00190}.
FT   BINDING    2629   2629       S-adenosyl-L-methionine.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00190}.
FT   BINDING    2704   2704       S-adenosyl-L-methionine.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00190}.
FT   MOD_RES       2      2       N-acetylalanine.
FT                                {ECO:0000244|PubMed:19413330}.
FT   MOD_RES     113    113       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:O08550}.
FT   MOD_RES     114    114       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:O08550}.
FT   MOD_RES     118    118       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:O08550}.
FT   MOD_RES     351    351       Phosphoserine.
FT                                {ECO:0000244|PubMed:23186163}.
FT   MOD_RES     821    821       Phosphoserine.
FT                                {ECO:0000244|PubMed:18669648,
FT                                ECO:0000244|PubMed:20068231,
FT                                ECO:0000244|PubMed:23186163}.
FT   MOD_RES     844    844       Phosphoserine.
FT                                {ECO:0000244|PubMed:18669648,
FT                                ECO:0000244|PubMed:23186163}.
FT   MOD_RES     861    861       Phosphoserine.
FT                                {ECO:0000244|PubMed:21406692,
FT                                ECO:0000244|PubMed:23186163,
FT                                ECO:0000244|PubMed:24275569}.
FT   MOD_RES     936    936       Phosphoserine.
FT                                {ECO:0000244|PubMed:23186163}.
FT   MOD_RES    1032   1032       Phosphoserine.
FT                                {ECO:0000244|PubMed:18669648}.
FT   MOD_RES    1035   1035       Phosphoserine.
FT                                {ECO:0000244|PubMed:18669648}.
FT   MOD_RES    1092   1092       Phosphoserine.
FT                                {ECO:0000244|PubMed:23186163}.
FT   MOD_RES    1095   1095       Phosphoserine.
FT                                {ECO:0000244|PubMed:23186163}.
FT   MOD_RES    1930   1930       Phosphoserine.
FT                                {ECO:0000244|PubMed:18669648}.
FT   MOD_RES    1936   1936       Phosphoserine.
FT                                {ECO:0000244|PubMed:23186163}.
FT   MOD_RES    2068   2068       Phosphothreonine.
FT                                {ECO:0000244|PubMed:19690332}.
FT   MOD_RES    2083   2083       Phosphothreonine.
FT                                {ECO:0000244|PubMed:19690332,
FT                                ECO:0000244|PubMed:23186163,
FT                                ECO:0000244|PubMed:24275569}.
FT   MOD_RES    2288   2288       Phosphoserine.
FT                                {ECO:0000244|PubMed:23186163}.
FT   MOD_RES    2348   2348       Phosphoserine.
FT                                {ECO:0000244|PubMed:23186163}.
FT   CROSSLNK    805    805       Glycyl lysine isopeptide (Lys-Gly)
FT                                (interchain with G-Cter in SUMO2).
FT                                {ECO:0000244|PubMed:28112733}.
FT   CROSSLNK   1136   1136       Glycyl lysine isopeptide (Lys-Gly)
FT                                (interchain with G-Cter in SUMO2).
FT                                {ECO:0000244|PubMed:28112733}.
FT   VAR_SEQ     532    582       VSARSSRVIKTPRRFMDEDPPKPPKVEVSPVLRPPITTSPP
FT                                VPQEPAPVPS -> PLSQSLLLPMTLQLSLSLGQWAAPTTS
FT                                ACLDSPLWSPLLLRPRCPLTGLQL (in isoform 2).
FT                                {ECO:0000305}.
FT                                /FTId=VSP_006668.
FT   VAR_SEQ     583   2715       Missing (in isoform 2). {ECO:0000305}.
FT                                /FTId=VSP_006669.
FT   VARIANT     172    172       T -> I (in dbSNP:rs60207923).
FT                                /FTId=VAR_061913.
FT   VARIANT     545   2715       Missing (in DYT28).
FT                                {ECO:0000269|PubMed:27839873}.
FT                                /FTId=VAR_080233.
FT   VARIANT     564   2715       Missing (in DYT28).
FT                                {ECO:0000269|PubMed:27992417}.
FT                                /FTId=VAR_080234.
FT   VARIANT     587    587       P -> R (in dbSNP:rs2242519).
FT                                /FTId=VAR_046563.
FT   VARIANT     754    754       P -> L (in dbSNP:rs179686).
FT                                /FTId=VAR_046564.
FT   VARIANT     810   2715       Missing (in DYT28).
FT                                {ECO:0000269|PubMed:27839873}.
FT                                /FTId=VAR_080235.
FT   VARIANT    1097   1097       P -> L (in dbSNP:rs34014681).
FT                                /FTId=VAR_046565.
FT   VARIANT    1515   2715       Missing (in DYT28).
FT                                {ECO:0000269|PubMed:27992417}.
FT                                /FTId=VAR_080236.
FT   VARIANT    1652   1652       G -> D (in DYT28; unknown pathological
FT                                significance).
FT                                {ECO:0000269|PubMed:27992417}.
FT                                /FTId=VAR_080237.
FT   VARIANT    1662   1662       F -> L (in DYT28; unknown pathological
FT                                significance).
FT                                {ECO:0000269|PubMed:27992417}.
FT                                /FTId=VAR_080238.
FT   VARIANT    1705   1705       R -> Q (in DYT28; unknown pathological
FT                                significance).
FT                                {ECO:0000269|PubMed:27992417}.
FT                                /FTId=VAR_080239.
FT   VARIANT    1762   1762       R -> C (in DYT28; unknown pathological
FT                                significance; dbSNP:rs1489232377).
FT                                {ECO:0000269|PubMed:27992417}.
FT                                /FTId=VAR_080240.
FT   VARIANT    1781   1781       L -> P (in DYT28; unknown pathological
FT                                significance).
FT                                {ECO:0000269|PubMed:27992417}.
FT                                /FTId=VAR_080241.
FT   VARIANT    1829   1829       P -> L (in dbSNP:rs16970649).
FT                                /FTId=VAR_052653.
FT   VARIANT    2364   2364       D -> G (in dbSNP:rs231591).
FT                                /FTId=VAR_052654.
FT   VARIANT    2408   2408       K -> N (in dbSNP:rs36062432).
FT                                /FTId=VAR_052655.
FT   VARIANT    2517   2517       R -> W (in DYT28; unknown pathological
FT                                significance; dbSNP:rs1057519285).
FT                                {ECO:0000269|PubMed:27992417}.
FT                                /FTId=VAR_080242.
FT   VARIANT    2674   2674       I -> T (in DYT28; unknown pathological
FT                                significance).
FT                                {ECO:0000269|PubMed:27992417}.
FT                                /FTId=VAR_080243.
FT   CONFLICT    834    834       K -> E (in Ref. 6; AAD17932).
FT                                {ECO:0000305}.
FT   CONFLICT    941    941       S -> Y (in Ref. 6; AAD17932).
FT                                {ECO:0000305}.
FT   CONFLICT   1317   1317       E -> Q (in Ref. 6; AAD17932).
FT                                {ECO:0000305}.
FT   CONFLICT   1362   1362       H -> Y (in Ref. 6; AAD17932).
FT                                {ECO:0000305}.
FT   CONFLICT   1438   1438       D -> N (in Ref. 6; AAD17932).
FT                                {ECO:0000305}.
FT   CONFLICT   1918   1920       PLA -> GTR (in Ref. 5; AAH09337).
FT                                {ECO:0000305}.
FT   CONFLICT   2622   2622       D -> H (in Ref. 6; AAD26112).
FT                                {ECO:0000305}.
FT   HELIX       970    973       {ECO:0000244|PDB:4PZI}.
FT   STRAND      979    981       {ECO:0000244|PDB:4PZI}.
FT   HELIX       982    985       {ECO:0000244|PDB:4PZI}.
FT   HELIX       988    990       {ECO:0000244|PDB:4PZI}.
FT   HELIX      1001   1003       {ECO:0000244|PDB:4PZI}.
FT   HELIX      1006   1015       {ECO:0000244|PDB:4PZI}.
FT   HELIX      2510   2512       {ECO:0000244|PDB:3UVM}.
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
//
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