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MGP001931

UniProt Annotations

Entry Information
Gene Namelysine (K)-specific methyltransferase 2A
Protein EntryKMT2A_HUMAN
UniProt IDQ03164
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=3; Name=1; IsoId=Q03164-1; Sequence=Displayed; Name=2; Synonyms=14P-18B; IsoId=Q03164-2; Sequence=VSP_006666; Name=3; IsoId=Q03164-3; Sequence=VSP_046879;
Catalytic ActivityS-adenosyl-L-methionine + L-lysine-[histone] = S-adenosyl-L-homocysteine + N(6)-methyl-L-lysine-[histone]. {ECO:0000269|PubMed:12453419, ECO:0000269|PubMed:19187761}.
DiseaseNote=A chromosomal aberration involving KMT2A may be a cause of chronic neutrophilic leukemia. Translocation t(4;11)(q21;q23) with SEPT11. {ECO:0000269|PubMed:10490642}.
DiseaseNote=Chromosomal aberrations involving KMT2A are a cause of acute leukemias. Translocation t(1;11)(q21;q23) with MLLT11/AF1Q; translocation t(3;11)(p21;q23) with NCKIPSD/AF3p21; translocation t(3,11)(q25,q23) with GMPS; translocation t(4;11)(q21;q23) with AFF1/MLLT2/AF4; insertion ins(5;11)(q31;q13q23) with AFF4/AF5Q31; translocation t(5;11)(q12;q23) with AF5-alpha/CENPK; translocation t(6;11)(q27;q23) with MLLT4/AF6; translocation t(9;11)(p22;q23) with MLLT3/AF9; translocation t(10;11)(p11.2;q23) with ABI1; translocation t(10;11)(p12;q23) with MLLT10/AF10; t(11;15)(q23;q14) with CASC5 and ZFYVE19; translocation t(11;17)(q23;q21) with MLLT6/AF17; translocation t(11;19)(q23;p13.3) with ELL; translocation t(11;19)(q23;p13.3) with MLLT1/ENL; translocation t(11;19)(q23;p23) with GAS7; translocation t(X;11)(q13;q23) with FOXO4/AFX1. Translocation t(3;11)(q28;q23) with LPP. Translocation t(10;11)(q22;q23) with TET1. Translocation t(9;11)(q34;q23) with DAB2IP. Translocation t(4;11)(p12;q23) with FRYL. Fusion proteins KMT2A-MLLT1, KMT2A- MLLT3 and KMT2A-ELL interact with PPP1R15A and, on the contrary to unfused KMT2A, inhibit PPP1R15A-induced apoptosis. {ECO:0000269|PubMed:10490642}.
DiseaseWiedemann-Steiner syndrome (WDSTS) [MIM:605130]: A syndrome characterized by hairy elbows (hypertrichosis cubiti), intellectual disability, a distinctive facial appearance, and short stature. Facial characteristics include long eyelashes, thick or arched eyebrows with a lateral flare, and downslanting and vertically narrow palpebral fissures. {ECO:0000269|PubMed:22795537}. Note=The disease is caused by mutations affecting the gene represented in this entry.
DomainThe 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors. {ECO:0000269|PubMed:17467953}.
DomainThe CXXC-type zinc finger binds bind to nonmethyl-CpG dinucleotides. {ECO:0000269|PubMed:16990798}.
DomainThe SET domain structure is atypical and is not in an optimal position to have methyltransferase activity. It requires other components of the MLL1/MLL complex, such as ASH2L or RBBP5, to order the active site and obtain optimal histone methyltransferase activity. {ECO:0000269|PubMed:19187761}.
FunctionHistone methyltransferase that plays an essential role in early development and hematopoiesis. Catalytic subunit of the MLL1/MLL complex, a multiprotein complex that mediates both methylation of 'Lys-4' of histone H3 (H3K4me) complex and acetylation of 'Lys-16' of histone H4 (H4K16ac). In the MLL1/MLL complex, it specifically mediates H3K4me, a specific tag for epigenetic transcriptional activation. Has weak methyltransferase activity by itself, and requires other component of the MLL1/MLL complex to obtain full methyltransferase activity. Has no activity toward histone H3 phosphorylated on 'Thr-3', less activity toward H3 dimethylated on 'Arg-8' or 'Lys-9', while it has higher activity toward H3 acetylated on 'Lys-9'. Required for transcriptional activation of HOXA9. Promotes PPP1R15A-induced apoptosis. Plays a critical role in the control of circadian gene expression and is essential for the transcriptional activation mediated by the CLOCK-ARNTL/BMAL1 heterodimer. Establishes a permissive chromatin state for circadian transcription by mediating a rhythmic methylation of 'Lys-4' of histone H3 (H3K4me) and this histone modification directs the circadian acetylation at H3K9 and H3K14 allowing the recruitment of CLOCK-ARNTL/BMAL1 to chromatin (By similarity). {ECO:0000250|UniProtKB:P55200, ECO:0000269|PubMed:10490642, ECO:0000269|PubMed:12453419, ECO:0000269|PubMed:15960975, ECO:0000269|PubMed:19556245}.
InteractionSelf; NbExp=5; IntAct=EBI-591370, EBI-591370; Q6P1J9:CDC73; NbExp=4; IntAct=EBI-591370, EBI-930143; P45481:Crebbp (xeno); NbExp=7; IntAct=EBI-591370, EBI-296306; Q6PD62:CTR9; NbExp=5; IntAct=EBI-591370, EBI-1019583; P68431:HIST1H3D; NbExp=11; IntAct=EBI-591370, EBI-79722; Q92794:KAT6A; NbExp=10; IntAct=EBI-2638616, EBI-948013; Q9H7Z6:KAT8; NbExp=3; IntAct=EBI-591370, EBI-896414; Q8N7H5:PAF1; NbExp=4; IntAct=EBI-591370, EBI-2607770; Q02548:PAX5; NbExp=2; IntAct=EBI-2610266, EBI-296331; Q9UNP9:PPIE; NbExp=4; IntAct=EBI-591370, EBI-591818; Q15291:RBBP5; NbExp=6; IntAct=EBI-591370, EBI-592823; P61964:WDR5; NbExp=10; IntAct=EBI-591370, EBI-540834;
PtmProteolytic cleavage by TASP1 generates MLL cleavage product N320 and MLL cleavage product C180, which reassemble through a non-covalent association. 2 cleavage sites exist, cleavage site 1 (CS1) and cleavage site 2 (CS2), to generate MLL cleavage products N320 and C180. CS2 is the major site. {ECO:0000269|PubMed:12482972, ECO:0000269|PubMed:14636557}.
Sequence CautionSequence=AAA58669.1; Type=Frameshift; Positions=317, 380; Evidence={ECO:0000305}; Sequence=AAG26332.2; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305}; Sequence=BAD92745.1; Type=Frameshift; Positions=1098; Evidence={ECO:0000305};
SimilarityBelongs to the class V-like SAM-binding methyltransferase superfamily. Histone-lysine methyltransferase family. TRX/MLL subfamily. {ECO:0000255|PROSITE-ProRule:PRU00190}.
SimilarityContains 1 bromo domain. {ECO:0000255|PROSITE- ProRule:PRU00035}.
SimilarityContains 1 CXXC-type zinc finger. {ECO:0000255|PROSITE-ProRule:PRU00509}.
SimilarityContains 1 FYR C-terminal domain. {ECO:0000255|PROSITE-ProRule:PRU00876}.
SimilarityContains 1 FYR N-terminal domain. {ECO:0000255|PROSITE-ProRule:PRU00875}.
SimilarityContains 1 post-SET domain. {ECO:0000255|PROSITE- ProRule:PRU00155}.
SimilarityContains 1 SET domain. {ECO:0000255|PROSITE- ProRule:PRU00190}.
SimilarityContains 3 A.T hook DNA-binding domains. {ECO:0000305}.
SimilarityContains 3 PHD-type zinc fingers. {ECO:0000255|PROSITE-ProRule:PRU00146}.
Subcellular LocationMLL cleavage product C180: Nucleus. Note=Localizes to a diffuse nuclear pattern when not associated with MLL cleavage product N320.
Subcellular LocationMLL cleavage product N320: Nucleus.
Subcellular LocationNucleus {ECO:0000269|PubMed:12482972}.
SubunitMLL cleavage product N320 heterodimerizes with MLL cleavage product C180 (via SET and FYRC domains). Component of some MLL1/MLL complex, at least composed of the core components KMT2A/MLL1, ASH2L, HCFC1/HCF1, HCFC2, WDR5, DPY30 and RBBP5, as well as the facultative components BAP18, CHD8, E2F6, HSP70, INO80C, KANSL1, LAS1L, MAX, MCRS1, MEN1, MGA, KAT8/MOF, PELP1, PHF20, PRP31, RING2, RUVB1/TIP49A, RUVB2/TIP49B, SENP3, TAF1, TAF4, TAF6, TAF7, TAF9 and TEX10. Interacts with WDR5; the interaction is direct. Interacts with KAT8/MOF; the interaction is direct. Interacts with SBF1 and PPP1R15A. Interacts with ZNF335. Interacts with CLOCK and ARNTL/BMAL1 in a circadian manner (By similarity). {ECO:0000250|UniProtKB:P55200, ECO:0000269|PubMed:10490642, ECO:0000269|PubMed:12482972, ECO:0000269|PubMed:14636557, ECO:0000269|PubMed:15199122, ECO:0000269|PubMed:15960975, ECO:0000269|PubMed:16253272, ECO:0000269|PubMed:16990798, ECO:0000269|PubMed:17500065, ECO:0000269|PubMed:18829459, ECO:0000269|PubMed:19187761, ECO:0000269|PubMed:19556245, ECO:0000269|PubMed:23178126, ECO:0000269|PubMed:9537414}.
Tissue SpecificityHeart, lung, brain and T- and B-lymphocytes.
Web ResourceName=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/MLLID13.html";
Web ResourceName=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/mll/";
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