Rabbit Anti-KMT2A Recombinant Antibody (CBFYM-1190) (CBMAB-M1347-FY)

Lysine Methyltransferase 2A

This gene encodes a transcriptional coactivator that plays an essential role in regulating gene expression during early development and hematopoiesis. The encoded protein contains multiple conserved functional domains. One of these domains, the SET domain, is responsible for its histone H3 lysine 4 methyltransferase activity which mediates chromatin modifications associated with epigenetic transcriptional activation. This protein is processed by the enzyme Taspase 1 into two fragments, MLL-C and MLL-N. These fragments reassociate and further assemble into different multiprotein complexes that regulate the transcription of specific target genes, including many of the HOX genes. Multiple chromosomal translocations involving this gene are the cause of certain acute lymphoid leukemias and acute myeloid leukemias. Alternate splicing results in multiple transcript variants.

Lysine Methyltransferase 2A; Myeloid/Lymphoid Or Mixed-Lineage Leukemia (Trithorax Homolog, Drosophila); Lysine (K)-Specific Methyltransferase 2A; CXXC-Type Zinc Finger Protein 7; Lysine N-Methyltransferase 2A; Zinc Finger Protein HRX; Trithorax-Like Protein; ALL-1; CXXC7; MLL1; TRX1; MLL; HRX

Histone methyltransferase that plays an essential role in early development and hematopoiesis (PubMed:15960975, PubMed:12453419, PubMed:15960975, PubMed:19556245, PubMed:19187761, PubMed:20677832, PubMed:21220120, PubMed:26886794).
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) (PubMed:15960975, PubMed:12453419, PubMed:15960975, PubMed:19556245, PubMed:24235145, PubMed:19187761, PubMed:20677832, PubMed:21220120, PubMed:26886794).
Catalyzes methyl group transfer from S-adenosyl-L-methionine to the epsilon-amino group of 'Lys-4' of histone H3 (H3K4) via a non-processive mechanism. Part of chromatin remodeling machinery predominantly forms H3K4me1 and H3K4me2 methylation marks at active chromatin sites where transcription and DNA repair take place (PubMed:25561738, PubMed:15960975, PubMed:12453419, PubMed:15960975, PubMed:19556245, PubMed:19187761, PubMed:20677832, PubMed:21220120, PubMed:26886794).
Has weak methyltransferase activity by itself, and requires other component of the MLL1/MLL complex to obtain full methyltransferase activity (PubMed:19187761, PubMed:26886794).
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' (PubMed:19187761).
Binds to unmethylated CpG elements in the promoter of target genes and helps maintain them in the nonmethylated state (PubMed:20010842).
Required for transcriptional activation of HOXA9 (PubMed:12453419, PubMed:20677832, PubMed:20010842).
Promotes PPP1R15A-induced apoptosis (PubMed:10490642).
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 (By similarity).
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).
Also has auto-methylation activity on Cys-3882 in absence of histone H3 substrate (PubMed:24235145).

Apoptotic processIEA:UniProtKB-KW
Chromatin organizationIEA:UniProtKB-KW
Circadian regulation of gene expressionISS:UniProtKB
Embryonic hemopoiesisManual Assertion Based On ExperimentTAS:UniProtKB
Histone H3-K4 dimethylationManual Assertion Based On ExperimentIDA:CACAO
Histone H3-K4 methylationManual Assertion Based On ExperimentIDA:UniProtKB
Histone H3-K4 monomethylationManual Assertion Based On ExperimentIDA:CACAO
Histone H3-K4 trimethylationManual Assertion Based On ExperimentIDA:BHF-UCL
Histone H4-K16 acetylationManual Assertion Based On ExperimentIMP:UniProtKB
Negative regulation of DNA methylationManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of histone H3-K4 methylationISS:UniProtKB
Positive regulation of transcription by RNA polymerase IIManual Assertion Based On ExperimentIDA:BHF-UCL
Positive regulation of transcription, DNA-templatedManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of transporter activityManual Assertion Based On ExperimentIMP:BHF-UCL
Protein-containing complex assemblyManual Assertion Based On ExperimentIDA:UniProtKB
Regulation of histone H3-K14 acetylationISS:UniProtKB
Regulation of histone H3-K9 acetylationISS:UniProtKB

Nucleus
MLL cleavage product N320:
Nucleus
MLL cleavage product C180:
Nucleus
Localizes to a diffuse nuclear pattern when not associated with MLL cleavage product N320.

Wiedemann-Steiner syndrome (WDSTS):
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.
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 AFDN; 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 KNL1 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. Fusion protein KMT2A-MLLT3 interacts with MEN1 and PSIP1 (PubMed:22936661, PubMed:25305204).
A chromosomal aberration involving KMT2A may be a cause of chronic neutrophilic leukemia. Translocation t(4;11)(q21;q23) with SEPT11

Proteolytic 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.
Phosphorylation increases its interaction with PSIP1.
Auto-methylated at Cys-3882: auto-methylation is inhibited by the WRAD complex and unmodified histone H3.