Human Gene KMT2A (ENST00000389506.10) from GENCODE V44
Description: Homo sapiens lysine methyltransferase 2A (KMT2A), transcript variant 2, mRNA. (from RefSeq NM_005933) RefSeq Summary (NM_005933): 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 (H3K4) 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.[provided by RefSeq, Oct 2010]. Gencode Transcript: ENST00000389506.10 Gencode Gene: ENSG00000118058.25 Transcript (Including UTRs) Position: hg38 chr11:118,436,490-118,523,917 Size: 87,428 Total Exon Count: 36 Strand: + Coding Region Position: hg38 chr11:118,436,513-118,522,172 Size: 85,660 Coding Exon Count: 36
ID:MLL1_HUMAN DESCRIPTION: RecName: Full=Histone-lysine N-methyltransferase MLL; EC=2.1.1.43; AltName: Full=ALL-1; AltName: Full=CXXC-type zinc finger protein 7; AltName: Full=Lysine N-methyltransferase 2A; Short=KMT2A; AltName: Full=Trithorax-like protein; AltName: Full=Zinc finger protein HRX; Contains: RecName: Full=MLL cleavage product N320; AltName: Full=N-terminal cleavage product of 320 kDa; Short=p320; Contains: RecName: Full=MLL cleavage product C180; AltName: Full=C-terminal cleavage product of 180 kDa; Short=p180; FUNCTION: Histone 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. CATALYTIC ACTIVITY: S-adenosyl-L-methionine + L-lysine-[histone] = S-adenosyl-L-homocysteine + N(6)-methyl-L-lysine-[histone]. SUBUNIT: MLL 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 MLL, ASH2L, HCFC1/HCF1, HCFC2, WDR5, DPY30 and RBBP5, as well as the facultative components C17orf49, 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. INTERACTION: Self; NbExp=5; IntAct=EBI-591370, EBI-591370; Q6P1J9:CDC73; NbExp=4; IntAct=EBI-591370, EBI-930143; Q6PD62:CTR9; NbExp=5; IntAct=EBI-591370, EBI-1019583; P68431:HIST1H3D; NbExp=10; 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; Q9UNP9:PPIE; NbExp=5; IntAct=EBI-591370, EBI-591818; Q15291:RBBP5; NbExp=4; IntAct=EBI-591370, EBI-592823; P61964:WDR5; NbExp=11; IntAct=EBI-591370, EBI-540834; SUBCELLULAR LOCATION: Nucleus. SUBCELLULAR LOCATION: MLL cleavage product N320: Nucleus. SUBCELLULAR LOCATION: MLL cleavage product C180: Nucleus. Note=Localizes to a diffuse nuclear pattern when not associated with MLL cleavage product N320. TISSUE SPECIFICITY: Heart, lung, brain and T- and B-lymphocytes. DOMAIN: the 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors. DOMAIN: The 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. DOMAIN: The CXXC-type zinc finger binds bind to nonmethyl-CpG dinucleotides. PTM: 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. DISEASE: Note=Chromosomal aberrations involving MLL 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 MLL-MLLT1, MLL-MLLT3 and MLL-ELL interact with PPP1R15A and, on the contrary to unfused MLL, inhibit PPP1R15A-induced apoptosis. DISEASE: Note=A chromosomal aberration involving MLL may be a cause of chronic neutrophilic leukemia. Translocation t(4;11)(q21;q23) with SEPT11. SIMILARITY: Belongs to the histone-lysine methyltransferase family. TRX/MLL subfamily. SIMILARITY: Contains 3 A.T hook DNA-binding domains. SIMILARITY: Contains 1 bromo domain. SIMILARITY: Contains 1 CXXC-type zinc finger. SIMILARITY: Contains 1 FYR C-terminal domain. SIMILARITY: Contains 1 FYR N-terminal domain. SIMILARITY: Contains 3 PHD-type zinc fingers. SIMILARITY: Contains 1 post-SET domain. SIMILARITY: Contains 1 SET domain. SEQUENCE CAUTION: Sequence=AAA58669.1; Type=Frameshift; Positions=317, 380; Sequence=AAG26332.2; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence; Sequence=BAD92745.1; Type=Frameshift; Positions=1098; WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/MLL.html"; WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/mll/";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q03164
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
D14540 - Homo sapiens mRNA for MLL, partial cds. L04284 - Human germline HRX mRNA, complete cds. L04731 - Homo sapiens translocation T(4:11) of ALL-1 gene to chromosome 4. AB209508 - Homo sapiens mRNA for myeloid/lymphoid or mixed-lineage leukemia (trithorax homolog, Drosophila) variant protein. S78570 - MLL=trx zinc-finger domain homolog {alternatively spliced, clone 14p-18B} [human, mRNA Partial, 1098 nt]. AF232001 - Homo sapiens MLL protein (MLL) mRNA, partial cds. AF272381 - Homo sapiens clone 1370-7 MLL protein mRNA, partial cds. L01986 - Human trithorax-like protein (TRX1) mRNA, partial cds. S66432 - MLL {translocation} [human, mRNA PartialMutant, 360 nt]. DQ437655 - Homo sapiens isolate t-137 chromosome der(19) ELL/MLL breakpoint junction mRNA, partial sequence. DQ299936 - Homo sapiens clone 3300-1 FRYL/MLL breakpoint junction mRNA sequence. AF487906 - Homo sapiens AF4/MLL fusion protein mRNA, partial cds. AF373587 - Homo sapiens translocation breakpoint MLLT1/MLL fusion mRNA, partial sequence. L22179 - Human MLL-AF4 der(11) fusion protein mRNA, complete cds. AF024540 - Homo sapiens rearranged MLL protein mRNA, partial cds. AY187942 - Homo sapiens transcription factor MLL UPN96240 mRNA, partial cds; alternatively spliced. AY187943 - Homo sapiens transcription factor MLL UPN96240 mRNA, partial cds; alternatively spliced. AY187945 - Homo sapiens transcription factor MLL UPN95022 mRNA, partial cds; alternatively spliced. AF272382 - Homo sapiens clone 1370-39 MLL protein mRNA, partial cds. FM165198 - Homo sapiens partial mRNA for TET1-MLL fusion transcript in acute lymphoblastic leukemia, patient 4765. AF422798 - Homo sapiens MLL/LAF4 fusion protein mRNA, partial cds. AY187921 - Homo sapiens MLL/ENL fusion mRNA, partial sequence. S67825 - Homo sapiens ALL1-AF4 fusion protein mRNA, partial cds. FM165195 - Homo sapiens partial mRNA for MLL-ACTN4 fusion transcript in acute lymphoblastic leukemia, patient 3279. KT444629 - Homo sapiens KMT2A/AFF1 fusion variant 2, mRNA, breakpoint junction region, partial sequence. AF272377 - Homo sapiens clone 1370-48 MLL protein mRNA, partial cds. AF272372 - Homo sapiens clone 1373-24 aberrant MLL protein transcript, partial sequence. AF231996 - Homo sapiens MLL/GAS7 fusion protein (MLL/GAS7) mRNA, partial cds. AF272375 - Homo sapiens clone 1370-44 MLL/AF-10 fusion protein mRNA, partial cds. AF272378 - Homo sapiens clone 1370-57 MLL protein mRNA, partial cds. AF297746 - Homo sapiens clone 1426-11 MLL/GMPS fusion protein mRNA, partial cds. AF272373 - Homo sapiens clone 1373-13 aberrant MLL/ELL fusion protein transcript, partial sequence. AF272379 - Homo sapiens clone 1370-10 aberrant MLL protein transcript, partial sequence. AF272370 - Homo sapiens clone 1373-28 MLL protein mRNA, partial cds. AF231998 - Homo sapiens MLL/GAS7 fusion protein (MLL/GAS7) mRNA, partial cds. AF231999 - Homo sapiens MLL/GAS7 fusion protein (MLL/GAS7) mRNA, partial cds. AF232000 - Homo sapiens MLL protein (MLL) mRNA, partial cds. AF272380 - Homo sapiens clone 1370-23 MLL protein mRNA, partial cds. AF272371 - Homo sapiens clone 1373-39 MLL protein mRNA, partial cds. GU353067 - Homo sapiens MLL/BTBD18 fusion protein isoform 1 (MLL/BTBD18 fusion) mRNA, partial cds, alternatively spliced. MH319861 - Homo sapiens isolate 24 KMT2A-NEBL breakpoint junction mRNA sequence. JF938535 - Homo sapiens MLL/LOC100131626 fusion gene isoform 1, mRNA sequence. JF938536 - Homo sapiens MLL/LOC100131626 fusion gene isoform 2, mRNA sequence. FM165199 - Homo sapiens partial mRNA for MLL-TET1 fusion transcript in acute lymphoblastic leukemia, patient 4765. MH746808 - Homo sapiens KMT2A/AFF1 fusion protein mRNA, partial cds. DQ451148 - Homo sapiens MLL-AF4 fusion protein (MLL/AF4 fusion) mRNA, partial cds. AF272374 - Homo sapiens clone 1523 MLL/ELL fusion protein mRNA, partial cds. AY187944 - Homo sapiens transcription factor MLL UPN95022 mRNA, partial cds; alternatively spliced. AF231995 - Homo sapiens MLL/GAS7 fusion protein (MLL/GAS7) mRNA, partial cds. AY187920 - Homo sapiens MLL/p300 fusion mRNA, partial sequence. KJ754384 - Homo sapiens MLL/FLNA fusion protein (MLL/FLNA fusion) mRNA, partial cds. AF272383 - Homo sapiens clone 1568-1 MLL/AF-10 fusion protein mRNA, partial cds. AF297748 - Homo sapiens MLL/GMPS fusion protein mRNA, partial cds. AF061154 - Homo sapiens MLL/hCDCrel fusion protein mRNA, partial cds. DQ387206 - Homo sapiens chromosome der(11) MLL/AF6 fusion protein (MLL/AF6 fusion) mRNA, partial cds. AF272384 - Homo sapiens clone 1568-2 MLL/AF-10 fusion protein mRNA, partial cds. AF297749 - Homo sapiens MLL/GMPS fusion protein mRNA, partial cds. JN169752 - Homo sapiens MLL/AF4 fusion protein (MLL/AF4 fusion) mRNA, partial cds. FM165196 - Homo sapiens partial mRNA for MLL-TET1 fusion transcript in acute lymphoblastic leukemia, patient 3811. MH319862 - Homo sapiens isolate 24 NEBL-KMT2A breakpoint junction mRNA sequence. FM165194 - Homo sapiens partial mRNA for ACTN4-MLL fusion transcript in acute lymphoblastic leukemia, patient 3279. KT444631 - Homo sapiens AFF1/KMT2A fusion variant 1, mRNA, breakpoint junction region, partial sequence. MH128093 - Homo sapiens KMT2A-USP10 fusion protein mRNA, partial cds. S78571 - MLL {14p-18A} [human, mRNA Partial, 114 nt]. MN238629 - Homo sapiens isolate 25037 KMT2A/GAS7 fusion protein (KMT2A/GAS7 fusion) mRNA, partial cds. MN238630 - Homo sapiens isolate 29804 KMT2A/BTK fusion protein (KMT2A/BTK fusion) mRNA, partial cds. MN238624 - Homo sapiens isolate 4295 KMT2A/ARHGAP26 fusion protein (KMT2A/ARHGAP26 fusion) mRNA, partial cds. AF492830 - Homo sapiens CDK6/MLL fusion protein mRNA, partial cds. AK303179 - Homo sapiens cDNA FLJ56868 partial cds, highly similar to Zinc finger protein HRX. AK295635 - Homo sapiens cDNA FLJ56846 complete cds, highly similar to Zinc finger protein HRX.
Biochemical and Signaling Pathways
Reactome (by CSHL, EBI, and GO)
Protein Q03164 (Reactome details) participates in the following event(s):
R-HSA-8865482 KMT2A (MLL) binds RUNX1 R-HSA-8865491 RUNX1:CBFB:KMT2A binds SPI1 (PU.1) gene R-NUL-8865513 RUNX1 recruits KMT2A to the Spi1 gene R-HSA-8865498 KMT2A trimethylates nucleosomes at the SPI1 gene locus producing H3K4Me3 mark R-NUL-8865525 KTM2A trimethylates nucleosomes at the Spi1 gene locus producing H3K4Me3 mark R-HSA-8935740 RUNX1 and GATA1 bind the promoter of the ITGA2B gene R-HSA-8936616 RUNX1 and GATA1 bind the promoter of the GP1BA gene R-HSA-8936979 RUNX1 and GATA1 bind the promoter of the THBS1 gene R-HSA-8937037 RUNX1 and GATA1 bind the promoter of the MIR27A gene R-HSA-8936481 Core MLL complex methylates H3K4Me2-Nucleosome at the ITGA2B gene promoter R-HSA-8936621 Core MLL complex methylates H3K4Me2-Nucleosome at the GP1BA gene promoter R-HSA-8937016 Core MLL complex methylates H3K4Me2-Nucleosome at the THBS1 gene promoter R-HSA-8937050 Core MLL complex methylates H3K4Me2-Nucleosome at the MIR27A gene promoter R-HSA-5159245 SETD3, SETD7 (KMT7), WHSC1L1 (KMT3F), Core MLL complex methylate lysine-5 of histone H3 (H3K4) R-HSA-5244692 Core MLL complex, SMYD3, PRDM9 methylate dimethyl-lysine-5 of histone H3 (H3K4) R-HSA-5637686 WHSC1L1 (KMT3F), Core MLL complex, SMYD3 (KMT3E) methylate methyl-lysine-5 of histone H3 (H3K4) R-HSA-8939236 RUNX1 regulates transcription of genes involved in differentiation of HSCs R-HSA-8878171 Transcriptional regulation by RUNX1 R-HSA-8936459 RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function R-HSA-212436 Generic Transcription Pathway R-HSA-73857 RNA Polymerase II Transcription R-HSA-3214841 PKMTs methylate histone lysines R-HSA-74160 Gene expression (Transcription) R-HSA-3247509 Chromatin modifying enzymes R-HSA-4839726 Chromatin organization
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