UniProt functional annotation for Q03164



	UniProt functional annotation for Q03164

UniProt code: Q03164.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: 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). In the MLL1/MLL complex, it specifically mediates H3K4me, a specific tag for epigenetic transcriptional activation (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). {ECO:0000250|UniProtKB:P55200, ECO:0000269|PubMed:10490642, ECO:0000269|PubMed:12453419, ECO:0000269|PubMed:15960975, ECO:0000269|PubMed:19187761, ECO:0000269|PubMed:19556245, ECO:0000269|PubMed:20010842, ECO:0000269|PubMed:21220120, ECO:0000269|PubMed:24235145, ECO:0000269|PubMed:26886794, ECO:0000305|PubMed:20677832}.

Catalytic activity: Reaction=L-lysyl(4)-[histone H3] + 3 S-adenosyl-L-methionine = 3 H(+) + N(6),N(6),N(6)-trimethyl-L-lysyl(4)-[histone H3] + 3 S-adenosyl-L- homocysteine; Xref=Rhea:RHEA:60260, Rhea:RHEA-COMP:15537, Rhea:RHEA- COMP:15547, ChEBI:CHEBI:15378, ChEBI:CHEBI:29969, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:61961; EC=2.1.1.354; Evidence={ECO:0000269|PubMed:12453419, ECO:0000269|PubMed:19187761, ECO:0000269|PubMed:24235145, ECO:0000269|PubMed:26886794}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60261; Evidence={ECO:0000269|PubMed:24235145};

Catalytic activity: Reaction=L-cysteinyl-[protein] + S-adenosyl-L-methionine = H(+) + S- adenosyl-L-homocysteine + S-methyl-L-cysteinyl-[protein]; Xref=Rhea:RHEA:66544, Rhea:RHEA-COMP:10131, Rhea:RHEA-COMP:10132, ChEBI:CHEBI:15378, ChEBI:CHEBI:29950, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:82612; Evidence={ECO:0000269|PubMed:24235145}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66545; Evidence={ECO:0000269|PubMed:24235145};

Biophysicochemical properties: Kinetic parameters: KM=10.4 uM for S-adenosyl-L-methionine (for histone-lysine N- methyltransferase activity) {ECO:0000269|PubMed:24235145}; KM=6.5 uM for S-adenosyl-L-methionine (for protein-cysteine methyltransferase) {ECO:0000269|PubMed:24235145};

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 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 (PubMed:15199122, PubMed:15960975, PubMed:17500065, PubMed:19556245, PubMed:19187761, PubMed:26886794). Interacts (via WIN motif) with WDR5; the interaction is direct (PubMed:19556245, PubMed:18829459, PubMed:22665483, PubMed:18840606). Interaction with WDR5 is required for stable interaction with ASH2L and RBBP5, and thereby also for optimal histone methyltransferase activity (PubMed:26886794). Interacts with KAT8/MOF; the interaction is direct (PubMed:15960975). Interacts with SBF1 and PPP1R15A (PubMed:9537414, PubMed:10490642). Interacts with ZNF335 (PubMed:23178126). Interacts with CLOCK and ARNTL/BMAL1 in a circadian manner (By similarity). Interacts with PPIE; this results in decreased histone H3 methyltransferase activity (PubMed:20677832, PubMed:20541251). Interacts with CREBBP (PubMed:16253272). Interacts with the WRAD complex composed of WDR5, RBBP5, ASH2L and DPY30 (PubMed:22665483). Interacts (via MBM motif) with MEN1 (PubMed:22936661, PubMed:22327296, PubMed:25305204). Interacts (via IBM motifs) with PSIP1 (via IBD domain) with moderate affinity whereas the KMT2A-MEN1 complex interacts with a greater affinity; MEN1 enhances interaction of KMT2A with PSIP1 (PubMed:22327296, PubMed:25305204, PubMed:25082813, PubMed:29997176). Phosphorylation increases its affinity for PSIP1 (PubMed:29997176). Forms a complex with CREBBP and CREB1 (PubMed:23651431). {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:18840606, ECO:0000269|PubMed:19187761, ECO:0000269|PubMed:19556245, ECO:0000269|PubMed:20541251, ECO:0000269|PubMed:20677832, ECO:0000269|PubMed:21220120, ECO:0000269|PubMed:22327296, ECO:0000269|PubMed:22665483, ECO:0000269|PubMed:23178126, ECO:0000269|PubMed:23651431, ECO:0000269|PubMed:25082813, ECO:0000269|PubMed:25305204, ECO:0000269|PubMed:26886794, ECO:0000269|PubMed:29997176, ECO:0000269|PubMed:9537414}.

Subcellular location: Nucleus {ECO:0000269|PubMed:12482972}.

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. {ECO:0000269|PubMed:17467953}.

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. {ECO:0000269|PubMed:19187761, ECO:0000269|PubMed:26886794}.

Domain: The CXXC-type zinc finger binds to DNA sequence elements containing unnmethylated CpG dinucleotides. {ECO:0000269|PubMed:16990798, ECO:0000269|PubMed:20010842, ECO:0000269|PubMed:29276034}.

Domain: The third PHD-type zinc-finger binds both trimethylated histone H3K4me3 and PPIE; histone and PPIE bind to distinct surfaces (PubMed:20677832, PubMed:20541251). Nevertheless, PPIE binding and histone binding are mutually inhibitory (PubMed:20677832). Isomerization of a peptidylproline bond in the linker between the third PHD-type zinc-finger and the bromo domain disrupts the interaction between the bromo domain and the third PHD-type zinc-finger, and thereby facilitates interaction with PPIE (PubMed:20541251). {ECO:0000269|PubMed:20541251, ECO:0000269|PubMed:20677832}.

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. {ECO:0000269|PubMed:12482972, ECO:0000269|PubMed:14636557}.

Ptm: Phosphorylation increases its interaction with PSIP1. {ECO:0000269|PubMed:29997176}.

Ptm: Auto-methylated at Cys-3882: auto-methylation is inhibited by the WRAD complex and unmodified histone H3. {ECO:0000269|PubMed:24235145}.

Disease: Wiedemann-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 variants affecting the gene represented in this entry.

Disease: Note=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). {ECO:0000269|PubMed:10490642, ECO:0000269|PubMed:22936661, ECO:0000269|PubMed:25305204}.

Disease: Note=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}.

Similarity: Belongs to the class V-like SAM-binding methyltransferase superfamily. Histone-lysine methyltransferase family. TRX/MLL subfamily. {ECO:0000255|PROSITE-ProRule:PRU00190}.

Sequence caution: Sequence=AAA58669.1; Type=Frameshift; Evidence={ECO:0000305}; Sequence=AAG26332.2; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305}; Sequence=BAD92745.1; Type=Frameshift; Evidence={ECO:0000305};

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		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). In the MLL1/MLL complex, it specifically mediates H3K4me, a specific tag for epigenetic transcriptional activation (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). {ECO:0000250\|UniProtKB:P55200, ECO:0000269\|PubMed:10490642, ECO:0000269\|PubMed:12453419, ECO:0000269\|PubMed:15960975, ECO:0000269\|PubMed:19187761, ECO:0000269\|PubMed:19556245, ECO:0000269\|PubMed:20010842, ECO:0000269\|PubMed:21220120, ECO:0000269\|PubMed:24235145, ECO:0000269\|PubMed:26886794, ECO:0000305\|PubMed:20677832}.


Catalytic activity:		Reaction=L-lysyl(4)-[histone H3] + 3 S-adenosyl-L-methionine = 3 H(+) + N(6),N(6),N(6)-trimethyl-L-lysyl(4)-[histone H3] + 3 S-adenosyl-L- homocysteine; Xref=Rhea:RHEA:60260, Rhea:RHEA-COMP:15537, Rhea:RHEA- COMP:15547, ChEBI:CHEBI:15378, ChEBI:CHEBI:29969, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:61961; EC=2.1.1.354; Evidence={ECO:0000269\|PubMed:12453419, ECO:0000269\|PubMed:19187761, ECO:0000269\|PubMed:24235145, ECO:0000269\|PubMed:26886794}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60261; Evidence={ECO:0000269\|PubMed:24235145};
Catalytic activity:		Reaction=L-cysteinyl-[protein] + S-adenosyl-L-methionine = H(+) + S- adenosyl-L-homocysteine + S-methyl-L-cysteinyl-[protein]; Xref=Rhea:RHEA:66544, Rhea:RHEA-COMP:10131, Rhea:RHEA-COMP:10132, ChEBI:CHEBI:15378, ChEBI:CHEBI:29950, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:82612; Evidence={ECO:0000269\|PubMed:24235145}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66545; Evidence={ECO:0000269\|PubMed:24235145};
Biophysicochemical properties:		Kinetic parameters: KM=10.4 uM for S-adenosyl-L-methionine (for histone-lysine N- methyltransferase activity) {ECO:0000269\|PubMed:24235145}; KM=6.5 uM for S-adenosyl-L-methionine (for protein-cysteine methyltransferase) {ECO:0000269\|PubMed:24235145};
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 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 (PubMed:15199122, PubMed:15960975, PubMed:17500065, PubMed:19556245, PubMed:19187761, PubMed:26886794). Interacts (via WIN motif) with WDR5; the interaction is direct (PubMed:19556245, PubMed:18829459, PubMed:22665483, PubMed:18840606). Interaction with WDR5 is required for stable interaction with ASH2L and RBBP5, and thereby also for optimal histone methyltransferase activity (PubMed:26886794). Interacts with KAT8/MOF; the interaction is direct (PubMed:15960975). Interacts with SBF1 and PPP1R15A (PubMed:9537414, PubMed:10490642). Interacts with ZNF335 (PubMed:23178126). Interacts with CLOCK and ARNTL/BMAL1 in a circadian manner (By similarity). Interacts with PPIE; this results in decreased histone H3 methyltransferase activity (PubMed:20677832, PubMed:20541251). Interacts with CREBBP (PubMed:16253272). Interacts with the WRAD complex composed of WDR5, RBBP5, ASH2L and DPY30 (PubMed:22665483). Interacts (via MBM motif) with MEN1 (PubMed:22936661, PubMed:22327296, PubMed:25305204). Interacts (via IBM motifs) with PSIP1 (via IBD domain) with moderate affinity whereas the KMT2A-MEN1 complex interacts with a greater affinity; MEN1 enhances interaction of KMT2A with PSIP1 (PubMed:22327296, PubMed:25305204, PubMed:25082813, PubMed:29997176). Phosphorylation increases its affinity for PSIP1 (PubMed:29997176). Forms a complex with CREBBP and CREB1 (PubMed:23651431). {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:18840606, ECO:0000269\|PubMed:19187761, ECO:0000269\|PubMed:19556245, ECO:0000269\|PubMed:20541251, ECO:0000269\|PubMed:20677832, ECO:0000269\|PubMed:21220120, ECO:0000269\|PubMed:22327296, ECO:0000269\|PubMed:22665483, ECO:0000269\|PubMed:23178126, ECO:0000269\|PubMed:23651431, ECO:0000269\|PubMed:25082813, ECO:0000269\|PubMed:25305204, ECO:0000269\|PubMed:26886794, ECO:0000269\|PubMed:29997176, ECO:0000269\|PubMed:9537414}.
Subcellular location:		Nucleus {ECO:0000269\|PubMed:12482972}.
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. {ECO:0000269\|PubMed:17467953}.
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. {ECO:0000269\|PubMed:19187761, ECO:0000269\|PubMed:26886794}.
Domain:		The CXXC-type zinc finger binds to DNA sequence elements containing unnmethylated CpG dinucleotides. {ECO:0000269\|PubMed:16990798, ECO:0000269\|PubMed:20010842, ECO:0000269\|PubMed:29276034}.
Domain:		The third PHD-type zinc-finger binds both trimethylated histone H3K4me3 and PPIE; histone and PPIE bind to distinct surfaces (PubMed:20677832, PubMed:20541251). Nevertheless, PPIE binding and histone binding are mutually inhibitory (PubMed:20677832). Isomerization of a peptidylproline bond in the linker between the third PHD-type zinc-finger and the bromo domain disrupts the interaction between the bromo domain and the third PHD-type zinc-finger, and thereby facilitates interaction with PPIE (PubMed:20541251). {ECO:0000269\|PubMed:20541251, ECO:0000269\|PubMed:20677832}.
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. {ECO:0000269\|PubMed:12482972, ECO:0000269\|PubMed:14636557}.
Ptm:		Phosphorylation increases its interaction with PSIP1. {ECO:0000269\|PubMed:29997176}.
Ptm:		Auto-methylated at Cys-3882: auto-methylation is inhibited by the WRAD complex and unmodified histone H3. {ECO:0000269\|PubMed:24235145}.
Disease:		Wiedemann-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 variants affecting the gene represented in this entry.
Disease:		Note=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). {ECO:0000269\|PubMed:10490642, ECO:0000269\|PubMed:22936661, ECO:0000269\|PubMed:25305204}.
Disease:		Note=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}.
Similarity:		Belongs to the class V-like SAM-binding methyltransferase superfamily. Histone-lysine methyltransferase family. TRX/MLL subfamily. {ECO:0000255\|PROSITE-ProRule:PRU00190}.
Sequence caution:		Sequence=AAA58669.1; Type=Frameshift; Evidence={ECO:0000305}; Sequence=AAG26332.2; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305}; Sequence=BAD92745.1; Type=Frameshift; Evidence={ECO:0000305};