Tchem KMT2A Histone-lysine N-methyltransferase 2A

Protein Summary

Description

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 (PubMed:12453419, PubMed:20677832, 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'. 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. 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). 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]

Uniprot Accession IDs

• Q03164
• E9PQG7
• Q13743
• Q13744
• Q14845
• Q16364
• Q59FF2
• Q6UBD1
• Q9HBJ3
• Q9UD94
• Q9UMA3
• Lysine N-methyltransferase 2A

Gene Name

• KMT2A

Ensembl ID

• ENST00000389506
• ENSP00000374157
• ENSG00000118058
• ENST00000534358
• ENSP00000436786
• ENST00000649699
• ENSP00000496927

Symbol

• ALL1
• CXXC7
• HRX
• HTRX
• MLL
• MLL1
• TRX1
• HRX
• MLL
• MLL1
• TRX1
• ALL-1
• CXXC7
• HTRX1
• MLL1A
• WDSTS

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
gene perturbation	1
protein domain	1
molecular function	0.99
biological process	0.96
drug perturbation	0.87

Protein Classes

No PANTHER Classes or DTO Classes found

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 730.04   (req: < 5)

Gene RIFs: 466   (req: <= 3)

Antibodies: 429   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 730.04   (req: >= 5)

Gene RIFs: 466   (req: > 3)

Antibodies: 429   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 30

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 6

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0