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: 568.2   (req: < 5)

Gene RIFs: 358   (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: 568.2   (req: >= 5)

Gene RIFs: 358   (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: 5

Tclin

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

Active Drug: 0

Protein Sequence and Structure

Residue Counts

Protein Sequence

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Expression Data (0 Tissues)

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No expression data found

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Target Illumination GWAS Analytics (TIGA)

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GENEVA

GENEVA (GENe Expression Variance Analysis) allows you to identify RNA-sequencing datasets from the Gene Expression Omnibus (GEO) that contain conditions modulating a gene or a gene signature.

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GlyGen

GlyGen is a data integration and dissemination project for carbohydrate and glycoconjugate related data.

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ARCHS4

ARCHS4 provides access to gene-function predictions based on RNA-seq co-expression, and gene expression levels across cell and tissues.

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Approved Drugs (0)

No approved drugs found

Active Ligands (5)

Explore Active Ligands

1 – 5 of 5

CHEMBL3798088

KMT2ATchem Epigenetic

pIC50 : 9.05

CHEMBL3883592

KMT2ATchem Epigenetic

pIC50 : 8.77

CHEMBL3799591

KMT2ATchem Epigenetic

pIC50 : 8.54

CHEMBL3957384

KMT2ATchem Epigenetic

pIC50 : 8.35

Verticillin A

KMT2ATchem Epigenetic

pIC50 : 6.1

Protein-Protein Interactions (259)

Explore Interacting Targets

1 – 10 of 259

• See Interactions on String-DB

HCFC2

Tbio

Novelty:  0.12260416

p_int:  0.999999828

p_ni:  1.4e-7

p_wrong:  3.2e-8

Score:  0.834

Data Source:  BioPlex,STRINGDB

WDR5

Tchem

Novelty:  0.0059945

p_int:  0.999998346

p_ni:  0.000001642

p_wrong:  1.2e-8

Score:  0.992

Data Source:  BioPlex,STRINGDB

CSNK2B

Tbio

Family:  Kinase

Novelty:  0.00152367

p_int:  0.999998045

p_ni:  0.000001955

Data Source:  BioPlex

CSNK2A2

Tchem

Family:  Kinase

Novelty:  0.00231447

p_int:  0.9999576

p_ni:  0.000042399

p_wrong:  1e-9

Score:  0.233

Data Source:  BioPlex,STRINGDB

PIH1D1

Tbio

Novelty:  0.10737369

p_int:  0.986706964

p_ni:  0.013293035

Score:  0.551

Data Source:  BioPlex,STRINGDB

ASB7

Tdark

Novelty:  0.21883348

p_int:  0.982902062

p_ni:  0.017097937

p_wrong:  1e-9

Score:  0.547

Data Source:  BioPlex,STRINGDB

EP300

Tchem

Family:  Epigenetic

Novelty:  0.00055009

Score:  0.993

Data Source:  STRINGDB

RBBP5

Tbio

Novelty:  0.02221059

Score:  0.991

Data Source:  STRINGDB

ASH2L

Tbio

Family:  Enzyme

Novelty:  0.01586766

Score:  0.99

Data Source:  STRINGDB

KMT2C

Tbio

Family:  Epigenetic

Novelty:  0.00689437

Score:  0.988

Data Source:  STRINGDB

Nearest Tclin Targets

Nearest Tclin calculations are only available for targets with KEGG Pathway annotations.

Pathways (17)

Reactome (11)

KEGG (3)

WikiPathways (3)

Chromatin modifying enzymes (R-HSA-3247509)

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5

1 – 5 of 11

Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Chromatin modifying enzymes	238 targets	R-HSA-3247509
Reactome	Chromatin organization	238 targets	R-HSA-4839726
Reactome	Developmental Biology	1055 targets	R-HSA-1266738
Reactome	Gene expression (Transcription)	1452 targets	R-HSA-74160
Reactome	Generic Transcription Pathway	1195 targets	R-HSA-212436

Name	Explore in Pharos	Explore in Source
Chromatin modifying enzymes	238 targets	R-HSA-3247509
Chromatin organization	238 targets	R-HSA-4839726
Developmental Biology	1055 targets	R-HSA-1266738
Gene expression (Transcription)	1452 targets	R-HSA-74160
Generic Transcription Pathway	1195 targets	R-HSA-212436

Viral Interactions (0)

No viral interactions found

Gene Ontology Terms (35)

Functions (12)

Components (5)

Processes (18)

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10

1 – 10 of 12

GO Term	Evidence	Assigned by
histone methyltransferase activity (H3-K4 specific)	Inferred from Direct Assay (IDA)	UniProtKB
lysine-acetylated histone binding	Inferred from Direct Assay (IDA)	UniProtKB
protein homodimerization activity	Inferred from Direct Assay (IDA)	UniProtKB
transcription regulatory region DNA binding	Inferred from Direct Assay (IDA)	UniProtKB
unmethylated CpG binding	Inferred from Direct Assay (IDA)	UniProtKB
zinc ion binding	Inferred from Direct Assay (IDA)	UniProtKB
identical protein binding	Inferred from Physical Interaction (IPI)	IntAct
RNA polymerase II distal enhancer sequence-specific DNA binding	Inferred from Sequence or structural Similarity (ISS)	UniProtKB
DNA-binding transcription factor activity, RNA polymerase II-specific	Inferred from Sequence Alignment (ISA)	NTNU_SB
histone-lysine N-methyltransferase activity	Traceable Author Statement (TAS)	Reactome

Disease Associations ()

No disease associations found

GWAS Traits (21)

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5

1 – 5 of 21

GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
glioma	EFO_0005543	5	3	0	1.4	94.9
central nervous system cancer	EFO_0000326	6	2	0	1.3	92.2
multiple sclerosis	EFO_0003885	1	1	0	1.1	67.4
triglyceride measurement	EFO_0004530	2	1	2		64.4
hematocrit	EFO_0004348	2	2	2		64.2

• Explore on Target Illumination GWAS Analytics (TIGA)

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1 – 5 of 21

GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
glioma	EFO_0005543	0	1.4	94.9
central nervous system cancer	EFO_0000326	0	1.3	92.2
multiple sclerosis	EFO_0003885	0	1.1	67.4
triglyceride measurement	EFO_0004530	2		64.4
hematocrit	EFO_0004348	2		64.2

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UniProt Keyword Find Similar Targets

No Header	No Header
3D-structure
Acetylation
Alternative splicing
Apoptosis
Biological rhythms
Bromodomain
Chromatin regulator
Chromosomal rearrangement
Complete proteome
Direct protein sequencing

GWAS Trait Find Similar Targets

No Header	No Header
age-related hearing impairment
alkaline phosphatase measurement
apolipoprotein A 1 measurement
celiac disease
central nervous system cancer
depressive symptom measurement
glioma
hematocrit
hemoglobin measurement
high density lipoprotein cholesterol measurement

MGI Phenotype Find Similar Targets

No Header	No Header
behavior/neurological phenotype
cardiovascular system phenotype
cellular phenotype
craniofacial phenotype
embryo phenotype
growth/size/body region phenotype
hearing/vestibular/ear phenotype
hematopoietic system phenotype
homeostasis/metabolism phenotype
immune system phenotype

IDG Resources

No IDG generated resources found

Orthologs (11)

1 – 5 of 11

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	lysine methyltransferase 2A	VGNC:7657	451587
Macaque	lysine methyltransferase 2A		705511
Mouse	lysine (K)-specific methyltransferase 2A	MGI:96995	214162
Rat	lysine methyltransferase 2A	RGD:1586165	315606
Dog	lysine methyltransferase 2A	VGNC:42489	479417

Species	Name	OMA	EggNOG	Inparanoid
Chimp	lysine methyltransferase 2A
Macaque	lysine methyltransferase 2A
Mouse	lysine (K)-specific methyltransferase 2A
Rat	lysine methyltransferase 2A
Dog	lysine methyltransferase 2A

Publication Statistics

PubMed Score 568.20

PubMed score by year

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PubTator Score 1651.79

PubTator score by year

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Related Publications

Text Mined References (426)

GeneRif Annotations (358)

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PMID	Year	Title