Tclin DNMT3A DNA (cytosine-5)-methyltransferase 3A

Protein Summary

Description

Required for genome-wide de novo methylation and is essential for the establishment of DNA methylation patterns during development. DNA methylation is coordinated with methylation of histones. It modifies DNA in a non-processive manner and also methylates non-CpG sites. May preferentially methylate DNA linker between 2 nucleosomal cores and is inhibited by histone H1. Plays a role in paternal and maternal imprinting. Required for methylation of most imprinted loci in germ cells. Acts as a transcriptional corepressor for ZBTB18. Recruited to trimethylated 'Lys-36' of histone H3 (H3K36me3) sites. Can actively repress transcription through the recruitment of HDAC activity. CpG methylation is an epigenetic modification that is important for embryonic development, imprinting, and X-chromosome inactivation. Studies in mice have demonstrated that DNA methylation is required for mammalian development. This gene encodes a DNA methyltransferase that is thought to function in de novo methylation, rather than maintenance methylation. The protein localizes to the cytoplasm and nucleus and its expression is developmentally regulated. [provided by RefSeq, Mar 2016]

Uniprot Accession IDs

• Q9Y6K1
• E9PEB8
• Q86TE8
• Q86XF5
• Q8IZV0
• Q8WXU9
• Dnmt3a

Gene Name

• DNMT3A

Ensembl ID

• ENST00000264709
• ENSP00000264709
• ENSG00000119772
• ENST00000321117
• ENSP00000324375
• ENST00000380746
• ENSP00000370122
• ENST00000406659
• ENSP00000384852

Symbol

• TBRS
• DNMT3A2
• M.HsaIIIA

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
biological term	0.95
transcription factor	0.93
transcription factor binding site profile	0.92
PubMedID	0.9
transcription factor perturbation	0.88

Related Tools

Target Illumination GWAS Analytics (TIGA)

TIGA scores and ranks GWAS discovered associations according to the quantity and quality of the evidence supporting the association.

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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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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: 1157   (req: < 5)

Gene RIFs: 319   (req: <= 3)

Antibodies: 914   (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: 1157   (req: >= 5)

Gene RIFs: 319   (req: > 3)

Antibodies: 914   (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 Ligand: 1

Tclin

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

Active Drugs: 2

Approved Drugs (2)

Explore Approved Drugs

1 – 2 of 2

decitabine

DNMT3ATclin Epigenetic

INHIBITOR :

azacitidine

DNMT3ATclin Epigenetic

INHIBITOR :

Active Ligands (1)

Explore Active Ligands

1 – 1 of 1

CHEMBL2336409

DNMT3ATclin Epigenetic

EC50 : 6.05

GWAS Traits (19)

• Explore on Target Illumination GWAS Analytics (TIGA)

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GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
body height	EFO_0004339	3	2	3		90.4
BMI-adjusted waist-hip ratio	EFO_0007788	2	2	2		89.3
heel bone mineral density	EFO_0009270	2	1	2		88.2
BMI-adjusted waist circumference	EFO_0007789	4	2	8		66.3
hematocrit	EFO_0004348	2	2	2		66.3

• Explore on Target Illumination GWAS Analytics (TIGA)

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GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
body height	EFO_0004339	3		90.4
BMI-adjusted waist-hip ratio	EFO_0007788	2		89.3
heel bone mineral density	EFO_0009270	2		88.2
BMI-adjusted waist circumference	EFO_0007789	8		66.3
hematocrit	EFO_0004348	2		66.3

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Orthologs (11)

1 – 5 of 11

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	DNA methyltransferase 3 alpha	VGNC:219	739139
Macaque	DNA methyltransferase 3 alpha		694822
Mouse	DNA methyltransferase 3A	MGI:1261827	13435
Rat	DNA methyltransferase 3 alpha	RGD:1303336	444984
Dog	DNA methyltransferase 3 alpha	VGNC:40036	482996

Species	Name	OMA	EggNOG	Inparanoid
Chimp	DNA methyltransferase 3 alpha
Macaque	DNA methyltransferase 3 alpha
Mouse	DNA methyltransferase 3A
Rat	DNA methyltransferase 3 alpha
Dog	DNA methyltransferase 3 alpha

Protein Structure (13 Structures, 1 AlphaFold Model)

Representation

  axes   backbone   ball+stick   cartoon   rocket   rope   spacefill

Color Scheme

  target   atomindex   bfactor   chainname   electrostatic   element   hydrophobicity   resname   sstruc

Click on a row in the table to change the structure displayed.
More information can be found at RCSB PDB

AF-Q9Y6K1-F1-model_v1

AlphaFold Structures Developed by DeepMind and EMBL-EBI

1 – 5 of 13

PDB Structure Id	Ligand	Method	Resolution (Å)	Residues	Fraction of Total Protein	Pub Year	Title

PDB Structure Id	Fraction of Total Protein	Resolution	Pub Year

Pathways (32)

Reactome (12)

KEGG (3)

PathwayCommons (1)

WikiPathways (16)

Chromatin modifying enzymes (R-HSA-3247509)

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Find Similar Targets

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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	DNA methylation	34 targets	R-HSA-5334118
Reactome	Epigenetic regulation of gene expression	118 targets	R-HSA-212165
Reactome	Gene expression (Transcription)	1452 targets	R-HSA-74160

Name	Explore in Pharos	Explore in Source
Chromatin modifying enzymes	238 targets	R-HSA-3247509
Chromatin organization	238 targets	R-HSA-4839726
DNA methylation	34 targets	R-HSA-5334118
Epigenetic regulation of gene expression	118 targets	R-HSA-212165
Gene expression (Transcription)	1452 targets	R-HSA-74160

Gene Ontology Terms (38)

Functions (9)

Components (8)

Processes (21)

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Items per page:

10

1 – 9 of 9

GO Term	Evidence	Assigned by
DNA (cytosine-5-)-methyltransferase activity	Inferred from Direct Assay (IDA)	UniProtKB
DNA binding	Inferred from Direct Assay (IDA)	UniProtKB
RNA polymerase II proximal promoter sequence-specific DNA binding	Inferred from Direct Assay (IDA)	BHF-UCL
identical protein binding	Inferred from Physical Interaction (IPI)	IntAct
transcription factor binding	Inferred from Physical Interaction (IPI)	BHF-UCL
DNA-binding transcription factor activity, RNA polymerase II-specific	Inferred from Sequence Alignment (ISA)	NTNU_SB
DNA-methyltransferase activity	Traceable Author Statement (TAS)	Reactome
chromatin binding	Inferred from Electronic Annotation (IEA)	Ensembl
metal ion binding	Inferred from Electronic Annotation (IEA)	UniProtKB-KW

Protein-Protein Interactions (272)

Explore Interacting Targets

1 – 10 of 272

• See Interactions on String-DB

TCL1A

Tbio

Novelty: 0.00606987

p_int: 0.999999991

p_ni: 8e-9

Score: 0.531

Data Source: BioPlex,STRINGDB

DNMT3B

Tchem

Family: Epigenetic

Novelty: 0.00118766

p_int: 0.99999999

p_ni: 6e-9

p_wrong: 3e-9

Score: 0.972

Data Source: BioPlex,STRINGDB

DNMT1

Tclin

Family: Enzyme

Novelty: 0.00042336

Score: 0.996

Data Source: STRINGDB

EZH2

Tclin

Family: Epigenetic

Novelty: 0.00052816

Score: 0.991

Data Source: Reactome,STRINGDB

DNMT3L

Tbio

Family: Enzyme

Novelty: 0.0070698

Score: 0.99

Data Source: Reactome,STRINGDB

MYC

Tbio

Family: TF

Novelty: 0.00005734

Score: 0.981

Data Source: STRINGDB

PRMT5

Tchem

Family: Epigenetic

Novelty: 0.00395474

Score: 0.981

Data Source: STRINGDB

CBX4

Tchem

Family: Epigenetic

Novelty: 0.02681197

Score: 0.972

Data Source: STRINGDB

SUZ12

Tbio

Novelty: 0.00402353

Score: 0.966

Data Source: Reactome,STRINGDB

HIST2H2AC

Tbio

Novelty: 0.00065524

Score: 0.959

Data Source: STRINGDB

Publication Statistics

PubMed Score  1157.00

PubMed score by year

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PubTator Score  670.16

PubTator score by year

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Amino Acid Sequence

Residue Counts

Protein Sequence

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UniProt Keyword Find Similar Targets

3D-structure
Alternative promoter usage
Alternative splicing
Chromatin regulator
Complete proteome
Cytoplasm
Disease mutation
DNA-binding
Isopeptide bond
Mental retardation

GWAS Trait Find Similar Targets

BMI-adjusted waist circumference
BMI-adjusted waist-hip ratio
body height
Crohn's disease
heel bone mineral density
hematocrit
hemoglobin measurement
lymphocyte count
lymphocyte percentage of leukocytes
monocyte count

MGI Phenotype Find Similar Targets

adipose tissue phenotype
behavior/neurological phenotype
cellular phenotype
embryo phenotype
endocrine/exocrine gland phenotype
growth/size/body region phenotype
hematopoietic system phenotype
homeostasis/metabolism phenotype
immune system phenotype
mortality/aging