Tbio TET3 Methylcytosine dioxygenase TET3

Protein Summary

Description

Dioxygenase that catalyzes the conversion of the modified genomic base 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC) and plays a key role in epigenetic chromatin reprogramming in the zygote following fertilization. Also mediates subsequent conversion of 5hmC into 5-formylcytosine (5fC), and conversion of 5fC to 5-carboxylcytosine (5caC). Conversion of 5mC into 5hmC, 5fC and 5caC probably constitutes the first step in cytosine demethylation (By similarity). Selectively binds to the promoter region of target genes and contributes to regulate the expression of numerous developmental genes (PubMed:23217707). In zygotes, DNA demethylation occurs selectively in the paternal pronucleus before the first cell division, while the adjacent maternal pronucleus and certain paternally-imprinted loci are protected from this process. Participates in DNA demethylation in the paternal pronucleus by mediating conversion of 5mC into 5hmC, 5fC and 5caC. Does not mediate DNA demethylation of maternal pronucleus because of the presence of DPPA3/PGC7 on maternal chromatin that prevents TET3-binding to chromatin (By similarity). In addition to its role in DNA demethylation, also involved in the recruitment of the O-GlcNAc transferase OGT to CpG-rich transcription start sites of active genes, thereby promoting histone H2B GlcNAcylation by OGT (PubMed:23353889). Members of the ten-eleven translocation (TET) gene family, including TET3, play a role in the DNA methylation process (Langemeijer et al., 2009 [PubMed 19923888]).[supplied by OMIM, Nov 2010]

Uniprot Accession IDs

• O43151
• A6NEI3
• K9JJH7
• Q86Z24
• Q8TBM9

Gene Name

• TET3

Ensembl ID

• ENST00000409262
• ENSP00000386869
• ENSG00000187605

Symbol

• KIAA0401
• hCG_40738

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
virus perturbation	0.79
biological process	0.73
cell line	0.68
small molecule perturbation	0.63
microRNA	0.59

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GENEVA

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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: 174.13   (req: < 5)

Gene RIFs: 33   (req: <= 3)

Antibodies: 286   (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: 174.13   (req: >= 5)

Gene RIFs: 33   (req: > 3)

Antibodies: 286   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 10

Tchem

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

Active Ligand: 0

Tclin

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

Active Drug: 0

GWAS Traits (6)

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GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
alcohol consumption measurement	EFO_0007878	2	1	2		83.7
smoking status measurement	EFO_0006527	1	1	1		75.2
eosinophil count	EFO_0004842	2	2	2		66.9
self reported educational attainment	EFO_0004784	1	1	1		60
risk-taking behaviour	EFO_0008579	2	1	2		46.1

• Explore on Target Illumination GWAS Analytics (TIGA)

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GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
alcohol consumption measurement	EFO_0007878	2		83.7
smoking status measurement	EFO_0006527	1		75.2
eosinophil count	EFO_0004842	2		66.9
self reported educational attainment	EFO_0004784	1		60
risk-taking behaviour	EFO_0008579	2		46.1

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Orthologs (9)

1 – 5 of 9

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	tet methylcytosine dioxygenase 3	VGNC:10784	459329
Macaque	tet methylcytosine dioxygenase 3		707759
Mouse	tet methylcytosine dioxygenase 3	MGI:2446229	194388
Rat	tet methylcytosine dioxygenase 3	RGD:1590584	680576
Dog	tet methylcytosine dioxygenase 3	VGNC:47262	483109

Species	Name	OMA	EggNOG	Inparanoid
Chimp	tet methylcytosine dioxygenase 3
Macaque	tet methylcytosine dioxygenase 3
Mouse	tet methylcytosine dioxygenase 3
Rat	tet methylcytosine dioxygenase 3
Dog	tet methylcytosine dioxygenase 3

Protein Structure (1 Structure, 1 AlphaFold Model)

Representation

  axes   backbone   ball+stick   cartoon   rocket   rope   spacefill

Color Scheme

  target   atomindex   bfactor   chainname   electrostatic   element   hydrophobicity   resname   sstruc

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More information can be found at RCSB PDB

AF-O43151-F1-model_v1

AlphaFold Structures Developed by DeepMind and EMBL-EBI

1 – 1 of 1

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 (5)

Reactome (3)

WikiPathways (2)

Epigenetic regulation of gene expression (R-HSA-212165)

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Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Epigenetic regulation of gene expression	118 targets	R-HSA-212165
Reactome	Gene expression (Transcription)	1452 targets	R-HSA-74160
Reactome	TET1,2,3 and TDG demethylate DNA	4 targets	R-HSA-5221030

Name	Explore in Pharos	Explore in Source
Epigenetic regulation of gene expression	118 targets	R-HSA-212165
Gene expression (Transcription)	1452 targets	R-HSA-74160
TET1,2,3 and TDG demethylate DNA	4 targets	R-HSA-5221030

Gene Ontology Terms (15)

Functions (4)

Components (5)

Processes (6)

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Items per page:

10

1 – 4 of 4

GO Term	Evidence	Assigned by
iron ion binding	Inferred from Biological aspect of Ancestor (IBA)	GO_Central
methylcytosine dioxygenase activity	Inferred from Sequence or structural Similarity (ISS)	UniProtKB
DNA-binding transcription factor activity, RNA polymerase II-specific	Inferred from Sequence Alignment (ISA)	NTNU_SB
DNA binding	Inferred from Electronic Annotation (IEA)	UniProtKB-KW

Protein-Protein Interactions (55)

Explore Interacting Targets

1 – 10 of 55

• See Interactions on String-DB

NUP62CL

Tdark

Novelty: 2.93223607

p_int: 0.999999915

p_ni: 1.1e-8

p_wrong: 7.4e-8

Data Source: BioPlex

DNMT3A

Tclin

Family: Epigenetic

Novelty: 0.00085974

Score: 0.824

Data Source: STRINGDB

TDG

Tbio

Family: Enzyme

Novelty: 0.00283178

Score: 0.813

Data Source: STRINGDB

DPPA3

Tbio

Novelty: 0.03361743

Score: 0.801

Data Source: STRINGDB

PRMT5

Tchem

Family: Epigenetic

Novelty: 0.00395474

Score: 0.8

Data Source: STRINGDB

DNMT1

Tclin

Family: Enzyme

Novelty: 0.00042336

Score: 0.792

Data Source: STRINGDB

OGDH

Tbio

Family: Enzyme

Novelty: 0.00674601

Score: 0.752

Data Source: STRINGDB

DNMT3B

Tchem

Family: Epigenetic

Novelty: 0.00118766

Score: 0.724

Data Source: STRINGDB

CA2

Tclin

Family: Enzyme

Novelty: 0.00040118

Score: 0.71

Data Source: STRINGDB

NANOG

Tbio

Family: TF

Novelty: 0.00054893

Score: 0.689

Data Source: STRINGDB

Publication Statistics

PubMed Score  174.13

PubMed score by year

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PubTator Score  69.84

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 splicing
Chromatin regulator
Chromosome
Complete proteome
Cytoplasm
Developmental protein
Dioxygenase
DNA-binding
Iron

GWAS Trait Find Similar Targets

alcohol consumption measurement
eosinophil count
eosinophil percentage of leukocytes
risk-taking behaviour
self reported educational attainment
smoking status measurement

MGI Phenotype Find Similar Targets

cellular phenotype
reproductive system phenotype