Tbio TCF3 Transcription factor E2-alpha

Protein Summary

Description

Transcriptional regulator. Involved in the initiation of neuronal differentiation. Heterodimers between TCF3 and tissue-specific basic helix-loop-helix (bHLH) proteins play major roles in determining tissue-specific cell fate during embryogenesis, like muscle or early B-cell differentiation. Dimers bind DNA on E-box motifs: 5'-CANNTG-3'. Binds to the kappa-E2 site in the kappa immunoglobulin gene enhancer. Binds to IEB1 and IEB2, which are short DNA sequences in the insulin gene transcription control region. This gene encodes a member of the E protein (class I) family of helix-loop-helix transcription factors. E proteins activate transcription by binding to regulatory E-box sequences on target genes as heterodimers or homodimers, and are inhibited by heterodimerization with inhibitor of DNA-binding (class IV) helix-loop-helix proteins. E proteins play a critical role in lymphopoiesis, and the encoded protein is required for B and T lymphocyte development. Deletion of this gene or diminished activity of the encoded protein may play a role in lymphoid malignancies. This gene is also involved in several chromosomal translocations that are associated with lymphoid malignancies including pre-B-cell acute lymphoblastic leukemia (t(1;19), with PBX1), childhood leukemia (t(19;19), with TFPT) and acute leukemia (t(12;19), with ZNF384). Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene, and a pseudogene of this gene is located on the short arm of chromosome 9. [provided by RefSeq, Sep 2011]

Uniprot Accession IDs

• P15923
• P15883
• Q14208
• Q14635
• Q14636
• Q2TB39
• Q2TB40
• Q9UPI9

Gene Name

• TCF3

Ensembl ID

• ENST00000262965
• ENSP00000262965
• ENSG00000071564
• ENST00000395423
• ENSP00000378813
• ENST00000588136
• ENSP00000468487
• ENST00000611869
• ENSP00000480564

Symbol

• BHLHB21
• E2A
• ITF1
• E2A
• E47
• p75
• AGM8
• ITF1
• VDIR
• TCF-3
• bHLHb21

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
molecular function	1
biological process	0.98
disease perturbation	0.97
PubMedID	0.97
hub protein	0.96

Protein Classes

PANTHER Classes

Protein / Transcription Factor / Basic Helix-loop-helix Transcription Factor / Transcription Factor E2-alpha

Protein / Nucleic Acid Binding / Transcription Factor E2-alpha

DTO Classes

Protein / Transcription Factor / Basic Helix-loop-helix Transcription Factor / Transcription Factor E2-alpha

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: 831.33   (req: < 5)

Gene RIFs: 94   (req: <= 3)

Antibodies: 533   (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: 831.33   (req: >= 5)

Gene RIFs: 94   (req: > 3)

Antibodies: 533   (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: 0

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)

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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Approved Drugs (0)

No approved drugs found

Active Ligands (0)

No active ligands found

Protein-Protein Interactions (226)

Explore Interacting Targets

1 – 10 of 226

• See Interactions on String-DB

FERD3L

Tbio

Family:  TF

Novelty:  0.06797434

p_int:  0.999999987

p_ni:  1.3e-8

Score:  0.813

Data Source:  BioPlex,STRINGDB

NEUROD1

Tbio

Family:  TF

Novelty:  0.00188624

p_int:  0.999999985

p_ni:  1.5e-8

Score:  0.975

Data Source:  BioPlex,STRINGDB

ID2

Tbio

Family:  TF

Novelty:  0.00256364

p_int:  0.999999936

p_ni:  6.4e-8

Score:  0.881

Data Source:  BioPlex,STRINGDB

NEUROG3

Tbio

Family:  TF

Novelty:  0.00341077

p_int:  0.999999935

p_ni:  6.5e-8

Score:  0.561

Data Source:  BioPlex,STRINGDB

MYF6

Tbio

Family:  TF

Novelty:  0.00509046

p_int:  0.99999991

p_ni:  9e-8

Score:  0.979

Data Source:  BioPlex,Reactome,STRINGDB

HAND2

Tbio

Family:  TF

Novelty:  0.00478924

p_int:  0.999999907

p_ni:  9.3e-8

Score:  0.644

Data Source:  BioPlex,STRINGDB

NHLH2

Tbio

Family:  TF

Novelty:  0.04744703

p_int:  0.999998322

p_ni:  0.000001678

Score:  0.464

Data Source:  BioPlex,STRINGDB

TWIST2

Tbio

Family:  TF

Novelty:  0.00748285

p_int:  0.999997523

p_ni:  0.000002477

Score:  0.645

Data Source:  BioPlex,STRINGDB

FKBP9

Tbio

Family:  Enzyme

Novelty:  0.16472204

p_int:  0.99962585

p_ni:  0.00037415

Score:  0.173

Data Source:  BioPlex,STRINGDB

TCF4

Tbio

Family:  TF

Novelty:  0.0019718

p_int:  0.996685679

p_ni:  0.003314301

p_wrong:  2e-8

Score:  0.983

Data Source:  BioPlex,STRINGDB

Nearest Tclin Targets (1)

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Upstream (1)

1 – 1 of 1

GSK3B

Tclin

Family:  Kinase

KEGG Distance:  2

Common Pathways:  1

1: Signaling pathways regulating pluripotency of stem cells

Pathways (22)

Reactome (7)

KEGG (3)

PathwayCommons (6)

WikiPathways (6)

Developmental Biology (R-HSA-1266738)

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1 – 5 of 7

Data Source	Name	Explore in Pharos	Explore in Source
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
Reactome	Myogenesis	29 targets	R-HSA-525793
Reactome	RNA Polymerase II Transcription	1314 targets	R-HSA-73857

Name	Explore in Pharos	Explore in Source
Developmental Biology	1055 targets	R-HSA-1266738
Gene expression (Transcription)	1452 targets	R-HSA-74160
Generic Transcription Pathway	1195 targets	R-HSA-212436
Myogenesis	29 targets	R-HSA-525793
RNA Polymerase II Transcription	1314 targets	R-HSA-73857

Viral Interactions (0)

No viral interactions found

Gene Ontology Terms (38)

Functions (15)

Components (8)

Processes (15)

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1 – 10 of 15

GO Term	Evidence	Assigned by
DNA binding	Inferred from Direct Assay (IDA)	UniProtKB
DNA-binding transcription factor activity	Inferred from Direct Assay (IDA)	BHF-UCL
E-box binding	Inferred from Direct Assay (IDA)	UniProtKB
protein heterodimerization activity	Inferred from Direct Assay (IDA)	UniProtKB
protein homodimerization activity	Inferred from Direct Assay (IDA)	UniProtKB
proximal promoter DNA-binding transcription repressor activity, RNA polymerase II-specific	Inferred from Direct Assay (IDA)	NTNU_SB
RNA polymerase II proximal promoter sequence-specific DNA binding	Inferred from Direct Assay (IDA)	NTNU_SB
transcription coactivator activity	Inferred from Direct Assay (IDA)	UniProtKB
vitamin D response element binding	Inferred from Direct Assay (IDA)	BHF-UCL
bHLH transcription factor binding	Inferred from Physical Interaction (IPI)	BHF-UCL

Disease Associations ()

No disease associations found

GWAS Traits (4)

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1 – 4 of 4

GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
Hodgkins lymphoma	EFO_0000183	1	1	0	1.2	39.6
type II diabetes mellitus	EFO_0001360	1	1	1		17.8
Urinary retention	HP_0000016	1	1	0	7.8	3.7
response to radiation	GO_0009314	1	1	0	7.8	3.7

• Explore on Target Illumination GWAS Analytics (TIGA)

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1 – 4 of 4

GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
Hodgkins lymphoma	EFO_0000183	0	1.2	39.6
type II diabetes mellitus	EFO_0001360	1		17.8
Urinary retention	HP_0000016	0	7.8	3.7
response to radiation	GO_0009314	0	7.8	3.7

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UniProt Keyword Find Similar Targets

No Header	No Header
3D-structure
Alternative splicing
Chromosomal rearrangement
Complete proteome
Differentiation
Disease mutation
DNA-binding
Isopeptide bond
Methylation
Neurogenesis

GWAS Trait Find Similar Targets

No Header	No Header
Hodgkins lymphoma
response to radiation
type II diabetes mellitus
Urinary retention

MGI Phenotype Find Similar Targets

No Header	No Header
cellular phenotype
endocrine/exocrine gland phenotype
growth/size/body region phenotype
hematopoietic system phenotype
homeostasis/metabolism phenotype
immune system phenotype
mortality/aging
neoplasm
reproductive 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	transcription factor 3	VGNC:13532	468650
Macaque	transcription factor 3		721325
Mouse	transcription factor 3	MGI:98510	21423
Rat	transcription factor 3	RGD:620914	171046
Dog	transcription factor 3 [Source:HGNC Symbol;Acc:HGNC:11633]

Species	Name	OMA	EggNOG	Inparanoid
Chimp	transcription factor 3
Macaque	transcription factor 3
Mouse	transcription factor 3
Rat	transcription factor 3
Dog	transcription factor 3 [Source:HGNC Symbol;Acc:HGNC:11633]

Publication Statistics

PubMed Score 831.33

PubMed score by year

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PubTator Score 402.06

PubTator score by year

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Related Publications

Text Mined References (188)

GeneRif Annotations (94)

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PMID	Year	Title