TCF3

TCF3
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2MH0, 2YPA, 2YPB, 3U5V
Identifiers
Aliases	TCF3, E2A, E47, ITF1, TCF-3, VDIR, bHLHb21, AGM8, transcription factor 3
External IDs	MGI: 98510 HomoloGene: 2408 GeneCards: TCF3
Genetically Related Diseases
Hodgkin's lymphoma[1]
Gene ontology Molecular function • DNA binding • sequence-specific DNA binding • protein dimerization activity • protein homodimerization activity • transcription factor activity, sequence-specific DNA binding • mitogen-activated protein kinase kinase kinase binding • vitamin D response element binding • transcription coactivator activity • transcription factor binding • enhancer binding • RNA polymerase II core promoter proximal region sequence-specific DNA binding • transcriptional repressor activity, RNA polymerase II core promoter proximal region sequence-specific binding • bHLH transcription factor binding • E-box binding • protein binding • protein heterodimerization activity • transcription regulatory region DNA binding • repressing transcription factor binding Cellular component • cytoplasm • transcription factor complex • nucleoplasm • protein complex • RNA polymerase II transcription factor complex • nuclear chromatin • nucleus Biological process • cell differentiation • regulation of transcription, DNA-templated • positive regulation of muscle cell differentiation • positive regulation of sequence-specific DNA binding transcription factor activity • negative regulation of transcription from RNA polymerase II promoter • transcription, DNA-templated • nervous system development • positive regulation of transcription, DNA-templated • regulation of G1/S transition of mitotic cell cycle • B cell lineage commitment • positive regulation of cell cycle • positive regulation of B cell proliferation • positive regulation of neuron differentiation • B cell differentiation • immunoglobulin V(D)J recombination • positive regulation of transcription from RNA polymerase II promoter Sources:Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	6929	21423
Ensembl	ENSG00000071564	ENSMUSG00000020167
UniProt	P15923	P15806
RefSeq (mRNA)	NM_001136139 NM_003200	NM_001164147 NM_001164148 NM_001164149 NM_001164150 NM_001164151 NM_001164152 NM_001164153 NM_011548
RefSeq (protein)	NP_001129611.1 NP_003191.1	NP_001157620.1 NP_001157621.1 NP_001157623.1 NP_035678.3
Location (UCSC)	Chr 19: 1.61 – 1.65 Mb	Chr 10: 80.41 – 80.43 Mb
PubMed search	[2]	[3]
Wikidata

Transcription factor 3 (E2A immunoglobulin enhancer-binding factors E12/E47), also known as TCF3, is a protein that in humans is encoded by the TCF3 gene.^[4][5][6] TCF3 has been shown to directly enhance Hes1 (a well-known target of Notch signaling) expression.^[7]

Function

This gene encodes a member of the E protein (class I) family of helix-loop-helix transcription factors. The 9aaTAD transactivation domains of E proteins and MLL are very similar and both bind to the KIX domain of general transcriptional mediator CBP.^[8][9] 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.^[4]

This gene regulates many developmental patterning processes such as lymphocyte and central nervous system (CNS) development. E proteins are involved in the development of lymphocytes.^[10] They initiate transcription by binding to regulatory E-box sequences on target genes. Additionally, development of the neocortex of the brain is controlled in part by a Wnt signaling pathway. This pathway is essential for proper neuronal differentiation and proliferation of neural precursor cells. However, Wnt must be suppressed until it is the appropriate time in development to initiate neuronal differentiation and proliferation of neural precursor cells.^[11] The TCF3 gene has been shown to play a role in suppressing Wnt for this purpose. Furthermore, TCF3 has been shown to represses β-catenin in this pathway as well.^[12] Undifferentiated neural precursor cells contain high expression of TCF3, but as those cells become more differentiated, the expression of TCF3 decreases. Therefore, lack of TCF3 increases neural precursor cell reprogramming and greater expression of TCF3 suppresses reprogramming of neural precursor cells.^[12] In a TCF3 knock out model in mice, the mesoderm forms, but the structures of the mesoderm, specifically structures of the CNS, are duplicated. Therefore, repressive functions of TCF3 are necessary for proper anterior-posterior axis development.^[13]

Clinical significance

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 and t(17;19), with HLF),^[14] childhood leukemia (t(19;19), with TFPT) and acute leukemia (t(12;19), with ZNF384).^[4]

Interactions

TCF3 has been shown to interact with:

References

Further reading

This article incorporates text from the United States National Library of Medicine, which is in the public domain.