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, p75
External IDs	OMIM: 147141; MGI: 98510; HomoloGene: 2408; GeneCards: TCF3; OMA:TCF3 - orthologs
Gene location (Human)
Chr.	Chromosome 19 (human)
End	1,652,605 bp
Gene location (Mouse)
Chr.	Chromosome 10 (mouse)
End	80,269,481 bp
RNA expression pattern
	Top expressed in
	ganglionic eminence; ; ventricular zone; ; right testis; ; left testis; ; pancreatic ductal cell; ; lymph node; ; bone marrow cells; ; gonad; ; appendix; ; stromal cell of endometrium;
	Top expressed in
	ventricular zone; ; genital tubercle; ; tail of embryo; ; mandibular prominence; ; maxillary prominence; ; lip; ; epiblast; ; somite; ; abdominal wall; ; yolk sac;
	More reference expression data
	; ; ; ;
	More reference expression data
Gene ontology
Molecular function	DNA binding; sequence-specific DNA binding; protein dimerization activity; protein homodimerization activity; DNA-binding transcription factor activity; mitogen-activated protein kinase kinase kinase binding; vitamin D response element binding; transcription coactivator activity; transcription factor binding; RNA polymerase II cis-regulatory region sequence-specific DNA binding; DNA-binding transcription repressor activity, RNA polymerase II-specific; bHLH transcription factor binding; E-box binding; protein binding; protein heterodimerization activity; DNA-binding transcription factor activity, RNA polymerase II-specific;
Cellular component	cytoplasm; transcription regulator complex; RNA polymerase II transcription regulator complex; nucleus; nuclear speck; nucleoplasm; protein-containing complex;
Biological process	cell differentiation; regulation of transcription, DNA-templated; positive regulation of muscle cell differentiation; positive regulation of DNA-binding transcription factor activity; negative regulation of transcription by RNA polymerase II; 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 by RNA polymerase II; regulation of hematopoietic stem cell differentiation;
	Sources:Amigo / QuickGO
Orthologs
	6929
	21423
	ENSG00000071564
	ENSMUSG00000020167
	P15923
	P15806
	NM_001136139; NM_003200; NM_001351778; NM_001351779
NM_001164147; NM_001164148; NM_001164149; NM_001164150; NM_001164151;
	NM_001164152; NM_001164153; NM_011548; NM_001378903; NM_001378904; NM_001378905; NM_001378908; NM_001378910; NM_001378912; NM_001378913; NM_001378914
	NP_001129611; NP_003191; NP_001338707; NP_001338708
NP_001157619; NP_001157620; NP_001157621; NP_001157622; NP_001157623;
	NP_001157624; NP_001157625; NP_035678; NP_001365832; NP_001365833; NP_001365834; NP_001365837; NP_001365839; NP_001365841; NP_001365842; NP_001365843
	Wikidata
View/Edit Human	View/Edit Mouse

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.^[5]^[6]^[7] TCF3 has been shown to directly enhance Hes1 (a well-known target of Notch signaling) expression.^[8]

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.^[9]^[10] 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 the B and T lymphocyte development.^[5]

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.^[11] They initiate transcription by binding to regulatory E-box sequences on target genes.

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),^[12] childhood leukemia (t(19;19), with TFPT) and acute leukemia (t(12;19), with ZNF384).^[5]

Interactions

TCF3 has been shown to interact with:

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000071564 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000020167 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ ^a ^b ^c "Entrez Gene: TCF3".
^ Henthorn P, McCarrick-Walmsley R, Kadesch T (February 1990). "Sequence of the cDNA encoding ITF-1, a positive-acting transcription factor". Nucleic Acids Research. 18 (3): 677. doi:10.1093/nar/18.3.677. PMC 333499. PMID 2308859.
^ Kamps MP, Murre C, Sun XH, Baltimore D (February 1990). "A new homeobox gene contributes the DNA binding domain of the t(1;19) translocation protein in pre-B ALL". Cell. 60 (4): 547–555. doi:10.1016/0092-8674(90)90658-2. PMID 1967983. S2CID 39661371.
^ E proteins and Notch signaling cooperate to promote T cell lineage specification and commitment
^ Piskacek S, Gregor M, Nemethova M, Grabner M, Kovarik P, Piskacek M (June 2007). "Nine-amino-acid transactivation domain: establishment and prediction utilities". Genomics. 89 (6): 756–768. doi:10.1016/j.ygeno.2007.02.003. PMID 17467953.
^ Piskacek M, Vasku A, Hajek R, Knight A (March 2015). "Shared structural features of the 9aaTAD family in complex with CBP". Molecular BioSystems. 11 (3): 844–851. doi:10.1039/c4mb00672k. PMID 25564305.
^ Quong MW, Romanow WJ, Murre C (2002). "E protein function in lymphocyte development". Annual Review of Immunology. 20: 301–322. doi:10.1146/annurev.immunol.20.092501.162048. PMID 11861605.
^ Herblot S, Aplan PD, Hoang T (February 2002). "Gradient of E2A activity in B-cell development". Molecular and Cellular Biology. 22 (3): 886–900. doi:10.1128/MCB.22.3.886-900.2002. PMC 133542. PMID 11784864.
^ ^a ^b ^c Goardon N, Lambert JA, Rodriguez P, Nissaire P, Herblot S, Thibault P, et al. (January 2006). "ETO2 coordinates cellular proliferation and differentiation during erythropoiesis". The EMBO Journal. 25 (2): 357–366. doi:10.1038/sj.emboj.7600934. PMC 1383517. PMID 16407974.
^ ^a ^b ^c Bradney C, Hjelmeland M, Komatsu Y, Yoshida M, Yao TP, Zhuang Y (January 2003). "Regulation of E2A activities by histone acetyltransferases in B lymphocyte development". The Journal of Biological Chemistry. 278 (4): 2370–2376. doi:10.1074/jbc.M211464200. PMID 12435739.
^ Maira SM, Wurtz JM, Wasylyk B (November 1996). "Net (ERP/SAP2) one of the Ras-inducible TCFs, has a novel inhibitory domain with resemblance to the helix-loop-helix motif". The EMBO Journal. 15 (21): 5849–5865. doi:10.1002/j.1460-2075.1996.tb00972.x. PMC 452333. PMID 8918463.
^ Deed RW, Jasiok M, Norton JD (April 1998). "Lymphoid-specific expression of the Id3 gene in hematopoietic cells. Selective antagonism of E2A basic helix-loop-helix protein associated with Id3-induced differentiation of erythroleukemia cells". The Journal of Biological Chemistry. 273 (14): 8278–8286. doi:10.1074/jbc.273.14.8278. PMID 9525934.
^ ^a ^b ^c Langlands K, Yin X, Anand G, Prochownik EV (August 1997). "Differential interactions of Id proteins with basic-helix-loop-helix transcription factors". The Journal of Biological Chemistry. 272 (32): 19785–19793. doi:10.1074/jbc.272.32.19785. PMID 9242638.
^ Johnson JD, Zhang W, Rudnick A, Rutter WJ, German MS (July 1997). "Transcriptional synergy between LIM-homeodomain proteins and basic helix-loop-helix proteins: the LIM2 domain determines specificity". Molecular and Cellular Biology. 17 (7): 3488–3496. doi:10.1128/mcb.17.7.3488. PMC 232202. PMID 9199284.
^ Miyamoto A, Cui X, Naumovski L, Cleary ML (May 1996). "Helix-loop-helix proteins LYL1 and E2a form heterodimeric complexes with distinctive DNA-binding properties in hematolymphoid cells". Molecular and Cellular Biology. 16 (5): 2394–2401. doi:10.1128/mcb.16.5.2394. PMC 231228. PMID 8628307.
^ Neufeld B, Grosse-Wilde A, Hoffmeyer A, Jordan BW, Chen P, Dinev D, et al. (July 2000). "Serine/Threonine kinases 3pK and MAPK-activated protein kinase 2 interact with the basic helix-loop-helix transcription factor E47 and repress its transcriptional activity". The Journal of Biological Chemistry. 275 (27): 20239–20242. doi:10.1074/jbc.C901040199. PMID 10781029.
^ Maleki SJ, Royer CA, Hurlburt BK (June 1997). "MyoD-E12 heterodimers and MyoD-MyoD homodimers are equally stable". Biochemistry. 36 (22): 6762–6767. doi:10.1021/bi970262m. PMID 9184158.
^ Chakraborty T, Martin JF, Olson EN (September 1992). "Analysis of the oligomerization of myogenin and E2A products in vivo using a two-hybrid assay system". The Journal of Biological Chemistry. 267 (25): 17498–17501. doi:10.1016/S0021-9258(19)37069-3. PMID 1325437.
^ Hsu HL, Wadman I, Baer R (April 1994). "Formation of in vivo complexes between the TAL1 and E2A polypeptides of leukemic T cells". Proceedings of the National Academy of Sciences of the United States of America. 91 (8): 3181–3185. Bibcode:1994PNAS...91.3181H. doi:10.1073/pnas.91.8.3181. PMC 43539. PMID 8159721.
^ El Ghouzzi V, Legeai-Mallet L, Aresta S, Benoist C, Munnich A, de Gunzburg J, et al. (March 2000). "Saethre-Chotzen mutations cause TWIST protein degradation or impaired nuclear location". Human Molecular Genetics. 9 (5): 813–819. doi:10.1093/hmg/9.5.813. PMID 10749989.
^ Huggins GS, Chin MT, Sibinga NE, Lee SL, Haber E, Lee ME (October 1999). "Characterization of the mUBC9-binding sites required for E2A protein degradation". The Journal of Biological Chemistry. 274 (40): 28690–28696. doi:10.1074/jbc.274.40.28690. PMID 10497239.

Function

Clinical significance

Interactions

References

Further reading