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)[1] Band 19p13.3 Start 1,609,290 bp[1] End 1,652,605 bp[1]
Gene location (Mouse) Chr. Chromosome 10 (mouse)[2] Band 10 C1|10 39.72 cM Start 80,245,348 bp[2] End 80,269,481 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) 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 BioGPS 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 Species Human Mouse Entrez 6929 21423 Ensembl ENSG00000071564 ENSMUSG00000020167 UniProt P15923 P15806 RefSeq (mRNA) 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 RefSeq (protein) 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 Location (UCSC) Chr 19: 1.61 – 1.65 Mb Chr 10: 80.25 – 80.27 Mb PubMed search [3] [4]
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:

• CBFA2T3,^[13]
• CREBBP,^[14]
• ELK3,^[15]
• EP300,^[14]
• ID3,^[16][17]
• LDB1,^[13]
• LMX1A,^[18]
• LYL1,^[19]
• MAPKAPK3,^[20]
• MyoD,^[17][21]
• Myogenin,^[17][22]
• PCAF,^[14]
• TAL1^[13][23]
• TWIST1,^[24] and
• UBE2I.^[25]

References

1. GRCh38: Ensembl release 89: ENSG00000071564 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000020167 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. "Entrez Gene: TCF3".
6. 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.
7. 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.
8. E proteins and Notch signaling cooperate to promote T cell lineage specification and commitment
9. 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.
10. 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.
11. 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.
12. 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.
13. 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.
14. 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.
15. 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.
16. 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.
17. 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.
18. 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.
19. 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.
20. 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.
21. 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.
22. 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.
23. 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.
24. 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.
25. 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.

Further reading

• LeBrun DP (May 2003). "E2A basic helix-loop-helix transcription factors in human leukemia". Frontiers in Bioscience. 8 (1–3): s206 – s222. doi:10.2741/1030. PMID 12700034.

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