Protein-coding gene in the species Homo sapiens
TCF3 |
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Available structures |
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PDB | Ortholog search: PDBe RCSB |
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List of PDB id codes |
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2MH0, 2YPA, 2YPB, 3U5V |
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Identifiers |
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Aliases | TCF3, E2A, E47, ITF1, TCF-3, VDIR, bHLHb21, AGM8, transcription factor 3, p75 |
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External IDs | OMIM: 147141; MGI: 98510; HomoloGene: 2408; GeneCards: TCF3; OMA:TCF3 - orthologs |
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Gene location (Human) |
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| Chr. | Chromosome 19 (human)[1] |
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| Band | 19p13.3 | Start | 1,609,290 bp[1] |
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End | 1,652,605 bp[1] |
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Gene location (Mouse) |
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| Chr. | Chromosome 10 (mouse)[2] |
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| Band | 10 C1|10 39.72 cM | Start | 80,245,348 bp[2] |
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End | 80,269,481 bp[2] |
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RNA expression pattern |
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Bgee | Human | Mouse (ortholog) |
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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
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| Top expressed in | - ventricular zone
- genital tubercle
- tail of embryo
- mandibular prominence
- maxillary prominence
- lip
- epiblast
- somite
- abdominal wall
- yolk sac
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| More reference expression data |
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BioGPS |
| More reference expression data |
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Gene ontology |
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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 |
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Orthologs |
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Species | Human | Mouse |
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Entrez | | |
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Ensembl | | |
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UniProt | | |
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RefSeq (mRNA) | |
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NM_001136139 NM_003200 NM_001351778 NM_001351779 |
| NM_001164147 NM_001164148 NM_001164149 NM_001164150 NM_001164151
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NM_001164152 NM_001164153 NM_011548 NM_001378903 NM_001378904 NM_001378905 NM_001378908 NM_001378910 NM_001378912 NM_001378913 NM_001378914 |
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RefSeq (protein) | |
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NP_001129611 NP_003191 NP_001338707 NP_001338708 |
| NP_001157619 NP_001157620 NP_001157621 NP_001157622 NP_001157623
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NP_001157624 NP_001157625 NP_035678 NP_001365832 NP_001365833 NP_001365834 NP_001365837 NP_001365839 NP_001365841 NP_001365842 NP_001365843 |
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Location (UCSC) | Chr 19: 1.61 – 1.65 Mb | Chr 10: 80.25 – 80.27 Mb |
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PubMed search | [3] | [4] |
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Wikidata |
View/Edit Human | View/Edit Mouse |
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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
- ^ 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.
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.
(1) Basic domains |
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(1.1) Basic leucine zipper (bZIP) | |
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(1.2) Basic helix-loop-helix (bHLH) | Group A | |
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Group B | |
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Group C bHLH-PAS | |
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Group D | |
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Group E | |
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Group F bHLH-COE | |
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(1.3) bHLH-ZIP | |
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(1.4) NF-1 | |
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(1.5) RF-X | |
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(1.6) Basic helix-span-helix (bHSH) | |
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(2) Zinc finger DNA-binding domains |
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(2.1) Nuclear receptor (Cys4) | subfamily 1 | |
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subfamily 2 | |
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subfamily 3 | |
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subfamily 4 | |
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subfamily 5 | |
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subfamily 6 | |
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subfamily 0 | |
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(2.2) Other Cys4 | |
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(2.3) Cys2His2 | |
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(2.4) Cys6 | |
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(2.5) Alternating composition | |
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(2.6) WRKY | |
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(4) β-Scaffold factors with minor groove contacts |
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(0) Other transcription factors |
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see also transcription factor/coregulator deficiencies |
This article incorporates text from the United States National Library of Medicine, which is in the public domain.