From Wikipedia, the free encyclopedia
Protein-coding gene in the species Homo sapiens
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 (Feb 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 (Feb 1990). "A new homeobox gene contributes the DNA binding domain of the t(1;19) translocation protein in pre-B ALL". Cell . 60 (4): 547–55.
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 (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, Martin; Vasku, A; Hajek, R; Knight, A (2015).
"Shared structural features of the 9aaTAD family in complex with CBP" . Mol. Biosyst . 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 : 301–22.
doi :
10.1146/annurev.immunol.20.092501.162048 .
PMID
11861605 .
^ Herblot, Sabine; Aplan, Peter D.; Hoang, Trang (2002-02-01).
"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 .
ISSN
0270-7306 .
PMC
133542 .
PMID
11784864 .
^
a
b
c Goardon N, Lambert JA, Rodriguez P, Nissaire P, Herblot S, Thibault P, Dumenil D, Strouboulis J, Romeo PH, Hoang T (Jan 2006).
"ETO2 coordinates cellular proliferation and differentiation during erythropoiesis" . The EMBO Journal . 25 (2): 357–66.
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 (Jan 2003).
"Regulation of E2A activities by histone acetyltransferases in B lymphocyte development" . The Journal of Biological Chemistry . 278 (4): 2370–6.
doi :
10.1074/jbc.M211464200 .
PMID
12435739 .
^ Maira SM, Wurtz JM, Wasylyk B (Nov 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): 5849–65.
doi :
10.1002/j.1460-2075.1996.tb00972.x .
PMC
452333 .
PMID
8918463 .
^ Deed RW, Jasiok M, Norton JD (Apr 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): 8278–86.
doi :
10.1074/jbc.273.14.8278 .
PMID
9525934 .
^
a
b
c Langlands K, Yin X, Anand G, Prochownik EV (Aug 1997).
"Differential interactions of Id proteins with basic-helix-loop-helix transcription factors" . The Journal of Biological Chemistry . 272 (32): 19785–93.
doi :
10.1074/jbc.272.32.19785 .
PMID
9242638 .
^ Johnson JD, Zhang W, Rudnick A, Rutter WJ, German MS (Jul 1997).
"Transcriptional synergy between LIM-homeodomain proteins and basic helix-loop-helix proteins: the LIM2 domain determines specificity" . Molecular and Cellular Biology . 17 (7): 3488–96.
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): 2394–401.
doi :
10.1128/mcb.16.5.2394 .
PMC
231228 .
PMID
8628307 .
^ Neufeld B, Grosse-Wilde A, Hoffmeyer A, Jordan BW, Chen P, Dinev D, Ludwig S, Rapp UR (Jul 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): 20239–42.
doi :
10.1074/jbc.C901040199 .
PMID
10781029 .
^ Maleki SJ, Royer CA, Hurlburt BK (Jun 1997). "MyoD-E12 heterodimers and MyoD-MyoD homodimers are equally stable". Biochemistry . 36 (22): 6762–7.
doi :
10.1021/bi970262m .
PMID
9184158 .
^ Chakraborty T, Martin JF, Olson EN (Sep 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): 17498–501.
doi :
10.1016/S0021-9258(19)37069-3 .
PMID
1325437 .
^ Hsu HL, Wadman I, Baer R (Apr 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): 3181–5.
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, Bonaventure J (Mar 2000).
"Saethre-Chotzen mutations cause TWIST protein degradation or impaired nuclear location" . Human Molecular Genetics . 9 (5): 813–9.
doi :
10.1093/hmg/9.5.813 .
PMID
10749989 .
^ Huggins GS, Chin MT, Sibinga NE, Lee SL, Haber E, Lee ME (Oct 1999).
"Characterization of the mUBC9-binding sites required for E2A protein degradation" . The Journal of Biological Chemistry . 274 (40): 28690–6.
doi :
10.1074/jbc.274.40.28690 .
PMID
10497239 .
Further reading
(1) Basic domains
(1.1) Basic
leucine zipper (
bZIP )(1.2) Basic helix-loop-helix (
bHLH )
Group A Group B Group C bHLH-
PAS Group D Group E Group F bHLH-COE
(1.3)
bHLH-ZIP (1.4) NF-1 (1.5) RF-X (1.6) Basic helix-span-helix (bHSH)
(2)
Zinc finger DNA-binding domains
(2.1)
Nuclear receptor (Cys4 )
subfamily 1 subfamily 2 subfamily 3 subfamily 4 subfamily 5 subfamily 6 subfamily 0
(2.2) Other Cys4 (2.3) Cys2 His2 (2.4) Cys6 (2.5) Alternating composition (2.6) WRKY
(4) β-Scaffold factors with minor groove contacts
(0) Other transcription factors
This article incorporates text from the
United States National Library of Medicine , which is in the
public domain .