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 SOX9
Homo sapiens
 HIF1A
Homo sapiens
 Pax6
Mus musculus
 PAX6
Homo sapiens
 Snai2
Mus musculus
 PPARA
Homo sapiens
 Ppara
Mus musculus
 Thrb
Mus musculus
 SNAI2
Homo sapiens
 Tbr1
Mus musculus
Transcription Factor Encyclopedia  BETA
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Isoforms

The Tcfe2a gene encodes two protein products, E12 and E47, that arise through differential splicing of the exon encoding both the DNA binding and dimerization domains. Both proteins feature a similar bHLH domain and the two activation domains, AD1 and AD2. No differences in DNA binding sequence preference or dimerization abilities have been noted thus far[1]. Despite this, E12 has a lower DNA binding affinity due to the inhibitory region present upstream of the bHLH domain[2].

References
  1. Kee BL et al. E2A proteins: essential regulators at multiple stages of B-cell development. Immunol. Rev., 175:138-49. (PMID 10933599)
  1. Sun XH and Baltimore D. An inhibitory domain of E12 transcription factor prevents DNA binding in E12 homodimers but not in E12 heterodimers. Cell, 64(2):459-70. (PMID 1846322)
Covalent modifications

E2A protein function is governed by various covalent modifications. UbcE2A is an E2A-selective ubiquitin-conjugating enzyme that targets E2A proteins for proteasomal degradation [1]. UbcE2A interacts with E2A via a 54 residue region upstream of the bHLH domain [1]. Additionally, Notch signaling through has been shown to accelerate E2A degradation through a mitogen-activated protein kinase-dependent and ubiquitin-mediated pathway [2].

The histone acetyl-transferases p300, creb-binding protein (CBP) and p300/CBP-associated factor (PCAF) have all been shown to acetylate E2A. Acetylation of E2A results in increased transcriptional activity and nuclear retention [3].

Casein kinase II and protein kinase A (PKA) have been shown to phosphorylate E2A on residues immediately N-terminal to the bHLH domain; phosphorylation of these residues blocked the DNA binding ability of E47 homodimers [4].

References
  1. Kho CJ et al. Degradation of E2A proteins through a ubiquitin-conjugating enzyme, UbcE2A. J. Biol. Chem., 272(6):3845-51. (PMID 9013644)
  2. Huang Z et al. Notch-induced E2A degradation requires CHIP and Hsc70 as novel facilitators of ubiquitination. Mol. Cell. Biol., 24(20):8951-62. (PMID 15456869)
  1. Bradney C et al. Regulation of E2A activities by histone acetyltransferases in B lymphocyte development. J. Biol. Chem., 278(4):2370-6. (PMID 12435739)
  2. Sloan SR et al. Phosphorylation of E47 as a potential determinant of B-cell-specific activity. Mol. Cell. Biol., 16(12):6900-8. (PMID 8943345)