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Homo sapiens
Homo sapiens
Mus musculus
Homo sapiens
Mus musculus
Homo sapiens
Mus musculus
Mus musculus
Homo sapiens
Mus musculus
Transcription Factor Encyclopedia  BETA
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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].

  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].

  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)