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Gene Review

DBT  -  dihydrolipoamide branched chain...

Bos taurus

Synonyms: BCKAD-E2, BCKADE2, E2, E2b
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Disease relevance of DBT

  • The primary structure of the inner E2 core domain of bovine E2b (fragment A) is very similar to those of three other E2 proteins (human E2p, Escherichia coli E2p, and E. coli E2k) [1].
  • Trans-activation of an upstream early gene promoter of bovine papilloma virus-1 by a product of the viral E2 gene [2].
  • Specific binding of the E2 subunit of pyruvate dehydrogenase to the upstream region of Bacillus thuringiensis protoxin genes [3].
  • The results suggest that the E2 protein activates transcription and polyomavirus DNA replication by similar mechanism(s) [4].
  • A vaccinia recombinant virus harboring the full length E2 coding sequence of BPV1 directs the synthesis of a 48 kD phosphoprotein with specific DNA binding activity [5].

High impact information on DBT

  • The bovine papillomavirus E2 protein regulates viral transcription by binding as a dimer to the DNA sequence ACCGN4CGGT [6].
  • Because E2 binding sites are positioned near several different BPV-1 promoters, such quantitative information may be important to understand transcriptional regulatory mechanisms in BPV-1 [7].
  • Gel retardation assays and DNA footprinting were used to quantitate the affinities of the E2 binding sites in the viral genome [7].
  • Specific recognition nucleotides and their DNA context determine the affinity of E2 protein for 17 binding sites in the BPV-1 genome [7].
  • The sequence elements responsible for E2 recognition of DNA were determined by missing contact analysis of several sites and a point mutation analysis of one site [7].

Chemical compound and disease context of DBT

  • The above data support the hypothesis that a conserved histidine residue in E2 acts as a general base for the transacylation reaction by analogy with E. coli chloramphenicol acetyltransferases [8].
  • Analysis of secreted virions showed that in the absence of glucosidase inhibitor, approximately 50% of the virion-associated BVDV E2 glycoprotein was resistant to endoglycosidase H (endo H) digestion, whereas intracellular E2 was completely sensitive to endo H digestion [9].

Biological context of DBT

  • Fragment A comprises residues 175 to 421 of the E2b protein and is the inner E2 core domain which contains the transacylase active site [1].
  • A bovine E2 cDNA (0.7 kb) was also isolated from a bovine liver cDNA library in lambda ZAP with the human E2 cDNA as a probe [10].
  • In contrast to other DNA-binding activator proteins described to date, the transcriptional activation by the E2 factor can occur without specific DNA binding [11].
  • Two mutated E2 proteins that lack portions of the conserved DNA-binding domain but which support DNA replication were identified using transient replication assays [12].
  • Since a single motif did not have a significant enhancer activity, it is likely that bound E2 molecules act cooperatively in activating transcription [13].

Anatomical context of DBT

  • Expression of the bovine papillomavirus E2 regulatory protein in human cervical carcinoma cell lines repressed expression of the resident human papillomavirus E6 and E7 oncogenes and within a few days caused essentially all of the cells to synchronously display numerous phenotypic markers characteristic of cells undergoing replicative senescence [14].
  • To determine the consequences of removing the E6 and E7 proteins from cervical cancer cells, we infected HeLa cells, a cervical carcinoma cell line that contains HPV18 DNA, with a recombinant virus that expresses the bovine papillomavirus E2 protein [15].
  • These data suggest that there are two pools of E2 in the cell nucleus: one that localizes on transcriptionally inactive compact chromatin and the other, which compartmentalizes to transcriptionally active nuclear structures of the cell [16].
  • To prevent synthesis of E2-p7, a translational stop codon was introduced after the last codon of the E2 gene and an internal ribosome entry site element followed by a signal peptide coding sequence was inserted upstream of the p7 gene [17].
  • E2 protein was found to have considerable influence upon LCR promoter activity in primary bovine palate keratinocytes [18].

Associations of DBT with chemical compounds

  • In this study, we demonstrate the inhibition of E2 DNA binding in vitro by reagents that oxidize or otherwise chemically modify the free sulfhydryl groups of reactive cysteine residues [19].
  • The major phosphorylation sites of the bovine papillomavirus E2 transactivator protein are two serine residues, 298 and 301, that are located in a flexible hinge region between the DNA binding and transactivation domains [20].
  • It was identified as the E2 subunit of pyruvate dehydrogenase [3].
  • Sodium dodecyl sulfate-polyacrylamide gel electrophoresis shows that the inner E2 core consists of two lipoate-free tryptic fragments, i.e. fragment A and fragment B with Mr = 26,000 and 22,000, respectively [21].
  • The E2 activity is strongly inhibited by arsenite [22].

Analytical, diagnostic and therapeutic context of DBT


  1. Characterization and conservation of the inner E2 core domain structure of branched-chain alpha-keto acid dehydrogenase complex from bovine liver. Construction of a cDNA encoding the entire transacylase (E2b) precursor. Griffin, T.A., Lau, K.S., Chuang, D.T. J. Biol. Chem. (1988) [Pubmed]
  2. Trans-activation of an upstream early gene promoter of bovine papilloma virus-1 by a product of the viral E2 gene. Haugen, T.H., Cripe, T.P., Ginder, G.D., Karin, M., Turek, L.P. EMBO J. (1987) [Pubmed]
  3. Specific binding of the E2 subunit of pyruvate dehydrogenase to the upstream region of Bacillus thuringiensis protoxin genes. Walter, T., Aronson, A. J. Biol. Chem. (1999) [Pubmed]
  4. Enhancer effect of bovine papillomavirus E2 protein in replication of polyomavirus DNA. Nilsson, M., Forsberg, M., You, Z.Y., Westin, G., Magnusson, G. Nucleic Acids Res. (1991) [Pubmed]
  5. The E2 trans-activating protein of bovine papillomavirus type 1 (BPV1) is serine-phosphorylated in vivo. Meneguzzi, G., Lathe, R., Kieny, M.P., Vogt, N. Oncogene (1989) [Pubmed]
  6. Amino acids necessary for DNA contact and dimerization imply novel motifs in the papillomavirus E2 trans-activator. Prakash, S.S., Grossman, S.R., Pepinsky, R.B., Laimins, L.A., Androphy, E.J. Genes Dev. (1992) [Pubmed]
  7. Specific recognition nucleotides and their DNA context determine the affinity of E2 protein for 17 binding sites in the BPV-1 genome. Li, R., Knight, J., Bream, G., Stenlund, A., Botchan, M. Genes Dev. (1989) [Pubmed]
  8. Genetic reconstruction and characterization of the recombinant transacylase (E2b) component of bovine branched-chain alpha-keto acid dehydrogenase complex. Implication of histidine 391 as an active site residue. Griffin, T.A., Chuang, D.T. J. Biol. Chem. (1990) [Pubmed]
  9. Inhibition of host ER glucosidase activity prevents Golgi processing of virion-associated bovine viral diarrhea virus E2 glycoproteins and reduces infectivity of secreted virions. Jordan, R., Nikolaeva, O.V., Wang, L., Conyers, B., Mehta, A., Dwek, R.A., Block, T.M. Virology (2002) [Pubmed]
  10. Conservation of primary structure in the lipoyl-bearing and dihydrolipoyl dehydrogenase binding domains of mammalian branched-chain alpha-keto acid dehydrogenase complex: molecular cloning of human and bovine transacylase (E2) cDNAs. Lau, K.S., Griffin, T.A., Hu, C.W., Chuang, D.T. Biochemistry (1988) [Pubmed]
  11. Sequence-specific and general transcriptional activation by the bovine papillomavirus-1 E2 trans-activator require an N-terminal amphipathic helix-containing E2 domain. Haugen, T.H., Turek, L.P., Mercurio, F.M., Cripe, T.P., Olson, B.J., Anderson, R.D., Seidl, D., Karin, M., Schiller, J. EMBO J. (1988) [Pubmed]
  12. Separation of the transcriptional activation and replication functions of the bovine papillomavirus-1 E2 protein. Winokur, P.L., McBride, A.A. EMBO J. (1992) [Pubmed]
  13. The specific DNA recognition sequence of the bovine papillomavirus E2 protein is an E2-dependent enhancer. Hawley-Nelson, P., Androphy, E.J., Lowy, D.R., Schiller, J.T. EMBO J. (1988) [Pubmed]
  14. Rapid induction of senescence in human cervical carcinoma cells. Goodwin, E.C., Yang, E., Lee, C.J., Lee, H.W., DiMaio, D., Hwang, E.S. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  15. Repression of human papillomavirus oncogenes in HeLa cervical carcinoma cells causes the orderly reactivation of dormant tumor suppressor pathways. Goodwin, E.C., DiMaio, D. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  16. Association of bovine papillomavirus E2 protein with nuclear structures in vivo. Kurg, R., Sild, K., Ilves, A., Sepp, M., Ustav, M. J. Virol. (2005) [Pubmed]
  17. E2-p7 region of the bovine viral diarrhea virus polyprotein: processing and functional studies. Harada, T., Tautz, N., Thiel, H.J. J. Virol. (2000) [Pubmed]
  18. Both viral E2 protein and the cellular factor PEBP2 regulate transcription via E2 consensus sites within the bovine papillomavirus type 4 long control region. Jackson, M.E., Campo, M.S. J. Virol. (1995) [Pubmed]
  19. Conserved cysteine residue in the DNA-binding domain of the bovine papillomavirus type 1 E2 protein confers redox regulation of the DNA-binding activity in vitro. McBride, A.A., Klausner, R.D., Howley, P.M. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  20. Casein Kinase II phosphorylation-induced conformational switch triggers degradation of the papillomavirus E2 protein. Penrose, K.J., Garcia-Alai, M., de Prat-Gay, G., McBride, A.A. J. Biol. Chem. (2004) [Pubmed]
  21. Subunit structure of the dihydrolipoyl transacylase component of branched-chain alpha-keto acid dehydrogenase complex from bovine liver. Characterization of the inner transacylase core. Chuang, D.T., Hu, C.W., Ku, L.S., Markovitz, P.J., Cox, R.P. J. Biol. Chem. (1985) [Pubmed]
  22. Catalytic and structural properties of the dihydrolipoyl transacylase component of bovine branched-chain alpha-keto acid dehydrogenase. Chuang, D.T., Hu, C.C., Ku, L.S., Niu, W.L., Myers, D.E., Cox, R.P. J. Biol. Chem. (1984) [Pubmed]
  23. The activation domain of the bovine papillomavirus E2 protein mediates association of DNA-bound dimers to form DNA loops. Knight, J.D., Li, R., Botchan, M. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  24. Cloning and expression in Escherichia coli of mature E1 beta subunit of bovine mitochondrial branched-chain alpha-keto acid dehydrogenase complex. Mapping of the E1 beta-binding region on E2. Wynn, R.M., Chuang, J.L., Davie, J.R., Fisher, C.W., Hale, M.A., Cox, R.P., Chuang, D.T. J. Biol. Chem. (1992) [Pubmed]
  25. Phosphorylation sites of the E2 transcriptional regulatory proteins of bovine papillomavirus type 1. McBride, A.A., Bolen, J.B., Howley, P.M. J. Virol. (1989) [Pubmed]
  26. Resolution and reconstitution of bovine kidney branched-chain 2-oxo acid dehydrogenase complex. Cook, K.G., Bradford, A.P., Yeaman, S.J. Biochem. J. (1985) [Pubmed]
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