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Gene Review

ECs4606  -  UhpA family transcriptional regulator

Escherichia coli O157:H7 str. Sakai

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Disease relevance of ECs4606

  • The UhpA protein is required for expression of the sugar phosphate transporter UhpT in Escherichia coli and is regulated by phosphate transfer from the transmembrane UhpBC sensor kinase complex [1].

High impact information on ECs4606

  • Binding to the -64 element exhibited positive cooperativity and was stimulated severalfold by phosphorylation of UhpA, whereas extension to the downstream region was more strongly affected by phosphorylation [2].
  • The consensus sequences for the high affinity UhpA-binding sites in the -64 element and for the downstream, low affinity sites are proposed [2].
  • Purified UhpA was phosphorylated by acetyl phosphate in a reaction that was dependent on Mg2+ and on the presence of aspartate 54, the site of phosphorylation in homologous response regulators [2].
  • Inorganic phosphate interfered with glucose 6-phosphate-dependent, UhpBC-mediated, as well as pyruvate-mediated activation of UhpA [3].
  • Together with the cytoplasmic response regulator UhpA, they constitute a typical two-component regulatory system based on His-to-Asp phosphoryl transfer [3].

Chemical compound and disease context of ECs4606


Biological context of ECs4606

  • These proteins are thought to regulate the phosphorylation of the transcription activator, UhpA [2].
  • Amino acid sequence comparisons showed that UhpA was homologous to a family of bacterial regulatory proteins, some of which act as transcriptional activators (OmpR, PhoB, NtrC, and DctD) [5].
  • The interference phenotype shown by UhpB in excess of UhpC appears to include the binding and sequestration of UhpA [4].
  • In vivo titration of transcriptional activator UhpA by the intact or mutant promoters on multicopy plasmids identified the -64 element as the UhpA-binding site [6].
  • Transcription activation by UhpA is stimulated by the catabolite gene activator protein (CAP)-cyclic AMP complex and depends on the C-terminal domains of the RNA polymerase RpoA and RpoD subunits [7].

Associations of ECs4606 with chemical compounds

  • UhpA activation could be made independent of transmembrane signaling when (Delta)uhpBC cells were grown on pyruvate [3].
  • Transmembrane induction of uhpT expression by external glucose 6-phosphate is positively regulated by the promoter-specific activator protein UhpA and the global regulator catabolite gene activator protein (CAP) [8].
  • The iron chelate FeBABE [iron (S)-1-(p-bromoacetamidobenzyl) EDTA] was covalently attached to engineered cysteine residues near the DNA-binding region in UhpA [7].
  • Like UhpA as a response regulator of a bacterial two-component regulatory system, ORF2 contained a helix-turn-helix DNA-binding domain at its COOH-terminal portion and an Asp residue (Asp-54) probably to be phosphorylated at its NH2-terminal portion [9].
  • To examine the possible roles of the two sets of UhpA-binding sites, a series of insertion and deletion mutations were introduced at the boundary between them, as suggested from the positions that were protected by UhpA against hydroxyl radical cleavage [10].

Analytical, diagnostic and therapeutic context of ECs4606

  • The two halves of the -64 inverted repeat did not contribute equally to promoter function and did not have to be intact for UhpA titration [6].


  1. Involvement of the amino-terminal phosphorylation module of UhpA in activation of uhpT transcription in Escherichia coli. Webber, C.A., Kadner, R.J. Mol. Microbiol. (1997) [Pubmed]
  2. Protein phosphorylation affects binding of the Escherichia coli transcription activator UhpA to the uhpT promoter. Dahl, J.L., Wei, B.Y., Kadner, R.J. J. Biol. Chem. (1997) [Pubmed]
  3. Cooperativity in signal transfer through the Uhp system of Escherichia coli. Verhamme, D.T., Postma, P.W., Crielaard, W., Hellingwerf, K.J. J. Bacteriol. (2002) [Pubmed]
  4. The histidine kinase domain of UhpB inhibits UhpA action at the Escherichia coli uhpT promoter. Wright, J.S., Olekhnovich, I.N., Touchie, G., Kadner, R.J. J. Bacteriol. (2000) [Pubmed]
  5. Role of uhp genes in expression of the Escherichia coli sugar-phosphate transport system. Weston, L.A., Kadner, R.J. J. Bacteriol. (1988) [Pubmed]
  6. Promoter elements required for positive control of transcription of the Escherichia coli uhpT gene. Merkel, T.J., Nelson, D.M., Brauer, C.L., Kadner, R.J. J. Bacteriol. (1992) [Pubmed]
  7. Mutational scanning and affinity cleavage analysis of UhpA-binding sites in the Escherichia coli uhpT promoter. Olekhnovich, I.N., Kadner, R.J. J. Bacteriol. (2002) [Pubmed]
  8. Transcription activation at the Escherichia coli uhpT promoter by the catabolite gene activator protein. Merkel, T.J., Dahl, J.L., Ebright, R.H., Kadner, R.J. J. Bacteriol. (1995) [Pubmed]
  9. A gene cluster involved in aerial mycelium formation in Streptomyces griseus encodes proteins similar to the response regulators of two-component regulatory systems and membrane translocators. Ueda, K., Miyake, K., Horinouchi, S., Beppu, T. J. Bacteriol. (1993) [Pubmed]
  10. Effect of altered spacing between uhpT promoter elements on transcription activation. Chen, Q., Kadner, R.J. J. Bacteriol. (2000) [Pubmed]
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