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Gene Review

arcA  -  two-component response regulator

Escherichia coli O157:H7 str. EDL933

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Disease relevance of arcA

  • The AD gene, designated arcA, was expressed from recombinant bacteriophage or in cells harboring plasmid subclones from this phage at a level up to 1,000-fold lower than the level in fully derepressed S. sanguis but apparently under the control of its own promoter [1].
  • To systematically investigate the contribution of Arc- and Fnr-dependent regulation in catabolism, glucose-limited chemostat cultures were conducted on wild-type E. coli, an arcA mutant, an fnr mutant, and an arcAfnr double mutant strains under a well-defined semi-aerobic condition [2].

High impact information on arcA

  • Diamide, an oxidant that causes the anaerobic biosynthesis of the MnSOD polypeptide and also facilitates insertion of manganese at the active site, was found to anaerobically induce MnSOD in both soxRS and fur arcA fnr strains [3].
  • Metal chelating agents also caused anaerobic induction of MnSOD in a fur arcA fnr triple mutant; however, this induction of MnSOD and of glucose-6-phosphate dehydrogenase (G6PD) by 1,10-phenanthroline was dependent on an intact soxRS locus [3].
  • A cDNA (arcA3) whose coding sequence is identical to the 2,4-D induced arcA cDNA cloned by Ishida et al [4].
  • Transcript and sequence analyses reveal that the arcA upstream regulatory region lies within a 530 bp non-coding DNA fragment, which contains five putative promoter sequences and a putative Fnr-binding site [5].
  • Gene fusion studies with the R1 PY promoter, the major promoter of the transfer operon, and a lacZ reporter gene, indicated that arcA is required for maximal expression from this promoter [6].

Chemical compound and disease context of arcA


Biological context of arcA

  • Evaluation of antibody titers and classical complement activities in various serum samples pointed to complement-mediated bactericidal activity as the factor that distinguishes between the arcA mutant and wild-type phenotypes [8].
  • However, the virulence of the arcA mutants for BALB/c mice was significantly reduced [8].
  • Deletion of arcA resulted in acetate reduction and increased the biomass yield due to the increased capacities of the TCA cycle and respiration [9].
  • Results from both the transposon array and insertion mutagenesis indicated that arcA, which is known to be a negative response regulator of genes in aerobic pathways, was important for competitiveness in E. coli PHL628 biofilms [10].
  • From the absence of anaerobic induction following inactivation of arcR and from the existence of a binding site upstream of the arcA transcription start point, it can be inferred that ArcR is an activator of the arginine deiminase pathway [11].

Anatomical context of arcA


Associations of arcA with chemical compounds

  • Glucose, on the other hand, was excreted mostly as acetate by the wild-type and by the arcA mutant [7].
  • In an arcA mutant devoid of the transcriptional regulator ArcA, glycerol was completely oxidized with nitrate as an electron acceptor, demonstrating derepression and function of the complete pathway [7].
  • Additional derepression of the glyxoylate pathway by inactivation of arcA, leading to a strain designated as SBS660MG, did not significantly increase the succinate yield and it decreased glucose consumption by 80% [14].


  1. Cloning and expression in Escherichia coli of the genes of the arginine deiminase system of Streptococcus sanguis NCTC 10904. Burne, R.A., Parsons, D.T., Marquis, R.E. Infect. Immun. (1989) [Pubmed]
  2. Effect of the global redox sensing/regulation networks on Escherichia coli and metabolic flux distribution based on C-13 labeling experiments. Zhu, J., Shalel-Levanon, S., Bennett, G., San, K.Y. Metab. Eng. (2006) [Pubmed]
  3. Induction of manganese-containing superoxide dismutase in anaerobic Escherichia coli by diamide and 1,10-phenanthroline: sites of transcriptional regulation. Privalle, C.T., Kong, S.E., Fridovich, I. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  4. Is arcA3 a possible mediator in the signal transduction pathway during agonist cell cycle arrest by salicylic acid and UV irradiation? Perennes, C., Glab, N., Guglieni, B., Doutriaux, M.P., Phan, T.H., Planchais, S., Bergounioux, C. J. Cell. Sci. (1999) [Pubmed]
  5. Anaerobic activation of arcA transcription in Escherichia coli: roles of Fnr and ArcA. Compan, I., Touati, D. Mol. Microbiol. (1994) [Pubmed]
  6. Signal transduction and bacterial conjugation: characterization of the role of ArcA in regulating conjugative transfer of the resistance plasmid R1. Strohmaier, H., Noiges, R., Kotschan, S., Sawers, G., Högenauer, G., Zechner, E.L., Koraimann, G. J. Mol. Biol. (1998) [Pubmed]
  7. Functional citric acid cycle in an arcA mutant of Escherichia coli during growth with nitrate under anoxic conditions. Prohl, C., Wackwitz, B., Vlad, D., Unden, G. Arch. Microbiol. (1998) [Pubmed]
  8. Two-component systems in Haemophilus influenzae: a regulatory role for ArcA in serum resistance. De Souza-Hart, J.A., Blackstock, W., Di Modugno, V., Holland, I.B., Kok, M. Infect. Immun. (2003) [Pubmed]
  9. Overflow Metabolism in Escherichia coli during Steady-State Growth: Transcriptional Regulation and Effect of the Redox Ratio. Vemuri, G.N., Altman, E., Sangurdekar, D.P., Khodursky, A.B., Eiteman, M.A. Appl. Environ. Microbiol. (2006) [Pubmed]
  10. Global analysis of candidate genes important for fitness in a competitive biofilm using DNA-array-based transposon mapping. Junker, L.M., Peters, J.E., Hay, A.G. Microbiology (Reading, Engl.) (2006) [Pubmed]
  11. Regulation of anaerobic arginine catabolism in Bacillus licheniformis by a protein of the Crp/Fnr family. Maghnouj, A., Abu-Bakr, A.A., Baumberg, S., Stalon, V., Vander Wauven, C. FEMS Microbiol. Lett. (2000) [Pubmed]
  12. Effect of the arcA Mutation on the Expression of Flagella Genes in Escherichia coli. Kato, Y., Sugiura, M., Mizuno, T., Aiba, H. Biosci. Biotechnol. Biochem. (2007) [Pubmed]
  13. Differentiation of arcA, arcB, and cpxA mutant phenotypes of Escherichia coli by sex pilus formation and enzyme regulation. Iuchi, S., Furlong, D., Lin, E.C. J. Bacteriol. (1989) [Pubmed]
  14. Novel pathway engineering design of the anaerobic central metabolic pathway in Escherichia coli to increase succinate yield and productivity. Sánchez, A.M., Bennett, G.N., San, K.Y. Metab. Eng. (2005) [Pubmed]
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