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Gene Review

gadA  -  glutamate decarboxylase A, PLP-dependent

Escherichia coli str. K-12 substr. MG1655

Synonyms: ECK3502, JW3485, gadS
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Disease relevance of gadA

  • The number of regulatory proteins (five), sigma factors (two) and regulatory feedback loops focused on gadA/BC expression make this one of the most intensively regulated systems in E. coli [1].
  • Using PCR primers that amplify a 670-bp segment from the gadA and gadB genes encoding GAD, we examined the distribution of the gadAB genes among enteric bacteria [2].
  • Identification of the promoter regions and sigma(s)-dependent regulation of the gadA and gadBC genes associated with glutamate-dependent acid resistance in Shigella flexneri [3].

High impact information on gadA

  • Herein, we provide evidence that the nucleoid-associated protein H-NS directly functions as repressor of gadA, one of the structural genes, and gadX, a regulatory gene encoding one of the primary activators of the gad system [4].
  • Moreover, we show that a maltose-binding protein MalE-GadX fusion is able to stimulate the promoter activity of gadA/BC, thus indicating that GadX is by itself able to up-regulate the gad genes and that a functional competition between H-NS and GadX takes place at the gadA promoter [4].
  • The expression of gadA and gadB, which encode two glutamate decarboxylases (GADs) of Escherichia coli, is induced by an acidic environment and participate in acid resistance [5].
  • The gadA, gadBC and gadE genes are all induced by low pH in exponential phase cells grown in minimal glucose media [1].
  • The structural genes gadA, gadB, and gadC encode two glutamate decarboxylase isoforms and a glutamate/gamma-aminobutyrate (GABA) antiporter, respectively [6].

Chemical compound and disease context of gadA

  • One very efficient E. coli acid resistance system encompasses two isoforms of glutamate decarboxylase (gadA and gadB) and a putative glutamate:gamma-amino butyric acid (GABA) antiporter (gadC) [7].

Biological context of gadA

  • DNA mobility shift experiments showed that purified GadX protein bound to the perA, gadA and gadB promoter regions in vitro, indicating that GadX is a transcriptional regulator of these genes [8].
  • The Escherichia coli chromosome contains two distantly located genes, gadA and gadB, which encode biochemically undistinguishable isoforms of glutamic acid decarboxylase (Gad) [9].
  • Autoregulation of the whole gad system is inferred by the positive effect of GadX on the gadA promoter and gadAX cotranscription [9].
  • Reporter lac fusion constructs showed base induction of sdaA encoding serine deaminase under anaerobiosis; in addition, the glutamate decarboxylase genes gadA and gadB were induced at the high pH anaerobically but not with aeration [10].
  • Deletions of the regulatory region upstream of gadA provided evidence that a 20 bp conserved region located 50 bp from the transcriptional start of both operons is required for expression [11].

Associations of gadA with chemical compounds

  • The cloned gene was functional, because one transformant of A. oryzae containing multiple copies of the gadA gene had 10-fold the GAD activity and a 12-fold increase in gamma-aminobutyric acid production compared with the control strain [12].

Other interactions of gadA

  • Analysis of a gadX mutant grown in the different culture media with acidic and alkaline pH showed that regulation of perA, gadA and gadB by GadX was altered by the external pH and the culture media condition [8].
  • Transcriptional expression of Escherichia coli glutamate-dependent acid resistance genes gadA and gadBC in an hns rpoS mutant [13].
  • Fusions between lacZ and the gadA and gadBC operons indicate that this control occurs at the transcriptional level [11].
  • Northern blot analysis showed that induction of gadA and gadB transcription in stationary phase and at pH 5.5 was decreased in the topA mutant [14].
  • The genotypic assays were performed with hybridization probes generated by PCR amplification of 670- and 623-bp segments of the gadA/B (GAD) and uidA (GUD) genes, respectively [15].

Analytical, diagnostic and therapeutic context of gadA


  1. GadE (YhiE) activates glutamate decarboxylase-dependent acid resistance in Escherichia coli K-12. Ma, Z., Gong, S., Richard, H., Tucker, D.L., Conway, T., Foster, J.W. Mol. Microbiol. (2003) [Pubmed]
  2. Glutamate decarboxylase genes as a prescreening marker for detection of pathogenic Escherichia coli groups. Grant, M.A., Weagant, S.D., Feng, P. Appl. Environ. Microbiol. (2001) [Pubmed]
  3. Identification of the promoter regions and sigma(s)-dependent regulation of the gadA and gadBC genes associated with glutamate-dependent acid resistance in Shigella flexneri. Waterman, S.R., Small, P.L. FEMS Microbiol. Lett. (2003) [Pubmed]
  4. Antagonistic role of H-NS and GadX in the regulation of the glutamate decarboxylase-dependent acid resistance system in Escherichia coli. Giangrossi, M., Zattoni, S., Tramonti, A., De Biase, D., Falconi, M. J. Biol. Chem. (2005) [Pubmed]
  5. Polyamines and glutamate decarboxylase-based acid resistance in Escherichia coli. Jung, I.L., Kim, I.G. J. Biol. Chem. (2003) [Pubmed]
  6. Mechanisms of Transcription Activation Exerted by GadX and GadW at the gadA and gadBC Gene Promoters of the Glutamate-Based Acid Resistance System in Escherichia coli. Tramonti, A., De Canio, M., Delany, I., Scarlato, V., De Biase, D. J. Bacteriol. (2006) [Pubmed]
  7. Collaborative regulation of Escherichia coli glutamate-dependent acid resistance by two AraC-like regulators, GadX and GadW (YhiW). Ma, Z., Richard, H., Tucker, D.L., Conway, T., Foster, J.W. J. Bacteriol. (2002) [Pubmed]
  8. An activator of glutamate decarboxylase genes regulates the expression of enteropathogenic Escherichia coli virulence genes through control of the plasmid-encoded regulator, Per. Shin, S., Castanie-Cornet, M.P., Foster, J.W., Crawford, J.A., Brinkley, C., Kaper, J.B. Mol. Microbiol. (2001) [Pubmed]
  9. Functional characterization and regulation of gadX, a gene encoding an AraC/XylS-like transcriptional activator of the Escherichia coli glutamic acid decarboxylase system. Tramonti, A., Visca, P., De Canio, M., Falconi, M., De Biase, D. J. Bacteriol. (2002) [Pubmed]
  10. pH-dependent catabolic protein expression during anaerobic growth of Escherichia coli K-12. Yohannes, E., Barnhart, D.M., Slonczewski, J.L. J. Bacteriol. (2004) [Pubmed]
  11. Escherichia coli acid resistance: cAMP receptor protein and a 20 bp cis-acting sequence control pH and stationary phase expression of the gadA and gadBC glutamate decarboxylase genes. Castanie-Cornet, M.P., Foster, J.W. Microbiology (Reading, Engl.) (2001) [Pubmed]
  12. Cloning and nucleotide sequence of the glutamate decarboxylase-encoding gene gadA from Aspergillus oryzae. Kato, Y., Kato, Y., Furukawa, K., Hara, S. Biosci. Biotechnol. Biochem. (2002) [Pubmed]
  13. Transcriptional expression of Escherichia coli glutamate-dependent acid resistance genes gadA and gadBC in an hns rpoS mutant. Waterman, S.R., Small, P.L. J. Bacteriol. (2003) [Pubmed]
  14. Loss of topoisomerase I function affects the RpoS-dependent and GAD systems of acid resistance in Escherichia coli. Stewart, N., Feng, J., Liu, X., Chaudhuri, D., Foster, J.W., Drolet, M., Tse-Dinh, Y.C. Microbiology (Reading, Engl.) (2005) [Pubmed]
  15. Confirmational identification of Escherichia coli, a comparison of genotypic and phenotypic assays for glutamate decarboxylase and beta-D-glucuronidase. McDaniels, A.E., Rice, E.W., Reyes, A.L., Johnson, C.H., Haugland, R.A., Stelma, G.N. Appl. Environ. Microbiol. (1996) [Pubmed]
  16. Escherichia coli has two homologous glutamate decarboxylase genes that map to distinct loci. Smith, D.K., Kassam, T., Singh, B., Elliott, J.F. J. Bacteriol. (1992) [Pubmed]
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