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Gene Review

nadA  -  quinolinate synthetase

Salmonella enterica subsp. enterica serovar Typhimurium str. LT2

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Disease relevance of nadA

  • In Salmonella typhimurium, de novo synthesis of NAD is regulated through the transcriptional control of the nadA and nadB loci [1].

High impact information on nadA

  • The nadI protein regulates transcription of the nadA and nadB biosynthetic genes and modulates activity of the NMN permease; both regulatory activities respond to the internal pyridine nucleotide level [2].
  • An inverted repeat of the sequence TAAACAA observed in the proposed promoter region of pncB is also present in the promoter of nadA, which, like pncB, is also regulated by the NadR (NadI) repressor [3].
  • Regulation of NAD metabolism in Salmonella typhimurium: molecular sequence analysis of the bifunctional nadR regulator and the nadA-pnuC operon [1].
  • The unusual NMN transport activity requires both the PnuC and NadR proteins, with the pnuC locus residing in an operon with nadA [1].
  • As NAD levels increase within the cell, the affinity of NadR for the operator regions of nadA, nadB, and pncB increases, repressing the transcription of these target genes [1].

Biological context of nadA


Associations of nadA with chemical compounds

  • The concentration of exogenously supplied pyridine nucleotide necessary to effect repression of NAPRTas was found to be that concentration which will result in a nadA mutant generation time of less than 60 min [6].
  • Increases in nadAB transcription directly correlated with decreases in intracellular NAD(P) levels, and kinetic studies indicated that the NAD analogue 6-amino NAD was ineffective in repressing either nadA or nadB [7].

Regulatory relationships of nadA

  • It has been reported that this gene and nadA are regulated by a positive regulatory protein encoded in the nadB region [8].

Other interactions of nadA

  • Polarity tests, with pnuC::Mu d-lac operon fusions, reveal that the pnuC gene is the promoter distal gene in an operon with the nadA gene, which encodes the second enzyme of the pyridine biosynthetic pathway [4].
  • The same gene, called envD, appears to be involved in both mutant strains. envD has been located at minute 33 of the Salmonella genetic map, between markers sucA and nadA, very close to the latter. envD also affects morphological characteristics of the cells [9].


  1. Regulation of NAD metabolism in Salmonella typhimurium: molecular sequence analysis of the bifunctional nadR regulator and the nadA-pnuC operon. Foster, J.W., Park, Y.K., Penfound, T., Fenger, T., Spector, M.P. J. Bacteriol. (1990) [Pubmed]
  2. Activity of the nicotinamide mononucleotide transport system is regulated in Salmonella typhimurium. Zhu, N., Olivera, B.M., Roth, J.R. J. Bacteriol. (1991) [Pubmed]
  3. Cloning and nucleic acid sequence of the Salmonella typhimurium pncB gene and structure of nicotinate phosphoribosyltransferase. Vinitsky, A., Teng, H., Grubmeyer, C.T. J. Bacteriol. (1991) [Pubmed]
  4. Genetic characterization of the pnuC gene, which encodes a component of the nicotinamide mononucleotide transport system in Salmonella typhimurium. Zhu, N., Olivera, B.M., Roth, J.R. J. Bacteriol. (1989) [Pubmed]
  5. Genetics of NAD metabolism in Salmonella typhimurium and cloning of the nadA and pnuC loci. Tirgari, S., Spector, M.P., Foster, J.W. J. Bacteriol. (1986) [Pubmed]
  6. Pyridine nucleotide cycle of Salmonella typhimurium: regulation of nicotinic acid phosphoribosyltransferase and nicotinamide deamidase. Foster, J.W., Kinney, D.M., Moat, A.G. J. Bacteriol. (1979) [Pubmed]
  7. Regulation of NAD biosynthesis in Salmonella typhimurium: expression of nad-lac gene fusions and identification of a nad regulatory locus. Holley, E.A., Spector, M.P., Foster, J.W. J. Gen. Microbiol. (1985) [Pubmed]
  8. Genetic characterization and regulation of the nadB locus of Salmonella typhimurium. Cookson, B.T., Olivera, B.M., Roth, J.R. J. Bacteriol. (1987) [Pubmed]
  9. Envelope mutation promoting autolysis in Salmonella typhimurium. Antón, D.N., Orce, L.V. Mol. Gen. Genet. (1976) [Pubmed]
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