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Gene Review

carA  -  carbamoyl phosphate synthetase small...

Escherichia coli str. K-12 substr. MG1655

Synonyms: ECK0033, JW0030, arg, cap, pyrA
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Disease relevance of carA

  • DNA sequence of the carA gene and the control region of carAB: tandem promoters, respectively controlled by arginine and the pyrimidines, regulate the synthesis of carbamoyl-phosphate synthetase in Escherichia coli K-12 [1].
  • Unorthodox expression of an enzyme: evidence for an untranslated region within carA from Pseudomonas aeruginosa [2].
  • This study demonstrates that treatment with rabbit anti-human C5a des arg antibodies attenuates ARDS and some of the systemic manifestations of sepsis in nonhuman primates [3].
  • In addition to both of these regions, another shigella chromosomal segment linked to the arg and mtl loci was necessary for fluid production in the rabbit ileal loop and for a positive Sereny reaction [4].
  • Although other gram-positive bacteria show similar arg clusters, this arrangement for carA is thus far unprecedented [5].

High impact information on carA

  • First, using leukocyte aggregometry, we demonstrated that the addition of a recently developed rabbit anti-human polyclonal antibody to C5a des arg to endotoxin-activated plasma prevented leukocyte aggregation in vitro [3].
  • Modifying the Arg residue in kalata with a keto aldehyde significantly reduced its activity against S. aureus whereas blocking the arg in CirA produced no significant effect [6].
  • Various fragments of the carA promoter-proximal region were fused in vitro with the lacZ gene [7].
  • Results obtained with these fusions indicate that (i) translation of the carA gene can be initiated in vivo without an AUG codon but very likely with an UUG or an AUU codon; (ii) the carAB downstream promoter is repressed by arginine; and (iii) the carAB upstream promoter is repressed by pyrimidines and subject to stringent control [7].
  • Aspergillus niger NW156 prtF pyrA leuA cspA transformed with the pyrA containing plasmid and a plasmid harboring the complete vaoA gene including the promoter and terminator was able to produce vaoA mRNA and active vanillyl-alcohol oxidase when grown on veratryl alcohol and anisyl alcohol [8].

Chemical compound and disease context of carA

  • A very high and thermostable N-acetylglutamate 5-phosphotransferase activity was detected in extracts of E. coli arg B mutants transformed with the 3.4 kb fragment on a plasmid [9].
  • Expression of arg genes of Escherichia coli during arginine limitation dependent upon stringent control of translation [10].
  • Erwinia sp. donors harboring pULB113 complemented mutations in various biosynthetic and catabolic genes (arg, gal, his, leu, met, pro, pur, thy) in Escherichia coli recA strains [11].
  • An E. coli strain carrying deletions in ndk and pyrA and pyrF, the structural genes for both pyruvate kinases, also grows and supports T4 infection [12].
  • Selected derivatives of NPYR were tested in the Escherichia coli K-12 (343/113) assay A specificity to revert the missense mutation at the arg locus and a dependence on phenobarbital-induced rat-liver S9 mix were noted with NPYR and its derivatives [13].

Biological context of carA

  • Evidence was obtained from subcloning, Southern blot hybridisation, enzyme stability studies and transformation of B. subtilis arginine auxotrophs that the 12 kbp EcoRI fragment carries all the arg genes [14].
  • Whereas carA and carB are separated by a short noncoding intercistronic region, the homologous sequences of the CAD gene encode an amino acid bridge [15].
  • However, comparison of the derived sequence for carA with the amino-terminal amino acid sequence for the small subunit suggested that codons 5 to 8 are not translated [2].
  • For this purpose an in-frame gene fusion between the A. niger trpC and Escherichia coli lacZ genes was constructed and shown to be functionally expressed after introduction into A. niger by cotransformation with the pyrA gene as selective marker [16].
  • The EcoRI segments define five cleavage sites near the arg region of the E. coli chromosome [17].

Anatomical context of carA

  • An S-100 supernatant freed of ribosomes was capable of producing hybridizable arg mRNA, but significant functional message was only produced when ribosomes were present [18].

Associations of carA with chemical compounds

  • The mutation is recessive to the wild-type allele and maps at or near the pyrA gene, but the mutant requires only arginine and not uracil for growth [19].
  • In vitro deletion of part of the vector's trp promoter did not affect complementation of the argB and C auxotrophs, implying that the S. coelicolor A3(2) arg genes may be expressed from their own promoter [20].
  • The P4XB2 strain, which is an arg R regulatory mutant, has a reduced lag effect in the presence of the tripeptide and appears to react to the intoxication by a further adjustment of the L-ornithine carbamoyltransferase cellular level [21].
  • This strain was previously found to receive Flac plasmid (N. Datta and R.W. Hedges, J. Gen Microbiol. 70:453-460, 1972). ilv, leu, met, arg, and his auxotrophs were complemented by plasmids carrying isofunctional genes; trp mutants were not complemented or were very poorly complemented [22].
  • We expressed three mutants of Corbicula AK domain 2 (His-60 to Gly or Arg, Asp-197 to Gly), and determined their K m arg and Vmax values [23].

Other interactions of carA

  • Duplications of arg genes produced in the Rec+ and in the recA genetic backgrounds are shown by heteroduplex analysis to be strictly tandem at the level of resolution of this technique [24].


  1. DNA sequence of the carA gene and the control region of carAB: tandem promoters, respectively controlled by arginine and the pyrimidines, regulate the synthesis of carbamoyl-phosphate synthetase in Escherichia coli K-12. Piette, J., Nyunoya, H., Lusty, C.J., Cunin, R., Weyens, G., Crabeel, M., Charlier, D., Glansdorff, N., Piérard, A. Proc. Natl. Acad. Sci. U.S.A. (1984) [Pubmed]
  2. Unorthodox expression of an enzyme: evidence for an untranslated region within carA from Pseudomonas aeruginosa. Wong, S.C., Abdelal, A.T. J. Bacteriol. (1990) [Pubmed]
  3. Effects of anti-C5a antibodies on the adult respiratory distress syndrome in septic primates. Stevens, J.H., O'Hanley, P., Shapiro, J.M., Mihm, F.G., Satoh, P.S., Collins, J.A., Raffin, T.A. J. Clin. Invest. (1986) [Pubmed]
  4. Alterations in the pathogenicity of Escherichia coli K-12 after transfer of plasmid and chromosomal genes from Shigella flexneri. Sansonetti, P.J., Hale, T.L., Dammin, G.J., Kapfer, C., Collins, H.H., Formal, S.B. Infect. Immun. (1983) [Pubmed]
  5. Arginine biosynthesis and regulation in Lactobacillus plantarum: the carA gene and the argCJBDF cluster are divergently transcribed. Bringel, F., Frey, L., Boivin, S., Hubert, J.C. J. Bacteriol. (1997) [Pubmed]
  6. An unusual structural motif of antimicrobial peptides containing end-to-end macrocycle and cystine-knot disulfides. Tam, J.P., Lu, Y.A., Yang, J.L., Chiu, K.W. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  7. Multiple regulatory signals in the control region of the Escherichia coli carAB operon. Bouvier, J., Patte, J.C., Stragier, P. Proc. Natl. Acad. Sci. U.S.A. (1984) [Pubmed]
  8. Molecular cloning, sequencing, and heterologous expression of the vaoA gene from Penicillium simplicissimum CBS 170.90 encoding vanillyl-alcohol oxidase. Benen, J.A., Sánchez-Torres, P., Wagemaker, M.J., Fraaije, M.W., van Berkel, W.J., Visser, J. J. Biol. Chem. (1998) [Pubmed]
  9. Primary structure, partial purification and regulation of key enzymes of the acetyl cycle of arginine biosynthesis in Bacillus stearothermophilus: dual function of ornithine acetyltransferase. Sakanyan, V., Charlier, D., Legrain, C., Kochikyan, A., Mett, I., Piérard, A., Glansdorff, N. J. Gen. Microbiol. (1993) [Pubmed]
  10. Expression of arg genes of Escherichia coli during arginine limitation dependent upon stringent control of translation. Williams, M.G., Rogers, P. J. Bacteriol. (1987) [Pubmed]
  11. pULB113, an RP4::mini-Mu plasmid, mediates chromosomal mobilization and R-prime formation in Erwinia amylovora, Erwinia chrysanthemi, and subspecies of Erwinia carotovora. Chatterjee, A.K., Ross, L.M., McEvoy, J.L., Thurn, K.K. Appl. Environ. Microbiol. (1985) [Pubmed]
  12. Effects of T4 phage infection and anaerobiosis upon nucleotide pools and mutagenesis in nucleoside diphosphokinase-defective Escherichia coli strains. Zhang, X., Lu, Q., Inouye, M., Mathews, C.K. J. Bacteriol. (1996) [Pubmed]
  13. Mutagenicity of N-nitrosopyrrolidine derivatives in Salmonella (Ames) and Escherichia coli K-12 (343/113) assays. Rao, T.K., Cox, J.T., Allen, B.E., Epler, J.L., Lijinsky, W. Mutat. Res. (1981) [Pubmed]
  14. Cloning of a Bacillus subtilis restriction fragment complementing auxotrophic mutants of eight Escherichia coli genes of arginine biosynthesis. Mountain, A., Mann, N.H., Munton, R.N., Baumberg, S. Mol. Gen. Genet. (1984) [Pubmed]
  15. Evidence that mammalian glutamine-dependent carbamyl phosphate synthetase arose through gene fusion. Kern, C.B., Lusty, C.J., Davidson, J.N. J. Mol. Evol. (1992) [Pubmed]
  16. Tryptophan auxotrophic mutants in Aspergillus niger: inactivation of the trpC gene by cotransformation mutagenesis. Goosen, T., van Engelenburg, F., Debets, F., Swart, K., Bos, K., van den Broek, H. Mol. Gen. Genet. (1989) [Pubmed]
  17. EcoRI cleavage sites in the argECBH region of the Escherichia coli chromosome. Devine, E.A., Moran, M.C., Jederlinic, P.J., Mazaitis, A.J., Vogel, H.J. J. Bacteriol. (1977) [Pubmed]
  18. Regulation and coupling of argECBH mRNA and enzyme synthesis in cell extracts of Escherichia coli. Zidwick, M.J., Keller, G., Rogers, P. J. Bacteriol. (1984) [Pubmed]
  19. Biochemical and genetic characterization of a carbamyl phosphate synthetase mutant of Escherichia coli K12. Bolivar, F., Galván, M., Martuscelli, J. J. Gen. Microbiol. (1976) [Pubmed]
  20. Cloning and expression in Escherichia coli of a Streptomyces coelicolor A3(2) argCJB gene cluster. Hindle, Z., Callis, R., Dowden, S., Rudd, B.A., Baumberg, S. Microbiology (Reading, Engl.) (1994) [Pubmed]
  21. Synthesis of a peptide form of N-delta-(phosphonoacetyl)-L-ornithine. Its antibacterial effect through the specific inhibition of Escherichia coli L-ornithine carbamoyltransferase. Penninckx, M., Gigot, D. J. Biol. Chem. (1979) [Pubmed]
  22. F'-plasmid transfer from Escherichia coli to Pseudomonas fluorescens. Mergeay, M., Gerits, J. J. Bacteriol. (1978) [Pubmed]
  23. Kinetic properties and structural characteristics of an unusual two-domain arginine kinase of the clam Corbicula japonica. Suzuki, T., Tomoyuki, T., Uda, K. FEBS Lett. (2003) [Pubmed]
  24. Tandem and inverted repeats of arginine genes in Escherichia coli: structural and evolutionary considerations. Charlier, D., Crabeel, M., Cunin, R., Glansdorff, N. Mol. Gen. Genet. (1979) [Pubmed]
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