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Gene Review

proA  -  gamma-glutamylphosphate reductase

Escherichia coli str. K-12 substr. MG1655

Synonyms: ECK0244, JW0233, pro
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Disease relevance of proA


High impact information on proA

  • No other proA sequences were required for toxin maturation, and excess Ca2+ prevented acylation of both lysines [6].
  • Nucleotide sequence analysis of the proBA locus allowed gene assignments consistent with the NH2 and COOH-terminal analyses and amino acid compositions of homogeneous preparations of the proB and proA proteins [7].
  • The stoichiometry of the oxidative phosphorylation of glutamic acid 5-semialdehyde by gamma-glutamyl phosphate reductase (glutamate semialdehyde dehydrogenase) has been established [8].
  • 3. Gamma-Glutamyl phosphate reductase and 1-pyrroline-5-carboxylate reductase (EC have mol.wts. of approx. 125000 and 190000 respectively, the specific activity of the latter being 5 X 10(3)-fold greater than either of the other two biosynthetic enzymes or of the total pathway in vivo [9].
  • These results suggest that the altered gamma-glutamyl kinase results in stabilization of the complex or has an indirect effect on gamma-glutamyl phosphate reductase activity, which leads to an increase in L-proline production in Saccharomyces cerevisiae [10].

Chemical compound and disease context of proA


Biological context of proA

  • Gamma-delta insertion mutagenesis of this subcloned fragment indicated that proB and proA genes of V. parahaemolyticus might be transcribed from different promoters [15].
  • The gene dosage analysis showed that the location of the remaining operon (now called rrnH) is between metD and proA [16].
  • Recombinant cosmids able to complement the thr-1, leuB, and proA mutations of the host were identified [17].
  • The Pro+ recombinant cosmid restored wild-type phenotype in proA and proB but not in the proC mutants of E. coli [17].
  • These tests revealed that the proBA genes of S. typhimurium form an operon, whose direction of transcription is from proB to proA [18].

Anatomical context of proA

  • The proA gene encodes a typical 21-aa N-terminal signal sequence which, when fused to alkaline phosphatase by means of transposon TnphoA, was able to mediate transport of the alkaline phosphatase to the periplasm in E. coli [19].

Associations of proA with chemical compounds

  • Mutants with a feedback resistant N-acetylglutamate synthase have been isolated from a proA/B, argD, argR strain by screening for proline excretion on minimal medium with arginine [20].
  • Together with a proA gene described earlier, these new genes describe the major C. glutamicum proline biosynthetic pathway [2].
  • However, the capacity of glutamate-gamma-semialdehyde dehydrogenase from the osmotolerant mutant to interact with the kinase was altered in thermal stability, suggesting that mutations in both proB and proA may be required for osmotolerance [21].
  • While a 3.9 kb fragment which complemented proA also complemented proB, a 15 kb fragment complementing leuB could not complement other leu mutations [22].
  • The hybrid plasmid pLC44-11 from the Clarke and Carbon collection, which was known to carry the proA gene, was shown also to contain the phoE gene [23].

Other interactions of proA


Analytical, diagnostic and therapeutic context of proA


  1. Cloning and expression in Escherichia coli K-12 of the structural gene for outer membrane PhoE protein from Enterobacter cloacae. Verhoef, C., van Koppen, C., Overduin, P., Lugtenberg, B., Korteland, J., Tommassen, J. Gene (1984) [Pubmed]
  2. Mutations in the Corynebacterium glutamicum proline biosynthetic pathway: a natural bypass of th proA step. Ankri, S., Serebrijski, I., Reyes, O., Leblon, G. J. Bacteriol. (1996) [Pubmed]
  3. Physical map of Salmonella typhimurium LT2 DNA in the vicinity of the proA gene. Riley, M., O'Reilly, C., McConnell, D. J. Bacteriol. (1984) [Pubmed]
  4. Identification and characterization of the proBA operon of Streptococcus bovis. Campanile, C., Forlani, G., Basso, A.L., Marasco, R., Ricca, E., Sacco, M., Ferrara, L., De Felice, M. Appl. Environ. Microbiol. (1993) [Pubmed]
  5. Increase in osmotolerance of Rhizobium fredii soybean isolate BD32 by the proB proA operon of Escherichia coli. Neumivakin, L.V., Solovjev, V.P., Sokhansanj, A., Tilba, V.A., Moseiko, N.A., Shachbasian, R.V., Piruzian, E.S. Biochem. Biophys. Res. Commun. (1995) [Pubmed]
  6. Independent interaction of the acyltransferase HlyC with two maturation domains of the Escherichia coli toxin HlyA. Stanley, P., Koronakis, V., Hardie, K., Hughes, C. Mol. Microbiol. (1996) [Pubmed]
  7. Analysis of the Escherichia coli proBA locus by DNA and protein sequencing. Deutch, A.H., Rushlow, K.E., Smith, C.J. Nucleic Acids Res. (1984) [Pubmed]
  8. Proline biosynthesis in Escherichia coli. Stoichiometry and end-product identification of the reaction catalysed by glutamate semialdehyde dehydrogenase. Hayzer, D.J., Leisinger, T. Biochem. J. (1981) [Pubmed]
  9. The enzymes of proline biosynthesis in Escherichia coli. Their molecular weights and the problem of enzyme aggregation. Hayzer, D.J., Moses, V. Biochem. J. (1978) [Pubmed]
  10. L-proline accumulation and freeze tolerance of Saccharomyces cerevisiae are caused by a mutation in the PRO1 gene encoding gamma-glutamyl kinase. Morita, Y., Nakamori, S., Takagi, H. Appl. Environ. Microbiol. (2003) [Pubmed]
  11. Insertion element IS121 is near proA in the chromosomes of Escherichia coli K-12 strains. Timmons, M.S., Spear, K., Deonier, R.C. J. Bacteriol. (1984) [Pubmed]
  12. Cloning, sequencing, and expression of the gene encoding 4-hydroxy-4-methyl-2-oxoglutarate aldolase from Pseudomonas ochraceae NGJ1. Maruyama, K., Miwa, M., Tsujii, N., Nagai, T., Tomita, N., Harada, T., Sobajima, H., Sugisaki, H. Biosci. Biotechnol. Biochem. (2001) [Pubmed]
  13. Cloning of genes for proline and leucine biosynthesis from Brucella abortus by functional complementation in Escherichia coli. Essenberg, R.C., Sharma, Y.K. J. Gen. Microbiol. (1993) [Pubmed]
  14. The gene-enzyme relationships of proline biosynthesis in Escherichia coli. Hayzer, D.J., Leisinger, T. J. Gen. Microbiol. (1980) [Pubmed]
  15. Genetic and physical characterization of proBA genes of the marine bacterium Vibrio parahaemolyticus. Datta, A.R., Ostroff, R., MacQuillan, A.M. Appl. Environ. Microbiol. (1987) [Pubmed]
  16. Chromosomal locations of the genes for rRNA in Escherichia coli K-12. Ellwood, M., Nomura, M. J. Bacteriol. (1982) [Pubmed]
  17. Functional expression of Aquaspirillum magnetotacticum genes in Escherichia coli K12. Waleh, N.S. Mol. Gen. Genet. (1988) [Pubmed]
  18. Genetic analysis of the proBA genes of Salmonella typhimurium: physical and genetic analyses of the cloned proB+ A+ genes of Escherichia coli and of a mutant allele that confers proline overproduction and enhanced osmotolerance. Mahan, M.J., Csonka, L.N. J. Bacteriol. (1983) [Pubmed]
  19. Nucleotide sequence of the Vibrio alginolyticus calcium-dependent, detergent-resistant alkaline serine exoprotease A. Deane, S.M., Robb, F.T., Robb, S.M., Woods, D.R. Gene (1989) [Pubmed]
  20. Isolation and characterization of mutants with a feedback resistant N-acetylglutamate synthase in Escherichia coli K 12. Eckhardt, T., Leisinger, T. Mol. Gen. Genet. (1975) [Pubmed]
  21. Characterization of a gamma-glutamyl kinase from Escherichia coli that confers proline overproduction and osmotic tolerance. Smith, L.T. J. Bacteriol. (1985) [Pubmed]
  22. Cloning of genes required for amino acid biosynthesis from Leptospira interrogans serovar icterohaemorrhagiae. Richaud, C., Margarita, D., Baranton, G., Saint Girons, I. J. Gen. Microbiol. (1990) [Pubmed]
  23. Cloning of phoE, the structural gene for the Escherichia coli phosphate limitation-inducible outer membrane pore protein. Tommassen, J., Overduin, P., Lugtenberg, B., Bergmans, H. J. Bacteriol. (1982) [Pubmed]
  24. Cloning in Escherichia coli of genes involved in the synthesis of proline and leucine in Desulfovibrio desulfuricans Norway. Fons, M., Cami, B., Patte, J.C., Chippaux, M. Mol. Gen. Genet. (1987) [Pubmed]
  25. Molecular characterization of extraintestinal pathogenic Escherichia coli (ExPEC) pathogenicity islands in F165-positive E. coli strain from a diseased animal. Dezfulian, H., Tremblay, D., Harel, J. FEMS Microbiol. Lett. (2004) [Pubmed]
  26. Construction of a novel hydroxyproline-producing recombinant Escherichia coli by introducing a proline 4-hydroxylase gene. Shibasaki, T., Hashimoto, S., Mori, H., Ozaki, A. J. Biosci. Bioeng. (2000) [Pubmed]
  27. Directed evolution of an artificial bifunctional enzyme, gamma-glutamyl kinase/gamma-glutamyl phosphate reductase, for improved osmotic tolerance of Escherichia coli transformants. Chen, M., Cao, J., Zheng, C., Liu, Q. FEMS Microbiol. Lett. (2006) [Pubmed]
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