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Gene Review

phoA  -  alkaline phosphatase

Escherichia coli O157:H7 str. EDL933

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Disease relevance of phoA

  • Consistent with this notion, the introduction of the E. coli phoA gene in S. flexneri resulted in the induction of alkaline phosphatase synthesis under phosphate limitation [1].
  • The isolation of a plaque-forming lambda transducing phage carrying the entire phoA gene is also described [2].
  • Self-cloning minitransposon phoA gene-fusion system promotes the rapid genetic analysis of secreted proteins in gram-negative bacteria [3].
  • Bacillus subtilis has an alkaline phosphatase multigene family [4].
  • Identification of Treponema pallidum subspecies pallidum genes encoding signal peptides and membrane-spanning sequences using a novel alkaline phosphatase expression vector [5].

High impact information on phoA


Chemical compound and disease context of phoA


Biological context of phoA

  • A number of mutant alleles affecting the Pst phosphate transport system have been divided into three complementation groups on the basis of constitutive alkaline phosphatase activity in appropriate partial diploid strains [11].
  • Heterodimeric alkaline phosphatases were created using two methods: (1) in vitro formation by dissociation at acid pH followed by reassociation at slightly alkaline pH conditions in the presence of zinc and magnesium ions; and (2) in vivo expression from a plasmid carrying two different phoA genes [12].
  • In addition, the phoR gene product acts as a negative regulator.--We describe a model for phoA gene expression consistent with this new evidence [13].
  • Use of gene fusions to determine the orientation of gene phoA on the Escherichia coli chromosome [14].
  • We present genetic evidence which demonstrates that the phoA gene is transcribed in the clockwise direction on the Escherichia coli chromosome, in contrast to an earlier proposal [14].

Anatomical context of phoA

  • One mutant selected for its impaired ability to invade epithelial cells had an insertion of a Tn phoA transposon within the nlpI gene encoding the lipoprotein NlpI [15].
  • Repressive effect of imbalance in the phospholipid composition and total charge of membranes of Escherichia coli on the phoA gene transcription [16].
  • The alkaline phosphatase activity increased drastically when positive charges were introduced, indicating that the SecY domain fused to PhoA showed a change in localization from the cytoplasm to the periplasm [17].
  • PLA2-stimulating activity is greatly enhanced after exposing isolated ganglia to phorbol dibutyrate (PDBu) and is reduced by treatment with immobilized E. coli alkaline phosphatase [18].

Associations of phoA with chemical compounds

  • Alkaline phosphatase synthesis was initiated by a temperature shift in a strain carrying a phoA amber mutation and a temperature-sensitive suppressor mutation; acid hexose phosphatase was studied after relief of catabolite repression [19].
  • We have used gene fusions between mtlA (encoding the permease) and 'phoA (encoding alkaline phosphatase lacking its signal sequence) to further investigate the topology of the mannitol permease [20].
  • T. pallidum-AP fusion proteins which partitioned into the hydrophobic detergent phase but did not incorporate palmitate were also identified [5].
  • Triton X-114 detergent phase partitioning of individual T. pallidum-AP fusions revealed several clones whose AP activity partitioned preferentially into the hydrophobic detergent phase [5].
  • The alkaline phosphatase (AP) superfamily is an ideal system to use in making such comparisons given the extensive data available on both nonenzymatic and enzymatic phosphoryl transfer reactions [21].

Other interactions of phoA

  • The orientation of phoA and the exact position of its N-terminal end on this map were determined by identifying a subfragment which carried the phoA promoter and by determining the nucleotide sequence of a 160 bp portion of this subfragment comprising the codons for the N-terminal end of pre-alkaline phosphatase [22].

Analytical, diagnostic and therapeutic context of phoA


  1. The pho regulon of Shigella flexneri. Scholten, M., Janssen, R., Bogaarts, C., van Strien, J., Tommassen, J. Mol. Microbiol. (1995) [Pubmed]
  2. Deletion map of the Escherichia coli structural gene for alkaline phosphatase, phoA. Sarthy, A., Michaelis, S., Beckwith, J. J. Bacteriol. (1981) [Pubmed]
  3. Self-cloning minitransposon phoA gene-fusion system promotes the rapid genetic analysis of secreted proteins in gram-negative bacteria. Bolton, A.J., Woods, D.E. BioTechniques (2000) [Pubmed]
  4. Bacillus subtilis alkaline phosphatases III and IV. Cloning, sequencing, and comparisons of deduced amino acid sequence with Escherichia coli alkaline phosphatase three-dimensional structure. Hulett, F.M., Kim, E.E., Bookstein, C., Kapp, N.V., Edwards, C.W., Wyckoff, H.W. J. Biol. Chem. (1991) [Pubmed]
  5. Identification of Treponema pallidum subspecies pallidum genes encoding signal peptides and membrane-spanning sequences using a novel alkaline phosphatase expression vector. Blanco, D.R., Giladi, M., Champion, C.I., Haake, D.A., Chikami, G.K., Miller, J.N., Lovett, M.A. Mol. Microbiol. (1991) [Pubmed]
  6. Phase variation of gonococcal protein II: regulation of gene expression by slipped-strand mispairing of a repetitive DNA sequence. Murphy, G.L., Connell, T.D., Barritt, D.S., Koomey, M., Cannon, J.G. Cell (1989) [Pubmed]
  7. Expression of separate isoforms of human tau protein: correlation with the tau pattern in brain and effects on tubulin polymerization. Goedert, M., Jakes, R. EMBO J. (1990) [Pubmed]
  8. Polymeric sequences reveal a functional interrelationship between hydrophobicity and length of signal peptides. Chou, M.M., Kendall, D.A. J. Biol. Chem. (1990) [Pubmed]
  9. Reduction of the multiple organ injury and dysfunction caused by endotoxemia in 5-lipoxygenase knockout mice and by the 5-lipoxygenase inhibitor zileuton. Collin, M., Rossi, A., Cuzzocrea, S., Patel, N.S., Di Paola, R., Hadley, J., Collino, M., Sautebin, L., Thiemermann, C. J. Leukoc. Biol. (2004) [Pubmed]
  10. Membrane topology of the chromate transporter ChrA of Pseudomonas aeruginosa. Jiménez-Mejía, R., Campos-García, J., Cervantes, C. FEMS Microbiol. Lett. (2006) [Pubmed]
  11. Genetic analysis of mutants affected in the Pst inorganic phosphate transport system. Cox, G.B., Rosenberg, H., Downie, J.A., Silver, S. J. Bacteriol. (1981) [Pubmed]
  12. Characterization of heterodimeric alkaline phosphatases from Escherichia coli: an investigation of intragenic complementation. Hehir, M.J., Murphy, J.E., Kantrowitz, E.R. J. Mol. Biol. (2000) [Pubmed]
  13. Mutants affected in alkaline phosphatase, expression: evidence for multiple positive regulators of the phosphate regulon in Escherichia coli. Wanner, B.L., Latterell, P. Genetics (1980) [Pubmed]
  14. Use of gene fusions to determine the orientation of gene phoA on the Escherichia coli chromosome. Sarthy, A., Michaelis, S., Beckwith, J. J. Bacteriol. (1981) [Pubmed]
  15. Involvement of lipoprotein NlpI in the virulence of adherent invasive Escherichia coli strain LF82 isolated from a patient with Crohn's disease. Barnich, N., Bringer, M.A., Claret, L., Darfeuille-Michaud, A. Infect. Immun. (2004) [Pubmed]
  16. Repressive effect of imbalance in the phospholipid composition and total charge of membranes of Escherichia coli on the phoA gene transcription. Krasovskaya, L.A., Anisimova, E.V., Golovastov, V.V., Kulaev, I.S., Nesmeyanova, M.A. Dokl. Biochem. Biophys. (2006) [Pubmed]
  17. A positively charged region is a determinant of the orientation of cytoplasmic membrane proteins in Escherichia coli. Yamane, K., Akiyama, Y., Ito, K., Mizushima, S. J. Biol. Chem. (1990) [Pubmed]
  18. A phospholipase A2-stimulating protein regulated by protein kinase C in Aplysia neurons. Calignano, A., Piomelli, D., Sacktor, T.C., Schwartz, J.H. Brain Res. Mol. Brain Res. (1991) [Pubmed]
  19. Enzyme secretion in Escherichia coli: synthesis of alkaline phosphatase and acid hexose phosphatase in the absence of phospholipid synthesis. Beacham, I.R., Taylor, N.S., Youell, M. J. Bacteriol. (1976) [Pubmed]
  20. Membrane topology analysis of Escherichia coli mannitol permease by using a nested-deletion method to create mtlA-phoA fusions. Sugiyama, J.E., Mahmoodian, S., Jacobson, G.R. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  21. Structural and functional comparisons of nucleotide pyrophosphatase/phosphodiesterase and alkaline phosphatase: implications for mechanism and evolution. Zalatan, J.G., Fenn, T.D., Brunger, A.T., Herschlag, D. Biochemistry (2006) [Pubmed]
  22. Recombinant plasmids with genes for the biosynthesis of alkaline phosphatase of Escherichia coli. Boidol, W., Simonis, M., Töpert, M., Siewert, G. Mol. Gen. Genet. (1982) [Pubmed]
  23. Regulation of the cytotoxic enterotoxin gene in Aeromonas hydrophila: characterization of an iron uptake regulator. Sha, J., Lu, M., Chopra, A.K. Infect. Immun. (2001) [Pubmed]
  24. Use of metal chelate affinity chromatography for removal of zinc ions from alkaline phosphatase from Escherichia coli. Lubińska, V.K., Muszyńska, G. J. Chromatogr. (1990) [Pubmed]
  25. A comparison of alkaline phosphatase and radiolabelled gene probes with bioassays for enterotoxigenic Escherichia coli. Bopp, C.A., Threatt, V.L., Moseley, S.L., Wells, J.G., Wachsmuth, I.K. Mol. Cell. Probes (1990) [Pubmed]
  26. Directed evolution of the 5'-untranslated region of the phoA gene in Escherichia coli simultaneously yields a stronger promoter and a stronger Shine-Dalgarno sequence. Huang, X., Zhang, X.E., Zhou, Y.F., Zhang, Z.P., Cass, A.E. Biotechnology journal (2006) [Pubmed]
  27. Optimizing the generation of recombinant single-chain antibodies against placental alkaline phosphatase. Sheikholvaezin, A., Sandström, P., Eriksson, D., Norgren, N., Riklund, K., Stigbrand, T. Hybridoma (2005) (2006) [Pubmed]
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