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Gene Review

PDR12  -  ATP-binding cassette multidrug transporter...

Saccharomyces cerevisiae S288c

Synonyms: ATP-dependent permease PDR12, LPE14C, YPL058C
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Disease relevance of PDR12

  • Sorbate hypersensitivity was detected in mutants of the shikimate biosynthesis pathway, strains lacking the PDR12 efflux pump or WAR1, a transcription factor mediating stress induction of PDR12 [1].
  • The normal physiological function of Pdr12 is perhaps to protect against the potential toxicity of weak organic acids secreted by competitor organisms, acids that will accumulate to inhibitory levels in cells at low pH [2].

High impact information on PDR12

  • However, sorbate treatment causes a dramatic induction of Pdr12 in the plasma membrane [2].
  • The appearance of phosphorylated War1p isoforms coincides with transcriptional activation of PDR12 [3].
  • Promoter deletion analysis identified a novel cis-acting weak acid response element (WARE) in the PDR12 promoter required for PDR12 induction [3].
  • The Saccharomyces cerevisiae ATP-binding cassette (ABC) transporter Pdr12p effluxes weak acids such as sorbate and benzoate, thus mediating stress adaptation [3].
  • Loss of Cmk1 Ca(2+)-calmodulin-dependent protein kinase in yeast results in constitutive weak organic acid resistance, associated with a post-transcriptional activation of the Pdr12 ATP-binding cassette transporter [4].

Chemical compound and disease context of PDR12


Biological context of PDR12


Anatomical context of PDR12

  • In Saccharomyces cerevisiae, this stress response leads to strong induction of the Pdr12 ATP-binding cassette (ABC) transporter, which catalyses the active efflux of weak acid anions from the cytosol of adapted cells [4].

Associations of PDR12 with chemical compounds

  • Its gene (PDR12) is strongly induced by sorbate, benzoate and certain other moderately lipophilic carboxylate compounds, but not by organic alcohols or high levels of acetate [7].
  • Moreover, our quantitative PCR showed that expression of PDR12 increased under acid shock response with lactic acid and decreased under acid adaptation with hydrochloric acid [8].
  • Exposure of Saccharomyces cerevisiae to sorbic acid strongly induces two plasma membrane proteins, one of which is identified in this study as the ATP-binding cassette (ABC) transporter Pdr12 [2].
  • Thus, we have shown that Pdr12 catalyzes the energy-dependent extrusion of fluorescein from the cytosol [6].

Other interactions of PDR12


  1. Global phenotypic analysis and transcriptional profiling defines the weak acid stress response regulon in Saccharomyces cerevisiae. Schüller, C., Mamnun, Y.M., Mollapour, M., Krapf, G., Schuster, M., Bauer, B.E., Piper, P.W., Kuchler, K. Mol. Biol. Cell (2004) [Pubmed]
  2. The pdr12 ABC transporter is required for the development of weak organic acid resistance in yeast. Piper, P., Mahé, Y., Thompson, S., Pandjaitan, R., Holyoak, C., Egner, R., Mühlbauer, M., Coote, P., Kuchler, K. EMBO J. (1998) [Pubmed]
  3. War1p, a novel transcription factor controlling weak acid stress response in yeast. Kren, A., Mamnun, Y.M., Bauer, B.E., Schüller, C., Wolfger, H., Hatzixanthis, K., Mollapour, M., Gregori, C., Piper, P., Kuchler, K. Mol. Cell. Biol. (2003) [Pubmed]
  4. Loss of Cmk1 Ca(2+)-calmodulin-dependent protein kinase in yeast results in constitutive weak organic acid resistance, associated with a post-transcriptional activation of the Pdr12 ATP-binding cassette transporter. Holyoak, C.D., Thompson, S., Ortiz Calderon, C., Hatzixanthis, K., Bauer, B., Kuchler, K., Piper, P.W., Coote, P.J. Mol. Microbiol. (2000) [Pubmed]
  5. A new physiological role for Pdr12p in Saccharomyces cerevisiae: export of aromatic and branched-chain organic acids produced in amino acid catabolism. Hazelwood, L.A., Tai, S.L., Boer, V.M., de Winde, J.H., Pronk, J.T., Daran, J.M. FEMS Yeast Res. (2006) [Pubmed]
  6. The Saccharomyces cerevisiae weak-acid-inducible ABC transporter Pdr12 transports fluorescein and preservative anions from the cytosol by an energy-dependent mechanism. Holyoak, C.D., Bracey, D., Piper, P.W., Kuchler, K., Coote, P.J. J. Bacteriol. (1999) [Pubmed]
  7. Moderately lipophilic carboxylate compounds are the selective inducers of the Saccharomyces cerevisiae Pdr12p ATP-binding cassette transporter. Hatzixanthis, K., Mollapour, M., Seymour, I., Bauer, B.E., Krapf, G., Schüller, C., Kuchler, K., Piper, P.W. Yeast (2003) [Pubmed]
  8. Yeast genes involved in response to lactic acid and acetic acid: acidic conditions caused by the organic acids in Saccharomyces cerevisiae cultures induce expression of intracellular metal metabolism genes regulated by Aft1p. Kawahata, M., Masaki, K., Fujii, T., Iefuji, H. FEMS Yeast Res. (2006) [Pubmed]
  9. Weak organic acid stress inhibits aromatic amino acid uptake by yeast, causing a strong influence of amino acid auxotrophies on the phenotypes of membrane transporter mutants. Bauer, B.E., Rossington, D., Mollapour, M., Mamnun, Y., Kuchler, K., Piper, P.W. Eur. J. Biochem. (2003) [Pubmed]
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