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Gene Review

CPR1  -  peptidylprolyl isomerase CPR1

Saccharomyces cerevisiae S288c

Synonyms: CPH, CPH1, CYP1, Cyclophilin, Cyclosporin A-binding protein, ...
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Disease relevance of CPR1


High impact information on CPR1

  • Calcineurin is potently inhibited by immunosuppressant drugs, cyclosporin A and FK506, in the presence of their respective cytoplasmic immunophilin proteins, cyclophilin and FK506-binding protein [5].
  • Pin1 is thus an essential PPIase that regulates mitosis presumably by interacting with NIMA and attenuating its mitosis-promoting activity [6].
  • Peptidyl-prolyl cis-trans isomerase (PPIase) catalyses the cis-trans isomerization of proline imidic peptide bonds in oligopeptides and has been shown to accelerate the refolding of several proteins in vitro [7].
  • Thus we propose that the peptidyl-prolyl cis-trans isomerizing activity of PPIase may be involved in events, such as those occurring early in T-cell activation, that are suppressed by cyclosporin A [7].
  • The biochemical basis of CsA action is not known: its primary cellular target has been suggested to be calmodulin, the prolactin receptor or cyclophilin, a CsA-binding protein originally isolated from the cytosol of bovine thymocytes [8].

Chemical compound and disease context of CPR1

  • The peptidyl-prolyl cis-trans isomerases cyclophilin A and FKBP12, respectively, mediate CsA and FK506 toxicity in the cev1 mutant strain [9].
  • 7. From these characteristics, CP2/PCB can be attributed to the Pr" photochemical type with gamma1 < or = 0.05, which comprises the minor phyA fraction (phyA"), phyB, Adiantum phy1 and Synechocystis Cph1 in contrast to the major phyA' fraction (Pr' type with gamma1 = 0.5) [10].

Biological context of CPR1


Anatomical context of CPR1


Associations of CPR1 with chemical compounds


Physical interactions of CPR1


Regulatory relationships of CPR1

  • The levels of Cpr1p were reduced in the Deltavid22 mutants, implying that the expression of Cpr1p is regulated by Vid22p [22].
  • When ammonium is absent or present at low concentrations, Mep2p activates both the Cph1p-dependent mitogen-activated protein (MAP) kinase pathway and the cAMP-dependent signalling pathway in a Ras1p-dependent fashion via its C-terminal cytoplasmic tail, which is essential for signalling but dispensable for ammonium transport [23].

Other interactions of CPR1

  • We have isolated a yeast cyclophilin gene, CPR3, which encodes a presumptive mitochondrial isoform [12].
  • Furthermore, the addition of purified Cpr1p restored FBPase import in both the Deltacpr1 and the Deltavid22 mutants [22].
  • RPA14 is a single copy gene that maps to chromosome IV and is flanked by CYP1 and HOM2 [24].
  • Our results suggest that Cpr1p mediates Vid22p function and is directly involved in the import of FBPase into Vid vesicles [22].
  • Crosstalk of prolyl isomerases, Pin1/Ess1, and cyclophilin A [25].

Analytical, diagnostic and therapeutic context of CPR1


  1. The CYP2 gene of Saccharomyces cerevisiae encodes a cyclosporin A-sensitive peptidyl-prolyl cis-trans isomerase with an N-terminal signal sequence. Koser, P.L., Bergsma, D.J., Cafferkey, R., Eng, W.K., McLaughlin, M.M., Ferrara, A., Silverman, C., Kasyan, K., Bossard, M.J., Johnson, R.K. Gene (1991) [Pubmed]
  2. Structure and expression of cytosolic cyclophilin/peptidyl-prolyl cis-trans isomerase of higher plants and production of active tomato cyclophilin in Escherichia coli. Gasser, C.S., Gunning, D.A., Budelier, K.A., Brown, S.M. Proc. Natl. Acad. Sci. U.S.A. (1990) [Pubmed]
  3. Cloning and characterization of ppiB, a Bacillus subtilis gene which encodes a cyclosporin A-sensitive peptidyl-prolyl cis-trans isomerase. Herrler, M., Bang, H., Marahiel, M.A. Mol. Microbiol. (1994) [Pubmed]
  4. A Candida albicans homolog of a human cyclophilin gene encodes a peptidyl-prolyl cis-trans isomerase. Koser, P.L., Livi, G.P., Levy, M.A., Rosenberg, M., Bergsma, D.J. Gene (1990) [Pubmed]
  5. Calcineurin: form and function. Rusnak, F., Mertz, P. Physiol. Rev. (2000) [Pubmed]
  6. A human peptidyl-prolyl isomerase essential for regulation of mitosis. Lu, K.P., Hanes, S.D., Hunter, T. Nature (1996) [Pubmed]
  7. Peptidyl-prolyl cis-trans isomerase is the cyclosporin A-binding protein cyclophilin. Takahashi, N., Hayano, T., Suzuki, M. Nature (1989) [Pubmed]
  8. Sensitivity to cyclosporin A is mediated by cyclophilin in Neurospora crassa and Saccharomyces cerevisiae. Tropschug, M., Barthelmess, I.B., Neupert, W. Nature (1989) [Pubmed]
  9. vph6 mutants of Saccharomyces cerevisiae require calcineurin for growth and are defective in vacuolar H(+)-ATPase assembly. Hemenway, C.S., Dolinski, K., Cardenas, M.E., Hiller, M.A., Jones, E.W., Heitman, J. Genetics (1995) [Pubmed]
  10. Recombinant phytochrome of the moss Ceratodon purpureus (CP2): fluorescence spectroscopy and photochemistry. Sineshchekov, V., Koppel, L., Hughes, J., Lamparter, T., Zeidler, M. J. Photochem. Photobiol. B, Biol. (2000) [Pubmed]
  11. Cyclophilin A peptidyl-prolyl isomerase activity promotes ZPR1 nuclear export. Ansari, H., Greco, G., Luban, J. Mol. Cell. Biol. (2002) [Pubmed]
  12. A yeast cyclophilin gene essential for lactate metabolism at high temperature. Davis, E.S., Becker, A., Heitman, J., Hall, M.N., Brennan, M.B. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  13. The yeast cyclophilin multigene family: purification, cloning and characterization of a new isoform. McLaughlin, M.M., Bossard, M.J., Koser, P.L., Cafferkey, R., Morris, R.A., Miles, L.M., Strickler, J., Bergsma, D.J., Levy, M.A., Livi, G.P. Gene (1992) [Pubmed]
  14. Calcineurin-dependent growth of an FK506- and CsA-hypersensitive mutant of Saccharomyces cerevisiae. Parent, S.A., Nielsen, J.B., Morin, N., Chrebet, G., Ramadan, N., Dahl, A.M., Hsu, M.J., Bostian, K.A., Foor, F. J. Gen. Microbiol. (1993) [Pubmed]
  15. Cyclophilin catalyzes protein folding in yeast mitochondria. Matouschek, A., Rospert, S., Schmid, K., Glick, B.S., Schatz, G. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  16. Specific cross-linking of the proline isomerase cyclophilin to a non-proline-containing peptide. McNew, J.A., Sykes, K., Goodman, J.M. Mol. Biol. Cell (1993) [Pubmed]
  17. Role of hyphal formation in interactions of Candida albicans with endothelial cells. Phan, Q.T., Belanger, P.H., Filler, S.G. Infect. Immun. (2000) [Pubmed]
  18. Investigation of two distinct flavone synthases for plant-specific flavone biosynthesis in Saccharomyces cerevisiae. Leonard, E., Yan, Y., Lim, K.H., Koffas, M.A. Appl. Environ. Microbiol. (2005) [Pubmed]
  19. Functional co-expression of human oxidoreductase and cytochrome P450 1A1 in Saccharomyces cerevisiae results in increased EROD activity. Eugster, H.P., Bärtsch, S., Würgler, F.E., Sengstag, C. Biochem. Biophys. Res. Commun. (1992) [Pubmed]
  20. The basic helix-loop-helix transcription factor Cph2 regulates hyphal development in Candida albicans partly via TEC1. Lane, S., Zhou, S., Pan, T., Dai, Q., Liu, H. Mol. Cell. Biol. (2001) [Pubmed]
  21. Immunophilins interact with calcineurin in the absence of exogenous immunosuppressive ligands. Cardenas, M.E., Hemenway, C., Muir, R.S., Ye, R., Fiorentino, D., Heitman, J. EMBO J. (1994) [Pubmed]
  22. Cyclophilin A mediates Vid22p function in the import of fructose-1,6-bisphosphatase into Vid vesicles. Brown, C.R., Cui, D.Y., Hung, G.G., Chiang, H.L. J. Biol. Chem. (2001) [Pubmed]
  23. The Mep2p ammonium permease controls nitrogen starvation-induced filamentous growth in Candida albicans. Biswas, K., Morschhäuser, J. Mol. Microbiol. (2005) [Pubmed]
  24. The association of three subunits with yeast RNA polymerase is stabilized by A14. Smid, A., Riva, M., Bouet, F., Sentenac, A., Carles, C. J. Biol. Chem. (1995) [Pubmed]
  25. Crosstalk of prolyl isomerases, Pin1/Ess1, and cyclophilin A. Fujimori, F., Gunji, W., Kikuchi, J., Mogi, T., Ohashi, Y., Makino, T., Oyama, A., Okuhara, K., Uchida, T., Murakami, Y. Biochem. Biophys. Res. Commun. (2001) [Pubmed]
  26. Purification and properties of multiple molecular forms of yeast peptidyl prolyl cis-trans isomerase. Hasumi, H., Nishikawa, T. Biochim. Biophys. Acta (1993) [Pubmed]
  27. Yeast cyclophilin: isolation and characterization of the protein, cDNA and gene. Haendler, B., Keller, R., Hiestand, P.C., Kocher, H.P., Wegmann, G., Movva, N.R. Gene (1989) [Pubmed]
  28. Identification and characterization of Cor33p, a novel protein implicated in tolerance towards oxidative stress in Candida albicans. Sohn, K., Roehm, M., Urban, C., Saunders, N., Rothenstein, D., Lottspeich, F., Schröppel, K., Brunner, H., Rupp, S. Eukaryotic Cell (2005) [Pubmed]
  29. Evidence for an interaction between the CYP1(HAP1) activator and a cellular factor during heme-dependent transcriptional regulation in the yeast Saccharomyces cerevisiae. Fytlovich, S., Gervais, M., Agrimonti, C., Guiard, B. EMBO J. (1993) [Pubmed]
  30. Substitution in position 3 of cyclosporin A abolishes the cyclophilin-mediated gain-of-function mechanism but not immunosuppression. Baumgrass, R., Zhang, Y., Erdmann, F., Thiel, A., Weiwad, M., Radbruch, A., Fischer, G. J. Biol. Chem. (2004) [Pubmed]
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