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Gene Review

Cpr  -  Cytochrome P450 reductase

Drosophila melanogaster

Synonyms: CCR, CG11567, CPR, DMR, DmCPR, ...
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Disease relevance of Cpr


High impact information on Cpr

  • Using the Somatic Mutation And Recombination Test (SMART) we have demonstrated that transgenic larvae expressing the P450 are hypersensitive to the anticancer drug cyclophosphamide, a procarcinogenic substrate which is activated by the enzyme [3].
  • In this study we have used precise genetic mapping to identify a mechanism of lufenuron resistance: the overexpression of the cytochrome P450 gene Cyp12a4 [4].
  • Shade is the Drosophila P450 enzyme that mediates the hydroxylation of ecdysone to the steroid insect molting hormone 20-hydroxyecdysone [5].
  • The present data show that the wild-type genes of two members of the Halloween family of embryonic lethals, disembodied (dib) and shadow (sad), code for mitochondrial cytochromes P450 that mediate the last two hydroxylation reactions in the ecdysteroidogenic pathway in Drosophila, namely the C22- and C2-hydroxylases [6].
  • Five different enzymatic activities, catalyzed by both microsomal and mitochondrial cytochrome P450 monooxygenases (CYPs), are strongly implicated in the biosynthesis of ecdysone (E) from cholesterol [6].

Biological context of Cpr

  • CPR is a single copy gene as shown by genomic Southern hybridisation and maps to the cytogenetic map position 26C on the second chromosome [7].
  • The cytochrome P450 gene superfamily is represented by 90 sequences in the Drosophila melanogaster genome [8].
  • In Drosophila, a number of P450 monooxygenases are involved in the metabolism of foreign chemicals [Dunkov et al. (1996) Cytochrome P450 gene cluster in Drosophila melanogaster, Mol. Gen. Genet. 251, 290-297] [7].
  • Of these 90 P450 sequences, 83 code for apparently functional genes whereas seven are apparent pseudogenes [8].
  • The largest cDNA of 2471 nucleotides in length contained an open reading frame of 693 amino acids that includes the putative CPR sequence [7].

Anatomical context of Cpr

  • In contrast, increases in the rate of BP turnover per molecule of cytochrome P-450, intensity of the hemoprotein band with apparent molecular weight 56,000 and the yield of BP 7,8-dihydrodiol and 9,10-dihydrodiol occurred only in microsomes of BP-pretreated 364yv flies but not of Turku ones [9].
  • Feeding of these compounds in combination with the inhibition of cytochrome P-450 by 1-phenylimidazole (PhI) allowed sufficient quantities of the mutagen to reach the gonads and to produce significant genetic damage [10].
  • These results indicate that the fat body participates in the P450-mediated metabolism of excess furanocoumarins unmetabolized by the midgut [11].

Associations of Cpr with chemical compounds


Other interactions of Cpr


Analytical, diagnostic and therapeutic context of Cpr

  • Sequence alignments were used to draw phylogenetic trees and to analyze the intron-exon organization of each functional P450 gene [8].
  • The use of a degenerate PCR primer targeted to the haem-binding decapeptide unique to the cytochrome P450 superfamily resulted in the identification of 14 novel cytochrome P450s in the Mediterranean Fruit Fly, Ceratitis capitata [17].
  • Although the chromosome 2 locus was not associated with a significant increase in cytochrome P-450 content, SDS polyacrylamide gel electrophoresis of microsomal proteins detected increased silver staining of a polypeptide having a relative molecular mass (Mr) of about 52,000 [18].


  1. The Drosophila cytochrome P450 gene Cyp6a2: structure, localization, heterologous expression, and induction by phenobarbital. Dunkov, B.C., Guzov, V.M., Mocelin, G., Shotkoski, F., Brun, A., Amichot, M., Ffrench-Constant, R.H., Feyereisen, R. DNA Cell Biol. (1997) [Pubmed]
  2. Relation between the somatic toxicity of dimethylnitrosamine and a genetically determined variation in the level and induction of cytochrome P450 in Drosophila melanogaster. Hällström, I., Magnusson, J., Ramel, C. Mutat. Res. (1982) [Pubmed]
  3. Mammalian genes expressed in Drosophila: a transgenic model for the study of mechanisms of chemical mutagenesis and metabolism. Jowett, T., Wajidi, M.F., Oxtoby, E., Wolf, C.R. EMBO J. (1991) [Pubmed]
  4. Cyp12a4 confers lufenuron resistance in a natural population of Drosophila melanogaster. Bogwitz, M.R., Chung, H., Magoc, L., Rigby, S., Wong, W., O'Keefe, M., McKenzie, J.A., Batterham, P., Daborn, P.J. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  5. Shade is the Drosophila P450 enzyme that mediates the hydroxylation of ecdysone to the steroid insect molting hormone 20-hydroxyecdysone. Petryk, A., Warren, J.T., Marqués, G., Jarcho, M.P., Gilbert, L.I., Kahler, J., Parvy, J.P., Li, Y., Dauphin-Villemant, C., O'Connor, M.B. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  6. Molecular and biochemical characterization of two P450 enzymes in the ecdysteroidogenic pathway of Drosophila melanogaster. Warren, J.T., Petryk, A., Marques, G., Jarcho, M., Parvy, J.P., Dauphin-Villemant, C., O'Connor, M.B., Gilbert, L.I. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  7. Drosophila melanogaster NADPH-cytochrome P450 oxidoreductase: pronounced expression in antennae may be related to odorant clearance. Hovemann, B.T., Sehlmeyer, F., Malz, J. Gene (1997) [Pubmed]
  8. The cytochrome P450 gene superfamily in Drosophila melanogaster: annotation, intron-exon organization and phylogeny. Tijet, N., Helvig, C., Feyereisen, R. Gene (2001) [Pubmed]
  9. Xenobiotic-metabolizing enzymes and benzo[a]pyrene metabolism in the benzo[a]pyrene-sensitive mutant strain of Drosophila simulans. Fuchs SYu, n.u.l.l., Spiegelman, V.S., Safaev, R.D., Belitsky, G.A. Mutat. Res. (1992) [Pubmed]
  10. Metabolic inactivation of mutagens in Drosophila melanogaster. Zijlstra, J.A., Vogel, E.W. Mutat. Res. (1988) [Pubmed]
  11. Expression of CYP6B1 and CYP6B3 cytochrome P450 monooxygenases and furanocoumarin metabolism in different tissues of Papilio polyxenes (Lepidoptera: Papilionidae). Petersen, R.A., Zangerl, A.R., Berenbaum, M.R., Schuler, M.A. Insect Biochem. Mol. Biol. (2001) [Pubmed]
  12. Drosophila melanogaster CYP6A8, an insect P450 that catalyzes lauric acid (omega-1)-hydroxylation. Helvig, C., Tijet, N., Feyereisen, R., Walker, F.A., Restifo, L.L. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  13. Unique features of recombinant heme oxygenase of Drosophila melanogaster compared with those of other heme oxygenases studied. Zhang, X., Sato, M., Sasahara, M., Migita, C.T., Yoshida, T. Eur. J. Biochem. (2004) [Pubmed]
  14. Xenobiotic response in Drosophila melanogaster: sex dependence of P450 and GST gene induction. Le Goff, G., Hilliou, F., Siegfried, B.D., Boundy, S., Wajnberg, E., Sofer, L., Audant, P., ffrench-Constant, R.H., Feyereisen, R. Insect Biochem. Mol. Biol. (2006) [Pubmed]
  15. Induction of two cytochrome P450 genes, Cyp6a2 and Cyp6a8, of Drosophila melanogaster by caffeine in adult flies and in cell culture. Bhaskara, S., Dean, E.D., Lam, V., Ganguly, R. Gene (2006) [Pubmed]
  16. Isolation of insecticide resistance-related forms of cytochrome P-450 from Drosophila melanogaster. Sundseth, S.S., Nix, C.E., Waters, L.C. Biochem. J. (1990) [Pubmed]
  17. Diversity of expressed cytochrome P450 genes in the adult Mediterranean Fruit Fly, Ceratitis capitata. Danielson, P.B., Foster, J.L., Cooper, S.K., Fogleman, J.C. Insect Mol. Biol. (1999) [Pubmed]
  18. Genes controlling malathion resistance in a laboratory-selected population of Drosophila melanogaster. Houpt, D.R., Pursey, J.C., Morton, R.A. Genome (1988) [Pubmed]
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