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Gene Review

Cyp6a2  -  Cytochrome P450-6a2

Drosophila melanogaster

Synonyms: 143127_at, 6a2, 91-R, 91R, CG9438, ...
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Disease relevance of Cyp6a2

  • To determine the impact of each mutation on the function of CYP6A2, the wild-type enzyme (CYP6A2wt) of Cyp6a2 was expressed in Escherichia coli as well as three variants carrying a single mutation, the double mutant CYP6A2vSV and the triple mutant CYP6A2vSVL [1].
  • Heterologous expression of the CYP6A2 protein in lepidopteran cells infected with a Cyp6a2-recombinant baculovirus was observed by Western blotting of cell lysates and by spectral characterization of the reduced-CO complex of the P450 [2].

High impact information on Cyp6a2

  • The cytochrome P450 Cyp6a2 and the diazepam-binding inhibitor gene (Dbi) were over transcribed in the two DDT-resistant genotypes when compared to the wild-type Drosophila, and this difference was significant at the most stringent statistical level, a Bonferroni correction [3].
  • The P450-B1 gene in 91-C contained a solitary long terminal repeat of transposable element 17.6 in its 3' untranslated region [4].
  • P450-A is present among all strains tested, whereas expression of P450-B is associated with resistance to insecticides [4].
  • On the basis of features of the long terminal repeat and its location in the gene of the susceptible fly, we propose that a posttranscriptional mechanism involving mRNA stability could be involved in regulating P450-B1 gene expression [4].
  • Four of these exons (6a1, 6a2, 6b1, and 6b2) are mutually exclusive and very similar in sequence [5].

Biological context of Cyp6a2

  • Taken together, these results suggest that the second chromosome-linked Cyp6a2 and Cypa8 genes are regulated by loci present on the third chromosome, and the wild-type function of these loci is to repress these two Cyp genes [6].
  • This suggested that the underproducer strains carry loci which downregulate Cyp6a2 and Cyp6a8 gene expression [6].
  • The polypeptides encoded by these two genes, Cyp6a8 and Cyp6a9, show 77 and 75% amino acid sequence similarity, and 60 and 55% identity with Cyp6a2 of D. melanogaster, respectively [7].
  • DNA from the Cyp6a2 promoter region was functional when linked to a luciferase reporter gene and transfected into D. melanogaster Schneider cells [2].
  • Promoter activity of the -11/-761 DNA of the overproducer 91-R strain was found to be 4-fold lower in the genome of underproducer ry(506) strain, which is wild type for the putative repressor gene, than in the genome of F1 hybrids of 91-R and ry(506) strains [8].

Anatomical context of Cyp6a2

  • The encoded protein had been isolated as an ecdysone-binding cytochrome P450 from microsomes of the same tissue in previous work [9].
  • Here, we report the cloning and sequencing of a full-length cDNA of a new cytochrome P450, classified as CYP6H1, from malpighian tubules of the locust, Locusta migratoria [9].
  • Baculovirus-mediated expression of the CYP6B4v1 protein in lepidopteran cell lines demonstrates that this P450 isozyme metabolizes isopimpinellin, imperatorin, and bergapten at high rates, xanthotoxin and psoralen at intermediate rates and angelicin, sphondin, and trioxsalen only at very low rates [10].

Associations of Cyp6a2 with chemical compounds


Regulatory relationships of Cyp6a2

  • Analysis of Cyp6a8 upstream DNA of the overproducer 91-R strain showed that DNA sequences between -199 and -761 bp are required for the highest constitutive and barbital-induced expression of Cyp6a8 [8].

Other interactions of Cyp6a2


Analytical, diagnostic and therapeutic context of Cyp6a2


  1. Point mutations associated with insecticide resistance in the Drosophila cytochrome P450 Cyp6a2 enable DDT metabolism. Amichot, M., Tarès, S., Brun-Barale, A., Arthaud, L., Bride, J.M., Bergé, J.B. Eur. J. Biochem. (2004) [Pubmed]
  2. 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]
  3. Genome-wide transcription profile of field- and laboratory-selected dichlorodiphenyltrichloroethane (DDT)-resistant Drosophila. Pedra, J.H., McIntyre, L.M., Scharf, M.E., Pittendrigh, B.R. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  4. Possible involvement of the long terminal repeat of transposable element 17.6 in regulating expression of an insecticide resistance-associated P450 gene in Drosophila. Waters, L.C., Zelhof, A.C., Shaw, B.J., Ch'ang, L.Y. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  5. Abnormal muscle development in the heldup3 mutant of Drosophila melanogaster is caused by a splicing defect affecting selected troponin I isoforms. Barbas, J.A., Galceran, J., Torroja, L., Prado, A., Ferrús, A. Mol. Cell. Biol. (1993) [Pubmed]
  6. Factors on the third chromosome affect the level of cyp6a2 and cyp6a8 expression in Drosophila melanogaster. Maitra, S., Dombrowski, S.M., Basu, M., Raustol, O., Waters, L.C., Ganguly, R. Gene (2000) [Pubmed]
  7. Three second chromosome-linked clustered Cyp6 genes show differential constitutive and barbital-induced expression in DDT-resistant and susceptible strains of Drosophila melanogaster. Maitra, S., Dombrowski, S.M., Waters, L.C., Ganguly, R. Gene (1996) [Pubmed]
  8. Cyp6a8 of Drosophila melanogaster: gene structure, and sequence and functional analysis of the upstream DNA. Maitra, S., Price, C., Ganguly, R. Insect Biochem. Mol. Biol. (2002) [Pubmed]
  9. Cloning of a cDNA encoding a novel cytochrome P450 from the insect Locusta migratoria: CYP6H1, a putative ecdysone 20-hydroxylase. Winter, J., Bilbe, G., Richener, H., Sehringer, B., Kayser, H. Biochem. Biophys. Res. Commun. (1999) [Pubmed]
  10. Isolation and characterization of CYP6B4, a furanocoumarin-inducible cytochrome P450 from a polyphagous caterpillar (Lepidoptera:papilionidae). Hung, C.F., Berenbaum, M.R., Schuler, M.A. Insect Biochem. Mol. Biol. (1997) [Pubmed]
  11. 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]
  12. 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]
  13. Expression of Cyp6g1 and Cyp12d1 in DDT resistant and susceptible strains of Drosophila melanogaster. Festucci-Buselli, R.A., Carvalho-Dias, A.S., de Oliveira-Andrade, M., Caixeta-Nunes, C., Li, H.M., Stuart, J.J., Muir, W., Scharf, M.E., Pittendrigh, B.R. Insect Mol. Biol. (2005) [Pubmed]
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