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. 1988 Jul 11;16(13):5783–5795. doi: 10.1093/nar/16.13.5783

A novel human cytochrome P450 gene (P450IIB): chromosomal localization and evidence for alternative splicing.

J S Miles 1, N K Spurr 1, A C Gough 1, T Jowett 1, A W McLaren 1, J D Brook 1, C R Wolf 1
PMCID: PMC336829  PMID: 2899870

Abstract

We have isolated from a single human liver cDNA library two clones which are highly homologous (78% over the coding region) to the major phenobarbital-inducible P450 from rat (P450IIB1). This is the first direct demonstration of the presence of the P450IIB gene subfamily in humans. This subfamily is much less extensive than the rodent homologues, but does appear to contain at least two genes. Of the cDNA clones isolated one is apparently normally spliced, whereas the other lacks exon 8 and retains all or part of intron 5. Both clones contain transcribed Alu sequences. The human P450IIB gene has been located to chromosome 19q12----19q13.2 using a probe derived from intron 5, and is close to the CYP 2A locus encoding cytochrome P450IIA2. Restriction fragment length polymorphisms have been found with the enzymes BamHI and MspI which will enable linkage to be determined between these two loci.

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Selected References

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  1. Amara S. G. Peptide diversity from exon choice: RNA processing regulation in the neuroendocrine system. Mol Cell Endocrinol. 1985 Oct;42(3):191–205. doi: 10.1016/0303-7207(85)90049-8. [DOI] [PubMed] [Google Scholar]
  2. Atchison M., Adesnik M. A cytochrome P-450 multigene family. Characterization of a gene activated by phenobarbital administration. J Biol Chem. 1983 Sep 25;258(18):11285–11295. [PubMed] [Google Scholar]
  3. Benton W. D., Davis R. W. Screening lambdagt recombinant clones by hybridization to single plaques in situ. Science. 1977 Apr 8;196(4286):180–182. doi: 10.1126/science.322279. [DOI] [PubMed] [Google Scholar]
  4. Biggin M. D., Gibson T. J., Hong G. F. Buffer gradient gels and 35S label as an aid to rapid DNA sequence determination. Proc Natl Acad Sci U S A. 1983 Jul;80(13):3963–3965. doi: 10.1073/pnas.80.13.3963. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Conney A. H. Pharmacological implications of microsomal enzyme induction. Pharmacol Rev. 1967 Sep;19(3):317–366. [PubMed] [Google Scholar]
  6. Davis M. B. Linkage between the loci for peptidase D and cytochrome P-450 (CYP1) on chromosome 19. Ann Hum Genet. 1987 Jan;51(Pt 1):9–12. doi: 10.1111/j.1469-1809.1987.tb00862.x. [DOI] [PubMed] [Google Scholar]
  7. Davis M. B., West L. F., Shephard E. A., Phillips I. R. Regional localization of a human cytochrome P-450 (CYP1) to chromosome 19q13.1-13.3. Ann Hum Genet. 1986 Jul;50(Pt 3):237–240. doi: 10.1111/j.1469-1809.1986.tb01044.x. [DOI] [PubMed] [Google Scholar]
  8. Eichelbaum M., Reetz K. P., Schmidt E. K., Zekorn C. The genetic polymorphism of sparteine metabolism. Xenobiotica. 1986 May;16(5):465–481. doi: 10.3109/00498258609050252. [DOI] [PubMed] [Google Scholar]
  9. Feinberg A. P., Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. doi: 10.1016/0003-2697(83)90418-9. [DOI] [PubMed] [Google Scholar]
  10. Fujii-Kuriyama Y., Mizukami Y., Kawajiri K., Sogawa K., Muramatsu M. Primary structure of a cytochrome P-450: coding nucleotide sequence of phenobarbital-inducible cytochrome P-450 cDNA from rat liver. Proc Natl Acad Sci U S A. 1982 May;79(9):2793–2797. doi: 10.1073/pnas.79.9.2793. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Gonzalez F. J., Skoda R. C., Kimura S., Umeno M., Zanger U. M., Nebert D. W., Gelboin H. V., Hardwick J. P., Meyer U. A. Characterization of the common genetic defect in humans deficient in debrisoquine metabolism. Nature. 1988 Feb 4;331(6155):442–446. doi: 10.1038/331442a0. [DOI] [PubMed] [Google Scholar]
  12. Grossberger D. Minipreps of DNA from bacteriophage lambda. Nucleic Acids Res. 1987 Aug 25;15(16):6737–6737. doi: 10.1093/nar/15.16.6737. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Jaiswal A. K., Gonzalez F. J., Nebert D. W. Human dioxin-inducible cytochrome P1-450: complementary DNA and amino acid sequence. Science. 1985 Apr 5;228(4695):80–83. doi: 10.1126/science.3838385. [DOI] [PubMed] [Google Scholar]
  14. Kariya Y., Kato K., Hayashizaki Y., Himeno S., Tarui S., Matsubara K. Revision of consensus sequence of human Alu repeats--a review. Gene. 1987;53(1):1–10. doi: 10.1016/0378-1119(87)90087-4. [DOI] [PubMed] [Google Scholar]
  15. Komori M., Imai Y., Tsunasawa S., Sato R. Microheterogeneity in the major phenobarbital-inducible forms of rabbit liver microsomal cytochrome P-450 as revealed by nucleotide sequencing of cloned cDNAs. Biochemistry. 1988 Jan 12;27(1):73–80. doi: 10.1021/bi00401a013. [DOI] [PubMed] [Google Scholar]
  16. Kumar A., Raphael C., Adesnik M. Cloned cytochrome P-450 cDNA. Nucleotide sequence and homology to multiple phenobarbital-induced mRNA species. J Biol Chem. 1983 Sep 25;258(18):11280–11284. [PubMed] [Google Scholar]
  17. Lehrman M. A., Goldstein J. L., Russell D. W., Brown M. S. Duplication of seven exons in LDL receptor gene caused by Alu-Alu recombination in a subject with familial hypercholesterolemia. Cell. 1987 Mar 13;48(5):827–835. doi: 10.1016/0092-8674(87)90079-1. [DOI] [PubMed] [Google Scholar]
  18. Meehan R. R., Gosden J. R., Rout D., Hastie N. D., Friedberg T., Adesnik M., Buckland R., van Heyningen V., Fletcher J., Spurr N. K. Human cytochrome P-450 PB-1: a multigene family involved in mephenytoin and steroid oxidations that maps to chromosome 10. Am J Hum Genet. 1988 Jan;42(1):26–37. [PMC free article] [PubMed] [Google Scholar]
  19. Meyer U. A., Gut J., Kronbach T., Skoda C., Meier U. T., Catin T., Dayer P. The molecular mechanisms of two common polymorphisms of drug oxidation--evidence for functional changes in cytochrome P-450 isozymes catalysing bufuralol and mephenytoin oxidation. Xenobiotica. 1986 May;16(5):449–464. doi: 10.3109/00498258609050251. [DOI] [PubMed] [Google Scholar]
  20. Mizukami Y., Sogawa K., Suwa Y., Muramatsu M., Fujii-Kuriyama Y. Gene structure of a phenobarbital-inducible cytochrome P-450 in rat liver. Proc Natl Acad Sci U S A. 1983 Jul;80(13):3958–3962. doi: 10.1073/pnas.80.13.3958. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Nebert D. W., Gonzalez F. J. P450 genes: structure, evolution, and regulation. Annu Rev Biochem. 1987;56:945–993. doi: 10.1146/annurev.bi.56.070187.004501. [DOI] [PubMed] [Google Scholar]
  22. Okino S. T., Quattrochi L. C., Pendurthi U. R., McBride O. W., Tukey R. H. Characterization of multiple human cytochrome P-450 1 cDNAs. The chromosomal localization of the gene and evidence for alternate RNA splicing. J Biol Chem. 1987 Nov 25;262(33):16072–16079. [PubMed] [Google Scholar]
  23. Phillips I. R., Shephard E. A., Ashworth A., Rabin B. R. Isolation and sequence of a human cytochrome P-450 cDNA clone. Proc Natl Acad Sci U S A. 1985 Feb;82(4):983–987. doi: 10.1073/pnas.82.4.983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Phillips I. R., Shephard E. A., Povey S., Davis M. B., Kelsey G., Monteiro M., West L. F., Cowell J. A cytochrome P-450 gene family mapped to human chromosome 19. Ann Hum Genet. 1985 Oct;49(Pt 4):267–274. doi: 10.1111/j.1469-1809.1985.tb01702.x. [DOI] [PubMed] [Google Scholar]
  25. Quattrochi L. C., Pendurthi U. R., Okino S. T., Potenza C., Tukey R. H. Human cytochrome P-450 4 mRNA and gene: part of a multigene family that contains Alu sequences in its mRNA. Proc Natl Acad Sci U S A. 1986 Sep;83(18):6731–6735. doi: 10.1073/pnas.83.18.6731. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Rampersaud A., Walz F. G., Jr At least six forms of extremely homologous cytochromes P-450 in rat liver are encoded at two closely linked genetic loci. Proc Natl Acad Sci U S A. 1983 Nov;80(21):6542–6546. doi: 10.1073/pnas.80.21.6542. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Rampersaud A., Walz F. G., Jr Mapping of genes for cytochromes P-450b, P-450e, P-450g, and P-450h in the rat. Demonstration of two gene clusters with P450-b,e localized on chromosome 1. J Biol Chem. 1987 Apr 25;262(12):5649–5653. [PubMed] [Google Scholar]
  28. Rigby P. W., Dieckmann M., Rhodes C., Berg P. Labeling deoxyribonucleic acid to high specific activity in vitro by nick translation with DNA polymerase I. J Mol Biol. 1977 Jun 15;113(1):237–251. doi: 10.1016/0022-2836(77)90052-3. [DOI] [PubMed] [Google Scholar]
  29. Ryan D. E., Thomas P. E., Levin W. Purification of characterization of a minor form of hepatic microsomal cytochrome P-450 from rats treated with polychlorinated biphenyls. Arch Biochem Biophys. 1982 Jun;216(1):272–288. doi: 10.1016/0003-9861(82)90212-0. [DOI] [PubMed] [Google Scholar]
  30. Sanger F., Coulson A. R., Barrell B. G., Smith A. J., Roe B. A. Cloning in single-stranded bacteriophage as an aid to rapid DNA sequencing. J Mol Biol. 1980 Oct 25;143(2):161–178. doi: 10.1016/0022-2836(80)90196-5. [DOI] [PubMed] [Google Scholar]
  31. Shapiro M. B., Senapathy P. RNA splice junctions of different classes of eukaryotes: sequence statistics and functional implications in gene expression. Nucleic Acids Res. 1987 Sep 11;15(17):7155–7174. doi: 10.1093/nar/15.17.7155. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Simmons D. L., Kasper C. B. Genetic polymorphisms for a phenobarbital-inducible cytochrome P-450 map to the Coh locus in mice. J Biol Chem. 1983 Aug 25;258(16):9585–9588. [PubMed] [Google Scholar]
  33. Song B. J., Gelboin H. V., Park S. S., Yang C. S., Gonzalez F. J. Complementary DNA and protein sequences of ethanol-inducible rat and human cytochrome P-450s. Transcriptional and post-transcriptional regulation of the rat enzyme. J Biol Chem. 1986 Dec 15;261(35):16689–16697. [PubMed] [Google Scholar]
  34. Spurr N. K., Goodfellow P. N., Docherty A. J. Chromosomal assignment of the gene encoding the human tissue inhibitor of metalloproteinases to Xp11.1-p11.4. Ann Hum Genet. 1987 Jul;51(Pt 3):189–194. doi: 10.1111/j.1469-1809.1987.tb00870.x. [DOI] [PubMed] [Google Scholar]
  35. Spurr N. K., Hughes D., Goodfellow P. N., Brook J. D., Padua R. A. Chromosomal assignment of c-MEL, a human transforming oncogene, to chromosome 19 (p13.2-q13.2). Somat Cell Mol Genet. 1986 Nov;12(6):637–640. doi: 10.1007/BF01671949. [DOI] [PubMed] [Google Scholar]
  36. Staden R. The current status and portability of our sequence handling software. Nucleic Acids Res. 1986 Jan 10;14(1):217–231. doi: 10.1093/nar/14.1.217. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Suwa Y., Mizukami Y., Sogawa K., Fujii-Kuriyama Y. Gene structure of a major form of phenobarbital-inducible cytochrome P-450 in rat liver. J Biol Chem. 1985 Jul 5;260(13):7980–7984. [PubMed] [Google Scholar]
  38. Wolf C. R., Seilman S., Oesch F., Mayer R. T., Burke M. D. Multiple forms of cytochrome P-450 related to forms induced marginally by phenobarbital. Differences in structure and in the metabolism of alkoxyresorufins. Biochem J. 1986 Nov 15;240(1):27–33. doi: 10.1042/bj2400027. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Wong G., Kawajiri K., Negishi M. Gene family of male-specific testosterone 16 alpha-hydroxylase (C-P-450(16) alpha) in mouse liver: cDNA sequences, neonatal imprinting, and reversible regulation by androgen. Biochemistry. 1987 Dec 29;26(26):8683–8690. doi: 10.1021/bi00400a029. [DOI] [PubMed] [Google Scholar]
  40. Zaphiropoulos P. G., Folk W. R., Coon M. J. Isolation and characterization of a novel cytochrome P-450-like pseudogene. Biochem Biophys Res Commun. 1986 Jan 29;134(2):499–505. doi: 10.1016/s0006-291x(86)80448-x. [DOI] [PubMed] [Google Scholar]

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