Cytochrome P450 2D6

NameCytochrome P450 2D6
Synonyms
  • 1.14.14.1
  • Cholesterol 25-hydroxylase
  • CYP2DL1
  • CYPIID6
  • Cytochrome P450-DB1
  • Debrisoquine 4-hydroxylase
Gene NameCYP2D6
OrganismHuman
Amino acid sequence
>lcl|BSEQ0004641|Cytochrome P450 2D6
MGLEALVPLAVIVAIFLLLVDLMHRRQRWAARYPPGPLPLPGLGNLLHVDFQNTPYCFDQ
LRRRFGDVFSLQLAWTPVVVLNGLAAVREALVTHGEDTADRPPVPITQILGFGPRSQGVF
LARYGPAWREQRRFSVSTLRNLGLGKKSLEQWVTEEAACLCAAFANHSGRPFRPNGLLDK
AVSNVIASLTCGRRFEYDDPRFLRLLDLAQEGLKEESGFLREVLNAVPVLLHIPALAGKV
LRFQKAFLTQLDELLTEHRMTWDPAQPPRDLTEAFLAEMEKAKGNPESSFNDENLRIVVA
DLFSAGMVTTSTTLAWGLLLMILHPDVQRRVQQEIDDVIGQVRRPEMGDQAHMPYTTAVI
HEVQRFGDIVPLGVTHMTSRDIEVQGFRIPKGTTLITNLSSVLKDEAVWEKPFRFHPEHF
LDAQGHFVKPEAFLPFSAGRRACLGEPLARMELFLFFTSLLQHFSFSVPTGQPRPSHHGV
FAFLVSPSPYELCAVPR
Number of residues497
Molecular Weight55768.94
Theoretical pI7.26
GO Classification
Functions
  • drug binding
  • oxidoreductase activity
  • aromatase activity
  • iron ion binding
  • heme binding
  • monooxygenase activity
  • oxygen binding
  • arachidonic acid epoxygenase activity
  • steroid hydroxylase activity
  • oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Processes
  • alkaloid catabolic process
  • steroid metabolic process
  • negative regulation of cellular organofluorine metabolic process
  • xenobiotic metabolic process
  • arachidonic acid metabolic process
  • drug metabolic process
  • exogenous drug catabolic process
  • isoquinoline alkaloid metabolic process
  • alkaloid metabolic process
  • drug catabolic process
  • heterocycle metabolic process
  • monoterpenoid metabolic process
  • oxidative demethylation
  • coumarin metabolic process
  • small molecule metabolic process
  • negative regulation of binding
  • oxidation-reduction process
Components
  • cytoplasm
  • mitochondrion
  • endoplasmic reticulum
  • endoplasmic reticulum membrane
General FunctionSteroid hydroxylase activity
Specific FunctionResponsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants.
Pfam Domain Function
Transmembrane RegionsNot Available
GenBank Protein ID181350
UniProtKB IDP10635
UniProtKB Entry NameCP2D6_HUMAN
Cellular LocationEndoplasmic reticulum membrane
Gene sequence
>lcl|BSEQ0019275|Cytochrome P450 2D6 (CYP2D6)
ATGGGGCTAGAAGCACTGGTGCCCCTGGCCGTGATAGTGGCCATCTTCCTGCTCCTGGTG
GACCTGATGCACCGGCGCCAACGCTGGGCTGCACGCTACCCACCAGGCCCCCTGCCACTG
CCCGGGCTGGGCAACCTGCTGCATGTGGACTTCCAGAACACACCATACTGCTTCGACCAG
TTGCGGCGCCGCTTCGGGGACGTGTTCAGCCTGCAGCTGGCCTGGACGCCGGTGGTCGTG
CTCAATGGGCTGGCGGCCGTGCGCGAGGCGCTGGTGACCCACGGCGAGGACACCGCCGAC
CGCCCGCCTGTGCCCATCACCCAGATCCTGGGTTTCGGGCCGCGTTCCCAAGGGGTGTTC
CTGGCGCGCTATGGGCCCGCGTGGCGCGAGCAGAGGCGCTTCTCCGTGTCCACCTTGCGC
AACTTGGGCCTGGGCAAGAAGTCGCTGGAGCAGTGGGTGACCGAGGAGGCCGCCTGCCTT
TGTGCCGCCTTCGCCAACCACTCCGGACGCCCCTTTCGCCCCAACGGTCTCTTGGACAAA
GCCGTGAGCAACGTGATCGCCTCCCTCACCTGCGGGCGCCGCTTCGAGTACGACGACCCT
CGCTTCCTCAGGCTGCTGGACCTAGCTCAGGAGGGACTGAAGGAGGAGTCGGGCTTTCTG
CGCGAGGTGCTGAATGCTGTCCCCGTCCTCCTGCATATCCCAGCGCTGGCTGGCAAGGTC
CTACGCTTCCAAAAGGCTTTCCTGACCCAGCTGGATGAGCTGCTAACTGAGCACAGGATG
ACCTGGGACCCAGCCCAGCCCCCCCGAGACCTGACTGAGGCCTTCCTGGCAGAGATGGAG
AAGGCCAAGGGGAACCCTGAGAGCAGCTTCAATGATGAGAACCTGCGCATAGTGGTGGCT
GACCTGTTCTCTGCCGGGATGGTGACCACCTCGACCACGCTGGCCTGGGGCCTCCTGCTC
ATGATCCTACATCCGGATGTGCAGCGCCGTGTCCAACAGGAGATCGACGACGTGATAGGG
CAGGTGCGGCGACCAGAGATGGGTGACCAGGCTCACATGCCCTACACCACTGCCGTGATT
CATGAGGTGCAGCGCTTTGGGGACATCGTCCCCCTGGGTGTGACCCATATGACATCCCGT
GACATCGAAGTACAGGGCTTCCGCATCCCTAAGGGAACGACACTCATCACCAACCTGTCA
TCGGTGCTGAAGGATGAGGCCGTCTGGGAGAAGCCCTTCCGCTTCCACCCCGAACACTTC
CTGGATGCCCAGGGCCACTTTGTGAAGCCGGAGGCCTTCCTGCCTTTCTCAGCAGGCCGC
CGTGCATGCCTCGGGGAGCCCCTGGCCCGCATGGAGCTCTTCCTCTTCTTCACCTCCCTG
CTGCAGCACTTCAGCTTCTCGGTGCCCACTGGACAGCCCCGGCCCAGCCACCATGGTGTC
TTTGCTTTCCTGGTGAGCCCATCCCCCTATGAGCTTTGTGCTGTGCCCCGCTAG
GenBank Gene IDM20403
GeneCard IDNot Available
GenAtlas IDCYP2D6
HGNC IDHGNC:2625
Chromosome Location22
Locus22q13.1
References
  1. Gonzalez FJ, Vilbois F, Hardwick JP, McBride OW, Nebert DW, Gelboin HV, Meyer UA: Human debrisoquine 4-hydroxylase (P450IID1): cDNA and deduced amino acid sequence and assignment of the CYP2D locus to chromosome 22. Genomics. 1988 Feb;2(2):174-9. 3410476
  2. Gonzalez FJ, Skoda RC, Kimura S, Umeno M, Zanger UM, Nebert DW, Gelboin HV, Hardwick JP, Meyer UA: Characterization of the common genetic defect in humans deficient in debrisoquine metabolism. Nature. 1988 Feb 4;331(6155):442-6. 3123997
  3. Kimura S, Umeno M, Skoda RC, Meyer UA, Gonzalez FJ: The human debrisoquine 4-hydroxylase (CYP2D) locus: sequence and identification of the polymorphic CYP2D6 gene, a related gene, and a pseudogene. Am J Hum Genet. 1989 Dec;45(6):889-904. 2574001
  4. Gaedigk A, Bhathena A, Ndjountche L, Pearce RE, Abdel-Rahman SM, Alander SW, Bradford LD, Rogan PK, Leeder JS: Identification and characterization of novel sequence variations in the cytochrome P4502D6 (CYP2D6) gene in African Americans. Pharmacogenomics J. 2005;5(3):173-82. 15768052
  5. Dunham I, Shimizu N, Roe BA, Chissoe S, Hunt AR, Collins JE, Bruskiewich R, Beare DM, Clamp M, Smink LJ, Ainscough R, Almeida JP, Babbage A, Bagguley C, Bailey J, Barlow K, Bates KN, Beasley O, Bird CP, Blakey S, Bridgeman AM, Buck D, Burgess J, Burrill WD, O'Brien KP, et al.: The DNA sequence of human chromosome 22. Nature. 1999 Dec 2;402(6761):489-95. 10591208
  6. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. 15489334
  7. Honda A, Miyazaki T, Ikegami T, Iwamoto J, Maeda T, Hirayama T, Saito Y, Teramoto T, Matsuzaki Y: Cholesterol 25-hydroxylation activity of CYP3A. J Lipid Res. 2011 Aug;52(8):1509-16. doi: 10.1194/jlr.M014084. Epub 2011 May 16. 21576599
  8. Rowland P, Blaney FE, Smyth MG, Jones JJ, Leydon VR, Oxbrow AK, Lewis CJ, Tennant MG, Modi S, Eggleston DS, Chenery RJ, Bridges AM: Crystal structure of human cytochrome P450 2D6. J Biol Chem. 2006 Mar 17;281(11):7614-22. Epub 2005 Dec 13. 16352597
  9. Tyndale R, Aoyama T, Broly F, Matsunaga T, Inaba T, Kalow W, Gelboin HV, Meyer UA, Gonzalez FJ: Identification of a new variant CYP2D6 allele lacking the codon encoding Lys-281: possible association with the poor metabolizer phenotype. Pharmacogenetics. 1991 Oct;1(1):26-32. 1844820
  10. Yokota H, Tamura S, Furuya H, Kimura S, Watanabe M, Kanazawa I, Kondo I, Gonzalez FJ: Evidence for a new variant CYP2D6 allele CYP2D6J in a Japanese population associated with lower in vivo rates of sparteine metabolism. Pharmacogenetics. 1993 Oct;3(5):256-63. 8287064
  11. Evert B, Griese EU, Eichelbaum M: A missense mutation in exon 6 of the CYP2D6 gene leading to a histidine 324 to proline exchange is associated with the poor metabolizer phenotype of sparteine. Naunyn Schmiedebergs Arch Pharmacol. 1994 Oct;350(4):434-9. 7845481
  12. Daly AK, Leathart JB, London SJ, Idle JR: An inactive cytochrome P450 CYP2D6 allele containing a deletion and a base substitution. Hum Genet. 1995 Mar;95(3):337-41. 7868129
  13. Masimirembwa C, Persson I, Bertilsson L, Hasler J, Ingelman-Sundberg M: A novel mutant variant of the CYP2D6 gene (CYP2D6*17) common in a black African population: association with diminished debrisoquine hydroxylase activity. Br J Clin Pharmacol. 1996 Dec;42(6):713-9. 8971426
  14. Marez D, Legrand M, Sabbagh N, Lo-Guidice JM, Boone P, Broly F: An additional allelic variant of the CYP2D6 gene causing impaired metabolism of sparteine. Hum Genet. 1996 May;97(5):668-70. 8655150
  15. Marez D, Legrand M, Sabbagh N, Lo Guidice JM, Spire C, Lafitte JJ, Meyer UA, Broly F: Polymorphism of the cytochrome P450 CYP2D6 gene in a European population: characterization of 48 mutations and 53 alleles, their frequencies and evolution. Pharmacogenetics. 1997 Jun;7(3):193-202. 9241659
  16. Wang SL, Lai MD, Huang JD: G169R mutation diminishes the metabolic activity of CYP2D6 in Chinese. Drug Metab Dispos. 1999 Mar;27(3):385-8. 10064570
  17. Solus JF, Arietta BJ, Harris JR, Sexton DP, Steward JQ, McMunn C, Ihrie P, Mehall JM, Edwards TL, Dawson EP: Genetic variation in eleven phase I drug metabolism genes in an ethnically diverse population. Pharmacogenomics. 2004 Oct;5(7):895-931. 15469410
  18. Dai DP, Geng PW, Wang SH, Cai J, Hu LM, Nie JJ, Hu JH, Hu GX, Cai JP: In vitro functional assessment of 22 newly identified CYP2D6 allelic variants in the Chinese population. Basic Clin Pharmacol Toxicol. 2015 Jul;117(1):39-43. doi: 10.1111/bcpt.12363. Epub 2015 Jan 14. 25469868