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Identification
HMDB Protein ID HMDBP01548
Secondary Accession Numbers
  • 6844
  • HMDBP07092
Name Cytochrome P450 2D6
Synonyms
  1. CYPIID6
  2. Cytochrome P450-DB1
  3. Debrisoquine 4-hydroxylase
Gene Name CYP2D6
Protein Type Unknown
Biological Properties
General Function Involved in monooxygenase activity
Specific Function Responsible 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.
Pathways
  • Acetaminophen Metabolism Pathway
  • Celecoxib Action Pathway
  • Celecoxib Metabolism Pathway
  • Citalopram Action Pathway
  • Citalopram Metabolism Pathway
  • Clomipramine Metabolism Pathway
  • Codeine Action Pathway
  • Codeine Metabolism Pathway
  • Desipramine Action Pathway
  • Desipramine Metabolism Pathway
  • Doxepin Metabolism Pathway
  • Drug metabolism - cytochrome P450
  • Fluoxetine Action Pathway
  • Fluoxetine Metabolism Pathway
  • Imipramine Action Pathway
  • Imipramine Metabolism Pathway
  • Metabolism of xenobiotics by cytochrome P450
  • Methadone Action Pathway
  • Methadone Metabolism Pathway
  • Nevirapine Metabolism Pathway
  • Serotonergic synapse
  • Tamoxifen Action Pathway
  • Tamoxifen Metabolism Pathway
  • Tramadol Metabolism Pathway
  • Venlafaxine Metabolism Pathway
Reactions
RH + reduced flavoprotein + Oxygen → ROH + oxidized flavoprotein + Water details
GO Classification
Biological Process
small molecule metabolic process
oxidative demethylation
coumarin metabolic process
response to organic substance
monoterpenoid metabolic process
steroid metabolic process
xenobiotic metabolic process
alkaloid catabolic process
arachidonic acid metabolic process
drug catabolic process
isoquinoline alkaloid metabolic process
negative regulation of binding
negative regulation of cellular organofluorine metabolic process
dopamine metabolic process
Cellular Component
endoplasmic reticulum membrane
mitochondrion
Function
ion binding
cation binding
metal ion binding
binding
catalytic activity
transition metal ion binding
electron carrier activity
iron ion binding
monooxygenase activity
heme binding
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
oxidoreductase activity
Molecular Function
electron carrier activity
monooxygenase activity
aromatase activity
iron ion binding
steroid 21-monooxygenase activity
heme binding
arachidonic acid monooxygenase activity
drug binding
Process
metabolic process
oxidation reduction
Cellular Location
  1. Peripheral membrane protein
  2. Peripheral membrane protein
  3. Endoplasmic reticulum membrane
  4. Microsome membrane
Gene Properties
Chromosome Location 22
Locus 22q13.1
SNPs CYP2D6
Gene Sequence
>1494 bp
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
Protein Properties
Number of Residues 497
Molecular Weight 55768.94
Theoretical pI 7.248
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence
>Cytochrome P450 2D6
MGLEALVPLAVIVAIFLLLVDLMHRRQRWAARYPPGPLPLPGLGNLLHVDFQNTPYCFDQ
LRRRFGDVFSLQLAWTPVVVLNGLAAVREALVTHGEDTADRPPVPITQILGFGPRSQGVF
LARYGPAWREQRRFSVSTLRNLGLGKKSLEQWVTEEAACLCAAFANHSGRPFRPNGLLDK
AVSNVIASLTCGRRFEYDDPRFLRLLDLAQEGLKEESGFLREVLNAVPVLLHIPALAGKV
LRFQKAFLTQLDELLTEHRMTWDPAQPPRDLTEAFLAEMEKAKGNPESSFNDENLRIVVA
DLFSAGMVTTSTTLAWGLLLMILHPDVQRRVQQEIDDVIGQVRRPEMGDQAHMPYTTAVI
HEVQRFGDIVPLGVTHMTSRDIEVQGFRIPKGTTLITNLSSVLKDEAVWEKPFRFHPEHF
LDAQGHFVKPEAFLPFSAGRRACLGEPLARMELFLFFTSLLQHFSFSVPTGQPRPSHHGV
FAFLVSPSPYELCAVPR
GenBank ID Protein 45024928
UniProtKB/Swiss-Prot ID P10635
UniProtKB/Swiss-Prot Entry Name CP2D6_HUMAN
PDB IDs
GenBank Gene ID AY545216
GeneCard ID CYP2D6
GenAtlas ID CYP2D6
HGNC ID HGNC:2625
References
General References
  1. 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. [PubMed:15489334 ]
  2. 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. [PubMed:10591208 ]
  3. 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. [PubMed:15469410 ]
  4. 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. [PubMed:3410476 ]
  5. 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. [PubMed:3123997 ]
  6. 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. [PubMed:2574001 ]
  7. 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. [PubMed:15768052 ]
  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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed: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. [PubMed:10064570 ]