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Identification
HMDB Protein ID HMDBP01567
Secondary Accession Numbers
  • 6863
  • HMDBP06128
Name Cytochrome P450 2A6
Synonyms
  1. CYPIIA6
  2. Coumarin 7-hydroxylase
  3. Cytochrome P450 IIA3
  4. Cytochrome P450(I)
  5. 1,4-cineole 2-exo-monooxygenase
Gene Name CYP2A6
Protein Type Unknown
Biological Properties
General Function Involved in monooxygenase activity
Specific Function Exhibits a high coumarin 7-hydroxylase activity. Can act in the hydroxylation of the anti-cancer drugs cyclophosphamide and ifosphamide. Competent in the metabolic activation of aflatoxin B1. Constitutes the major nicotine C-oxidase. Acts as a 1,4-cineole 2-exo-monooxygenase. Possesses low phenacetin O-deethylation activity.
Pathways
  • Acetaminophen Metabolism Pathway
  • Caffeine metabolism
  • Caffeine Metabolism
  • Chemical carcinogenesis
  • Cyclophosphamide Action Pathway
  • Cyclophosphamide Metabolism Pathway
  • Drug metabolism - cytochrome P450
  • Drug metabolism - other enzymes
  • Ifosfamide Action Pathway
  • Ifosfamide Metabolism Pathway
  • Metabolism of xenobiotics by cytochrome P450
  • Nicotine Action Pathway
  • Nicotine Metabolism Pathway
  • Retinol metabolism
  • Retinol Metabolism
  • Valproic Acid Metabolism Pathway
  • Vitamin A Deficiency
Reactions
1,4-cineole + NADPH + Oxygen → 2-exo-hydroxy-1,4-cineole + NADP + Water details
GO Classification
Biological Process
small molecule metabolic process
exogenous drug catabolic process
steroid metabolic process
xenobiotic metabolic process
coumarin catabolic process
Cellular Component
endoplasmic reticulum membrane
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
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
iron ion binding
coumarin 7-hydroxylase activity
heme 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 19
Locus 19q13.2
SNPs CYP2A6
Gene Sequence
>1485 bp
ATGCTGGCCTCAGGGATGCTTCTGGTGGCCTTGCTGGTCTGCCTGACTGTAATGGTCTTG
ATGTCTGTTTGGCAGCAGAGGAAGAGCAAGGGGAAGCTGCCTCCGGGACCCACCCCATTG
CCCTTCATTGGAAACTACCTGCAGCTGAACACAGAGCAGATGTACAACTCCCTCATGAAG
ATCAGTGAGCGCTATGGCCCCGTGTTCACCATTCACTTGGGGCCCCGGCGGGTCGTGGTG
CTGTGTGGACATGATGCCGTCAGGGAGGCTCTGGTGGACCAGGCTGAGGAGTTCAGCGGG
CGAGGCGAGCAAGCCACCTTCGACTGGGTCTTCAAAGGCTATGGCGTGGTATTCAGCAAC
GGGGAGCGCGCCAAGCAGCTCCGGCGCTTCTCCATCGCCACCCTGCGGGACTTCGGGGTG
GGCAAGCGAGGCATCGAGGAGCGCATCCAGGAGGAGGCGGGCTTCCTCATCGACGCCCTC
CGGGGCACTGGCGGCGCCAATATCGATCCCACCTTCTTCCTGAGCCGCACAGTCTCCAAT
GTCATCAGCTCCATTGTCTTTGGGGACCGCTTTGACTATAAGGACAAAGAGTTCCTGTCA
CTGTTGCGCATGATGCTAGGAATCTTCCAGTTCACGTCAACCTCCACGGGGCAGCTCTAT
GAGATGTTCTCTTCGGTGATGAAACACCTGCCAGGACCACAGCAACAGGCCTTTCAGTTG
CTGCAAGGGCTGGAGGACTTCATAGCCAAGAAGGTGGAGCACAACCAGCGCACGCTGGAT
CCCAATTCCCCACGGGACTTCATTGACTCCTTTCTCATCCGCATGCAGGAGGAGGAGAAG
AACCCCAACACGGAGTTCTACTTGAAAAACCTGGTGATGACCACGTTGAACCTCTTCATT
GGGGGCACCGAGACCGTCAGCACCACCCTGCGCTATGGCTTCTTGCTGCTCATGAAGCAC
CCAGAGGTGGAGGCCAAGGTCCATGAGGAGATTGACAGAGTGATCGGCAAGAACCGGCAG
CCCAAGTTTGAGGACCGGGCCAAGATGCCCTACATGGAGGCAGTGATCCACGAGATCCAA
AGATTTGGAGACGTGATCCCCATGAGTTTGGCCCGCAGAGTCAAAAAGGACACCAAGTTT
CGGGATTTCTTCCTCCCTAAGGGCACCGAAGTGTACCCTATGCTGGGCTCTGTGCTGAGA
GACCCCAGTTTCTTCTCCAACCCCCAGGACTTCAATCCCCAGCACTTCCTGAATGAGAAG
GGGCAGTTTAAGAAGAGTGATGCTTTTGTGCCCTTTTCCATCGGAAAGCGGAACTGTTTC
GGAGAAGGCCTGGCCAGAATGGAGCTCTTTCTCTTCTTCACCACCGTCATGCAGAACTTC
CGCCTCAAGTCCTCCCAGTCACCTAAGGACATTGACGTGTCCCCCAAACACGTGGGCTTT
GCCACGATCCCACGAAACTACACCATGAGCTTCCTGCCCCGCTGA
Protein Properties
Number of Residues 494
Molecular Weight 56517.005
Theoretical pI 9.193
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence
>Cytochrome P450 2A6
MLASGMLLVALLVCLTVMVLMSVWQQRKSKGKLPPGPTPLPFIGNYLQLNTEQMYNSLMK
ISERYGPVFTIHLGPRRVVVLCGHDAVREALVDQAEEFSGRGEQATFDWVFKGYGVVFSN
GERAKQLRRFSIATLRDFGVGKRGIEERIQEEAGFLIDALRGTGGANIDPTFFLSRTVSN
VISSIVFGDRFDYKDKEFLSLLRMMLGIFQFTSTSTGQLYEMFSSVMKHLPGPQQQAFQL
LQGLEDFIAKKVEHNQRTLDPNSPRDFIDSFLIRMQEEEKNPNTEFYLKNLVMTTLNLFI
GGTETVSTTLRYGFLLLMKHPEVEAKVHEEIDRVIGKNRQPKFEDRAKMPYMEAVIHEIQ
RFGDVIPMSLARRVKKDTKFRDFFLPKGTEVFPMLGSVLRDPSFFSNPQDFNPQHFLNEK
GQFKKSDAFVPFSIGKRNCFGEGLARMELFLFFTTVMQNFRLKSSQSPKDIDVSPKHVGF
ATIPRNYTMSFLPR
GenBank ID Protein 189339233
UniProtKB/Swiss-Prot ID P11509
UniProtKB/Swiss-Prot Entry Name CP2A6_HUMAN
PDB IDs
GenBank Gene ID NM_000762.5
GeneCard ID CYP2A6
GenAtlas ID CYP2A6
HGNC ID HGNC:2610
References
General References
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  4. Saito S, Iida A, Sekine A, Kawauchi S, Higuchi S, Ogawa C, Nakamura Y: Catalog of 680 variations among eight cytochrome p450 ( CYP) genes, nine esterase genes, and two other genes in the Japanese population. J Hum Genet. 2003;48(5):249-70. Epub 2003 Apr 29. [PubMed:12721789 ]
  5. 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 ]
  6. DeVore NM, Smith BD, Urban MJ, Scott EE: Key residues controlling phenacetin metabolism by human cytochrome P450 2A enzymes. Drug Metab Dispos. 2008 Dec;36(12):2582-90. doi: 10.1124/dmd.108.023770. Epub 2008 Sep 8. [PubMed:18779312 ]
  7. Yamano S, Tatsuno J, Gonzalez FJ: The CYP2A3 gene product catalyzes coumarin 7-hydroxylation in human liver microsomes. Biochemistry. 1990 Feb 6;29(5):1322-9. [PubMed:2322567 ]
  8. Miles JS, Bickmore W, Brook JD, McLaren AW, Meehan R, Wolf CR: Close linkage of the human cytochrome P450IIA and P450IIB gene subfamilies: implications for the assignment of substrate specificity. Nucleic Acids Res. 1989 Apr 25;17(8):2907-17. [PubMed:2726448 ]
  9. Yamano S, Nagata K, Yamazoe Y, Kato R, Gelboin HV, Gonzalez FJ: cDNA and deduced amino acid sequences of human P450 IIA3 (CYP2A3). Nucleic Acids Res. 1989 Jun 26;17(12):4888. [PubMed:2748347 ]
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  12. Kitagawa K, Kunugita N, Kitagawa M, Kawamoto T: CYP2A6*6, a novel polymorphism in cytochrome p450 2A6, has a single amino acid substitution (R128Q) that inactivates enzymatic activity. J Biol Chem. 2001 May 25;276(21):17830-5. Epub 2001 Feb 16. [PubMed:11278503 ]
  13. Phillips IR, Shephard EA, Ashworth A, Rabin BR: Isolation and sequence of a human cytochrome P-450 cDNA clone. Proc Natl Acad Sci U S A. 1985 Feb;82(4):983-7. [PubMed:3856261 ]
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  16. Hadidi H, Zahlsen K, Idle JR, Cholerton S: A single amino acid substitution (Leu160His) in cytochrome P450 CYP2A6 causes switching from 7-hydroxylation to 3-hydroxylation of coumarin. Food Chem Toxicol. 1997 Sep;35(9):903-7. [PubMed:9409631 ]
  17. Oscarson M, McLellan RA, Gullsten H, Agundez JA, Benitez J, Rautio A, Raunio H, Pelkonen O, Ingelman-Sundberg M: Identification and characterisation of novel polymorphisms in the CYP2A locus: implications for nicotine metabolism. FEBS Lett. 1999 Oct 29;460(2):321-7. [PubMed:10544257 ]
  18. Ariyoshi N, Sawamura Y, Kamataki T: A novel single nucleotide polymorphism altering stability and activity of CYP2a6. Biochem Biophys Res Commun. 2001 Mar 2;281(3):810-4. [PubMed:11237731 ]
  19. Kiyotani K, Fujieda M, Yamazaki H, Shimada T, Guengerich FP, Parkinson A, Nakagawa K, Ishizaki T, Kamataki T: Twenty one novel single nucleotide polymorphisms (SNPs) of the CYP2A6 gene in Japanese and Caucasians. Drug Metab Pharmacokinet. 2002;17(5):482-7. [PubMed:15618701 ]
  20. Mwenifumbo JC, Al Koudsi N, Ho MK, Zhou Q, Hoffmann EB, Sellers EM, Tyndale RF: Novel and established CYP2A6 alleles impair in vivo nicotine metabolism in a population of Black African descent. Hum Mutat. 2008 May;29(5):679-88. doi: 10.1002/humu.20698. [PubMed:18360915 ]
  21. Ho MK, Mwenifumbo JC, Zhao B, Gillam EM, Tyndale RF: A novel CYP2A6 allele, CYP2A6*23, impairs enzyme function in vitro and in vivo and decreases smoking in a population of Black-African descent. Pharmacogenet Genomics. 2008 Jan;18(1):67-75. doi: 10.1097/FPC.0b013e3282f3606e. [PubMed:18216723 ]