CYP2A6

Cytochrome P450 2A6 (abbreviated CYP2A6) is a member of the cytochrome P450 mixed-function oxidase system, which is involved in the metabolism of xenobiotics in the body. CYP2A6 is the primary enzyme responsible for the oxidation of nicotine and cotinine. It is also involved in the metabolism of several pharmaceuticals, carcinogens, and a number of coumarin-type alkaloids. CYP2A6 is the only enzyme in the human body that appreciably catalyzes the 7-hydroxylation of coumarin, such that the formation of the product of this reaction, 7-hydroxycoumarin, is used as a probe for CYP2A6 activity.

CYP2A6
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 4RUI, 1Z10, 1Z11, 2FDU, 2FDV, 2FDW, 2FDY, 3EBS, 3T3Q, 3T3R, 4EJJ
Identifiers
Aliases	CYP2A6, CPA6, CYP2A, CYP2A3, CYPIIA6, P450C2A, P450PB, cytochrome P450 family 2 subfamily A member 6
External IDs	OMIM: 122720; MGI: 88597; HomoloGene: 85917; GeneCards: CYP2A6; OMA:CYP2A6 - orthologs
Gene location (Human) Chr. Chromosome 19 (human)[1] Band 19q13.2 Start 40,843,541 bp[1] End 40,850,447 bp[1]
Gene location (Mouse) Chr. Chromosome 7 (mouse)[2] Band 7 A3|7 15.54 cM Start 26,534,730 bp[2] End 26,542,973 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right lobe of liver paraflocculus of cerebellum middle frontal gyrus frontal pole Brodmann area 10 nasal epithelium cerebellar vermis male germ cell sperm Thalamus Top expressed in proximal tubule human kidney right kidney hepatobiliary system liver esophagus respiratory epithelium thymus nasal epithelium olfactory epithelium More reference expression data BioGPS n/a
Gene ontology Molecular function iron ion binding arachidonic acid epoxygenase 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 metal ion binding monooxygenase activity heme binding oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen enzyme binding oxidoreductase activity coumarin 7-hydroxylase activity steroid hydroxylase activity Cellular component organelle membrane endoplasmic reticulum membrane membrane intracellular membrane-bounded organelle endoplasmic reticulum cytoplasmic microtubule cytoplasm Biological process steroid metabolic process epoxygenase P450 pathway coumarin catabolic process coumarin metabolic process organic acid metabolic process xenobiotic metabolic process Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 1548 13087 Ensembl ENSG00000255974 ENSMUSG00000005547 UniProt P11509 P20852 RefSeq (mRNA) NM_000762 NM_007812 RefSeq (protein) NP_000753 n/a Location (UCSC) Chr 19: 40.84 – 40.85 Mb Chr 7: 26.53 – 26.54 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

The CYP2A6 gene is part of a large cluster of cytochrome P450 genes from the CYP2A, CYP2B and CYP2F subfamilies on chromosome 19q. The gene was formerly referred to as CYP2A3; however, it has been renamed CYP2A6.^[5]

Interactive pathway map

Click on genes, proteins and metabolites below to link to respective articles.^{[§ 1]}

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|alt=Fluorouracil (5-FU) Activity edit]]

Fluorouracil (5-FU) Activity edit

1. The interactive pathway map can be edited at WikiPathways: "FluoropyrimidineActivity_WP1601".

Distribution

CYP2A6 localizes to the endoplasmic reticulum and is found predominantly in the liver.

Variability

Significant interindividual variability in CYP2A6 apoprotein and mRNA levels has been observed.

Induction

CYP2A6 is known to be inducible by phenobarbital and rifampicin, and it is suspected that other antiepileptic drugs may also have this effect.

CYP2A6 Ligands

Selected inducers, inhibitors and substrates of CYP2A6

Substrates	Inhibitors	Inducers
Many Carcinogens MNAN NNK NDEA MTBE Other toxins aflatoxin B1 (mycotoxin) 1,3-butadiene (in synthetic rubber) coumarin (anticoagulant, found in cinnamon) DCBN (herbicide) 7-ethoxycoumarin (test substrate) skatole quinoline MOCA (in polyurethane production) halothane (anaesthetic) losigamone (anticonvulsant) methoxyflurane (anaesthetic) cotinine (metabolite of nicotine) nicotine (stimulant) SM-12502 (PAF antagonist) valproic acid (anticonvulsant, mood-stabilizing) dexmedetomidine (sedative)[6]	amiodarone (antiarrhythmic agent)[6] amlodipine (calcium channel blocker)[6] buprenorphine (semisynthetic opioid)[6] clofibrate (fibrate)[6] clotrimazole (antifungal)[6] desipramine (tricyclic antidepressant)[6] disulfiram (acetaldehyde dehydrogenase inhibitor)[6] entacapone (COMT inhibitor, used in Parkinson's disease)[6] fenofibrate (fibrate)[6] gabapentin (anticonvulsant) grapefruit juice flavonoids isoniazid (antibacterial)[6][7] ketoconazole (antifungal)[6] letrozole (aromatase inhibitor, used in breast cancer)[6] methimazole (antithyroid agent)[6] methoxsalen (furanocoumarin, used in psoriasis)[6] metyrapone (used to diagnose adrenal insufficiency)[6] miconazole (antifungal)[6] modafinil (wakefulness-promoting agent)[6] nicotine (stimulant)[6] orphenadrine (antihistamine)[6] pilocarpine (muscarinic receptor agonist)[6] pregabalin (anticonvulsant) selegiline (monoamine oxidase inhibitor)[6][8] sulconazole (antifungal)[6] tioconazole (antifungal)[6] tranylcypromine (monoamine oxidase inhibitor)[6]	Barbiturates amobarbital[6] pentobarbital[6] phenobarbital[6] secobarbital[6] rifampicin (antibacterial)[6]

See also

• List of cytochrome P450 modulators