CYP2A6 Knowpia

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
Gene location (Human)
Chr.	Chromosome 19 (human)
End	40,850,447 bp
Gene location (Mouse)
Chr.	Chromosome 7 (mouse)
End	26,542,973 bp
RNA expression pattern
	Top expressed in
	right lobe of liver; ; middle frontal gyrus; ; frontal pole; ; Brodmann area 10; ; cerebellar vermis; ; sperm; ; thymus; ; synovial membrane; ; trachea; ; pons;
	Top expressed in
	proximal tubule; ; kidney; ; hepatobiliary system; ; liver; ; esophagus; ; respiratory epithelium; ; thymus; ; olfactory epithelium; ; lung; ; ovary;
	More reference expression data
	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
	1548
	13087
	ENSG00000255974
	ENSMUSG00000005547
	P11509
	P20852
	NM_000762
	NM_007812
	NP_000753
	n/a
	Wikidata
View/Edit Human	View/Edit Mouse

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.

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 edit

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

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

Distribution edit

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

Variability edit

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

Induction edit

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 edit

**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]

References edit

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000255974 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000005547 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ This article incorporates public domain material from "Entrez Gene: CYP2A6 cytochrome P450, family 2, subfamily A, polypeptide 6". Reference Sequence collection. National Center for Biotechnology Information.
^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k ^l ^m ⁿ ^o ^p ^q ^r ^s ^t ^u ^v ^w ^x ^y ^z ^aa ^ab ^ac ^ad Lacy CF, Armstrong LL, Goldman MP, Lance LL (2007). Cytochrome P450 Enzymes: Substrates, Inhibitors, and Inducers. Hudson, OH: LexiComp Inc. pp. 1899–1912.
^ Wen X, Wang JS, Neuvonen PJ, Backman JT (2002). "Isoniazid is a mechanism-based inhibitor of cytochrome P450 1A2, 2A6, 2C19 and 3A4 isoforms in human liver microsomes". Eur. J. Clin. Pharmacol. 57 (11): 799–804. doi:10.1007/s00228-001-0396-3. PMID 11868802. S2CID 19299097.
^ Siu EC, Tyndale RF (2008). "Selegiline is a mechanism-based inactivator of CYP2A6 inhibiting nicotine metabolism in humans and mice". J. Pharmacol. Exp. Ther. 324 (3): 992–9. doi:10.1124/jpet.107.133900. PMID 18065502. S2CID 9833233.

External links edit

Human CPA6 genome location and CPA6 gene details page in the UCSC Genome Browser.
Human CYP2A6 genome location and CYP2A6 gene details page in the UCSC Genome Browser.

[WikiPathways-6] The interactive pathway map can be edited at WikiPathways: "FluoropyrimidineActivity_WP1601".

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000255974 – Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000005547 – Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[5] This article incorporates public domain material from "Entrez Gene: CYP2A6 cytochrome P450, family 2, subfamily A, polypeptide 6". Reference Sequence collection. National Center for Biotechnology Information.

[:0-7] ^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k ^l ^m ⁿ ^o ^p ^q ^r ^s ^t ^u ^v ^w ^x ^y ^z ^aa ^ab ^ac ^ad Lacy CF, Armstrong LL, Goldman MP, Lance LL (2007). Cytochrome P450 Enzymes: Substrates, Inhibitors, and Inducers. Hudson, OH: LexiComp Inc. pp. 1899–1912.

[pmid11868802-8] Wen X, Wang JS, Neuvonen PJ, Backman JT (2002). "Isoniazid is a mechanism-based inhibitor of cytochrome P450 1A2, 2A6, 2C19 and 3A4 isoforms in human liver microsomes". Eur. J. Clin. Pharmacol. 57 (11): 799–804. doi:10.1007/s00228-001-0396-3. PMID 11868802. S2CID 19299097.

[pmid18065502-9] Siu EC, Tyndale RF (2008). "Selegiline is a mechanism-based inactivator of CYP2A6 inhibiting nicotine metabolism in humans and mice". J. Pharmacol. Exp. Ther. 324 (3): 992–9. doi:10.1124/jpet.107.133900. PMID 18065502. S2CID 9833233.

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Summary