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P11509 (CP2A6_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 171. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Cytochrome P450 2A6

EC=1.14.13.-
Alternative name(s):
1,4-cineole 2-exo-monooxygenase
CYPIIA6
Coumarin 7-hydroxylase
Cytochrome P450 IIA3
Cytochrome P450(I)
Gene names
Name:CYP2A6
Synonyms:CYP2A3
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length494 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

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. Ref.10 Ref.11 Ref.14 Ref.15 Ref.16 Ref.17

Catalytic activity

1,4-cineole + NADPH + O2 = 2-exo-hydroxy-1,4-cineole + NADP+ + H2O. Ref.14

Cofactor

Heme group.

Subcellular location

Endoplasmic reticulum membrane; Peripheral membrane protein. Microsome membrane; Peripheral membrane protein Ref.10 Ref.11.

Tissue specificity

Liver. Ref.10 Ref.11

Induction

By phenobarbital and dexamethasone. Ref.10 Ref.11

Sequence similarities

Belongs to the cytochrome P450 family.

Biophysicochemical properties

Kinetic parameters:

KM=0.23 µM for coumarin Ref.14 Ref.15

KM=530 µM for 1,4-cineole

Vmax=3.5 nmol/min/nmol enzyme toward 2-exo-hydroxy-1,4-cineole

Sequence caution

The sequence AAA52147.1 differs from that shown. Reason: Numerous conflicts and frameshifts.

Ontologies

Keywords
   Cellular componentEndoplasmic reticulum
Membrane
Microsome
   Coding sequence diversityPolymorphism
   LigandHeme
Iron
Metal-binding
NADP
   Molecular functionMonooxygenase
Oxidoreductase
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processcoumarin catabolic process

Inferred from direct assay PubMed 19029318. Source: BHF-UCL

coumarin metabolic process

Inferred from direct assay PubMed 19651758. Source: BHF-UCL

drug metabolic process

Inferred from direct assay PubMed 19651758. Source: BHF-UCL

exogenous drug catabolic process

Inferred from direct assay PubMed 15680923. Source: BHF-UCL

small molecule metabolic process

Traceable author statement. Source: Reactome

steroid metabolic process

Inferred from mutant phenotype PubMed 18356043. Source: BHF-UCL

xenobiotic metabolic process

Traceable author statement. Source: Reactome

   Cellular_componentcytoplasmic microtubule

Inferred from direct assay PubMed 23264731. Source: UniProtKB

endoplasmic reticulum membrane

Traceable author statement. Source: Reactome

   Molecular_functioncoumarin 7-hydroxylase activity

Inferred from direct assay Ref.15. Source: UniProtKB

enzyme binding

Inferred from physical interaction PubMed 15680923. Source: BHF-UCL

heme binding

Inferred from direct assay Ref.15. Source: UniProtKB

iron ion binding

Inferred from electronic annotation. Source: InterPro

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

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 494494Cytochrome P450 2A6
PRO_0000051668

Sites

Metal binding4391Iron (heme axial ligand)
Binding site1071Substrate Probable
Binding site2971Substrate

Natural variations

Natural variant51G → R in allele CYP2A6*13. Ref.21 Ref.23
Corresponds to variant rs28399434 [ dbSNP | Ensembl ].
VAR_018330
Natural variant291S → N in allele CYP2A6*14. Ref.1 Ref.21 Ref.23
Corresponds to variant rs28399435 [ dbSNP | Ensembl ].
VAR_018331
Natural variant1101V → L in allele CYP2A6*24, increases phenacetin O-deethylation activity 4 fold. Ref.17 Ref.24
Corresponds to variant rs72549435 [ dbSNP | Ensembl ].
VAR_055035
Natural variant1181F → L in allele CYP2A6*25 and allele CYP2A6*26. Ref.23 Ref.24
Corresponds to variant rs28399440 [ dbSNP | Ensembl ].
VAR_024711
Natural variant1281R → L in allele CYP2A6*26. Ref.24
VAR_055036
Natural variant1281R → Q in allele CYP2A6*6; loss of activity. Ref.12 Ref.23
Corresponds to variant rs4986891 [ dbSNP | Ensembl ].
VAR_011577
Natural variant1311S → A in allele CYP2A6*26. Ref.24
Corresponds to variant rs59552350 [ dbSNP | Ensembl ].
VAR_055037
Natural variant1601L → H in allele CYP2A6*2; unable to catalyze 7-hydroxylation of coumarin; causes switching from coumarin 7-hydroxylation to 3-hydroxylation. Ref.2 Ref.3 Ref.6 Ref.9 Ref.18
Corresponds to variant rs1801272 [ dbSNP | Ensembl ].
VAR_001249
Natural variant1941K → E in allele CYP2A6*15. Ref.21
VAR_018332
Natural variant2031R → C in allele CYP2A6*23; greatly reduced activity toward nicotine C-oxidation as well as reduced coumarin 7-hydroxylation. Ref.6 Ref.25
Corresponds to variant rs56256500 [ dbSNP | Ensembl ].
VAR_055034
Natural variant2031R → S in allele CYP2A6*16. Ref.21 Ref.25
Corresponds to variant rs56256500 [ dbSNP | Ensembl ].
VAR_018333
Natural variant2241S → P. Ref.23
Corresponds to variant rs111033610 [ dbSNP | Ensembl ].
VAR_024712
Natural variant2921V → M.
Corresponds to variant rs2644906 [ dbSNP | Ensembl ].
VAR_059149
Natural variant2941T → S.
Corresponds to variant rs4997557 [ dbSNP | Ensembl ].
VAR_048448
Natural variant3651V → M in allele CYP2A6*17, increases phenacetin O-deethylation activity 2 fold. Ref.6 Ref.17 Ref.23 Ref.25
Corresponds to variant rs28399454 [ dbSNP | Ensembl ].
VAR_024713
Natural variant3921F → Y. Ref.1 Ref.2 Ref.3 Ref.4 Ref.5 Ref.6 Ref.8 Ref.9 Ref.13
Corresponds to variant rs1809810 [ dbSNP | Ensembl ].
VAR_055033
Natural variant4181N → D in allele CYP2A6*28. Ref.6 Ref.23 Ref.24
Corresponds to variant rs28399463 [ dbSNP | Ensembl ].
VAR_024714
Natural variant4191E → D in allele CYP2A6*28. Ref.6 Ref.22 Ref.23 Ref.24
Corresponds to variant rs8192730 [ dbSNP | Ensembl ].
VAR_018375
Natural variant4381N → Y in allele CYP2A6*24. Ref.24
VAR_055038
Natural variant4711I → T in allele CYP2A6*7. Ref.20 Ref.22 Ref.23
Corresponds to variant rs5031016 [ dbSNP | Ensembl ].
VAR_011578
Natural variant4761K → R. Ref.9 Ref.23
Corresponds to variant rs6413474 [ dbSNP | Ensembl ].
VAR_024715
Natural variant4791G → V in allele CYP2A6*5; loss of activity. Ref.19
Corresponds to variant rs5031017 [ dbSNP | Ensembl ].
VAR_008356
Natural variant4851R → L in allele CYP2A6*8. Ref.20 Ref.23
Corresponds to variant rs28399468 [ dbSNP | Ensembl ].
VAR_011579

Experimental info

Mutagenesis2081I → S: Increases phenacetin O-deethylation activity 10 fold; when associated with F-300 and A-301. Increases phenacetin O-deethylation activity 38 fold; when associated with F-300; A-301 and G-369. Ref.17
Mutagenesis2131S → A: No effect on phenacetin O-deethylation activity. Ref.17
Mutagenesis3001I → F: Increases phenacetin O-deethylation activity 3 fold. Increases phenacetin O-deethylation activity 8 fold; when associated with A-301. Increases phenacetin O-deethylation activity 10 fold; when associated with S-208 and A-301. Increases phenacetin O-deethylation activity 12 fold; when associated with A-301 and G-369. Increases phenacetin O-deethylation activity 38 fold; when associated with S-208; A-301 and G-369. Ref.17
Mutagenesis3011G → A: Slightly decreases phenacetin O-deethylation activity. Increases phenacetin O-deethylation activity 8 fold; when associated with F-300. Increases phenacetin O-deethylation activity 10 fold; when associated with S-208 and F-300. Increases phenacetin O-deethylation activity 12 fold; when associated with F-300 and G-369. Increases phenacetin O-deethylation activity 38 fold; when associated with S-208; F-300 and G-369. Ref.17
Mutagenesis3691S → G: Increases phenacetin O-deethylation activity 3 fold. Increases phenacetin O-deethylation activity 38 fold; when associated with S-208; F-300 and A-301. Ref.17
Mutagenesis3721R → H: Increases phenacetin O-deethylation activity 2 fold. Ref.17
Sequence conflict3 – 75Missing in CAA32097. Ref.1
Sequence conflict2551N → K in CAA32097. Ref.1
Sequence conflict3261K → Q in CAA32097. Ref.1

Secondary structure

...................................................................... 494
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P11509 [UniParc].

Last modified October 5, 2010. Version 3.
Checksum: 8C05CBF0EFC698AF

FASTA49456,501
        10         20         30         40         50         60 
MLASGMLLVA LLVCLTVMVL MSVWQQRKSK GKLPPGPTPL PFIGNYLQLN TEQMYNSLMK 

        70         80         90        100        110        120 
ISERYGPVFT IHLGPRRVVV LCGHDAVREA LVDQAEEFSG RGEQATFDWV FKGYGVVFSN 

       130        140        150        160        170        180 
GERAKQLRRF SIATLRDFGV GKRGIEERIQ EEAGFLIDAL RGTGGANIDP TFFLSRTVSN 

       190        200        210        220        230        240 
VISSIVFGDR FDYKDKEFLS LLRMMLGIFQ FTSTSTGQLY EMFSSVMKHL PGPQQQAFQL 

       250        260        270        280        290        300 
LQGLEDFIAK KVEHNQRTLD PNSPRDFIDS FLIRMQEEEK NPNTEFYLKN LVMTTLNLFI 

       310        320        330        340        350        360 
GGTETVSTTL RYGFLLLMKH PEVEAKVHEE IDRVIGKNRQ PKFEDRAKMP YMEAVIHEIQ 

       370        380        390        400        410        420 
RFGDVIPMSL ARRVKKDTKF RDFFLPKGTE VFPMLGSVLR DPSFFSNPQD FNPQHFLNEK 

       430        440        450        460        470        480 
GQFKKSDAFV PFSIGKRNCF GEGLARMELF LFFTTVMQNF RLKSSQSPKD IDVSPKHVGF 

       490 
ATIPRNYTMS FLPR 

« Hide

References

« Hide 'large scale' references
[1]"Close linkage of the human cytochrome P450IIA and P450IIB gene subfamilies: implications for the assignment of substrate specificity."
Miles J.S., Bickmore W., Brook J.D., McLaren A.W., Meehan R., Wolf C.R.
Nucleic Acids Res. 17:2907-2917(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS ASN-29 AND TYR-392.
Tissue: Liver.
[2]"cDNA and deduced amino acid sequences of human P450 IIA3 (CYP2A3)."
Yamano S., Nagata K., Yamazoe Y., Kato R., Gelboin H.V., Gonzalez F.J.
Nucleic Acids Res. 17:4888-4888(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS HIS-160 AND TYR-392.
Tissue: Hepatocyte.
[3]"The CYP2A3 gene product catalyzes coumarin 7-hydroxylation in human liver microsomes."
Yamano S., Tatsuno J., Gonzalez F.J.
Biochemistry 29:1322-1329(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS HIS-160 AND TYR-392, CHARACTERIZATION OF VARIANT HIS-160.
Tissue: Hepatocyte.
[4]"Sequence of a new human cytochrome P450-2A6 cDNA."
Zhuge J., Qian Y., Xie H., Yu Y.
Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT TYR-392.
Tissue: Liver.
[5]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT TYR-392.
Tissue: Mammary gland.
[6]NIEHS SNPs program
Submitted (SEP-2007) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS HIS-160; CYS-203; MET-365; TYR-392; ASP-418 AND ASP-419.
[7]"The DNA sequence and biology of human chromosome 19."
Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V. expand/collapse author list , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M.
Nature 428:529-535(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT TYR-392.
[9]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANTS HIS-160; TYR-392 AND ARG-476.
[10]"Isolation and characterization of a cytochrome P450 of the IIA subfamily from human liver microsomes."
Maurice M., Emiliani S., Dalet-Beluche I., Derancourt J., Lange R.
Eur. J. Biochem. 200:511-517(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 1-20, FUNCTION, SUBCELLULAR LOCATION, INDUCTION, TISSUE SPECIFICITY.
[11]"Purification and characterization of human liver microsomal cytochrome P-450 2A6."
Yun C.H., Shimada T., Guengerich F.P.
Mol. Pharmacol. 40:679-685(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 1-13, FUNCTION, SUBCELLULAR LOCATION, INDUCTION, TISSUE SPECIFICITY.
[12]"CYP2A6*6, a novel polymorphism in cytochrome p450 2A6, has a single amino acid substitution (R128Q) that inactivates enzymatic activity."
Kitagawa K., Kunugita N., Kitagawa M., Kawamoto T.
J. Biol. Chem. 276:17830-17835(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 116-164, VARIANT CYP2A6*6 GLN-128.
[13]"Isolation and sequence of a human cytochrome P-450 cDNA clone."
Phillips I.R., Shephard E.A., Ashworth A., Rabin B.R.
Proc. Natl. Acad. Sci. U.S.A. 82:983-987(1985) [PubMed] [Europe PMC] [Abstract]
Cited for: PRELIMINARY NUCLEOTIDE SEQUENCE [MRNA] OF 163-494, VARIANT TYR-392.
[14]"Roles of cytochrome P450 3A enzymes in the 2-hydroxylation of 1,4-cineole, a monoterpene cyclic ether, by rat and human liver microsomes."
Miyazawa M., Shindo M., Shimada T.
Xenobiotica 31:713-723(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: CATALYTIC ACTIVITY, FUNCTION AS 1,4-CINEOLE 2-EXO-MONOOXYGENASE, BIOPHYSICOCHEMICAL PROPERTIES.
[15]"Structures of human microsomal cytochrome P450 2A6 complexed with coumarin and methoxsalen."
Yano J.K., Hsu M.H., Griffin K.J., Stout C.D., Johnson E.F.
Nat. Struct. Mol. Biol. 12:822-823(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 29-494 IN COMPLEX WITH COUMARIN; HEME AND THE INHIBITOR METHOXSALEN, FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES.
[16]"Synthetic inhibitors of cytochrome P-450 2A6: inhibitory activity, difference spectra, mechanism of inhibition, and protein cocrystallization."
Yano J.K., Denton T.T., Cerny M.A., Zhang X., Johnson E.F., Cashman J.R.
J. Med. Chem. 49:6987-7001(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS) OF 29-494 IN COMPLEX WITH PHENACETIN AND HEME, FUNCTION.
[17]"Key residues controlling phenacetin metabolism by human cytochrome P450 2A enzymes."
DeVore N.M., Smith B.D., Urban M.J., Scott E.E.
Drug Metab. Dispos. 36:2582-2590(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS) OF 29-494 IN COMPLEX WITH PHENACETIN AND HEME, FUNCTION, CHARACTERIZATION OF VARIANTS LEU-110 AND MET-365, MUTAGENESIS OF ILE-208; SER-213; ILE-300; GLY-301; SER-369 AND ARG-372.
[18]"A single amino acid substitution (Leu160His) in cytochrome P450 CYP2A6 causes switching from 7-hydroxylation to 3-hydroxylation of coumarin."
Hadidi H., Zahlsen K., Idle J.R., Cholerton S.
Food Chem. Toxicol. 35:903-907(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANT CYP2A6*2 HIS-160.
[19]"Identification and characterisation of novel polymorphisms in the CYP2A locus: implications for nicotine metabolism."
Oscarson M., McLellan R.A., Gullsten H., Agundez J.A., Benitez J., Rautio A., Raunio H., Pelkonen O., Ingelman-Sundberg M.
FEBS Lett. 460:321-327(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CYP2A6*5 VAL-479.
[20]"A novel single nucleotide polymorphism altering stability and activity of CYP2a6."
Ariyoshi N., Sawamura Y., Kamataki T.
Biochem. Biophys. Res. Commun. 281:810-814(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CYP2A6*7 THR-471 AND CYP2A6*8 LEU-485.
[21]"Twenty one novel single nucleotide polymorphisms (SNPs) of the CYP2A6 gene in Japanese and Caucasians."
Kiyotani K., Fujieda M., Yamazaki H., Shimada T., Guengerich F.P., Parkinson A., Nakagawa K., Ishizaki T., Kamataki T.
Drug Metab. Pharmacokinet. 17:482-487(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CYP2A6*13 ARG-5; CYP2A6*14 ASN-29; CYP2A6*15 GLU-194 AND CYP2A6*16 SER-203.
[22]"Catalog of 680 variations among eight cytochrome p450 (CYP) genes, nine esterase genes, and two other genes in the Japanese population."
Saito S., Iida A., Sekine A., Kawauchi S., Higuchi S., Ogawa C., Nakamura Y.
J. Hum. Genet. 48:249-270(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS ASP-419 AND THR-471.
[23]"Genetic variation in eleven phase I drug metabolism genes in an ethnically diverse population."
Solus J.F., Arietta B.J., Harris J.R., Sexton D.P., Steward J.Q., McMunn C., Ihrie P., Mehall J.M., Edwards T.L., Dawson E.P.
Pharmacogenomics 5:895-931(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS ARG-5; ASN-29; LEU-118; GLN-128; PRO-224; MET-365; ASP-418; ASP-419; THR-471; ARG-476 AND LEU-485.
[24]"Novel and established CYP2A6 alleles impair in vivo nicotine metabolism in a population of Black African descent."
Mwenifumbo J.C., Al Koudsi N., Ho M.K., Zhou Q., Hoffmann E.B., Sellers E.M., Tyndale R.F.
Hum. Mutat. 29:679-688(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS LEU-110; LEU-118; LEU-128; ALA-131; ASP-418; ASP-419 AND TYR-438.
[25]"A novel CYP2A6 allele, CYP2A6*23, impairs enzyme function in vitro and in vivo and decreases smoking in a population of Black-African descent."
Ho M.K., Mwenifumbo J.C., Zhao B., Gillam E.M., Tyndale R.F.
Pharmacogenet. Genomics 18:67-75(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CYS-203; SER-203 AND MET-365, CHARACTERIZATION OF VARIANT CYS-203.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X13897 mRNA. Translation: CAA32097.1.
X13929 mRNA. Translation: CAA32117.1.
X13930 mRNA. Translation: CAA32118.1.
M33318 mRNA. Translation: AAA52067.1.
AF182275 mRNA. Translation: AAF13600.1.
AK312964 mRNA. Translation: BAG35803.1.
EU135979 Genomic DNA. Translation: ABV02584.1.
FJ440681 Genomic DNA. Translation: ACK44068.1.
AC008537 Genomic DNA. No translation available.
CH471126 Genomic DNA. Translation: EAW57012.1.
BC096253 mRNA. Translation: AAH96253.3.
BC096254 mRNA. Translation: AAH96254.1.
BC096255 mRNA. Translation: AAH96255.1.
BC096256 mRNA. Translation: AAH96256.1.
AF326721 Genomic DNA. Translation: AAG45229.1.
K03192 mRNA. Translation: AAA52147.1. Sequence problems.
PIRO4HUPB. A00190.
O4HUA6. S04698.
RefSeqNP_000753.3. NM_000762.5.
UniGeneHs.250615.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1Z10X-ray1.90A/B/C/D29-494[»]
1Z11X-ray2.05A/B/C/D29-494[»]
2FDUX-ray1.85A/B/C/D29-494[»]
2FDVX-ray1.65A/B/C/D29-494[»]
2FDWX-ray2.05A/B/C/D29-494[»]
2FDYX-ray1.95A/B/C/D29-494[»]
3EBSX-ray2.15A/B/C/D29-494[»]
3T3QX-ray2.10A/B/C/D29-494[»]
3T3RX-ray2.40A/B/C/D29-494[»]
4EJJX-ray2.30A/B/C/D29-494[»]
ProteinModelPortalP11509.
SMRP11509. Positions 30-494.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107927. 2 interactions.

Chemistry

BindingDBP11509.
ChEMBLCHEMBL5282.
DrugBankDB00356. Chlorzoxazone.
DB00255. Diethylstilbestrol.
DB00783. Estradiol.
DB00977. Ethinyl Estradiol.
DB00983. Formoterol.
DB01159. Halothane.
DB01006. Letrozole.
DB00553. Methoxsalen.
DB01011. Metyrapone.
DB00184. Nicotine.
DB01085. Pilocarpine.
DB01124. Tolbutamide.
DB00752. Tranylcypromine.

PTM databases

PhosphoSiteP11509.

Polymorphism databases

DMDM308153612.

Proteomic databases

PaxDbP11509.
PRIDEP11509.

Protocols and materials databases

DNASU1548.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000301141; ENSP00000301141; ENSG00000255974.
GeneID1548.
KEGGhsa:1548.
UCSCuc002opl.4. human.

Organism-specific databases

CTD1548.
GeneCardsGC19M041352.
HGNCHGNC:2610. CYP2A6.
HPAHPA046713.
HPA047262.
MIM122720. gene+phenotype.
neXtProtNX_P11509.
PharmGKBPA121.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG2124.
HOVERGENHBG015789.
InParanoidP11509.
KOK17683.
OMADTHGANI.
OrthoDBEOG7RBZ85.
PhylomeDBP11509.
TreeFamTF352043.

Enzyme and pathway databases

BioCycMetaCyc:HS10343-MONOMER.
ReactomeREACT_111217. Metabolism.
SABIO-RKP11509.

Gene expression databases

ArrayExpressP11509.
BgeeP11509.
GenevestigatorP11509.

Family and domain databases

Gene3D1.10.630.10. 1 hit.
InterProIPR001128. Cyt_P450.
IPR017972. Cyt_P450_CS.
IPR002401. Cyt_P450_E_grp-I.
IPR008067. Cyt_P450_E_grp-I_CYP2A-like.
[Graphical view]
PfamPF00067. p450. 1 hit.
[Graphical view]
PRINTSPR00463. EP450I.
PR01684. EP450ICYP2A.
PR00385. P450.
SUPFAMSSF48264. SSF48264. 1 hit.
PROSITEPS00086. CYTOCHROME_P450. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSCYP2A6. human.
EvolutionaryTraceP11509.
GeneWikiCYP2A6.
GenomeRNAi1548.
NextBio6401.
PROP11509.
SOURCESearch...

Entry information

Entry nameCP2A6_HUMAN
AccessionPrimary (citable) accession number: P11509
Secondary accession number(s): A7YAE5 expand/collapse secondary AC list , B2R7F6, P00190, P10890, Q16803, Q4VAT9, Q4VAU0, Q4VAU1, Q9H1Z7, Q9UCU0, Q9UK48
Entry history
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: October 5, 2010
Last modified: April 16, 2014
This is version 171 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 19

Human chromosome 19: entries, gene names and cross-references to MIM