P11509 (CP2A6_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	494 AA.
Sequence status	Complete.
Protein existence	Evidence 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 component	Endoplasmic reticulum Membrane Microsome
Coding sequence diversity	Polymorphism
Ligand	Heme Iron Metal-binding NADP
Molecular function	Monooxygenase Oxidoreductase
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	coumarin catabolic process Inferred from direct assay PubMed 19029318. 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_component	cytoplasmic microtubule Inferred from direct assay PubMed 23264731. Source: UniProtKB endoplasmic reticulum membrane Traceable author statement. Source: Reactome
Molecular_function	coumarin 7-hydroxylase activity Inferred from direct assay Ref.15. Source: UniProtKB electron carrier activity Inferred from electronic annotation. Source: InterPro 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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 494

494

Cytochrome P450 2A6

PRO_0000051668

Sites

Metal binding

439

1

Iron (heme axial ligand)

Binding site

107

1

Substrate Probable

Binding site

297

1

Substrate

Natural variations

Natural variant

5

1

G → R in allele CYP2A6*13. Ref.21 Ref.23
Corresponds to variant rs28399434 [ dbSNP | Ensembl ].

VAR_018330

Natural variant

29

1

S → N in allele CYP2A6*14. Ref.1 Ref.21 Ref.23
Corresponds to variant rs28399435 [ dbSNP | Ensembl ].

VAR_018331

Natural variant

110

1

V → L in allele CYP2A6*24, increases phenacetin O-deethylation activity 4 fold. Ref.17 Ref.24

VAR_055035

Natural variant

118

1

F → L in allele CYP2A6*25 and allele CYP2A6*26. Ref.23 Ref.24
Corresponds to variant rs28399440 [ dbSNP | Ensembl ].

VAR_024711

Natural variant

128

1

R → L in allele CYP2A6*26. Ref.24

VAR_055036

Natural variant

128

1

R → Q in allele CYP2A6*6; loss of activity. Ref.12 Ref.23
Corresponds to variant rs4986891 [ dbSNP | Ensembl ].

VAR_011577

Natural variant

131

1

S → A in allele CYP2A6*26. Ref.24
Corresponds to variant rs59552350 [ dbSNP | Ensembl ].

VAR_055037

Natural variant

160

1

L → 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 variant

194

1

K → E in allele CYP2A6*15. Ref.21

VAR_018332

Natural variant

203

1

R → C in allele CYP2A6*23; greatly reduced activity toward nicotine C-oxidation as well as reduced coumarin 7-hydroxylation. Ref.6 Ref.25

VAR_055034

Natural variant

203

1

R → S in allele CYP2A6*16. Ref.21 Ref.25
Corresponds to variant rs56256500 [ dbSNP | Ensembl ].

VAR_018333

Natural variant

224

1

S → P. Ref.23

VAR_024712

Natural variant

292

1

V → M.
Corresponds to variant rs2644906 [ dbSNP | Ensembl ].

VAR_059149

Natural variant

294

1

T → S.
Corresponds to variant rs4997557 [ dbSNP | Ensembl ].

VAR_048448

Natural variant

365

1

V → 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 variant

392

1

F → 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 variant

418

1

N → D in allele CYP2A6*28. Ref.6 Ref.23 Ref.24
Corresponds to variant rs28399463 [ dbSNP | Ensembl ].

VAR_024714

Natural variant

419

1

E → D in allele CYP2A6*28. Ref.6 Ref.22 Ref.23 Ref.24
Corresponds to variant rs8192730 [ dbSNP | Ensembl ].

VAR_018375

Natural variant

438

1

N → Y in allele CYP2A6*24. Ref.24

VAR_055038

Natural variant

471

1

I → T in allele CYP2A6*7. Ref.20 Ref.22 Ref.23
Corresponds to variant rs5031016 [ dbSNP | Ensembl ].

VAR_011578

Natural variant

476

1

K → R. Ref.9 Ref.23
Corresponds to variant rs6413474 [ dbSNP | Ensembl ].

VAR_024715

Natural variant

479

1

G → V in allele CYP2A6*5; loss of activity. Ref.19
Corresponds to variant rs5031017 [ dbSNP | Ensembl ].

VAR_008356

Natural variant

485

1

R → L in allele CYP2A6*8. Ref.20 Ref.23
Corresponds to variant rs28399468 [ dbSNP | Ensembl ].

VAR_011579

Experimental info

Mutagenesis

208

1

I → 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

Mutagenesis

213

1

S → A: No effect on phenacetin O-deethylation activity. Ref.17

Mutagenesis

300

1

I → 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

Mutagenesis

301

1

G → 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

Mutagenesis

369

1

S → 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

Mutagenesis

372

1

R → H: Increases phenacetin O-deethylation activity 2 fold. Ref.17

Sequence conflict

3 – 7

5

Missing in CAA32097. Ref.1

Sequence conflict

255

1

N → K in CAA32097. Ref.1

Sequence conflict

326

1

K → Q in CAA32097. Ref.1

Secondary structure

1

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494

Helix Strand Turn

Details...

Turn

41 – 43

3

Helix

46 – 48

3

Helix

51 – 53

3

Helix

54 – 65

12

Beta strand

67 – 73

7

Beta strand

76 – 81

6

Helix

84 – 91

8

Turn

92 – 98

7

Helix

105 – 111

7

Beta strand

115 – 118

4

Helix

121 – 137

17

Turn

138 – 141

4

Helix

143 – 162

20

Turn

163 – 165

3

Helix

171 – 187

17

Helix

196 – 212

17

Helix

215 – 227

13

Beta strand

230 – 232

3

Helix

233 – 256

24

Helix

267 – 277

11

Turn

278 – 280

3

Helix

288 – 319

32

Helix

321 – 334

14

Beta strand

337 – 339

3

Helix

343 – 348

6

Helix

350 – 363

14

Beta strand

378 – 380

3

Beta strand

383 – 385

3

Beta strand

390 – 393

4

Helix

395 – 399

5

Turn

402 – 404

3

Helix

413 – 416

4

Beta strand

419 – 421

3

Helix

442 – 459

18

Beta strand

460 – 466

7

Helix

468 – 470

3

Beta strand

476 – 483

8

Beta strand

489 – 493

5

Sequences

	Sequence		Length	Mass (Da)
	P11509 [UniParc]. Last modified October 5, 2010. Version 3. Checksum: 8C05CBF0EFC698AF	FASTA	494	56,501
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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. , 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.

Web resources

Cytochrome P450 Allele Nomenclature Committee

CYP2A6 alleles

NIEHS-SNPs

Wikipedia

CYP2A6 entry

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.

IPI

IPI00299568.

PIR

O4HUPB. A00190.
O4HUA6. S04698.

RefSeq

NP_000753.3. NM_000762.5.

UniGene

Hs.250615.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1Z10	X-ray	1.90	A/B/C/D	29-494	[»]
1Z11	X-ray	2.05	A/B/C/D	29-494	[»]
2FDU	X-ray	1.85	A/B/C/D	29-494	[»]
2FDV	X-ray	1.65	A/B/C/D	29-494	[»]
2FDW	X-ray	2.05	A/B/C/D	29-494	[»]
2FDY	X-ray	1.95	A/B/C/D	29-494	[»]
3EBS	X-ray	2.15	A/B/C/D	29-494	[»]
3T3Q	X-ray	2.10	A/B/C/D	29-494	[»]
3T3R	X-ray	2.40	A/B/C/D	29-494	[»]
4EJJ	X-ray	2.30	A/B/C/D	29-494	[»]

ProteinModelPortal

P11509.

SMR

P11509. Positions 30-494.

ModBase

Search...

PTM databases

PhosphoSite

P11509.

Polymorphism databases

DMDM

308153612.

Proteomic databases

PaxDb

P11509.

PRIDE

P11509.

Protocols and materials databases

DNASU

1548.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000301141; ENSP00000301141; ENSG00000255974.

GeneID

1548.

KEGG

hsa:1548.

UCSC

uc002opl.4. human.

Organism-specific databases

CTD

1548.

GeneCards

GC19M041352.

HGNC

HGNC:2610. CYP2A6.

MIM

122720. gene+phenotype.

neXtProt

NX_P11509.

PharmGKB

PA121.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG2124.

HOVERGEN

HBG015789.

InParanoid

P11509.

KO

K07411.

OMA

GGANIDP.

OrthoDB

EOG4K9BC2.

PhylomeDB

P11509.

Enzyme and pathway databases

BioCyc

MetaCyc:HS10343-MONOMER.

Reactome

REACT_111217. Metabolism.

SABIO-RK

P11509.

Gene expression databases

Bgee

P11509.

Genevestigator

P11509.

GermOnline

ENSG00000198077. Homo sapiens.

Family and domain databases

Gene3D

1.10.630.10. 1 hit.

InterPro

IPR001128. Cyt_P450.
IPR017972. Cyt_P450_CS.
IPR002401. Cyt_P450_E_grp-I.
IPR008067. Cyt_P450_E_grp-I_CYP2A-like.
[Graphical view]

Pfam

PF00067. p450. 1 hit.
[Graphical view]

PRINTS

PR00463. EP450I.
PR01684. EP450ICYP2A.
PR00385. P450.

SUPFAM

SSF48264. Cytochrome_P450. 1 hit.

PROSITE

PS00086. CYTOCHROME_P450. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P11509.

ChEMBL

CHEMBL5282.

ChiTaRS

CYP2A6. human.

DrugBank

DB00356. 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.

EvolutionaryTrace

P11509.

GenomeRNAi

1548.

NextBio

6401.

SOURCE

Search...

Entry information

Entry name

CP2A6_HUMAN

Accession

Primary (citable) accession number: P11509
Secondary accession number(s): A7YAE5 , 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:	May 1, 2013
This is version 162 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.