P10635 (CP2D6_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Cytochrome P450 2D6
EC=1.14.14.1

Alternative name(s):
CYPIID6
Cytochrome P450-DB1
Debrisoquine 4-hydroxylase

Gene names

Name:	CYP2D6
Synonyms:	CYP2DL1

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	497 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants. Ref.9
Catalytic activity	RH + reduced flavoprotein + O2 = ROH + oxidized flavoprotein + H2O.
Cofactor	Heme group.
Subcellular location	Endoplasmic reticulum membrane; Peripheral membrane protein. Microsome membrane; Peripheral membrane protein.
Induction	By pregnancy.
Polymorphism	Genetic variations in CYP2D6 are the cause of poor drug metabolism CYP2D6-related [MIM:608902]. The CYP2D6 gene is highly polymorphic. CYP2D6 activity ranges widely within a population comprising ultrarapid (UM), extensive (EM), intermediate (IM) and poor (PM) metabolizer phenotypes. UM and PM are those most at risk for treatment failure or dose-dependent drug toxicity, respectively. Of the Caucasian populations of Europe and North America, 5%-10% are of the PM phenotype and are unable to metabolize the antihypersensitive drug debrisoquine and numerous other drugs. Allele CYP2D6*7 was also known as CYP2D6E, allele CYP2D6*9 as CYP2D6C, allele CYP2D6*10 as CYP2D6J, allele CYP2D6*17 as CYP2D6Z. Isozymes CYP2D6.45 (Lys-155, Cys-296 and Thr-486) and CYP2D6.46 (His-26, Lys-155, Cys-296 and Thr-486) are functional.
Sequence similarities	Belongs to the cytochrome P450 family.

Ontologies

Keywords
Cellular component	Endoplasmic reticulum Membrane Microsome
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	Heme Iron Metal-binding
Molecular function	Monooxygenase Oxidoreductase
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	alkaloid catabolic process Inferred from direct assay PubMed 15039299. Source: BHF-UCL coumarin metabolic process Inferred from direct assay PubMed 19438707. Source: BHF-UCL drug catabolic process Inferred from direct assay PubMed 15039299. Source: BHF-UCL isoquinoline alkaloid metabolic process Inferred from direct assay PubMed 19448135. Source: BHF-UCL monoterpenoid metabolic process Inferred from direct assay PubMed 16401082. Source: BHF-UCL negative regulation of binding Inferred from direct assay PubMed 19448135. Source: BHF-UCL negative regulation of cellular organofluorine metabolic process Inferred from direct assay PubMed 19448135. Source: BHF-UCL oxidative demethylation Inferred from direct assay PubMed 15039299PubMed 19438707. 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 PubMed 19438707. Source: BHF-UCL
Cellular_component	endoplasmic reticulum membrane Traceable author statement. Source: Reactome mitochondrion Inferred from direct assay PubMed 19438707. Source: BHF-UCL
Molecular_function	aromatase activity Inferred from electronic annotation. Source: EC drug binding Inferred from direct assay PubMed 19448135. Source: BHF-UCL electron carrier activity Inferred from electronic annotation. Source: InterPro heme binding Inferred from direct assay Ref.9. Source: UniProtKB iron ion binding Inferred from electronic annotation. Source: InterPro monooxygenase activity Inferred from direct assay PubMed 15327587PubMed 19651758. Source: BHF-UCL
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P10635-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: P10635-2)

The sequence of this isoform differs from the canonical sequence as follows:
     118-168: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 497

497

Cytochrome P450 2D6

PRO_0000051731

Sites

Metal binding

443

1

Iron (heme axial ligand)

Binding site

301

1

Substrate Probable

Natural variations

Alternative sequence

118 – 168

51

Missing in isoform 2.

VSP_044486

Natural variant

11

1

V → M in allele CYP2D6*35. Ref.18
Corresponds to variant rs769258 [ dbSNP | Ensembl ].

VAR_008366

Natural variant

26

1

R → H in allele CYP2D6*21 and allele CYP2D6*46. Ref.4 Ref.6 Ref.18
Corresponds to variant rs28371696 [ dbSNP | Ensembl ].

VAR_008367

Natural variant

28

1

R → C in allele CYP2D6*22.

VAR_008368

Natural variant

34

1

P → S in allele CYP2D6*10 and allele CYP2D6*14; poor debrisquone metabolism. Ref.11 Ref.18
Corresponds to variant rs1065852 [ dbSNP | Ensembl ].

VAR_008336

Natural variant

42

1

G → R in allele CYP2D6*12; impaired metabolism of sparteine. Ref.15
Corresponds to variant rs5030862 [ dbSNP | Ensembl ].

VAR_001256

Natural variant

85

1

A → V in allele CYP2D6*23.

VAR_008369

Natural variant

91

1

L → M. Ref.18
Corresponds to variant rs28371703 [ dbSNP | Ensembl ].

VAR_024720

Natural variant

94

1

H → R. Ref.18
Corresponds to variant rs28371704 [ dbSNP | Ensembl ].

VAR_024721

Natural variant

107

1

T → I in allele CYP2D6*17; poor debrisquone metabolism. Ref.14 Ref.18
Corresponds to variant rs28371706 [ dbSNP | Ensembl ].

VAR_008337

Natural variant

120

1

F → I. Ref.18
Corresponds to variant rs1135822 [ dbSNP | Ensembl ].

VAR_024722

Natural variant

155

1

E → K in allele CYP2D6*45A, allele CYP2D6*45B and allele CYP2D6*46. Ref.4 Ref.18
Corresponds to variant rs28371710 [ dbSNP | Ensembl ].

VAR_024723

Natural variant

169

1

G → R in allele CYP2D6*14; poor debrisquone metabolism. Ref.17

VAR_008338

Natural variant

212

1

G → E in allele CYP2D6*6B and allele CYP2D6*6C. Ref.13
Corresponds to variant rs5030866 [ dbSNP | Ensembl ].

VAR_008339

Natural variant

231

1

L → P.
Corresponds to variant rs17002853 [ dbSNP | Ensembl ].

VAR_045679

Natural variant

237

1

A → S in allele CYP2D6*33. Ref.18
Corresponds to variant rs28371717 [ dbSNP | Ensembl ].

VAR_008370

Natural variant

281

1

Missing in allele CYP2D6*9. Ref.10

VAR_008347

Natural variant

296

1

R → C in allele CYP2D6*2, allele CYP2D6*12, allele CYP2D6*14, allele CYP2D6*17, allele CYP2D6*45A, allele CYP2D6*45B and allele CYP2D6*46. Ref.4 Ref.7 Ref.8 Ref.18
Corresponds to variant rs16947 [ dbSNP | Ensembl ].

VAR_008340

Natural variant

297

1

I → L in allele CYP2D6*24.

VAR_008371

Natural variant

300

1

A → G.
Corresponds to variant rs1058170 [ dbSNP | Ensembl ].

VAR_045680

Natural variant

311

1

S → L.
Corresponds to variant rs1800754 [ dbSNP | Ensembl ].

VAR_014633

Natural variant

324

1

H → P in allele CYP2D6*7; loss of activity. Ref.12
Corresponds to variant rs5030867 [ dbSNP | Ensembl ].

VAR_008348

Natural variant

329

1

R → L.
Corresponds to variant rs3915951 [ dbSNP | Ensembl ].

VAR_059150

Natural variant

343

1

R → G in allele CYP2D6*25.

VAR_008372

Natural variant

365

1

R → H.
Corresponds to variant rs1058172 [ dbSNP | Ensembl ].

VAR_045681

Natural variant

369

1

I → T in allele CYP2D6*26.

VAR_008373

Natural variant

373

1

G → S.
Corresponds to variant rs2856959 [ dbSNP | Ensembl ].

VAR_059151

Natural variant

410

1

E → K in allele CYP2D6*27.

VAR_008374

Natural variant

418

1

E → K. Ref.18

VAR_024724

Natural variant

469

1

P → A. Ref.18
Corresponds to variant rs1135833 [ dbSNP | Ensembl ].

VAR_024725

Natural variant

478

1

H → Y. Ref.18
Corresponds to variant rs28371735 [ dbSNP | Ensembl ].

VAR_024726

Natural variant

486

1

S → T in allele CYP2D6*2, allele CYP2D6*10, allele CYP2D6*12, allele CYP2D6*14, allele CYP2D6*17, allele CYP2D6*45A, allele CYP2D6*45B and allele CYP2D6*46; impaired metabolism of sparteine. Ref.4 Ref.7 Ref.8 Ref.11 Ref.18
Corresponds to variant rs1135840 [ dbSNP | Ensembl ].

VAR_008341

Experimental info

Sequence conflict

374

1

V → M in AAA52153. Ref.1

Sequence conflict

374

1

V → M in CAA30807. Ref.2

Secondary structure

1

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497

Helix Strand Turn

Details...

Turn

41 – 43

3

Helix

46 – 48

3

Helix

54 – 65

12

Beta strand

67 – 73

7

Beta strand

76 – 81

6

Helix

83 – 91

9

Turn

92 – 94

3

Helix

95 – 97

3

Helix

105 – 110

6

Turn

118 – 121

4

Helix

126 – 141

16

Turn

143 – 145

3

Helix

148 – 165

18

Turn

166 – 169

4

Helix

175 – 191

17

Helix

200 – 214

15

Helix

219 – 226

8

Helix

228 – 232

5

Helix

234 – 240

7

Helix

242 – 261

20

Helix

271 – 281

11

Turn

282 – 284

3

Helix

292 – 323

32

Helix

325 – 338

14

Beta strand

341 – 343

3

Helix

347 – 350

4

Helix

354 – 367

14

Beta strand

370 – 372

3

Beta strand

382 – 384

3

Beta strand

387 – 389

3

Beta strand

394 – 397

4

Helix

399 – 403

5

Turn

406 – 408

3

Beta strand

409 – 411

3

Helix

417 – 420

4

Helix

446 – 463

18

Beta strand

464 – 467

4

Beta strand

479 – 487

9

Beta strand

492 – 496

5

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified December 20, 2005. Version 2. Checksum: 542B1D505DF3CDAC	FASTA	497	55,769
	10 20 30 40 50 60 MGLEALVPLA VIVAIFLLLV DLMHRRQRWA ARYPPGPLPL PGLGNLLHVD FQNTPYCFDQ 70 80 90 100 110 120 LRRRFGDVFS LQLAWTPVVV LNGLAAVREA LVTHGEDTAD RPPVPITQIL GFGPRSQGVF 130 140 150 160 170 180 LARYGPAWRE QRRFSVSTLR NLGLGKKSLE QWVTEEAACL CAAFANHSGR PFRPNGLLDK 190 200 210 220 230 240 AVSNVIASLT CGRRFEYDDP RFLRLLDLAQ EGLKEESGFL REVLNAVPVL LHIPALAGKV 250 260 270 280 290 300 LRFQKAFLTQ LDELLTEHRM TWDPAQPPRD LTEAFLAEME KAKGNPESSF NDENLRIVVA 310 320 330 340 350 360 DLFSAGMVTT STTLAWGLLL MILHPDVQRR VQQEIDDVIG QVRRPEMGDQ AHMPYTTAVI 370 380 390 400 410 420 HEVQRFGDIV PLGVTHMTSR DIEVQGFRIP KGTTLITNLS SVLKDEAVWE KPFRFHPEHF 430 440 450 460 470 480 LDAQGHFVKP EAFLPFSAGR RACLGEPLAR MELFLFFTSL LQHFSFSVPT GQPRPSHHGV 490 FAFLVSPSPY ELCAVPR
	Isoform 2 [UniParc]. Checksum: D1FB49C5A4B10965	FASTA	446	50,061
	10 20 30 40 50 60 MGLEALVPLA VIVAIFLLLV DLMHRRQRWA ARYPPGPLPL PGLGNLLHVD FQNTPYCFDQ 70 80 90 100 110 120 LRRRFGDVFS LQLAWTPVVV LNGLAAVREA LVTHGEDTAD RPPVPITQIL GFGPRSQGRP 130 140 150 160 170 180 FRPNGLLDKA VSNVIASLTC GRRFEYDDPR FLRLLDLAQE GLKEESGFLR EVLNAVPVLL 190 200 210 220 230 240 HIPALAGKVL RFQKAFLTQL DELLTEHRMT WDPAQPPRDL TEAFLAEMEK AKGNPESSFN 250 260 270 280 290 300 DENLRIVVAD LFSAGMVTTS TTLAWGLLLM ILHPDVQRRV QQEIDDVIGQ VRRPEMGDQA 310 320 330 340 350 360 HMPYTTAVIH EVQRFGDIVP LGVTHMTSRD IEVQGFRIPK GTTLITNLSS VLKDEAVWEK 370 380 390 400 410 420 PFRFHPEHFL DAQGHFVKPE AFLPFSAGRR ACLGEPLARM ELFLFFTSLL QHFSFSVPTG 430 440 QPRPSHHGVF AFLVSPSPYE LCAVPR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human debrisoquine 4-hydroxylase (P450IID1): cDNA and deduced amino acid sequence and assignment of the CYP2D locus to chromosome 22." Gonzalez F.J., Vilbois F., Hardwick J.P., McBride O.W., Nebert D.W., Gelboin H.V., Meyer U.A. Genomics 2:174-179(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	"Characterization of the common genetic defect in humans deficient in debrisoquine metabolism." Gonzalez F.J., Skoda R.C., Kimura S., Umeno M., Zanger U.M., Nebert D.W., Gelboin H.V., Hardwick J.P., Meyer U.A. Nature 331:442-446(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Liver.
[3]	"The human debrisoquine 4-hydroxylase (CYP2D) locus: sequence and identification of the polymorphic CYP2D6 gene, a related gene, and a pseudogene." Kimura S., Umeno M., Skoda R.C., Meyer U.A., Gonzalez F.J. Am. J. Hum. Genet. 45:889-904(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"Identification and characterization of novel sequence variations in the cytochrome P4502D6 (CYP2D6) gene in African Americans." Gaedigk A., Bhathena A., Ndjountche L., Pearce R.E., Abdel-Rahman S.M., Alander S.W., Bradford L.D., Rogan P.K., Leeder J.S. Pharmacogenomics J. 5:173-182(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ALLELE CYP2D6*1), IDENTIFICATION OF ALLELES CYP2D6*41B; CYP2D6*45A; CYP2D6*45B AND CYP2D6*46, VARIANTS HIS-26; LYS-155; CYS-296 AND THR-486, CHARACTERIZATION OF ISOZYMES CYP2D6.45 AND CYP2D6.46.
[5]	Erratum Gaedigk A., Bhathena A., Ndjountche L., Pearce R.E., Abdel-Rahman S.M., Alander S.W., Bradford L.D., Rogan P.K., Leeder J.S. Pharmacogenomics J. 5:276-276(2005)
[6]	"CYP2D6 evolution and allele diversity among human races." Koch W.H., Nikoloff D.M., Lu W., Pan R.M., deLeon J., Wedlund P.J. Submitted (NOV-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT HIS-26.
[7]	"The DNA sequence of human chromosome 22." Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M., Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C., Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E., Bridgeman A.M. , Buck D., Burgess J., Burrill W.D., Burton J., Carder C., Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G., Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V., Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A., Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C., Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E., Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F., Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M., Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A., Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D., Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S., Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E., Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L., Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L., Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N., Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A., Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L., Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P., Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P., Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q., Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J., Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J., Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D., Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T., Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R., Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L., McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J., Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E., Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P., Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y., Wright H. Nature 402:489-495(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANTS CYS-296 AND THR-486.
[8]	"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] (ISOFORMS 1 AND 2), VARIANTS CYS-296 AND THR-486.
[9]	"Crystal structure of human cytochrome P450 2D6." Rowland P., Blaney F.E., Smyth M.G., Jones J.J., Leydon V.R., Oxbrow A.K., Lewis C.J., Tennant M.G., Modi S., Eggleston D.S., Chenery R.J., Bridges A.M. J. Biol. Chem. 281:7614-7622(2006) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 34-497 IN COMPLEX WITH HEME, FUNCTION.
[10]	"Identification of a new variant CYP2D6 allele lacking the codon encoding Lys-281: possible association with the poor metabolizer phenotype." Tyndale R., Aoyama T., Broly F., Matsunaga T., Inaba T., Kalow W., Gelboin H.V., Meyer U.A., Gonzalez F.J. Pharmacogenetics 1:26-32(1991) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT CYP2D6*9 LYS-281 DEL.
[11]	"Evidence for a new variant CYP2D6 allele CYP2D6J in a Japanese population associated with lower in vivo rates of sparteine metabolism." Yokota H., Tamura S., Furuya H., Kimura S., Watanabe M., Kanazawa I., Kondo I., Gonzalez F.J. Pharmacogenetics 3:256-263(1993) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS CYP2D6*10 SER-34 AND THR-486.
[12]	"A missense mutation in exon 6 of the CYP2D6 gene leading to a histidine 324 to proline exchange is associated with the poor metabolizer phenotype of sparteine." Evert B., Griese E.U., Eichelbaum M. Naunyn Schmiedebergs Arch. Pharmacol. 350:434-439(1994) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT CYP2D6*7 PRO-324.
[13]	"An inactive cytochrome P450 CYP2D6 allele containing a deletion and a base substitution." Daly A.K., Leathart J.B., London S.J., Idle J.R. Hum. Genet. 95:337-341(1995) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT CYP2D6*6B/6C GLU-212.
[14]	"A novel mutant variant of the CYP2D6 gene (CYP2D6*17) common in a black African population: association with diminished debrisoquine hydroxylase activity." Masimirembwa C., Persson I., Bertilsson L., Hasler J., Ingelman-Sundberg M. Br. J. Clin. Pharmacol. 42:713-719(1996) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT CYP2D6*17 ILE-107.
[15]	"An additional allelic variant of the CYP2D6 gene causing impaired metabolism of sparteine." Marez D., Legrand M., Sabbagh N., Lo-Guidice J.-M., Boone P., Broly F. Hum. Genet. 97:668-670(1996) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT CYP2D6*12 ARG-42.
[16]	"Polymorphism of the cytochrome P450 CYP2D6 gene in a European population: characterization of 48 mutations and 53 alleles, their frequencies and evolution." Marez D., Legrand M., Sabbagh N., Guidice J.M., Spire C., Lafitte J.J., Meyer U.A., Broly F. Pharmacogenetics 7:193-202(1997) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS.
[17]	"G169R mutation diminishes the metabolic activity of CYP2D6 in Chinese." Wang S.L., Lai M.D., Huang J.D. Drug Metab. Dispos. 27:385-388(1999) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT CYP2D6*14 ARG-169.
[18]	"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 MET-11; HIS-26; SER-34; MET-91; ARG-94; ILE-107; ILE-120; LYS-155; SER-237; CYS-296; LYS-418; ALA-469; TYR-478 AND THR-486.
+	Additional computationally mapped references.

Web resources

Cytochrome P450 Allele Nomenclature Committee

CYP2D6 alleles

Wikipedia

CYP2D6 entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M20403 mRNA. Translation: AAA52153.1.
X08006 mRNA. Translation: CAA30807.1.
M33388 Genomic DNA. Translation: AAA53500.1.
AY545216 Genomic DNA. Translation: AAS55001.1.
DQ282144 Genomic DNA. Translation: ABB77895.1.
DQ282145 Genomic DNA. Translation: ABB77896.1.
DQ282146 Genomic DNA. Translation: ABB77897.1.
DQ282151 Genomic DNA. Translation: ABB77899.1.
DQ282154 Genomic DNA. Translation: ABB77902.1.
DQ282155 Genomic DNA. Translation: ABB77903.1.
BX247885 Genomic DNA. Translation: CAP58857.1.
BC066877 mRNA. Translation: AAH66877.1.
BC075023 mRNA. Translation: AAH75023.1.
BC075024 mRNA. Translation: AAH75024.1.

IPI

IPI00433508.
IPI00943274.

PIR

O4HUD1. S01199.

RefSeq

NP_000097.3. NM_000106.5.
NP_001020332.2. NM_001025161.2.

UniGene

Hs.333497.
Hs.648256.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2F9Q	X-ray	3.00	A/B/C/D	34-497	[»]
3QM4	X-ray	2.85	A/B	34-497	[»]
3TBG	X-ray	2.10	A/B/C/D	34-497	[»]
3TDA	X-ray	2.67	A/B/C/D	34-497	[»]

ProteinModelPortal

P10635.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000353820.

PTM databases

PhosphoSite

P10635.

Polymorphism databases

DMDM

84028191.

Proteomic databases

PaxDb

P10635.

PRIDE

P10635.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000359033; ENSP00000351927; ENSG00000100197.

GeneID

1565.

KEGG

hsa:1565.

Organism-specific databases

CTD

1565.

GeneCards

GC22M042522.

HGNC

HGNC:2625. CYP2D6.

HPA

HPA045223.

MIM

124030. gene+phenotype.
608902. phenotype.

neXtProt

NX_P10635.

Orphanet

240847. Amitriptyline toxicity.
240849. Antipsychotics toxicity.
240865. Clomipramine toxicity.
240867. Codeine toxicity.
240883. Imipramine toxicity.
240893. Nortriptyline toxicity.
240931. Resistance to amitriptyline in the treatment of depression.
240933. Resistance to clomipramine in the treatment of depression.
240939. Resistance to imipramine in the treatment of depression.
240941. Resistance to nortripilline in the treatment of depression.
240947. Resistance to tamoxifene in breast cancer.
240949. Resistance to trimipramine in the treatment of depression.
240951. Resistance to venlafaxine in the treatment of depression.
240957. Susceptibility to adverse reaction due to amitriptyline treatment.
240959. Susceptibility to adverse reaction due to antipsychotics treatment.
240965. Susceptibility to adverse reaction due to clomipramine treatment.
240967. Susceptibility to adverse reaction due to codeine treatment.
240971. Susceptibility to adverse reaction due to imipramine treatment.
240979. Susceptibility to adverse reaction due to nortriptyline treatment.
240987. Susceptibility to adverse reaction due to trimipramine treatment.
240989. Susceptibility to adverse reaction due to venlafaxine treatment.
240915. Trimipramine toxicity.
240919. Venlafaxine toxicity.

PharmGKB

PA128.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG2124.

HOVERGEN

HBG015789.

KO

K07414.

Enzyme and pathway databases

Reactome

REACT_111217. Metabolism.

SABIO-RK

P10635.

Gene expression databases

ArrayExpress

P10635.

Bgee

P10635.

CleanEx

HS_CYP2D6.

Genevestigator

P10635.

GermOnline

ENSG00000100197. 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.
IPR008069. Cyt_P450_E_grp-I_CYP2D-like.
[Graphical view]

Pfam

PF00067. p450. 1 hit.
[Graphical view]

PRINTS

PR00463. EP450I.
PR01686. EP450ICYP2D.
PR00385. P450.

SUPFAM

SSF48264. Cytochrome_P450. 1 hit.

PROSITE

PS00086. CYTOCHROME_P450. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P10635.

ChEMBL

CHEMBL289.

DrugBank

DB01193. Acebutolol.
DB00918. Almotriptan.
DB00866. Alprenolol.
DB01118. Amiodarone.
DB00321. Amitriptyline.
DB00613. Amodiaquine.
DB00182. Amphetamine.
DB01274. Arformoterol.
DB01238. Aripiprazole.
DB00335. Atenolol.
DB00289. Atomoxetine.
DB00972. Azelastine.
DB00612. Bisoprolol.
DB00921. Buprenorphine.
DB01156. Bupropion.
DB01197. Captopril.
DB00521. Carteolol.
DB01136. Carvedilol.
DB00482. Celecoxib.
DB00185. Cevimeline.
DB01114. Chlorpheniramine.
DB00477. Chlorpromazine.
DB00672. Chlorpropamide.
DB00356. Chlorzoxazone.
DB01410. Ciclesonide.
DB00501. Cimetidine.
DB01012. Cinacalcet.
DB00215. Citalopram.
DB01242. Clomipramine.
DB00575. Clonidine.
DB00257. Clotrimazole.
DB00363. Clozapine.
DB00318. Codeine.
DB00496. Darifenacin.
DB04840. Debrisoquin.
DB00705. Delavirdine.
DB01151. Desipramine.
DB00967. Desloratadine.
DB01191. Dexfenfluramine.
DB01576. Dextroamphetamine.
DB00514. Dextromethorphan.
DB00527. Dibucaine.
DB00586. Diclofenac.
DB00343. Diltiazem.
DB01075. Diphenhydramine.
DB00757. Dolasetron.
DB00843. Donepezil.
DB01142. Doxepin.
DB00476. Duloxetine.
DB01228. Encainide.
DB01175. Escitalopram.
DB00736. Esomeprazole.
DB00574. Fenfluramine.
DB01195. Flecainide.
DB00623. Fluphenazine.
DB00176. Fluvoxamine.
DB00983. Formoterol.
DB00674. Galantamine.
DB00317. Gefitinib.
DB01218. Halofantrine.
DB00502. Haloperidol.
DB00956. Hydrocodone.
DB00327. Hydromorphone.
DB00557. Hydroxyzine.
DB00458. Imipramine.
DB00332. Ipratropium.
DB01167. Itraconazole.
DB01026. Ketoconazole.
DB01210. Levobunolol.
DB00281. Lidocaine.
DB00455. Loratadine.
DB00934. Maprotiline.
DB00454. Meperidine.
DB00532. Mephenytoin.
DB01071. Mequitazine.
DB00933. Mesoridazine.
DB01403. Methotrimeprazine.
DB01233. Metoclopramide.
DB00264. Metoprolol.
DB00379. Mexiletine.
DB06148. Mianserin.
DB01110. Miconazole.
DB00683. Midazolam.
DB00805. Minaprine.
DB00370. Mirtazapine.
DB01171. Moclobemide.
DB00295. Morphine.
DB01149. Nefazodone.
DB00622. Nicardipine.
DB00699. Nicergoline.
DB01115. Nifedipine.
DB00540. Nortriptyline.
DB00904. Ondansetron.
DB00497. Oxycodone.
DB01192. Oxymorphone.
DB01267. Paliperidone.
DB00377. Palonosetron.
DB00715. Paroxetine.
DB01074. Perhexiline.
DB00850. Perphenazine.
DB00914. Phenformin.
DB00830. Phenmetrazine.
DB00960. Pindolol.
DB01035. Procainamide.
DB00433. Prochlorperazine.
DB01131. Proguanil.
DB01069. Promethazine.
DB01182. Propafenone.
DB00647. Propoxyphene.
DB00571. Propranolol.
DB01224. Quetiapine.
DB00908. Quinidine.
DB00468. Quinine.
DB00863. Ranitidine.
DB00243. Ranolazine.
DB00234. Reboxetine.
DB00734. Risperidone.
DB00503. Ritonavir.
DB01037. Selegiline.
DB06144. Sertindole.
DB01104. Sertraline.
DB00675. Tamoxifen.
DB00857. Terbinafine.
DB00342. Terfenadine.
DB00679. Thioridazine.
DB00373. Timolol.
DB01409. Tiotropium.
DB01124. Tolbutamide.
DB01036. Tolterodine.
DB00193. Tramadol.
DB00752. Tranylcypromine.
DB00656. Trazodone.
DB00726. Trimipramine.
DB00285. Venlafaxine.
DB01624. Zuclopenthixol.

EvolutionaryTrace

P10635.

GenomeRNAi

1565.

NextBio

6449.

SOURCE

Search...

Entry information

Entry name

CP2D6_HUMAN

Accession

Primary (citable) accession number: P10635
Secondary accession number(s): Q16752 , Q2XND6, Q2XND7, Q2XNE0, Q6B012, Q6NXU8

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 1, 1989
Last sequence update:	December 20, 2005
Last modified:	May 1, 2013
This is version 149 of the entry and version 2 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.