CP2D6_HUMAN
ID CP2D6_HUMAN Reviewed; 497 AA.
AC P10635; Q16752; Q2XND6; Q2XND7; Q2XNE0; Q6B012; Q6NXU8;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 20-DEC-2005, sequence version 2.
DT 03-AUG-2022, entry version 226.
DE RecName: Full=Cytochrome P450 2D6 {ECO:0000303|PubMed:18698000};
DE EC=1.14.14.- {ECO:0000269|PubMed:18698000, ECO:0000269|PubMed:21289075};
DE AltName: Full=CYPIID6;
DE AltName: Full=Cholesterol 25-hydroxylase {ECO:0000305|PubMed:21576599};
DE AltName: Full=Cytochrome P450-DB1;
DE AltName: Full=Debrisoquine 4-hydroxylase;
GN Name=CYP2D6 {ECO:0000303|PubMed:21289075, ECO:0000312|HGNC:HGNC:2625};
GN Synonyms=CYP2DL1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=3410476; DOI=10.1016/0888-7543(88)90100-0;
RA Gonzalez F.J., Vilbois F., Hardwick J.P., McBride O.W., Nebert D.W.,
RA Gelboin H.V., Meyer U.A.;
RT "Human debrisoquine 4-hydroxylase (P450IID1): cDNA and deduced amino acid
RT sequence and assignment of the CYP2D locus to chromosome 22.";
RL Genomics 2:174-179(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Liver;
RX PubMed=3123997; DOI=10.1038/331442a0;
RA Gonzalez F.J., Skoda R.C., Kimura S., Umeno M., Zanger U.M., Nebert D.W.,
RA Gelboin H.V., Hardwick J.P., Meyer U.A.;
RT "Characterization of the common genetic defect in humans deficient in
RT debrisoquine metabolism.";
RL Nature 331:442-446(1988).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2574001;
RA Kimura S., Umeno M., Skoda R.C., Meyer U.A., Gonzalez F.J.;
RT "The human debrisoquine 4-hydroxylase (CYP2D) locus: sequence and
RT identification of the polymorphic CYP2D6 gene, a related gene, and a
RT pseudogene.";
RL Am. J. Hum. Genet. 45:889-904(1989).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ALLELE CYP2D6*1), IDENTIFICATION OF
RP ALLELES CYP2D6*41B; CYP2D6*45A; CYP2D6*45B AND CYP2D6*46, VARIANTS HIS-26;
RP LYS-155; CYS-296 AND THR-486, AND CHARACTERIZATION OF ISOZYMES CYP2D6.45
RP AND CYP2D6.46.
RX PubMed=15768052; DOI=10.1038/sj.tpj.6500305;
RA Gaedigk A., Bhathena A., Ndjountche L., Pearce R.E., Abdel-Rahman S.M.,
RA Alander S.W., Bradford L.D., Rogan P.K., Leeder J.S.;
RT "Identification and characterization of novel sequence variations in the
RT cytochrome P4502D6 (CYP2D6) gene in African Americans.";
RL Pharmacogenomics J. 5:173-182(2005).
RN [5]
RP ERRATUM OF PUBMED:15768052.
RA Gaedigk A., Bhathena A., Ndjountche L., Pearce R.E., Abdel-Rahman S.M.,
RA Alander S.W., Bradford L.D., Rogan P.K., Leeder J.S.;
RL Pharmacogenomics J. 5:276-276(2005).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT HIS-26.
RA Koch W.H., Nikoloff D.M., Lu W., Pan R.M., deLeon J., Wedlund P.J.;
RT "CYP2D6 evolution and allele diversity among human races.";
RL Submitted (NOV-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANTS CYS-296 AND
RP THR-486.
RX PubMed=10591208; DOI=10.1038/990031;
RA Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M.,
RA Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C.,
RA Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E.,
RA Bridgeman A.M., Buck D., Burgess J., Burrill W.D., Burton J., Carder C.,
RA Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G.,
RA Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V.,
RA Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M.,
RA Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A.,
RA Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C.,
RA Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E.,
RA Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F.,
RA Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M.,
RA Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A.,
RA Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D.,
RA Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y.,
RA Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S.,
RA Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E.,
RA Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L.,
RA Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L.,
RA Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N.,
RA Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A.,
RA Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L.,
RA Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P.,
RA Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P.,
RA Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q.,
RA Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J.,
RA Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J.,
RA Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D.,
RA Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T.,
RA Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P.,
RA Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K.,
RA Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R.,
RA Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L.,
RA McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J.,
RA Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E.,
RA Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P.,
RA Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y.,
RA Wright H.;
RT "The DNA sequence of human chromosome 22.";
RL Nature 402:489-495(1999).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANTS
RP CYS-296 AND THR-486.
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND PATHWAY.
RX PubMed=10681376;
RA Chen H., Howald W.N., Juchau M.R.;
RT "Biosynthesis of all-trans-retinoic acid from all-trans-retinol: catalysis
RT of all-trans-retinol oxidation by human P-450 cytochromes.";
RL Drug Metab. Dispos. 28:315-322(2000).
RN [10]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=18698000; DOI=10.1124/jpet.108.141796;
RA Snider N.T., Sikora M.J., Sridar C., Feuerstein T.J., Rae J.M.,
RA Hollenberg P.F.;
RT "The endocannabinoid anandamide is a substrate for the human polymorphic
RT cytochrome P450 2D6.";
RL J. Pharmacol. Exp. Ther. 327:538-545(2008).
RN [11]
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=19965576; DOI=10.1194/jlr.m003061;
RA Lucas D., Goulitquer S., Marienhagen J., Fer M., Dreano Y., Schwaneberg U.,
RA Amet Y., Corcos L.;
RT "Stereoselective epoxidation of the last double bond of polyunsaturated
RT fatty acids by human cytochromes P450.";
RL J. Lipid Res. 51:1125-1133(2010).
RN [12]
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=20972997; DOI=10.1002/rcm.4760;
RA Mesaros C., Lee S.H., Blair I.A.;
RT "Analysis of epoxyeicosatrienoic acids by chiral liquid
RT chromatography/electron capture atmospheric pressure chemical ionization
RT mass spectrometry using [13C]-analog internal standards.";
RL Rapid Commun. Mass Spectrom. 24:3237-3247(2010).
RN [13]
RP FUNCTION, CATALYTIC ACTIVITY, AND CHARACTERIZATION OF VARIANT CYS-296.
RX PubMed=21289075; DOI=10.1124/dmd.110.036707;
RA Sridar C., Snider N.T., Hollenberg P.F.;
RT "Anandamide oxidation by wild-type and polymorphically expressed CYP2B6 and
RT CYP2D6.";
RL Drug Metab. Dispos. 39:782-788(2011).
RN [14]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, AND PATHWAY.
RX PubMed=21576599; DOI=10.1194/jlr.m014084;
RA Honda A., Miyazaki T., Ikegami T., Iwamoto J., Maeda T., Hirayama T.,
RA Saito Y., Teramoto T., Matsuzaki Y.;
RT "Cholesterol 25-hydroxylation activity of CYP3A.";
RL J. Lipid Res. 52:1509-1516(2011).
RN [15]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [16]
RP X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 34-497 IN COMPLEX WITH HEME, AND
RP FUNCTION.
RX PubMed=16352597; DOI=10.1074/jbc.m511232200;
RA Rowland P., Blaney F.E., Smyth M.G., Jones J.J., Leydon V.R., Oxbrow A.K.,
RA Lewis C.J., Tennant M.G., Modi S., Eggleston D.S., Chenery R.J.,
RA Bridges A.M.;
RT "Crystal structure of human cytochrome P450 2D6.";
RL J. Biol. Chem. 281:7614-7622(2006).
RN [17]
RP VARIANT CYP2D6*9 LYS-281 DEL.
RX PubMed=1844820; DOI=10.1097/00008571-199110000-00005;
RA Tyndale R., Aoyama T., Broly F., Matsunaga T., Inaba T., Kalow W.,
RA Gelboin H.V., Meyer U.A., Gonzalez F.J.;
RT "Identification of a new variant CYP2D6 allele lacking the codon encoding
RT Lys-281: possible association with the poor metabolizer phenotype.";
RL Pharmacogenetics 1:26-32(1991).
RN [18]
RP VARIANTS CYP2D6*10 SER-34 AND THR-486.
RX PubMed=8287064; DOI=10.1097/00008571-199310000-00005;
RA Yokota H., Tamura S., Furuya H., Kimura S., Watanabe M., Kanazawa I.,
RA Kondo I., Gonzalez F.J.;
RT "Evidence for a new variant CYP2D6 allele CYP2D6J in a Japanese population
RT associated with lower in vivo rates of sparteine metabolism.";
RL Pharmacogenetics 3:256-263(1993).
RN [19]
RP VARIANT CYP2D6*7 PRO-324.
RX PubMed=7845481; DOI=10.1007/bf00178963;
RA Evert B., Griese E.U., Eichelbaum M.;
RT "A missense mutation in exon 6 of the CYP2D6 gene leading to a histidine
RT 324 to proline exchange is associated with the poor metabolizer phenotype
RT of sparteine.";
RL Naunyn Schmiedebergs Arch. Pharmacol. 350:434-439(1994).
RN [20]
RP VARIANT CYP2D6*6B/6C GLU-212.
RX PubMed=7868129; DOI=10.1007/bf00225204;
RA Daly A.K., Leathart J.B., London S.J., Idle J.R.;
RT "An inactive cytochrome P450 CYP2D6 allele containing a deletion and a base
RT substitution.";
RL Hum. Genet. 95:337-341(1995).
RN [21]
RP VARIANT CYP2D6*17 ILE-107.
RX PubMed=8971426; DOI=10.1046/j.1365-2125.1996.00489.x;
RA Masimirembwa C., Persson I., Bertilsson L., Hasler J.,
RA Ingelman-Sundberg M.;
RT "A novel mutant variant of the CYP2D6 gene (CYP2D6*17) common in a black
RT African population: association with diminished debrisoquine hydroxylase
RT activity.";
RL Br. J. Clin. Pharmacol. 42:713-719(1996).
RN [22]
RP VARIANT CYP2D6*12 ARG-42.
RX PubMed=8655150; DOI=10.1007/bf02281880;
RA Marez D., Legrand M., Sabbagh N., Lo-Guidice J.-M., Boone P., Broly F.;
RT "An additional allelic variant of the CYP2D6 gene causing impaired
RT metabolism of sparteine.";
RL Hum. Genet. 97:668-670(1996).
RN [23]
RP VARIANTS.
RX PubMed=9241659; DOI=10.1097/00008571-199706000-00004;
RA Marez D., Legrand M., Sabbagh N., Guidice J.M., Spire C., Lafitte J.J.,
RA Meyer U.A., Broly F.;
RT "Polymorphism of the cytochrome P450 CYP2D6 gene in a European population:
RT characterization of 48 mutations and 53 alleles, their frequencies and
RT evolution.";
RL Pharmacogenetics 7:193-202(1997).
RN [24]
RP VARIANT CYP2D6*14 ARG-169.
RX PubMed=10064570;
RA Wang S.L., Lai M.D., Huang J.D.;
RT "G169R mutation diminishes the metabolic activity of CYP2D6 in Chinese.";
RL Drug Metab. Dispos. 27:385-388(1999).
RN [25]
RP VARIANTS MET-11; HIS-26; SER-34; MET-91; ARG-94; ILE-107; ILE-120; LYS-155;
RP SER-237; CYS-296; LYS-418; ALA-469; TYR-478 AND THR-486.
RX PubMed=15469410; DOI=10.1517/14622416.5.7.895;
RA Solus J.F., Arietta B.J., Harris J.R., Sexton D.P., Steward J.Q.,
RA McMunn C., Ihrie P., Mehall J.M., Edwards T.L., Dawson E.P.;
RT "Genetic variation in eleven phase I drug metabolism genes in an ethnically
RT diverse population.";
RL Pharmacogenomics 5:895-931(2004).
RN [26]
RP VARIANTS CYP2D6*87 VAL-5; GLN-25; CYP2D6*10 SER-34; CYP2D6*88 ALA-104;
RP CYP2D6*89 SER-142; CYP2D6*90 ARG-147; CYP2D6*91 SER-161; LEU-164; LYS-215;
RP SER-219; CYP2D6*93 PRO-249; CYP2D6*2 CYS-296; MET-327; ASN-336; CYP2D6*94
RP GLY-337; MET-342; GLN-344; CYS-440; CYP2D6*97 LEU-457; CYP2D6*98 ASP-463;
RP CYP2D6*10/2 THR-486 AND CYS-497.
RX PubMed=25469868; DOI=10.1111/bcpt.12363;
RA Dai D.P., Geng P.W., Wang S.H., Cai J., Hu L.M., Nie J.J., Hu J.H.,
RA Hu G.X., Cai J.P.;
RT "In vitro functional assessment of 22 newly identified CYP2D6 allelic
RT variants in the Chinese population.";
RL Basic Clin. Pharmacol. Toxicol. 117:39-43(2015).
CC -!- FUNCTION: A cytochrome P450 monooxygenase involved in the metabolism of
CC fatty acids, steroids and retinoids (PubMed:18698000, PubMed:19965576,
CC PubMed:20972997, PubMed:21289075, PubMed:21576599). Mechanistically,
CC uses molecular oxygen inserting one oxygen atom into a substrate, and
CC reducing the second into a water molecule, with two electrons provided
CC by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase)
CC (PubMed:18698000, PubMed:19965576, PubMed:20972997, PubMed:21289075,
CC PubMed:21576599). Catalyzes the epoxidation of double bonds of
CC polyunsaturated fatty acids (PUFA) (PubMed:19965576, PubMed:20972997).
CC Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to
CC 20-hydroxyeicosatetraenoic acid ethanolamide (20-HETE-EA) and 8,9-,
CC 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs),
CC potentially modulating endocannabinoid system signaling
CC (PubMed:18698000, PubMed:21289075). Catalyzes the hydroxylation of
CC carbon-hydrogen bonds. Metabolizes cholesterol toward 25-
CC hydroxycholesterol, a physiological regulator of cellular cholesterol
CC homeostasis (PubMed:21576599). Catalyzes the oxidative transformations
CC of all-trans retinol to all-trans retinal, a precursor for the active
CC form all-trans-retinoic acid (PubMed:10681376). Also involved in the
CC oxidative metabolism of drugs such as antiarrhythmics, adrenoceptor
CC antagonists, and tricyclic antidepressants.
CC {ECO:0000269|PubMed:10681376, ECO:0000269|PubMed:16352597,
CC ECO:0000269|PubMed:18698000, ECO:0000269|PubMed:19965576,
CC ECO:0000269|PubMed:20972997, ECO:0000269|PubMed:21289075,
CC ECO:0000269|PubMed:21576599}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 + reduced [NADPH--
CC hemoprotein reductase] = (8R,9S)-epoxy-(5Z,11Z,14Z)-eicosatrienoate +
CC H(+) + H2O + oxidized [NADPH--hemoprotein reductase];
CC Xref=Rhea:RHEA:49884, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:32395, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:131975; Evidence={ECO:0000269|PubMed:20972997};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49885;
CC Evidence={ECO:0000305|PubMed:20972997};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 + reduced [NADPH--
CC hemoprotein reductase] = (11R,12S)-epoxy-(5Z,8Z,14Z)-eicosatrienoate
CC + H(+) + H2O + oxidized [NADPH--hemoprotein reductase];
CC Xref=Rhea:RHEA:49880, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:32395, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:131970; Evidence={ECO:0000269|PubMed:20972997};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49881;
CC Evidence={ECO:0000305|PubMed:20972997};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 + reduced [NADPH--
CC hemoprotein reductase] = (14S,15R)-epoxy-(5Z,8Z,11Z)-eicosatrienoate
CC + H(+) + H2O + oxidized [NADPH--hemoprotein reductase];
CC Xref=Rhea:RHEA:49856, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:32395, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:131964; Evidence={ECO:0000269|PubMed:19965576,
CC ECO:0000269|PubMed:20972997};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49857;
CC Evidence={ECO:0000305|PubMed:20972997};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine + O2 + reduced
CC [NADPH--hemoprotein reductase] = H(+) + H2O + N-(8,9-epoxy-
CC 5Z,11Z,14Z-eicosatrienoyl)-ethanolamine + oxidized [NADPH--
CC hemoprotein reductase]; Xref=Rhea:RHEA:53140, Rhea:RHEA-COMP:11964,
CC Rhea:RHEA-COMP:11965, ChEBI:CHEBI:2700, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:57618,
CC ChEBI:CHEBI:58210, ChEBI:CHEBI:136989;
CC Evidence={ECO:0000269|PubMed:18698000, ECO:0000269|PubMed:21289075};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53141;
CC Evidence={ECO:0000305|PubMed:21289075};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine + O2 + reduced
CC [NADPH--hemoprotein reductase] = H(+) + H2O + N-(11,12-epoxy-
CC 5Z,8Z,14Z-eicosatrienoyl)-ethanolamine + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:53144, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, ChEBI:CHEBI:2700, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:136990; Evidence={ECO:0000269|PubMed:18698000,
CC ECO:0000269|PubMed:21289075};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53145;
CC Evidence={ECO:0000305|PubMed:21289075};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine + O2 + reduced
CC [NADPH--hemoprotein reductase] = H(+) + H2O + N-(14,15-epoxy-
CC 5Z,8Z,11Z-eicosatrienoyl)-ethanolamine + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:53148, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, ChEBI:CHEBI:2700, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:136991; Evidence={ECO:0000269|PubMed:18698000,
CC ECO:0000269|PubMed:21289075};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53149;
CC Evidence={ECO:0000305|PubMed:21289075};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine + O2 + reduced
CC [NADPH--hemoprotein reductase] = H(+) + H2O + N-(20-hydroxy-
CC 5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine + oxidized [NADPH--
CC hemoprotein reductase]; Xref=Rhea:RHEA:53152, Rhea:RHEA-COMP:11964,
CC Rhea:RHEA-COMP:11965, ChEBI:CHEBI:2700, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:57618,
CC ChEBI:CHEBI:58210, ChEBI:CHEBI:136992;
CC Evidence={ECO:0000269|PubMed:18698000, ECO:0000269|PubMed:21289075};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53153;
CC Evidence={ECO:0000305|PubMed:21289075};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate + O2 + reduced [NADPH--
CC hemoprotein reductase] = (17S,18R)-epoxy-(5Z,8Z,11Z,14Z)-
CC eicosatetraenoate + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:39783, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:58562,
CC ChEBI:CHEBI:76635; Evidence={ECO:0000269|PubMed:19965576};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39784;
CC Evidence={ECO:0000305|PubMed:19965576};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate + O2 + reduced
CC [NADPH--hemoprotein reductase] = (19R,20S)-epoxy-(4Z,7Z,10Z,13Z,16Z)-
CC docosapentaenoate + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:52120, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:77016,
CC ChEBI:CHEBI:136410; Evidence={ECO:0000269|PubMed:19965576};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52121;
CC Evidence={ECO:0000305|PubMed:19965576};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate + O2 + reduced
CC [NADPH--hemoprotein reductase] = (19S,20R)-epoxy-(4Z,7Z,10Z,13Z,16Z)-
CC docosapentaenoate + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:52124, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:77016,
CC ChEBI:CHEBI:136411; Evidence={ECO:0000269|PubMed:19965576};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52125;
CC Evidence={ECO:0000305|PubMed:19965576};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=cholesterol + O2 + reduced [NADPH--hemoprotein reductase] =
CC 25-hydroxycholesterol + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:50256, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:16113, ChEBI:CHEBI:42977, ChEBI:CHEBI:57618,
CC ChEBI:CHEBI:58210; Evidence={ECO:0000269|PubMed:21576599};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50257;
CC Evidence={ECO:0000305|PubMed:21576599};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=all-trans-retinol + O2 + reduced [NADPH--hemoprotein
CC reductase] = all-trans-retinal + H(+) + 2 H2O + oxidized [NADPH--
CC hemoprotein reductase]; Xref=Rhea:RHEA:42092, Rhea:RHEA-COMP:11964,
CC Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:17336, ChEBI:CHEBI:17898,
CC ChEBI:CHEBI:57618, ChEBI:CHEBI:58210;
CC Evidence={ECO:0000269|PubMed:10681376};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42093;
CC Evidence={ECO:0000305|PubMed:10681376};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=67 uM for all-trans retinol {ECO:0000269|PubMed:10681376};
CC KM=1.3 uM for anandamide (oxidation to 20-HETE)
CC {ECO:0000269|PubMed:18698000};
CC KM=2.1 uM for anandamide (oxidation to 8,9-EpETrE-EA)
CC {ECO:0000269|PubMed:18698000};
CC KM=2.6 uM for anandamide (oxidation to 11,12-EpETrE-EA)
CC {ECO:0000269|PubMed:18698000};
CC KM=2.8 uM for anandamide (oxidation to 14,15-EpETrE-EA)
CC {ECO:0000269|PubMed:18698000};
CC Vmax=193 pmol/min/nmol enzyme toward all-trans retinol
CC {ECO:0000269|PubMed:10681376};
CC Vmax=3.7 pmol/min/nmol enzyme toward anandamide (oxidation to 20-
CC HETE) {ECO:0000269|PubMed:18698000};
CC Vmax=1.6 pmol/min/nmol enzyme toward anandamide (oxidation to 8,9-
CC EpETrE-EA) {ECO:0000269|PubMed:18698000};
CC Vmax=1.1 pmol/min/nmol enzyme toward anandamide (oxidation to 11,12-
CC EpETrE-EA) {ECO:0000269|PubMed:18698000};
CC Vmax=1.3 pmol/min/nmol enzyme toward anandamide (oxidation to 14,15-
CC EpETrE-EA) {ECO:0000269|PubMed:18698000};
CC -!- PATHWAY: Cofactor metabolism; retinol metabolism.
CC {ECO:0000269|PubMed:10681376}.
CC -!- PATHWAY: Lipid metabolism; fatty acid metabolism.
CC {ECO:0000269|PubMed:19965576, ECO:0000269|PubMed:20972997}.
CC -!- PATHWAY: Steroid metabolism; cholesterol metabolism.
CC {ECO:0000269|PubMed:21576599}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Peripheral
CC membrane protein. Microsome membrane {ECO:0000269|PubMed:21576599};
CC Peripheral membrane protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P10635-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P10635-2; Sequence=VSP_044486;
CC -!- INDUCTION: By pregnancy.
CC -!- POLYMORPHISM: Genetic variations in CYP2D6 are the cause of poor drug
CC metabolism CYP2D6-related [MIM:608902]. The CYP2D6 gene is highly
CC polymorphic. CYP2D6 activity ranges widely within a population
CC comprising ultrarapid (UM), extensive (EM), intermediate (IM) and poor
CC (PM) metabolizer phenotypes. UM and PM are those most at risk for
CC treatment failure or dose-dependent drug toxicity, respectively. Of the
CC Caucasian populations of Europe and North America, 5%-10% are of the PM
CC phenotype and are unable to metabolize the antihypersensitive drug
CC debrisoquine and numerous other drugs. Different alleles are known,
CC including CYP2D6*1 (PubMed:15768052), CYP2D6*2 (PubMed:25469868),
CC CYP2D6*6B/6C (PubMed:7868129), CYP2D6*7 also known CYP2D6E
CC (PubMed:7845481), CYP2D6*9 also known CYP2D6C (PubMed:1844820),
CC CYP2D6*10 also known CYP2D6J (PubMed:8287064, PubMed:25469868),
CC CYP2D6*12 (PubMed:8655150), CYP2D6*14 (PubMed:10064570), CYP2D6*17 also
CC known CYP2D6Z (PubMed:8971426), CYP2D6*41B (PubMed:15768052),
CC CYP2D6*45A (PubMed:15768052), CYP2D6*45B (PubMed:15768052), CYP2D6*46
CC (PubMed:15768052), CYP2D6*87 (PubMed:25469868), CYP2D6*88
CC (PubMed:25469868), CYP2D6*89 (PubMed:25469868), CYP2D6*90
CC (PubMed:25469868), CYP2D6*91 (PubMed:25469868), CYP2D6*93
CC (PubMed:25469868), C CYP2D6*94 (PubMed:25469868), CYP2D6*97
CC (PubMed:25469868) and CYP2D6*98 (PubMed:25469868). Isozymes CYP2D6.45
CC (Lys-155, Cys-296 and Thr-486) and CYP2D6.46 (His-26, Lys-155, Cys-296
CC and Thr-486) are functional (PubMed:15768052). The sequence shown is
CC that of isozyme CYP2D6.1 corresponding to allele CYP2D6*1.
CC {ECO:0000269|PubMed:10064570, ECO:0000269|PubMed:15768052,
CC ECO:0000269|PubMed:16352597, ECO:0000269|PubMed:1844820,
CC ECO:0000269|PubMed:25469868, ECO:0000269|PubMed:7845481,
CC ECO:0000269|PubMed:7868129, ECO:0000269|PubMed:8655150,
CC ECO:0000269|PubMed:8971426}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=PharmVar Pharmacogen Variation Consortium;
CC Note=CYP2D6 alleles;
CC URL="https://www.pharmvar.org/gene/CYP2D6";
CC -!- WEB RESOURCE: Name=Wikipedia; Note=CYP2D6 entry;
CC URL="https://en.wikipedia.org/wiki/CYP2D6";
CC ---------------------------------------------------------------------------
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DR EMBL; M20403; AAA52153.1; -; mRNA.
DR EMBL; X08006; CAA30807.1; -; mRNA.
DR EMBL; M33388; AAA53500.1; -; Genomic_DNA.
DR EMBL; AY545216; AAS55001.1; -; Genomic_DNA.
DR EMBL; DQ282144; ABB77895.1; -; Genomic_DNA.
DR EMBL; DQ282145; ABB77896.1; -; Genomic_DNA.
DR EMBL; DQ282146; ABB77897.1; -; Genomic_DNA.
DR EMBL; DQ282151; ABB77899.1; -; Genomic_DNA.
DR EMBL; DQ282154; ABB77902.1; -; Genomic_DNA.
DR EMBL; DQ282155; ABB77903.1; -; Genomic_DNA.
DR EMBL; BX247885; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC066877; AAH66877.1; -; mRNA.
DR EMBL; BC075023; AAH75023.1; -; mRNA.
DR EMBL; BC075024; AAH75024.1; -; mRNA.
DR CCDS; CCDS33657.1; -. [P10635-2]
DR CCDS; CCDS46721.1; -. [P10635-1]
DR PIR; S01199; O4HUD1.
DR RefSeq; NP_000097.3; NM_000106.5. [P10635-1]
DR RefSeq; NP_001020332.2; NM_001025161.2. [P10635-2]
DR PDB; 2F9Q; X-ray; 3.00 A; A/B/C/D=34-497.
DR PDB; 3QM4; X-ray; 2.85 A; A/B=34-497.
DR PDB; 3TBG; X-ray; 2.10 A; A/B/C/D=34-497.
DR PDB; 3TDA; X-ray; 2.67 A; A/B/C/D=34-497.
DR PDB; 4WNT; X-ray; 2.60 A; A/B=34-497.
DR PDB; 4WNU; X-ray; 2.26 A; A/B/C/D=34-497.
DR PDB; 4WNV; X-ray; 2.35 A; A/B/C/D=48-497.
DR PDB; 4WNW; X-ray; 3.30 A; A/B=34-497.
DR PDB; 4XRY; X-ray; 2.50 A; A/B/C/D=34-497.
DR PDB; 4XRZ; X-ray; 2.40 A; A/B/C/D=34-497.
DR PDB; 5TFT; X-ray; 2.71 A; A/B/C/D=34-497.
DR PDB; 5TFU; X-ray; 2.75 A; A/B/C/D=34-497.
DR PDB; 6CSB; X-ray; 2.39 A; A/B/C/D=34-497.
DR PDB; 6CSD; X-ray; 2.39 A; A/B=34-497.
DR PDBsum; 2F9Q; -.
DR PDBsum; 3QM4; -.
DR PDBsum; 3TBG; -.
DR PDBsum; 3TDA; -.
DR PDBsum; 4WNT; -.
DR PDBsum; 4WNU; -.
DR PDBsum; 4WNV; -.
DR PDBsum; 4WNW; -.
DR PDBsum; 4XRY; -.
DR PDBsum; 4XRZ; -.
DR PDBsum; 5TFT; -.
DR PDBsum; 5TFU; -.
DR PDBsum; 6CSB; -.
DR PDBsum; 6CSD; -.
DR AlphaFoldDB; P10635; -.
DR BMRB; P10635; -.
DR SMR; P10635; -.
DR BioGRID; 107940; 32.
DR STRING; 9606.ENSP00000353820; -.
DR BindingDB; P10635; -.
DR ChEMBL; CHEMBL289; -.
DR DrugBank; DB01562; 1-(2-Phenylethyl)-4-phenyl-4-acetoxypiperidine.
DR DrugBank; DB01472; 4-Methoxyamphetamine.
DR DrugBank; DB14010; 5-methoxy-N,N-dimethyltryptamine.
DR DrugBank; DB12001; Abemaciclib.
DR DrugBank; DB05812; Abiraterone.
DR DrugBank; DB01193; Acebutolol.
DR DrugBank; DB00316; Acetaminophen.
DR DrugBank; DB00918; Almotriptan.
DR DrugBank; DB06203; Alogliptin.
DR DrugBank; DB00866; Alprenolol.
DR DrugBank; DB01424; Aminophenazone.
DR DrugBank; DB01118; Amiodarone.
DR DrugBank; DB00321; Amitriptyline.
DR DrugBank; DB00381; Amlodipine.
DR DrugBank; DB00613; Amodiaquine.
DR DrugBank; DB00543; Amoxapine.
DR DrugBank; DB00182; Amphetamine.
DR DrugBank; DB00701; Amprenavir.
DR DrugBank; DB11785; Anisodamine.
DR DrugBank; DB01435; Antipyrine.
DR DrugBank; DB01429; Aprindine.
DR DrugBank; DB01274; Arformoterol.
DR DrugBank; DB01238; Aripiprazole.
DR DrugBank; DB14185; Aripiprazole lauroxil.
DR DrugBank; DB09204; Arotinolol.
DR DrugBank; DB11638; Artenimol.
DR DrugBank; DB06216; Asenapine.
DR DrugBank; DB00637; Astemizole.
DR DrugBank; DB11586; Asunaprevir.
DR DrugBank; DB00335; Atenolol.
DR DrugBank; DB00289; Atomoxetine.
DR DrugBank; DB01076; Atorvastatin.
DR DrugBank; DB00972; Azelastine.
DR DrugBank; DB04957; Azimilide.
DR DrugBank; DB09013; Befunolol.
DR DrugBank; DB16703; Belumosudil.
DR DrugBank; DB01086; Benzocaine.
DR DrugBank; DB06770; Benzyl alcohol.
DR DrugBank; DB01244; Bepridil.
DR DrugBank; DB15982; Berotralstat.
DR DrugBank; DB00195; Betaxolol.
DR DrugBank; DB01295; Bevantolol.
DR DrugBank; DB01128; Bicalutamide.
DR DrugBank; DB04889; Bicifadine.
DR DrugBank; DB00810; Biperiden.
DR DrugBank; DB13975; Black cohosh.
DR DrugBank; DB08807; Bopindolol.
DR DrugBank; DB00188; Bortezomib.
DR DrugBank; DB09128; Brexpiprazole.
DR DrugBank; DB12151; Brincidofovir.
DR DrugBank; DB12752; Bucindolol.
DR DrugBank; DB06726; Bufuralol.
DR DrugBank; DB00297; Bupivacaine.
DR DrugBank; DB08808; Bupranolol.
DR DrugBank; DB00921; Buprenorphine.
DR DrugBank; DB01156; Bupropion.
DR DrugBank; DB00490; Buspirone.
DR DrugBank; DB09173; Butyrfentanyl.
DR DrugBank; DB00201; Caffeine.
DR DrugBank; DB09061; Cannabidiol.
DR DrugBank; DB06016; Cariprazine.
DR DrugBank; DB00521; Carteolol.
DR DrugBank; DB01136; Carvedilol.
DR DrugBank; DB00482; Celecoxib.
DR DrugBank; DB04846; Celiprolol.
DR DrugBank; DB00439; Cerivastatin.
DR DrugBank; DB00185; Cevimeline.
DR DrugBank; DB00608; Chloroquine.
DR DrugBank; DB01114; Chlorpheniramine.
DR DrugBank; DB00477; Chlorpromazine.
DR DrugBank; DB00356; Chlorzoxazone.
DR DrugBank; DB01410; Ciclesonide.
DR DrugBank; DB01166; Cilostazol.
DR DrugBank; DB00501; Cimetidine.
DR DrugBank; DB01012; Cinacalcet.
DR DrugBank; DB00568; Cinnarizine.
DR DrugBank; DB00604; Cisapride.
DR DrugBank; DB00215; Citalopram.
DR DrugBank; DB12499; Clascoterone.
DR DrugBank; DB00283; Clemastine.
DR DrugBank; DB04920; Clevidipine.
DR DrugBank; DB14025; Clinafloxacin.
DR DrugBank; DB00349; Clobazam.
DR DrugBank; DB00845; Clofazimine.
DR DrugBank; DB01242; Clomipramine.
DR DrugBank; DB00575; Clonidine.
DR DrugBank; DB13508; Cloranolol.
DR DrugBank; DB00257; Clotrimazole.
DR DrugBank; DB00363; Clozapine.
DR DrugBank; DB09065; Cobicistat.
DR DrugBank; DB00907; Cocaine.
DR DrugBank; DB00318; Codeine.
DR DrugBank; DB11672; Curcumin.
DR DrugBank; DB14635; Curcumin sulfate.
DR DrugBank; DB00924; Cyclobenzaprine.
DR DrugBank; DB00091; Cyclosporine.
DR DrugBank; DB11963; Dacomitinib.
DR DrugBank; DB06292; Dapagliflozin.
DR DrugBank; DB04884; Dapoxetine.
DR DrugBank; DB00496; Darifenacin.
DR DrugBank; DB01264; Darunavir.
DR DrugBank; DB09183; Dasabuvir.
DR DrugBank; DB04840; Debrisoquine.
DR DrugBank; DB00705; Delavirdine.
DR DrugBank; DB06512; Deramciclane.
DR DrugBank; DB01151; Desipramine.
DR DrugBank; DB06700; Desvenlafaxine.
DR DrugBank; DB12161; Deutetrabenazine.
DR DrugBank; DB13679; Dexchlorpheniramine.
DR DrugBank; DB09555; Dexchlorpheniramine maleate.
DR DrugBank; DB01191; Dexfenfluramine.
DR DrugBank; DB00633; Dexmedetomidine.
DR DrugBank; DB01576; Dextroamphetamine.
DR DrugBank; DB00514; Dextromethorphan.
DR DrugBank; DB00647; Dextropropoxyphene.
DR DrugBank; DB11994; Diacerein.
DR DrugBank; DB01551; Dihydrocodeine.
DR DrugBank; DB00343; Diltiazem.
DR DrugBank; DB01093; Dimethyl sulfoxide.
DR DrugBank; DB01075; Diphenhydramine.
DR DrugBank; DB00757; Dolasetron.
DR DrugBank; DB01184; Domperidone.
DR DrugBank; DB00843; Donepezil.
DR DrugBank; DB09167; Dosulepin.
DR DrugBank; DB00590; Doxazosin.
DR DrugBank; DB01142; Doxepin.
DR DrugBank; DB00997; Doxorubicin.
DR DrugBank; DB04855; Dronedarone.
DR DrugBank; DB00476; Duloxetine.
DR DrugBank; DB00625; Efavirenz.
DR DrugBank; DB11979; Elagolix.
DR DrugBank; DB00216; Eletriptan.
DR DrugBank; DB15444; Elexacaftor.
DR DrugBank; DB09039; Eliglustat.
DR DrugBank; DB13874; Enasidenib.
DR DrugBank; DB01228; Encainide.
DR DrugBank; DB06735; Enclomiphene.
DR DrugBank; DB11718; Encorafenib.
DR DrugBank; DB00494; Entacapone.
DR DrugBank; DB13757; Epanolol.
DR DrugBank; DB00751; Epinastine.
DR DrugBank; DB00530; Erlotinib.
DR DrugBank; DB13443; Esatenolol.
DR DrugBank; DB01175; Escitalopram.
DR DrugBank; DB06678; Esmirtazapine.
DR DrugBank; DB00187; Esmolol.
DR DrugBank; DB00330; Ethambutol.
DR DrugBank; DB01466; Ethylmorphine.
DR DrugBank; DB01628; Etoricoxib.
DR DrugBank; DB01590; Everolimus.
DR DrugBank; DB12500; Fedratinib.
DR DrugBank; DB01023; Felodipine.
DR DrugBank; DB00574; Fenfluramine.
DR DrugBank; DB06702; Fesoterodine.
DR DrugBank; DB12265; Fexinidazole.
DR DrugBank; DB01195; Flecainide.
DR DrugBank; DB04841; Flunarizine.
DR DrugBank; DB00472; Fluoxetine.
DR DrugBank; DB00623; Fluphenazine.
DR DrugBank; DB01095; Fluvastatin.
DR DrugBank; DB00176; Fluvoxamine.
DR DrugBank; DB00983; Formoterol.
DR DrugBank; DB02703; Fusidic acid.
DR DrugBank; DB00674; Galantamine.
DR DrugBank; DB00317; Gefitinib.
DR DrugBank; DB08909; Glycerol phenylbutyrate.
DR DrugBank; DB00986; Glycopyrronium.
DR DrugBank; DB01218; Halofantrine.
DR DrugBank; DB00502; Haloperidol.
DR DrugBank; DB00956; Hydrocodone.
DR DrugBank; DB01611; Hydroxychloroquine.
DR DrugBank; DB01005; Hydroxyurea.
DR DrugBank; DB00557; Hydroxyzine.
DR DrugBank; DB09053; Ibrutinib.
DR DrugBank; DB01177; Idarubicin.
DR DrugBank; DB04946; Iloperidone.
DR DrugBank; DB00619; Imatinib.
DR DrugBank; DB00458; Imipramine.
DR DrugBank; DB08952; Indenolol.
DR DrugBank; DB00224; Indinavir.
DR DrugBank; DB06370; Indisulam.
DR DrugBank; DB13293; Ipecac.
DR DrugBank; DB04818; Iproniazid.
DR DrugBank; DB11633; Isavuconazole.
DR DrugBank; DB00951; Isoniazid.
DR DrugBank; DB11757; Istradefylline.
DR DrugBank; DB00602; Ivermectin.
DR DrugBank; DB09570; Ixazomib.
DR DrugBank; DB01026; Ketoconazole.
DR DrugBank; DB00598; Labetalol.
DR DrugBank; DB12212; Landiolol.
DR DrugBank; DB00448; Lansoprazole.
DR DrugBank; DB11732; Lasmiditan.
DR DrugBank; DB09078; Lenvatinib.
DR DrugBank; DB00528; Lercanidipine.
DR DrugBank; DB12070; Letermovir.
DR DrugBank; DB09351; Levobetaxolol.
DR DrugBank; DB01210; Levobunolol.
DR DrugBank; DB08918; Levomilnacipran.
DR DrugBank; DB00281; Lidocaine.
DR DrugBank; DB01255; Lisdexamfetamine.
DR DrugBank; DB04948; Lofexidine.
DR DrugBank; DB01206; Lomustine.
DR DrugBank; DB00836; Loperamide.
DR DrugBank; DB01601; Lopinavir.
DR DrugBank; DB00455; Loratadine.
DR DrugBank; DB04871; Lorcaserin.
DR DrugBank; DB09195; Lorpiprazole.
DR DrugBank; DB06708; Lumefantrine.
DR DrugBank; DB04829; Lysergic acid diethylamide.
DR DrugBank; DB09238; Manidipine.
DR DrugBank; DB00934; Maprotiline.
DR DrugBank; DB00737; Meclizine.
DR DrugBank; DB14009; Medical Cannabis.
DR DrugBank; DB09224; Melperone.
DR DrugBank; DB00170; Menadione.
DR DrugBank; DB00454; Meperidine.
DR DrugBank; DB00532; Mephenytoin.
DR DrugBank; DB13530; Mepindolol.
DR DrugBank; DB06691; Mepyramine.
DR DrugBank; DB01071; Mequitazine.
DR DrugBank; DB00933; Mesoridazine.
DR DrugBank; DB01577; Metamfetamine.
DR DrugBank; DB00333; Methadone.
DR DrugBank; DB00763; Methimazole.
DR DrugBank; DB01403; Methotrimeprazine.
DR DrugBank; DB01028; Methoxyflurane.
DR DrugBank; DB09241; Methylene blue.
DR DrugBank; DB01214; Metipranolol.
DR DrugBank; DB01233; Metoclopramide.
DR DrugBank; DB00264; Metoprolol.
DR DrugBank; DB00379; Mexiletine.
DR DrugBank; DB06148; Mianserin.
DR DrugBank; DB01388; Mibefradil.
DR DrugBank; DB01110; Miconazole.
DR DrugBank; DB00211; Midodrine.
DR DrugBank; DB01454; Midomafetamine.
DR DrugBank; DB06595; Midostaurin.
DR DrugBank; DB00834; Mifepristone.
DR DrugBank; DB00805; Minaprine.
DR DrugBank; DB08893; Mirabegron.
DR DrugBank; DB00370; Mirtazapine.
DR DrugBank; DB12523; Mizolastine.
DR DrugBank; DB01171; Moclobemide.
DR DrugBank; DB00745; Modafinil.
DR DrugBank; DB14011; Nabiximols.
DR DrugBank; DB09049; Naloxegol.
DR DrugBank; DB00731; Nateglinide.
DR DrugBank; DB04861; Nebivolol.
DR DrugBank; DB01149; Nefazodone.
DR DrugBank; DB00220; Nelfinavir.
DR DrugBank; DB09048; Netupitant.
DR DrugBank; DB00238; Nevirapine.
DR DrugBank; DB00627; Niacin.
DR DrugBank; DB00622; Nicardipine.
DR DrugBank; DB00699; Nicergoline.
DR DrugBank; DB02701; Nicotinamide.
DR DrugBank; DB00184; Nicotine.
DR DrugBank; DB01115; Nifedipine.
DR DrugBank; DB04868; Nilotinib.
DR DrugBank; DB00540; Nortriptyline.
DR DrugBank; DB00334; Olanzapine.
DR DrugBank; DB14881; Oliceridine.
DR DrugBank; DB00338; Omeprazole.
DR DrugBank; DB00904; Ondansetron.
DR DrugBank; DB11130; Opium.
DR DrugBank; DB04911; Oritavancin.
DR DrugBank; DB01173; Orphenadrine.
DR DrugBank; DB11837; Osilodrostat.
DR DrugBank; DB04938; Ospemifene.
DR DrugBank; DB01096; Oxamniquine.
DR DrugBank; DB01580; Oxprenolol.
DR DrugBank; DB01062; Oxybutynin.
DR DrugBank; DB00497; Oxycodone.
DR DrugBank; DB06412; Oxymetholone.
DR DrugBank; DB01192; Oxymorphone.
DR DrugBank; DB01267; Paliperidone.
DR DrugBank; DB00377; Palonosetron.
DR DrugBank; DB06603; Panobinostat.
DR DrugBank; DB00715; Paroxetine.
DR DrugBank; DB06589; Pazopanib.
DR DrugBank; DB00022; Peginterferon alfa-2b.
DR DrugBank; DB01359; Penbutolol.
DR DrugBank; DB00738; Pentamidine.
DR DrugBank; DB01074; Perhexiline.
DR DrugBank; DB08922; Perospirone.
DR DrugBank; DB00850; Perphenazine.
DR DrugBank; DB03783; Phenacetin.
DR DrugBank; DB00780; Phenelzine.
DR DrugBank; DB00914; Phenformin.
DR DrugBank; DB06819; Phenylbutyric acid.
DR DrugBank; DB00252; Phenytoin.
DR DrugBank; DB05316; Pimavanserin.
DR DrugBank; DB01100; Pimozide.
DR DrugBank; DB00960; Pindolol.
DR DrugBank; DB00592; Piperazine.
DR DrugBank; DB01621; Pipotiazine.
DR DrugBank; DB04951; Pirfenidone.
DR DrugBank; DB11642; Pitolisant.
DR DrugBank; DB08901; Ponatinib.
DR DrugBank; DB01297; Practolol.
DR DrugBank; DB15822; Pralsetinib.
DR DrugBank; DB01087; Primaquine.
DR DrugBank; DB01035; Procainamide.
DR DrugBank; DB00433; Prochlorperazine.
DR DrugBank; DB00396; Progesterone.
DR DrugBank; DB01131; Proguanil.
DR DrugBank; DB00420; Promazine.
DR DrugBank; DB01069; Promethazine.
DR DrugBank; DB09288; Propacetamol.
DR DrugBank; DB01182; Propafenone.
DR DrugBank; DB00571; Propranolol.
DR DrugBank; DB01224; Quetiapine.
DR DrugBank; DB00908; Quinidine.
DR DrugBank; DB00468; Quinine.
DR DrugBank; DB01129; Rabeprazole.
DR DrugBank; DB00863; Ranitidine.
DR DrugBank; DB00243; Ranolazine.
DR DrugBank; DB00234; Reboxetine.
DR DrugBank; DB14761; Remdesivir.
DR DrugBank; DB00409; Remoxipride.
DR DrugBank; DB06506; Repinotan.
DR DrugBank; DB11855; Revefenacin.
DR DrugBank; DB13174; Rhein.
DR DrugBank; DB11753; Rifamycin.
DR DrugBank; DB08864; Rilpivirine.
DR DrugBank; DB14840; Ripretinib.
DR DrugBank; DB00734; Risperidone.
DR DrugBank; DB12693; Ritanserin.
DR DrugBank; DB00503; Ritonavir.
DR DrugBank; DB09291; Rolapitant.
DR DrugBank; DB15119; Ropeginterferon alfa-2b.
DR DrugBank; DB00412; Rosiglitazone.
DR DrugBank; DB05271; Rotigotine.
DR DrugBank; DB12332; Rucaparib.
DR DrugBank; DB11614; Rupatadine.
DR DrugBank; DB06654; Safinamide.
DR DrugBank; DB01232; Saquinavir.
DR DrugBank; DB01037; Selegiline.
DR DrugBank; DB06144; Sertindole.
DR DrugBank; DB01104; Sertraline.
DR DrugBank; DB00203; Sildenafil.
DR DrugBank; DB00641; Simvastatin.
DR DrugBank; DB01591; Solifenacin.
DR DrugBank; DB00398; Sorafenib.
DR DrugBank; DB00489; Sotalol.
DR DrugBank; DB06727; Sparteine.
DR DrugBank; DB01323; St. John's Wort.
DR DrugBank; DB09118; Stiripentol.
DR DrugBank; DB06820; Sulconazole.
DR DrugBank; DB06729; Sulfaphenazole.
DR DrugBank; DB06608; Tafenoquine.
DR DrugBank; DB11770; Talinolol.
DR DrugBank; DB00675; Tamoxifen.
DR DrugBank; DB00706; Tamsulosin.
DR DrugBank; DB06204; Tapentadol.
DR DrugBank; DB01079; Tegaserod.
DR DrugBank; DB06287; Temsirolimus.
DR DrugBank; DB00857; Terbinafine.
DR DrugBank; DB00342; Terfenadine.
DR DrugBank; DB13775; Tertatolol.
DR DrugBank; DB04905; Tesmilifene.
DR DrugBank; DB04844; Tetrabenazine.
DR DrugBank; DB00277; Theophylline.
DR DrugBank; DB00679; Thioridazine.
DR DrugBank; DB01623; Thiothixene.
DR DrugBank; DB00208; Ticlopidine.
DR DrugBank; DB00373; Timolol.
DR DrugBank; DB01409; Tiotropium.
DR DrugBank; DB00932; Tipranavir.
DR DrugBank; DB06137; Tirbanibulin.
DR DrugBank; DB01036; Tolterodine.
DR DrugBank; DB05109; Trabectedin.
DR DrugBank; DB00193; Tramadol.
DR DrugBank; DB00752; Tranylcypromine.
DR DrugBank; DB00656; Trazodone.
DR DrugBank; DB12245; Triclabendazole.
DR DrugBank; DB00726; Trimipramine.
DR DrugBank; DB00792; Tripelennamine.
DR DrugBank; DB00209; Trospium.
DR DrugBank; DB15328; Ubrogepant.
DR DrugBank; DB09076; Umeclidinium.
DR DrugBank; DB13609; Umifenovir.
DR DrugBank; DB15091; Upadacitinib.
DR DrugBank; DB11915; Valbenazine.
DR DrugBank; DB08881; Vemurafenib.
DR DrugBank; DB00285; Venlafaxine.
DR DrugBank; DB00661; Verapamil.
DR DrugBank; DB06217; Vernakalant.
DR DrugBank; DB06684; Vilazodone.
DR DrugBank; DB00570; Vinblastine.
DR DrugBank; DB00361; Vinorelbine.
DR DrugBank; DB09068; Vortioxetine.
DR DrugBank; DB01392; Yohimbine.
DR DrugBank; DB00549; Zafirlukast.
DR DrugBank; DB00425; Zolpidem.
DR DrugBank; DB01624; Zuclopenthixol.
DR DrugCentral; P10635; -.
DR GuidetoPHARMACOLOGY; 1329; -.
DR SwissLipids; SLP:000001204; -.
DR iPTMnet; P10635; -.
DR PhosphoSitePlus; P10635; -.
DR BioMuta; CYP2D6; -.
DR DMDM; 84028191; -.
DR jPOST; P10635; -.
DR MassIVE; P10635; -.
DR PaxDb; P10635; -.
DR PeptideAtlas; P10635; -.
DR PRIDE; P10635; -.
DR ProteomicsDB; 52623; -. [P10635-1]
DR ProteomicsDB; 66778; -.
DR Antibodypedia; 13178; 631 antibodies from 38 providers.
DR DNASU; 1565; -.
DR Ensembl; ENST00000359033.4; ENSP00000351927.4; ENSG00000100197.23. [P10635-2]
DR Ensembl; ENST00000612990.2; ENSP00000483677.1; ENSG00000275211.4.
DR Ensembl; ENST00000645361.2; ENSP00000496150.1; ENSG00000100197.23. [P10635-1]
DR GeneID; 1565; -.
DR KEGG; hsa:1565; -.
DR MANE-Select; ENST00000645361.2; ENSP00000496150.1; NM_000106.6; NP_000097.3.
DR UCSC; uc003bce.4; human. [P10635-1]
DR CTD; 1565; -.
DR DisGeNET; 1565; -.
DR GeneCards; CYP2D6; -.
DR HGNC; HGNC:2625; CYP2D6.
DR HPA; ENSG00000100197; Tissue enriched (liver).
DR MalaCards; CYP2D6; -.
DR MIM; 124030; gene.
DR MIM; 608902; phenotype.
DR neXtProt; NX_P10635; -.
DR OpenTargets; ENSG00000100197; -.
DR Orphanet; 240867; Prediction of codeine toxicity.
DR Orphanet; 240947; Prediction of resistance to tamoxifene.
DR Orphanet; 413667; Prediction of toxicity or dose selection of antidepressants or antipsychotics.
DR PharmGKB; PA128; -.
DR VEuPathDB; HostDB:ENSG00000100197; -.
DR eggNOG; KOG0156; Eukaryota.
DR GeneTree; ENSGT00940000153331; -.
DR HOGENOM; CLU_001570_22_3_1; -.
DR InParanoid; P10635; -.
DR OMA; ETYRPIQ; -.
DR PhylomeDB; P10635; -.
DR TreeFam; TF352043; -.
DR BioCyc; MetaCyc:HS01997-MON; -.
DR BRENDA; 1.14.14.1; 2681.
DR BRENDA; 1.14.99.38; 2681.
DR PathwayCommons; P10635; -.
DR Reactome; R-HSA-211935; Fatty acids.
DR Reactome; R-HSA-211958; Miscellaneous substrates.
DR Reactome; R-HSA-211981; Xenobiotics.
DR Reactome; R-HSA-211999; CYP2E1 reactions.
DR Reactome; R-HSA-9027307; Biosynthesis of maresin-like SPMs.
DR Reactome; R-HSA-9749641; Aspirin ADME.
DR SABIO-RK; P10635; -.
DR SIGNOR; P10635; -.
DR UniPathway; UPA00199; -.
DR UniPathway; UPA00296; -.
DR UniPathway; UPA00912; -.
DR BioGRID-ORCS; 1565; 10 hits in 1062 CRISPR screens.
DR EvolutionaryTrace; P10635; -.
DR GeneWiki; CYP2D6; -.
DR GenomeRNAi; 1565; -.
DR Pharos; P10635; Tclin.
DR PRO; PR:P10635; -.
DR Proteomes; UP000005640; Chromosome 22.
DR RNAct; P10635; protein.
DR Bgee; ENSG00000100197; Expressed in right lobe of liver and 92 other tissues.
DR ExpressionAtlas; P10635; baseline and differential.
DR Genevisible; P10635; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005783; C:endoplasmic reticulum; TAS:BHF-UCL.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IBA:GO_Central.
DR GO; GO:0005739; C:mitochondrion; IDA:BHF-UCL.
DR GO; GO:0062188; F:anandamide 11,12 epoxidase activity; IDA:UniProtKB.
DR GO; GO:0062189; F:anandamide 14,15 epoxidase activity; IDA:UniProtKB.
DR GO; GO:0062187; F:anandamide 8,9 epoxidase activity; IDA:UniProtKB.
DR GO; GO:0020037; F:heme binding; IDA:UniProtKB.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0004497; F:monooxygenase activity; IDA:BHF-UCL.
DR GO; GO:0016491; F:oxidoreductase activity; IDA:BHF-UCL.
DR GO; GO:0016712; F: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; IBA:GO_Central.
DR GO; GO:0008395; F:steroid hydroxylase activity; IBA:GO_Central.
DR GO; GO:0009822; P:alkaloid catabolic process; IDA:BHF-UCL.
DR GO; GO:0009820; P:alkaloid metabolic process; IDA:BHF-UCL.
DR GO; GO:0019369; P:arachidonic acid metabolic process; IBA:GO_Central.
DR GO; GO:0008203; P:cholesterol metabolic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0009804; P:coumarin metabolic process; IDA:BHF-UCL.
DR GO; GO:0008210; P:estrogen metabolic process; IDA:UniProtKB.
DR GO; GO:0046483; P:heterocycle metabolic process; IDA:BHF-UCL.
DR GO; GO:0033076; P:isoquinoline alkaloid metabolic process; IDA:BHF-UCL.
DR GO; GO:0042759; P:long-chain fatty acid biosynthetic process; TAS:Reactome.
DR GO; GO:0016098; P:monoterpenoid metabolic process; IDA:BHF-UCL.
DR GO; GO:0051100; P:negative regulation of binding; IDA:BHF-UCL.
DR GO; GO:0090350; P:negative regulation of cellular organofluorine metabolic process; IDA:BHF-UCL.
DR GO; GO:0006082; P:organic acid metabolic process; IBA:GO_Central.
DR GO; GO:0070989; P:oxidative demethylation; IDA:BHF-UCL.
DR GO; GO:0042572; P:retinol metabolic process; IDA:UniProtKB.
DR GO; GO:0008202; P:steroid metabolic process; IMP:BHF-UCL.
DR GO; GO:0042178; P:xenobiotic catabolic process; IDA:BHF-UCL.
DR GO; GO:0006805; P:xenobiotic metabolic process; IDA:BHF-UCL.
DR Gene3D; 1.10.630.10; -; 1.
DR InterPro; IPR001128; Cyt_P450.
DR InterPro; IPR017972; Cyt_P450_CS.
DR InterPro; IPR002401; Cyt_P450_E_grp-I.
DR InterPro; IPR008069; Cyt_P450_E_grp-I_CYP2D-like.
DR InterPro; IPR036396; Cyt_P450_sf.
DR Pfam; PF00067; p450; 1.
DR PRINTS; PR00463; EP450I.
DR PRINTS; PR01686; EP450ICYP2D.
DR PRINTS; PR00385; P450.
DR SUPFAM; SSF48264; SSF48264; 1.
DR PROSITE; PS00086; CYTOCHROME_P450; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cholesterol metabolism;
KW Endoplasmic reticulum; Fatty acid metabolism; Heme; Iron; Lipid metabolism;
KW Membrane; Metal-binding; Microsome; Monooxygenase; Oxidoreductase;
KW Reference proteome; Steroid metabolism; Sterol metabolism.
FT CHAIN 1..497
FT /note="Cytochrome P450 2D6"
FT /id="PRO_0000051731"
FT BINDING 301
FT /ligand="substrate"
FT /evidence="ECO:0000305"
FT BINDING 443
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT VAR_SEQ 118..168
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_044486"
FT VARIANT 5
FT /note="A -> V (in allele CYP2D6*87; dbSNP:rs773790593)"
FT /evidence="ECO:0000269|PubMed:25469868"
FT /id="VAR_072764"
FT VARIANT 11
FT /note="V -> M (in allele CYP2D6*35; dbSNP:rs769258)"
FT /evidence="ECO:0000269|PubMed:15469410"
FT /id="VAR_008366"
FT VARIANT 25
FT /note="R -> Q (in dbSNP:rs138417770)"
FT /evidence="ECO:0000269|PubMed:25469868"
FT /id="VAR_072765"
FT VARIANT 26
FT /note="R -> H (in allele CYP2D6*21 and allele CYP2D6*46;
FT dbSNP:rs28371696)"
FT /evidence="ECO:0000269|PubMed:15469410,
FT ECO:0000269|PubMed:15768052, ECO:0000269|Ref.6"
FT /id="VAR_008367"
FT VARIANT 28
FT /note="R -> C (in allele CYP2D6*22; dbSNP:rs138100349)"
FT /id="VAR_008368"
FT VARIANT 34
FT /note="P -> S (in allele CYP2D6*10 and allele CYP2D6*14;
FT poor debrisquone metabolism; dbSNP:rs1065852)"
FT /evidence="ECO:0000269|PubMed:15469410,
FT ECO:0000269|PubMed:25469868, ECO:0000269|PubMed:8287064"
FT /id="VAR_008336"
FT VARIANT 42
FT /note="G -> R (in allele CYP2D6*12; impaired metabolism of
FT sparteine; dbSNP:rs5030862)"
FT /evidence="ECO:0000269|PubMed:8655150"
FT /id="VAR_001256"
FT VARIANT 85
FT /note="A -> V (in allele CYP2D6*23; dbSNP:rs267608310)"
FT /id="VAR_008369"
FT VARIANT 91
FT /note="L -> M (in dbSNP:rs28371703)"
FT /evidence="ECO:0000269|PubMed:15469410"
FT /id="VAR_024720"
FT VARIANT 94
FT /note="H -> R (in dbSNP:rs28371704)"
FT /evidence="ECO:0000269|PubMed:15469410"
FT /id="VAR_024721"
FT VARIANT 104
FT /note="V -> A (in allele CYP2D6*88; dbSNP:rs76187628)"
FT /evidence="ECO:0000269|PubMed:25469868"
FT /id="VAR_072766"
FT VARIANT 107
FT /note="T -> I (in allele CYP2D6*17; poor debrisquone
FT metabolism; dbSNP:rs28371706)"
FT /evidence="ECO:0000269|PubMed:15469410,
FT ECO:0000269|PubMed:8971426"
FT /id="VAR_008337"
FT VARIANT 120
FT /note="F -> I (in dbSNP:rs1135822)"
FT /evidence="ECO:0000269|PubMed:15469410"
FT /id="VAR_024722"
FT VARIANT 142
FT /note="L -> S (in allele CYP2D6*89; >90% decrease of
FT monooxygenase activity towards dextromethorphan and
FT bufuralol; dbSNP:rs375135093)"
FT /evidence="ECO:0000269|PubMed:25469868"
FT /id="VAR_072767"
FT VARIANT 147
FT /note="K -> R (in allele CYP2D6*90; dbSNP:rs569229126)"
FT /evidence="ECO:0000269|PubMed:25469868"
FT /id="VAR_072768"
FT VARIANT 155
FT /note="E -> K (in allele CYP2D6*45A, allele CYP2D6*45B and
FT allele CYP2D6*46; dbSNP:rs28371710)"
FT /evidence="ECO:0000269|PubMed:15469410,
FT ECO:0000269|PubMed:15768052"
FT /id="VAR_024723"
FT VARIANT 161
FT /note="C -> S (in allele CYP2D6*91)"
FT /evidence="ECO:0000269|PubMed:25469868"
FT /id="VAR_072769"
FT VARIANT 164
FT /note="F -> L"
FT /evidence="ECO:0000269|PubMed:25469868"
FT /id="VAR_072770"
FT VARIANT 169
FT /note="G -> R (in allele CYP2D6*14; poor debrisquone
FT metabolism; dbSNP:rs5030865)"
FT /evidence="ECO:0000269|PubMed:10064570"
FT /id="VAR_008338"
FT VARIANT 212
FT /note="G -> E (in allele CYP2D6*6B and allele CYP2D6*6C;
FT dbSNP:rs5030866)"
FT /evidence="ECO:0000269|PubMed:7868129"
FT /id="VAR_008339"
FT VARIANT 215
FT /note="E -> K (>90% decrease of monooxygenase activity
FT towards dextromethorphan and bufuralol; dbSNP:rs567606867)"
FT /evidence="ECO:0000269|PubMed:25469868"
FT /id="VAR_072771"
FT VARIANT 219
FT /note="F -> S (in dbSNP:rs371793722)"
FT /evidence="ECO:0000269|PubMed:25469868"
FT /id="VAR_072772"
FT VARIANT 231
FT /note="L -> P (in dbSNP:rs17002853)"
FT /id="VAR_045679"
FT VARIANT 237
FT /note="A -> S (in allele CYP2D6*33; dbSNP:rs28371717)"
FT /evidence="ECO:0000269|PubMed:15469410"
FT /id="VAR_008370"
FT VARIANT 249
FT /note="T -> P (in allele CYP2D6*93; >90% decrease of
FT monooxygenase activity towards dextromethorphan and
FT bufuralol)"
FT /evidence="ECO:0000269|PubMed:25469868"
FT /id="VAR_072773"
FT VARIANT 281
FT /note="Missing (in allele CYP2D6*9)"
FT /evidence="ECO:0000269|PubMed:1844820"
FT /id="VAR_008347"
FT VARIANT 296
FT /note="R -> C (in allele CYP2D6*2, allele CYP2D6*12, allele
FT CYP2D6*14, allele CYP2D6*17, allele CYP2D6*45A, allele
FT CYP2D6*45B and allele CYP2D6*46; significantly reduced
FT monooxygenase activity toward anandamide; slight decrease
FT of monooxygenase activity towards bufuralol;
FT dbSNP:rs16947)"
FT /evidence="ECO:0000269|PubMed:10591208,
FT ECO:0000269|PubMed:15469410, ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:15768052, ECO:0000269|PubMed:21289075,
FT ECO:0000269|PubMed:25469868"
FT /id="VAR_008340"
FT VARIANT 297
FT /note="I -> L (in allele CYP2D6*24; dbSNP:rs949717872)"
FT /id="VAR_008371"
FT VARIANT 300
FT /note="A -> G (in dbSNP:rs1058170)"
FT /id="VAR_045680"
FT VARIANT 311
FT /note="S -> L (in dbSNP:rs1800754)"
FT /id="VAR_014633"
FT VARIANT 324
FT /note="H -> P (in allele CYP2D6*7; loss of activity;
FT dbSNP:rs5030867)"
FT /evidence="ECO:0000269|PubMed:7845481"
FT /id="VAR_008348"
FT VARIANT 327
FT /note="V -> M"
FT /evidence="ECO:0000269|PubMed:25469868"
FT /id="VAR_072774"
FT VARIANT 329
FT /note="R -> L (in dbSNP:rs3915951)"
FT /id="VAR_059150"
FT VARIANT 336
FT /note="D -> N (in dbSNP:rs745746329)"
FT /evidence="ECO:0000269|PubMed:25469868"
FT /id="VAR_072775"
FT VARIANT 337
FT /note="D -> G (in allele CYP2D6*94; dbSNP:rs748712690)"
FT /evidence="ECO:0000269|PubMed:25469868"
FT /id="VAR_072776"
FT VARIANT 342
FT /note="V -> M (in dbSNP:rs750996195)"
FT /evidence="ECO:0000269|PubMed:25469868"
FT /id="VAR_072777"
FT VARIANT 343
FT /note="R -> G (in allele CYP2D6*25; dbSNP:rs267608295)"
FT /id="VAR_008372"
FT VARIANT 344
FT /note="R -> Q (in dbSNP:rs76088846)"
FT /evidence="ECO:0000269|PubMed:25469868"
FT /id="VAR_072778"
FT VARIANT 365
FT /note="R -> H (in dbSNP:rs1058172)"
FT /id="VAR_045681"
FT VARIANT 369
FT /note="I -> T (in allele CYP2D6*26)"
FT /id="VAR_008373"
FT VARIANT 373
FT /note="G -> S (in dbSNP:rs61737946)"
FT /id="VAR_059151"
FT VARIANT 410
FT /note="E -> K (in allele CYP2D6*27; dbSNP:rs769157652)"
FT /id="VAR_008374"
FT VARIANT 418
FT /note="E -> K (in dbSNP:rs28371733)"
FT /evidence="ECO:0000269|PubMed:15469410"
FT /id="VAR_024724"
FT VARIANT 440
FT /note="R -> C (>90% decrease of monooxygenase activity
FT towards dextromethorphan and bufuralol; dbSNP:rs777560972)"
FT /evidence="ECO:0000269|PubMed:25469868"
FT /id="VAR_072779"
FT VARIANT 457
FT /note="F -> L (in allele CYP2D6*97)"
FT /evidence="ECO:0000269|PubMed:25469868"
FT /id="VAR_072780"
FT VARIANT 463
FT /note="H -> D (in allele CYP2D6*98)"
FT /evidence="ECO:0000269|PubMed:25469868"
FT /id="VAR_072781"
FT VARIANT 469
FT /note="P -> A (in dbSNP:rs1135833)"
FT /evidence="ECO:0000269|PubMed:15469410"
FT /id="VAR_024725"
FT VARIANT 478
FT /note="H -> Y (in dbSNP:rs28371735)"
FT /evidence="ECO:0000269|PubMed:15469410"
FT /id="VAR_024726"
FT VARIANT 486
FT /note="S -> T (in allele CYP2D6*2, allele CYP2D6*10, allele
FT CYP2D6*12, allele CYP2D6*14, allele CYP2D6*17, allele
FT CYP2D6*45A, allele CYP2D6*45B and allele CYP2D6*46;
FT impaired metabolism of sparteine; dbSNP:rs1135840)"
FT /evidence="ECO:0000269|PubMed:10591208,
FT ECO:0000269|PubMed:15469410, ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:15768052, ECO:0000269|PubMed:25469868,
FT ECO:0000269|PubMed:8287064"
FT /id="VAR_008341"
FT VARIANT 497
FT /note="R -> C (in dbSNP:rs370580423)"
FT /evidence="ECO:0000269|PubMed:25469868"
FT /id="VAR_072782"
FT CONFLICT 374
FT /note="V -> M (in Ref. 1; AAA52153 and 2; CAA30807)"
FT /evidence="ECO:0000305"
FT TURN 41..43
FT /evidence="ECO:0007829|PDB:3TBG"
FT HELIX 46..48
FT /evidence="ECO:0007829|PDB:3TBG"
FT STRAND 51..53
FT /evidence="ECO:0007829|PDB:6CSD"
FT HELIX 54..65
FT /evidence="ECO:0007829|PDB:3TBG"
FT STRAND 67..73
FT /evidence="ECO:0007829|PDB:3TBG"
FT STRAND 76..81
FT /evidence="ECO:0007829|PDB:3TBG"
FT HELIX 83..91
FT /evidence="ECO:0007829|PDB:3TBG"
FT TURN 92..94
FT /evidence="ECO:0007829|PDB:3TBG"
FT HELIX 95..97
FT /evidence="ECO:0007829|PDB:3TBG"
FT HELIX 105..110
FT /evidence="ECO:0007829|PDB:3TBG"
FT STRAND 119..121
FT /evidence="ECO:0007829|PDB:4WNU"
FT HELIX 126..141
FT /evidence="ECO:0007829|PDB:3TBG"
FT STRAND 145..147
FT /evidence="ECO:0007829|PDB:4WNU"
FT HELIX 148..165
FT /evidence="ECO:0007829|PDB:3TBG"
FT TURN 166..169
FT /evidence="ECO:0007829|PDB:3TBG"
FT HELIX 175..191
FT /evidence="ECO:0007829|PDB:3TBG"
FT HELIX 200..214
FT /evidence="ECO:0007829|PDB:3TBG"
FT HELIX 219..226
FT /evidence="ECO:0007829|PDB:3TBG"
FT HELIX 228..232
FT /evidence="ECO:0007829|PDB:3TBG"
FT HELIX 234..240
FT /evidence="ECO:0007829|PDB:3TBG"
FT HELIX 242..261
FT /evidence="ECO:0007829|PDB:3TBG"
FT HELIX 271..281
FT /evidence="ECO:0007829|PDB:3TBG"
FT TURN 282..284
FT /evidence="ECO:0007829|PDB:3TBG"
FT HELIX 292..323
FT /evidence="ECO:0007829|PDB:3TBG"
FT HELIX 325..338
FT /evidence="ECO:0007829|PDB:3TBG"
FT STRAND 341..343
FT /evidence="ECO:0007829|PDB:3TBG"
FT HELIX 347..350
FT /evidence="ECO:0007829|PDB:3TBG"
FT HELIX 354..367
FT /evidence="ECO:0007829|PDB:3TBG"
FT STRAND 370..372
FT /evidence="ECO:0007829|PDB:3QM4"
FT STRAND 382..384
FT /evidence="ECO:0007829|PDB:3TBG"
FT STRAND 387..389
FT /evidence="ECO:0007829|PDB:3TBG"
FT STRAND 394..397
FT /evidence="ECO:0007829|PDB:3TBG"
FT HELIX 399..403
FT /evidence="ECO:0007829|PDB:3TBG"
FT TURN 406..408
FT /evidence="ECO:0007829|PDB:3TBG"
FT STRAND 409..411
FT /evidence="ECO:0007829|PDB:3TBG"
FT HELIX 417..420
FT /evidence="ECO:0007829|PDB:3TBG"
FT HELIX 439..441
FT /evidence="ECO:0007829|PDB:4WNV"
FT HELIX 446..463
FT /evidence="ECO:0007829|PDB:3TBG"
FT STRAND 464..467
FT /evidence="ECO:0007829|PDB:3TBG"
FT STRAND 470..472
FT /evidence="ECO:0007829|PDB:4WNW"
FT STRAND 479..487
FT /evidence="ECO:0007829|PDB:3TBG"
FT STRAND 492..496
FT /evidence="ECO:0007829|PDB:3TBG"
SQ SEQUENCE 497 AA; 55769 MW; 542B1D505DF3CDAC CRC64;
MGLEALVPLA VIVAIFLLLV DLMHRRQRWA ARYPPGPLPL PGLGNLLHVD FQNTPYCFDQ
LRRRFGDVFS LQLAWTPVVV LNGLAAVREA LVTHGEDTAD RPPVPITQIL GFGPRSQGVF
LARYGPAWRE QRRFSVSTLR NLGLGKKSLE QWVTEEAACL CAAFANHSGR PFRPNGLLDK
AVSNVIASLT CGRRFEYDDP RFLRLLDLAQ EGLKEESGFL REVLNAVPVL LHIPALAGKV
LRFQKAFLTQ LDELLTEHRM TWDPAQPPRD LTEAFLAEME KAKGNPESSF NDENLRIVVA
DLFSAGMVTT STTLAWGLLL MILHPDVQRR VQQEIDDVIG QVRRPEMGDQ AHMPYTTAVI
HEVQRFGDIV PLGVTHMTSR DIEVQGFRIP KGTTLITNLS SVLKDEAVWE KPFRFHPEHF
LDAQGHFVKP EAFLPFSAGR RACLGEPLAR MELFLFFTSL LQHFSFSVPT GQPRPSHHGV
FAFLVSPSPY ELCAVPR
