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 27-MAR-2024, entry version 235. 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 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 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 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 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 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 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 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 VAL-5; GLN-25; SER-34; ALA-104; SER-142; ARG-147; SER-161; RP LEU-164; LYS-215; SER-219; PRO-249; CYS-296; MET-327; ASN-336; GLY-337; RP MET-342; GLN-344; CYS-440; LEU-457; ASP-463; 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 CC [NADPH--hemoprotein reductase] = (8R,9S)-epoxy-(5Z,11Z,14Z)- CC eicosatrienoate + H(+) + H2O + oxidized [NADPH--hemoprotein CC reductase]; Xref=Rhea:RHEA:49884, Rhea:RHEA-COMP:11964, Rhea:RHEA- CC COMP:11965, 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 CC [NADPH--hemoprotein reductase] = (11R,12S)-epoxy-(5Z,8Z,14Z)- CC eicosatrienoate + H(+) + H2O + oxidized [NADPH--hemoprotein CC reductase]; Xref=Rhea:RHEA:49880, Rhea:RHEA-COMP:11964, Rhea:RHEA- CC COMP:11965, 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 CC [NADPH--hemoprotein reductase] = (14S,15R)-epoxy-(5Z,8Z,11Z)- CC eicosatrienoate + H(+) + H2O + oxidized [NADPH--hemoprotein CC reductase]; Xref=Rhea:RHEA:49856, Rhea:RHEA-COMP:11964, Rhea:RHEA- CC COMP:11965, 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 CC [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:53140, Rhea:RHEA- CC COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:2700, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, CC ChEBI:CHEBI:57618, 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 CC [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:53152, Rhea:RHEA- CC COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:2700, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, CC ChEBI:CHEBI:57618, 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 CC [NADPH--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 CC [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:42092, Rhea:RHEA- CC COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:17336, CC ChEBI:CHEBI:17898, 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 CC 20-HETE) {ECO:0000269|PubMed:18698000}; CC Vmax=1.6 pmol/min/nmol enzyme toward anandamide (oxidation to CC 8,9-EpETrE-EA) {ECO:0000269|PubMed:18698000}; CC Vmax=1.1 pmol/min/nmol enzyme toward anandamide (oxidation to CC 11,12-EpETrE-EA) {ECO:0000269|PubMed:18698000}; CC Vmax=1.3 pmol/min/nmol enzyme toward anandamide (oxidation to CC 14,15-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 --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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.ENSP00000496150; -. 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; DB15568; Adagrasib. 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; DB14737; Cannabinol. 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; DB05239; Cobimetinib. 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; DB16650; Deucravacitinib. 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; DB00470; Dronabinol. 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; DB15149; Futibatinib. DR DrugBank; DB00674; Galantamine. DR DrugBank; DB05087; Ganaxolone. 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; DB14921; Mavacamten. 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; 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; DB04216; Quercetin. 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; DB02709; Resveratrol. 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; DB12713; Sotagliflozin. 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; DB06083; Tapinarof. DR DrugBank; DB01079; Tegaserod. DR DrugBank; DB12095; Telotristat ethyl. 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; DB09185; Viloxazine. DR DrugBank; DB00570; Vinblastine. DR DrugBank; DB00361; Vinorelbine. DR DrugBank; DB11739; Vonoprazan. 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; 9606-ENSP00000353820; -. DR PeptideAtlas; P10635; -. DR ProteomicsDB; 52623; -. [P10635-1] DR ProteomicsDB; 66778; -. DR Antibodypedia; 13178; 704 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 AGR; HGNC:2625; -. 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 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; RYGHVWK; -. DR OrthoDB; 2900138at2759; -. DR PhylomeDB; P10635; -. DR TreeFam; TF352043; -. DR BioCyc; MetaCyc:HS01997-MONOMER; -. 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 1140 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 93 other cell types or tissues. DR ExpressionAtlas; P10635; baseline and differential. 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: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: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 CDD; cd20663; CYP2D; 1. DR Gene3D; 1.10.630.10; Cytochrome P450; 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 PANTHER; PTHR24300:SF1; CYTOCHROME P450 2D6-RELATED; 1. DR PANTHER; PTHR24300; CYTOCHROME P450 508A4-RELATED; 1. DR Pfam; PF00067; p450; 1. DR PRINTS; PR00463; EP450I. DR PRINTS; PR01686; EP450ICYP2D. DR PRINTS; PR00385; P450. DR SUPFAM; SSF48264; Cytochrome P450; 1. DR PROSITE; PS00086; CYTOCHROME_P450; 1. DR Genevisible; P10635; HS. 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 //