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 04-FEB-2015, entry version 167. DE RecName: Full=Cytochrome P450 2D6; DE EC=1.14.14.1; DE AltName: Full=CYPIID6; DE AltName: Full=Cytochrome P450-DB1; DE AltName: Full=Debrisoquine 4-hydroxylase; GN Name=CYP2D6; Synonyms=CYP2DL1; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; 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 RT acid 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., RA Nebert D.W., 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 RP HIS-26; LYS-155; CYS-296 AND THR-486, AND CHARACTERIZATION OF ISOZYMES RP CYP2D6.45 AND CYP2D6.46. RX PubMed=15768052; DOI=10.1038/sj.tpj.6500305; RA Gaedigk A., Bhathena A., Ndjountche L., Pearce R.E., RA Abdel-Rahman S.M., Alander S.W., Bradford L.D., Rogan P.K., RA Leeder J.S.; RT "Identification and characterization of novel sequence variations in RT the cytochrome P4502D6 (CYP2D6) gene in African Americans."; RL Pharmacogenomics J. 5:173-182(2005). RN [5] RP ERRATUM. RA Gaedigk A., Bhathena A., Ndjountche L., Pearce R.E., RA Abdel-Rahman S.M., Alander S.W., Bradford L.D., Rogan P.K., RA 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 RP AND THR-486. RX PubMed=10591208; DOI=10.1038/990031; RA Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., RA Clamp M., Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., RA Bagguley C., Bailey J., Barlow K.F., Bates K.N., Beasley O.P., RA Bird C.P., Blakey S.E., Bridgeman A.M., Buck D., Burgess J., RA Burrill W.D., Burton J., Carder C., Carter N.P., Chen Y., Clark G., RA Clegg S.M., Cobley V.E., Cole C.G., Collier R.E., Connor R., RA Conroy D., Corby N.R., Coville G.J., Cox A.V., Davis J., Dawson E., RA Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., Ellington A.G., RA 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., RA Hunt S.E., Jones M.C., Kershaw J., Kimberley A.M., King A., RA Laird G.K., Langford C.F., Leversha M.A., Lloyd C., Lloyd D.M., RA Martyn I.D., Mashreghi-Mohammadi M., Matthews L.H., Mccann O.T., RA Mcclay J., Mclaren S., McMurray A.A., Milne S.A., Mortimore B.J., RA Odell C.N., Pavitt R., Pearce A.V., Pearson D., Phillimore B.J.C.T., RA Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., Rogers L., Ross M.T., RA Scott C.E., Sehra H.K., Skuce C.D., Smalley S., Smith M.L., RA Soderlund C., Spragon L., Steward C.A., Sulston J.E., Swann R.M., RA 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., RA Shintani A., Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., RA Roe B.A., Chen F., Chu L., Crabtree J., Deschamps S., Do A., Do T., RA Dorman A., Fang F., Fu Y., Hu P., Hua A., Kenton S., Lai H., Lao H.I., RA Lewis J., Lewis S., Lin S.-P., Loh P., Malaj E., Nguyen T., Pan H., RA Phan S., Qi S., Qian Y., Ray L., Ren Q., Shaull S., Sloan D., Song L., RA Wang Q., Wang Y., Wang Z., White J., Willingham D., Wu H., Yao Z., RA Zhan M., Zhang G., Chissoe S., Murray J., Miller N., Minx P., RA Fulton R., Johnson D., Bemis G., Bentley D., Bradshaw H., Bourne S., RA Cordes M., Du Z., Fulton L., Goela D., Graves T., Hawkins J., RA Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., Rohlfing T., RA Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., Nelson J., RA Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R., RA Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., RA Budarf M.L., McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., RA Edelmann L., Kim U.J., Shizuya H., Simon M.I., Dumanski J.P., RA Peyrard M., Kedra D., Seroussi E., Fransson I., Tapia I., Bruder C.E., RA O'Brien K.P., Wilkinson P., Bodenteich A., Hartman K., Hu X., RA Khan A.S., Lane L., Tilahun Y., 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 RP VARIANTS 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [9] RP X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 34-497 IN COMPLEX WITH HEME, RP AND FUNCTION. RX PubMed=16352597; DOI=10.1074/jbc.M511232200; RA Rowland P., Blaney F.E., Smyth M.G., Jones J.J., Leydon V.R., RA Oxbrow A.K., Lewis C.J., Tennant M.G., Modi S., Eggleston D.S., RA Chenery R.J., Bridges A.M.; RT "Crystal structure of human cytochrome P450 2D6."; RL J. Biol. Chem. 281:7614-7622(2006). RN [10] RP VARIANT CYP2D6*9 LYS-281 DEL. RX PubMed=1844820; 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 RT encoding Lys-281: possible association with the poor metabolizer RT phenotype."; RL Pharmacogenetics 1:26-32(1991). RN [11] RP VARIANTS CYP2D6*10 SER-34 AND THR-486. RX PubMed=8287064; 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 RT population associated with lower in vivo rates of sparteine RT metabolism."; RL Pharmacogenetics 3:256-263(1993). RN [12] 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 RT histidine 324 to proline exchange is associated with the poor RT metabolizer phenotype of sparteine."; RL Naunyn Schmiedebergs Arch. Pharmacol. 350:434-439(1994). RN [13] 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 RT base substitution."; RL Hum. Genet. 95:337-341(1995). RN [14] 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 RT black African population: association with diminished debrisoquine RT hydroxylase activity."; RL Br. J. Clin. Pharmacol. 42:713-719(1996). RN [15] 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., RA 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 [16] RP VARIANTS. RX PubMed=9241659; RA Marez D., Legrand M., Sabbagh N., Guidice J.M., Spire C., RA Lafitte J.J., Meyer U.A., Broly F.; RT "Polymorphism of the cytochrome P450 CYP2D6 gene in a European RT population: characterization of 48 mutations and 53 alleles, their RT frequencies and evolution."; RL Pharmacogenetics 7:193-202(1997). RN [17] 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 RT Chinese."; RL Drug Metab. Dispos. 27:385-388(1999). RN [18] RP VARIANTS MET-11; HIS-26; SER-34; MET-91; ARG-94; ILE-107; ILE-120; RP LYS-155; 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 RT ethnically diverse population."; RL Pharmacogenomics 5:895-931(2004). CC -!- FUNCTION: Responsible for the metabolism of many drugs and CC environmental chemicals that it oxidizes. It is involved in the CC metabolism of drugs such as antiarrhythmics, adrenoceptor CC antagonists, and tricyclic antidepressants. CC {ECO:0000269|PubMed:16352597}. CC -!- CATALYTIC ACTIVITY: RH + reduced flavoprotein + O(2) = ROH + CC oxidized flavoprotein + H(2)O. CC -!- COFACTOR: CC Name=heme; Xref=ChEBI:CHEBI:30413; CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Peripheral CC membrane protein. Microsome membrane; 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 Note=No experimental confirmation available.; CC -!- INDUCTION: By pregnancy. CC -!- POLYMORPHISM: Genetic variations in CYP2D6 are the cause of poor CC drug metabolism CYP2D6-related [MIM:608902]. The CYP2D6 gene is CC highly polymorphic. CYP2D6 activity ranges widely within a CC population comprising ultrarapid (UM), extensive (EM), CC intermediate (IM) and poor (PM) metabolizer phenotypes. UM and PM CC are those most at risk for treatment failure or dose-dependent CC drug toxicity, respectively. Of the Caucasian populations of CC Europe and North America, 5%-10% are of the PM phenotype and are CC unable to metabolize the antihypersensitive drug debrisoquine and CC numerous other drugs. CC -!- POLYMORPHISM: Allele CYP2D6*7 was also known as CYP2D6E, allele CC CYP2D6*9 as CYP2D6C, allele CYP2D6*10 as CYP2D6J, allele CYP2D6*17 CC as CYP2D6Z. CC -!- POLYMORPHISM: Isozymes CYP2D6.45 (Lys-155, Cys-296 and Thr-486) CC and CYP2D6.46 (His-26, Lys-155, Cys-296 and Thr-486) are CC functional. CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}. CC -!- WEB RESOURCE: Name=Cytochrome P450 Allele Nomenclature Committee; CC Note=CYP2D6 alleles; CC URL="http://www.cypalleles.ki.se/cyp2d6.htm"; CC -!- WEB RESOURCE: Name=Wikipedia; Note=CYP2D6 entry; CC URL="http://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; CAP58857.1; -; 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 UniGene; Hs.333497; -. DR UniGene; Hs.648256; -. 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 PDBsum; 2F9Q; -. DR PDBsum; 3QM4; -. DR PDBsum; 3TBG; -. DR PDBsum; 3TDA; -. DR ProteinModelPortal; P10635; -. DR SMR; P10635; 48-497. DR STRING; 9606.ENSP00000353820; -. DR BindingDB; P10635; -. DR ChEMBL; CHEMBL289; -. DR DrugBank; DB05812; Abiraterone. DR DrugBank; DB01193; Acebutolol. DR DrugBank; DB00316; Acetaminophen. DR DrugBank; DB01426; Ajmaline. 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; DB00276; Amsacrine. DR DrugBank; DB01435; Antipyrine. DR DrugBank; DB01429; Aprindine. DR DrugBank; DB01274; Arformoterol. DR DrugBank; DB01238; Aripiprazole. DR DrugBank; DB06697; Artemether. DR DrugBank; DB06216; Asenapine. DR DrugBank; DB00637; Astemizole. DR DrugBank; DB00289; Atomoxetine. DR DrugBank; DB01076; Atorvastatin. DR DrugBank; DB00972; Azelastine. DR DrugBank; DB00245; Benzatropine. DR DrugBank; DB06770; Benzyl alcohol. DR DrugBank; DB01244; Bepridil. DR DrugBank; DB00195; Betaxolol. DR DrugBank; DB01128; Bicalutamide. DR DrugBank; DB00810; Biperiden. DR DrugBank; DB00612; Bisoprolol. DR DrugBank; DB00188; Bortezomib. DR DrugBank; DB00835; Brompheniramine. DR DrugBank; DB00297; Bupivacaine. DR DrugBank; DB00921; Buprenorphine. DR DrugBank; DB01156; Bupropion. DR DrugBank; DB00490; Buspirone. DR DrugBank; DB00201; Caffeine. DR DrugBank; DB01197; Captopril. DR DrugBank; DB00748; Carbinoxamine. DR DrugBank; DB00521; Carteolol. DR DrugBank; DB01136; Carvedilol. DR DrugBank; DB00482; Celecoxib. DR DrugBank; DB00567; Cephalexin. DR DrugBank; DB00185; Cevimeline. DR DrugBank; DB00475; Chlordiazepoxide. DR DrugBank; DB00608; Chloroquine. DR DrugBank; DB01114; Chlorphenamine. DR DrugBank; DB00477; Chlorpromazine. DR DrugBank; DB00356; Chlorzoxazone. DR DrugBank; DB00169; Cholecalciferol. 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; DB00283; Clemastine. DR DrugBank; DB04920; Clevidipine. DR DrugBank; DB01242; Clomipramine. DR DrugBank; DB00575; Clonidine. DR DrugBank; DB00257; Clotrimazole. DR DrugBank; DB00363; Clozapine. DR DrugBank; DB00907; Cocaine. DR DrugBank; DB00318; Codeine. DR DrugBank; DB00924; Cyclobenzaprine. DR DrugBank; DB00531; Cyclophosphamide. DR DrugBank; DB00091; Cyclosporine. DR DrugBank; DB06292; Dapagliflozin. DR DrugBank; DB00496; Darifenacin. DR DrugBank; DB04840; Debrisoquin. DR DrugBank; DB00705; Delavirdine. DR DrugBank; DB01151; Desipramine. DR DrugBank; DB00967; Desloratadine. DR DrugBank; DB01234; Dexamethasone. DR DrugBank; DB01191; Dexfenfluramine. DR DrugBank; DB00633; Dexmedetomidine. DR DrugBank; DB06701; Dexmethylphenidate. DR DrugBank; DB01576; Dextroamphetamine. DR DrugBank; DB00514; Dextromethorphan. DR DrugBank; DB00647; Dextropropoxyphene. 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; DB00988; Dopamine. 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; DB00216; Eletriptan. DR DrugBank; DB01228; Encainide. DR DrugBank; DB08899; Enzalutamide. DR DrugBank; DB00751; Epinastine. DR DrugBank; DB00530; Erlotinib. DR DrugBank; DB01175; Escitalopram. DR DrugBank; DB01466; Ethylmorphine. DR DrugBank; DB01628; Etoricoxib. DR DrugBank; DB01023; Felodipine. DR DrugBank; DB06702; Fesoterodine. DR DrugBank; DB00950; Fexofenadine. DR DrugBank; DB08868; Fingolimod. 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; DB00674; Galantamine. DR DrugBank; DB00317; Gefitinib. DR DrugBank; DB01437; Glutethimide. DR DrugBank; DB00889; Granisetron. DR DrugBank; DB01218; Halofantrine. DR DrugBank; DB00502; Haloperidol. DR DrugBank; DB01159; Halothane. DR DrugBank; DB00667; Histamine Phosphate. DR DrugBank; DB00956; Hydrocodone. DR DrugBank; DB00327; Hydromorphone. DR DrugBank; DB01611; Hydroxychloroquine. DR DrugBank; DB01005; Hydroxyurea. DR DrugBank; DB00557; Hydroxyzine. DR DrugBank; DB01177; Idarubicin. DR DrugBank; DB04946; Iloperidone. DR DrugBank; DB00619; Imatinib. DR DrugBank; DB00458; Imipramine. DR DrugBank; DB00224; Indinavir. DR DrugBank; DB00332; Ipratropium bromide. DR DrugBank; DB01029; Irbesartan. DR DrugBank; DB00951; Isoniazid. DR DrugBank; DB01167; Itraconazole. DR DrugBank; DB01026; Ketoconazole. DR DrugBank; DB01235; L-DOPA. DR DrugBank; DB00598; Labetalol. DR DrugBank; DB00448; Lansoprazole. DR DrugBank; DB00528; Lercanidipine. DR DrugBank; DB08918; Levomilnacipran. DR DrugBank; DB00281; Lidocaine. DR DrugBank; DB00589; Lisuride. DR DrugBank; DB01206; Lomustine. DR DrugBank; DB00836; Loperamide. DR DrugBank; DB01601; Lopinavir. DR DrugBank; DB00455; Loratadine. DR DrugBank; DB04871; Lorcaserin. DR DrugBank; DB00227; Lovastatin. DR DrugBank; DB06708; Lumefantrine. DR DrugBank; DB00934; Maprotiline. DR DrugBank; DB00358; Mefloquine. DR DrugBank; DB06691; Mepyramine. DR DrugBank; DB01071; Mequitazine. DR DrugBank; DB00933; Mesoridazine. DR DrugBank; DB00333; Methadone. DR DrugBank; DB01577; Methamphetamine. DR DrugBank; DB00703; Methazolamide. DR DrugBank; DB00763; Methimazole. DR DrugBank; DB01403; Methotrimeprazine. DR DrugBank; DB01028; Methoxyflurane. DR DrugBank; DB06800; Methylnaltrexone. DR DrugBank; DB00422; Methylphenidate. DR DrugBank; DB01107; Methyprylon. DR DrugBank; DB01233; Metoclopramide. DR DrugBank; DB00264; Metoprolol. DR DrugBank; DB00379; Mexiletine. DR DrugBank; DB06148; Mianserin. DR DrugBank; DB01110; Miconazole. DR DrugBank; DB00211; Midodrine. DR DrugBank; DB00834; Mifepristone. DR DrugBank; DB00805; Minaprine. DR DrugBank; DB08893; Mirabegron. DR DrugBank; DB00370; Mirtazapine. DR DrugBank; DB01171; Moclobemide. DR DrugBank; DB00295; Morphine. DR DrugBank; DB00731; Nateglinide. DR DrugBank; DB04861; Nebivolol. DR DrugBank; DB01149; Nefazodone. DR DrugBank; DB00220; Nelfinavir. DR DrugBank; DB00238; Nevirapine. DR DrugBank; DB00627; Niacin. DR DrugBank; DB00622; Nicardipine. DR DrugBank; DB00699; Nicergoline. DR DrugBank; DB00184; Nicotine. DR DrugBank; DB01115; Nifedipine. DR DrugBank; DB04868; Nilotinib. DR DrugBank; DB00336; Nitrofural. DR DrugBank; DB00540; Nortriptyline. DR DrugBank; DB00334; Olanzapine. DR DrugBank; DB00338; Omeprazole. DR DrugBank; DB00904; Ondansetron. DR DrugBank; DB01096; Oxamniquine. DR DrugBank; DB01580; Oxprenolol. DR DrugBank; DB01062; Oxybutynin. DR DrugBank; DB00497; Oxycodone. DR DrugBank; DB01192; Oxymorphone. DR DrugBank; DB01267; Paliperidone. DR DrugBank; DB00377; Palonosetron. DR DrugBank; DB00715; Paroxetine. DR DrugBank; DB06589; Pazopanib. DR DrugBank; DB00738; Pentamidine. DR DrugBank; DB01186; Pergolide. DR DrugBank; DB01074; Perhexiline. DR DrugBank; DB00850; Perphenazine. DR DrugBank; DB00454; Pethidine. DR DrugBank; DB00914; Phenformin. DR DrugBank; DB00191; Phentermine. DR DrugBank; DB01100; Pimozide. DR DrugBank; DB00960; Pindolol. DR DrugBank; DB01132; Pioglitazone. DR DrugBank; DB00592; Piperazine. DR DrugBank; DB01621; Pipotiazine. DR DrugBank; DB08901; Ponatinib. DR DrugBank; DB00175; Pravastatin. DR DrugBank; DB01058; Praziquantel. DR DrugBank; DB01087; Primaquine. DR DrugBank; DB01035; Procainamide. DR DrugBank; DB00433; Prochlorperazine. DR DrugBank; DB00396; Progesterone. DR DrugBank; DB01131; Proguanil. DR DrugBank; DB01069; Promethazine. DR DrugBank; DB01182; Propafenone. DR DrugBank; DB00818; Propofol. DR DrugBank; DB00571; Propranolol. DR DrugBank; DB00344; Protriptyline. DR DrugBank; DB00852; Pseudoephedrine. DR DrugBank; DB00205; Pyrimethamine. 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; DB00409; Remoxipride. DR DrugBank; DB01201; Rifapentine. DR DrugBank; DB00734; Risperidone. DR DrugBank; DB00503; Ritonavir. DR DrugBank; DB00989; Rivastigmine. DR DrugBank; DB00268; Ropinirole. DR DrugBank; DB00296; Ropivacaine. DR DrugBank; DB00412; Rosiglitazone. DR DrugBank; DB05271; Rotigotine. 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; DB00398; Sorafenib. DR DrugBank; DB00259; Sulfanilamide. DR DrugBank; DB06729; Sulfaphenazole. DR DrugBank; DB00675; Tamoxifen. DR DrugBank; DB00706; Tamsulosin. DR DrugBank; DB06204; Tapentadol. DR DrugBank; DB00976; Telithromycin. DR DrugBank; DB06287; Temsirolimus. DR DrugBank; DB00857; Terbinafine. 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; DB01036; Tolterodine. DR DrugBank; DB05109; Trabectedin. DR DrugBank; DB00193; Tramadol. DR DrugBank; DB00752; Tranylcypromine. DR DrugBank; DB00656; Trazodone. DR DrugBank; DB00726; Trimipramine. DR DrugBank; DB00792; Tripelennamine. DR DrugBank; DB00427; Triprolidine. DR DrugBank; DB00209; Trospium. DR DrugBank; DB08881; Vemurafenib. DR DrugBank; DB00285; Venlafaxine. DR DrugBank; DB00661; Verapamil. DR DrugBank; DB06684; Vilazodone. DR DrugBank; DB00570; Vinblastine. DR DrugBank; DB00361; Vinorelbine. DR DrugBank; DB01392; Yohimbine. DR DrugBank; DB00549; Zafirlukast. DR DrugBank; DB00943; Zalcitabine. DR DrugBank; DB00246; Ziprasidone. DR DrugBank; DB00425; Zolpidem. DR PhosphoSite; P10635; -. DR DMDM; 84028191; -. DR PaxDb; P10635; -. DR PRIDE; P10635; -. DR Ensembl; ENST00000359033; ENSP00000351927; ENSG00000100197. [P10635-2] DR Ensembl; ENST00000360608; ENSP00000353820; ENSG00000100197. [P10635-1] DR Ensembl; ENST00000612990; ENSP00000483677; ENSG00000275211. DR GeneID; 1565; -. DR KEGG; hsa:1565; -. DR UCSC; uc003bce.3; human. [P10635-1] DR UCSC; uc003bcf.3; human. [P10635-2] DR CTD; 1565; -. DR GeneCards; GC22M042522; -. DR HGNC; HGNC:2625; CYP2D6. DR HPA; HPA045223; -. DR MIM; 124030; gene. DR MIM; 608902; phenotype. DR neXtProt; NX_P10635; -. DR Orphanet; 240847; Amitriptyline toxicity. DR Orphanet; 240849; Antipsychotics toxicity. DR Orphanet; 240865; Clomipramine toxicity. DR Orphanet; 240867; Codeine toxicity. DR Orphanet; 240883; Imipramine toxicity. DR Orphanet; 240893; Nortriptyline toxicity. DR Orphanet; 240931; Resistance to amitriptyline in the treatment of depression. DR Orphanet; 240933; Resistance to clomipramine in the treatment of depression. DR Orphanet; 240939; Resistance to imipramine in the treatment of depression. DR Orphanet; 240941; Resistance to nortripilline in the treatment of depression. DR Orphanet; 240947; Resistance to tamoxifene in breast cancer. DR Orphanet; 240949; Resistance to trimipramine in the treatment of depression. DR Orphanet; 240951; Resistance to venlafaxine in the treatment of depression. DR Orphanet; 240957; Susceptibility to adverse reaction due to amitriptyline treatment. DR Orphanet; 240959; Susceptibility to adverse reaction due to antipsychotics treatment. DR Orphanet; 240965; Susceptibility to adverse reaction due to clomipramine treatment. DR Orphanet; 240967; Susceptibility to adverse reaction due to codeine treatment. DR Orphanet; 240971; Susceptibility to adverse reaction due to imipramine treatment. DR Orphanet; 240979; Susceptibility to adverse reaction due to nortriptyline treatment. DR Orphanet; 240987; Susceptibility to adverse reaction due to trimipramine treatment. DR Orphanet; 240989; Susceptibility to adverse reaction due to venlafaxine treatment. DR Orphanet; 240915; Trimipramine toxicity. DR Orphanet; 240919; Venlafaxine toxicity. DR PharmGKB; PA128; -. DR eggNOG; COG2124; -. DR GeneTree; ENSGT00760000118775; -. DR HOVERGEN; HBG015789; -. DR InParanoid; P10635; -. DR KO; K17712; -. DR PhylomeDB; P10635; -. DR TreeFam; TF352043; -. DR Reactome; REACT_13425; Miscellaneous substrates. DR Reactome; REACT_13543; Xenobiotics. DR Reactome; REACT_13797; CYP2E1 reactions. DR Reactome; REACT_13814; Fatty acids. DR SABIO-RK; P10635; -. DR EvolutionaryTrace; P10635; -. DR GeneWiki; CYP2D6; -. DR GenomeRNAi; 1565; -. DR NextBio; 6449; -. DR PRO; PR:P10635; -. DR Proteomes; UP000005640; Chromosome 22. DR Proteomes; UP000005640; Unplaced. DR Bgee; P10635; -. DR CleanEx; HS_CYP2D6; -. DR ExpressionAtlas; P10635; baseline. DR Genevestigator; P10635; -. DR GO; GO:0005783; C:endoplasmic reticulum; TAS:BHF-UCL. DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome. DR GO; GO:0005739; C:mitochondrion; IDA:BHF-UCL. DR GO; GO:0008392; F:arachidonic acid epoxygenase activity; IBA:GO_Central. DR GO; GO:0070330; F:aromatase activity; IEA:UniProtKB-EC. DR GO; GO:0008144; F:drug binding; IDA:BHF-UCL. 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:0019825; F:oxygen binding; 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:0009804; P:coumarin metabolic process; IDA:BHF-UCL. DR GO; GO:0042737; P:drug catabolic process; IDA:BHF-UCL. DR GO; GO:0017144; P:drug metabolic process; IDA:BHF-UCL. DR GO; GO:0042738; P:exogenous drug catabolic process; IBA:GO_Central. 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: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:0055114; P:oxidation-reduction process; IDA:BHF-UCL. DR GO; GO:0070989; P:oxidative demethylation; IDA:BHF-UCL. DR GO; GO:0044281; P:small molecule metabolic process; TAS:Reactome. DR GO; GO:0008202; P:steroid metabolic process; IMP:BHF-UCL. DR GO; GO:0006805; P:xenobiotic metabolic process; TAS: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 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; Complete proteome; KW Endoplasmic reticulum; Heme; Iron; Membrane; Metal-binding; Microsome; KW Monooxygenase; Oxidoreductase; Polymorphism; Reference proteome. FT CHAIN 1 497 Cytochrome P450 2D6. FT /FTId=PRO_0000051731. FT METAL 443 443 Iron (heme axial ligand). FT BINDING 301 301 Substrate. {ECO:0000305}. FT VAR_SEQ 118 168 Missing (in isoform 2). FT {ECO:0000303|PubMed:15489334}. FT /FTId=VSP_044486. FT VARIANT 11 11 V -> M (in allele CYP2D6*35; FT dbSNP:rs769258). FT {ECO:0000269|PubMed:15469410}. FT /FTId=VAR_008366. FT VARIANT 26 26 R -> H (in allele CYP2D6*21 and allele FT CYP2D6*46; dbSNP:rs28371696). FT {ECO:0000269|PubMed:15469410, FT ECO:0000269|PubMed:15768052, FT ECO:0000269|Ref.6}. FT /FTId=VAR_008367. FT VARIANT 28 28 R -> C (in allele CYP2D6*22). FT /FTId=VAR_008368. FT VARIANT 34 34 P -> S (in allele CYP2D6*10 and allele FT CYP2D6*14; poor debrisquone metabolism; FT dbSNP:rs1065852). FT {ECO:0000269|PubMed:15469410, FT ECO:0000269|PubMed:8287064}. FT /FTId=VAR_008336. FT VARIANT 42 42 G -> R (in allele CYP2D6*12; impaired FT metabolism of sparteine; FT dbSNP:rs5030862). FT {ECO:0000269|PubMed:8655150}. FT /FTId=VAR_001256. FT VARIANT 85 85 A -> V (in allele CYP2D6*23). FT /FTId=VAR_008369. FT VARIANT 91 91 L -> M (in dbSNP:rs28371703). FT {ECO:0000269|PubMed:15469410}. FT /FTId=VAR_024720. FT VARIANT 94 94 H -> R (in dbSNP:rs28371704). FT {ECO:0000269|PubMed:15469410}. FT /FTId=VAR_024721. FT VARIANT 107 107 T -> I (in allele CYP2D6*17; poor FT debrisquone metabolism; FT dbSNP:rs28371706). FT {ECO:0000269|PubMed:15469410, FT ECO:0000269|PubMed:8971426}. FT /FTId=VAR_008337. FT VARIANT 120 120 F -> I (in dbSNP:rs1135822). FT {ECO:0000269|PubMed:15469410}. FT /FTId=VAR_024722. FT VARIANT 155 155 E -> K (in allele CYP2D6*45A, allele FT CYP2D6*45B and allele CYP2D6*46; FT dbSNP:rs28371710). FT {ECO:0000269|PubMed:15469410, FT ECO:0000269|PubMed:15768052}. FT /FTId=VAR_024723. FT VARIANT 169 169 G -> R (in allele CYP2D6*14; poor FT debrisquone metabolism). FT {ECO:0000269|PubMed:10064570}. FT /FTId=VAR_008338. FT VARIANT 212 212 G -> E (in allele CYP2D6*6B and allele FT CYP2D6*6C; dbSNP:rs5030866). FT {ECO:0000269|PubMed:7868129}. FT /FTId=VAR_008339. FT VARIANT 231 231 L -> P (in dbSNP:rs17002853). FT /FTId=VAR_045679. FT VARIANT 237 237 A -> S (in allele CYP2D6*33; FT dbSNP:rs28371717). FT {ECO:0000269|PubMed:15469410}. FT /FTId=VAR_008370. FT VARIANT 281 281 Missing (in allele CYP2D6*9). FT {ECO:0000269|PubMed:1844820}. FT /FTId=VAR_008347. FT VARIANT 296 296 R -> C (in allele CYP2D6*2, allele FT CYP2D6*12, allele CYP2D6*14, allele FT CYP2D6*17, allele CYP2D6*45A, allele FT CYP2D6*45B and allele CYP2D6*46; FT dbSNP:rs16947). FT {ECO:0000269|PubMed:10591208, FT ECO:0000269|PubMed:15469410, FT ECO:0000269|PubMed:15489334, FT ECO:0000269|PubMed:15768052}. FT /FTId=VAR_008340. FT VARIANT 297 297 I -> L (in allele CYP2D6*24). FT /FTId=VAR_008371. FT VARIANT 300 300 A -> G (in dbSNP:rs1058170). FT /FTId=VAR_045680. FT VARIANT 311 311 S -> L (in dbSNP:rs1800754). FT /FTId=VAR_014633. FT VARIANT 324 324 H -> P (in allele CYP2D6*7; loss of FT activity; dbSNP:rs5030867). FT {ECO:0000269|PubMed:7845481}. FT /FTId=VAR_008348. FT VARIANT 329 329 R -> L (in dbSNP:rs3915951). FT /FTId=VAR_059150. FT VARIANT 343 343 R -> G (in allele CYP2D6*25). FT /FTId=VAR_008372. FT VARIANT 365 365 R -> H (in dbSNP:rs1058172). FT /FTId=VAR_045681. FT VARIANT 369 369 I -> T (in allele CYP2D6*26). FT /FTId=VAR_008373. FT VARIANT 373 373 G -> S (in dbSNP:rs2856959). FT /FTId=VAR_059151. FT VARIANT 410 410 E -> K (in allele CYP2D6*27). FT /FTId=VAR_008374. FT VARIANT 418 418 E -> K. {ECO:0000269|PubMed:15469410}. FT /FTId=VAR_024724. FT VARIANT 469 469 P -> A (in dbSNP:rs1135833). FT {ECO:0000269|PubMed:15469410}. FT /FTId=VAR_024725. FT VARIANT 478 478 H -> Y (in dbSNP:rs28371735). FT {ECO:0000269|PubMed:15469410}. FT /FTId=VAR_024726. FT VARIANT 486 486 S -> T (in allele CYP2D6*2, allele FT CYP2D6*10, allele CYP2D6*12, allele FT CYP2D6*14, allele CYP2D6*17, allele FT CYP2D6*45A, allele CYP2D6*45B and allele FT CYP2D6*46; impaired metabolism of FT sparteine; dbSNP:rs1135840). FT {ECO:0000269|PubMed:10591208, FT ECO:0000269|PubMed:15469410, FT ECO:0000269|PubMed:15489334, FT ECO:0000269|PubMed:15768052, FT ECO:0000269|PubMed:8287064}. FT /FTId=VAR_008341. FT CONFLICT 374 374 V -> M (in Ref. 1; AAA52153 and 2; FT CAA30807). {ECO:0000305}. FT TURN 41 43 {ECO:0000244|PDB:3TBG}. FT HELIX 46 48 {ECO:0000244|PDB:3TBG}. FT HELIX 54 65 {ECO:0000244|PDB:3TBG}. FT STRAND 67 73 {ECO:0000244|PDB:3TBG}. FT STRAND 76 81 {ECO:0000244|PDB:3TBG}. FT HELIX 83 91 {ECO:0000244|PDB:3TBG}. FT TURN 92 94 {ECO:0000244|PDB:3TBG}. FT HELIX 95 97 {ECO:0000244|PDB:3TBG}. FT HELIX 105 110 {ECO:0000244|PDB:3TBG}. FT TURN 118 121 {ECO:0000244|PDB:3QM4}. FT HELIX 126 141 {ECO:0000244|PDB:3TBG}. FT TURN 143 145 {ECO:0000244|PDB:3TDA}. FT HELIX 148 165 {ECO:0000244|PDB:3TBG}. FT TURN 166 169 {ECO:0000244|PDB:3TBG}. FT HELIX 175 191 {ECO:0000244|PDB:3TBG}. FT HELIX 200 214 {ECO:0000244|PDB:3TBG}. FT HELIX 219 226 {ECO:0000244|PDB:3TBG}. FT HELIX 228 232 {ECO:0000244|PDB:3TBG}. FT HELIX 234 240 {ECO:0000244|PDB:3TBG}. FT HELIX 242 261 {ECO:0000244|PDB:3TBG}. FT HELIX 271 281 {ECO:0000244|PDB:3TBG}. FT TURN 282 284 {ECO:0000244|PDB:3TBG}. FT HELIX 292 323 {ECO:0000244|PDB:3TBG}. FT HELIX 325 338 {ECO:0000244|PDB:3TBG}. FT STRAND 341 343 {ECO:0000244|PDB:3TBG}. FT HELIX 347 350 {ECO:0000244|PDB:3TBG}. FT HELIX 354 367 {ECO:0000244|PDB:3TBG}. FT STRAND 370 372 {ECO:0000244|PDB:3QM4}. FT STRAND 382 384 {ECO:0000244|PDB:3TBG}. FT STRAND 387 389 {ECO:0000244|PDB:3TBG}. FT STRAND 394 397 {ECO:0000244|PDB:3TBG}. FT HELIX 399 403 {ECO:0000244|PDB:3TBG}. FT TURN 406 408 {ECO:0000244|PDB:3TBG}. FT STRAND 409 411 {ECO:0000244|PDB:3TBG}. FT HELIX 417 420 {ECO:0000244|PDB:3TBG}. FT HELIX 446 463 {ECO:0000244|PDB:3TBG}. FT STRAND 464 467 {ECO:0000244|PDB:3TBG}. FT STRAND 479 487 {ECO:0000244|PDB:3TBG}. FT STRAND 492 496 {ECO:0000244|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 //