ID CP2B6_HUMAN Reviewed; 491 AA. AC P20813; B4DWP3; Q2V565; Q9UK46; DT 01-FEB-1991, integrated into UniProtKB/Swiss-Prot. DT 01-FEB-1991, sequence version 1. DT 10-OCT-2018, entry version 197. DE RecName: Full=Cytochrome P450 2B6; DE EC=1.14.13.-; DE AltName: Full=1,4-cineole 2-exo-monooxygenase; DE AltName: Full=CYPIIB6; DE AltName: Full=Cytochrome P450 IIB1; GN Name=CYP2B6; 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). RC TISSUE=Liver; RX PubMed=2573390; DOI=10.1021/bi00444a029; RA Yamano S., Nhamburo P.T., Aoyama T., Meyer U.A., Inaba T., Kalow W., RA Gelboin H.V., McBride O.W., Gonzalez F.J.; RT "cDNA cloning and sequence and cDNA-directed expression of human P450 RT IIB1: identification of a normal and two variant cDNAs derived from RT the CYP2B locus on chromosome 19 and differential expression of the RT IIB mRNAs in human liver."; RL Biochemistry 28:7340-7348(1989). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANTS ALA-167; HIS-172 RP AND ARG-262. RC TISSUE=Liver; RA Zhuge J., Qian Y., Xie H., Yu Y.; RT "Sequence of a new human cytochrome P450-2B6 cDNA."; RL Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Colon; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS CYS-22; SER-26; RP GLY-28; SER-29; HIS-172; ARG-262; LYS-289; SER-306; THR-328 AND RP CYS-487. RG NIEHS SNPs program; RL Submitted (NOV-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15057824; DOI=10.1038/nature02399; RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., RA Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., RA Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., RA Caenepeel S., Carrano A.V., Caoile C., Chan Y.M., Christensen M., RA Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., RA Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., RA Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., RA Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., RA Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., RA Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., RA Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., RA Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., RA Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., RA Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., RA Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., RA Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., RA Rubin E.M., Lucas S.M.; RT "The DNA sequence and biology of human chromosome 19."; RL Nature 428:529-535(2004). RN [6] RP NUCLEOTIDE SEQUENCE [MRNA] OF 26-491 (ISOFORM 1). RX PubMed=2813061; DOI=10.1093/nar/17.20.8241; RA Miles J.S., McLaren A.W., Wolf C.R.; RT "Alternative splicing in the human cytochrome P450IIB6 gene generates RT a high level of aberrant messages."; RL Nucleic Acids Res. 17:8241-8255(1989). RN [7] RP TISSUE SPECIFICITY. RX PubMed=10768437; DOI=10.1016/S0140-6736(00)99016-0; RA Thum T., Borlak J.; RT "Gene expression in distinct regions of the heart."; RL Lancet 355:979-983(2000). RN [8] RP CATALYTIC ACTIVITY, FUNCTION AS 1,4-CINEOLE 2-EXO-MONOOXYGENASE, AND RP BIOPHYSICOCHEMICAL PROPERTIES. RX PubMed=11695850; DOI=10.1080/00498250110065595; RA Miyazawa M., Shindo M., Shimada T.; RT "Roles of cytochrome P450 3A enzymes in the 2-hydroxylation of 1,4- RT cineole, a monoterpene cyclic ether, by rat and human liver RT microsomes."; RL Xenobiotica 31:713-723(2001). RN [9] 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., RA Wang L., Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human RT liver phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [10] RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 30-491 OF VARIANT ARG-262 IN RP COMPLEX WITH HEME AND SYNTHETIC INHIBITOR, FUNCTION, COFACTOR, AND RP IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=20061448; DOI=10.1124/mol.109.062570; RA Gay S.C., Shah M.B., Talakad J.C., Maekawa K., Roberts A.G., RA Wilderman P.R., Sun L., Yang J.Y., Huelga S.C., Hong W.X., Zhang Q., RA Stout C.D., Halpert J.R.; RT "Crystal structure of a cytochrome P450 2B6 genetic variant in complex RT with the inhibitor 4-(4-chlorophenyl)imidazole at 2.0-A resolution."; RL Mol. Pharmacol. 77:529-538(2010). RN [11] RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 30-491 OF VARIANT ARG-262 IN RP COMPLEX WITH HEME AND SYNTHETIC INHIBITOR, FUNCTION, AND COFACTOR. RX PubMed=21875942; DOI=10.1124/mol.111.074427; RA Shah M.B., Pascual J., Zhang Q., Stout C.D., Halpert J.R.; RT "Structures of cytochrome P450 2B6 bound to 4-benzylpyridine and 4-(4- RT nitrobenzyl)pyridine: insight into inhibitor binding and rearrangement RT of active site side chains."; RL Mol. Pharmacol. 80:1047-1055(2011). RN [12] RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 30-491 IN COMPLEX WITH HEME RP AND AMLODIPINE, FUNCTION, AND COFACTOR. RX PubMed=22909231; DOI=10.1021/bi300894z; RA Shah M.B., Wilderman P.R., Pascual J., Zhang Q., Stout C.D., RA Halpert J.R.; RT "Conformational adaptation of human cytochrome P450 2B6 and rabbit RT cytochrome P450 2B4 revealed upon binding multiple amlodipine RT molecules."; RL Biochemistry 51:7225-7238(2012). RN [13] RP POLYMORPHISM, INVOLVEMENT IN EFAVIRENZ POOR METABOLISM, AND RP SUSCEPTIBILITY TO EFAVIRENZ TOXICITY. RX PubMed=15622315; RA Haas D.W., Ribaudo H.J., Kim R.B., Tierney C., Wilkinson G.R., RA Gulick R.M., Clifford D.B., Hulgan T., Marzolini C., Acosta E.P.; RT "Pharmacogenetics of efavirenz and central nervous system side RT effects: an Adult AIDS Clinical Trials Group study."; RL AIDS 18:2391-2400(2004). RN [14] RP POLYMORPHISM, INVOLVEMENT IN EFAVIRENZ POOR METABOLISM, AND RP SUSCEPTIBILITY TO EFAVIRENZ TOXICITY. RX PubMed=20639527; DOI=10.1093/jac/dkq260; RA Carr D.F., la Porte C.J., Pirmohamed M., Owen A., Cortes C.P.; RT "Haplotype structure of CYP2B6 and association with plasma efavirenz RT concentrations in a Chilean HIV cohort."; RL J. Antimicrob. Chemother. 65:1889-1893(2010). RN [15] RP POLYMORPHISM, INVOLVEMENT IN EFAVIRENZ POOR METABOLISM, AND RP SUSCEPTIBILITY TO EFAVIRENZ TOXICITY. RX PubMed=20860463; DOI=10.2217/pgs.10.94; RA Elens L., Vandercam B., Yombi J.C., Lison D., Wallemacq P., RA Haufroid V.; RT "Influence of host genetic factors on efavirenz plasma and RT intracellular pharmacokinetics in HIV-1-infected patients."; RL Pharmacogenomics 11:1223-1234(2010). RN [16] RP VARIANT HIS-172. RX PubMed=11243870; DOI=10.1006/bbrc.2001.4524; RA Ariyoshi N., Miyazaki M., Toide K., Sawamura Y.I., Kamataki T.; RT "A single nucleotide polymorphism of CYP2b6 found in Japanese enhances RT catalytic activity by autoactivation."; RL Biochem. Biophys. Res. Commun. 281:1256-1260(2001). RN [17] RP VARIANTS CYS-22; HIS-172; ARG-259; ARG-262 AND CYS-487. RX PubMed=11470993; DOI=10.1097/00008571-200107000-00004; RA Lang T., Klein K., Fischer J., Nussler A.K., Neuhaus P., Hofmann U., RA Eichelbaum M., Schwab M., Zanger U.M.; RT "Extensive genetic polymorphism in the human CYP2B6 gene with impact RT on expression and function in human liver."; RL Pharmacogenetics 11:399-415(2001). RN [18] RP CHARACTERIZATION OF VARIANTS CYS-22; HIS-172; ARG-259; ARG-262 AND RP CYS-487. RX PubMed=12642465; DOI=10.1124/dmd.31.4.398; RA Jinno H., Tanaka-Kagawa T., Ohno A., Makino Y., Matsushima E., RA Hanioka N., Ando M.; RT "Functional characterization of cytochrome P450 2B6 allelic RT variants."; RL Drug Metab. Dispos. 31:398-403(2003). RN [19] RP VARIANTS CYS-22; ALA-167; HIS-172 AND CYS-487. RX PubMed=12721789; DOI=10.1007/s10038-003-0021-7; RA Saito S., Iida A., Sekine A., Kawauchi S., Higuchi S., Ogawa C., RA Nakamura Y.; RT "Catalog of 680 variations among eight cytochrome p450 (CYP) genes, RT nine esterase genes, and two other genes in the Japanese population."; RL J. Hum. Genet. 48:249-270(2003). RN [20] RP VARIANTS CYS-22; GLU-139; HIS-172 AND CYS-487. RX PubMed=14551287; DOI=10.1124/jpet.103.054866; RA Lamba V., Lamba J., Yasuda K., Strom S., Davila J., Hancock M.L., RA Fackenthal J.D., Rogan P.K., Ring B., Wrighton S.A., Schuetz E.G.; RT "Hepatic CYP2B6 expression: gender and ethnic differences and RT relationship to CYP2B6 genotype and CAR (constitutive androstane RT receptor) expression."; RL J. Pharmacol. Exp. Ther. 307:906-922(2003). RN [21] RP VARIANTS LEU-21; VAL-46; GLU-99; GLU-139; GLN-140 AND ASN-391. RX PubMed=15190123; DOI=10.1124/jpet.104.068973; RA Lang T., Klein K., Richter T., Zibat A., Kerb R., Eichelbaum M., RA Schwab M., Zanger U.M.; RT "Multiple novel nonsynonymous CYP2B6 gene polymorphisms in Caucasians: RT demonstration of phenotypic null alleles."; RL J. Pharmacol. Exp. Ther. 311:34-43(2004). RN [22] RP VARIANTS CYS-22; HIS-172; ARG-262; THR-328 AND CYS-487. 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: Cytochromes P450 are a group of heme-thiolate CC monooxygenases. In liver microsomes, this enzyme is involved in an CC NADPH-dependent electron transport pathway. It oxidizes a variety CC of structurally unrelated compounds, including steroids, fatty CC acids, and xenobiotics. Acts as a 1,4-cineole 2-exo-monooxygenase. CC {ECO:0000269|PubMed:11695850, ECO:0000269|PubMed:20061448, CC ECO:0000269|PubMed:21875942, ECO:0000269|PubMed:22909231}. CC -!- CATALYTIC ACTIVITY: 1,4-cineole + NADPH + O(2) = 2-exo-hydroxy- CC 1,4-cineole + NADP(+) + H(2)O. {ECO:0000269|PubMed:11695850}. CC -!- COFACTOR: CC Name=heme; Xref=ChEBI:CHEBI:30413; CC Evidence={ECO:0000269|PubMed:20061448, CC ECO:0000269|PubMed:21875942, ECO:0000269|PubMed:22909231}; CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=360 uM for 1,4-cineole {ECO:0000269|PubMed:11695850}; CC Vmax=3.4 nmol/min/nmol enzyme toward 2-exo-hydroxy-1,4-cineole CC {ECO:0000269|PubMed:11695850}; 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=P20813-1; Sequence=Displayed; CC Name=2; CC IsoId=P20813-2; Sequence=VSP_055571, VSP_055572; CC Note=No experimental confirmation available.; CC -!- TISSUE SPECIFICITY: Expressed in liver, lung and heart right CC ventricle. {ECO:0000269|PubMed:10768437}. CC -!- INDUCTION: By phenobarbital. CC -!- PTM: Phosphorylation is accompanied by a decrease in enzyme CC activity. {ECO:0000250}. CC -!- POLYMORPHISM: Genetic variations in CYP2B6 are responsible for CC poor metabolism of efavirenz and, therefore, susceptibility to CC efavirenz toxicity in the central nervous system [MIM:614546]. CC Efavirenz is a non-nucleoside reverse transcriptase inhibitor CC frequently prescribed with 2 nucleoside reverse transcriptase CC inhibitors as initial therapy for human immunodeficiency virus CC (HIV) infection. Up to half of patients treated with efavirenz, CC experience side effects in the central nervous system, including CC dizziness, insomnia, impaired concentration, somnolence, and CC abnormal dreams. Severe depression, aggressive behavior, and CC paranoid or manic reactions may also occur, depending on efavirenz CC concentration in the plasma. CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}. CC -!- WEB RESOURCE: Name=Cytochrome P450 Allele Nomenclature Committee; CC Note=CYP2B6 alleles; CC URL="http://www.cypalleles.ki.se/cyp2b6.htm"; CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/cyp2b6/"; 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; M29874; AAA52144.1; -; mRNA. DR EMBL; AF182277; AAF13602.1; -; mRNA. DR EMBL; AK301620; BAG63105.1; -; mRNA. DR EMBL; DQ298753; ABB84469.1; -; Genomic_DNA. DR EMBL; AC023172; AAF32444.1; -; Genomic_DNA. DR EMBL; AC011541; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; X13494; -; NOT_ANNOTATED_CDS; mRNA. DR CCDS; CCDS12570.1; -. [P20813-1] DR PIR; A32969; A32969. DR RefSeq; NP_000758.1; NM_000767.4. [P20813-1] DR RefSeq; XP_011524852.1; XM_011526550.2. DR UniGene; Hs.1360; -. DR PDB; 3IBD; X-ray; 2.00 A; A=30-491. DR PDB; 3QOA; X-ray; 2.10 A; A=27-491. DR PDB; 3QU8; X-ray; 2.80 A; A/B/C/D/E/F=27-491. DR PDB; 3UA5; X-ray; 2.80 A; A/B=27-491. DR PDB; 4I91; X-ray; 2.00 A; A=27-491. DR PDB; 4RQL; X-ray; 2.10 A; A/B=27-491. DR PDB; 4RRT; X-ray; 2.20 A; A/B=27-491. DR PDB; 4ZV8; X-ray; 2.24 A; A=30-491. DR PDB; 5UAP; X-ray; 2.03 A; A/B=20-491. DR PDB; 5UDA; X-ray; 1.93 A; A/B=20-491. DR PDB; 5UEC; X-ray; 2.27 A; A=20-491. DR PDB; 5UFG; X-ray; 1.76 A; A=20-491. DR PDB; 5WBG; X-ray; 2.99 A; A/B/C/D/E/F=20-491. DR PDBsum; 3IBD; -. DR PDBsum; 3QOA; -. DR PDBsum; 3QU8; -. DR PDBsum; 3UA5; -. DR PDBsum; 4I91; -. DR PDBsum; 4RQL; -. DR PDBsum; 4RRT; -. DR PDBsum; 4ZV8; -. DR PDBsum; 5UAP; -. DR PDBsum; 5UDA; -. DR PDBsum; 5UEC; -. DR PDBsum; 5UFG; -. DR PDBsum; 5WBG; -. DR ProteinModelPortal; P20813; -. DR SMR; P20813; -. DR BioGrid; 107933; 4. DR STRING; 9606.ENSP00000324648; -. DR BindingDB; P20813; -. DR ChEMBL; CHEMBL4729; -. DR DrugBank; DB08369; 1-(biphenyl-4-ylmethyl)-1H-imidazole. DR DrugBank; DB02974; 4-(4-Chlorophenyl)Imidazole. DR DrugBank; DB00321; Amitriptyline. DR DrugBank; DB00381; Amlodipine. DR DrugBank; DB00701; Amprenavir. DR DrugBank; DB01435; Antipyrine. DR DrugBank; DB06413; Armodafinil. DR DrugBank; DB06697; Artemether. DR DrugBank; DB01076; Atorvastatin. DR DrugBank; DB00972; Azelastine. DR DrugBank; DB04975; Banoxantrone. DR DrugBank; DB00865; Benzphetamine. DR DrugBank; DB06770; Benzyl alcohol. DR DrugBank; DB04794; Bifonazole. DR DrugBank; DB00835; Brompheniramine. DR DrugBank; DB01156; Bupropion. DR DrugBank; DB00564; Carbamazepine. DR DrugBank; DB00748; Carbinoxamine. DR DrugBank; DB00439; Cerivastatin. DR DrugBank; DB00169; Cholecalciferol. DR DrugBank; DB00568; Cinnarizine. DR DrugBank; DB00604; Cisapride. DR DrugBank; DB00515; Cisplatin. DR DrugBank; DB00215; Citalopram. DR DrugBank; DB00349; Clobazam. DR DrugBank; DB00636; Clofibrate. DR DrugBank; DB00758; Clopidogrel. DR DrugBank; DB01559; Clotiazepam. DR DrugBank; DB00257; Clotrimazole. DR DrugBank; DB01394; Colchicine. DR DrugBank; DB05219; Crisaborole. DR DrugBank; DB08865; Crizotinib. DR DrugBank; DB04664; Cyclohexyl-pentyl-maltoside. DR DrugBank; DB00531; Cyclophosphamide. DR DrugBank; DB01151; Desipramine. DR DrugBank; DB01234; Dexamethasone. DR DrugBank; DB00514; Dextromethorphan. DR DrugBank; DB00829; Diazepam. DR DrugBank; DB00586; Diclofenac. DR DrugBank; DB01075; Diphenhydramine. DR DrugBank; DB01184; Domperidone. DR DrugBank; DB00997; Doxorubicin. DR DrugBank; DB00625; Efavirenz. DR DrugBank; DB08899; Enzalutamide. DR DrugBank; DB00751; Epinastine. DR DrugBank; DB00199; Erythromycin. DR DrugBank; DB00655; Estrone. DR DrugBank; DB00898; Ethanol. DR DrugBank; DB01466; Ethylmorphine. DR DrugBank; DB04841; Flunarizine. DR DrugBank; DB01544; Flunitrazepam. DR DrugBank; DB00472; Fluoxetine. DR DrugBank; DB01095; Fluvastatin. DR DrugBank; DB00176; Fluvoxamine. DR DrugBank; DB01320; Fosphenytoin. DR DrugBank; DB01159; Halothane. DR DrugBank; DB09054; Idelalisib. DR DrugBank; DB01181; Ifosfamide. DR DrugBank; DB00458; Imipramine. DR DrugBank; DB00762; Irinotecan. DR DrugBank; DB00753; Isoflurane. DR DrugBank; DB01167; Itraconazole. DR DrugBank; DB09570; Ixazomib. DR DrugBank; DB01221; Ketamine. DR DrugBank; DB06738; Ketobemidone. DR DrugBank; DB01026; Ketoconazole. DR DrugBank; DB00281; Lidocaine. DR DrugBank; DB00836; Loperamide. DR DrugBank; DB01601; Lopinavir. DR DrugBank; DB04871; Lorcaserin. DR DrugBank; DB09280; Lumacaftor. DR DrugBank; DB00772; Malathion. DR DrugBank; DB01043; Memantine. DR DrugBank; DB00532; Mephenytoin. DR DrugBank; DB04817; Metamizole. DR DrugBank; DB00333; Methadone. DR DrugBank; DB00763; Methimazole. DR DrugBank; DB01028; Methoxyflurane. DR DrugBank; DB00849; Methylphenobarbital. DR DrugBank; DB06710; Methyltestosterone. DR DrugBank; DB00379; Mexiletine. DR DrugBank; DB06148; Mianserin. DR DrugBank; DB01110; Miconazole. DR DrugBank; DB00683; Midazolam. DR DrugBank; DB00745; Modafinil. DR DrugBank; DB00220; Nelfinavir. DR DrugBank; DB00238; Nevirapine. DR DrugBank; DB00622; Nicardipine. DR DrugBank; DB00184; Nicotine. DR DrugBank; DB01115; Nifedipine. DR DrugBank; DB04868; Nilotinib. DR DrugBank; DB00435; Nitric Oxide. DR DrugBank; DB09074; Olaparib. DR DrugBank; DB01173; Orphenadrine. DR DrugBank; DB04938; Ospemifene. DR DrugBank; DB00715; Paroxetine. DR DrugBank; DB01074; Perhexiline. DR DrugBank; DB04930; Permethrin. DR DrugBank; DB00850; Perphenazine. DR DrugBank; DB00454; Pethidine. DR DrugBank; DB03575; Phencyclidine. DR DrugBank; DB01174; Phenobarbital. DR DrugBank; DB00252; Phenytoin. DR DrugBank; DB06209; Prasugrel. DR DrugBank; DB00794; Primidone. DR DrugBank; DB01069; Promethazine. DR DrugBank; DB00818; Propofol. DR DrugBank; DB01589; Quazepam. DR DrugBank; DB00908; Quinidine. DR DrugBank; DB00481; Raloxifene. DR DrugBank; DB08896; Regorafenib. DR DrugBank; DB01045; Rifampicin. DR DrugBank; DB08864; Rilpivirine. DR DrugBank; DB00503; Ritonavir. DR DrugBank; DB06176; Romidepsin. DR DrugBank; DB00296; Ropivacaine. DR DrugBank; DB00778; Roxithromycin. DR DrugBank; DB01037; Selegiline. DR DrugBank; DB01104; Sertraline. DR DrugBank; DB01236; Sevoflurane. DR DrugBank; DB00641; Simvastatin. DR DrugBank; DB00398; Sorafenib. DR DrugBank; DB06729; Sulfaphenazole. DR DrugBank; DB01138; Sulfinpyrazone. DR DrugBank; DB00675; Tamoxifen. DR DrugBank; DB00231; Temazepam. DR DrugBank; DB00624; Testosterone. DR DrugBank; DB04572; Thiotepa. DR DrugBank; DB00208; Ticlopidine. DR DrugBank; DB00193; Tramadol. DR DrugBank; DB00755; Tretinoin. DR DrugBank; DB00197; Troglitazone. DR DrugBank; DB00313; Valproic Acid. DR DrugBank; DB00285; Venlafaxine. DR DrugBank; DB00661; Verapamil. DR DrugBank; DB09068; Vortioxetine. DR GuidetoPHARMACOLOGY; 1324; -. DR SwissLipids; SLP:000001346; -. DR iPTMnet; P20813; -. DR PhosphoSitePlus; P20813; -. DR BioMuta; CYP2B6; -. DR DMDM; 117205; -. DR EPD; P20813; -. DR PaxDb; P20813; -. DR PeptideAtlas; P20813; -. DR PRIDE; P20813; -. DR ProteomicsDB; 53803; -. DR Ensembl; ENST00000324071; ENSP00000324648; ENSG00000197408. [P20813-1] DR Ensembl; ENST00000643956; ENSP00000495579; ENSG00000197408. [P20813-1] DR GeneID; 1555; -. DR KEGG; hsa:1555; -. DR UCSC; uc002opr.2; human. [P20813-1] DR CTD; 1555; -. DR DisGeNET; 1555; -. DR EuPathDB; HostDB:ENSG00000197408.8; -. DR GeneCards; CYP2B6; -. DR HGNC; HGNC:2615; CYP2B6. DR HPA; CAB033866; -. DR HPA; HPA048124; -. DR HPA; HPA062973; -. DR MalaCards; CYP2B6; -. DR MIM; 123930; gene. DR MIM; 614546; phenotype. DR neXtProt; NX_P20813; -. DR OpenTargets; ENSG00000197408; -. DR Orphanet; 240869; Efavirenz toxicity. DR PharmGKB; PA123; -. DR eggNOG; KOG0156; Eukaryota. DR eggNOG; COG2124; LUCA. DR GeneTree; ENSGT00880000137861; -. DR HOGENOM; HOG000036992; -. DR HOVERGEN; HBG015789; -. DR InParanoid; P20813; -. DR KO; K17709; -. DR OMA; HTSFRGY; -. DR OrthoDB; EOG091G0BT8; -. DR PhylomeDB; P20813; -. DR TreeFam; TF352043; -. DR BioCyc; MetaCyc:HS09587-MONOMER; -. DR BRENDA; 1.14.14.1; 2681. DR Reactome; R-HSA-211935; Fatty acids. DR Reactome; R-HSA-211981; Xenobiotics. DR Reactome; R-HSA-211999; CYP2E1 reactions. DR SABIO-RK; P20813; -. DR SIGNOR; P20813; -. DR EvolutionaryTrace; P20813; -. DR GeneWiki; CYP2B6; -. DR GenomeRNAi; 1555; -. DR PRO; PR:P20813; -. DR Proteomes; UP000005640; Chromosome 19. DR Bgee; ENSG00000197408; Expressed in 75 organ(s), highest expression level in right lobe of liver. DR CleanEx; HS_CYP2B6; -. DR ExpressionAtlas; P20813; baseline and differential. DR Genevisible; P20813; HS. DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome. DR GO; GO:0031090; C:organelle membrane; IEA:UniProtKB-SubCell. DR GO; GO:0008392; F:arachidonic acid epoxygenase activity; IBA:GO_Central. 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: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; IEA:InterPro. DR GO; GO:0008395; F:steroid hydroxylase activity; IBA:GO_Central. DR GO; GO:0042180; P:cellular ketone metabolic process; IDA:BHF-UCL. DR GO; GO:0017144; P:drug metabolic process; IDA:BHF-UCL. DR GO; GO:0019373; P:epoxygenase P450 pathway; IBA:GO_Central. DR GO; GO:0042738; P:exogenous drug catabolic process; IDA:BHF-UCL. DR GO; GO:0055114; P:oxidation-reduction process; IDA:BHF-UCL. DR GO; GO:0008202; P:steroid metabolic process; IMP:BHF-UCL. DR GO; GO:0006805; P:xenobiotic metabolic process; IDA:UniProtKB. 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; IPR008068; Cyt_P450_E_grp-I_CYP2B-like. DR InterPro; IPR036396; Cyt_P450_sf. DR Pfam; PF00067; p450; 1. DR PRINTS; PR00463; EP450I. DR PRINTS; PR01685; EP450ICYP2B. 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; NADP; Oxidoreductase; Phosphoprotein; Polymorphism; KW Reference proteome. FT CHAIN 1 491 Cytochrome P450 2B6. FT /FTId=PRO_0000051683. FT METAL 436 436 Iron (heme axial ligand). FT MOD_RES 128 128 Phosphoserine; by PKA. {ECO:0000250}. FT VAR_SEQ 1 57 MELSVLLFLALLTGLLLLLVQRHPNTHDRLPPGPRPLPLLG FT NLLQMDRRGLLKSFLR -> MRCMLTNSHPWCGCDWQ (in FT isoform 2). FT {ECO:0000303|PubMed:14702039}. FT /FTId=VSP_055571. FT VAR_SEQ 162 321 Missing (in isoform 2). FT {ECO:0000303|PubMed:14702039}. FT /FTId=VSP_055572. FT VARIANT 21 21 Q -> L (in allele CYP2B6*10; FT dbSNP:rs34883432). FT {ECO:0000269|PubMed:15190123}. FT /FTId=VAR_023563. FT VARIANT 22 22 R -> C (in allele CYP2B6*2 and allele FT CYP2B6*10; dbSNP:rs8192709). FT {ECO:0000269|PubMed:11470993, FT ECO:0000269|PubMed:12642465, FT ECO:0000269|PubMed:12721789, FT ECO:0000269|PubMed:14551287, FT ECO:0000269|PubMed:15469410, FT ECO:0000269|Ref.4}. FT /FTId=VAR_016927. FT VARIANT 26 26 T -> S (in dbSNP:rs33973337). FT {ECO:0000269|Ref.4}. FT /FTId=VAR_025206. FT VARIANT 28 28 D -> G (in dbSNP:rs33980385). FT {ECO:0000269|Ref.4}. FT /FTId=VAR_025207. FT VARIANT 29 29 R -> P (in dbSNP:rs34284776). FT /FTId=VAR_033819. FT VARIANT 29 29 R -> S (in dbSNP:rs33926104). FT {ECO:0000269|Ref.4}. FT /FTId=VAR_025208. FT VARIANT 46 46 M -> V (in allele CYP2B6*11; FT dbSNP:rs35303484). FT {ECO:0000269|PubMed:15190123}. FT /FTId=VAR_023564. FT VARIANT 99 99 G -> E (in allele CYP2B6*12; FT dbSNP:rs36060847). FT {ECO:0000269|PubMed:15190123}. FT /FTId=VAR_023565. FT VARIANT 139 139 K -> E (in allele CYP2B6*8 and allele FT CYP2B6*13; dbSNP:rs12721655). FT {ECO:0000269|PubMed:14551287, FT ECO:0000269|PubMed:15190123}. FT /FTId=VAR_016948. FT VARIANT 140 140 R -> Q (in allele CYP2B6*14; FT dbSNP:rs35773040). FT {ECO:0000269|PubMed:15190123}. FT /FTId=VAR_023566. FT VARIANT 167 167 P -> A (in dbSNP:rs3826711). FT {ECO:0000269|PubMed:12721789, FT ECO:0000269|Ref.2}. FT /FTId=VAR_016924. FT VARIANT 172 172 Q -> H (in allele CYP2B6*6, allele FT CYP2B6*7, allele CYP2B6*9 and allele FT CYP2B6*13; dbSNP:rs3745274). FT {ECO:0000269|PubMed:11243870, FT ECO:0000269|PubMed:11470993, FT ECO:0000269|PubMed:12642465, FT ECO:0000269|PubMed:12721789, FT ECO:0000269|PubMed:14551287, FT ECO:0000269|PubMed:15469410, FT ECO:0000269|Ref.2, ECO:0000269|Ref.4}. FT /FTId=VAR_016925. FT VARIANT 259 259 S -> R (in allele CYP2B6*3; FT dbSNP:rs45482602). FT {ECO:0000269|PubMed:11470993, FT ECO:0000269|PubMed:12642465}. FT /FTId=VAR_016928. FT VARIANT 262 262 K -> R (in allele CYP2B6*4, allele FT CYP2B6*6, allele CYP2B6*7 and allele FT CYP2B6*13; slight decrease in activity; FT dbSNP:rs2279343). FT {ECO:0000269|PubMed:11470993, FT ECO:0000269|PubMed:12642465, FT ECO:0000269|PubMed:15469410, FT ECO:0000269|Ref.2, ECO:0000269|Ref.4}. FT /FTId=VAR_016926. FT VARIANT 289 289 N -> K (in dbSNP:rs34277950). FT {ECO:0000269|Ref.4}. FT /FTId=VAR_025209. FT VARIANT 306 306 T -> S (in dbSNP:rs34698757). FT {ECO:0000269|Ref.4}. FT /FTId=VAR_025210. FT VARIANT 328 328 I -> T (in dbSNP:rs28399499). FT {ECO:0000269|PubMed:15469410, FT ECO:0000269|Ref.4}. FT /FTId=VAR_024716. FT VARIANT 391 391 I -> N (in allele CYP2B6*15; FT dbSNP:rs35979566). FT {ECO:0000269|PubMed:15190123}. FT /FTId=VAR_023567. FT VARIANT 487 487 R -> C (in allele CYP2B6*5 and allele FT CYP2B6*7; dbSNP:rs3211371). FT {ECO:0000269|PubMed:11470993, FT ECO:0000269|PubMed:12642465, FT ECO:0000269|PubMed:12721789, FT ECO:0000269|PubMed:14551287, FT ECO:0000269|PubMed:15469410, FT ECO:0000269|Ref.4}. FT /FTId=VAR_016929. FT CONFLICT 146 146 I -> T (in Ref. 2; AAF13602). FT {ECO:0000305}. FT CONFLICT 238 238 L -> P (in Ref. 2; AAF13602). FT {ECO:0000305}. FT TURN 38 40 {ECO:0000244|PDB:5UFG}. FT HELIX 43 45 {ECO:0000244|PDB:5UFG}. FT HELIX 51 62 {ECO:0000244|PDB:5UFG}. FT STRAND 64 70 {ECO:0000244|PDB:5UFG}. FT STRAND 73 78 {ECO:0000244|PDB:5UFG}. FT HELIX 80 88 {ECO:0000244|PDB:5UFG}. FT TURN 89 91 {ECO:0000244|PDB:5UFG}. FT HELIX 92 95 {ECO:0000244|PDB:5UFG}. FT TURN 102 104 {ECO:0000244|PDB:5UFG}. FT HELIX 105 108 {ECO:0000244|PDB:5UFG}. FT TURN 113 115 {ECO:0000244|PDB:5UFG}. FT HELIX 118 131 {ECO:0000244|PDB:5UFG}. FT TURN 135 137 {ECO:0000244|PDB:3IBD}. FT HELIX 142 158 {ECO:0000244|PDB:5UFG}. FT TURN 159 162 {ECO:0000244|PDB:5UFG}. FT HELIX 168 183 {ECO:0000244|PDB:5UFG}. FT HELIX 193 210 {ECO:0000244|PDB:5UFG}. FT HELIX 212 224 {ECO:0000244|PDB:5UFG}. FT HELIX 230 255 {ECO:0000244|PDB:5UFG}. FT HELIX 264 274 {ECO:0000244|PDB:5UFG}. FT TURN 275 277 {ECO:0000244|PDB:5UFG}. FT STRAND 278 280 {ECO:0000244|PDB:3QU8}. FT HELIX 285 316 {ECO:0000244|PDB:5UFG}. FT HELIX 318 331 {ECO:0000244|PDB:5UFG}. FT STRAND 334 336 {ECO:0000244|PDB:5UFG}. FT HELIX 340 345 {ECO:0000244|PDB:5UFG}. FT HELIX 347 360 {ECO:0000244|PDB:5UFG}. FT STRAND 375 377 {ECO:0000244|PDB:5UFG}. FT STRAND 380 382 {ECO:0000244|PDB:5UFG}. FT STRAND 387 390 {ECO:0000244|PDB:5UFG}. FT HELIX 392 396 {ECO:0000244|PDB:5UFG}. FT TURN 399 401 {ECO:0000244|PDB:5UFG}. FT STRAND 402 404 {ECO:0000244|PDB:5UFG}. FT HELIX 410 413 {ECO:0000244|PDB:5UFG}. FT HELIX 432 434 {ECO:0000244|PDB:3IBD}. FT HELIX 439 456 {ECO:0000244|PDB:5UFG}. FT STRAND 457 460 {ECO:0000244|PDB:5UFG}. FT HELIX 465 467 {ECO:0000244|PDB:5UFG}. FT STRAND 473 480 {ECO:0000244|PDB:5UFG}. FT STRAND 486 490 {ECO:0000244|PDB:5UFG}. SQ SEQUENCE 491 AA; 56278 MW; B9799164BE8FBF1D CRC64; MELSVLLFLA LLTGLLLLLV QRHPNTHDRL PPGPRPLPLL GNLLQMDRRG LLKSFLRFRE KYGDVFTVHL GPRPVVMLCG VEAIREALVD KAEAFSGRGK IAMVDPFFRG YGVIFANGNR WKVLRRFSVT TMRDFGMGKR SVEERIQEEA QCLIEELRKS KGALMDPTFL FQSITANIIC SIVFGKRFHY QDQEFLKMLN LFYQTFSLIS SVFGQLFELF SGFLKYFPGA HRQVYKNLQE INAYIGHSVE KHRETLDPSA PKDLIDTYLL HMEKEKSNAH SEFSHQNLNL NTLSLFFAGT ETTSTTLRYG FLLMLKYPHV AERVYREIEQ VIGPHRPPEL HDRAKMPYTE AVIYEIQRFS DLLPMGVPHI VTQHTSFRGY IIPKDTEVFL ILSTALHDPH YFEKPDAFNP DHFLDANGAL KKTEAFIPFS LGKRICLGEG IARAELFLFF TTILQNFSMA SPVAPEDIDL TPQECGVGKI PPTYQIRFLP R //