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 27-MAR-2024, entry version 229. DE RecName: Full=Cytochrome P450 2B6; DE EC=1.14.13.- {ECO:0000269|PubMed:12865317, ECO:0000269|PubMed:21289075}; DE AltName: Full=1,4-cineole 2-exo-monooxygenase {ECO:0000303|PubMed:11695850}; DE AltName: Full=CYPIIB6; DE AltName: Full=Cytochrome P450 IIB1 {ECO:0000303|PubMed:2573390}; GN Name=CYP2B6 {ECO:0000303|PubMed:21289075, ECO:0000312|HGNC:HGNC:2615}; 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). 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 IIB1: RT identification of a normal and two variant cDNAs derived from the CYP2B RT locus on chromosome 19 and differential expression of the IIB mRNAs in RT human liver."; RL Biochemistry 28:7340-7348(1989). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANTS ALA-167; HIS-172 AND RP 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., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., 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., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA 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; GLY-28; RP SER-29; HIS-172; ARG-262; LYS-289; SER-306; THR-328 AND 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., Lamerdin J.E., RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A., RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., RA Dubchak I., 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 a RT 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-cineole, RT a monoterpene cyclic ether, by rat and human liver microsomes."; RL Xenobiotica 31:713-723(2001). RN [9] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=12865317; DOI=10.1210/en.2003-0192; RA Lee A.J., Cai M.X., Thomas P.E., Conney A.H., Zhu B.T.; RT "Characterization of the oxidative metabolites of 17beta-estradiol and RT estrone formed by 15 selectively expressed human cytochrome p450 RT isoforms."; RL Endocrinology 144:3382-3398(2003). RN [10] RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND RP POLYMORPHISM. 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 [11] 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 [12] RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 30-491 OF VARIANT ARG-262 IN RP COMPLEX WITH HEME AND SYNTHETIC INHIBITOR, COFACTOR, AND IDENTIFICATION BY RP 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 with RT the inhibitor 4-(4-chlorophenyl)imidazole at 2.0-A resolution."; RL Mol. Pharmacol. 77:529-538(2010). RN [13] RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 30-491 OF VARIANT ARG-262 IN RP COMPLEX WITH HEME AND SYNTHETIC INHIBITOR, 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 of RT active site side chains."; RL Mol. Pharmacol. 80:1047-1055(2011). RN [14] RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 30-491 IN COMPLEX WITH HEME AND RP 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., Halpert J.R.; RT "Conformational adaptation of human cytochrome P450 2B6 and rabbit RT cytochrome P450 2B4 revealed upon binding multiple amlodipine molecules."; RL Biochemistry 51:7225-7238(2012). RN [15] RP POLYMORPHISM, INVOLVEMENT IN EFAVIRENZ POOR METABOLISM, AND SUSCEPTIBILITY RP TO EFAVIRENZ TOXICITY. RX PubMed=15622315; RA Haas D.W., Ribaudo H.J., Kim R.B., Tierney C., Wilkinson G.R., Gulick R.M., RA Clifford D.B., Hulgan T., Marzolini C., Acosta E.P.; RT "Pharmacogenetics of efavirenz and central nervous system side effects: an RT Adult AIDS Clinical Trials Group study."; RL AIDS 18:2391-2400(2004). RN [16] RP POLYMORPHISM, INVOLVEMENT IN EFAVIRENZ POOR METABOLISM, AND SUSCEPTIBILITY RP TO EFAVIRENZ TOXICITY. RX PubMed=15194512; DOI=10.1016/j.bbrc.2004.05.116; RA Tsuchiya K., Gatanaga H., Tachikawa N., Teruya K., Kikuchi Y., Yoshino M., RA Kuwahara T., Shirasaka T., Kimura S., Oka S.; RT "Homozygous CYP2B6 *6 (Q172H and K262R) correlates with high plasma RT efavirenz concentrations in HIV-1 patients treated with standard efavirenz- RT containing regimens."; RL Biochem. Biophys. Res. Commun. 319:1322-1326(2004). RN [17] RP POLYMORPHISM, INVOLVEMENT IN EFAVIRENZ POOR METABOLISM, AND SUSCEPTIBILITY RP 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 [18] RP POLYMORPHISM, INVOLVEMENT IN EFAVIRENZ POOR METABOLISM, AND SUSCEPTIBILITY RP TO EFAVIRENZ TOXICITY. RX PubMed=20860463; DOI=10.2217/pgs.10.94; RA Elens L., Vandercam B., Yombi J.C., Lison D., Wallemacq P., Haufroid V.; RT "Influence of host genetic factors on efavirenz plasma and intracellular RT pharmacokinetics in HIV-1-infected patients."; RL Pharmacogenomics 11:1223-1234(2010). RN [19] 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 [20] 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 on RT expression and function in human liver."; RL Pharmacogenetics 11:399-415(2001). RN [21] RP CHARACTERIZATION OF VARIANTS CYS-22; HIS-172; ARG-259; ARG-262 AND CYS-487. RX PubMed=12642465; DOI=10.1124/dmd.31.4.398; RA Jinno H., Tanaka-Kagawa T., Ohno A., Makino Y., Matsushima E., Hanioka N., RA Ando M.; RT "Functional characterization of cytochrome P450 2B6 allelic variants."; RL Drug Metab. Dispos. 31:398-403(2003). RN [22] 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, nine RT esterase genes, and two other genes in the Japanese population."; RL J. Hum. Genet. 48:249-270(2003). RN [23] 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 relationship RT to CYP2B6 genotype and CAR (constitutive androstane receptor) expression."; RL J. Pharmacol. Exp. Ther. 307:906-922(2003). RN [24] 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., Schwab M., RA 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 [25] 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 ethnically RT diverse population."; RL Pharmacogenomics 5:895-931(2004). CC -!- FUNCTION: A cytochrome P450 monooxygenase involved in the metabolism of CC endocannabinoids and steroids (PubMed:21289075, PubMed:12865317). CC Mechanistically, uses molecular oxygen inserting one oxygen atom into a CC substrate, and reducing the second into a water molecule, with two CC electrons provided by NADPH via cytochrome P450 reductase CC (NADPH--hemoprotein reductase). Catalyzes the epoxidation of double CC bonds of arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and CC 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially CC modulating endocannabinoid system signaling (PubMed:21289075). CC Hydroxylates steroid hormones, including testosterone at C-16 and CC estrogens at C-2 (PubMed:21289075, PubMed:12865317). Plays a role in CC the oxidative metabolism of xenobiotics, including plant lipids and CC drugs (PubMed:11695850, PubMed:22909231). Acts as a 1,4-cineole 2-exo- CC monooxygenase (PubMed:11695850). {ECO:0000269|PubMed:11695850, CC ECO:0000269|PubMed:12865317, ECO:0000269|PubMed:21289075, CC ECO:0000269|PubMed:22909231}. CC -!- FUNCTION: Allele 2B6*9: Has low affinity for anandamide and can only CC produce 11,12 EpETrE-EAs. {ECO:0000269|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: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-(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: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-(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:21289075}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53141; CC Evidence={ECO:0000305|PubMed:21289075}; CC -!- CATALYTIC ACTIVITY: CC Reaction=O2 + reduced [NADPH--hemoprotein reductase] + testosterone = CC 16alpha,17beta-dihydroxyandrost-4-en-3-one + H(+) + H2O + oxidized CC [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:53196, Rhea:RHEA- CC COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:17347, CC ChEBI:CHEBI:34172, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210; CC Evidence={ECO:0000269|PubMed:21289075}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53197; CC Evidence={ECO:0000305|PubMed:21289075}; CC -!- CATALYTIC ACTIVITY: CC Reaction=O2 + reduced [NADPH--hemoprotein reductase] + testosterone = CC 16beta,17beta-dihydroxyandrost-4-en-3-one + H(+) + H2O + oxidized CC [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:46304, Rhea:RHEA- CC COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:17347, CC ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:83027; CC Evidence={ECO:0000269|PubMed:21289075}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46305; CC Evidence={ECO:0000305|PubMed:21289075}; CC -!- CATALYTIC ACTIVITY: CC Reaction=17beta-estradiol + O2 + reduced [NADPH--hemoprotein reductase] CC = 2-hydroxy-17beta-estradiol + H(+) + H2O + oxidized CC [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:47212, Rhea:RHEA- CC COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:16469, CC ChEBI:CHEBI:28744, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210; CC Evidence={ECO:0000269|PubMed:12865317}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47213; CC Evidence={ECO:0000305|PubMed:21289075}; CC -!- CATALYTIC ACTIVITY: CC Reaction=estrone + O2 + reduced [NADPH--hemoprotein reductase] = 2- CC hydroxyestrone + H(+) + H2O + oxidized [NADPH--hemoprotein CC reductase]; Xref=Rhea:RHEA:47208, Rhea:RHEA-COMP:11964, Rhea:RHEA- CC COMP:11965, ChEBI:CHEBI:1156, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:15379, ChEBI:CHEBI:17263, ChEBI:CHEBI:57618, CC ChEBI:CHEBI:58210; Evidence={ECO:0000269|PubMed:12865317}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47209; CC Evidence={ECO:0000305|PubMed:21289075}; CC -!- CATALYTIC ACTIVITY: CC Reaction=1,4-cineole + O2 + reduced [NADPH--hemoprotein reductase] = 2- CC exo-hydroxy-1,4-cineole + H(+) + H2O + oxidized [NADPH--hemoprotein CC reductase]; Xref=Rhea:RHEA:49160, 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:80788, CC ChEBI:CHEBI:90956; Evidence={ECO:0000269|PubMed:11695850}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49161; CC Evidence={ECO:0000305|PubMed:11695850}; CC -!- COFACTOR: CC Name=heme; Xref=ChEBI:CHEBI:30413; CC Evidence={ECO:0000269|PubMed:20061448, ECO:0000269|PubMed:21875942, CC ECO:0000269|PubMed:22909231}; CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=360 uM for 1,4-cineole {ECO:0000269|PubMed:11695850}; CC KM=13.3 uM for testosterone (16-alpha-hydroxylation) CC {ECO:0000269|PubMed:21289075}; CC KM=27.7 uM for testosterone (16-beta-hydroxylation) CC {ECO:0000269|PubMed:21289075}; CC KM=3.6 uM for N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine CC (14,15-epoxidation) {ECO:0000269|PubMed:21289075}; CC KM=1.32 uM for N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine CC (11,12-epoxidation) {ECO:0000269|PubMed:21289075}; CC KM=1.21 uM for N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine CC (8,9-epoxidation) {ECO:0000269|PubMed:21289075}; CC Vmax=3.4 nmol/min/nmol enzyme toward 1,4-cineole CC {ECO:0000269|PubMed:11695850}; CC Vmax=2.04 pmol/min/pmol enzyme toward CC N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine (14,15-epoxidation) CC {ECO:0000269|PubMed:21289075}; CC Vmax=7.56 pmol/min/pmol enzyme toward CC N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine (11,12-epoxidation) CC {ECO:0000269|PubMed:21289075}; CC Vmax=3.12 pmol/min/pmol enzyme toward CC N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine (8,9-epoxidation) CC {ECO:0000269|PubMed:21289075}; 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 -!- TISSUE SPECIFICITY: Expressed in liver, lung and heart right ventricle. CC {ECO:0000269|PubMed:10768437}. CC -!- INDUCTION: By phenobarbital. CC -!- PTM: Phosphorylation is accompanied by a decrease in enzyme activity. CC {ECO:0000250}. CC -!- POLYMORPHISM: Variability among CYP2B6 alleles may account for CC differential metabolism of endogenous steroids and endocannabinoids CC among individuals. For 16-alpha hydroxylation of testosterone, Vmax/Km CC values between alleles decrease in the following order: 2B6*1 > 2B6*6 > CC 2B6*9 > 2B7*4. For 16-beta hydroxylation of testosterone, 2B6*6 has the CC highest catalytic efficiency. For anandamide metabolism, 2B6*6 and CC 2B6*9 alleles show significantly lower rates of epoxidation CC (PubMed:21289075). 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 (HIV) CC infection. Up to half of patients treated with efavirenz, experience CC side effects in the central nervous system, including dizziness, CC insomnia, impaired concentration, somnolence, and abnormal dreams. CC Severe depression, aggressive behavior, and paranoid or manic reactions CC may also occur, depending on efavirenz concentration in the plasma. CC Patients homozygous for 2B6*6 have significantly higher plasma CC efavirenz levels when compared to 2B6*6 heterozygous ones CC (PubMed:15622315, PubMed:15194512, PubMed:20639527). CC {ECO:0000269|PubMed:15194512, ECO:0000269|PubMed:15622315, CC ECO:0000269|PubMed:20639527, ECO:0000269|PubMed:21289075}. CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}. CC -!- WEB RESOURCE: Name=PharmVar Pharmacogen Variation Consortium; CC Note=CYP2B6 alleles; CC URL="https://www.pharmvar.org/gene/CYP2B6"; 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 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 AlphaFoldDB; P20813; -. DR SMR; P20813; -. DR BioGRID; 107933; 7. DR IntAct; P20813; 5. 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; DB11932; Abametapir. DR DrugBank; DB12001; Abemaciclib. DR DrugBank; DB14973; Abrocitinib. DR DrugBank; DB15568; Adagrasib. DR DrugBank; DB00321; Amitriptyline. DR DrugBank; DB00381; Amlodipine. DR DrugBank; DB00701; Amprenavir. DR DrugBank; DB01435; Antipyrine. DR DrugBank; DB00714; Apomorphine. DR DrugBank; DB06413; Armodafinil. DR DrugBank; DB06697; Artemether. DR DrugBank; DB13132; Artemisinin. DR DrugBank; DB11586; Asunaprevir. DR DrugBank; DB01076; Atorvastatin. DR DrugBank; DB15011; Avacopan. DR DrugBank; DB00972; Azelastine. DR DrugBank; DB08822; Azilsartan medoxomil. DR DrugBank; DB13997; Baloxavir marboxil. DR DrugBank; DB04975; Banoxantrone. DR DrugBank; DB01086; Benzocaine. DR DrugBank; DB00865; Benzphetamine. DR DrugBank; DB00443; Betamethasone. DR DrugBank; DB04794; Bifonazole. DR DrugBank; DB12151; Brincidofovir. DR DrugBank; DB05541; Brivaracetam. DR DrugBank; DB01222; Budesonide. DR DrugBank; DB01156; Bupropion. DR DrugBank; DB09061; Cannabidiol. DR DrugBank; DB14737; Cannabinol. DR DrugBank; DB00564; Carbamazepine. DR DrugBank; DB06119; Cenobamate. DR DrugBank; DB00439; Cerivastatin. DR DrugBank; DB00568; Cinnarizine. DR DrugBank; DB00604; Cisapride. DR DrugBank; DB00515; Cisplatin. DR DrugBank; DB12499; Clascoterone. DR DrugBank; DB00349; Clobazam. DR DrugBank; DB06470; Clomethiazole. 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; DB11672; Curcumin. DR DrugBank; DB14635; Curcumin sulfate. DR DrugBank; DB04664; Cyclohexyl-pentyl-maltoside. DR DrugBank; DB00531; Cyclophosphamide. DR DrugBank; DB08912; Dabrafenib. DR DrugBank; DB01151; Desipramine. DR DrugBank; DB16650; Deucravacitinib. DR DrugBank; DB01234; Dexamethasone. DR DrugBank; DB14649; Dexamethasone acetate. DR DrugBank; DB04856; Dexloxiglumide. DR DrugBank; DB00514; Dextromethorphan. DR DrugBank; DB00829; Diazepam. DR DrugBank; DB00586; Diclofenac. DR DrugBank; DB01184; Domperidone. DR DrugBank; DB00997; Doxorubicin. DR DrugBank; DB00470; Dronabinol. DR DrugBank; DB00476; Duloxetine. DR DrugBank; DB00625; Efavirenz. DR DrugBank; DB15444; Elexacaftor. DR DrugBank; DB13874; Enasidenib. DR DrugBank; DB08899; Enzalutamide. DR DrugBank; DB00751; Epinastine. DR DrugBank; DB11823; Esketamine. DR DrugBank; DB00655; Estrone. DR DrugBank; DB00898; Ethanol. DR DrugBank; DB01466; Ethylmorphine. DR DrugBank; DB00574; Fenfluramine. DR DrugBank; DB12265; Fexinidazole. DR DrugBank; DB01544; Flunitrazepam. DR DrugBank; DB00472; Fluoxetine. DR DrugBank; DB01095; Fluvastatin. DR DrugBank; DB00176; Fluvoxamine. DR DrugBank; DB01320; Fosphenytoin. DR DrugBank; DB05087; Ganaxolone. DR DrugBank; DB00986; Glycopyrronium. DR DrugBank; DB01159; Halothane. DR DrugBank; DB00956; Hydrocodone. DR DrugBank; DB00741; Hydrocortisone. DR DrugBank; DB09054; Idelalisib. DR DrugBank; DB01181; Ifosfamide. DR DrugBank; DB00458; Imipramine. DR DrugBank; DB00762; Irinotecan. DR DrugBank; DB11633; Isavuconazole. DR DrugBank; DB00753; Isoflurane. DR DrugBank; DB11757; Istradefylline. DR DrugBank; DB01167; Itraconazole. DR DrugBank; DB14568; Ivosidenib. DR DrugBank; DB09570; Ixazomib. DR DrugBank; DB01221; Ketamine. DR DrugBank; DB06738; Ketobemidone. DR DrugBank; DB01026; Ketoconazole. DR DrugBank; DB11951; Lemborexant. DR DrugBank; DB09078; Lenvatinib. DR DrugBank; DB12070; Letermovir. DR DrugBank; DB05667; Levoketoconazole. DR DrugBank; DB00281; Lidocaine. DR DrugBank; DB00836; Loperamide. DR DrugBank; DB01601; Lopinavir. DR DrugBank; DB00455; Loratadine. DR DrugBank; DB04871; Lorcaserin. DR DrugBank; DB12130; Lorlatinib. DR DrugBank; DB09280; Lumacaftor. DR DrugBank; DB00772; Malathion. DR DrugBank; DB09238; Manidipine. DR DrugBank; DB14921; Mavacamten. DR DrugBank; DB14009; Medical Cannabis. DR DrugBank; DB01043; Memantine. DR DrugBank; DB00170; Menadione. DR DrugBank; DB00454; Meperidine. DR DrugBank; DB00532; Mephenytoin. DR DrugBank; DB04817; Metamizole. DR DrugBank; DB00333; Methadone. DR DrugBank; DB00763; Methimazole. DR DrugBank; DB01028; Methoxyflurane. DR DrugBank; DB09241; Methylene blue. DR DrugBank; DB00849; Methylphenobarbital. DR DrugBank; DB00959; Methylprednisolone. DR DrugBank; DB06710; Methyltestosterone. DR DrugBank; DB00379; Mexiletine. DR DrugBank; DB06148; Mianserin. DR DrugBank; DB01110; Miconazole. DR DrugBank; DB06595; Midostaurin. DR DrugBank; DB16236; Mitapivat. 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; DB00957; Norgestimate. DR DrugBank; DB09074; Olaparib. DR DrugBank; DB11632; Opicapone. DR DrugBank; DB01173; Orphenadrine. DR DrugBank; DB11837; Osilodrostat. DR DrugBank; DB04938; Ospemifene. DR DrugBank; DB00715; Paroxetine. DR DrugBank; DB08883; Perampanel. DR DrugBank; DB01074; Perhexiline. DR DrugBank; DB04930; Permethrin. DR DrugBank; DB12978; Pexidartinib. DR DrugBank; DB03575; Phencyclidine. DR DrugBank; DB01174; Phenobarbital. DR DrugBank; DB00252; Phenytoin. DR DrugBank; DB13941; Piperaquine. DR DrugBank; DB11642; Pitolisant. DR DrugBank; DB06209; Prasugrel. DR DrugBank; DB14631; Prednisolone phosphate. DR DrugBank; DB00635; Prednisone. 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; DB11853; Relugolix. DR DrugBank; DB02709; Resveratrol. DR DrugBank; DB00615; Rifabutin. DR DrugBank; DB01045; Rifampicin. DR DrugBank; DB11753; Rifamycin. DR DrugBank; DB01201; Rifapentine. DR DrugBank; DB08864; Rilpivirine. DR DrugBank; DB00503; Ritonavir. DR DrugBank; DB06176; Romidepsin. DR DrugBank; DB00296; Ropivacaine. DR DrugBank; DB00412; Rosiglitazone. DR DrugBank; DB00778; Roxithromycin. DR DrugBank; DB01037; Selegiline. DR DrugBank; DB06739; Seratrodast. DR DrugBank; DB01104; Sertraline. DR DrugBank; DB01236; Sevoflurane. DR DrugBank; DB00641; Simvastatin. DR DrugBank; DB00398; Sorafenib. DR DrugBank; DB15569; Sotorasib. DR DrugBank; DB09118; Stiripentol. DR DrugBank; DB06729; Sulfaphenazole. DR DrugBank; DB01138; Sulfinpyrazone. DR DrugBank; DB00675; Tamoxifen. DR DrugBank; DB12020; Tecovirimat. DR DrugBank; DB12095; Telotristat ethyl. DR DrugBank; DB00231; Temazepam. DR DrugBank; DB00624; Testosterone. DR DrugBank; DB13943; Testosterone cypionate. DR DrugBank; DB13944; Testosterone enanthate. DR DrugBank; DB13946; Testosterone undecanoate. DR DrugBank; DB01041; Thalidomide. DR DrugBank; DB09499; Thiosulfuric acid. DR DrugBank; DB04572; Thiotepa. DR DrugBank; DB08816; Ticagrelor. DR DrugBank; DB00208; Ticlopidine. DR DrugBank; DB06137; Tirbanibulin. DR DrugBank; DB00193; Tramadol. DR DrugBank; DB00755; Tretinoin. DR DrugBank; DB12245; Triclabendazole. DR DrugBank; DB12808; Trifarotene. DR DrugBank; DB00197; Troglitazone. DR DrugBank; DB00313; Valproic acid. DR DrugBank; DB11613; Velpatasvir. DR DrugBank; DB08881; Vemurafenib. DR DrugBank; DB00661; Verapamil. DR DrugBank; DB09185; Viloxazine. DR DrugBank; DB11739; Vonoprazan. DR DrugBank; DB00582; Voriconazole. DR DrugBank; DB09068; Vortioxetine. DR DrugBank; DB14975; Voxelotor. DR DrugBank; DB15035; Zanubrutinib. DR DrugCentral; P20813; -. DR GuidetoPHARMACOLOGY; 1324; -. DR SwissLipids; SLP:000001346; -. DR iPTMnet; P20813; -. DR PhosphoSitePlus; P20813; -. DR BioMuta; CYP2B6; -. DR DMDM; 117205; -. DR EPD; P20813; -. DR MassIVE; P20813; -. DR PaxDb; 9606-ENSP00000324648; -. DR PeptideAtlas; P20813; -. DR ProteomicsDB; 5366; -. DR ProteomicsDB; 53803; -. [P20813-1] DR Antibodypedia; 30684; 420 antibodies from 32 providers. DR DNASU; 1555; -. DR Ensembl; ENST00000324071.10; ENSP00000324648.2; ENSG00000197408.10. [P20813-1] DR GeneID; 1555; -. DR KEGG; hsa:1555; -. DR MANE-Select; ENST00000324071.10; ENSP00000324648.2; NM_000767.5; NP_000758.1. DR UCSC; uc002opr.2; human. [P20813-1] DR AGR; HGNC:2615; -. DR CTD; 1555; -. DR DisGeNET; 1555; -. DR GeneCards; CYP2B6; -. DR HGNC; HGNC:2615; CYP2B6. DR HPA; ENSG00000197408; Tissue enriched (liver). DR MalaCards; CYP2B6; -. DR MIM; 123930; gene. DR MIM; 614546; phenotype. DR neXtProt; NX_P20813; -. DR OpenTargets; ENSG00000197408; -. DR PharmGKB; PA123; -. DR VEuPathDB; HostDB:ENSG00000197408; -. DR eggNOG; KOG0156; Eukaryota. DR GeneTree; ENSGT00940000157162; -. DR HOGENOM; CLU_001570_22_3_1; -. DR InParanoid; P20813; -. DR OMA; YTVSVIM; -. DR OrthoDB; 2900138at2759; -. DR PhylomeDB; P20813; -. DR TreeFam; TF352043; -. DR BioCyc; MetaCyc:HS09587-MONOMER; -. DR BRENDA; 1.14.14.1; 2681. DR PathwayCommons; P20813; -. DR Reactome; R-HSA-211935; Fatty acids. DR Reactome; R-HSA-211945; Phase I - Functionalization of compounds. DR Reactome; R-HSA-211981; Xenobiotics. DR Reactome; R-HSA-211999; CYP2E1 reactions. DR SABIO-RK; P20813; -. DR SignaLink; P20813; -. DR SIGNOR; P20813; -. DR BioGRID-ORCS; 1555; 11 hits in 1145 CRISPR screens. DR EvolutionaryTrace; P20813; -. DR GeneWiki; CYP2B6; -. DR GenomeRNAi; 1555; -. DR Pharos; P20813; Tchem. DR PRO; PR:P20813; -. DR Proteomes; UP000005640; Chromosome 19. DR RNAct; P20813; Protein. DR Bgee; ENSG00000197408; Expressed in right lobe of liver and 70 other cell types or tissues. DR ExpressionAtlas; P20813; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. 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: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:0008392; F:arachidonic acid epoxygenase activity; IBA:GO_Central. DR GO; GO:0101021; F:estrogen 2-hydroxylase 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: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:0008390; F:testosterone 16-alpha-hydroxylase activity; IDA:UniProtKB. DR GO; GO:0062184; F:testosterone 16-beta-hydroxylase activity; IDA:UniProtKB. DR GO; GO:0042180; P:cellular ketone metabolic process; IDA:BHF-UCL. DR GO; GO:0019373; P:epoxygenase P450 pathway; IBA:GO_Central. 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:UniProtKB. DR CDD; cd20672; CYP2B; 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; IPR008068; Cyt_P450_E_grp-I_CYP2B-like. DR InterPro; IPR036396; Cyt_P450_sf. DR PANTHER; PTHR24300:SF388; CYTOCHROME P450 2B6; 1. DR PANTHER; PTHR24300; CYTOCHROME P450 508A4-RELATED; 1. DR Pfam; PF00067; p450; 1. DR PRINTS; PR00463; EP450I. DR PRINTS; PR01685; EP450ICYP2B. DR PRINTS; PR00385; P450. DR SUPFAM; SSF48264; Cytochrome P450; 1. DR PROSITE; PS00086; CYTOCHROME_P450; 1. DR Genevisible; P20813; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Endoplasmic reticulum; Heme; Iron; KW Lipid metabolism; Membrane; Metal-binding; Microsome; Monooxygenase; NADP; KW Oxidoreductase; Phosphoprotein; Reference proteome. FT CHAIN 1..491 FT /note="Cytochrome P450 2B6" FT /id="PRO_0000051683" FT BINDING 436 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 MOD_RES 128 FT /note="Phosphoserine; by PKA" FT /evidence="ECO:0000250" FT VAR_SEQ 1..57 FT /note="MELSVLLFLALLTGLLLLLVQRHPNTHDRLPPGPRPLPLLGNLLQMDRRGLL FT KSFLR -> MRCMLTNSHPWCGCDWQ (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_055571" FT VAR_SEQ 162..321 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_055572" FT VARIANT 21 FT /note="Q -> L (in allele CYP2B6*10; dbSNP:rs34883432)" FT /evidence="ECO:0000269|PubMed:15190123" FT /id="VAR_023563" FT VARIANT 22 FT /note="R -> C (in allele CYP2B6*2 and allele CYP2B6*10; FT dbSNP:rs8192709)" FT /evidence="ECO:0000269|PubMed:11470993, FT ECO:0000269|PubMed:12642465, ECO:0000269|PubMed:12721789, FT ECO:0000269|PubMed:14551287, ECO:0000269|PubMed:15469410, FT ECO:0000269|Ref.4" FT /id="VAR_016927" FT VARIANT 26 FT /note="T -> S (in dbSNP:rs33973337)" FT /evidence="ECO:0000269|Ref.4" FT /id="VAR_025206" FT VARIANT 28 FT /note="D -> G (in dbSNP:rs33980385)" FT /evidence="ECO:0000269|Ref.4" FT /id="VAR_025207" FT VARIANT 29 FT /note="R -> P (in dbSNP:rs34284776)" FT /id="VAR_033819" FT VARIANT 29 FT /note="R -> S (in dbSNP:rs33926104)" FT /evidence="ECO:0000269|Ref.4" FT /id="VAR_025208" FT VARIANT 46 FT /note="M -> V (in allele CYP2B6*11; dbSNP:rs35303484)" FT /evidence="ECO:0000269|PubMed:15190123" FT /id="VAR_023564" FT VARIANT 99 FT /note="G -> E (in allele CYP2B6*12; dbSNP:rs36060847)" FT /evidence="ECO:0000269|PubMed:15190123" FT /id="VAR_023565" FT VARIANT 139 FT /note="K -> E (in allele CYP2B6*8 and allele CYP2B6*13; FT dbSNP:rs12721655)" FT /evidence="ECO:0000269|PubMed:14551287, FT ECO:0000269|PubMed:15190123" FT /id="VAR_016948" FT VARIANT 140 FT /note="R -> Q (in allele CYP2B6*14; dbSNP:rs35773040)" FT /evidence="ECO:0000269|PubMed:15190123" FT /id="VAR_023566" FT VARIANT 167 FT /note="P -> A (in dbSNP:rs3826711)" FT /evidence="ECO:0000269|PubMed:12721789, ECO:0000269|Ref.2" FT /id="VAR_016924" FT VARIANT 172 FT /note="Q -> H (in allele CYP2B6*6, allele CYP2B6*7, allele FT CYP2B6*9 and allele CYP2B6*13; dbSNP:rs3745274)" FT /evidence="ECO:0000269|PubMed:11243870, FT ECO:0000269|PubMed:11470993, ECO:0000269|PubMed:12642465, FT ECO:0000269|PubMed:12721789, ECO:0000269|PubMed:14551287, FT ECO:0000269|PubMed:15469410, ECO:0000269|Ref.2, FT ECO:0000269|Ref.4" FT /id="VAR_016925" FT VARIANT 259 FT /note="S -> R (in allele CYP2B6*3; dbSNP:rs45482602)" FT /evidence="ECO:0000269|PubMed:11470993, FT ECO:0000269|PubMed:12642465" FT /id="VAR_016928" FT VARIANT 262 FT /note="K -> R (in allele CYP2B6*4, allele CYP2B6*6, allele FT CYP2B6*7 and allele CYP2B6*13; slight decrease in activity; FT dbSNP:rs2279343)" FT /evidence="ECO:0000269|PubMed:11470993, FT ECO:0000269|PubMed:12642465, ECO:0000269|PubMed:15469410, FT ECO:0000269|Ref.2, ECO:0000269|Ref.4" FT /id="VAR_016926" FT VARIANT 289 FT /note="N -> K (in dbSNP:rs34277950)" FT /evidence="ECO:0000269|Ref.4" FT /id="VAR_025209" FT VARIANT 306 FT /note="T -> S (in dbSNP:rs34698757)" FT /evidence="ECO:0000269|Ref.4" FT /id="VAR_025210" FT VARIANT 328 FT /note="I -> T (in dbSNP:rs28399499)" FT /evidence="ECO:0000269|PubMed:15469410, ECO:0000269|Ref.4" FT /id="VAR_024716" FT VARIANT 391 FT /note="I -> N (in allele CYP2B6*15; dbSNP:rs35979566)" FT /evidence="ECO:0000269|PubMed:15190123" FT /id="VAR_023567" FT VARIANT 487 FT /note="R -> C (in allele CYP2B6*5 and allele CYP2B6*7; FT dbSNP:rs3211371)" FT /evidence="ECO:0000269|PubMed:11470993, FT ECO:0000269|PubMed:12642465, ECO:0000269|PubMed:12721789, FT ECO:0000269|PubMed:14551287, ECO:0000269|PubMed:15469410, FT ECO:0000269|Ref.4" FT /id="VAR_016929" FT CONFLICT 146 FT /note="I -> T (in Ref. 2; AAF13602)" FT /evidence="ECO:0000305" FT CONFLICT 238 FT /note="L -> P (in Ref. 2; AAF13602)" FT /evidence="ECO:0000305" FT TURN 38..40 FT /evidence="ECO:0007829|PDB:5UFG" FT HELIX 43..45 FT /evidence="ECO:0007829|PDB:5UFG" FT HELIX 51..62 FT /evidence="ECO:0007829|PDB:5UFG" FT STRAND 64..70 FT /evidence="ECO:0007829|PDB:5UFG" FT STRAND 73..78 FT /evidence="ECO:0007829|PDB:5UFG" FT HELIX 80..88 FT /evidence="ECO:0007829|PDB:5UFG" FT TURN 89..91 FT /evidence="ECO:0007829|PDB:5UFG" FT HELIX 92..95 FT /evidence="ECO:0007829|PDB:5UFG" FT TURN 102..104 FT /evidence="ECO:0007829|PDB:5UFG" FT HELIX 105..108 FT /evidence="ECO:0007829|PDB:5UFG" FT TURN 113..115 FT /evidence="ECO:0007829|PDB:5UFG" FT HELIX 118..131 FT /evidence="ECO:0007829|PDB:5UFG" FT TURN 135..137 FT /evidence="ECO:0007829|PDB:3IBD" FT HELIX 142..158 FT /evidence="ECO:0007829|PDB:5UFG" FT TURN 159..162 FT /evidence="ECO:0007829|PDB:5UFG" FT HELIX 168..183 FT /evidence="ECO:0007829|PDB:5UFG" FT HELIX 193..210 FT /evidence="ECO:0007829|PDB:5UFG" FT HELIX 212..224 FT /evidence="ECO:0007829|PDB:5UFG" FT HELIX 230..255 FT /evidence="ECO:0007829|PDB:5UFG" FT HELIX 264..274 FT /evidence="ECO:0007829|PDB:5UFG" FT TURN 275..277 FT /evidence="ECO:0007829|PDB:5UFG" FT STRAND 278..280 FT /evidence="ECO:0007829|PDB:3QU8" FT HELIX 285..316 FT /evidence="ECO:0007829|PDB:5UFG" FT HELIX 318..331 FT /evidence="ECO:0007829|PDB:5UFG" FT STRAND 334..336 FT /evidence="ECO:0007829|PDB:5UFG" FT HELIX 340..345 FT /evidence="ECO:0007829|PDB:5UFG" FT HELIX 347..360 FT /evidence="ECO:0007829|PDB:5UFG" FT STRAND 375..377 FT /evidence="ECO:0007829|PDB:5UFG" FT STRAND 380..382 FT /evidence="ECO:0007829|PDB:5UFG" FT STRAND 387..390 FT /evidence="ECO:0007829|PDB:5UFG" FT HELIX 392..396 FT /evidence="ECO:0007829|PDB:5UFG" FT TURN 399..401 FT /evidence="ECO:0007829|PDB:5UFG" FT STRAND 402..404 FT /evidence="ECO:0007829|PDB:5UFG" FT HELIX 410..413 FT /evidence="ECO:0007829|PDB:5UFG" FT HELIX 432..434 FT /evidence="ECO:0007829|PDB:3IBD" FT HELIX 439..456 FT /evidence="ECO:0007829|PDB:5UFG" FT STRAND 457..460 FT /evidence="ECO:0007829|PDB:5UFG" FT HELIX 465..467 FT /evidence="ECO:0007829|PDB:5UFG" FT STRAND 473..480 FT /evidence="ECO:0007829|PDB:5UFG" FT STRAND 486..490 FT /evidence="ECO:0007829|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 //