CP2B6_HUMAN
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 03-AUG-2022, entry version 220.
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 (NADPH--
CC hemoprotein reductase). Catalyzes the epoxidation of double bonds of
CC arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-
CC 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 [NADPH--
CC hemoprotein reductase]; Xref=Rhea:RHEA:53140, Rhea:RHEA-COMP:11964,
CC Rhea:RHEA-COMP:11965, ChEBI:CHEBI:2700, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:57618,
CC ChEBI:CHEBI:58210, ChEBI:CHEBI:136989;
CC Evidence={ECO:0000269|PubMed: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 [NADPH--
CC hemoprotein reductase]; Xref=Rhea:RHEA:47212, Rhea:RHEA-COMP:11964,
CC Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:16469, ChEBI:CHEBI:28744,
CC 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 (14,15-
CC 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 (8,9-
CC 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 N-(5Z,8Z,11Z,14Z-
CC eicosatetraenoyl)-ethanolamine (14,15-epoxidation)
CC {ECO:0000269|PubMed:21289075};
CC Vmax=7.56 pmol/min/pmol enzyme toward N-(5Z,8Z,11Z,14Z-
CC eicosatetraenoyl)-ethanolamine (11,12-epoxidation)
CC {ECO:0000269|PubMed:21289075};
CC Vmax=3.12 pmol/min/pmol enzyme toward N-(5Z,8Z,11Z,14Z-
CC 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; 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; DB06729; Sulfaphenazole.
DR DrugBank; DB01138; Sulfinpyrazone.
DR DrugBank; DB00675; Tamoxifen.
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; 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; 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; P20813; -.
DR PeptideAtlas; P20813; -.
DR PRIDE; P20813; -.
DR ProteomicsDB; 5366; -.
DR ProteomicsDB; 53803; -. [P20813-1]
DR Antibodypedia; 30684; 366 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 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 Orphanet; 240869; Prediction of efavirenz toxicity.
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; HPKAYGR; -.
DR OrthoDB; 702827at2759; -.
DR PhylomeDB; P20813; -.
DR TreeFam; TF352043; -.
DR BioCyc; MetaCyc:HS09587-MON; -.
DR BRENDA; 1.14.14.1; 2681.
DR PathwayCommons; P20813; -.
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 SignaLink; P20813; -.
DR SIGNOR; P20813; -.
DR BioGRID-ORCS; 1555; 11 hits in 1065 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 tissues.
DR ExpressionAtlas; P20813; baseline and differential.
DR Genevisible; P20813; HS.
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:0008395; F:steroid hydroxylase activity; 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:0006082; P:organic acid metabolic process; 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 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; 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
