IED ID | IndEnz0010000177 |
Enzyme Type ID | esterase000177 |
Protein Name |
Cytochrome P450 2B6 EC 1.14.13.- 1,4-cineole 2-exo-monooxygenase CYPIIB6 Cytochrome P450 IIB1 |
Gene Name | CYP2B6 |
Organism | Homo sapiens (Human) |
Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Primates Haplorrhini Simiiformes Catarrhini Hominoidea (apes) Hominidae (great apes) Homininae Homo Homo sapiens (Human) |
Enzyme Sequence | MELSVLLFLALLTGLLLLLVQRHPNTHDRLPPGPRPLPLLGNLLQMDRRGLLKSFLRFREKYGDVFTVHLGPRPVVMLCGVEAIREALVDKAEAFSGRGKIAMVDPFFRGYGVIFANGNRWKVLRRFSVTTMRDFGMGKRSVEERIQEEAQCLIEELRKSKGALMDPTFLFQSITANIICSIVFGKRFHYQDQEFLKMLNLFYQTFSLISSVFGQLFELFSGFLKYFPGAHRQVYKNLQEINAYIGHSVEKHRETLDPSAPKDLIDTYLLHMEKEKSNAHSEFSHQNLNLNTLSLFFAGTETTSTTLRYGFLLMLKYPHVAERVYREIEQVIGPHRPPELHDRAKMPYTEAVIYEIQRFSDLLPMGVPHIVTQHTSFRGYIIPKDTEVFLILSTALHDPHYFEKPDAFNPDHFLDANGALKKTEAFIPFSLGKRICLGEGIARAELFLFFTTILQNFSMASPVAPEDIDLTPQECGVGKIPPTYQIRFLPR |
Enzyme Length | 491 |
Uniprot Accession Number | P20813 |
Absorption | |
Active Site | |
Activity Regulation | |
Binding Site | |
Calcium Binding | |
catalytic Activity | CATALYTIC ACTIVITY: Reaction=N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine + O2 + reduced [NADPH--hemoprotein reductase] = H(+) + H2O + N-(14,15-epoxy-5Z,8Z,11Z-eicosatrienoyl)-ethanolamine + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:53148, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:2700, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:136991; Evidence={ECO:0000269|PubMed:21289075};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53149; Evidence={ECO:0000305|PubMed:21289075}; CATALYTIC ACTIVITY: Reaction=N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine + O2 + reduced [NADPH--hemoprotein reductase] = H(+) + H2O + N-(11,12-epoxy-5Z,8Z,14Z-eicosatrienoyl)-ethanolamine + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:53144, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:2700, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:136990; Evidence={ECO:0000269|PubMed:21289075};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53145; Evidence={ECO:0000305|PubMed:21289075}; CATALYTIC ACTIVITY: Reaction=N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine + O2 + reduced [NADPH--hemoprotein reductase] = H(+) + H2O + N-(8,9-epoxy-5Z,11Z,14Z-eicosatrienoyl)-ethanolamine + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:53140, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:2700, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:136989; Evidence={ECO:0000269|PubMed:21289075};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53141; Evidence={ECO:0000305|PubMed:21289075}; CATALYTIC ACTIVITY: Reaction=O2 + reduced [NADPH--hemoprotein reductase] + testosterone = 16alpha,17beta-dihydroxyandrost-4-en-3-one + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:53196, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:17347, ChEBI:CHEBI:34172, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210; Evidence={ECO:0000269|PubMed:21289075};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53197; Evidence={ECO:0000305|PubMed:21289075}; CATALYTIC ACTIVITY: Reaction=O2 + reduced [NADPH--hemoprotein reductase] + testosterone = 16beta,17beta-dihydroxyandrost-4-en-3-one + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:46304, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:17347, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:83027; Evidence={ECO:0000269|PubMed:21289075};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46305; Evidence={ECO:0000305|PubMed:21289075}; CATALYTIC ACTIVITY: Reaction=17beta-estradiol + O2 + reduced [NADPH--hemoprotein reductase] = 2-hydroxy-17beta-estradiol + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:47212, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:16469, ChEBI:CHEBI:28744, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210; Evidence={ECO:0000269|PubMed:12865317};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47213; Evidence={ECO:0000305|PubMed:21289075}; CATALYTIC ACTIVITY: Reaction=estrone + O2 + reduced [NADPH--hemoprotein reductase] = 2-hydroxyestrone + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:47208, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:1156, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:17263, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210; Evidence={ECO:0000269|PubMed:12865317};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47209; Evidence={ECO:0000305|PubMed:21289075}; CATALYTIC ACTIVITY: Reaction=1,4-cineole + O2 + reduced [NADPH--hemoprotein reductase] = 2-exo-hydroxy-1,4-cineole + H(+) + H2O + oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:49160, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:80788, ChEBI:CHEBI:90956; Evidence={ECO:0000269|PubMed:11695850};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49161; Evidence={ECO:0000305|PubMed:11695850}; |
DNA Binding | |
EC Number | 1.14.13.- |
Enzyme Function | FUNCTION: A cytochrome P450 monooxygenase involved in the metabolism of endocannabinoids and steroids (PubMed:21289075, PubMed:12865317). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the epoxidation of double bonds of arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:21289075). Hydroxylates steroid hormones, including testosterone at C-16 and estrogens at C-2 (PubMed:21289075, PubMed:12865317). Plays a role in the oxidative metabolism of xenobiotics, including plant lipids and drugs (PubMed:11695850, PubMed:22909231). Acts as a 1,4-cineole 2-exo-monooxygenase (PubMed:11695850). {ECO:0000269|PubMed:11695850, ECO:0000269|PubMed:12865317, ECO:0000269|PubMed:21289075, ECO:0000269|PubMed:22909231}.; FUNCTION: Allele 2B6*9: Has low affinity for anandamide and can only produce 11,12 EpETrE-EAs. {ECO:0000269|PubMed:21289075}. |
Temperature Dependency | |
PH Dependency | |
Pathway | |
nucleotide Binding | |
Features | Alternative sequence (2); Beta strand (11); Chain (1); Helix (21); Metal binding (1); Modified residue (1); Natural variant (19); Sequence conflict (2); Turn (8) |
Keywords | 3D-structure;Alternative splicing;Endoplasmic reticulum;Heme;Iron;Lipid metabolism;Membrane;Metal-binding;Microsome;Monooxygenase;NADP;Oxidoreductase;Phosphoprotein;Reference proteome |
Interact With | |
Induction | INDUCTION: By phenobarbital. |
Subcellular Location | SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Peripheral membrane protein. Microsome membrane; Peripheral membrane protein. |
Modified Residue | MOD_RES 128; /note=Phosphoserine; by PKA; /evidence=ECO:0000250 |
Post Translational Modification | PTM: Phosphorylation is accompanied by a decrease in enzyme activity. {ECO:0000250}. |
Signal Peptide | |
Structure 3D | X-ray crystallography (13) |
Cross Reference PDB | 3IBD; 3QOA; 3QU8; 3UA5; 4I91; 4RQL; 4RRT; 4ZV8; 5UAP; 5UDA; 5UEC; 5UFG; 5WBG; |
Mapped Pubmed ID | 10383923; 10731522; 10741631; 11701230; 11991950; 12207635; 12242601; 12439223; 12490624; 12571232; 12629583; 12738724; 14515060; 14977870; 15178651; 15196988; 15248218; 15284537; 15383491; 15563456; 15572372; 15825040; 15864119; 16116487; 16125881; 16183265; 16267764; 16338275; 16392089; 16433869; 16495778; 16506047; 16538176; 16623664; 1664256; 16772608; 16815693; 16912957; 16951995; 17015050; 17047492; 17054410; 17178267; 17223085; 17235330; 17329992; 17352764; 17356468; 17391322; 17407229; 17455229; 17465455; 17502835; 17559344; 17654295; 17682072; 17885627; 17900275; 17918089; 18004205; 18024866; 18057928; 18090046; 18171905; 18223457; 18281305; 18287571; 18303024; 18332083; 18496131; 18621926; 18728241; 18784455; 18839779; 18854779; 18978480; 18979093; 18989234; 19005482; 19076156; 19106084; 19124658; 19144407; 19218571; 19225447; 19228205; 19239339; 19282874; 19290787; 19343046; 19371316; 19376514; 19414633; 19425200; 19433561; 19464434; 19467232; 19474465; 19486190; 19531981; 19593168; 19659438; 19682083; 19693007; 19696793; 19702527; 19704172; 19779319; 19797611; 19812066; 19833192; 19916993; 19926050; 19944064; 20017669; 20079471; 20089352; 20096935; 20137387; 20173083; 20179710; 2025243; 20307138; 20338069; 20350955; 20361990; 20418888; 20459744; 20517174; 20529763; 20583967; 20602615; 20610889; 20622021; 20624854; 20625352; 20642445; 20662624; 20668445; 20677014; 20696882; 20720517; 20723261; 20734064; 20841522; 20861742; 20876786; 20878158; 20881953; 20952238; 20952418; 20966044; 20970553; 21108329; 21156812; 21158011; 21169260; 21486104; 21694616; 21715435; 21746968; 21790905; 21821736; 21886015; 22232427; 22281205; 22397853; 22462748; 22471906; 22519658; 22680342; 22685215; 22815312; 22936314; 22942317; 22950382; 23238783; 23249875; 23254426; 23288240; 23298916; 23344581; 23399569; 23524664; 23539296; 23550066; 23591849; 23615745; 23687222; 23746185; 23774940; 23786449; 23824676; 23834474; 23837472; 23840296; 23846872; 23886699; 23970651; 24128861; 24153159; 24260284; 24262967; 24293076; 24293093; 24445070; 24488272; 24497997; 24562623; 24586425; 24729586; 24831655; 24832206; 24885815; 24956253; 24988984; 25271170; 25303294; 25326287; 25409894; 25424204; 25489907; 25585967; 25677220; 25702819; 25722197; 25839716; 25933954; 26002734; 26107207; 26107645; 26126958; 26141406; 26319176; 26366873; 26544874; 26580670; 26602960; 26608082; 26648056; 26681005; 26830411; 26982502; 27010727; 27015760; 27045425; 27195527; 27208383; 27333947; 27388155; 27439448; 27509478; 27538916; 27665700; 27763887; 27826892; 27865701; 28081574; 28117133; 28145050; 28252572; 28320034; 28368100; 28389387; 28492729; 28646080; 28723731; 28816644; 28886044; 28931220; 29095103; 29319893; 29463407; 29468507; 29596329; 29637923; 29973058; 30778771; 30864294; 31549442; 31564857; 31628422; 31636355; 31766967; 31796940; 32119768; 32238417; 32279544; 32307645; 32538291; 32772362; 32817462; 33872945; 33895159; 34100292; 34397877; 34398016; 34752647; 34752660; 34758708; 34910759; 34949964; 497175; 8627510; 8631948; 8637342; 8647857; 8913342; 9028626; 9103523; 9842986; 9884161; |
Motif | |
Gene Encoded By | |
Mass | 56,278 |
Kinetics | BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=360 uM for 1,4-cineole {ECO:0000269|PubMed:11695850}; KM=13.3 uM for testosterone (16-alpha-hydroxylation) {ECO:0000269|PubMed:21289075}; KM=27.7 uM for testosterone (16-beta-hydroxylation) {ECO:0000269|PubMed:21289075}; KM=3.6 uM for N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine (14,15-epoxidation) {ECO:0000269|PubMed:21289075}; KM=1.32 uM for N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine (11,12-epoxidation) {ECO:0000269|PubMed:21289075}; KM=1.21 uM for N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine (8,9-epoxidation) {ECO:0000269|PubMed:21289075}; Vmax=3.4 nmol/min/nmol enzyme toward 1,4-cineole {ECO:0000269|PubMed:11695850}; Vmax=2.04 pmol/min/pmol enzyme toward N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine (14,15-epoxidation) {ECO:0000269|PubMed:21289075}; Vmax=7.56 pmol/min/pmol enzyme toward N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine (11,12-epoxidation) {ECO:0000269|PubMed:21289075}; Vmax=3.12 pmol/min/pmol enzyme toward N-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-ethanolamine (8,9-epoxidation) {ECO:0000269|PubMed:21289075}; |
Metal Binding | METAL 436; /note=Iron (heme axial ligand) |
Rhea ID | RHEA:53148; RHEA:53149; RHEA:53144; RHEA:53145; RHEA:53140; RHEA:53141; RHEA:53196; RHEA:53197; RHEA:46304; RHEA:46305; RHEA:47212; RHEA:47213; RHEA:47208; RHEA:47209; RHEA:49160; RHEA:49161 |
Cross Reference Brenda | 1.14.14.1; |