IED Industry Enzyme Database

Detail Information for IndEnz0010000177
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;