| IED ID | IndEnz0010000193 |
| Enzyme Type ID | esterase000193 |
| Protein Name |
Cytochrome P450 2A6 EC 1.14.14.- 1,4-cineole 2-exo-monooxygenase CYPIIA6 Coumarin 7-hydroxylase Cytochrome P450 IIA3 Cytochrome P450 I |
| Gene Name | CYP2A6 CYP2A3 |
| 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 | MLASGMLLVALLVCLTVMVLMSVWQQRKSKGKLPPGPTPLPFIGNYLQLNTEQMYNSLMKISERYGPVFTIHLGPRRVVVLCGHDAVREALVDQAEEFSGRGEQATFDWVFKGYGVVFSNGERAKQLRRFSIATLRDFGVGKRGIEERIQEEAGFLIDALRGTGGANIDPTFFLSRTVSNVISSIVFGDRFDYKDKEFLSLLRMMLGIFQFTSTSTGQLYEMFSSVMKHLPGPQQQAFQLLQGLEDFIAKKVEHNQRTLDPNSPRDFIDSFLIRMQEEEKNPNTEFYLKNLVMTTLNLFIGGTETVSTTLRYGFLLLMKHPEVEAKVHEEIDRVIGKNRQPKFEDRAKMPYMEAVIHEIQRFGDVIPMSLARRVKKDTKFRDFFLPKGTEVYPMLGSVLRDPSFFSNPQDFNPQHFLNEKGQFKKSDAFVPFSIGKRNCFGEGLARMELFLFFTTVMQNFRLKSSQSPKDIDVSPKHVGFATIPRNYTMSFLPR |
| Enzyme Length | 494 |
| Uniprot Accession Number | P11509 |
| Absorption | |
| Active Site | |
| Activity Regulation | |
| Binding Site | BINDING 107; /note=Substrate; /evidence=ECO:0000305; BINDING 297; /note=Substrate |
| Calcium Binding | |
| catalytic Activity | 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}; |
| DNA Binding | |
| EC Number | 1.14.14.- |
| Enzyme Function | FUNCTION: Exhibits a high coumarin 7-hydroxylase activity. Can act in the hydroxylation of the anti-cancer drugs cyclophosphamide and ifosphamide. Competent in the metabolic activation of aflatoxin B1. Constitutes the major nicotine C-oxidase. Acts as a 1,4-cineole 2-exo-monooxygenase. Possesses low phenacetin O-deethylation activity. {ECO:0000269|PubMed:11695850, ECO:0000269|PubMed:16086027, ECO:0000269|PubMed:17125252, ECO:0000269|PubMed:18779312, ECO:0000269|PubMed:1889415, ECO:0000269|PubMed:1944238}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Beta strand (13); Binding site (2); Chain (1); Helix (20); Metal binding (1); Mutagenesis (6); Natural variant (23); Sequence caution (1); Sequence conflict (3); Turn (6) |
| Keywords | 3D-structure;Direct protein sequencing;Endoplasmic reticulum;Heme;Iron;Lipid metabolism;Membrane;Metal-binding;Microsome;Monooxygenase;NADP;Oxidoreductase;Reference proteome |
| Interact With | |
| Induction | INDUCTION: By phenobarbital and dexamethasone. {ECO:0000269|PubMed:1889415, ECO:0000269|PubMed:1944238}. |
| Subcellular Location | SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Peripheral membrane protein. Microsome membrane; Peripheral membrane protein. |
| Modified Residue | |
| Post Translational Modification | |
| Signal Peptide | |
| Structure 3D | X-ray crystallography (11) |
| Cross Reference PDB | 1Z10; 1Z11; 2FDU; 2FDV; 2FDW; 2FDY; 3EBS; 3T3Q; 3T3R; 4EJJ; 4RUI; |
| Mapped Pubmed ID | 10383923; 10731522; 10741631; 11054771; 11207029; 11241319; 11259349; 11434509; 11684323; 11701230; 11725533; 11805739; 11927498; 11927840; 11960911; 11960914; 12115524; 12162851; 12164325; 12172220; 12223434; 12325023; 12406643; 12419832; 12445030; 12708602; 12749606; 12832682; 12844137; 12883749; 14568264; 14583682; 15196988; 15203795; 15225612; 15308589; 15327835; 15370155; 15454735; 15475735; 15534625; 15564629; 15592323; 15660270; 15665333; 15671201; 15861035; 15861044; 15900015; 15940289; 15993850; 16006997; 16041240; 16048566; 16126166; 16176798; 16207711; 16272956; 16372023; 16378601; 16402086; 16402128; 16452582; 16470306; 16636685; 1664256; 16720336; 16758265; 16857725; 16891249; 16952495; 17015050; 17036930; 17112802; 17130279; 17156750; 17207267; 17220563; 17259654; 17267622; 17454707; 17522595; 17540336; 17646279; 17683511; 17916905; 17927692; 17934923; 17979512; 18004205; 18188752; 18212800; 18380793; 18425152; 18510611; 18666753; 18698229; 18715882; 18936436; 18941913; 18976031; 18979093; 19012698; 19040121; 19082995; 19225447; 19279561; 19290787; 19300303; 19303722; 19339270; 19343046; 19361454; 19365400; 19371316; 19387893; 19406142; 19415821; 19454817; 19479063; 19533856; 19537956; 19604090; 19643819; 19659438; 19702528; 19703308; 19779319; 19789190; 19845430; 19921195; 19956635; 20012030; 20061389; 20089352; 20136358; 20139165; 20155256; 20173083; 20177288; 20336063; 20418888; 20437850; 20438369; 20506136; 20596643; 20647221; 20656072; 20701904; 20719908; 20734048; 20734064; 20860463; 20887713; 21205058; 21265876; 21326246; 21410749; 21418183; 21473878; 21521021; 21685187; 21745589; 21747048; 21765098; 21791872; 21964962; 22051186; 22073590; 22160797; 22217675; 22271297; 22322240; 22465937; 22497566; 22498344; 22547082; 22614024; 22696418; 22700965; 22706231; 22847926; 22850738; 22854688; 22890016; 23049750; 23178447; 23203414; 23292114; 23371292; 23462429; 23471717; 23528144; 23649654; 23733493; 23813797; 24033696; 24127329; 24163286; 24192532; 24305170; 24651583; 24988984; 25006744; 25072098; 25220663; 25526961; 25585967; 25683822; 25710939; 25744963; 25857233; 26091970; 26098700; 26247835; 26343999; 26366873; 26370685; 26407342; 26644138; 26648056; 26662855; 26715117; 26757861; 26818358; 27035242; 27113016; 27322236; 27488534; 27625140; 27702941; 27815364; 27865452; 27902773; 27974382; 28032407; 28182203; 28231062; 28273397; 28432340; 28472995; 28734893; 28811232; 28886044; 28921760; 28931220; 29568101; 29724170; 30048196; 30094551; 30815984; 31163215; 31453782; 31796940; 31959879; 32131765; 32385545; 32803792; 33038907; 33091566; 33437219; 33455085; 34006188; 34050721; 34576282; 34655463; 497175; 8627510; 8637342; 9028626; 9103523; 9884161; |
| Motif | |
| Gene Encoded By | |
| Mass | 56,517 |
| Kinetics | BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=0.23 uM for coumarin {ECO:0000269|PubMed:16086027}; KM=530 uM for 1,4-cineole {ECO:0000269|PubMed:11695850}; Vmax=3.5 nmol/min/nmol enzyme toward 1,4-cineole {ECO:0000269|PubMed:11695850}; |
| Metal Binding | METAL 439; /note=Iron (heme axial ligand) |
| Rhea ID | RHEA:49160 |
| Cross Reference Brenda | 1.14.14.1; |