Detail Information for IndEnz0010000193
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;