P00187 · CP1A2_RABIT
- ProteinCytochrome P450 1A2
- GeneCYP1A2
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids516 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids, steroid hormones and vitamins. 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 hydroxylation of carbon-hydrogen bonds. Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2. Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis. May act as a major enzyme for all-trans retinoic acid biosynthesis in the liver. Catalyzes two successive oxidative transformation of all-trans retinol to all-trans retinal and then to the active form all-trans retinoic acid. Primarily catalyzes stereoselective epoxidation of the last double bond of polyunsaturated fatty acids (PUFA), displaying a strong preference for the (R,S) stereoisomer. Catalyzes bisallylic hydroxylation and omega-1 hydroxylation of PUFA. May also participate in eicosanoids metabolism by converting hydroperoxide species into oxo metabolites (lipoxygenase-like reaction, NADPH-independent). Plays a role in the oxidative metabolism of xenobiotics. Catalyzes the N-hydroxylation of heterocyclic amines and the O-deethylation of phenacetin. Metabolizes caffeine via N3-demethylation.
Catalytic activity
- an organic molecule + reduced [NADPH--hemoprotein reductase] + O2 = an alcohol + oxidized [NADPH--hemoprotein reductase] + H2O + H+This reaction proceeds in the forward direction.
- 17beta-estradiol + reduced [NADPH--hemoprotein reductase] + O2 = 2-hydroxy-17beta-estradiol + oxidized [NADPH--hemoprotein reductase] + H2O + H+This reaction proceeds in the forward direction.
- 17beta-estradiol + reduced [NADPH--hemoprotein reductase] + O2 = 4-hydroxy-17beta-estradiol + oxidized [NADPH--hemoprotein reductase] + H2O + H+This reaction proceeds in the forward direction.
- estrone + reduced [NADPH--hemoprotein reductase] + O2 = 2-hydroxyestrone + oxidized [NADPH--hemoprotein reductase] + H2O + H+This reaction proceeds in the forward direction.
- estrone + reduced [NADPH--hemoprotein reductase] + O2 = 4-hydroxyestrone + oxidized [NADPH--hemoprotein reductase] + H2O + H+This reaction proceeds in the forward direction.
- cholesterol + reduced [NADPH--hemoprotein reductase] + O2 = 25-hydroxycholesterol + oxidized [NADPH--hemoprotein reductase] + H2O + H+This reaction proceeds in the forward direction.
- all-trans-retinol + reduced [NADPH--hemoprotein reductase] + O2 = all-trans-retinal + oxidized [NADPH--hemoprotein reductase] + 2 H2O + H+This reaction proceeds in the forward direction.
- all-trans-retinal + reduced [NADPH--hemoprotein reductase] + O2 = all-trans-retinoate + oxidized [NADPH--hemoprotein reductase] + H2O + 2 H+This reaction proceeds in the forward direction.
- (5Z,8Z,11Z,14Z)-eicosatetraenoate + reduced [NADPH--hemoprotein reductase] + O2 = (14R,15S)-epoxy-(5Z,8Z,11Z)-eicosatrienoate + oxidized [NADPH--hemoprotein reductase] + H2O + H+This reaction proceeds in the forward direction.
- (5Z,8Z,11Z,14Z)-eicosatetraenoate + reduced [NADPH--hemoprotein reductase] + O2 = (14S,15R)-epoxy-(5Z,8Z,11Z)-eicosatrienoate + oxidized [NADPH--hemoprotein reductase] + H2O + H+This reaction proceeds in the forward direction.
- (5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate + reduced [NADPH--hemoprotein reductase] + O2 = (17R,18S)-epoxy-(5Z,8Z,11Z,14Z)-eicosatetraenoate + oxidized [NADPH--hemoprotein reductase] + H2O + H+This reaction proceeds in the forward direction.
- (4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate + reduced [NADPH--hemoprotein reductase] + O2 = (19R,20S)-epoxy-(4Z,7Z,10Z,13Z,16Z)-docosapentaenoate + oxidized [NADPH--hemoprotein reductase] + H2O + H+This reaction proceeds in the forward direction.
- (5S)-hydroperoxy-(6E,8Z,11Z,14Z)-eicosatetraenoate = 5-oxo-(6E,8Z,11Z,14Z)-eicosatetraenoate + H2OThis reaction proceeds in the forward direction.
- (15S)-hydroperoxy-(5Z,8Z,11Z,13E)-eicosatetraenoate = 15-oxo-(5Z,8Z,11Z,13E)-eicosatetraenoate + H2OThis reaction proceeds in the forward direction.
- (13S)-hydroperoxy-(9Z,11E)-octadecadienoate = 13-oxo-(9Z,11E)-octadecadienoate + H2OThis reaction proceeds in the forward direction.
- (5Z,8Z,11Z,14Z)-eicosatetraenoate + reduced [NADPH--hemoprotein reductase] + O2 = 13-hydroxy-(5Z,8Z,11Z,14Z)-eicosatetraenoate + oxidized [NADPH--hemoprotein reductase] + H2O + H+This reaction proceeds in the forward direction.
- (5Z,8Z,11Z,14Z)-eicosatetraenoate + reduced [NADPH--hemoprotein reductase] + O2 = 19-hydroxy-(5Z,8Z,11Z,14Z)-eicosatetraenoate + oxidized [NADPH--hemoprotein reductase] + H2O + H+This reaction proceeds in the forward direction.
- (9Z,12Z)-octadecadienoate + reduced [NADPH--hemoprotein reductase] + O2 = 11-hydroxy-(9Z,12Z)-octadecadienoate + oxidized [NADPH--hemoprotein reductase] + H2O + H+This reaction proceeds in the forward direction.
Cofactor
Pathway
Cofactor metabolism; retinol metabolism.
Steroid metabolism; cholesterol metabolism.
Lipid metabolism; arachidonate metabolism.
Features
Showing features for binding site, site.
Type | ID | Position(s) | Description | ||
---|---|---|---|---|---|
Binding site | 226 | substrate | |||
Binding site | 361-365 | substrate | |||
Site | 403 | Involved in electron transfer with reductase | |||
Binding site | 458 | Fe (UniProtKB | ChEBI) of heme (UniProtKB | ChEBI); axial binding residue | |||
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | endoplasmic reticulum membrane | |
Molecular Function | estrogen 16-alpha-hydroxylase activity | |
Molecular Function | estrogen 2-hydroxylase activity | |
Molecular Function | heme binding | |
Molecular Function | hydroperoxy icosatetraenoate dehydratase activity | |
Molecular Function | iron ion binding | |
Molecular Function | 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 | |
Molecular Function | steroid 17-alpha-monooxygenase activity | |
Biological Process | arachidonate metabolic process | |
Biological Process | cholesterol metabolic process | |
Biological Process | estrogen metabolic process | |
Biological Process | hormone biosynthetic process | |
Biological Process | progesterone metabolic process | |
Biological Process | retinol metabolic process |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameCytochrome P450 1A2
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Strain
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Lagomorpha > Leporidae > Oryctolagus
Accessions
- Primary accessionP00187
- Secondary accessions
Proteomes
Subcellular Location
UniProt Annotation
GO Annotation
Endoplasmic reticulum membrane ; Peripheral membrane protein
Microsome membrane ; Peripheral membrane protein
Keywords
- Cellular component
Phenotypes & Variants
Features
Showing features for natural variant.
Type | ID | Position(s) | Description | ||
---|---|---|---|---|---|
Natural variant | 174 | ||||
Natural variant | 233 | ||||
Natural variant | 299 | ||||
Variants
![](/variants.8e7f84.jpg)
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 3 variants from UniProt as well as other sources including ClinVar and dbSNP.
Expression
Induction
By beta-naphthoflavone and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).
Interaction
Subunit
Interacts with PGRMC1; the interaction requires PGRMC1 homodimerization.
Protein-protein interaction databases
Structure
Sequence
- Sequence statusComplete
- Length516
- Mass (Da)58,334
- Last updated2007-01-23 v3
- MD5 Checksum0D28F718054607B07A88A78D92D96683
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | ||
---|---|---|---|---|---|
Sequence conflict | 22 | in Ref. 3; AA sequence | |||
Sequence conflict | 67 | in Ref. 1; AAA31437 | |||
Sequence conflict | 70 | in Ref. 3; AA sequence | |||
Sequence conflict | 92 | in Ref. 3; AA sequence | |||
Sequence conflict | 93 | in Ref. 4; AAA31433 | |||
Sequence conflict | 121 | in Ref. 2; CAA29171 | |||
Sequence conflict | 172 | in Ref. 3; AA sequence | |||
Sequence conflict | 194 | in Ref. 3; AA sequence | |||
Sequence conflict | 208 | in Ref. 1; AAA31437/CAA32066 and 4; AAA31433 | |||
Sequence conflict | 208-212 | in Ref. 3; AA sequence | |||
Sequence conflict | 247-251 | in Ref. 3; AA sequence | |||
Sequence conflict | 288 | in Ref. 4; AAA31433 | |||
Sequence conflict | 291-302 | in Ref. 4; AAA31433 | |||
Sequence conflict | 309 | in Ref. 4; AAA31433 | |||
Sequence conflict | 354-355 | in Ref. 1; AAA31437/CAA32066 | |||
Sequence conflict | 358 | in Ref. 4; AAA31433 | |||
Sequence conflict | 359 | in Ref. 3; AA sequence and 4; AAA31433 | |||
Sequence conflict | 462 | in Ref. 4; AAA31433 | |||
Sequence conflict | 494 | in Ref. 3; AA sequence | |||
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
M36538 EMBL· GenBank· DDBJ | AAA31437.1 EMBL· GenBank· DDBJ | mRNA | ||
X13853 EMBL· GenBank· DDBJ | CAA32066.1 EMBL· GenBank· DDBJ | mRNA | ||
X05686 EMBL· GenBank· DDBJ | CAA29171.1 EMBL· GenBank· DDBJ | mRNA | ||
M11728 EMBL· GenBank· DDBJ | AAA31433.1 EMBL· GenBank· DDBJ | mRNA |