Q5KQT7 · CP1A1_FELCA
- ProteinCytochrome P450 1A1
- GeneCYP1A1
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids517 (go to sequence)
- Protein existenceEvidence at transcript 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 (CPR; NADPH-ferrihemoprotein 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, as well as D-ring hydroxylated E1 and E2 at the C15alpha and C16alpha positions. Displays different regioselectivities for polyunsaturated fatty acids (PUFA) hydroxylation. Catalyzes the epoxidation of double bonds of certain PUFA. Converts arachidonic acid toward epoxyeicosatrienoic acid (EET) regioisomers, 8,9-, 11,12-, and 14,15-EET, that function as lipid mediators in the vascular system. Displays an absolute stereoselectivity in the epoxidation of eicosapentaenoic acid (EPA) producing the 17(R),18(S) enantiomer. May play an important role in all-trans retinoic acid biosynthesis in extrahepatic tissues. Catalyzes two successive oxidative transformation of all-trans retinol to all-trans retinal and then to the active form all-trans retinoic acid. May also participate in eicosanoids metabolism by converting hydroperoxide species into oxo metabolites (lipoxygenase-like reaction, NADPH-independent).
Catalytic activity
- an organic molecule + O2 + reduced [NADPH--hemoprotein reductase] = an alcohol + H+ + H2O + oxidized [NADPH--hemoprotein reductase]This reaction proceeds in the backward direction.
- estrone + O2 + reduced [NADPH--hemoprotein reductase] = 2-hydroxyestrone + H+ + H2O + oxidized [NADPH--hemoprotein reductase]This reaction proceeds in the forward direction.
- estrone + O2 + reduced [NADPH--hemoprotein reductase] = 4-hydroxyestrone + H+ + H2O + oxidized [NADPH--hemoprotein reductase]This reaction proceeds in the forward direction.
- estrone + O2 + reduced [NADPH--hemoprotein reductase] = 6alpha-hydroxyestrone + H+ + H2O + oxidized [NADPH--hemoprotein reductase]This reaction proceeds in the forward direction.
- estrone + O2 + reduced [NADPH--hemoprotein reductase] = 15alpha-hydroxyestrone + H+ + H2O + oxidized [NADPH--hemoprotein reductase]This reaction proceeds in the forward direction.
- estrone + O2 + reduced [NADPH--hemoprotein reductase] = 16alpha-hydroxyestrone + H+ + H2O + oxidized [NADPH--hemoprotein reductase]This reaction proceeds in the forward direction.
- 17beta-estradiol + O2 + reduced [NADPH--hemoprotein reductase] = 2-hydroxy-17beta-estradiol + H+ + H2O + oxidized [NADPH--hemoprotein reductase]This reaction proceeds in the forward direction.
- 17beta-estradiol + O2 + reduced [NADPH--hemoprotein reductase] = 4-hydroxy-17beta-estradiol + H+ + H2O + oxidized [NADPH--hemoprotein reductase]This reaction proceeds in the forward direction.
- 17beta-estradiol + O2 + reduced [NADPH--hemoprotein reductase] = 6alpha-hydroxy-17beta-estradiol + H+ + H2O + oxidized [NADPH--hemoprotein reductase]This reaction proceeds in the forward direction.
- 17beta-estradiol + O2 + reduced [NADPH--hemoprotein reductase] = 7alpha-hydroxy-17beta-estradiol + H+ + H2O + oxidized [NADPH--hemoprotein reductase]This reaction proceeds in the forward direction.
- 17beta-estradiol + O2 + reduced [NADPH--hemoprotein reductase] = 15alpha-hydroxy-17beta-estradiol + H+ + H2O + oxidized [NADPH--hemoprotein reductase]This reaction proceeds in the forward direction.
- (5Z,8Z,11Z)-eicosatrienoate + O2 + reduced [NADPH--hemoprotein reductase] = 19-hydroxy-(5Z,8Z,11Z)-eicosatrienoate + H+ + H2O + oxidized [NADPH--hemoprotein reductase]This reaction proceeds in the forward direction.
- (5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 + reduced [NADPH--hemoprotein reductase] = 16-hydroxy-(5Z,8Z,11Z,14Z)-eicosatetraenoate + H+ + H2O + oxidized [NADPH--hemoprotein reductase]This reaction proceeds in the forward direction.
- (5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 + reduced [NADPH--hemoprotein reductase] = 17-hydroxy-(5Z,8Z,11Z,14Z)-eicosatetraenoate + H+ + H2O + oxidized [NADPH--hemoprotein reductase]This reaction proceeds in the forward direction.
- (5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 + reduced [NADPH--hemoprotein reductase] = 18-hydroxy-(5Z,8Z,11Z,14Z)-eicosatetraenoate + H+ + H2O + oxidized [NADPH--hemoprotein reductase]This reaction proceeds in the forward direction.
- (5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 + reduced [NADPH--hemoprotein reductase] = 19-hydroxy-(5Z,8Z,11Z,14Z)-eicosatetraenoate + H+ + H2O + oxidized [NADPH--hemoprotein reductase]This reaction proceeds in the forward direction.
- (5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate + O2 + reduced [NADPH--hemoprotein reductase] = 19-hydroxy-(5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate + H+ + H2O + oxidized [NADPH--hemoprotein reductase]This reaction proceeds in the forward direction.
- (5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 + reduced [NADPH--hemoprotein reductase] = (8R,9S)-epoxy-(5Z,11Z,14Z)-eicosatrienoate + H+ + H2O + oxidized [NADPH--hemoprotein reductase]This reaction proceeds in the forward direction.
- (5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 + reduced [NADPH--hemoprotein reductase] = (11R,12S)-epoxy-(5Z,8Z,14Z)-eicosatrienoate + H+ + H2O + oxidized [NADPH--hemoprotein reductase]This reaction proceeds in the forward direction.
- (5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 + reduced [NADPH--hemoprotein reductase] = (14S,15R)-epoxy-(5Z,8Z,11Z)-eicosatrienoate + H+ + H2O + oxidized [NADPH--hemoprotein reductase]This reaction proceeds in the forward direction.
- (5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 + reduced [NADPH--hemoprotein reductase] = (14R,15S)-epoxy-(5Z,8Z,11Z)-eicosatrienoate + H+ + H2O + oxidized [NADPH--hemoprotein reductase]This reaction proceeds in the forward direction.
- (5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate + O2 + reduced [NADPH--hemoprotein reductase] = (17R,18S)-epoxy-(5Z,8Z,11Z,14Z)-eicosatetraenoate + H+ + H2O + oxidized [NADPH--hemoprotein reductase]This reaction proceeds in the forward direction.
- (4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate + O2 + reduced [NADPH--hemoprotein reductase] = (19S,20R)-epoxy-(4Z,7Z,10Z,13Z,16Z)-docosapentaenoate + H+ + H2O + oxidized [NADPH--hemoprotein reductase]This reaction proceeds in the forward direction.
- (4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate + O2 + reduced [NADPH--hemoprotein reductase] = (19R,20S)-epoxy-(4Z,7Z,10Z,13Z,16Z)-docosapentaenoate + H+ + H2O + oxidized [NADPH--hemoprotein reductase]This reaction proceeds in the forward direction.
- all-trans-retinol + O2 + reduced [NADPH--hemoprotein reductase] = all-trans-retinal + H+ + 2 H2O + oxidized [NADPH--hemoprotein reductase]This reaction proceeds in the forward direction.
- all-trans-retinal + O2 + reduced [NADPH--hemoprotein reductase] = all-trans-retinoate + 2 H+ + H2O + oxidized [NADPH--hemoprotein reductase]This reaction proceeds in the forward direction.
- (13S)-hydroperoxy-(9Z,11E)-octadecadienoate = 13-oxo-(9Z,11E)-octadecadienoate + 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.
- (5S)-hydroperoxy-(6E,8Z,11Z,14Z)-eicosatetraenoate = 5-oxo-(6E,8Z,11Z,14Z)-eicosatetraenoate + H2OThis reaction proceeds in the forward direction.
Cofactor
Pathway
Steroid hormone biosynthesis.
Lipid metabolism; fatty acid metabolism.
Cofactor metabolism; retinol metabolism.
Features
Showing features for binding site.
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | endoplasmic reticulum membrane | |
Cellular Component | intracellular membrane-bounded organelle | |
Cellular Component | mitochondrial inner membrane | |
Molecular Function | aromatase activity | |
Molecular Function | estrogen 16-alpha-hydroxylase activity | |
Molecular Function | estrogen 2-hydroxylase activity | |
Molecular Function | heme binding | |
Molecular Function | Hsp70 protein binding | |
Molecular Function | Hsp90 protein binding | |
Molecular Function | hydroperoxy icosatetraenoate dehydratase activity | |
Molecular Function | iron ion binding | |
Molecular Function | monooxygenase activity | |
Biological Process | estrogen metabolic process | |
Biological Process | fatty acid metabolic process | |
Biological Process | retinol metabolic process | |
Biological Process | steroid biosynthetic process |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameCytochrome P450 1A1
- EC number
- Alternative names
Gene names
Organism names
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Laurasiatheria > Carnivora > Feliformia > Felidae > Felinae > Felis
Accessions
- Primary accessionQ5KQT7
Proteomes
Subcellular Location
UniProt Annotation
GO Annotation
Endoplasmic reticulum membrane ; Peripheral membrane protein
Mitochondrion inner membrane ; Peripheral membrane protein
Microsome membrane ; Peripheral membrane protein
Keywords
- Cellular component
PTM/Processing
Features
Showing features for chain, glycosylation.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000226726 | 1-517 | Cytochrome P450 1A1 | |||
Sequence: MMLSVFGLSVPISATELLLASFVFCLVFWVVRAWQPRVPKGLKSPPGPWGWPLLGHVLTLGKNPHLVLARLSQHYGDVLQIRIGSTPVLVLSGLDTIRQALVRQGDDFKGRPNLYSFTLISEGQSMSFSPDSGPVWAARRRLAQNALKSFSIASDPASSSSCYLEDHVSKEAEYLIGKFQELMAKVGHFDPYRYVVVSVANVICAMCFGRRYDHDDQELLSIVNLSNEFGDGTASGNPVDFFPILRYLPNPALDFFKDVNEKFSIFIHKMVKEHYKTFEKGHIRDITDSLIEHCQDKRLDENANIQLSDEKIVNVVSDLFGAGFDTVTTAISWCLMYLVTSPNVQEKIQKELDTVIGRERQPRLSDRLQLPYMEAFILEMFRHTSFVPFTIPHSTTKDTSLSGFYIPKERCVFVNQWQINHDQKLWGDPSEFRPERFLTPDGTINKALSEKVILFGLGKRKCIGETIARLEVFLFLAILLQQVEFSVPQGTKVDMTPIYGLTMKHARCEHFQVRMRT | ||||||
Glycosylation | 72 | O-linked (GlcNAc) serine | ||||
Sequence: S |
Keywords
- PTM
Proteomic databases
PTM databases
Interaction
Subunit
Interacts with cytosolic chaperones HSP70 and HSP90; this interaction is required for initial targeting to mitochondria. Interacts (via mitochondrial targeting signal) with TOMM40 (via N-terminus); this interaction is required for translocation across the mitochondrial outer membrane.
Structure
Family & Domains
Features
Showing features for region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 34-45 | Mitochondrial targeting signal | ||||
Sequence: WQPRVPKGLKSP |
Sequence similarities
Belongs to the cytochrome P450 family.
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length517
- Mass (Da)58,707
- Last updated2005-02-15 v1
- Checksum9CB7E5E3419362D1
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AB199730 EMBL· GenBank· DDBJ | BAD86852.1 EMBL· GenBank· DDBJ | mRNA |