P00185 · CP1A1_RAT
- ProteinCytochrome P450 1A1
- GeneCyp1a1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids524 (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 (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 (By similarity).
Displays different regioselectivities for polyunsaturated fatty acids (PUFA) hydroxylation (By similarity).
Catalyzes the epoxidation of double bonds of certain PUFA (PubMed:20972997).
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 (By similarity).
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 (By similarity).
May also participate in eicosanoids metabolism by converting hydroperoxide species into oxo metabolites (lipoxygenase-like reaction, NADPH-independent) (By similarity).
Displays different regioselectivities for polyunsaturated fatty acids (PUFA) hydroxylation (By similarity).
Catalyzes the epoxidation of double bonds of certain PUFA (PubMed:20972997).
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 (By similarity).
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 (By similarity).
May also participate in eicosanoids metabolism by converting hydroperoxide species into oxo metabolites (lipoxygenase-like reaction, NADPH-independent) (By similarity).
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] = (11S,12R)-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] = (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
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Chemistry
Names & Taxonomy
Protein names
- Recommended nameCytochrome P450 1A1
- EC number
- Short namesCYP1A1
- Alternative names
- Cleaved into 2 chains
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Rattus
Accessions
- Primary accessionP00185
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Cytochrome P450 1A1
Cytochrome P450MT2A
Endoplasmic reticulum membrane ; Peripheral membrane protein
Mitochondrion inner membrane ; Peripheral membrane protein
Microsome membrane ; Peripheral membrane protein
Cytochrome P450MT2B
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 initiator methionine, chain, glycosylation.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Initiator methionine | 1 | Removed | ||||
Sequence: M | ||||||
Chain | PRO_0000003564 | 2-524 | Cytochrome P450 1A1 | |||
Sequence: PSVYGFPAFTSATELLLAVTTFCLGFWVVRVTRTWVPKGLKSPPGPWGLPFIGHVLTLGKNPHLSLTKLSQQYGDVLQIRIGSTPVVVLSGLNTIKQALVKQGDDFKGRPDLYSFTLIANGQSMTFNPDSGPLWAARRRLAQNALKSFSIASDPTLASSCYLEEHVSKEAEYLISKFQKLMAEVGHFDPFKYLVVSVANVICAICFGRRYDHDDQELLSIVNLSNEFGEVTGSGYPADFIPILRYLPNSSLDAFKDLNKKFYSFMKKLIKEHYRTFEKGHIRDITDSLIEHCQDRRLDENANVQLSDDKVITIVFDLFGAGFDTITTAISWSLMYLVTNPRIQRKIQEELDTVIGRDRQPRLSDRPQLPYLEAFILETFRHSSFVPFTIPHSTIRDTSLNGFYIPKGHCVFVNQWQVNHDQELWGDPNEFRPERFLTSSGTLDKHLSEKVILFGLGKRKCIGETIGRLEVFLFLAILLQQMEFNVSPGEKVDMTPAYGLTLKHARCEHFQVQMRSSGPQHLQA | ||||||
Chain | PRO_0000003565 | 5-524 | Cytochrome P450MT2A | |||
Sequence: YGFPAFTSATELLLAVTTFCLGFWVVRVTRTWVPKGLKSPPGPWGLPFIGHVLTLGKNPHLSLTKLSQQYGDVLQIRIGSTPVVVLSGLNTIKQALVKQGDDFKGRPDLYSFTLIANGQSMTFNPDSGPLWAARRRLAQNALKSFSIASDPTLASSCYLEEHVSKEAEYLISKFQKLMAEVGHFDPFKYLVVSVANVICAICFGRRYDHDDQELLSIVNLSNEFGEVTGSGYPADFIPILRYLPNSSLDAFKDLNKKFYSFMKKLIKEHYRTFEKGHIRDITDSLIEHCQDRRLDENANVQLSDDKVITIVFDLFGAGFDTITTAISWSLMYLVTNPRIQRKIQEELDTVIGRDRQPRLSDRPQLPYLEAFILETFRHSSFVPFTIPHSTIRDTSLNGFYIPKGHCVFVNQWQVNHDQELWGDPNEFRPERFLTSSGTLDKHLSEKVILFGLGKRKCIGETIGRLEVFLFLAILLQQMEFNVSPGEKVDMTPAYGLTLKHARCEHFQVQMRSSGPQHLQA | ||||||
Chain | PRO_0000003566 | 33-524 | Cytochrome P450MT2B | |||
Sequence: TRTWVPKGLKSPPGPWGLPFIGHVLTLGKNPHLSLTKLSQQYGDVLQIRIGSTPVVVLSGLNTIKQALVKQGDDFKGRPDLYSFTLIANGQSMTFNPDSGPLWAARRRLAQNALKSFSIASDPTLASSCYLEEHVSKEAEYLISKFQKLMAEVGHFDPFKYLVVSVANVICAICFGRRYDHDDQELLSIVNLSNEFGEVTGSGYPADFIPILRYLPNSSLDAFKDLNKKFYSFMKKLIKEHYRTFEKGHIRDITDSLIEHCQDRRLDENANVQLSDDKVITIVFDLFGAGFDTITTAISWSLMYLVTNPRIQRKIQEELDTVIGRDRQPRLSDRPQLPYLEAFILETFRHSSFVPFTIPHSTIRDTSLNGFYIPKGHCVFVNQWQVNHDQELWGDPNEFRPERFLTSSGTLDKHLSEKVILFGLGKRKCIGETIGRLEVFLFLAILLQQMEFNVSPGEKVDMTPAYGLTLKHARCEHFQVQMRSSGPQHLQA | ||||||
Glycosylation | 71 | O-linked (GlcNAc) serine | ||||
Sequence: S |
Post-translational modification
Two forms; MT2A (long form) and MT2B (short form); are produced by NH2-terminal proteolytic cleavage. This cleavage activates a cryptic mitochondrial targeting signal.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Liver.
Induction
By 3-methylcholanthrene (3MC) and beta-naphthoflavone (BNF).
Gene expression databases
Interaction
Subunit
Both Cytochrome P450MT2A and Cytochrome P450MT2B interact with cytosolic chaperones HSP70 and HSP90; this interaction is required for initial targeting to mitochondria. P450MT2B interacts (via mitochondrial targeting signal) with TOMM40 (via N-terminus); this interaction is required for translocation across the mitochondrial outer membrane.
Protein-protein interaction databases
Chemistry
Structure
Family & Domains
Features
Showing features for region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 33-44 | Mitochondrial targeting signal | ||||
Sequence: TRTWVPKGLKSP |
Domain
Contains a chimeric signal that facilitates targeting of the protein to both the endoplasmic reticulum and mitochondria. A 12 amino acid sequence between 33 and 44 functions as a putative mitochondrial-targeting signal. The removal of the first 4- or 32-amino acid residues from the intact protein positions the mitochondrial targeting signal for efficient binding to the mitochondrial import receptors. The membrane-free P4501A1 seems to be more sensitive to proteolysis.
Sequence similarities
Belongs to the cytochrome P450 family.
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length524
- Mass (Da)59,393
- Last updated1986-07-21 v1
- ChecksumC766DF8044D598C5
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 21-22 | in Ref. 5; AA sequence | ||||
Sequence: TT → VV | ||||||
Sequence conflict | 53 | in Ref. 2; CAA25153 | ||||
Sequence: I → M | ||||||
Sequence conflict | 494 | in Ref. 3; AAA41025 | ||||
Sequence: M → S |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
K02246 EMBL· GenBank· DDBJ | AAA41027.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
X00469 EMBL· GenBank· DDBJ | CAA25153.1 EMBL· GenBank· DDBJ | mRNA | ||
M26129 EMBL· GenBank· DDBJ | AAA41025.1 EMBL· GenBank· DDBJ | Genomic DNA |