P00187 · CP1A2_RABIT

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.
    EC:1.14.14.1 (UniProtKB | ENZYME | Rhea)
  • 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 + H2O
    This reaction proceeds in the forward direction.
  • (12S)-hydroperoxy-(5Z,8Z,10E,14Z)-eicosatetraenoate = 12-oxo-(5Z,8Z,10E,14Z)-eicosatetraenoate + H2O
    This reaction proceeds in the forward direction.
    EC:4.2.1.152 (UniProtKB | ENZYME | Rhea)
  • (15S)-hydroperoxy-(5Z,8Z,11Z,13E)-eicosatetraenoate = 15-oxo-(5Z,8Z,11Z,13E)-eicosatetraenoate + H2O
    This reaction proceeds in the forward direction.
  • (13S)-hydroperoxy-(9Z,11E)-octadecadienoate = 13-oxo-(9Z,11E)-octadecadienoate + H2O
    This 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

heme (UniProtKB | Rhea| CHEBI:30413 )

Pathway

Cofactor metabolism; retinol metabolism.
Steroid metabolism; cholesterol metabolism.
Lipid metabolism; arachidonate metabolism.

Features

Showing features for binding site, site.

Type
IDPosition(s)Description
Binding site226substrate
Binding site361-365substrate
Site403Involved in electron transfer with reductase
Binding site458Fe (UniProtKB | ChEBI) of heme (UniProtKB | ChEBI); axial binding residue

GO annotations

AspectTerm
Cellular Componentendoplasmic reticulum membrane
Molecular Functionestrogen 16-alpha-hydroxylase activity
Molecular Functionestrogen 2-hydroxylase activity
Molecular Functionheme binding
Molecular Functionhydroperoxy icosatetraenoate dehydratase activity
Molecular Functioniron ion binding
Molecular Functionoxidoreductase 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 Functionsteroid 17-alpha-monooxygenase activity
Biological Processarachidonate metabolic process
Biological Processcholesterol metabolic process
Biological Processestrogen metabolic process
Biological Processhormone biosynthetic process
Biological Processprogesterone metabolic process
Biological Processretinol metabolic process

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    Cytochrome P450 1A2
  • EC number
  • Alternative names
    • CYPIA2
    • Cholesterol 25-hydroxylase
    • Cytochrome P450 isozyme 4 (Cytochrome P450 LM4)
    • Cytochrome P450-PM4
    • Hydroperoxy icosatetraenoate dehydratase (EC:4.2.1.152
      ) . EC:4.2.1.152 (UniProtKB | ENZYME | Rhea)

Gene names

    • Name
      CYP1A2

Organism names

  • Taxonomic identifier
  • Strain
    • New Zealand white
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Lagomorpha > Leporidae > Oryctolagus

Accessions

  • Primary accession
    P00187
  • Secondary accessions
    • Q29526

Proteomes

Subcellular Location

Endoplasmic reticulum membrane
; Peripheral membrane protein
Microsome membrane
; Peripheral membrane protein

Keywords

Phenotypes & Variants

Features

Showing features for natural variant.

TypeIDPosition(s)Description
Natural variant174
Natural variant233
Natural variant299

Variants

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.

Go to variant viewer

PTM/Processing

Features

Showing features for initiator methionine, chain, glycosylation.

Type
IDPosition(s)Description
Initiator methionine1Removed
ChainPRO_00000516552-516Cytochrome P450 1A2
Glycosylation69O-linked (GlcNAc) serine

Keywords

Proteomic databases

PTM databases

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

Family & Domains

Sequence similarities

Belongs to the cytochrome P450 family.

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    516
  • Mass (Da)
    58,334
  • Last updated
    2007-01-23 v3
  • MD5 Checksum
    0D28F718054607B07A88A78D92D96683
MAMSPAAPLSVTELLLVSAVFCLVFWAVRASRPKVPKGLKRLPGPWGWPLLGHLLTLGKNPHVALARLSRRYGDVFQIRLGSTPVVVLSGLDTIKQALVRQGDDFKGRPDLYSSSFITEGQSMTFSPDSGPVWAARRRLAQDSLKSFSIASNPASSSSCYLEEHVSQEAENLIGRFQELMAAVGRFDPYSQLVVSAARVIGAMCFGRRFPQGSEEMLDVVRNSSKFVETASSGSPVDFFPILRYLPNRPLQRFKDFNQRFLRFLQKTVREHYEDFDRNSIQDITGALFKHSEKNSKANSGLIPQEKIVNLVNDIFGAGFDTITTALSWSLMYLVTNPRRQRKIQEELDAVVGRARQPRLSDRPQLPYLEAFILELFRHTSFVPFTIPHSTTRDTTLNGFHIPKECCIFINQWQINHDPQLWGDPEEFRPERFLTADGAAINKPLSEKVTLFGLGKRRCIGETLARWEVFLFLAILLQRLEFSVPPGVPVDLTPIYGLTMKHPRCEHVQARPRFSDQ

Features

Showing features for sequence conflict.

TypeIDPosition(s)Description
Sequence conflict22in Ref. 3; AA sequence
Sequence conflict67in Ref. 1; AAA31437
Sequence conflict70in Ref. 3; AA sequence
Sequence conflict92in Ref. 3; AA sequence
Sequence conflict93in Ref. 4; AAA31433
Sequence conflict121in Ref. 2; CAA29171
Sequence conflict172in Ref. 3; AA sequence
Sequence conflict194in Ref. 3; AA sequence
Sequence conflict208in Ref. 1; AAA31437/CAA32066 and 4; AAA31433
Sequence conflict208-212in Ref. 3; AA sequence
Sequence conflict247-251in Ref. 3; AA sequence
Sequence conflict288in Ref. 4; AAA31433
Sequence conflict291-302in Ref. 4; AAA31433
Sequence conflict309in Ref. 4; AAA31433
Sequence conflict354-355in Ref. 1; AAA31437/CAA32066
Sequence conflict358in Ref. 4; AAA31433
Sequence conflict359in Ref. 3; AA sequence and 4; AAA31433
Sequence conflict462in Ref. 4; AAA31433
Sequence conflict494in Ref. 3; AA sequence

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
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

Genome annotation databases

Similar Proteins

Disclaimer

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