Q00557 · CP1A1_MESAU

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.
    EC:1.14.14.1 (UniProtKB | ENZYME | Rhea)
  • 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 + 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.
  • (5S)-hydroperoxy-(6E,8Z,11Z,14Z)-eicosatetraenoate = 5-oxo-(6E,8Z,11Z,14Z)-eicosatetraenoate + H2O
    This reaction proceeds in the forward direction.

Cofactor

heme (UniProtKB | Rhea| CHEBI:30413 )

Pathway

Steroid hormone biosynthesis.
Lipid metabolism; fatty acid metabolism.
Cofactor metabolism; retinol metabolism.

Features

Showing features for binding site.

TypeIDPosition(s)Description
Binding site228substrate
Binding site461Fe (UniProtKB | ChEBI) of heme (UniProtKB | ChEBI); axial binding residue

GO annotations

AspectTerm
Cellular Componentendoplasmic reticulum membrane
Cellular Componentmitochondrial inner membrane
Molecular Functionaromatase activity
Molecular Functionestrogen 16-alpha-hydroxylase activity
Molecular Functionestrogen 2-hydroxylase activity
Molecular Functionheme binding
Molecular FunctionHsp70 protein binding
Molecular FunctionHsp90 protein binding
Molecular Functionhydroperoxy icosatetraenoate dehydratase activity
Molecular Functioniron ion binding
Molecular Functionsteroid 17-alpha-monooxygenase activity
Biological Processestrogen metabolic process
Biological Processfatty acid metabolic process
Biological Processhormone biosynthetic process
Biological Processprogesterone metabolic process
Biological Processretinol metabolic process
Biological Processsteroid biosynthetic process

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    Cytochrome P450 1A1
  • EC number
  • Alternative names
    • CYPIA1
    • Cytochrome P-450MC
    • Cytochrome P450 form 6
    • Cytochrome P450-C
    • Cytochrome P450-P1
    • Hydroperoxy icosatetraenoate dehydratase (EC:4.2.1.152
      ) . EC:4.2.1.152 (UniProtKB | ENZYME | Rhea)

Gene names

    • Name
      CYP1A1

Organism names

  • Taxonomic identifier
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Cricetidae > Cricetinae > Mesocricetus

Accessions

  • Primary accession
    Q00557
  • Secondary accessions
    • Q64665

Proteomes

Subcellular Location

Endoplasmic reticulum membrane
; Peripheral membrane protein
Mitochondrion inner membrane
; Peripheral membrane protein
Microsome membrane
; Peripheral membrane protein
Cytoplasm

Keywords

PTM/Processing

Features

Showing features for chain, glycosylation.

TypeIDPosition(s)Description
ChainPRO_00000516301-524Cytochrome P450 1A1
Glycosylation71O-linked (GlcNAc) serine

Keywords

PTM databases

Expression

Induction

By 3-methylcholanthrene (3MC).

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.

Protein-protein interaction databases

Structure

Family & Domains

Features

Showing features for region.

TypeIDPosition(s)Description
Region33-44Mitochondrial targeting signal

Sequence similarities

Belongs to the cytochrome P450 family.

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    524
  • Mass (Da)
    59,136
  • Last updated
    1998-12-15 v2
  • Checksum
    2A4C6AF9AE5FD8E0
MSSIYGLLNFMSATELLLAITVFCLGFWVVRALRTQVPKGLKTPPGPWGLPILGHVLTLGKNPHLSLTKLSKQYGDVLQIRIGSTPVVVLSGLDTIRQALVRQGDDFKGRPDFYSFTLITNGKSMTFNPDCGPVWAARRRLAQDALKSFSIALDPASASSCYLEEYVIKEADYLISKFQKLMAEVGHFDPDRYLVVSVTNVICAMCFGQRYDHDDQELLSIVNLSNEFGKVTGSGYPPDFIPILRYLPNSSLDAFKDLNKKFYSFMQKSVKEHYRTFEKGHIRDITDSLIEHCQDKSLDENANVQLSDDRVINIIVDLFGAGFDTVTTAISWSLMYLVTNPGVQRKIQEELDTVIGRSRRPRLCDRSQLPYLEAFILETFRHSSFLPFTIPHSTTRDTSLCGFYIPKGHCVFVNQWQINHNQELWGDPNKFRPERFLTSSGTLDKVLSGKVTLFGLGKRKCIGETIGRLEVFLFLAILLQQIEFTVSPGEKVDMTPIYGLTLKHARCEYFQAQTRSSGPQHPQA

Features

Showing features for sequence conflict.

TypeIDPosition(s)Description
Sequence conflict18in Ref. 1; BAA01096
Sequence conflict521in Ref. 1; BAA01096

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
D10251
EMBL· GenBank· DDBJ
BAA01096.1
EMBL· GenBank· DDBJ
mRNA
D12977
EMBL· GenBank· DDBJ
BAA02354.1
EMBL· GenBank· DDBJ
mRNA
D10913
EMBL· GenBank· DDBJ
BAA01717.1
EMBL· GenBank· DDBJ
Genomic DNA

Genome annotation databases

Similar Proteins

Disclaimer

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