Cytochrome P450 1A2

UniProt P05177 Organism Homo sapiens Gene CYP1A2 EC 1.14.14.1, 4.2.1.152

Also known as: CYP1A2

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 (Probable).

Classification

Family (Pfam): PF00067 p450
InterPro: Cyt_P450, Cyt_P450_CS, Cyt_P450_E_grp-I, Cyt_P450_E_grp-I_CYP1, Cyt_P450_sf
Functional cluster: Secreted Growth Factors & Cytokines

Experimental structures · PDB · 1

2HI4 X-ray 1.95A

A predicted model is available from AlphaFold.

Gene Ontology · 33

Neighborhood · nearest proteins

Nearest neighbours of Cytochrome P450 1A2: 3 by sequence/function similarity (left); 3 co-cited in the literature (right).

Related proteins · sequence + function similarity

Co-cited proteins · studied together in the literature

Cytochrome P450 1A1 9 shared papers
Cytochrome P450 3A4 8 shared papers
Cytochrome P450 2C9 5 shared papers
Cytochrome P450 1B1 4 shared papers
Cytochrome P450 2S1 1 shared papers
Cytochrome P450 2D6 4 shared papers
Cytochrome P450 3A5 3 shared papers
Cytochrome P450 2B6 2 shared papers
Cytochrome P450 2J2 1 shared papers
Membrane-associated progesterone receptor component 1 1 shared papers
Cytochrome P450 2C19 2 shared papers
Cytochrome P450 2C8 2 shared papers

Literature · 26 cited papers

Haem-dependent dimerization of PGRMC1/Sigma-2 receptor facilitates cancer proliferation and chemoresistance. Nat. Commun. · 2016
An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J. Proteomics · 2014
Cholesterol 25-hydroxylation activity of CYP3A. J. Lipid Res. · 2011
Human CYP2S1 metabolizes cyclooxygenase- and lipoxygenase-derived eicosanoids. Drug Metab. Dispos. · 2011
Stereoselective epoxidation of the last double bond of polyunsaturated fatty acids by human cytochromes P450. J. Lipid Res. · 2010
Adaptations for the oxidation of polycyclic aromatic hydrocarbons exhibited by the structure of human P450 1A2. J. Biol. Chem. · 2007
Coffee, CYP1A2 genotype, and risk of myocardial infarction. JAMA · 2006
Single nucleotide polymorphisms and haplotypes of CYP1A2 in a Japanese population. Drug Metab. Pharmacokinet. · 2005
Toward the evaluation of function in genetic variability: characterizing human SNP frequencies and establishing BAC-transgenic mice carrying the human CYP1A1_CYP1A2 locus. Hum. Mutat. · 2005
The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
Genetic variation in eleven phase I drug metabolism genes in an ethnically diverse population. Pharmacogenomics · 2004
Functional characterization of four allelic variants of human cytochrome P450 1A2. Arch. Biochem. Biophys. · 2004
… and 14 more in the literature graph

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