CYP2J2

Description

The CYP2J2 (cytochrome P450 family 2 subfamily J member 2) is a protein-coding gene located on chromosome 1.

Cytochrome P450 2J2 (CYP2J2) is a protein that in humans is encoded by the CYP2J2 gene. CYP2J2 is a member of the cytochrome P450 superfamily of enzymes. The enzymes are oxygenases which catalyze many reactions involved in the metabolism of drugs and other xenobiotics) as well as in the synthesis of cholesterol, steroids and other lipids.

== Protein structure == The CYP2J2 contains the following domains: • Hydrophobic binding domains • F-G loop (containing non-conservative mutations) primary membrane binding motif The protein also contains an N-terminal anchor.

=== F-G loop === The F-G loop mediates the binding and passage of substrates, and its hydrophobic region containing residues Trp-235, Phe-239 and Ille-236 allows the enzyme to interact with cellular membranes. Mutations to hydrophilic residues in the F-G loop alter the binding mechanism by changing insertion depth of the enzyme into the membrane.

== Tissue distribution == CYP2J2 is expressed predominately in the heart and, to a lesser extent, in other tissues such as the liver, gastrointestinal tract, pancreas, lung, and central nervous system.

== Function == CYP2J2 localizes to the endoplasmic reticulum and is thought to be a prominent enzyme responsible for metabolizing endogenous polyunsaturated fatty acids to signaling molecules. It metabolizes arachidonic acid to the following eicosatrienoic acid epoxides (termed EETs): 5,6-epoxy-8Z,11Z,14Z-EET, 8,9-epoxy-8Z,11Z,14Z-EET, 11,12-epoxy-5Z,8Z,14Z-EET, and 14,15-epoxy-5Z,8Z,11Z-EET. CYP2J2 also metabolizes linoleic acid to 9,10-epoxy octadecenoic acids (also termed vernolic acid, linoleic acid 9:10-oxide, or leukotoxin) and 12,13-epoxy-octadecenoic (also termed coronaric acid, linoleic acid 12,13-oxide, or isoleukotoxin); docosahexaenoic acid to various epoxydocosapentaenoic acids (also termed EDPs); and eicosapentaenoic acid to various epoxyeicosatetraenoic acids (also termed EEQs). CYP2J2, along with CYP219, CYP2C8, CYP2C9, and possibly CYP2S1 are the main producers of EETs and, very likely EEQs, EDPs, and the epoxides of linoleic acid.

CYP2J2 is a cytochrome P450 monooxygenase involved in the metabolism of polyunsaturated fatty acids (PUFAs) in the cardiovascular system. It 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). CYP2J2 catalyzes the epoxidation of double bonds of PUFAs, converting arachidonic acid to four regioisomeric epoxyeicosatrienoic acids (EpETrE). This enzyme likely plays a major role in the epoxidation of endogenous cardiac arachidonic acid pools. In endothelial cells, CYP2J2 participates in eicosanoid metabolism by converting hydroperoxide species into hydroxy epoxy metabolites. In combination with 15-lipoxygenase, it metabolizes arachidonic acid and converts hydroperoxyicosatetraenoates (HpETEs) into hydroxy epoxy eicosatrienoates (HEETs), which are precursors of vasodilatory trihydroxyicosatrienoic acids (THETAs). This hydroperoxide isomerase activity is NADPH- and O2-independent. CYP2J2 also catalyzes the monooxygenation of various xenobiotics, such as danazol, amiodarone, terfenadine, astemizole, thioridazine, tamoxifen, cyclosporin A, and nabumetone. It catalyzes hydroxylation of the anthelmintics albendazole and fenbendazole, as well as the sulfoxidation of fenbendazole.

CYP2J2 is also known as CPJ2, CYPIIJ2.

Associated Diseases

WES Whole Exome Sequencing

Clinical Exome Sequencing