CYP4F2

CYP4F2 (Cytochrome P450 Family 4 Subfamily F Member 2) is a Protein Coding gene. Diseases associated with CYP4F2 include Vitamin K Antagonists Toxicity Or Dose Selection and Inflammatory Bowel Disease 6. Among its related pathways are Arachidonic acid metabolism and Metabolism. Gene Ontology (GO) annotations related to this gene include iron ion binding and oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen. An important paralog of this gene is CYP4F3.

Cytochrome P450 Family 4 Subfamily F Member 2

A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids, eicosanoids and vitamins (PubMed:18577768, PubMed:10833273, PubMed:10660572, PubMed:11997390, PubMed:17341693, PubMed:18574070).

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 predominantly the oxidation of the terminal carbon (omega-oxidation) of long- and very long-chain fatty acids. Displays high omega-hydroxylase activity toward polyunsaturated fatty acids (PUFAs) (PubMed:18577768).

Participates in the conversion of arachidonic acid to omega-hydroxyeicosatetraenoic acid (20-HETE), a signaling molecule acting both as vasoconstrictive and natriuretic with overall effect on arterial blood pressure (PubMed:10660572, PubMed:17341693, PubMed:18574070).

Plays a role in the oxidative inactivation of eicosanoids, including both proinflammatory and anti-inflammatory mediators such as leukotriene B4 (LTB4), lipoxin A4 (LXA4), and several HETEs (PubMed:8026587, PubMed:9799565, PubMed:10833273, PubMed:10660572, PubMed:17341693, PubMed:18574070, PubMed:18577768).

Catalyzes omega-hydroxylation of 3-hydroxy fatty acids (PubMed:18065749).

Converts monoepoxides of linoleic acid leukotoxin and isoleukotoxin to omega-hydroxylated metabolites (PubMed:15145985).

Contributes to the degradation of very long-chain fatty acids (VLCFAs) by catalyzing successive omega-oxidations and chain shortening (PubMed:16547005, PubMed:18182499).

Plays an important role in vitamin metabolism by chain shortening. Catalyzes omega-hydroxylation of the phytyl chain of tocopherols (forms of vitamin E), with preference for gamma-tocopherols over alpha-tocopherols, thus promoting retention of alpha-tocopherols in tissues (PubMed:11997390).

Omega-hydroxylates and inactivates phylloquinone (vitamin K1), and menaquinone-4 (MK-4, a form of vitamin K2), both acting as cofactors in blood coagulation (PubMed:19297519, PubMed:24138531).

Arachidonic acid metabolic process Source: UniProtKB
Blood coagulation Source: UniProtKB
Drug metabolic process Source: UniProtKB
Epoxygenase P450 pathway Source: UniProtKB
Icosanoid metabolic process Source: Reactome
Leukotriene B4 catabolic process Source: UniProtKB
Leukotriene metabolic process Source: Reactome
Long-chain fatty acid metabolic process Source: BHF-UCL
Menaquinone catabolic process Source: UniProtKB
Negative regulation of icosanoid secretion Source: UniProtKB
Omega-hydroxylase P450 pathway Source: UniProtKB
Phylloquinone catabolic process Source: UniProtKB
Positive regulation of icosanoid secretion Source: UniProtKB
Pressure natriuresis Source: UniProtKB
Regulation of blood pressure Source: UniProtKB
Renal water homeostasis Source: UniProtKB
Sodium ion homeostasis Source: UniProtKB
Very long-chain fatty acid metabolic process Source: BHF-UCL
Vitamin E metabolic process Source: UniProtKB
Vitamin K catabolic process Source: UniProtKB

Endoplasmic reticulum membrane; Microsome membrane

Coumarin resistance (CMRES):
Disease susceptibility may be associated with variants affecting the gene represented in this entry. The variant Met-433 is associated with coumarin (the brand name of warfarin) resistance by increasing coumarin maintenance dose in patients on this anti-coagulant therapy. This is probably due to decreased activity of the phylloquinone omega-hydroxylase activity, leading to an increase in hepatic vitamin K levels that warfarin must antagonize (PubMed:24138531).
A condition characterized by partial or complete resistance to warfarin or other 4-hydroxycoumarin derivatives. These drugs are used as anti-coagulants for the prevention of thromboembolic diseases in subjects with deep vein thrombosis, atrial fibrillation, or mechanical heart valve replacement.