A cytochrome P450 monooxygenase involved in polyunsaturated fatty acids (PUFAs) metabolism and signaling (PubMed:15084647). Catalyzes preferentially the epoxidation of double bonds of PUFAs (PubMed:15084647). Converts arachidonic acid (ARA, C20:4(n-6)) primarily to stereospecific products 8R,9S-epoxyeicosatrienoate (EET) and 11R,12S-EET (PubMed:15084647). Plays a major role in the formation of EETs and hydroxy-EETs (HEETs) in kidney. Via EETs may inhibit the epithelial sodium channels (ENaCs) in nephron segments, preventing excessive sodium absorption during high dietary salt intake (PubMed:24966089, PubMed:24368771). Participates in the formation of anti-inflammatory hydroxyepoxyeicosatrienoic acids (HEETs) by converting 20-hydroxyeicosatetraenoic acid (20-HETE) to 20,8,9-HEET, an activator of PPARA (By similarity). Metabolizes eicosapentaenoic acid (EPA, C20:5(n-3)) to epoxyeicosatetraenoic acid (EETeTr) regioisomers, 8,9-, 11,12-, 14,15-, and 17,18- EETeTr, preferentially producing 17R,18S enantiomer (By similarity). 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) (PubMed:15084647). (5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 + reduced [NADPH--hemoprotein reductase] = (8R,9S)-epoxy-(5Z,11Z,14Z)-eicosatrienoate + H(+) + H2O + oxidized [NADPH--hemoprotein reductase] (5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 + reduced [NADPH--hemoprotein reductase] = (11R,12S)-epoxy-(5Z,8Z,14Z)-eicosatrienoate + H(+) + H2O + oxidized [NADPH--hemoprotein reductase] (5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 + reduced [NADPH--hemoprotein reductase] = 14,15-epoxy-(5Z,8Z,11Z)-eicosatrienoate + H(+) + H2O + oxidized [NADPH--hemoprotein reductase] (5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate + O2 + reduced [NADPH--hemoprotein reductase] = 8,9-epoxy-(5Z,11Z,14Z,17Z)-eicosatetraenoate + H(+) + H2O + oxidized [NADPH--hemoprotein reductase] (5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate + O2 + reduced [NADPH--hemoprotein reductase] = 11,12-epoxy-(5Z,8Z,14Z,17Z)-eicosatetraenoate + H(+) + H2O + oxidized [NADPH--hemoprotein reductase] (5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate + O2 + reduced [NADPH--hemoprotein reductase] = 14,15-epoxy-(5Z,8Z,11Z,17Z)-eicosatetraenoate + H(+) + H2O + oxidized [NADPH--hemoprotein reductase] (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] (5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate + O2 + reduced [NADPH--hemoprotein reductase] = (17S,18R)-epoxy-(5Z,8Z,11Z,14Z)-eicosatetraenoate + H(+) + H2O + oxidized [NADPH--hemoprotein reductase] 20-hydroxy-(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 + reduced [NADPH--hemoprotein reductase] = 20-hydroxy-8,9-epoxy-(5Z,11Z,14Z)-eicosatrienoate + H(+) + H2O + oxidized [NADPH--hemoprotein reductase] Lipid metabolism; arachidonate metabolism. Highly expressed in liver, particularly in hepatocytes and bile duct epithelial cells (at protein level) (PubMed:24966089). Expressed in nephron segments (PubMed:24966089, PubMed:15084647). Prominent expression is detected in proximal tubules at the corticomedullary junction (at protein level) (PubMed:15084647). Also expressed in renal cortical collecting duct (PubMed:15084647). Lower expression levels are detected in adrenal glands (PubMed:15084647). Up-regulated by high sodium or high potassium diets. High sodium intake increases expression in thick ascending limb and distal convoluted tubule. An increase in dietary potassium intake induces expression in distal convoluted tubule and cortical collecting duct. Mutant mice have normal development and lack symptoms of disease or organ malformation (PubMed:24368771). Become hypertensive in response to high sodium or high potassium diets (PubMed:24368771, PubMed:24966089). Belongs to the cytochrome P450 family.