A cytochrome P450 monooxygenase involved in polyunsaturated fatty acids (PUFAs) metabolism and signaling. Catalyzes preferentially the epoxidation of double bonds of PUFAs. Converts arachidonic acid (ARA, C20:4(n-6)) primarily to stereospecific products 8R,9S-, 11R,12S-, and 14S,15R-EET (PubMed:8246128, PubMed:14742258, PubMed:10491410). Plays a major role in the formation of EETs and hydroxy-EETs (HEETs) in kidney (PubMed:10491410, PubMed:14742258). Via EETs may inhibit the epithelial sodium channels (ENaCs) in nephron segments, preventing excessive sodium absorption during high dietary salt intake (By similarity). 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 (PubMed:14742258). 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 (PubMed:15766564). 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) (PubMed:8246128). (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] = (11S,12R)-epoxy-(5Z,8Z,14Z)-eicosatrienoate + H(+) + H2O + oxidized [NADPH--hemoprotein reductase] (5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 + reduced [NADPH--hemoprotein reductase] = (14R,15S)-epoxy-(5Z,8Z,11Z)-eicosatrienoate + H(+) + H2O + oxidized [NADPH--hemoprotein reductase] (5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 + reduced [NADPH--hemoprotein reductase] = (14S,15R)-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. Expressed in kidney and liver. Expressed in cortical tubules of kidney (at protein level). Constitutively expressed. Up-regulated by fenofibrate. Belongs to the cytochrome P450 family.