Non-heme iron-containing dioxygenase that catalyzes the stereo-specific peroxidation of free and esterified polyunsaturated fatty acids (PUFAs) generating a spectrum of bioactive lipid mediators (    ) (Probable). It inserts peroxyl groups at C15 of arachidonate ((5Z,8Z,11Z,14Z)-eicosatetraenoate) producing (15S)-hydroperoxyeicosatetraenoate/(15S)-HPETE (   ) (Probable). Also peroxidizes linoleate ((9Z,12Z)-octadecadienoate) to 13-hydroperoxyoctadecadienoate/13-HPODE (Probable) (, ). Oxygenates arachidonyl derivatives such as 2-arachidonoylglycerol (2-AG) leading to the production and extracellular release of 15-hydroxyeicosatetraenoyl glycerol (15-HETE-G) that acts as a peroxisome proliferator-activated receptor alpha agonist ( ). Has the ability to efficiently class-switch ALOX5 pro-inflammatory mediators into anti-inflammatory intermediates . Participates in the sequential oxidations of DHA ((4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate) to generate specialized pro-resolving mediators (SPMs) resolvin D5 ((7S,17S)-diHPDHA), which can actively down-regulate the immune response and have anti-aggregation properties with platelets . In addition to free PUFAs hydrolyzed from phospholipids, it directly oxidizes PUFAs esterified to membrane-bound phospholipids . Has no detectable 8S-lipoxygenase activity on arachidonate but reacts with (8S)-HPETE to produce (8S,15S)-diHPETE (Probable). May regulate progression through the cell cycle and cell proliferation (, ). May also regulate cytokine secretion by macrophages and therefore play a role in the immune response . May also regulate macrophage differentiation into proatherogenic foam cells .
Does not convert arachidonic acid to 15S-hydroperoxyeicosatetraenoic acid/(15S)-HPETE.
Subcellular locations: Nucleus
Other isoforms are excluded from the nucleus.
Subcellular locations: Cytoplasm, Cytosol, Cell membrane, Cytoplasm, Cytoskeleton, Membrane, Cell junction, Adherens junction, Cell junction, Focal adhesion
Predominantly cytosolic; becomes enriched at membranes upon calcium binding.
Expressed in hair, prostate, lung, ovary, lymph node, spinal cord and cornea.