ALOX15B
Domain
The PLAT domain can bind calcium ions; this promotes association with membranes.
Function
Isoform A
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) (PubMed:10542053, PubMed:10625675, PubMed:12704195, PubMed:17493578, PubMed:18311922, PubMed:24282679, PubMed:24497644, PubMed:32404334, PubMed:9177185). It inserts peroxyl groups at C15 of arachidonate ((5Z,8Z,11Z,14Z)-eicosatetraenoate) producing (15S)-hydroperoxyeicosatetraenoate/(15S)-HPETE (Probable) (PubMed:10625675, PubMed:11956198, PubMed:12704195, PubMed:17493578, PubMed:24282679, PubMed:24497644, PubMed:9177185). Also peroxidizes linoleate ((9Z,12Z)-octadecadienoate) to 13-hydroperoxyoctadecadienoate/13-HPODE (Probable) (PubMed:10542053, PubMed:27435673). 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 (PubMed:11956198, PubMed:17493578, PubMed:18311922). Has the ability to efficiently class-switch ALOX5 pro-inflammatory mediators into anti-inflammatory intermediates (PubMed:27145229). 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 (PubMed:32404334). In addition to free PUFAs hydrolyzed from phospholipids, it directly oxidizes PUFAs esterified to membrane-bound phospholipids (PubMed:27435673). 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 (PubMed:11839751, PubMed:12704195). May also regulate cytokine secretion by macrophages and therefore play a role in the immune response (PubMed:18067895). May also regulate macrophage differentiation into proatherogenic foam cells (PubMed:22912809).
Isoform B
Does not convert arachidonic acid to 15S-hydroperoxyeicosatetraenoic acid/(15S)-HPETE.
Pathway
Lipid metabolism; hydroperoxy eicosatetraenoic acid biosynthesis.
Sequence Similarities
Belongs to the lipoxygenase family.
Tissue Specificity
Expressed in hair, prostate, lung, ovary, lymph node, spinal cord and cornea.
Cellular localization
- Isoform A
- Nucleus
- Other isoforms are excluded from the nucleus.
- Cytoplasm
- Cytosol
- Cell membrane
- Cytoplasm
- Cytoskeleton
- Membrane
- Peripheral membrane protein
- Cell junction
- Adherens junction
- Cell junction
- Focal adhesion
- Predominantly cytosolic; becomes enriched at membranes upon calcium binding.
Alternative names
Polyunsaturated fatty acid lipoxygenase ALOX15B, 15-lipoxygenase 2, Arachidonate 15-lipoxygenase B, Arachidonate 15-lipoxygenase type II, Linoleate 13-lipoxygenase 15-LOb, 15-LOX-2, 15-LOX-B, ALOX15B