ALOX15B

This gene encodes a member of the lipoxygenase family of structurally related nonheme iron dioxygenases involved in the production of fatty acid hydroperoxides. The encoded protein converts arachidonic acid exclusively to 15S-hydroperoxyeicosatetraenoic acid, while metabolizing linoleic acid less effectively. This gene is located in a cluster of related genes and a pseudogene that spans approximately 100 kilobases on the short arm of chromosome 17. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq]

Full Name

arachidonate 15-lipoxygenase, type B

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 (PubMed:9177185, PubMed:10625675, PubMed:12704195, PubMed:17493578, PubMed:18311922, PubMed:24282679, PubMed:10542053, PubMed:24497644, PubMed:32404334) (Probable). It inserts peroxyl groups at C15 of arachidonate ((5Z,8Z,11Z,14Z)-eicosatetraenoate) producing (15S)-hydroperoxyeicosatetraenoate/(15S)-HPETE (PubMed:17493578, PubMed:12704195, PubMed:24282679, PubMed:9177185, PubMed:11956198, PubMed:10625675, PubMed:24497644) (Probable). 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:18311922, PubMed:17493578, PubMed:11956198). 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 downregulate 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:12704195, PubMed:11839751). 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.

Biological Process

Apoptotic process Source: UniProtKB
Arachidonic acid metabolic process Source: UniProtKB
Cannabinoid biosynthetic process Source: UniProtKB
Endocannabinoid signaling pathway Source: UniProtKB
Hepoxilin biosynthetic process Source: UniProtKB
Linoleic acid metabolic process Source: GO_Central
Lipid metabolic process Source: UniProtKB
Lipid oxidation Source: GO_Central
Lipoxin A4 biosynthetic process Source: UniProtKB
Lipoxygenase pathway Source: GO_Central
Negative regulation of cell cycle Source: UniProtKB
Negative regulation of cell migration Source: UniProtKB
Negative regulation of cell population proliferation Source: UniProtKB
Negative regulation of growth Source: UniProtKB
Phospholipid metabolic process Source: UniProtKB
Positive regulation of chemokine production Source: UniProtKB
Positive regulation of keratinocyte differentiation Source: Ensembl
Positive regulation of macrophage derived foam cell differentiation Source: UniProtKB
Positive regulation of peroxisome proliferator activated receptor signaling pathway Source: Ensembl
Prostate gland development Source: UniProtKB
Regulation of epithelial cell differentiation

Cellular Location

Isoform A: Nucleus. Other isoforms are excluded from the nucleus. Cytosol; Cell membrane; Cytoskeleton; Membrane; Adherens junction; Focal adhesion. Predominantly cytosolic; becomes enriched at membranes upon calcium binding.