Alox15

This gene encodes a member of the lipoxygenase family of proteins. The encoded enzyme acts on various polyunsaturated fatty acid substrates to generate various bioactive lipid mediators such as eicosanoids, hepoxilins, lipoxins, and other molecules. The encoded enzyme and its reaction products have been shown to regulate inflammation and immunity. Multiple pseudogenes of this gene have been identified in the human genome. [provided by RefSeq, Aug 2017]

Arachidonate 15-Lipoxygenase

Non-heme iron-containing dioxygenase that catalyzes the stereo-specific peroxidation of free and esterified polyunsaturated fatty acids generating a spectrum of bioactive lipid mediators (PubMed:1944593, PubMed:8334154, PubMed:17052953, PubMed:24282679, PubMed:25293588, PubMed:32404334). It inserts peroxyl groups at C12 or C15 of arachidonate ((5Z,8Z,11Z,14Z)-eicosatetraenoate) producing both 12-hydroperoxyeicosatetraenoate/12-HPETE and 15-hydroperoxyeicosatetraenoate/15-HPETE (PubMed:1944593, PubMed:8334154, PubMed:17052953, PubMed:24282679). It may then act on 12-HPETE to produce hepoxilins, which may show proinflammatory properties (By similarity). Can also peroxidize linoleate ((9Z,12Z)-octadecadienoate) to 13-hydroperoxyoctadecadienoate/13-HPODE (PubMed:8334154). May participate in the sequential oxidations of DHA ((4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate) to generate specialized pro-resolving mediators (SPMs)like resolvin D5 ((7S,17S)-diHPDHA) and (7S,14S)-diHPDHA, that actively downregulate the immune response and have anti-aggregation properties with platelets (PubMed:32404334). Can convert epoxy fatty acids to hydroperoxy-epoxides derivatives followed by an intramolecular nucleophilic substitution leading to the formation of monocyclic endoperoxides (PubMed:25293588). Plays an important role during the maintenance of self-tolerance by peroxidizing membrane-bound phosphatidylethanolamine which can then signal the sorting process for clearance of apoptotic cells during inflammation and prevent an autoimmune response. In addition to its role in the immune and inflammatory responses, this enzyme may play a role in epithelial wound healing in the cornea through production of lipoxin A4 (LXA4) and docosahexaenoic acid-derived neuroprotectin D1 (NPD1; 10R,17S-HDHA), both lipid autacoids exhibit anti-inflammatory and neuroprotective properties. Furthermore, it may regulate actin polymerization which is crucial for several biological processes such as the phagocytosis of apoptotic cells. It is also implicated in the generation of endogenous ligands for peroxisome proliferator activated receptor (PPAR-gamma), hence modulating macrophage development and function. It may also exert a negative effect on skeletal development by regulating bone mass through this pathway. As well as participates in ER stress and downstream inflammation in adipocytes, pancreatic islets, and liver (By similarity). Finally, it is also involved in the cellular response to IL13/interleukin-13 (PubMed:21831839).

Apoptotic cell clearance Source: UniProtKB
Arachidonic acid metabolic process Source: UniProtKB
Bone mineralization Source: UniProtKB
Cellular response to calcium ion Source: UniProtKB
Cellular response to interleukin-13 Source: UniProtKB
Cytokine-mediated signaling pathway Source: Reactome
Fatty acid oxidation Source: UniProtKB
Hepoxilin biosynthetic process Source: UniProtKB
Inflammatory response Source: ProtInc
Leukotriene metabolic process Source: Reactome
Linoleic acid metabolic process Source: UniProtKB
Lipid metabolic process Source: UniProtKB
Lipid oxidation Source: GO_Central
Lipoxin A4 biosynthetic process Source: UniProtKB
Lipoxygenase pathway Source: UniProtKB
Long-chain fatty acid biosynthetic process Source: Reactome
Negative regulation of adaptive immune response Source: UniProtKB
Ossification Source: UniProtKB
Phosphatidylethanolamine biosynthetic process Source: UniProtKB
Positive regulation of actin filament polymerization Source: UniProtKB
Positive regulation of cell-substrate adhesion Source: UniProtKB
Positive regulation of ERK1 and ERK2 cascade Source: UniProtKB
Positive regulation of heterotypic cell-cell adhesion Source: Ensembl
Regulation of engulfment of apoptotic cell Source: UniProtKB
Regulation of inflammatory response Source: UniProtKB
Regulation of peroxisome proliferator activated receptor signaling pathway Source: UniProtKB
Response to endoplasmic reticulum stress Source: UniProtKB
Wound healing Source: UniProtKB

Cytosol; Cell membrane; Lipid droplet. Predominantly cytosolic; becomes enriched at membranes upon calcium binding (By similarity). Translocates from the cytosol to the plasma membrane when stimulated by IL13/interleukin-13 and in macrophages binding apoptotic cells (By similarity).

Disease susceptibility may be associated with variants affecting the gene represented in this entry. Met at position 560 may confer interindividual susceptibility to coronary artery disease (CAD) (PubMed:17959182).