The information on this page was automatically extracted from online scientific databases.
From NCBI Gene:
This gene encodes a member of the lipoxygenase gene family and plays a dual role in the synthesis of leukotrienes from arachidonic acid. The encoded protein, which is expressed specifically in bone marrow-derived cells, catalyzes the conversion of arachidonic acid to 5(S)-hydroperoxy-6-trans-8,11,14-cis-eicosatetraenoic acid, and further to the allylic epoxide 5(S)-trans-7,9-trans-11,14-cis-eicosatetrenoic acid (leukotriene A4). Leukotrienes are important mediators of a number of inflammatory and allergic conditions. Mutations in the promoter region of this gene lead to a diminished response to antileukotriene drugs used in the treatment of asthma and may also be associated with atherosclerosis and several cancers. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]
Catalyzes the oxygenation of arachidonic acid to 5-hydroperoxyicosatetraenoic acid (5-HPETE) followed by the dehydration of the hydroperoxide into an epoxide, 5,6- oxidoicosatetraenoic acid (LTA4), thereby participates in the first step in leukotriene biosynthesis and in the inflammatory processes (PubMed:8631361, PubMed:21233389, PubMed:22516296, PubMed:24282679, PubMed:19022417, PubMed:23246375, PubMed:8615788, PubMed:24893149, PubMed:31664810). Also catalyzes the oxygenation of arachidonic acid into 8-hydroperoxyicosatetraenoic acid (8-HPETE) and 12-hydroperoxyicosatetraenoic acid (12-HPETE) (PubMed:23246375). Although arachidonic acid is the preferred substrate, can also metabolize oxidized fatty acids derived from arachidonic acid such as (15S)-HETE, eicosapentaenoic acid (EPA) such as (18R)- and (18S)-HEPE or docosahexaenoic (DHA) acid which leads to the formation of specialized pro-resolving mediators (SPM) lipoxin and resolvins E and D respectively, therefore plays a role in anti-inflammatory response (PubMed:21206090, PubMed:31664810, PubMed:8615788, PubMed:17114001). Also displays lipoxin synthase activity being able to convert (15S)-HETE into a conjugate tetraene (PubMed:31664810). Oxidation of docosahexaenoic acid directly inhibits endothelial cell proliferation and sprouting angiogenesis via peroxisome proliferator-activated receptor gamma (PPARgamma) (By similarity). Does not catalyze the oxygenation of linoleic acid and does not convert (5S)-HETE to lipoxins isomers (PubMed:31664810). In addition to inflammatory processes, participates in dendritic cell migration, wound healing through an antioxidant mechanism based on HO1 regulation expression, monocyte adhesion to the endothelium via ITGAM expression on monocytes (By similarity). Moreover, establishes an adaptive humoral immunity by regulating primary resting B cells and follicular helper T cells and participates in the CD40-induced production of reactive oxygen species (ROS) after CD40 ligation in B cells through interaction with PIK3R1 that bridges ALOX5 with CD40 (PubMed:21200133). Also may play a role in glucose homeostasis, regulation of INS secretion and palmitic acid-induced insulin resistance via AMPK (By similarity). Can regulate bone mineralization and fat cell differentiation increases in induced pluripotent stem cells (By similarity).