FEATURES

FAMILY

DESCRIPTION

Also known as LOX5_HUMAN, ALOX5, LOG5. Catalyzes the oxygenation of arachidonate ((5Z, 8Z, 11Z, 14Z)-eicosatetraenoate) to 5-hydroperoxyeicosatetraenoate (5-HPETE) followed by the dehydration to 5, 6- epoxyeicosatetraenoate (Leukotriene A4/LTA4), the first two steps in the biosynthesis of leukotrienes, which are potent mediators of inflammation (PubMed:8631361, PubMed:21233389, PubMed:22516296, PubMed:24282679, PubMed:19022417, PubMed:23246375, PubMed:8615788, PubMed:24893149, PubMed:31664810). Also catalyzes the oxygenation of arachidonate into 8-hydroperoxyicosatetraenoate (8-HPETE) and 12-hydroperoxyicosatetraenoate (12-HPETE) (PubMed:23246375). Displays lipoxin synthase activity being able to convert (15S)-HETE into a conjugate tetraene (PubMed:31664810). Although arachidonate is the preferred substrate, this enzyme can also metabolize oxidized fatty acids derived from arachidonate such as (15S)-HETE, eicosapentaenoate (EPA) such as (18R)- and (18S)-HEPE or docosahexaenoate (DHA) which lead to the formation of specialized pro-resolving mediators (SPM) lipoxin and resolvins E and D respectively, therefore it participates in anti-inflammatory responses (PubMed:21206090, PubMed:31664810, PubMed:8615788, PubMed:17114001, PubMed:32404334). Oxidation of DHA directly inhibits endothelial cell proliferation and sprouting angiogenesis via peroxisome proliferator-activated receptor gamma (PPARgamma) (By similarity). It does not catalyze the oxygenation of linoleic acid and does not convert (5S)-HETE to lipoxin isomers (PubMed:31664810). In addition to inflammatory processes, it participates in dendritic cell migration, wound healing through an antioxidant mechanism based on heme oxygenase-1 (HO-1) regulation expression, monocyte adhesion to the endothelium via ITGAM expression on monocytes (By similarity). Moreover, it helps establish 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). May also play a role in glucose homeostasis, regulation of insulin 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). Homodimer (PubMed:22516296, PubMed:21233389). Interacts with ALOX5AP and LTC4S (PubMed:19233132). Interacts with COTL1, the interaction is required for stability and efficient catalytic activity (PubMed:19807693). Interacts with PIK3R1; this interaction bridges ALOX5 with CD40 after CD40 ligation in B cells and leads to the production of reactive oxygen species (ROS) (PubMed:21200133). Interacts (via PLAT domain) with DICER1 (via Dicer dsRNA-binding fold domain); this interaction enhances arachidonate 5-lipoxygenase activity and modifies the miRNA precursor processing activity of DICER1 (PubMed:19022417).

EXTERNAL LINKS

ALOX5

Polyunsaturated fatty acid 5-lipoxygenase

ALOX5

Molecular Synopsis