Catalyzes the oxygenation of arachidonate 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:7629107, PubMed:7809134, PubMed:7969451, PubMed:23246375, PubMed:31642348). Also catalyzes the oxygenation of arachidonic acid into 8-hydroperoxyicosatetraenoic acid (8-HPETE) and 12-hydroperoxyicosatetraenoic acid (12-HPETE) (PubMed:23246375). Displays lipoxin synthase activity being able to convert (15S)-HETE into a conjugate tetraene (By similarity). 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:31642348). Oxidation of DHA directly inhibits endothelial cell proliferation and sprouting angiogenesis via peroxisome proliferator-activated receptor gamma (PPARgamma)(PubMed:21307302). It does not catalyze the oxygenation of linoleic acid and does not convert (5S)-HETE to lipoxin isomers (PubMed:31642348). In addition to inflammatory processes, 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 (PubMed:24226420, PubMed:23720274, PubMed:17392829, PubMed:28965882). 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:21224059). May also play a role in glucose homeostasis, regulation of insulin secretion and palmitic acid-induced insulin resistance via AMPK (PubMed:28694473, PubMed:18421434). Can regulate bone mineralization and fat cell differentiation increases in induced pluripotent stem cells (PubMed:24906289). (5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 = (5S)-hydroperoxy-(6E,8Z,11Z,14Z)-eicosatetraenoate (5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 = H2O + leukotriene A4 (5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 = (8S)-hydroperoxy-(5Z,9E,11Z,14Z)-eicosatetraenoate (5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 = (12S)-hydroperoxy-(5Z,8Z,10E,14Z)-eicosatetraenoate 18-HEPE + O2 = (5S)-hydroperoxy-18-hydroxy-(7E,9E,11Z,14Z,16E)-eicosapentaenoate (18R)-hydroxy-(5Z,8Z,11Z,14Z,16E)-eicosapentaenoate + O2 = (5S)-hydroperoxy-(18R)-hydroxy-(6E,8Z,11Z,14Z,16E)-eicosapentaenoate (18S)-hydroxy-(5Z,8Z,11Z,14Z,16E)-eicosapentaenoate + O2 = (5S)-hydroperoxy-(18S)-hydroxy-(6E,8Z,11Z,14Z,16E)-eicosapentaenoate (5S)-hydroperoxy-(18S)-hydroxy-(6E,8Z,11Z,14Z,16E)-eicosapentaenoate = (5S,6S)-epoxy-(18S)-hydroxy-(7E,9E,11Z,14Z,16E)-eicosapentaenoate + H2O (5S)-hydroperoxy-(18R)-hydroxy-(6E,8Z,11Z,14Z,16E)-eicosapentaenoate = (5S,6S)-epoxy-(18R)-hydroxy-(7E,9E,11Z,14Z,16E)-eicosapentaenoate + H2O (5S)-hydroperoxy-18-hydroxy-(7E,9E,11Z,14Z,16E)-eicosapentaenoate = (5S,6S)-epoxy-18-hydroxy-(7E,9E,11Z,14Z,16E)-eicosapentaenoate + H2O (5Z,8Z,11Z,13E,15S)-hydroxyeicosatetraenoate + O2 = (5S)-hydroperoxy-(15S)-hydroxy-(6E,8Z,11Z,13E)-eicosatetraenoate (5S)-hydroperoxy-(6E,8Z,11Z,14Z)-eicosatetraenoate = H2O + leukotriene A4 (5Z,8Z)-eicosadienoate + O2 = (5S)-hydroperoxy-(6E,8Z)-eicosadienoate (12S)-hydroxy-(5Z,8Z,10E,14Z)-eicosatetraenoate + O2 = (5S)-hydroperoxy-(12S)-hydroxy-(6E,8Z,10E,14Z)-eicosatetraenoate (5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate + O2 = 5-hydroperoxy-(6E,8Z,11Z,14Z,17Z)-eicosapentaenoate (4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate + O2 = (14S)-hydroperoxy-(4Z,7Z,10Z,12E,16Z,19Z)-docosahexaenoate (4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate + O2 = (7S)-hydroperoxy-(4Z,8E,10Z,13Z,16Z,19Z)-docosahexaenoate (4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate + O2 = (17S)-hydroperoxy-(4Z,7Z,10Z,13Z,15E,19Z)-docosahexaenoate Binds 1 Fe cation per subunit. Lipid metabolism; leukotriene A4 biosynthesis. Homodimer. Interacts with ALOX5AP and LTC4S. Interacts with COTL1, the interaction is required for stability and efficient catalytic activity. 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). 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. Shuttles between cytoplasm and nucleus. Found exclusively in the nucleus, when phosphorylated on Ser-272. Calcium binding promotes translocation from the cytosol and the nuclear matrix to the nuclear envelope and membrane association. Expressed in skin Langerhans cells and their emigrated counterparts in draining lymph nodes (PubMed:17392829). Highly expressed in circulating leukocytes (PubMed:21307302). IncreaseD by both NF-kappa-B and SP1 in LPS-treated monocytes. Serine phosphorylation by MAPKAPK2 is stimulated by arachidonic acid. Phosphorylation on Ser-524 by PKA has an inhibitory effect. Phosphorylation on Ser-272 prevents export from the nucleus. Phosphorylation at Ser-524 is stimulated by 8-bromo-3',5'-cyclic AMP or prostaglandin E2. Homozygous mice for ALOX5 are also present in the expected ratios. Mice are indistinguishable in growth and size from wild type littermates (PubMed:7809134). Homozygous mice for ALOX5 show no apparent abnormalities up to ten months of age under normal physiological conditions, except that the spleen is usually smaller for 8-week-old mice (PubMed:7969451). Can be converted from pro-inflammatory 5-lipoxygenase to anti-inflammatory 15-lipoxygenase by reducing the volume of the substrate-binding pocket. Belongs to the lipoxygenase family.