UniprotKB/SwissProt ID: P48999 (P48999)
Gene Name:
Alox5
Organism: Mus musculus (Mouse)
Function: 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:23246375, PubMed:31642348, PubMed:7629107, PubMed:7809134, PubMed:7969451). 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:17392829, PubMed:23720274, PubMed:24226420, 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:18421434, PubMed:28694473). Can regulate bone mineralization and fat cell differentiation increases in induced pluripotent stem cells (PubMed:24906289)
Other Modifications: View all modification sites in dbPTM
Protein Subcellular Localization: Cytoplasm. Nucleus matrix. Nucleus membrane. Cytoplasm, perinuclear region. Cytoplasm, cytosol. Nucleus envelope. Nucleus intermembrane space
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