Protein: Polyunsaturated fatty acid lipoxygenase ALOX15B (15-lipoxygenase 2) (15-LOX-2) (Arachidonate 15-lipoxygenase B) (15-LOX-B) (EC 1.13.11.33) (Arachidonate 15-lipoxygenase type II) (Linoleate 13-lipoxygenase 15-LOb) (EC 1.13.11.-) (O15296)
Organism: Homo sapiens (Human)
Function: Non-heme iron-containing dioxygenase that catalyzes the stereo-specific peroxidation of free and esterified polyunsaturated fatty acids (PUFAs) generating a spectrum of bioactive lipid mediators (Probable). It inserts peroxyl groups at C15 of arachidonate ((5Z,8Z,11Z,14Z)-eicosatetraenoate) producing (15S)-hydroperoxyeicosatetraenoate/(15S)-HPETE (Probable). Also peroxidizes linoleate ((9Z,12Z)-octadecadienoate) to 13-hydroperoxyoctadecadienoate/13-HPODE (Probable). Oxygenates arachidonyl derivatives such as 2-arachidonoylglycerol (2-AG) leading to the production and extracellular release of 15-hydroxyeicosatetraenoyl glycerol (15-HETE-G) that acts as a peroxisome proliferator-activated receptor alpha agonist. Has the ability to efficiently class-switch ALOX5 pro-inflammatory mediators into anti-inflammatory intermediates. Participates in the sequential oxidations of DHA ((4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate) to generate specialized pro-resolving mediators (SPMs) resolvin D5 ((7S,17S)-diHPDHA), which can actively down-regulate the immune response and have anti-aggregation properties with platelets. In addition to free PUFAs hydrolyzed from phospholipids, it directly oxidizes PUFAs esterified to membrane-bound phospholipids. Has no detectable 8S-lipoxygenase activity on arachidonate but reacts with (8S)-HPETE to produce (8S,15S)-diHPETE (Probable). May regulate progression through the cell cycle and cell proliferation. May also regulate cytokine secretion by macrophages and therefore play a role in the immune response. May also regulate macrophage differentiation into proatherogenic foam cells.
Subcellular location: [Isoform A]: Nucleus {ECO:0000269|PubMed:12704195}. Note=Other isoforms are excluded from the nucleus. {ECO:0000269|PubMed:12704195}.; SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:12704195}. Cell membrane {ECO:0000269|PubMed:12704195, ECO:0000269|PubMed:27435673}. Cytoplasm, cytoskeleton {ECO:0000269|PubMed:12704195}. Membrane {ECO:0000269|PubMed:10542053, ECO:0000269|PubMed:24497644}; Peripheral membrane protein {ECO:0000269|PubMed:24497644}. Cell junction, adherens junction {ECO:0000269|PubMed:12704195}. Cell junction, focal adhesion {ECO:0000269|PubMed:12704195}. Note=Predominantly cytosolic; becomes enriched at membranes upon calcium binding. {ECO:0000269|PubMed:10542053, ECO:0000269|PubMed:12704195, ECO:0000269|PubMed:24497644, ECO:0000269|PubMed:27435673}.
Interaction partners:
- Prostaglandin G/H synthase 2
- Prostaglandin G/H synthase 1
- Cytochrome P450 4F8
- Glutathione peroxidase 3
- Cytochrome P450 4F3
- Polyunsaturated fatty acid lipoxygenase ALOX12
- Cytochrome P450 4A11
- Cytochrome P450 2J2))
- Glutathione peroxidase 6
- Epididymal secretory glutathione peroxidase
Sequence:
MAEFRVRVSTGEAFGAGTWDKVSVSIVGTRGESPPLPLDNLGKEFTAGAEEDFQVTLPEDVGRVLLLRVHKAPPVLPLLGPLAPDAWFCRWFQLTPPRGGHLLFPCYQWLEGAGTLVLQEGTAKVSWADHHPVLQQQRQEELQARQEMYQWKAYNPGWPHCLDEKTVEDLELNIKYSTAKNANFYLQAGSAFAEMKIKGLLDRKGLWRSLNEMKRIFNFRRTPAAEHAFEHWQEDAFFASQFLNGLNPVLIRRCHYLPKNFPVTDAMVASVLGPGTSLQAELEKGSLFLVDHGILSGIQTNVINGKPQFSAAPMTLLYQSPGCGPLLPLAIQLSQTPGPNSPIFLPTDDKWDWLLAKTWVRNAEFSFHEALTHLLHSHLLPEVFTLATLRQLPHCHPLFKLLIPHTRYTLHINTLARELLIVPGQVVDRSTGIGIEGFSELIQRNMKQLNYSLLCLPEDIRTRGVEDIPGYYYRDDGMQIWGAVERFVSEIIGIYYPSDESVQDDRELQAWVREIFSKGFLNQESSGIPSSLETREALVQYVTMVIFTCSAKHAAVSAGQFDSCAWMPNLPPSMQLPPPTSKGLATCEGFIATLPPVNATCDVILALWLLSKEPGDQRPLGTYPDEHFTEEAPRRSIATFQSRLAQISRGIQERNQGLVLPYTYLDPPLIENSVSI