Protein: Polyunsaturated fatty acid 5-lipoxygenase (EC 1.13.11.-) (Arachidonate 5-lipoxygenase) (5-LO) (5-lipoxygenase) (EC 1.13.11.34) (P09917)
Organism: Homo sapiens (Human)
Function: 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. Also catalyzes the oxygenation of arachidonate into 8-hydroperoxyicosatetraenoate (8-HPETE) and 12-hydroperoxyicosatetraenoate (12-HPETE). Displays lipoxin synthase activity being able to convert (15S)-HETE into a conjugate tetraene. 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. 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. 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. 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).
Subcellular location: Cytoplasm {ECO:0000250|UniProtKB:P48999, ECO:0000269|PubMed:18978352}. Nucleus matrix {ECO:0000269|PubMed:19233132}. Nucleus membrane {ECO:0000269|PubMed:16275640}; Peripheral membrane protein {ECO:0000269|PubMed:16275640}. Cytoplasm, perinuclear region {ECO:0000269|PubMed:19022417}. Cytoplasm, cytosol {ECO:0000269|PubMed:19233132}. Nucleus envelope {ECO:0000269|PubMed:16275640, ECO:0000269|PubMed:19233132, ECO:0000269|PubMed:8245774}. Nucleus intermembrane space {ECO:0000269|PubMed:8245774}. Note=Shuttles between cytoplasm and nucleus (PubMed:19233132). Found exclusively in the nucleus, when phosphorylated on Ser-272 (PubMed:18978352). Calcium binding promotes translocation from the cytosol and the nuclear matrix to the nuclear envelope and membrane association (PubMed:16275640, PubMed:19233132, PubMed:3118366, PubMed:8245774). {ECO:0000269|PubMed:16275640, ECO:0000269|PubMed:18978352, ECO:0000269|PubMed:19233132, ECO:0000269|PubMed:3118366, ECO:0000269|PubMed:8245774}.
Interaction partners:
- Arachidonate 5-lipoxygenase-activating protein
- Leukotriene A-4 hydrolase
- Coactosin-like protein
- Leukotriene C4 synthase
- Prostaglandin G/H synthase 2
- Prostaglandin G/H synthase 1
- Cytochrome P450 2C9
- Cytochrome P450 2C19
- Glutathione peroxidase 3
- Glutathione peroxidase 2
Sequence:
MPSYTVTVATGSQWFAGTDDYIYLSLVGSAGCSEKHLLDKPFYNDFERGAVDSYDVTVDEELGEIQLVRIEKRKYWLNDDWYLKYITLKTPHGDYIEFPCYRWITGDVEVVLRDGRAKLARDDQIHILKQHRRKELETRQKQYRWMEWNPGFPLSIDAKCHKDLPRDIQFDSEKGVDFVLNYSKAMENLFINRFMHMFQSSWNDFADFEKIFVKISNTISERVMNHWQEDLMFGYQFLNGCNPVLIRRCTELPEKLPVTTEMVECSLERQLSLEQEVQQGNIFIVDFELLDGIDANKTDPCTLQFLAAPICLLYKNLANKIVPIAIQLNQIPGDENPIFLPSDAKYDWLLAKIWVRSSDFHVHQTITHLLRTHLVSEVFGIAMYRQLPAVHPIFKLLVAHVRFTIAINTKAREQLICECGLFDKANATGGGGHVQMVQRAMKDLTYASLCFPEAIKARGMESKEDIPYYFYRDDGLLVWEAIRTFTAEVVDIYYEGDQVVEEDPELQDFVNDVYVYGMRGRKSSGFPKSVKSREQLSEYLTVVIFTASAQHAAVNFGQYDWCSWIPNAPPTMRAPPPTAKGVVTIEQIVDTLPDRGRSCWHLGAVWALSQFQENELFLGMYPEEHFIEKPVKEAMARFRKNLEAIVSVIAERNKKKQLPYYYLSPDRIPNSVAI