Protein: Polyunsaturated fatty acid 5-lipoxygenase (EC 1.13.11.-) (Arachidonate 5-lipoxygenase) (5-LO) (5-lipoxygenase) (EC 1.13.11.34) (P48999)
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. Also catalyzes the oxygenation of arachidonic acid into 8-hydroperoxyicosatetraenoic acid (8-HPETE) and 12-hydroperoxyicosatetraenoic acid (12-HPETE). 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. Oxidation of DHA directly inhibits endothelial cell proliferation and sprouting angiogenesis via peroxisome proliferator-activated receptor gamma (PPARgamma). It does not catalyze the oxygenation of linoleic acid and does not convert (5S)-HETE to lipoxin isomers. 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. 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. Can regulate bone mineralization and fat cell differentiation increases in induced pluripotent stem cells.
Subcellular location: Cytoplasm {ECO:0000250|UniProtKB:P09917, ECO:0000255|PROSITE-ProRule:PRU00726, ECO:0000269|PubMed:7629107}. Nucleus matrix {ECO:0000269|PubMed:7629107}. Nucleus membrane {ECO:0000250|UniProtKB:P09917}; Peripheral membrane protein {ECO:0000250|UniProtKB:P09917}. Cytoplasm, perinuclear region {ECO:0000250|UniProtKB:P09917}. Cytoplasm, cytosol {ECO:0000250|UniProtKB:P09917}. Nucleus envelope {ECO:0000250|UniProtKB:P09917}. Nucleus intermembrane space {ECO:0000250|UniProtKB:P09917}. Note=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. {ECO:0000250|UniProtKB:P09917}.
Sequence: MPSYTVTVATGSQWFAGTDDYIYLSLIGSAGCSEKHLLDKAFYNDFERGAVDSYDVTVDEELGEIYLVKIEKRKYWLHDDWYLKYITLKTPHGDYIEFPCYRWITGEGEIVLRDGRAKLARDDQIHILKQHRRKELEARQKQYRWMEWNPGFPLSIDAKCHKDLPRDIQFDSEKGVDFVLNYSKAMENLFINRFMHMFQSSWHDFADFEKIFVKISNTISERVKNHWQEDLMFGYQFLNGCNPVLIKRCTALPPKLPVTTEMVECSLERQLSLEQEVQEGNIFIVDYELLDGIDANKTDPCTHQFLAAPICLLYKNLANKIVPIAIQLNQTPGESNPIFLPTDSKYDWLLAKIWVRSSDFHVHQTITHLLRTHLVSEVFGIAMYRQLPAVHPLFKLLVAHVRFTIAINTKAREQLICEYGLFDKANATGGGGHVQMVQRAVQDLTYSSLCFPEAIKARGMDSTEDIPFYFYRDDGLLVWEAIQSFTMEVVSIYYENDQVVEEDQELQDFVKDVYVYGMRGKKASGFPKSIKSREKLSEYLTVVIFTASAQHAAVNFGQYDWCSWIPNAPPTMRAPPPTAKGVVTIEQIVDTLPDRGRSCWHLGAVWALSQFQENELFLGMYPEEHFIEKPVKEAMIRFRKNLEAIVSVIAERNKNKKLPYYYLSPDRIPNSVAI
InterPro domains: - IPR042062: Lipoxygenase, vertebrates, PLAT domain (domain) [2-115]
- IPR000907: Lipoxygenase (family) [5-674]
- IPR036226: Lipoxigenase, C-terminal domain superfamily (homologous_superfamily) [111-674]
- IPR020834: Lipoxygenase, conserved site (conserved_site) [390-400]
- IPR001024: PLAT/LH2 domain (domain) [2-118]
- IPR020833: Lipoxygenase, iron binding site (binding_site) [363-377]
- IPR001885: Lipoxygenase, mammalian (family) [11-608]
- IPR013819: Lipoxygenase, C-terminal (domain) [118-674]
- IPR036392: PLAT/LH2 domain superfamily (homologous_superfamily) [1-109]
Interaction partners: - Leukotriene A-4 hydrolase
- Leukotriene C4 synthase
- Arachidonate 5-lipoxygenase-activating protein
- Cytosolic phospholipase A2
- Prostaglandin G/H synthase 2
- Prostaglandin G/H synthase 1
- Cytosolic phospholipase A2 gamma
- Cytosolic phospholipase A2 beta
- Cytosolic phospholipase A2 delta
- Cytosolic phospholipase A2 zeta
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0003824 (catalytic activity), GO:0016491 (oxidoreductase activity), GO:0051213 (dioxygenase activity), GO:0016701 (oxidoreductase activity, acting on single donors with incorporation of molecular oxygen), GO:0016702 (oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen)
Biological Process (BP): GO:0008150 (biological process), GO:0008152 (metabolic process), GO:0009987 (cellular process), GO:0009058 (biosynthetic process), GO:0044237 (cellular metabolic process), GO:0044281 (small molecule metabolic process), GO:0071704 (organic substance metabolic process), GO:0044238 (primary metabolic process), GO:1901576 (organic substance biosynthetic process), GO:0006629 (lipid metabolic process), GO:0044283 (small molecule biosynthetic process), GO:0120254 (olefinic compound metabolic process), GO:0006082 (organic acid metabolic process), GO:0044255 (cellular lipid metabolic process), GO:0044249 (cellular biosynthetic process), GO:0019369 (arachidonic acid metabolic process), GO:0006631 (fatty acid metabolic process), GO:0043436 (oxoacid metabolic process), GO:0016053 (organic acid biosynthetic process), GO:0008610 (lipid biosynthetic process), GO:0006633 (fatty acid biosynthetic process), GO:0019752 (carboxylic acid metabolic process), GO:0033559 (unsaturated fatty acid metabolic process), GO:0001676 (long-chain fatty acid metabolic process), GO:0046394 (carboxylic acid biosynthetic process), GO:0019372 (lipoxygenase pathway), GO:0072330 (monocarboxylic acid biosynthetic process), GO:0042759 (long-chain fatty acid biosynthetic process), GO:0032787 (monocarboxylic acid metabolic process), GO:0006690 (icosanoid metabolic process)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0043229 (intracellular organelle), GO:0043227 (membrane-bounded organelle), GO:0043231 (intracellular membrane-bounded organelle), GO:0005634 (nucleus)