ID  P12527;
PN  Polyunsaturated fatty acid 5-lipoxygenase;
GN  Alox5;
OS  10116;
SL  Nucleus Position: SL-0178;
SL  Nucleus Position: SL-0182;
SL  Nucleus Position: SL-0184;
SL  Nucleus Position: SL-0198;
SL  Comments: Cytoplasm {ECO:0000250|UniProtKB:P09917, ECO:0000250|UniProtKB:P48999}. Nucleus matrix {ECO:0000250|UniProtKB:P09917}. 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}.
DR  UNIPROT: P12527;
DR  Pfam: PF00305;
DR  Pfam: PF01477;
DR  PROSITE: PS00711;
DR  PROSITE: PS00081;
DR  PROSITE: PS51393;
DR  PROSITE: PS50095;
DE  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 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 (By similarity). 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, 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. 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 (By similarity). {ECO:0000250|UniProtKB:P09917, ECO:0000250|UniProtKB:P48999}.
DE  Reference Proteome: Yes;
DE  Interaction: P20291; IntAct: EBI-15746644; Score: 0.49
GO  GO:0005737;
GO  GO:0005829;
GO  GO:0030425;
GO  GO:0005635;
GO  GO:0005641;
GO  GO:0016363;
GO  GO:0031965;
GO  GO:0005634;
GO  GO:0048471;
GO  GO:0042383;
GO  GO:0004052;
GO  GO:0004051;
GO  GO:0036403;
GO  GO:0016787;
GO  GO:0005506;
GO  GO:0016702;
GO  GO:0002526;
GO  GO:0019369;
GO  GO:0036336;
GO  GO:0042593;
GO  GO:0051122;
GO  GO:0006959;
GO  GO:0006954;
GO  GO:0002232;
GO  GO:0002523;
GO  GO:1901753;
GO  GO:0019370;
GO  GO:0006691;
GO  GO:0002540;
GO  GO:0043651;
GO  GO:0034440;
GO  GO:2001301;
GO  GO:0019372;
GO  GO:0016525;
GO  GO:0001937;
GO  GO:0050728;
GO  GO:1903573;
GO  GO:1903671;
GO  GO:0061044;
GO  GO:0061045;
GO  GO:0030501;
GO  GO:1904960;
GO  GO:1904999;
GO  GO:0045907;
GO  GO:1900407;
GO  GO:1900015;
GO  GO:0045598;
GO  GO:0050727;
GO  GO:0106014;
GO  GO:0050796;
GO  GO:1903426;
GO  GO:0055093;
GO  GO:0007584;
GO  GO:0019233;
TP  Membrane Topology: Peripheral; Source: UniProt - By Similarity {ECO:0000250|UniProtKB:P09917};
SQ  MPSYTVTVATGSQWFAGTDDYIYLSLIGSAGCSEKHLLDKAFYNDFERGGRDSYDVTVDEELGEIYLVKIEKRKYRLHDD
SQ  WYLKYITLKTPHDYIEFPCYRWITGEGEIVLRDGCAKLARDDQIHILKQHRRKELETRQKQYRWMEWNPGFPLSIDAKCH
SQ  KDLPRDIQFDSEKGVDFVLNYSKAMENLFINRFMHMFQSSWHDFADFEKIFVKISNTISERVKNHWQEDLMFGYQFLNGC
SQ  NPVLIKRCTELPKKLPVTTEMVECSLERQLSLEQEVQEGNIFIVDYELLDGIDANKTDPCTHQFLAAPICLLYKNLANKI
SQ  VPIAIQLNQTPGEKNPIFLPTDSKYDWLLAKIWVRSSDFHIHQTITHLLRTHLVSEVFGIAMYRQLPAVHPLFKLLVAHV
SQ  RFTIAINTKAREQLNCEYGLFDKANATGGGGHVQMVQRAVQDLTYSSLCFPEAIKARGMDNTEDIPYYFYRDDGLLVWEA
SQ  IQSFTTEVVSIYYEDDQVVEEDQELQDFVKDVYVYGMRGRKASGFPKSIKSREKLSEYLTVVIFTASAQHAAVNFGQYDW
SQ  CSWIPNAPPTMRAPPPTAKGVVTIEQIVDTLPDRGRSCWHLGAVWALSQFQENELFLGMYPEEHFIEKPVKEAMIRFRKN
SQ  LEAIVSVIAERNKNKKLPYYYLSPDRIPNSVAI
//