ID  P09917;
PN  Polyunsaturated fatty acid 5-lipoxygenase;
GN  ALOX5;
OS  9606;
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: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:19233132, PubMed:3118366, PubMed:8245774, PubMed:16275640). {ECO:0000269|PubMed:16275640, ECO:0000269|PubMed:18978352, ECO:0000269|PubMed:19233132, ECO:0000269|PubMed:3118366, ECO:0000269|PubMed:8245774}.
DR  UNIPROT: P09917;
DR  UNIPROT: B7ZLS0;
DR  UNIPROT: E5FPY5;
DR  UNIPROT: E5FPY7;
DR  UNIPROT: E5FPY8;
DR  UNIPROT: Q5JQ14;
DR  PDB: 3O8Y;
DR  PDB: 3V92;
DR  PDB: 3V98;
DR  PDB: 3V99;
DR  PDB: 6N2W;
DR  PDB: 6NCF;
DR  Pfam: PF00305;
DR  Pfam: PF01477;
DR  PROSITE: PS00711;
DR  PROSITE: PS00081;
DR  PROSITE: PS51393;
DR  PROSITE: PS50095;
DR  OMIM: 152390;
DR  DisGeNET: 240;
DE  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 (PubMed:8631361, PubMed:21233389, PubMed:22516296, PubMed:24282679, PubMed:19022417, PubMed:23246375, PubMed:8615788, PubMed:24893149, PubMed:31664810). Also catalyzes the oxygenation of arachidonate into 8- hydroperoxyicosatetraenoate (8-HPETE) and 12- hydroperoxyicosatetraenoate (12-HPETE) (PubMed:23246375). Displays lipoxin synthase activity being able to convert (15S)-HETE into a conjugate tetraene (PubMed:31664810). 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:21206090, PubMed:31664810, PubMed:8615788, PubMed:17114001, PubMed:32404334). 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 (PubMed:31664810). 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 (PubMed:21200133). 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). {ECO:0000250|UniProtKB:P48999, ECO:0000269|PubMed:17114001, ECO:0000269|PubMed:19022417, ECO:0000269|PubMed:21200133, ECO:0000269|PubMed:21206090, ECO:0000269|PubMed:21233389, ECO:0000269|PubMed:22516296, ECO:0000269|PubMed:23246375, ECO:0000269|PubMed:24282679, ECO:0000269|PubMed:24893149, ECO:0000269|PubMed:31664810, ECO:0000269|PubMed:32404334, ECO:0000269|PubMed:8615788, ECO:0000269|PubMed:8631361}.
DE  Reference Proteome: Yes;
DE  Interaction: Q14019; IntAct: EBI-79944; Score: 0.70
DE  Interaction: Q8CLD8; IntAct: EBI-2865332; Score: 0.00
DE  Interaction: Q8D078; IntAct: EBI-2865325; Score: 0.00
DE  Interaction: P49137; IntAct: EBI-9207055; Score: 0.44
DE  Interaction: P07947; IntAct: EBI-9207225; Score: 0.44
DE  Interaction: P17612; IntAct: EBI-9207166; Score: 0.44
DE  Interaction: P08631; IntAct: EBI-9207213; Score: 0.44
DE  Interaction: P09769; IntAct: EBI-9207193; Score: 0.44
DE  Interaction: Q13555; IntAct: EBI-9207248; Score: 0.44
DE  Interaction: P50221; IntAct: EBI-10196635; Score: 0.56
DE  Interaction: Q04864; IntAct: EBI-10196645; Score: 0.56
DE  Interaction: Q6UWX4; IntAct: EBI-10196663; Score: 0.72
DE  Interaction: Q86Y26; IntAct: EBI-10196677; Score: 0.67
DE  Interaction: Q8IYX8; IntAct: EBI-10196689; Score: 0.56
DE  Interaction: Q8N0S2; IntAct: EBI-10196701; Score: 0.72
DE  Interaction: Q96MT8; IntAct: EBI-24376612; Score: 0.72
DE  Interaction: Q9Y6D9; IntAct: EBI-10196727; Score: 0.81
DE  Interaction: P31025; IntAct: EBI-25265094; Score: 0.56
DE  Interaction: Q9P0N9; IntAct: EBI-25265715; Score: 0.56
DE  Interaction: P14061; IntAct: EBI-24629482; Score: 0.56
DE  Interaction: A6NGQ2; IntAct: EBI-24683876; Score: 0.56
DE  Interaction: Q6PII3; IntAct: EBI-24692426; Score: 0.56
DE  Interaction: Q8IYJ2; IntAct: EBI-24699339; Score: 0.56
DE  Interaction: O43716; IntAct: EBI-24435599; Score: 0.56
DE  Interaction: Q6FHY5; IntAct: EBI-24476244; Score: 0.56
DE  Interaction: Q6P2R3; IntAct: EBI-12696314; Score: 0.56
DE  Interaction: Q15811; IntAct: EBI-21805075; Score: 0.35
DE  Interaction: O94830; IntAct: EBI-21805075; Score: 0.35
DE  Interaction: Q9UQ49; IntAct: EBI-21805075; Score: 0.35
DE  Interaction: Q9UPU7; IntAct: EBI-21805075; Score: 0.35
DE  Interaction: Q9NYA4; IntAct: EBI-21805075; Score: 0.35
DE  Interaction: Q9BXB4; IntAct: EBI-21805075; Score: 0.35
DE  Interaction: Q9BWT6; IntAct: EBI-21805075; Score: 0.35
DE  Interaction: Q96RR4; IntAct: EBI-21805075; Score: 0.35
DE  Interaction: Q96L93; IntAct: EBI-21805075; Score: 0.35
DE  Interaction: Q96C34; IntAct: EBI-21805075; Score: 0.35
DE  Interaction: Q96AD5; IntAct: EBI-21805075; Score: 0.35
DE  Interaction: Q92530; IntAct: EBI-21805075; Score: 0.35
DE  Interaction: Q8WXG6; IntAct: EBI-21805075; Score: 0.35
DE  Interaction: Q8ND83; IntAct: EBI-21805075; Score: 0.35
DE  Interaction: Q8N3R9; IntAct: EBI-21805075; Score: 0.35
DE  Interaction: Q8IY63; IntAct: EBI-21805075; Score: 0.35
DE  Interaction: Q86SX3; IntAct: EBI-21805075; Score: 0.35
DE  Interaction: Q7Z2K6; IntAct: EBI-21805075; Score: 0.35
DE  Interaction: Q7LBC6; IntAct: EBI-21805075; Score: 0.35
DE  Interaction: Q6PJ69; IntAct: EBI-21805075; Score: 0.35
DE  Interaction: Q6P474; IntAct: EBI-21805075; Score: 0.35
DE  Interaction: Q6P1M9; IntAct: EBI-21805075; Score: 0.35
DE  Interaction: Q6P1K2; IntAct: EBI-21805075; Score: 0.35
DE  Interaction: Q4VCS5; IntAct: EBI-21805075; Score: 0.35
DE  Interaction: Q2NKX8; IntAct: EBI-21805075; Score: 0.35
DE  Interaction: Q15349; IntAct: EBI-21805075; Score: 0.35
DE  Interaction: Q15042; IntAct: EBI-21805075; Score: 0.35
DE  Interaction: Q14746; IntAct: EBI-21805075; Score: 0.35
DE  Interaction: Q14008; IntAct: EBI-21805075; Score: 0.35
DE  Interaction: Q13615; IntAct: EBI-21805075; Score: 0.35
DE  Interaction: Q13042; IntAct: EBI-21805075; Score: 0.35
DE  Interaction: Q09019; IntAct: EBI-21805075; Score: 0.35
DE  Interaction: Q00653; IntAct: EBI-21805075; Score: 0.35
DE  Interaction: P48449; IntAct: EBI-21805075; Score: 0.35
DE  Interaction: P30566; IntAct: EBI-21805075; Score: 0.35
DE  Interaction: P29144; IntAct: EBI-21805075; Score: 0.35
DE  Interaction: Q92542; IntAct: EBI-21836991; Score: 0.35
DE  Interaction: Q9Y252; IntAct: EBI-21839887; Score: 0.35
DE  Interaction: Q7Z699; IntAct: EBI-25930186; Score: 0.56
GO  GO:0005829;
GO  GO:0005576;
GO  GO:0005615;
GO  GO:1904813;
GO  GO:0005635;
GO  GO:0005641;
GO  GO:0016363;
GO  GO:0031965;
GO  GO:0005654;
GO  GO:0048471;
GO  GO:0034774;
GO  GO:0004052;
GO  GO:0004051;
GO  GO:0036403;
GO  GO:0016787;
GO  GO:0005506;
GO  GO:0016702;
GO  GO:0019369;
GO  GO:0036336;
GO  GO:0042593;
GO  GO:0051122;
GO  GO:0006959;
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:0042759;
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:1904999;
GO  GO:1900407;
GO  GO:1900015;
GO  GO:0045598;
GO  GO:0050727;
GO  GO:0106014;
GO  GO:0050796;
GO  GO:1903426;
TP  Membrane Topology: Peripheral; Source: UniProt - Experimental Evidence {ECO:0000269|PubMed:16275640};
SQ  MPSYTVTVATGSQWFAGTDDYIYLSLVGSAGCSEKHLLDKPFYNDFERGAVDSYDVTVDEELGEIQLVRIEKRKYWLNDD
SQ  WYLKYITLKTPHGDYIEFPCYRWITGDVEVVLRDGRAKLARDDQIHILKQHRRKELETRQKQYRWMEWNPGFPLSIDAKC
SQ  HKDLPRDIQFDSEKGVDFVLNYSKAMENLFINRFMHMFQSSWNDFADFEKIFVKISNTISERVMNHWQEDLMFGYQFLNG
SQ  CNPVLIRRCTELPEKLPVTTEMVECSLERQLSLEQEVQQGNIFIVDFELLDGIDANKTDPCTLQFLAAPICLLYKNLANK
SQ  IVPIAIQLNQIPGDENPIFLPSDAKYDWLLAKIWVRSSDFHVHQTITHLLRTHLVSEVFGIAMYRQLPAVHPIFKLLVAH
SQ  VRFTIAINTKAREQLICECGLFDKANATGGGGHVQMVQRAMKDLTYASLCFPEAIKARGMESKEDIPYYFYRDDGLLVWE
SQ  AIRTFTAEVVDIYYEGDQVVEEDPELQDFVNDVYVYGMRGRKSSGFPKSVKSREQLSEYLTVVIFTASAQHAAVNFGQYD
SQ  WCSWIPNAPPTMRAPPPTAKGVVTIEQIVDTLPDRGRSCWHLGAVWALSQFQENELFLGMYPEEHFIEKPVKEAMARFRK
SQ  NLEAIVSVIAERNKKKQLPYYYLSPDRIPNSVAI
//