ALOX5
entrez
240
canonical
uniprot
P09917
canonical
ensembl
ENSG00000012779
resolver
ensembl
ENSG00000275565
resolver
ensp
ENSP00000363512
resolver
ensp
ENSP00000437634
resolver
ensp
ENSP00000521701
resolver
ensp
ENSP00000521703
resolver
ensp
ENSP00000521705
resolver
ensp
ENSP00000631248
resolver
genesymbol
ALOX5
resolver
genesymbol_syn
LOG5
resolver
hgnc
HGNC:435
resolver
uniprot
B7ZLS0
resolver
uniprot
E5FPY5
resolver
uniprot
E5FPY7
resolver
uniprot
E5FPY8
resolver
uniprot
Q5JQ14
resolver
uniprot_entry
LOX5_HUMAN
resolver
uniprot_sec
B7ZLS0
resolver
uniprot_sec
E5FPY5
resolver
uniprot_sec
E5FPY7
resolver
uniprot_sec
E5FPY8
resolver
uniprot_sec
Q5JQ14
resolver
activity_regulation
ACTIVITY REGULATION: Undergoes a sequential loss of the oxygenase and pseudoperoxidase activities which is dependent on the structural characteristics of the substrate for the reaction, on oxygen concentration and on exposure to phospholipids and calcium (PubMed:8631361). 15-HETE and other 15-mono-hydroxyeicosanoids exhibit the highest inhibitory potencies in their capability of suppressing 5-lipoxygenation of arachidonic acid, whereas the other HETEs, (5S,15S)-dihydroxy-(6E,8Z,11Z,13E)-eicosatetraenoic acid (5,15-diHETE) as well as octadecanoids, are modest or poor inhibitors (PubMed:8615788). The formation of (5S)-hydroperoxy-(15S)-hydroxy-(6E,8Z,11Z,13E)-eicosatetraenoate is strongly stimulated by either hydroperoxypolyenoic fatty acids or arachidonic acid (PubMed:8615788). Arachidonate 5-lipoxygenase and leukotriene A4 synthase activities are allosterically increased by ATP (PubMed:24893149). {ECO:0000269|PubMed:24893149, ECO:0000269|PubMed:8615788, ECO:0000269|PubMed:8631361}.
uniprot
proteins
amino_acid_sequence
MPSYTVTVATGSQWFAGTDDYIYLSLVGSAGCSEKHLLDKPFYNDFERGAVDSYDVTVDEELGEIQLVRIEKRKYWLNDDWYLKYITLKTPHGDYIEFPCYRWITGDVEVVLRDGRAKLARDDQIHILKQHRRKELETRQKQYRWMEWNPGFPLSIDAKCHKDLPRDIQFDSEKGVDFVLNYSKAMENLFINRFMHMFQSSWNDFADFEKIFVKISNTISERVMNHWQEDLMFGYQFLNGCNPVLIRRCTELPEKLPVTTEMVECSLERQLSLEQEVQQGNIFIVDFELLDGIDANKTDPCTLQFLAAPICLLYKNLANKIVPIAIQLNQIPGDENPIFLPSDAKYDWLLAKIWVRSSDFHVHQTITHLLRTHLVSEVFGIAMYRQLPAVHPIFKLLVAHVRFTIAINTKAREQLICECGLFDKANATGGGGHVQMVQRAMKDLTYASLCFPEAIKARGMESKEDIPYYFYRDDGLLVWEAIRTFTAEVVDIYYEGDQVVEEDPELQDFVNDVYVYGMRGRKSSGFPKSVKSREQLSEYLTVVIFTASAQHAAVNFGQYDWCSWIPNAPPTMRAPPPTAKGVVTIEQIVDTLPDRGRSCWHLGAVWALSQFQENELFLGMYPEEHFIEKPVKEAMARFRKNLEAIVSVIAERNKKKQLPYYYLSPDRIPNSVAI
uniprot
proteins
ec_number
1.13.11.-
uniprot
proteins
ec_number
1.13.11.34
uniprot
proteins
function
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:19022417, PubMed:21233389, PubMed:22516296, PubMed:23246375, PubMed:24282679, PubMed:24893149, PubMed:31664810, PubMed:8615788, PubMed:8631361). 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:17114001, PubMed:21206090, PubMed:31664810, PubMed:32404334, PubMed:32841762, PubMed:8615788). 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:32841762, ECO:0000269|PubMed:8615788, ECO:0000269|PubMed:8631361}.
uniprot
proteins
mass_dalton
77983
uniprot
proteins
mutagenesis
MUTAGEN 14; /note="W->A: Impairs interaction with DICER1; when associated with A-76 and A-103."; /evidence="ECO:0000269|PubMed:19022417"; MUTAGEN 76; /note="W->A: Impairs interaction with DICER1; when associated with A-14 and A-103."; /evidence="ECO:0000269|PubMed:19022417"; MUTAGEN 103; /note="W->A: Abolishes binding to COTL1. Impairs interaction with DICER; when associated with A-14 and A-76."; /evidence="ECO:0000269|PubMed:19022417, ECO:0000269|PubMed:19807693"; MUTAGEN 272; /note="S->A: Loss of phosphorylation site. Permits export from the nucleus."; /evidence="ECO:0000269|PubMed:18978352"; MUTAGEN 359; /note="D->N: No loss of activity."; MUTAGEN 360; /note="F->W: Loss of (5S)-lipoxygenase activity; when associated with I-425 and M-426. Loss of (5S)-lipoxygenase activity; when associated with I-425; M-426 and I-604. Exhibits a major (15S)-lipoxygenase activity; when associated with I-425 and M-426. Exhibits a major (15S)-lipoxygenase activity; when associated with I-425; M-426 and I-604. Does not catalyze oxygenation of arachodonic acid to 5-HETE; when associated with I-425: M-426 and I-604. Catalyzes oxygenation of arachodonic acid to form mostly (15S)-HETE and (8S)-HETE but also 12-HETE; when associated with I-425: M-426 and I-604. Abolishes the LTA4-synthase activity; when associated with I-425: M-426 and I-604. Catalyzes oxygenation of linoleic acid to (13S)- and (9S)-HODE; when associated with I-425: M-426 and I-604. Catalyzes oxygenation of (11S)- and (11R)-deutero-linoleic acid to 9-HODE and (13S)-HODE respectively; when associated with I-425: M-426 and I-604. Catalyzes oxygenation of alpha-linolenic acid (ALA) to 13-HOTrE(n-3); when associated with I-425: M-426 and I-604. Catalyzes oxygenation of gamma-linolenic acid (GLA) to 13-HOTrE(n-6) and 10-HOTrE; when associated with I-425: M-426 and I-604. Catalyzes the oxygenation of eicosapentaenoic acid (EPA) to 12- and 15-HEPA; when associated with I-425: M-426 and I-604. Catalyzes the oxygenation of docosahexaenoic acid (DHA) to 10- and 17-HDHA; when associated with I-425: M-426 and I-604. Exhibits a lipoxin synthase activity towards (5S)-HETE as major substrates followed by (5S),(15S)-DiHETE and (15S)-HETE; when associated with I-425: M-426 and I-604."; /evidence="ECO:0000269|PubMed:23246375, ECO:0000269|PubMed:31664810"; MUTAGEN 363; /note="H->S,N: Still some substantial activity."; /evidence="ECO:0000269|PubMed:1939225"; MUTAGEN 368; /note="H->S,N,A: No activity."; /evidence="ECO:0000269|PubMed:1540191, ECO:0000269|PubMed:1939225"; MUTAGEN 373; /note="H->S,N: No activity."; /evidence="ECO:0000269|PubMed:1540191, ECO:0000269|PubMed:1939225"; MUTAGEN 377; /note="E->Q: No activity."; /evidence="ECO:0000269|PubMed:1540191"; MUTAGEN 391; /note="H->A: No activity."; /evidence="ECO:0000269|PubMed:1540191, ECO:0000269|PubMed:1939225"; MUTAGEN 391; /note="H->S,N: Still some substantial activity."; /evidence="ECO:0000269|PubMed:1540191, ECO:0000269|PubMed:1939225"; MUTAGEN 400; /note="H->A: No activity."; /evidence="ECO:0000269|PubMed:1540191, ECO:0000269|PubMed:1939225"; MUTAGEN 400; /note="H->S,N: Still some substantial activity."; /evidence="ECO:0000269|PubMed:1540191, ECO:0000269|PubMed:1939225"; MUTAGEN 425; /note="A->I: Loss of (5S)-lipoxygenase activity; when associated with W-360 and M-426. Loss of (5S)-lipoxygenase activity; when associated with W-360; M-426 and I-604. Exhibits a major (15S)-lipoxygenase activity; when associated with W-360 and M-426. Exhibits a major (15S)-lipoxygenase activity; when associated with W-360; M-426 and I-604. Does not catalyze oxygenation of arachodonic acid to 5-HETE; when associated with W-360; M-426 and I-604. Catalyzes oxygenation of arachodonic acid to form in majority (15S)-HETE and (8S)-HETE but also 12-HETE; when associated with W-360; M-426 and I-604. Abolishes the LTA4-synthase activity; when associated with W-360; M-426 and I-604. Catalyzes oxygenation of linoleic acid to (13S)- and (9S)-HODE; when associated with W-360; M-426 and I-604. Catalyzes oxygenation of (11S)- and (11R)-deutero-linoleic acid to 9-HODE and (13S)-HODE respectively; when associated with W-360; M-426 and I-604. Catalyzes oxygenation of alpha-linolenic acid (ALA) to 13-HOTrE(n-3); when associated with W-360; M-426 and I-604. Catalyzes oxygenation of gamma-linolenic acid (GLA) to 13-HOTrE(n-6) and 10-HOTrE; when associated with W-360; M-426 and I-604. Catalyzes the oxygenation of eicosapentaenoic acid (EPA) to 12- and 15-HEPA; when associated with W-360; M-426 and I-604. Catalyzes the oxygenation of docosahexaenoic acid (DHA) to 10- and 17-HDHA; when associated with W-360; M-426 and I-604. Exhibits a lipoxin synthase activity towards (5S)-HETE as major substrates followed by (5S),(15S)-DiHETE and (15S)-HETE; when associated with W-360; M-426 and I-604."; /evidence="ECO:0000269|PubMed:23246375, ECO:0000269|PubMed:31664810"; MUTAGEN 426; /note="N->M: Loss of (5S)-lipoxygenase activity; when associated with W-360 and I-425. Loss of (5S)-lipoxygenase activity; when associated with W-360; I-425 and I-604. Exhibits a major (15S)-lipoxygenase activity; when associated with W-360 and I-425. Exhibits a major (15S)-lipoxygenase activity; when associated with W-360; I-425 and I-604. Does not catalyze oxygenation of arachodonic acid to 5-HETE; when associated with W-360; I-425 and I-604. Catalyzes oxygenation of arachodonic acid to form in majority (15S)-HETE and (8S)-HETE but also 12-HETE; when associated with W-360; I-425 and I-604. Abolishes the LTA4-synthase activity; when associated with W-360; I-425 and I-604. Catalyzes oxygenation of linoleic acid to (13S)- and (9S)-HODE; when associated with W-360; I-425 and I-604. Catalyzes oxygenation of (11S)- and (11R)-deutero-linoleic acid to 9-HODE and (13S)-HODE respectively; when associated with W-360; I-425 and I-604. Catalyzes oxygenation of alpha-linolenic acid (ALA) to 13-HOTrE(n-3); when associated with W-360; I-425 and I-604. Catalyzes oxygenation of gamma-linolenic acid (GLA) to 13-HOTrE(n-6) and 10-HOTrE; when associated with W-360; I-425 and I-604. Catalyzes the oxygenation of eicosapentaenoic acid (EPA) to 12- and 15-HEPA; when associated with W-360; I-425 and I-604. Catalyzes the oxygenation of docosahexaenoic acid (DHA) to 10- and 17-HDHA; when associated with W-360; I-425 and I-604. Exhibits a lipoxin synthase activity towards (5S)-HETE as major substrates followed by (5S),(15S)-DiHETE and (15S)-HETE; when associated with W-360; I-425 and I-604."; /evidence="ECO:0000269|PubMed:23246375, ECO:0000269|PubMed:31664810"; MUTAGEN 433; /note="H->N,A: Almost no loss of activity."; MUTAGEN 524; /note="S->A: Prevents phosphorylation by PKA."; /evidence="ECO:0000269|PubMed:15280375"; MUTAGEN 551; /note="H->N,A: No activity."; /evidence="ECO:0000269|PubMed:1540191"; MUTAGEN 604; /note="A->I: Loss of (5S)-lipoxygenase activity. Loss of (5S)-lipoxygenase activity; when associated with W-360; I-425 and M-426. Exhibits a major (15S)-lipoxygenase activity;when associated with W-360; I-425 and M-426. Does not catalyze oxygenation of arachodonic acid to 5-HETE; when associated with W-360; I-425 and M-426. Catalyzes oxygenation of arachodonic acid to form in majority (15S)-HETE and (8S)-HETE but also 12-HETE; when associated with W-360; I-425 and M-426. Abolishes the LTA4-synthase activity; when associated with W-360; I-425 and M-426. Catalyzes oxygenation of linoleic acid to (13S)- and (9 S)-HODE; when associated with W-360; I-425 and M-426. Catalyzes oxygenation of (11S)- and (11R)-deutero-linoleic acid to 9-HODE and (13S)-HODE respectively; when associated with W-360; I-425 and M-426. Catalyzes oxygenation of alpha-linolenic acid (ALA) to 13-HOTrE(n-3); when associated with W-360; I-425 and M-426. Catalyzes oxygenation of gamma-linolenic acid (GLA) to 13-HOTrE(n-6) and 10-HOTrE; when associated with W-360; I-425 and M-426. Catalyzes the oxygenation of eicosapentaenoic acid (EPA) to 12- and 15-HEPA; when associated with W-360; I-425 and M-426. Catalyzes the oxygenation of docosahexaenoic acid (DHA) to 10- and 17-HDHA; when associated with W-360; I-425 and M-426. Exhibits a lipoxin synthase activity towards (5S)-HETE as major substrates followed by (5S),(15S)-DiHETE and (15S)-HETE; when associated with W-360; I-425 and M-426."; /evidence="ECO:0000269|PubMed:23246375, ECO:0000269|PubMed:31664810"; MUTAGEN 664; /note="S->A: Does not affect arachidonate 5-lipoxygenase activity. Does not oxygenate arachidonate typical 15-lipoxygenase substrates such as dihomo-gamma-linolenic acid and N-arachidonyl glycine."; /evidence="ECO:0000269|PubMed:22516296"; MUTAGEN 664; /note="S->D: Enhances affinity for arachidonic acid. Impairs arachidonate 5-lipoxygenase activity. Induces arachidonate 15-lipoxygenase activity. Oxygenates typical arachidonate 15-lipoxygenase substrates such as dihomo-gamma-linolenic acid and N-arachidonyl glycine. Synthesizes lipoxin A4 when incubated with a stable 5-lipoxygenase."; /evidence="ECO:0000269|PubMed:22516296
uniprot
proteins
pathway_participation
PATHWAY: Lipid metabolism; leukotriene A4 biosynthesis. {ECO:0000269|PubMed:8631361}.
uniprot
proteins
post_translational_modification
PTM: Serine phosphorylation by MAPKAPK2 is stimulated by arachidonic acid (PubMed:11844797, PubMed:18978352). Phosphorylation on Ser-524 by PKA has an inhibitory effect (PubMed:15280375). Phosphorylation on Ser-272 prevents export from the nucleus (PubMed:11844797, PubMed:18978352). Phosphorylation at Ser-524 is stimulated by 8-bromo-3',5'-cyclic AMP or prostaglandin E2 (PubMed:26210919). {ECO:0000269|PubMed:11844797, ECO:0000269|PubMed:15280375, ECO:0000269|PubMed:18978352, ECO:0000269|PubMed:26210919}.
uniprot
proteins
protein_family
Lipoxygenase family
uniprot
proteins
pubmed
11844797
uniprot
proteins
pubmed
15164054
uniprot
proteins
pubmed
15280375
uniprot
proteins
pubmed
15308583
uniprot
proteins
pubmed
1540191
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16275640
uniprot
proteins
pubmed
17114001
uniprot
proteins
pubmed
18978352
uniprot
proteins
pubmed
19022417
uniprot
proteins
pubmed
19233132
uniprot
proteins
pubmed
1939225
uniprot
proteins
pubmed
19807693
uniprot
proteins
pubmed
21098726
uniprot
proteins
pubmed
21200133
uniprot
proteins
pubmed
21206090
uniprot
proteins
pubmed
21233389
uniprot
proteins
pubmed
2251250
uniprot
proteins
pubmed
22516296
uniprot
proteins
pubmed
23246375
uniprot
proteins
pubmed
24282679
uniprot
proteins
pubmed
24893149
uniprot
proteins
pubmed
2526519
uniprot
proteins
pubmed
2565035
uniprot
proteins
pubmed
26210919
uniprot
proteins
pubmed
2829172
uniprot
proteins
pubmed
3118366
uniprot
proteins
pubmed
31664810
uniprot
proteins
pubmed
32404334
uniprot
proteins
pubmed
32841762
uniprot
proteins
pubmed
3422434
uniprot
proteins
pubmed
7929073
uniprot
proteins
pubmed
8245774
uniprot
proteins
pubmed
8615788
uniprot
proteins
pubmed
8631361
uniprot
proteins
sequence_length
674
uniprot
proteins
subcellular_location
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}.
uniprot
proteins