Alox5
entrez
11689
canonical
uniprot
P48999
canonical
ensembl
ENSMUSG00000025701
resolver
ensp
ENSMUSP00000026795
resolver
enst
ENSMUST00000026795
resolver
genesymbol
Alox5
resolver
uniprot
Q3TB75
resolver
uniprot_entry
LOX5_MOUSE
resolver
uniprot_sec
Q3TB75
resolver
amino_acid_sequence
MPSYTVTVATGSQWFAGTDDYIYLSLIGSAGCSEKHLLDKAFYNDFERGAVDSYDVTVDEELGEIYLVKIEKRKYWLHDDWYLKYITLKTPHGDYIEFPCYRWITGEGEIVLRDGRAKLARDDQIHILKQHRRKELEARQKQYRWMEWNPGFPLSIDAKCHKDLPRDIQFDSEKGVDFVLNYSKAMENLFINRFMHMFQSSWHDFADFEKIFVKISNTISERVKNHWQEDLMFGYQFLNGCNPVLIKRCTALPPKLPVTTEMVECSLERQLSLEQEVQEGNIFIVDYELLDGIDANKTDPCTHQFLAAPICLLYKNLANKIVPIAIQLNQTPGESNPIFLPTDSKYDWLLAKIWVRSSDFHVHQTITHLLRTHLVSEVFGIAMYRQLPAVHPLFKLLVAHVRFTIAINTKAREQLICEYGLFDKANATGGGGHVQMVQRAVQDLTYSSLCFPEAIKARGMDSTEDIPFYFYRDDGLLVWEAIQSFTMEVVSIYYENDQVVEEDQELQDFVKDVYVYGMRGKKASGFPKSIKSREKLSEYLTVVIFTASAQHAAVNFGQYDWCSWIPNAPPTMRAPPPTAKGVVTIEQIVDTLPDRGRSCWHLGAVWALSQFQENELFLGMYPEEHFIEKPVKEAMIRFRKNLEAIVSVIAERNKNKKLPYYYLSPDRIPNSVAI
uniprot
proteins
ec_number
1.13.11.-
uniprot
proteins
ec_number
1.13.11.34
uniprot
proteins
function
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 (PubMed:23246375, PubMed:31642348, PubMed:7629107, PubMed:7809134, PubMed:7969451). Also catalyzes the oxygenation of arachidonic acid into 8-hydroperoxyicosatetraenoic acid (8-HPETE) and 12-hydroperoxyicosatetraenoic acid (12-HPETE) (PubMed:23246375). 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 (PubMed:31642348). Oxidation of DHA directly inhibits endothelial cell proliferation and sprouting angiogenesis via peroxisome proliferator-activated receptor gamma (PPARgamma) (PubMed:21307302). It does not catalyze the oxygenation of linoleic acid and does not convert (5S)-HETE to lipoxin isomers (PubMed:31642348). 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 (PubMed:17392829, PubMed:23720274, PubMed:24226420, PubMed:28965882). 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:21224059). May also play a role in glucose homeostasis, regulation of insulin secretion and palmitic acid-induced insulin resistance via AMPK (PubMed:18421434, PubMed:28694473). Can regulate bone mineralization and fat cell differentiation increases in induced pluripotent stem cells (PubMed:24906289). {ECO:0000250|UniProtKB:P09917, ECO:0000269|PubMed:17392829, ECO:0000269|PubMed:18421434, ECO:0000269|PubMed:21224059, ECO:0000269|PubMed:21307302, ECO:0000269|PubMed:23246375, ECO:0000269|PubMed:23720274, ECO:0000269|PubMed:24226420, ECO:0000269|PubMed:24906289, ECO:0000269|PubMed:28694473, ECO:0000269|PubMed:28965882, ECO:0000269|PubMed:31642348, ECO:0000269|PubMed:7629107, ECO:0000269|PubMed:7809134, ECO:0000269|PubMed:7969451}.
uniprot
proteins
mass_dalton
77967
uniprot
proteins
mutagenesis
MUTAGEN 360; /note="F->W: Increases formation of (8S)-hydroperoxyicosatetraenoic acid ((8S)-HPETE). Exhibits a (8S)-lipoxygenase activity; when associated with I-425. Exhibits a (15S)-lipoxygenase activity; when associated with I-425 and M-426. Loss of arachidonate (5S)-lipoxygenase activity; when associated with G-411; I-425 and M-426. Forms 11(R)-hydroperoxyicosatetraenoic acid (11(R)-HPETE) as the major arachidonic acid oxygenation product; when associated with G-411; I-425 and M-426. Does not oxygenate arachidonic acid into 5-HETE; when associated with I-425 and M-426. Catalyzes oxygenation of arachidonic acid into a major product (15S)-HETE followed by 12-HETE and 8-HETE;when associated with I-425 and M-426. Catalyzes oxygenation of linoleic acid, gamma-linolenic acid, arachidonic acid, eicosapentaenoic acid and docosahexaenoic acid; when associated with I-425 and M-426. Catalyzes oxygenation of anandamide to 15-OH-ANA. Knockin mice are viable, fertile, and develop normally; when associated with I-425 and M-426. Mice convert arachidonic to 15-HETE, 12-HETE, and 8-HETE; when associated with I-425 and M-426. Mice cannot synthesize pro-inflammatory leukotrienes but show significantly attenuated plasma levels of lipolytic endocannabinoids; when associated with I-425 and M-426. When aging, animals gain significantly more body weight probably due to higher levels of 13-HODE in the adipose tissue; when associated with I-425 and M-426."; /evidence="ECO:0000269|PubMed:23246375, ECO:0000269|PubMed:31642348"; MUTAGEN 411; /note="A->G: Decreases (5S)-lipoxygenase activity. Forms 9-hydroperoxyicosatetraenoic acid (9-HPETE) as the major arachidonic acid oxygenation product. Loss of arachidonate (5S)-lipoxygenase activity; when associated with W-360; I-425 and M-426. Forms 11(R)-hydroperoxyicosatetraenoic acid (11(R)-HPETE) as the major arachidonic acid oxygenation product; when associated with W-360; I-425 and M-426."; /evidence="ECO:0000269|PubMed:23246375"; MUTAGEN 425; /note="A->I: Decreases arachidonate (5S)-lipoxygenase activity. Decreases arachidonate 5 lipoxygenase activity; when associated with A-604. Exhibits a (8S)-lipoxygenase activity; when associated with W-360. Exhibits a (15S)-lipoxygenase activity; when associated with W-360 and M-426. Loss of arachidonate (5S)-lipoxygenase activity; when associated with W-360; G-411 and M-426. Forms 11(R)-hydroperoxyicosatetraenoic acid (11(R)-HPETE) as the major arachidonic acid oxygenation product; when associated with W-360; G-411 and M-426. Does not oxygenate arachidonic acid into 5-HETE; when associated with I-425 and M-426. Catalyzes oxygenation of arachidonic acid into a major product (15S)-HETE followed by 12-HETE and 8-HETE; when associated with I-425 and M-426. Catalyzes oxygenation of linoleic acid, gamma-linolenic acid, arachidonic acid, eicosapentaenoic acid and docosahexaenoic acid; when associated with I-425 and M-426. Catalyzes oxygenation of anandamide to 15-OH-ANA. Knockin mice are viable, fertile, and develop normally; when associated with I-425 and M-426. Mice convert arachidonic to 15-HETE, 12-HETE, and 8-HETE; when associated with I-425 and M-426. Mice cannot synthesize pro-inflammatory leukotrienes but show significantly attenuated plasma levels of lipolytic endocannabinoids; when associated with I-425 and M-426. When aging, animals gain significantly more body weight probably due to higher levels of 13-HODE in the adipose tissue; when associated with I-425 and M-426."; /evidence="ECO:0000269|PubMed:23246375, ECO:0000269|PubMed:31642348"; MUTAGEN 426; /note="N->M: Increases formation of (8S)-hydroperoxyicosatetraenoic acid ((8S)-HPETE) and (12S)-hydroperoxyicosatetraenoic acid ((12S)-HPETE). Exhibits a (15S)-lipoxygenase activity; when associated with W-360 and I-425. Loss of arachidonate (5S)-lipoxygenase activity; when associated with W-360; G-411 and I-425. Forms 11(R)-hydroperoxyicosatetraenoic acid (11(R)-HPETE) as the major arachidonic acid oxygenation product; when associated with W-360; G-411 and I-425."; /evidence="ECO:0000269|PubMed:23246375, ECO:0000269|PubMed:31642348"; MUTAGEN 604; /note="A->I: Decreases arachidonate (5S)-lipoxygenase activity."; /evidence="ECO:0000269|PubMed:23246375"; MUTAGEN 672; /note="V->M: Loss of activity."; /evidence="ECO:0000269|PubMed:7629107
uniprot
proteins
pathway_participation
PATHWAY: Lipid metabolism; leukotriene A4 biosynthesis. {ECO:0000269|PubMed:31642348}.
uniprot
proteins
post_translational_modification
PTM: Serine phosphorylation by MAPKAPK2 is stimulated by arachidonic acid. Phosphorylation on Ser-524 by PKA has an inhibitory effect. Phosphorylation on Ser-272 prevents export from the nucleus. Phosphorylation at Ser-524 is stimulated by 8-bromo-3',5'-cyclic AMP or prostaglandin E2. {ECO:0000250|UniProtKB:P09917}.
uniprot
proteins
protein_family
Lipoxygenase family
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16141072
uniprot
proteins
pubmed
17392829
uniprot
proteins
pubmed
18421434
uniprot
proteins
pubmed
21183079
uniprot
proteins
pubmed
21224059
uniprot
proteins
pubmed
21307302
uniprot
proteins
pubmed
23246375
uniprot
proteins
pubmed
23720274
uniprot
proteins
pubmed
24226420
uniprot
proteins
pubmed
24906289
uniprot
proteins
pubmed
28694473
uniprot
proteins
pubmed
28965882
uniprot
proteins
pubmed
31642348
uniprot
proteins
pubmed
7629107
uniprot
proteins
pubmed
7809134
uniprot
proteins
pubmed
7969451
uniprot
proteins
sequence_length
674
uniprot
proteins
subcellular_location
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}.
uniprot
proteins