P12527 · LOX5_RAT
- ProteinPolyunsaturated fatty acid 5-lipoxygenase
- GeneAlox5
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids673 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
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. 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).
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).
Catalytic activity
- (5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 = H2O + leukotriene A4This reaction proceeds in the forward direction.
- 18-HEPE + O2 = (5S)-hydroperoxy-18-hydroxy-(7E,9E,11Z,14Z,16E)-eicosapentaenoateThis reaction proceeds in the forward direction.
- (18R)-hydroxy-(5Z,8Z,11Z,14Z,16E)-eicosapentaenoate + O2 = (5S)-hydroperoxy-(18R)-hydroxy-(6E,8Z,11Z,14Z,16E)-eicosapentaenoateThis reaction proceeds in the forward direction.
- (18S)-hydroxy-(5Z,8Z,11Z,14Z,16E)-eicosapentaenoate + O2 = (5S)-hydroperoxy-(18S)-hydroxy-(6E,8Z,11Z,14Z,16E)-eicosapentaenoateThis reaction proceeds in the forward direction.
- (5S)-hydroperoxy-(18S)-hydroxy-(6E,8Z,11Z,14Z,16E)-eicosapentaenoate = (5S,6S)-epoxy-(18S)-hydroxy-(7E,9E,11Z,14Z,16E)-eicosapentaenoate + H2OThis reaction proceeds in the forward direction.
- (5S)-hydroperoxy-(18R)-hydroxy-(6E,8Z,11Z,14Z,16E)-eicosapentaenoate = (5S,6S)-epoxy-(18R)-hydroxy-(7E,9E,11Z,14Z,16E)-eicosapentaenoate + H2OThis reaction proceeds in the forward direction.
- (5S)-hydroperoxy-18-hydroxy-(7E,9E,11Z,14Z,16E)-eicosapentaenoate = (5S,6S)-epoxy-18-hydroxy-(7E,9E,11Z,14Z,16E)-eicosapentaenoate + H2OThis reaction proceeds in the forward direction.
- (5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 = (5S)-hydroperoxy-(6E,8Z,11Z,14Z)-eicosatetraenoateThis reaction proceeds in the forward direction.
- (15S)-hydroxy-(5Z,8Z,11Z,13E)-eicosatetraenoate + O2 = (5S)-hydroperoxy-(15S)-hydroxy-(6E,8Z,11Z,13E)-eicosatetraenoateThis reaction proceeds in the forward direction.
- (5S)-hydroperoxy-(6E,8Z,11Z,14Z)-eicosatetraenoate = H2O + leukotriene A4This reaction proceeds in the forward direction.
- (5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 = (8S)-hydroperoxy-(5Z,9E,11Z,14Z)-eicosatetraenoateThis reaction proceeds in the forward direction.
- (5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 = (12S)-hydroperoxy-(5Z,8Z,10E,14Z)-eicosatetraenoateThis reaction proceeds in the forward direction.
- (5Z,8Z)-eicosadienoate + O2 = (5S)-hydroperoxy-(6E,8Z)-eicosadienoate
- (12S)-hydroxy-(5Z,8Z,10E,14Z)-eicosatetraenoate + O2 = (5S)-hydroperoxy-(12S)-hydroxy-(6E,8Z,10E,14Z)-eicosatetraenoate
- (5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate + O2 = 5-hydroperoxy-(6E,8Z,11Z,14Z,17Z)-eicosapentaenoateThis reaction proceeds in the forward direction.
- (4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate + O2 = (14S)-hydroperoxy-(4Z,7Z,10Z,12E,16Z,19Z)-docosahexaenoateThis reaction proceeds in the forward direction.
- (4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate + O2 = (7S)-hydroperoxy-(4Z,8E,10Z,13Z,16Z,19Z)-docosahexaenoateThis reaction proceeds in the forward direction.
- (4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate + O2 = (17S)-hydroperoxy-(4Z,7Z,10Z,13Z,15E,19Z)-docosahexaenoateThis reaction proceeds in the forward direction.
Cofactor
Note: Binds 1 Fe cation per subunit.
Pathway
Lipid metabolism; leukotriene A4 biosynthesis.
Features
Showing features for binding site, site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 17 | Ca2+ 1 (UniProtKB | ChEBI); structural | ||||
Sequence: G | ||||||
Binding site | 18 | Ca2+ 2 (UniProtKB | ChEBI); structural | ||||
Sequence: T | ||||||
Binding site | 19 | Ca2+ 2 (UniProtKB | ChEBI); structural | ||||
Sequence: D | ||||||
Binding site | 44 | Ca2+ 2 (UniProtKB | ChEBI); structural | ||||
Sequence: N | ||||||
Binding site | 45 | Ca2+ 2 (UniProtKB | ChEBI); structural | ||||
Sequence: D | ||||||
Binding site | 47 | Ca2+ 2 (UniProtKB | ChEBI); structural | ||||
Sequence: E | ||||||
Binding site | 79 | Ca2+ 1 (UniProtKB | ChEBI); structural | ||||
Sequence: D | ||||||
Binding site | 80 | Ca2+ 1 (UniProtKB | ChEBI); structural | ||||
Sequence: D | ||||||
Site | 103 | Essential for stabilizing binding to COTL1 | ||||
Sequence: I | ||||||
Binding site | 367 | Fe cation (UniProtKB | ChEBI); catalytic | ||||
Sequence: H | ||||||
Binding site | 372 | Fe cation (UniProtKB | ChEBI); catalytic | ||||
Sequence: H | ||||||
Binding site | 550 | Fe cation (UniProtKB | ChEBI); catalytic | ||||
Sequence: H | ||||||
Binding site | 554 | Fe cation (UniProtKB | ChEBI); catalytic | ||||
Sequence: N | ||||||
Binding site | 673 | Fe cation (UniProtKB | ChEBI); catalytic | ||||
Sequence: I |
GO annotations
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended namePolyunsaturated fatty acid 5-lipoxygenase
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Rattus
Accessions
- Primary accessionP12527
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Nucleus membrane ; Peripheral membrane protein
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.
Keywords
- Cellular component
Phenotypes & Variants
Chemistry
PTM/Processing
Features
Showing features for chain, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000220696 | 1-673 | Polyunsaturated fatty acid 5-lipoxygenase | |||
Sequence: MPSYTVTVATGSQWFAGTDDYIYLSLIGSAGCSEKHLLDKAFYNDFERGGRDSYDVTVDEELGEIYLVKIEKRKYRLHDDWYLKYITLKTPHDYIEFPCYRWITGEGEIVLRDGCAKLARDDQIHILKQHRRKELETRQKQYRWMEWNPGFPLSIDAKCHKDLPRDIQFDSEKGVDFVLNYSKAMENLFINRFMHMFQSSWHDFADFEKIFVKISNTISERVKNHWQEDLMFGYQFLNGCNPVLIKRCTELPKKLPVTTEMVECSLERQLSLEQEVQEGNIFIVDYELLDGIDANKTDPCTHQFLAAPICLLYKNLANKIVPIAIQLNQTPGEKNPIFLPTDSKYDWLLAKIWVRSSDFHIHQTITHLLRTHLVSEVFGIAMYRQLPAVHPLFKLLVAHVRFTIAINTKAREQLNCEYGLFDKANATGGGGHVQMVQRAVQDLTYSSLCFPEAIKARGMDNTEDIPYYFYRDDGLLVWEAIQSFTTEVVSIYYEDDQVVEEDQELQDFVKDVYVYGMRGRKASGFPKSIKSREKLSEYLTVVIFTASAQHAAVNFGQYDWCSWIPNAPPTMRAPPPTAKGVVTIEQIVDTLPDRGRSCWHLGAVWALSQFQENELFLGMYPEEHFIEKPVKEAMIRFRKNLEAIVSVIAERNKNKKLPYYYLSPDRIPNSVAI | ||||||
Modified residue | 271 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 523 | Phosphoserine | ||||
Sequence: S |
Post-translational modification
Serine phosphorylation by MAPKAPK2 is stimulated by arachidonic acid. Phosphorylation on Ser-523 by PKA has an inhibitory effect. Phosphorylation on Ser-271 prevents export from the nucleus. Phosphorylation at Ser-523 is stimulated by 8-bromo-3',5'-cyclic AMP or prostaglandin E2.
Keywords
- PTM
Proteomic databases
PTM databases
Interaction
Subunit
Homodimer. Interacts with ALOX5AP and LTC4S. Interacts with COTL1, the interaction is required for stability and efficient catalytic activity. Interacts with PIK3R1; this interaction bridges ALOX5 with CD40 after CD40 ligation in B cells and leads to the production of reactive oxygen species (ROS). Interacts (via PLAT domain) with DICER1 (via Dicer dsRNA-binding fold domain); this interaction enhances arachidonate 5-lipoxygenase activity and modifies the miRNA precursor processing activity of DICER1.
Protein-protein interaction databases
Chemistry
Structure
Family & Domains
Features
Showing features for domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 2-117 | PLAT | ||||
Sequence: PSYTVTVATGSQWFAGTDDYIYLSLIGSAGCSEKHLLDKAFYNDFERGGRDSYDVTVDEELGEIYLVKIEKRKYRLHDDWYLKYITLKTPHDYIEFPCYRWITGEGEIVLRDGCAK | ||||||
Domain | 118-673 | Lipoxygenase | ||||
Sequence: LARDDQIHILKQHRRKELETRQKQYRWMEWNPGFPLSIDAKCHKDLPRDIQFDSEKGVDFVLNYSKAMENLFINRFMHMFQSSWHDFADFEKIFVKISNTISERVKNHWQEDLMFGYQFLNGCNPVLIKRCTELPKKLPVTTEMVECSLERQLSLEQEVQEGNIFIVDYELLDGIDANKTDPCTHQFLAAPICLLYKNLANKIVPIAIQLNQTPGEKNPIFLPTDSKYDWLLAKIWVRSSDFHIHQTITHLLRTHLVSEVFGIAMYRQLPAVHPLFKLLVAHVRFTIAINTKAREQLNCEYGLFDKANATGGGGHVQMVQRAVQDLTYSSLCFPEAIKARGMDNTEDIPYYFYRDDGLLVWEAIQSFTTEVVSIYYEDDQVVEEDQELQDFVKDVYVYGMRGRKASGFPKSIKSREKLSEYLTVVIFTASAQHAAVNFGQYDWCSWIPNAPPTMRAPPPTAKGVVTIEQIVDTLPDRGRSCWHLGAVWALSQFQENELFLGMYPEEHFIEKPVKEAMIRFRKNLEAIVSVIAERNKNKKLPYYYLSPDRIPNSVAI |
Sequence similarities
Belongs to the lipoxygenase family.
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length673
- Mass (Da)78,087
- Last updated2007-01-23 v3
- Checksum536B0BC27CB0A608
Computationally mapped potential isoform sequences
There are 2 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A0G2JU29 | A0A0G2JU29_RAT | Alox5 | 617 | ||
F1LMM5 | F1LMM5_RAT | Alox5 | 674 |
Sequence caution
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
J03960 EMBL· GenBank· DDBJ | AAA41538.1 EMBL· GenBank· DDBJ | mRNA | Frameshift |