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MGP000132

UniProt Annotations

Entry Information
Gene Namearachidonate 15-lipoxygenase
Protein EntryLOX15_HUMAN
UniProt IDP16050
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=2; Name=1; IsoId=P16050-1; Sequence=Displayed; Name=2; IsoId=P16050-2; Sequence=VSP_056681; Note=No experimental confirmation available.;
Catalytic ActivityArachidonate + O(2) = (5Z,8Z,10E,14Z)-(12S)- 12-hydroperoxyicosa-5,8,10,14-tetraenoate.
Catalytic ActivityArachidonate + O(2) = (5Z,8Z,11Z,13E)-(15S)- 15-hydroperoxyicosa-5,8,11,13-tetraenoate.
CofactorName=Fe cation; Xref=ChEBI:CHEBI:24875; Evidence={ECO:0000255|PROSITE-ProRule:PRU00726}; Note=Binds 1 Fe cation per subunit. {ECO:0000255|PROSITE- ProRule:PRU00726};
DiseaseNote=Disease susceptibility may be associated with variations affecting the gene represented in this entry. Met at position 560 may confer interindividual susceptibility to coronary artery disease (CAD) (PubMed:17959182). {ECO:0000269|PubMed:17959182}.
DomainThe PLAT domain can bind calcium ions; this promotes association with membranes. {ECO:0000250}.
Enzyme RegulationActivity is increased by binding phosphatidylinositol phosphates, especially phosphatidylinositol 3,4-bisphosphate and phosphatidylinositol 4,5-bisphosphate. {ECO:0000269|PubMed:17052953}.
FunctionNon-heme iron-containing dioxygenase that catalyzes the stereo-specific peroxidation of free and esterified polyunsaturated fatty acids generating a spectrum of bioactive lipid mediators. Converts arachidonic acid into 12- hydroperoxyeicosatetraenoic acid/12-HPETE and 15- hydroperoxyeicosatetraenoic acid/15-HPETE. Also converts linoleic acid to 13-hydroperoxyoctadecadienoic acid. May also act on (12S)- hydroperoxyeicosatetraenoic acid/(12S)-HPETE to produce hepoxilin A3. Probably plays an important role in the immune and inflammatory responses. Through the oxygenation of membrane-bound phosphatidylethanolamine in macrophages may favor clearance of apoptotic cells during inflammation by resident macrophages and prevent an autoimmune response associated with the clearance of apoptotic cells by inflammatory monocytes. In parallel, may regulate actin polymerization which is crucial for several biological processes, including macrophage function. May also regulate macrophage function through regulation of the peroxisome proliferator activated receptor signaling pathway. Finally, it is also involved in the cellular response to IL13/interleukin-13. In addition to its role in the immune and inflammatory responses, may play a role in epithelial wound healing in the cornea maybe through production of lipoxin A4. May also play a role in endoplasmic reticulum stress response and the regulation of bone mass. {ECO:0000269|PubMed:17052953, ECO:0000269|PubMed:21831839}.
InductionUp-regulated by UV-irradiation. {ECO:0000269|PubMed:18755188}.
PathwayLipid metabolism; hydroperoxy eicosatetraenoic acid biosynthesis.
SimilarityBelongs to the lipoxygenase family. {ECO:0000305}.
SimilarityContains 1 lipoxygenase domain. {ECO:0000255|PROSITE- ProRule:PRU00726}.
SimilarityContains 1 PLAT domain. {ECO:0000255|PROSITE- ProRule:PRU00152}.
Subcellular LocationCytoplasm, cytosol. Cell membrane; Peripheral membrane protein. Lipid droplet. Note=Predominantly cytosolic; becomes enriched at membranes upon calcium binding. Translocates from the cytosol to the plasma membrane when stimulated by IL13/interleukin-13 and in macrophages binding apoptotic cells.
SubunitInteracts with PEBP1; in response to IL13/interleukin-13, prevents the interaction of PEBP1 with RAF1 to activate the ERK signaling cascade. {ECO:0000269|PubMed:21831839}.
Tissue SpecificityDetected in monocytes and eosinophils (at protein level). Expressed in airway epithelial cells. {ECO:0000269|PubMed:21831839, ECO:0000269|PubMed:9414270}.
Web ResourceName=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/ALOX15ID42986ch17p13.html";
Web ResourceName=SeattleSNPs; URL="http://pga.gs.washington.edu/data/alox15/";
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