ALOX12

This gene encodes a member of the lipoxygenase family of proteins. The encoded enzyme acts on different polyunsaturated fatty acid substrates to generate bioactive lipid mediators including eicosanoids and lipoxins. The encoded enzyme and its reaction products have been shown to regulate platelet function. Elevated expression of this gene has been observed in pancreatic islets derived from human diabetes patients. Allelic variants in this gene may be associated with susceptibility to toxoplasmosis. Multiple pseudogenes of this gene have been identified in the human genome. [provided by RefSeq, Aug 2017]

Arachidonate 12-Lipoxygenase, 12S Type

Catalyzes the regio and stereo-specific incorporation of molecular oxygen into free and esterified polyunsaturated fatty acids generating lipid hydroperoxides that can be further reduced to the corresponding hydroxy species (PubMed:17493578, PubMed:1851637, PubMed:8319693, PubMed:8500694, PubMed:18311922, PubMed:32404334). Mainly converts arachidonate ((5Z,8Z,11Z,14Z)-eicosatetraenoate) to the specific bioactive lipid (12S)-hydroperoxyeicosatetraenoate/(12S)-HPETE (PubMed:17493578, PubMed:22984144, PubMed:24282679, PubMed:8319693, PubMed:8500694). Through the production of bioactive lipids like (12S)-HPETE it regulates different biological processes including platelet activation (PubMed:8319693, PubMed:8500694). It can also catalyze the epoxidation of double bonds of polyunsaturated fatty acids such as (14S)-hydroperoxy-docosahexaenoate/(14S)-HPDHA resulting in the formation of (13S,14S)-epoxy-DHA (PubMed:23504711). Furthermore, it may participate in the sequential oxidations of DHA ((4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate) to generate specialized pro-resolving mediators (SPMs) like resolvin D5 ((7S,17S)-diHPDHA) and (7S,14S)-diHPDHA, that actively downregulate the immune response and have anti-aggregation properties with platelets (PubMed:32404334). An additional function involves a multistep process by which it transforms leukotriene A4/LTA4 into the bioactive lipids lipoxin A4/LXA4 and lipoxin B4/LXB4, both are vasoactive and LXA4 may regulate neutrophil function via occupancy of specific recognition sites (PubMed:8250832). Can also peroxidize linoleate ((9Z,12Z)-octadecadienoate) to (13S)-hydroperoxyoctadecadienoate/ (13S-HPODE) (By similarity). Due to its role in regulating both the expression of the vascular endothelial growth factor (VEGF, an angiogenic factor involved in the survival and metastasis of solid tumors) and the expression of integrin beta-1 (known to affect tumor cell migration and proliferation), it can be regarded as protumorigenic (PubMed:9751607, PubMed:16638750, PubMed:22237009). Important for cell survival, as it may play a role not only in proliferation but also in the prevention of apoptosis in vascular smooth muscle cells (PubMed:23578768).

Aging Source: Ensembl
Arachidonic acid metabolic process Source: UniProtKB
Cellular response to lipid Source: Ensembl
Establishment of skin barrier Source: UniProtKB
Fatty acid oxidation Source: UniProtKB
Hepoxilin biosynthetic process Source: UniProtKB
Hepoxilin metabolic process Source: Reactome
Leukotriene A4 metabolic process Source: UniProtKB
Linoleic acid metabolic process Source: UniProtKB
Lipid metabolic process Source: UniProtKB
Lipid oxidation Source: GO_Central
Lipoxin A4 biosynthetic process Source: UniProtKB
Lipoxin B4 biosynthetic process Source: UniProtKB
Lipoxin biosynthetic process Source: Reactome
Lipoxygenase pathway Source: UniProtKB
Long-chain fatty acid biosynthetic process Source: Reactome
Negative regulation of muscle cell apoptotic process Source: UniProtKB
Negative regulation of platelet aggregation Source: UniProtKB
Positive regulation of apoptotic process Source: Ensembl
Positive regulation of blood vessel endothelial cell migration Source: Ensembl
Positive regulation of cysteine-type endopeptidase activity involved in apoptotic process Source: Ensembl
Positive regulation of endothelial tube morphogenesis Source: Ensembl
Positive regulation of gene expression Source: Ensembl
Positive regulation of mitochondrial depolarization Source: Ensembl
Positive regulation of smooth muscle cell proliferation Source: Ensembl
Superoxide anion generation Source: UniProtKB
Unsaturated fatty acid metabolic process Source: UniProtKB

Cytosol; Membrane. Membrane association is stimulated by EGF.

Esophageal cancer (ESCR): Disease susceptibility may be associated with variants affecting the gene represented in this entry. Gln at position 261 may confer interindividual susceptibility to esophageal cancer (PubMed:17460548). A malignancy of the esophagus. The most common types are esophageal squamous cell carcinoma and adenocarcinoma. Cancer of the esophagus remains a devastating disease because it is usually not detected until it has progressed to an advanced incurable stage.
Colorectal cancer (CRC): Disease susceptibility may be associated with variants affecting the gene represented in this entry. Gln at position 261 may confer interindividual susceptibility to colorectal cancer (PubMed:17460548). A complex disease characterized by malignant lesions arising from the inner wall of the large intestine (the colon) and the rectum. Genetic alterations are often associated with progression from premalignant lesion (adenoma) to invasive adenocarcinoma. Risk factors for cancer of the colon and rectum include colon polyps, long-standing ulcerative colitis, and genetic family history.