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MGP000128

UniProt Annotations

Entry Information
Gene Namearachidonate 12-lipoxygenase
Protein EntryLOX12_HUMAN
UniProt IDP18054
SpeciesHuman
Comments
Comment typeDescription
Biophysicochemical PropertiesKinetic parameters: KM=8 uM for arachidonate (PubMed:1851637, at pH 7.0 and 37 degrees Celsius) {ECO:0000269|PubMed:1851637, ECO:0000269|PubMed:8250832, ECO:0000269|PubMed:8319693}; KM=10 uM for arachidonate (PubMed:8319693, at pH 8.0 and 25 degrees Celsius) {ECO:0000269|PubMed:1851637, ECO:0000269|PubMed:8250832, ECO:0000269|PubMed:8319693}; KM=6.2 uM for arachidonate (PubMed:8250832, at pH 7.4) {ECO:0000269|PubMed:1851637, ECO:0000269|PubMed:8250832, ECO:0000269|PubMed:8319693}; KM=9 uM for linoleate (PubMed:8319693, at pH 8.0 and 25 degrees Celsius) {ECO:0000269|PubMed:1851637, ECO:0000269|PubMed:8250832, ECO:0000269|PubMed:8319693}; KM=7.9 uM for leukotriene A4 (PubMed:8250832, at pH 7.4) {ECO:0000269|PubMed:1851637, ECO:0000269|PubMed:8250832, ECO:0000269|PubMed:8319693}; KM=3 uM for eicosa-5,8,11,14,17-pentaenoate (PubMed:1851637, at pH 7.0 and 37 degrees Celsius) {ECO:0000269|PubMed:1851637, ECO:0000269|PubMed:8250832, ECO:0000269|PubMed:8319693}; KM=35 uM for eicosa-8,11,14-trienoate (PubMed:1851637, at pH 7.0 and 37 degrees Celsius) {ECO:0000269|PubMed:1851637, ECO:0000269|PubMed:8250832, ECO:0000269|PubMed:8319693}; KM=14.3 uM for 5,6-epoxy-8,11,14-eicosatrienoate (PubMed:8250832, at pH 7.4) {ECO:0000269|PubMed:1851637, ECO:0000269|PubMed:8250832, ECO:0000269|PubMed:8319693}; Vmax=3 umol/min/mg enzyme with arachidonate as substrate (PubMed:8319693, at pH 8.0 and 25 degrees Celsius) {ECO:0000269|PubMed:1851637, ECO:0000269|PubMed:8250832, ECO:0000269|PubMed:8319693}; Vmax=1.057 umol/min/mg enzyme with arachidonate as substrate (PubMed:8250832, at pH 7.4) {ECO:0000269|PubMed:1851637, ECO:0000269|PubMed:8250832, ECO:0000269|PubMed:8319693}; Vmax=0.0375 umol/min/mg enzyme with linoleate as substrate (PubMed:8319693, at pH 8.0 and 25 degrees Celsius) {ECO:0000269|PubMed:1851637, ECO:0000269|PubMed:8250832, ECO:0000269|PubMed:8319693}; Vmax=0.025 umol/min/mg enzyme with leukotriene A4 as substrate (PubMed:8250832, at pH 7.4) {ECO:0000269|PubMed:1851637, ECO:0000269|PubMed:8250832, ECO:0000269|PubMed:8319693}; Vmax=0.985 umol/min/mg enzyme with 5,6-epoxy-8,11,14- eicosatrienoate as substrate (PubMed:8250832, at pH 7.4) {ECO:0000269|PubMed:1851637, ECO:0000269|PubMed:8250832, ECO:0000269|PubMed:8319693}; pH dependence: Optimum pH is 7.5-8.0 (for arachidonate 12-lipoxygenase activity). {ECO:0000269|PubMed:8250832, ECO:0000269|PubMed:8319693};
Catalytic Activity(7E,9E,11Z,14Z)-(5S,6S)-5,6-epoxyicosa- 7,9,11,14-tetraenoate + H(2)O = (5S,14R,15S)-trihydroxy- (6E,8Z,10E,12E)-eicosatetraenoate.
Catalytic Activity(7E,9E,11Z,14Z)-(5S,6S)-5,6-epoxyicosa- 7,9,11,14-tetraenoate + H(2)O = (5S,6R,15S)-trihydroxy- (7E,9E,11Z,13E)-eicosatetraenoate.
Catalytic ActivityArachidonate + O(2) = (5Z,8Z,10E,14Z)-(12S)- 12-hydroperoxyicosa-5,8,10,14-tetraenoate.
CofactorName=Fe cation; Xref=ChEBI:CHEBI:24875; Note=Binds 1 Fe cation per subunit.;
DiseaseColorectal cancer (CRC) [MIM:114500]: 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. {ECO:0000269|PubMed:17151091}. Note=Disease susceptibility may be associated with variations affecting the gene represented in this entry. Gln at position 261 may confer interindividual susceptibility to colorectal cancer (PubMed:17460548). {ECO:0000269|PubMed:17460548}.
DiseaseEsophageal cancer (ESCR) [MIM:133239]: 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. {ECO:0000269|PubMed:17460548}. Note=Disease susceptibility may be associated with variations affecting the gene represented in this entry. Gln at position 261 may confer interindividual susceptibility to esophageal cancer (PubMed:17460548). {ECO:0000269|PubMed:17460548}.
Enzyme RegulationActivated by EGF. {ECO:0000269|PubMed:8912711}.
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. Mainly converts arachidonic acid to (12S)- hydroperoxyeicosatetraenoic acid/(12S)-HPETE but can also metabolize linoleic acid. Has a dual activity since it also converts leukotriene A4/LTA4 into both the bioactive lipoxin A4/LXA4 and lipoxin B4/LXB4. Through the production of specific bioactive lipids like (12S)-HPETE it regulates different biological processes including platelet activation. It also probably positively regulates angiogenesis through regulation of the expression of the vascular endothelial growth factor. Plays a role in apoptotic process, promoting the survival of vascular smooth muscle cells for instance. May also play a role in the control of cell migration and proliferation. {ECO:0000269|PubMed:16638750, ECO:0000269|PubMed:22237009, ECO:0000269|PubMed:23578768, ECO:0000269|PubMed:8250832, ECO:0000269|PubMed:9751607}.
InductionDown-regulated upon starvation, by UV-irradiation and 15-lipoxygenase metabolites. {ECO:0000269|PubMed:18755188, ECO:0000269|PubMed:8912711}.
InteractionP13647:KRT5; NbExp=7; IntAct=EBI-1633210, EBI-702187; P02545:LMNA; NbExp=4; IntAct=EBI-1633210, EBI-351935;
PathwayLipid metabolism; hydroperoxy eicosatetraenoic acid biosynthesis. {ECO:0000269|PubMed:1851637}.
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. Membrane. Note=Membrane association is stimulated by EGF.
Tissue SpecificityExpressed in vascular smooth muscle cells. {ECO:0000269|PubMed:23578768}.
Web ResourceName=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/ALOX12ID620ch17p13.html";
Web ResourceName=SeattleSNPs; URL="http://pga.gs.washington.edu/data/alox12/";
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