ALOX12
entrez
239
canonical
uniprot
P18054
canonical
ensembl
ENSG00000108839
resolver
ensp
ENSP00000251535
resolver
enst
ENST00000251535
resolver
genesymbol
ALOX12
resolver
genesymbol_syn
12LO
resolver
genesymbol_syn
LOG12
resolver
hgnc
HGNC:429
resolver
uniprot
O95569
resolver
uniprot
Q6ISF8
resolver
uniprot
Q9UQM4
resolver
uniprot_entry
LOX12_HUMAN
resolver
uniprot_sec
O95569
resolver
uniprot_sec
Q6ISF8
resolver
uniprot_sec
Q9UQM4
resolver
activity_regulation
ACTIVITY REGULATION: Activated by EGF (PubMed:8912711). Arachidonic acid conversion is inhibited by (13S,14S)-epoxy-(4Z,7Z,9E,11E,16Z,19Z)-docosahexaenoate (13S,14S-epoxy-DHA) (PubMed:23504711). Arachidonate 12-lipoxygenase activity is decreased when PH decreases from 7.4 to 6 (By similarity). {ECO:0000250|UniProtKB:P39655, ECO:0000269|PubMed:23504711, ECO:0000269|PubMed:8912711}.
uniprot
proteins
amino_acid_sequence
MGRYRIRVATGAWLFSGSYNRVQLWLVGTRGEAELELQLRPARGEEEEFDHDVAEDLGLLQFVRLRKHHWLVDDAWFCDRITVQGPGACAEVAFPCYRWVQGEDILSLPEGTARLPGDNALDMFQKHREKELKDRQQIYCWATWKEGLPLTIAADRKDDLPPNMRFHEEKRLDFEWTLKAGALEMALKRVYTLLSSWNCLEDFDQIFWGQKSALAEKVRQCWQDDELFSYQFLNGANPMLLRRSTSLPSRLVLPSGMEELQAQLEKELQNGSLFEADFILLDGIPANVIRGEKQYLAAPLVMLKMEPNGKLQPMVIQIQPPNPSSPTPTLFLPSDPPLAWLLAKSWVRNSDFQLHEIQYHLLNTHLVAEVIAVATMRCLPGLHPIFKFLIPHIRYTMEINTRARTQLISDGGIFDKAVSTGGGGHVQLLRRAAAQLTYCSLCPPDDLADRGLLGLPGALYAHDALRLWEIIARYVEGIVHLFYQRDDIVKGDPELQAWCREITEVGLCQAQDRGFPVSFQSQSQLCHFLTMCVFTCTAQHAAINQGQLDWYAWVPNAPCTMRMPPPTTKEDVTMATVMGSLPDVRQACLQMAISWHLSRRQPDMVPLGHHKEKYFSGPKPKAVLNQFRTDLEKLEKEITARNEQLDWPYEYLKPSCIENSVTI
uniprot
proteins
disease_involvement
DISEASE: Esophageal 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 variants affecting the gene represented in this entry. Gln at position 261 may confer interindividual susceptibility to esophageal cancer (PubMed:17460548). {ECO:0000269|PubMed:17460548}.; DISEASE: Colorectal 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 variants affecting the gene represented in this entry. Gln at position 261 may confer interindividual susceptibility to colorectal cancer (PubMed:17460548). {ECO:0000269|PubMed:17460548}.
uniprot
proteins
ec_number
1.13.11.-
uniprot
proteins
ec_number
1.13.11.31
uniprot
proteins
ec_number
1.13.11.33
uniprot
proteins
function
FUNCTION: 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:18311922, PubMed:1851637, PubMed:32404334, PubMed:8319693, PubMed:8500694). 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 down-regulate 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:16638750, PubMed:22237009, PubMed:9751607). 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). {ECO:0000250|UniProtKB:P39655, ECO:0000269|PubMed:16638750, ECO:0000269|PubMed:17493578, ECO:0000269|PubMed:18311922, ECO:0000269|PubMed:1851637, ECO:0000269|PubMed:22237009, ECO:0000269|PubMed:22984144, ECO:0000269|PubMed:23504711, ECO:0000269|PubMed:23578768, ECO:0000269|PubMed:24282679, ECO:0000269|PubMed:32404334, ECO:0000269|PubMed:8250832, ECO:0000269|PubMed:8319693, ECO:0000269|PubMed:8500694, ECO:0000269|PubMed:9751607}.
uniprot
proteins
mass_dalton
75694
uniprot
proteins
mutagenesis
MUTAGEN 355; /note="H->Q: No effect on arachidonate 12(S)-lipoxygenase activity."; /evidence="ECO:0000269|PubMed:8500694"; MUTAGEN 360; /note="H->Q,Y: Complete loss of arachidonate 12(S)-lipoxygenase activity."; /evidence="ECO:0000269|PubMed:8500694"; MUTAGEN 365; /note="H->Q: Complete loss of arachidonate 12(S)-lipoxygenase activity."; /evidence="ECO:0000269|PubMed:8500694"; MUTAGEN 383; /note="H->Q: Alteredarachidonate 12(S)-lipoxygenase activity and protein expression."; /evidence="ECO:0000269|PubMed:8500694"; MUTAGEN 392; /note="H->Q: No effect on arachidonate 12(S)-lipoxygenase activity."; /evidence="ECO:0000269|PubMed:8500694"; MUTAGEN 416; /note="K->Q: Reduced arachidonate 12(S)-lipoxygenase activity. No effect on the stereoselectivity of the oxygenation reaction."; /evidence="ECO:0000269|PubMed:8500694"; MUTAGEN 417; /note="A->I: Reduced arachidonate 12(S)-lipoxygenase activity. Alters the stereoselectivity of the oxygenation reaction."; /evidence="ECO:0000269|PubMed:8500694"; MUTAGEN 418; /note="V->M: No effect onarachidonate 12(S)-lipoxygenase activity. No effect on the stereoselectivity of the oxygenation reaction."; /evidence="ECO:0000269|PubMed:8500694"; MUTAGEN 540; /note="H->Q: Complete loss of arachidonate 12(S)-lipoxygenase activity."; /evidence="ECO:0000269|PubMed:8500694
uniprot
proteins
pathway_participation
PATHWAY: Lipid metabolism; hydroperoxy eicosatetraenoic acid biosynthesis. {ECO:0000269|PubMed:1851637}.
uniprot
proteins
protein_family
Lipoxygenase family
uniprot
proteins
pubmed
1447217
uniprot
proteins
pubmed
15308583
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
1570320
uniprot
proteins
pubmed
16625196
uniprot
proteins
pubmed
16638750
uniprot
proteins
pubmed
17151091
uniprot
proteins
pubmed
17460548
uniprot
proteins
pubmed
17493578
uniprot
proteins
pubmed
18311922
uniprot
proteins
pubmed
1851637
uniprot
proteins
pubmed
18755188
uniprot
proteins
pubmed
2217179
uniprot
proteins
pubmed
22237009
uniprot
proteins
pubmed
2244907
uniprot
proteins
pubmed
22984144
uniprot
proteins
pubmed
23504711
uniprot
proteins
pubmed
23578768
uniprot
proteins
pubmed
2377602
uniprot
proteins
pubmed
24282679
uniprot
proteins
pubmed
25036362
uniprot
proteins
pubmed
32404334
uniprot
proteins
pubmed
8250832
uniprot
proteins
pubmed
8304420
uniprot
proteins
pubmed
8319693
uniprot
proteins
pubmed
8500694
uniprot
proteins
pubmed
8912711
uniprot
proteins
pubmed
9751607
uniprot
proteins
sequence_length
663
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm, cytosol. Membrane. Note=Membrane association is stimulated by EGF.
uniprot
proteins