General Information of Target

Target ID LDTP02936
Target Name Polyunsaturated fatty acid lipoxygenase ALOX12 (ALOX12)
Gene Name ALOX12
Gene ID 239
Synonyms
12LO; LOG12; Polyunsaturated fatty acid lipoxygenase ALOX12; EC 1.13.11.-; Arachidonate; 12S)-lipoxygenase; 12S-LOX; 12S-lipoxygenase; EC 1.13.11.31; Arachidonate; 15S)-lipoxygenase; EC 1.13.11.33; Linoleate; 13S)-lipoxygenase; Lipoxin synthase 12-LO; EC 3.3.2.-; Platelet-type lipoxygenase 12
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MGRYRIRVATGAWLFSGSYNRVQLWLVGTRGEAELELQLRPARGEEEEFDHDVAEDLGLL
QFVRLRKHHWLVDDAWFCDRITVQGPGACAEVAFPCYRWVQGEDILSLPEGTARLPGDNA
LDMFQKHREKELKDRQQIYCWATWKEGLPLTIAADRKDDLPPNMRFHEEKRLDFEWTLKA
GALEMALKRVYTLLSSWNCLEDFDQIFWGQKSALAEKVRQCWQDDELFSYQFLNGANPML
LRRSTSLPSRLVLPSGMEELQAQLEKELQNGSLFEADFILLDGIPANVIRGEKQYLAAPL
VMLKMEPNGKLQPMVIQIQPPNPSSPTPTLFLPSDPPLAWLLAKSWVRNSDFQLHEIQYH
LLNTHLVAEVIAVATMRCLPGLHPIFKFLIPHIRYTMEINTRARTQLISDGGIFDKAVST
GGGGHVQLLRRAAAQLTYCSLCPPDDLADRGLLGLPGALYAHDALRLWEIIARYVEGIVH
LFYQRDDIVKGDPELQAWCREITEVGLCQAQDRGFPVSFQSQSQLCHFLTMCVFTCTAQH
AAINQGQLDWYAWVPNAPCTMRMPPPTTKEDVTMATVMGSLPDVRQACLQMAISWHLSRR
QPDMVPLGHHKEKYFSGPKPKAVLNQFRTDLEKLEKEITARNEQLDWPYEYLKPSCIENS
VTI
Target Type
Literature-reported
Target Bioclass
Enzyme
Family
Lipoxygenase family
Subcellular location
Cytoplasm, cytosol
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 . Mainly converts arachidonate ((5Z,8Z,11Z,14Z)-eicosatetraenoate) to the specific bioactive lipid (12S)-hydroperoxyeicosatetraenoate/(12S)-HPETE. Through the production of bioactive lipids like (12S)-HPETE it regulates different biological processes including platelet activation. 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. 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. 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. Can also peroxidize linoleate ((9Z,12Z)-octadecadienoate) to (13S)-hydroperoxyoctadecadienoate/ (13S-HPODE). 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. 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.
TTD ID
T35527
Uniprot ID
P18054
DrugMap ID
TT12ABZ
Ensemble ID
ENST00000251535.11
HGNC ID
HGNC:429
ChEMBL ID
CHEMBL3687

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 1 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
HPAP
 Probe Info 
3.60  LDD0064  [1]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0014  Panhematin hPBMC 3.60  LDD0064  [1]

The Interaction Atlas With This Target

The Protein(s) Related To This Target

Other
Click To Hide/Show 2 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Keratin, type II cytoskeletal 5 (KRT5) Intermediate filament family P13647
Prelamin-A/C (LMNA) Intermediate filament family P02545

The Drug(s) Related To This Target

Investigative
Click To Hide/Show 19 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
(+)-(5s,8s,10s)-20-methoxy-9,15-ene-puupehenol Small molecular drug D02LUF
(+)-(5s,8s,10s)-20-methoxypuupehenol Small molecular drug D0K0QU
(+)-(5s,8s,9r,10s)-20-methoxypuupehenone Small molecular drug D0H8FG
(-)-7-n-methyldibromophakellin Small molecular drug D0M6KL
2,3,4,5-tetrabromo-6-(2,4-dibromo-phenoxy)-phenol Small molecular drug D0X4CI
3,4,6-tribromo-2-(2,4-dibromo-phenoxy)-phenol Small molecular drug D03YMX
Chloropuupehenone Small molecular drug D0W5DZ
Dimethylnordihydroguarierate Acid Small molecular drug D0I6ZS
Dysidenin Small molecular drug D08WDW
Isojaspic Acid Small molecular drug D0F9FG
Jaspic Acid Small molecular drug D07JRW
Mangostin Small molecular drug D06PRC
Neodysidenin Small molecular drug D0Q0LD
Nsc-125034 Small molecular drug D0S7AY
Nsc-172033 Small molecular drug D0X4BT
Nsc-292213 Small molecular drug D04JWS
Polybrominated Diphenyl Ether Derivative Small molecular drug D0A3QB
Puupehedione Small molecular drug D05FJM
Puupehenone Small molecular drug D07BXV
Discontinued
Click To Hide/Show 1 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Nsc-661755 Small molecular drug D0F4JL

References

1 A Chemical Proteomic Map of Heme-Protein Interactions. J Am Chem Soc. 2022 Aug 24;144(33):15013-15019. doi: 10.1021/jacs.2c06104. Epub 2022 Aug 12.
Mass spectrometry data entry: PXD034651