General Information of Target

Target ID LDTP02821
Target Name Polyunsaturated fatty acid lipoxygenase ALOX15 (ALOX15)
Gene Name ALOX15
Gene ID 246
Synonyms
LOG15; Polyunsaturated fatty acid lipoxygenase ALOX15; 12/15-lipoxygenase; Arachidonate 12-lipoxygenase, leukocyte-type; 12-LOX; EC 1.13.11.31; Arachidonate 15-lipoxygenase; 15-LOX; 15-LOX-1; EC 1.13.11.33; Arachidonate omega-6 lipoxygenase; Hepoxilin A3 synthase Alox15; EC 1.13.11.-; Linoleate 13S-lipoxygenase; EC 1.13.11.12
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MGLYRIRVSTGASLYAGSNNQVQLWLVGQHGEAALGKRLWPARGKETELKVEVPEYLGPL
LFVKLRKRHLLKDDAWFCNWISVQGPGAGDEVRFPCYRWVEGNGVLSLPEGTGRTVGEDP
QGLFQKHREEELEERRKLYRWGNWKDGLILNMAGAKLYDLPVDERFLEDKRVDFEVSLAK
GLADLAIKDSLNVLTCWKDLDDFNRIFWCGQSKLAERVRDSWKEDALFGYQFLNGANPVV
LRRSAHLPARLVFPPGMEELQAQLEKELEGGTLFEADFSLLDGIKANVILCSQQHLAAPL
VMLKLQPDGKLLPMVIQLQLPRTGSPPPPLFLPTDPPMAWLLAKCWVRSSDFQLHELQSH
LLRGHLMAEVIVVATMRCLPSIHPIFKLIIPHLRYTLEINVRARTGLVSDMGIFDQIMST
GGGGHVQLLKQAGAFLTYSSFCPPDDLADRGLLGVKSSFYAQDALRLWEIIYRYVEGIVS
LHYKTDVAVKDDPELQTWCREITEIGLQGAQDRGFPVSLQARDQVCHFVTMCIFTCTGQH
ASVHLGQLDWYSWVPNAPCTMRLPPPTTKDATLETVMATLPNFHQASLQMSITWQLGRRQ
PVMVAVGQHEEEYFSGPEPKAVLKKFREELAALDKEIEIRNAKLDMPYEYLRPSVVENSV
AI
Target Type
Patented-recorded
Target Bioclass
Enzyme
Family
Lipoxygenase family
Subcellular location
Cytoplasm, cytosol
Function
Non-heme iron-containing dioxygenase that catalyzes the stereo-specific peroxidation of free and esterified polyunsaturated fatty acids generating a spectrum of bioactive lipid mediators . It inserts peroxyl groups at C12 or C15 of arachidonate ((5Z,8Z,11Z,14Z)-eicosatetraenoate) producing both 12-hydroperoxyeicosatetraenoate/12-HPETE and 15-hydroperoxyeicosatetraenoate/15-HPETE. It may then act on 12-HPETE to produce hepoxilins, which may show pro-inflammatory properties. Can also peroxidize linoleate ((9Z,12Z)-octadecadienoate) to 13-hydroperoxyoctadecadienoate/13-HPODE. 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. Can convert epoxy fatty acids to hydroperoxy-epoxides derivatives followed by an intramolecular nucleophilic substitution leading to the formation of monocyclic endoperoxides. Plays an important role during the maintenance of self-tolerance by peroxidizing membrane-bound phosphatidylethanolamine which can then signal the sorting process for clearance of apoptotic cells during inflammation and prevent an autoimmune response. In addition to its role in the immune and inflammatory responses, this enzyme may play a role in epithelial wound healing in the cornea through production of lipoxin A4 (LXA(4)) and docosahexaenoic acid-derived neuroprotectin D1 (NPD1; 10R,17S-HDHA), both lipid autacoids exhibit anti-inflammatory and neuroprotective properties. Furthermore, it may regulate actin polymerization which is crucial for several biological processes such as the phagocytosis of apoptotic cells. It is also implicated in the generation of endogenous ligands for peroxisome proliferator activated receptor (PPAR-gamma), hence modulating macrophage development and function. It may also exert a negative effect on skeletal development by regulating bone mass through this pathway. As well as participates in ER stress and downstream inflammation in adipocytes, pancreatic islets, and liver. Finally, it is also involved in the cellular response to IL13/interleukin-13.
TTD ID
T16042
Uniprot ID
P16050
DrugMap ID
TTN9T81
Ensemble ID
ENST00000293761.8
HGNC ID
HGNC:433
ChEMBL ID
CHEMBL2903

Target Site Mutations in Different Cell Lines

Cell line Mutation details Probe for labeling this protein in this cell
AU565 SNV: p.Q125H .
COLO792 SNV: p.E224K .
EFO21 SNV: p.H246D .
HCT116 SNV: p.Q317H .
HCT15 SNV: p.L453M .
HEC1 SNV: p.E369G .
KNS81FD SNV: p.V602I .
LS123 SNV: p.T375N .
MEWO SNV: p.G412E .
NCIH358 SNV: p.P41H .
RKO SNV: p.G28D .
SNU1079 SNV: p.Q358K .
SW480 SNV: p.R377K .
SW620 SNV: p.R377K .

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
DBIA
 Probe Info 
C209(1.77)  LDD3368  [1]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0022  KB02 OAW-28 C209(1.58)  LDD2534  [1]
 LDCM0023  KB03 OAW-28 C209(1.95)  LDD2951  [1]
 LDCM0024  KB05 OAW-28 C209(1.77)  LDD3368  [1]

References

1 DrugMap: A quantitative pan-cancer analysis of cysteine ligandability. Cell. 2024 May 9;187(10):2536-2556.e30. doi: 10.1016/j.cell.2024.03.027. Epub 2024 Apr 22.
Mass spectrometry data entry: PXD047840