General Information of Target

Target ID LDTP00602
Target Name Polyunsaturated fatty acid lipoxygenase ALOX15B (ALOX15B)
Gene Name ALOX15B
Gene ID 247
Synonyms
Polyunsaturated fatty acid lipoxygenase ALOX15B; 15-lipoxygenase 2; 15-LOX-2; Arachidonate 15-lipoxygenase B; 15-LOX-B; EC 1.13.11.33; Arachidonate 15-lipoxygenase type II; Linoleate 13-lipoxygenase 15-LOb; EC 1.13.11.-
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MAEFRVRVSTGEAFGAGTWDKVSVSIVGTRGESPPLPLDNLGKEFTAGAEEDFQVTLPED
VGRVLLLRVHKAPPVLPLLGPLAPDAWFCRWFQLTPPRGGHLLFPCYQWLEGAGTLVLQE
GTAKVSWADHHPVLQQQRQEELQARQEMYQWKAYNPGWPHCLDEKTVEDLELNIKYSTAK
NANFYLQAGSAFAEMKIKGLLDRKGLWRSLNEMKRIFNFRRTPAAEHAFEHWQEDAFFAS
QFLNGLNPVLIRRCHYLPKNFPVTDAMVASVLGPGTSLQAELEKGSLFLVDHGILSGIQT
NVINGKPQFSAAPMTLLYQSPGCGPLLPLAIQLSQTPGPNSPIFLPTDDKWDWLLAKTWV
RNAEFSFHEALTHLLHSHLLPEVFTLATLRQLPHCHPLFKLLIPHTRYTLHINTLARELL
IVPGQVVDRSTGIGIEGFSELIQRNMKQLNYSLLCLPEDIRTRGVEDIPGYYYRDDGMQI
WGAVERFVSEIIGIYYPSDESVQDDRELQAWVREIFSKGFLNQESSGIPSSLETREALVQ
YVTMVIFTCSAKHAAVSAGQFDSCAWMPNLPPSMQLPPPTSKGLATCEGFIATLPPVNAT
CDVILALWLLSKEPGDQRPLGTYPDEHFTEEAPRRSIATFQSRLAQISRGIQERNQGLVL
PYTYLDPPLIENSVSI
Target Bioclass
Enzyme
Family
Lipoxygenase family
Subcellular location
Nucleus; Cytoplasm, cytosol
Function
[Isoform A]: Non-heme iron-containing dioxygenase that catalyzes the stereo-specific peroxidation of free and esterified polyunsaturated fatty acids (PUFAs) generating a spectrum of bioactive lipid mediators (Probable). It inserts peroxyl groups at C15 of arachidonate ((5Z,8Z,11Z,14Z)-eicosatetraenoate) producing (15S)-hydroperoxyeicosatetraenoate/(15S)-HPETE (Probable). Also peroxidizes linoleate ((9Z,12Z)-octadecadienoate) to 13-hydroperoxyoctadecadienoate/13-HPODE (Probable). Oxygenates arachidonyl derivatives such as 2-arachidonoylglycerol (2-AG) leading to the production and extracellular release of 15-hydroxyeicosatetraenoyl glycerol (15-HETE-G) that acts as a peroxisome proliferator-activated receptor alpha agonist. Has the ability to efficiently class-switch ALOX5 pro-inflammatory mediators into anti-inflammatory intermediates. Participates in the sequential oxidations of DHA ((4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate) to generate specialized pro-resolving mediators (SPMs) resolvin D5 ((7S,17S)-diHPDHA), which can actively down-regulate the immune response and have anti-aggregation properties with platelets. In addition to free PUFAs hydrolyzed from phospholipids, it directly oxidizes PUFAs esterified to membrane-bound phospholipids. Has no detectable 8S-lipoxygenase activity on arachidonate but reacts with (8S)-HPETE to produce (8S,15S)-diHPETE (Probable). May regulate progression through the cell cycle and cell proliferation. May also regulate cytokine secretion by macrophages and therefore play a role in the immune response. May also regulate macrophage differentiation into proatherogenic foam cells.; [Isoform B]: Does not convert arachidonic acid to 15S-hydroperoxyeicosatetraenoic acid/(15S)-HPETE.
Uniprot ID
O15296
Ensemble ID
ENST00000380173.6
HGNC ID
HGNC:434
ChEMBL ID
CHEMBL2457

Target Site Mutations in Different Cell Lines

Cell line Mutation details Probe for labeling this protein in this cell
HT SNV: p.D666G .
JURKAT SNV: p.A228V .
LS180 SNV: p.N183D .
LS513 SNV: p.S334I .
MFE280 SNV: p.P423L .
NCIH661 SNV: p.G527A .

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 4 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
ONAyne
 Probe Info 
K175(0.44)  LDD0274  [1]
DBIA
 Probe Info 
C395(1.56)  LDD2267  [2]
CY-1
 Probe Info 
N.A.  LDD0246  [3]
NAIA_4
 Probe Info 
N.A.  LDD2226  [4]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0022  KB02 BRX142 C395(1.56)  LDD2267  [2]
 LDCM0023  KB03 BRX142 C395(1.79)  LDD2684  [2]
 LDCM0024  KB05 BRX211 C89(1.82); C161(2.10); C455(1.64)  LDD3102  [2]

The Interaction Atlas With This Target

The Protein(s) Related To This Target

Enzyme
Click To Hide/Show 2 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
E3 ubiquitin-protein ligase TRAIP (TRAIP) TRAIP family Q9BWF2
E3 ubiquitin-protein ligase TRIM21 (TRIM21) TRIM/RBCC family P19474
Transporter and channel
Click To Hide/Show 1 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Potassium voltage-gated channel subfamily F member 1 (KCNF1) Potassium channel family Q9H3M0
Transcription factor
Click To Hide/Show 1 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Retinoic acid receptor alpha (RARA) Nuclear hormone receptor family P10276
Other
Click To Hide/Show 2 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Cancer/testis antigen 1 (CTAG1A; CTAG1B) CTAG/PCC1 family P78358
Coiled-coil domain-containing protein 115 (CCDC115) . Q96NT0

References

1 A Paal-Knorr agent for chemoproteomic profiling of targets of isoketals in cells. Chem Sci. 2021 Oct 15;12(43):14557-14563. doi: 10.1039/d1sc02230j. eCollection 2021 Nov 10.
Mass spectrometry data entry: PXD028270
2 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
3 Cyclopropenone, Cyclopropeniminium Ion, and Cyclopropenethione as Novel Electrophilic Warheads for Potential Target Discovery of Triple-Negative Breast Cancer. J Med Chem. 2023 Feb 23;66(4):2851-2864. doi: 10.1021/acs.jmedchem.2c01889. Epub 2023 Feb 10.
4 N-Acryloylindole-alkyne (NAIA) enables imaging and profiling new ligandable cysteines and oxidized thiols by chemoproteomics. Nat Commun. 2023 Jun 15;14(1):3564. doi: 10.1038/s41467-023-39268-w.
Mass spectrometry data entry: PXD041264