General Information of the Ferroptosis Target (ID: TAR10010)
Target Name Polyunsaturated fatty acid lipoxygenase ALOX15B (ALOX15B)
Synonyms
15-lipoxygenase 2 ; Arachidonate 15-lipoxygenase B; Arachidonate 15-lipoxygenase type II; Linoleate 13-lipoxygenase 15-LOb
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Gene Name ALOX15B
Sequence
MAEFRVRVSTGEAFGAGTWDKVSVSIVGTRGESPPLPLDNLGKEFTAGAEEDFQVTLPED
VGRVLLLRVHKAPPVLPLLGPLAPDAWFCRWFQLTPPRGGHLLFPCYQWLEGAGTLVLQE
GTAKVSWADHHPVLQQQRQEELQARQEMYQWKAYNPGWPHCLDEKTVEDLELNIKYSTAK
NANFYLQAGSAFAEMKIKGLLDRKGLWRSLNEMKRIFNFRRTPAAEHAFEHWQEDAFFAS
QFLNGLNPVLIRRCHYLPKNFPVTDAMVASVLGPGTSLQAELEKGSLFLVDHGILSGIQT
NVINGKPQFSAAPMTLLYQSPGCGPLLPLAIQLSQTPGPNSPIFLPTDDKWDWLLAKTWV
RNAEFSFHEALTHLLHSHLLPEVFTLATLRQLPHCHPLFKLLIPHTRYTLHINTLARELL
IVPGQVVDRSTGIGIEGFSELIQRNMKQLNYSLLCLPEDIRTRGVEDIPGYYYRDDGMQI
WGAVERFVSEIIGIYYPSDESVQDDRELQAWVREIFSKGFLNQESSGIPSSLETREALVQ
YVTMVIFTCSAKHAAVSAGQFDSCAWMPNLPPSMQLPPPTSKGLATCEGFIATLPPVNAT
CDVILALWLLSKEPGDQRPLGTYPDEHFTEEAPRRSIATFQSRLAQISRGIQERNQGLVL
PYTYLDPPLIENSVSI

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Family Lipoxygenase family
Function
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.

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Gene ID 247
Uniprot ID
O15296
Target Type Driver Suppressor Marker
Mechanism Diagram Click to View the Original Diagram
Tissue Relative Abundances of This Target
Full List of Regulator(s) of This Ferroptosis Target and Corresponding Disease/Drug Response(s)
ALOX15B can be involved in and affect the ferroptosis by the following regulators, and result in corresponding disease/drug response(s). You can browse corresponding disease or drug response(s) resulting from the regulation of certain regulators.
Browse Regulator related Disease
Phosphatidylethanolamine-binding protein 1 (PEBP1)
Health [ICD-11: N.A.]
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response of This Regulator [1]
Regulator for Ferroptosis Driver
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
hAECs (Human airway epithelial cells)
HT22 cells Normal Mus musculus CVCL_0321
HK-2 cells Normal Homo sapiens CVCL_0302
In Vivo Model
Male 20 weeks old CD-1 mice were obtained from Charles River Laboratories. The mice were randomly assigned (using random number generator in Excel) to receive 5 mg/kg Fer-1 (Abcam, cat #ab146169) or 1.5% DMSO (vehicle) 60 minutes before injection of folic acid (Sigma-Aldrich) of 250 mg/kg in 0.3 mol/L sodium bicarbonate intraperitoneally. Mice were euthanized 48 h later.

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Response Description PEBP1, a scaffold protein inhibitor of protein kinase cascades, complexes with two 15LO isoforms, 15LO1 (ALOX15) and 15LO2 (ALOX15B) , and changes their substrate competence to generate hydroperoxy-PE. Inadequate reduction of hydroperoxy-PE due to insufficiency or dysfunction of a selenoperoxidase, GPX4, leads to ferroptosis.
References
Ref 1 PEBP1 Wardens Ferroptosis by Enabling Lipoxygenase Generation of Lipid Death Signals. Cell. 2017 Oct 19;171(3):628-641.e26. doi: 10.1016/j.cell.2017.09.044.