Ferroptosis Target Information
General Information of the Ferroptosis Target (ID: TAR10010)
Target Name | Polyunsaturated fatty acid lipoxygenase ALOX15B (ALOX15B) | ||||
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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 Click to Show/Hide
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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 | |||||
Target Type | Driver Suppressor Marker | ||||
Mechanism Diagram | Click to View the Original Diagram | ||||
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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. | ||||