Target Information
Target General Infomation | |||||
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Target ID |
T16042
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Former ID |
TTDR00234
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Target Name |
Arachidonate 15-lipoxygenase
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Gene Name |
ALOX15
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Synonyms |
15-LOX; 15-Lipoxygenase; Arachidonate omega-6 lipoxygenase; ALOX15
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Target Type |
Discontinued
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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. Converts arachidonic acid into 12- hydroperoxyeicosatetraenoic acid/12-HPETE and 15- hydroperoxyeicosatetraenoic acid/15-HPETE. Also converts linoleic acid to 13-hydroperoxyoctadecadienoic acid. May also act on (12S)- hydroperoxyeicosatetraenoic acid/(12S)-HPETE to produce hepoxilin A3. Probably plays an important role in the immune and inflammatory responses. Through the oxygenation of membrane-bound phosphatidylethanolamine in macrophages may favor clearance of apoptotic cells during inflammation by resident macrophages and prevent an autoimmune response associated with the clearance of apoptotic cells by inflammatory monocytes. In parallel, may regulate actin polymerization which is crucial for several biological processes, including macrophage function. May also regulate macrophage function through regulation of the peroxisome proliferator activated receptor signaling pathway. Finally, it is also involved in the cellular response to IL13/interleukin-13. In addition to its role in the immune and inflammatory responses, may play a role in epithelial wound healing in the cornea maybe through production of lipoxin A4. May also play a role in endoplasmic reticulum stress response and the regulation of bone mass.
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BioChemical Class |
Oxidoreductases acting on single donors
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Target Validation |
T16042
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UniProt ID | |||||
EC Number |
EC 1.13.11.33
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Sequence |
MGLYRIRVSTGASLYAGSNNQVQLWLVGQHGEAALGKRLWPARGKETELKVEVPEYLGPL
LFVKLRKRHLLKDDAWFCNWISVQGPGAGDEVRFPCYRWVEGNGVLSLPEGTGRTVGEDP QGLFQKHREEELEERRKLYRWGNWKDGLILNMAGAKLYDLPVDERFLEDKRVDFEVSLAK GLADLAIKDSLNVLTCWKDLDDFNRIFWCGQSKLAERVRDSWKEDALFGYQFLNGANPVV LRRSAHLPARLVFPPGMEELQAQLEKELEGGTLFEADFSLLDGIKANVILCSQQHLAAPL VMLKLQPDGKLLPMVIQLQLPRTGSPPPPLFLPTDPPMAWLLAKCWVRSSDFQLHELQSH LLRGHLMAEVIVVATMRCLPSIHPIFKLIIPHLRYTLEINVRARTGLVSDMGIFDQIMST GGGGHVQLLKQAGAFLTYSSFCPPDDLADRGLLGVKSSFYAQDALRLWEIIYRYVEGIVS LHYKTDVAVKDDPELQTWCREITEIGLQGAQDRGFPVSLQARDQVCHFVTMCIFTCTGQH ASVHLGQLDWYSWVPNAPCTMRLPPPTTKDATLETVMATLPNFHQASLQMSITWQLGRRQ PVMVAVGQHEEEYFSGPEPKAVLKKFREELAALDKEIEIRNAKLDMPYEYLRPSVVENSV AI |
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Structure |
2ABT
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Drugs and Mode of Action | |||||
Inhibitor | (+)-(5S,8S,10S)-20-methoxy-9,15-ene-puupehenol | Drug Info | [526556] | ||
(+)-(5S,8S,10S)-20-methoxypuupehenol | Drug Info | [526556] | |||
(+)-(5S,8S,9R,10S)-20-methoxypuupehenone | Drug Info | [526556] | |||
(+)-3,3'-bisdemethyltanegool | Drug Info | [528750] | |||
(-)-3,3'-bisdemethylpinoresinol | Drug Info | [528750] | |||
(-)-pinoresinol | Drug Info | [528750] | |||
(2E)-3-(2-OCT-1-YN-1-YLPHENYL)ACRYLIC ACID | Drug Info | [551374] | |||
2,3,4,5-Tetrabromo-6-(2,4-dibromo-phenoxy)-phenol | Drug Info | [527145] | |||
3,4,6-Tribromo-2-(2,4-dibromo-phenoxy)-phenol | Drug Info | [527145] | |||
3,4-Dibromo-2-(5-bromo-2-hydroxy-phenoxy)-phenol | Drug Info | [527145] | |||
3,6,8-Tribromo-dibenzo[1,4]dioxin-1-ol | Drug Info | [527145] | |||
Benzothiopyranoindole | Drug Info | [534839] | |||
CHLOROPUUPEHENONE | Drug Info | [526556] | |||
Dimethylnordihydroguarierate acid | Drug Info | [526556] | |||
DYSIDENIN | Drug Info | [529029] | |||
Halisulfate 1 | Drug Info | [526556] | |||
Hydrohalisulfate 1 | Drug Info | [526556] | |||
IGERNELLIN | Drug Info | [526556] | |||
Isojaspic acid | Drug Info | [530468] | |||
ISOSCOPOLETIN | Drug Info | [528750] | |||
JASPAQUINOL | Drug Info | [530468] | |||
Jaspic acid | Drug Info | [526556] | |||
KAEMPFEROL | Drug Info | [528750] | |||
Nonsteroidal anti-inflammatory drugs (NSAIDs) | Drug Info | [535013] | |||
NSC-172033 | Drug Info | [529029] | |||
NSC-30552 | Drug Info | [529029] | |||
NSC-661755 | Drug Info | [529029] | |||
Polybrominated diphenyl ether derivative | Drug Info | [527145] | |||
PUUPEHEDIONE | Drug Info | [530468] | |||
PUUPEHENONE | Drug Info | [530468] | |||
SCOPOLETIN | Drug Info | [528750] | |||
SPONGIADIOXIN A | Drug Info | [527145] | |||
Subersic acid | Drug Info | [526556] | |||
Pathways | |||||
BioCyc Pathway | Resolvin D biosynthesis | ||||
Lipoxin biosynthesis | |||||
KEGG Pathway | Arachidonic acid metabolism | ||||
Linoleic acid metabolism | |||||
Metabolic pathways | |||||
Serotonergic synapse | |||||
NetPath Pathway | IL4 Signaling Pathway | ||||
PANTHER Pathway | Inflammation mediated by chemokine and cytokine signaling pathway | ||||
Pathway Interaction Database | IL4-mediated signaling events | ||||
PathWhiz Pathway | Arachidonic Acid Metabolism | ||||
WikiPathways | Arachidonic acid metabolism | ||||
Eicosanoid Synthesis | |||||
References | |||||
Ref 526556 | J Nat Prod. 2003 Feb;66(2):230-5.Exploring sponge-derived terpenoids for their potency and selectivity against 12-human, 15-human, and 15-soybean lipoxygenases. | ||||
Ref 527145 | J Med Chem. 2004 Jul 29;47(16):4060-5.Probing the activity differences of simple and complex brominated aryl compounds against 15-soybean, 15-human, and 12-human lipoxygenase. | ||||
Ref 528750 | J Nat Prod. 2007 May;70(5):859-62. Epub 2007 Mar 23.Lipoxygenase inhibitory constituents of the fruits of noni (Morinda citrifolia) collected in Tahiti. | ||||
Ref 529029 | Bioorg Med Chem. 2007 Nov 15;15(22):6900-8. Epub 2007 Aug 22.Discovery of platelet-type 12-human lipoxygenase selective inhibitors by high-throughput screening of structurally diverse libraries. | ||||
Ref 530468 | J Nat Prod. 2009 Oct;72(10):1857-63.Using enzyme assays to evaluate the structure and bioactivity of sponge-derived meroterpenes. | ||||
Ref 534839 | 15-Lipoxygenase and its inhibition: a novel therapeutic target for vascular disease. Curr Pharm Des. 1999 Jan;5(1):11-20. |
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