General Information of the Protein
Protein ID |
PT01242
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Protein Name |
Polyunsaturated fatty acid 5-lipoxygenase
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Secondarily Protein Name |
Arachidonate 5-lipoxygenase
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Gene Name |
ALOX5
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Secondarily Gene Name |
LOG5
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Sequence |
MPSYTVTVATGSQWFAGTDDYIYLSLVGSAGCSEKHLLDKPFYNDFERGAVDSYDVTVDEELGEIQLVRIEKRKYWLNDDWYLKYITLKTPHGDYIEFPCYRWITGDVEVVLRDGRAKLARDDQIHILKQHRRKELETRQKQYRWMEWNPGFPLSIDAKCHKDLPRDIQFDSEKGVDFVLNYSKAMENLFINRFMHMFQSSWNDFADFEKIFVKISNTISERVMNHWQEDLMFGYQFLNGCNPVLIRRCTELPEKLPVTTEMVECSLERQLSLEQEVQQGNIFIVDFELLDGIDANKTDPCTLQFLAAPICLLYKNLANKIVPIAIQLNQIPGDENPIFLPSDAKYDWLLAKIWVRSSDFHVHQTITHLLRTHLVSEVFGIAMYRQLPAVHPIFKLLVAHVRFTIAINTKAREQLICECGLFDKANATGGGGHVQMVQRAMKDLTYASLCFPEAIKARGMESKEDIPYYFYRDDGLLVWEAIRTFTAEVVDIYYEGDQVVEEDPELQDFVNDVYVYGMRGRKSSGFPKSVKSREQLSEYLTVVIFTASAQHAAVNFGQYDWCSWIPNAPPTMRAPPPTAKGVVTIEQIVDTLPDRGRSCWHLGAVWALSQFQENELFLGMYPEEHFIEKPVKEAMARFRKNLEAIVSVIAERNKKKQLPYYYLSPDRIPNSVAI
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Organism |
Homo sapiens, Human
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Protein Classification |
Enzyme
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Oxidoreductase
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Function |
Catalyzes the oxygenation of arachidonate ((5Z,8Z,11Z,14Z)-eicosatetraenoate) to 5-hydroperoxyeicosatetraenoate (5-HPETE) followed by the dehydration to 5,6- epoxyeicosatetraenoate (Leukotriene A4/LTA4), the first two steps in the biosynthesis of leukotrienes, which are potent mediators of inflammation (PubMed:8631361, PubMed:21233389, PubMed:22516296, PubMed:24282679, PubMed:19022417, PubMed:23246375, PubMed:8615788, PubMed:24893149, PubMed:31664810). Also catalyzes the oxygenation of arachidonate into 8-hydroperoxyicosatetraenoate (8-HPETE) and 12-hydroperoxyicosatetraenoate (12-HPETE) (PubMed:23246375). Displays lipoxin synthase activity being able to convert (15S)-HETE into a conjugate tetraene (PubMed:31664810). Although arachidonate is the preferred substrate, this enzyme can also metabolize oxidized fatty acids derived from arachidonate such as (15S)-HETE, eicosapentaenoate (EPA) such as (18R)- and (18S)-HEPE or docosahexaenoate (DHA) which lead to the formation of specialized pro-resolving mediators (SPM) lipoxin and resolvins E and D respectively, therefore it participates in anti-inflammatory responses (PubMed:21206090, PubMed:31664810, PubMed:8615788, PubMed:17114001, PubMed:32404334). Oxidation of DHA directly inhibits endothelial cell proliferation and sprouting angiogenesis via peroxisome proliferator-activated receptor gamma (PPARgamma) (By similarity). It does not catalyze the oxygenation of linoleic acid and does not convert (5S)-HETE to lipoxin isomers (PubMed:31664810). In addition to inflammatory processes, it participates in dendritic cell migration, wound healing through an antioxidant mechanism based on heme oxygenase-1 (HO-1) regulation expression, monocyte adhesion to the endothelium via ITGAM expression on monocytes (By similarity). Moreover, it helps establish an adaptive humoral immunity by regulating primary resting B cells and follicular helper T cells and participates in the CD40-induced production of reactive oxygen species (ROS) after CD40 ligation in B cells through interaction with PIK3R1 that bridges ALOX5 with CD40 (PubMed:21200133). May also play a role in glucose homeostasis, regulation of insulin secretion and palmitic acid-induced insulin resistance via AMPK (By similarity). Can regulate bone mineralization and fat cell differentiation increases in induced pluripotent stem cells (By similarity).
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Uniprot ID |
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Ensembl ID | |||||
HGNC ID | |||||
Subcellular Location |
Cytoplasm
Nucleus matrix
Nucleus membrane
Cytoplasm
Perinuclear region
Cytoplasm
Cytosol
Nucleus envelope
Nucleus intermembrane space
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Map of Molecular Bioactivity Related to the Protein
Map of Molecular Bioactivity Related to the Protein Protein Cell Line Compound Bioactivity Value: <= 0.1 μM > 0.1 μM and <= 10 μM > 10 μM Imprecise Activity |
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Table of Molecular Bioactivities Related to the Protein
Cell Line ID: CL000006 , HEK293
Cell Line ID: CL000831 , PMNL
Cell Line ID: CL000194 , RBL-1
Cell Line ID: CL000013 , Sf9
Biochemical Assays
Clinical Information about the Protein
Target 1 ( Arachidonate 5-lipoxygenase (5-LOX) )
Target Type | Successful Target | ||||
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Disease | 20 Target-related Diseases | 20 | |||
1 | Asthma [ICD-11: CA23] | ||||
2 | Thrombocytopenia [ICD-11: 3B64] | ||||
3 | Non-small-cell lung cancer [ICD-11: 2C25.Y] | ||||
4 | Inflammation [ICD-11: 1A00-CA43.1] | ||||
5 | Rheumatoid arthritis [ICD-11: FA20] | ||||
6 | Influenza virus infection [ICD-11: 1E30-1E32] | ||||
7 | Acromegaly [ICD-11: 5A60.0] | ||||
8 | Psoriasis vulgaris [ICD-11: EA90] | ||||
9 | Respiratory disease [ICD-11: CB40] | ||||
10 | Pruritus [ICD-11: EC90] | ||||
11 | Thrombosis [ICD-11: DB61-GB90] | ||||
12 | Dermatitis [ICD-11: EA80-EA89] | ||||
13 | Chronic obstructive pulmonary disease [ICD-11: CA22] | ||||
14 | Cardiac disease [ICD-11: BA00-BE2Z] | ||||
15 | Pain [ICD-11: MG30-MG3Z] | ||||
16 | Osteoarthritis [ICD-11: FA00-FA05] | ||||
17 | Allergy [ICD-11: 4A80-4A85] | ||||
18 | Arthritis [ICD-11: FA20] | ||||
19 | Arteriosclerosis [ICD-11: BD40] | ||||
20 | Malaria [ICD-11: 1F40-1F45] | ||||
Approved Drug(s) | 2 Approved Drugs | 2 | |||
1 | Zileuton | Approved | |||
2 | 3,4-Dihydroxycinnamic Acid | Phase 4 | |||
Clinical Trial Drug(s) | 9 Clinical Trial Drugs | 9 | |||
1 | ABT-761 | Phase 3 | |||
2 | Avastin+/-Tarceva | Phase 3 | |||
3 | FPL-62064 | Phase 3 | |||
4 | Tenidap | Phase 3 | |||
5 | Darbufelone | Phase 2/3 | |||
6 | BAICALEIN | Phase 2 | |||
7 | BIM23A760 | Phase 2 | |||
8 | CMI-392 | Phase 2 | |||
9 | Tepoxalin | Phase 2 | |||
Discontinued Drug(s) | 22 Discontinued Drugs | 22 | |||
1 | Ibuproxam | Withdrawn from market | |||
2 | CJ-13610 | Discontinued in Phase 2 | |||
3 | DuP-654 | Discontinued in Phase 2 | |||
4 | E-3040 | Discontinued in Phase 2 | |||
5 | ETH615 | Discontinued in Phase 2 | |||
6 | MK-591 | Discontinued in Phase 2 | |||
7 | MK-886 | Discontinued in Phase 2 | |||
8 | MLN-977 | Discontinued in Phase 2 | |||
9 | OPC-21268 | Discontinued in Phase 2 | |||
10 | R-68151 | Discontinued in Phase 2 | |||
11 | TEBUFELONE | Discontinued in Phase 2 | |||
12 | Licofelone | Discontinued in Phase 1 | |||
13 | A-78773 | Terminated | |||
14 | A-79175 | Terminated | |||
15 | AA-861 | Terminated | |||
16 | BW A4C | Terminated | |||
17 | BW B70C | Terminated | |||
18 | BW755C | Terminated | |||
19 | Epocarbazolin-A | Terminated | |||
20 | PD-146176 | Terminated | |||
21 | WY-28342 | Terminated | |||
22 | ZM-230487 | Terminated | |||
Investigative Drug(s) | 1 Investigative Drug | 1 | |||
1 | 5,8-Dihydroxy-1,4-naphthoquinone | Investigative |
Target 2 ( LOX-5 messenger RNA (ALOX5 mRNA) )
Target Type | Discontinued Target | ||||
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Disease | 3 Target-related Diseases | 3 | |||
1 | Pain [ICD-11: MG30-MG3Z] | ||||
2 | Asthma [ICD-11: CA23] | ||||
3 | Arthritis [ICD-11: FA20] | ||||
Discontinued Drug(s) | 3 Discontinued Drugs | 3 | |||
1 | TEBUFELONE | Discontinued in Phase 2 | |||
2 | ZD-2138 | Discontinued in Phase 2 | |||
3 | BW A4C | Terminated |
Similar Protein(s) and Bioactivity Statistics
50% Identity
Protein ID | Protein Name | Protein Organism | |
PT00205 | 5-lipoxygenase | Bos taurus, Bovine | |
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PT01743 | Polyunsaturated fatty acid 5-lipoxygenase | Rattus norvegicus, Rat |