Human Gene ALOX5 (ENST00000374391.7) from GENCODE V44
Description: Homo sapiens arachidonate 5-lipoxygenase (ALOX5), transcript variant 5, mRNA. (from RefSeq NM_001320862) RefSeq Summary (NM_000698): This gene encodes a member of the lipoxygenase gene family and plays a dual role in the synthesis of leukotrienes from arachidonic acid. The encoded protein, which is expressed specifically in bone marrow-derived cells, catalyzes the conversion of arachidonic acid to 5(S)-hydroperoxy-6-trans-8,11,14-cis-eicosatetraenoic acid, and further to the allylic epoxide 5(S)-trans-7,9-trans-11,14-cis-eicosatetrenoic acid (leukotriene A4). Leukotrienes are important mediators of a number of inflammatory and allergic conditions. Mutations in the promoter region of this gene lead to a diminished response to antileukotriene drugs used in the treatment of asthma and may also be associated with atherosclerosis and several cancers. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]. Gencode Transcript: ENST00000374391.7 Gencode Gene: ENSG00000012779.12 Transcript (Including UTRs) Position: hg38 chr10:45,374,216-45,446,117 Size: 71,902 Total Exon Count: 14 Strand: + Coding Region Position: hg38 chr10:45,374,280-45,445,687 Size: 71,408 Coding Exon Count: 14
ID:LOX5_HUMAN DESCRIPTION: RecName: Full=Arachidonate 5-lipoxygenase; Short=5-LO; Short=5-lipoxygenase; EC=1.13.11.34; FUNCTION: Catalyzes the first step in leukotriene biosynthesis, and thereby plays a role in inflammatory processes. CATALYTIC ACTIVITY: Arachidonate + O(2) = leukotriene A(4) + H(2)O. COFACTOR: Binds 1 iron ion per subunit. COFACTOR: Binds 2 calcium ions per subunit (By similarity). PATHWAY: Lipid metabolism; leukotriene A4 biosynthesis. SUBUNIT: Interacts with ALOX5AP and LTC4S. INTERACTION: Q14019:COTL1; NbExp=4; IntAct=EBI-79934, EBI-79926; SUBCELLULAR LOCATION: Cytoplasm. Nucleus matrix. Nucleus membrane; Peripheral membrane protein. Note=Shuttles between cytoplasm and nucleus. Found exclusively in the nucleus, when phosphorylated on Ser-272. Calcium binding promotes translocation from the cytosol and the nuclear matrix to the nuclear envelope and membrane association. PTM: Serine phosphorylation by MAPKAPK2 is stimulated by arachidonic acid. Phosphorylation on Ser-523 by PKA has an inhibitory effect. Phosphorylation on Ser-272 prevents export from the nucleus. SIMILARITY: Belongs to the lipoxygenase family. SIMILARITY: Contains 1 lipoxygenase domain. SIMILARITY: Contains 1 PLAT domain. WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/ALOX5ID42985ch10q11.html";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P09917
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Gene Ontology (GO) Annotations with Structured Vocabulary
Molecular Function: GO:0004051 arachidonate 5-lipoxygenase activity GO:0005506 iron ion binding GO:0005515 protein binding GO:0016491 oxidoreductase activity GO:0016702 oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen GO:0046872 metal ion binding GO:0051213 dioxygenase activity
Biological Process: GO:0002540 leukotriene production involved in inflammatory response GO:0006691 leukotriene metabolic process GO:0006954 inflammatory response GO:0019221 cytokine-mediated signaling pathway GO:0019370 leukotriene biosynthetic process GO:0019372 lipoxygenase pathway GO:0035655 interleukin-18-mediated signaling pathway GO:0042759 long-chain fatty acid biosynthetic process GO:0043312 neutrophil degranulation GO:0055114 oxidation-reduction process
BioCarta from NCI Cancer Genome Anatomy Project h_eicosanoidPathway - Eicosanoid Metabolism
Reactome (by CSHL, EBI, and GO)
Protein P09917 (Reactome details) participates in the following event(s):
R-HSA-429016 ALOX5 is phosphorylated by MAPKAP2 R-HSA-9018858 ALOX5 oxidises 18(S)-HEPE to 5(S)-Hp-18(S)-HEPE R-HSA-9018859 ALOX5 oxidises 5(S)-Hp-18(S)-HEPE to 5S,6S-epoxy-18(S)-HEPE R-HSA-9018863 ALOX5 oxidises 18(R)-HEPE to 5(S)-Hp-18(R)-HEPE R-HSA-9018894 ALOX5 oxidises 5(S)-Hp-18(R)-HEPE to 5S,6S-epoxy-18(R)-HEPE R-HSA-9020251 ALOX5 oxidises 17(R)-HDHA to 7(S)-Hp-17(R)-HDHA R-HSA-9020255 ALOX5 dehydrogenates 7(S)-Hp-17(S)-HDHA to 7S(8)-epoxy-17S-HDHA R-HSA-9020256 ALOX5 dehydrogenates 7(S)-Hp-17R-HDHA to 7S(8)-epoxy-17R-HDHA R-HSA-9020259 ALOX5 oxidises 17(R)-HDHA to 4(S)-Hp-17(R)-HDHA R-HSA-9020264 ALOX5 oxidises 17(S)-HDHA to 4(S)-Hp-17(S)-HDHA R-HSA-9020277 ALOX5 dehydrogenates 4(S)-Hp-17(S)-HDHA to 4S(5)-epoxy-17(S)-HDHA R-HSA-9020278 ALOX5 dehydrogenates 4(S)-Hp-17(R)-HDHA to 4S(5)-epoxy-17(R)-HDHA R-HSA-9020282 ALOX5 oxidises 17(S)-HDHA to 7(S)-Hp-17(S)-HDHA R-HSA-9024997 ALOX5 oxidises 14(S)-Hp-DHA to 7(S),14(S)-diHp-DHA R-HSA-9025995 ALOX5 dehydrogenates 7,17-diHp-DPAn-3 to 7,8-epoxy,17-HDPAn-3 R-HSA-9025996 ALOX5 oxidises 17(S)-Hp-DPAn-3 to 7,17-diHp-DPAn-3 R-HSA-9025999 ALOX5 dehydrogenates 17(S)-Hp-DPAn-3 to 16(S),17(S)-epoxy-DPAn-3 R-HSA-9026005 ALOX5 oxidises 14(S)-Hp-DPAn-3 to MaR3n-3 DPA R-HSA-9026405 ALOX5 oxidises 13(R)-HDPAn-3 to RvT1-4 R-HSA-9027624 ALOX5 oxidises DHA to 7-HDHA R-HSA-9027628 ALOX5 oxidises EPA to 5-HEPE R-HSA-9027633 ALOX5 oxidises DPAn-3 to 7-HDPAn-3 R-HSA-6800434 Exocytosis of ficolin-rich granule lumen proteins R-HSA-6798748 Exocytosis of secretory granule lumen proteins R-HSA-265296 Arachidonic acid is oxidised to 5S-HpETE by ALOX5 R-HSA-266051 5S-HpETE is dehydrated to LTA4 by ALOX5 R-HSA-266050 LTA4 is converted to LTC4 by LTC4S R-HSA-2161907 15R-HETE is converted to 15epi-LXA4/B4 by ALOX5 R-HSA-2161917 15S-HpETE is oxidised to LXA4/B4 by ALOX5 R-HSA-2161768 EXA4 is converted to EXC4 by LTC4S R-HSA-2142691 Synthesis of Leukotrienes (LT) and Eoxins (EX) R-HSA-6785807 Interleukin-4 and 13 signaling R-HSA-9012546 Interleukin-18 signaling R-HSA-9018896 Biosynthesis of E-series 18(S)-resolvins R-HSA-9023661 Biosynthesis of E-series 18(R)-resolvins R-HSA-9020265 Biosynthesis of aspirin-triggered D-series resolvins R-HSA-9018676 Biosynthesis of D-series resolvins R-HSA-9018682 Biosynthesis of maresins R-HSA-9026286 Biosynthesis of DPAn-3-derived protectins and resolvins R-HSA-9026290 Biosynthesis of DPAn-3-derived maresins R-HSA-9026403 Biosynthesis of DPAn-3-derived 13-series resolvins R-HSA-9027604 Biosynthesis of electrophilic ω-3 PUFA oxo-derivatives R-HSA-6798695 Neutrophil degranulation R-HSA-2142753 Arachidonic acid metabolism R-HSA-449147 Signaling by Interleukins R-HSA-446652 Interleukin-1 family signaling R-HSA-9018679 Biosynthesis of EPA-derived SPMs R-HSA-9018677 Biosynthesis of DHA-derived SPMs R-HSA-9025094 Biosynthesis of DPAn-3 SPMs R-HSA-9018678 Biosynthesis of specialized proresolving mediators (SPMs) R-HSA-168249 Innate Immune System R-HSA-8978868 Fatty acid metabolism R-HSA-1280215 Cytokine Signaling in Immune system R-HSA-9018683 Biosynthesis of DPA-derived SPMs R-HSA-2142688 Synthesis of 5-eicosatetraenoic acids R-HSA-2142700 Synthesis of Lipoxins (LX) R-HSA-168256 Immune System R-HSA-556833 Metabolism of lipids R-HSA-1430728 Metabolism