ID LOX15_HUMAN Reviewed; 662 AA. AC P16050; A8K2P4; B7ZA11; Q8N6R7; Q99657; DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 3. DT 24-JAN-2024, entry version 215. DE RecName: Full=Polyunsaturated fatty acid lipoxygenase ALOX15 {ECO:0000305}; DE AltName: Full=12/15-lipoxygenase {ECO:0000250|UniProtKB:P39654}; DE AltName: Full=Arachidonate 12-lipoxygenase, leukocyte-type {ECO:0000250|UniProtKB:Q02759}; DE Short=12-LOX; DE EC=1.13.11.31 {ECO:0000269|PubMed:1944593}; DE AltName: Full=Arachidonate 15-lipoxygenase; DE Short=15-LOX; DE Short=15-LOX-1; DE EC=1.13.11.33 {ECO:0000269|PubMed:17052953, ECO:0000269|PubMed:1944593, ECO:0000269|PubMed:24282679, ECO:0000269|PubMed:8334154}; DE AltName: Full=Arachidonate omega-6 lipoxygenase {ECO:0000303|PubMed:3356688}; DE AltName: Full=Hepoxilin A3 synthase Alox15 {ECO:0000250|UniProtKB:Q02759}; DE EC=1.13.11.- {ECO:0000250|UniProtKB:Q02759}; DE AltName: Full=Linoleate 13S-lipoxygenase; DE EC=1.13.11.12 {ECO:0000269|PubMed:8334154}; GN Name=ALOX15 {ECO:0000312|HGNC:HGNC:433}; Synonyms=LOG15; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND SUBCELLULAR LOCATION. RX PubMed=3202857; DOI=10.1016/s0006-291x(88)80271-7; RA Sigal E., Craik C.S., Highland E., Grunberger D., Costello L.L., RA Dixon R.A.F., Nadel J.A.; RT "Molecular cloning and primary structure of human 15-lipoxygenase."; RL Biochem. Biophys. Res. Commun. 157:457-464(1988). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=9224951; DOI=10.1016/s0167-4781(97)00005-5; RA Kritzik M.R., Ziober A.F., Dicharry S., Conrad D.J., Sigal E.; RT "Characterization and sequence of an additional 15-lipoxygenase transcript RT and of the human gene."; RL Biochim. Biophys. Acta 1352:267-281(1997). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Tongue; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS HIS-90; LYS-103 AND RP GLN-205. RG SeattleSNPs variation discovery resource; RL Submitted (DEC-2003) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16625196; DOI=10.1038/nature04689; RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.; RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the RT human lineage."; RL Nature 440:1045-1049(2006). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT PRO-461. RC TISSUE=Brain, and Lung; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-46. RX PubMed=9700053; DOI=10.1023/a:1006813009006; RA Kelavkar U., Wang S., Montero A., Murtagh J., Shah K., Badr K.; RT "Human 15-lipoxygenase gene promoter: analysis and identification of DNA RT binding sites for IL-13-induced regulatory factors in monocytes."; RL Mol. Biol. Rep. 25:173-182(1998). RN [8] RP PROTEIN SEQUENCE OF 2-16. RX PubMed=3356688; DOI=10.1016/s0021-9258(18)60719-7; RA Sigal E., Grunberger D., Craik C.S., Caughey G.H., Nadel J.A.; RT "Arachidonate 15-lipoxygenase (omega-6 lipoxygenase) from human leukocytes. RT Purification and structural homology to other mammalian lipoxygenases."; RL J. Biol. Chem. 263:5328-5332(1988). RN [9] RP PROTEIN SEQUENCE OF 2-31; 38-45; 157-168 AND 626-631. RC TISSUE=Eosinophil, and Leukocyte; RX PubMed=1662607; DOI=10.1111/j.1432-1033.1991.tb16495.x; RA Izumi T., Raadmark O., Joernvall H., Samuelsson B.; RT "Purification of two forms of arachidonate 15-lipoxygenase from human RT leukocytes."; RL Eur. J. Biochem. 202:1231-1238(1991). RN [10] RP CATALYTIC ACTIVITY, FUNCTION, AND MUTAGENESIS OF MET-418. RX PubMed=1944593; DOI=10.1038/354149a0; RA Sloane D.L., Leung R., Craik C.S., Sigal E.; RT "A primary determinant for lipoxygenase positional specificity."; RL Nature 354:149-152(1991). RN [11] RP CATALYTIC ACTIVITY, FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, AND ACTIVITY RP REGULATION. RX PubMed=8334154; DOI=10.1016/0005-2760(93)90085-n; RA Kuehn H., Barnett J., Grunberger D., Baecker P., Chow J., Nguyen B., RA Bursztyn-Pettegrew H., Chan H., Sigal E.; RT "Overexpression, purification and characterization of human recombinant 15- RT lipoxygenase."; RL Biochim. Biophys. Acta 1169:80-89(1993). RN [12] RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=9414270; RA Brinckmann R., Schnurr K., Heydeck D., Rosenbach T., Kolde G., Kuehn H.; RT "Membrane translocation of 15-lipoxygenase in hematopoietic cells is RT calcium-dependent and activates the oxygenase activity of the enzyme."; RL Blood 91:64-74(1998). RN [13] RP SUBCELLULAR LOCATION. RX PubMed=11418015; DOI=10.1054/plef.2001.0263; RA Hsi L.C., Kamitani H., Cornicelli J.A., Eling T.E.; RT "Evaluation of the activity and localization of 15-lipoxygenase-1 after RT introduction into human colorectal carcinoma Caco-2 cells."; RL Prostaglandins Leukot. Essent. Fatty Acids 64:217-225(2001). RN [14] RP LIPID-BINDING, SUBCELLULAR LOCATION, CATALYTIC ACTIVITY, FUNCTION, AND RP ACTIVITY REGULATION. RX PubMed=17052953; DOI=10.1016/j.bbalip.2006.09.007; RA Andersson E., Schain F., Svedling M., Claesson H.E., Forsell P.K.; RT "Interaction of human 15-lipoxygenase-1 with phosphatidylinositol RT bisphosphates results in increased enzyme activity."; RL Biochim. Biophys. Acta 1761:1498-1505(2006). RN [15] RP INDUCTION BY UV. RX PubMed=18755188; DOI=10.1016/j.febslet.2008.08.017; RA Yoo H., Jeon B., Jeon M.S., Lee H., Kim T.Y.; RT "Reciprocal regulation of 12- and 15-lipoxygenases by UV-irradiation in RT human keratinocytes."; RL FEBS Lett. 582:3249-3253(2008). RN [16] RP SUBCELLULAR LOCATION. RX PubMed=19528634; DOI=10.1194/jlr.m900081-jlr200; RA Weibel G.L., Joshi M.R., Wei C., Bates S.R., Blair I.A., Rothblat G.H.; RT "15(S)-Lipoxygenase-1 associates with neutral lipid droplets in macrophage RT foam cells: evidence of lipid droplet metabolism."; RL J. Lipid Res. 50:2371-2376(2009). RN [17] RP FUNCTION IN IL13 SIGNALING, INTERACTION WITH PEBP1, SUBCELLULAR LOCATION, RP AND TISSUE SPECIFICITY. RX PubMed=21831839; DOI=10.1073/pnas.1018075108; RA Zhao J., O'Donnell V.B., Balzar S., St Croix C.M., Trudeau J.B., RA Wenzel S.E.; RT "15-Lipoxygenase 1 interacts with phosphatidylethanolamine-binding protein RT to regulate MAPK signaling in human airway epithelial cells."; RL Proc. Natl. Acad. Sci. U.S.A. 108:14246-14251(2011). RN [18] RP CATALYTIC ACTIVITY, AND FUNCTION. RX PubMed=23242647; DOI=10.1194/jlr.m033746; RA Jin J., Zheng Y., Boeglin W.E., Brash A.R.; RT "Biosynthesis, isolation, and NMR analysis of leukotriene A epoxides: RT substrate chirality as a determinant of the cis or trans epoxide RT configuration."; RL J. Lipid Res. 54:754-761(2013). RN [19] RP CATALYTIC ACTIVITY, FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, VARIANTS RP GLN-205; TRP-402; ARG-422; GLU-422; MET-560 AND SER-617, AND RP CHARACTERIZATION OF VARIANTS GLN-205; TRP-402; ARG-422; GLU-422; MET-560 RP AND SER-617. RX PubMed=24282679; DOI=10.1016/j.redox.2013.11.001; RA Horn T., Reddy Kakularam K., Anton M., Richter C., Reddanna P., Kuhn H.; RT "Functional characterization of genetic enzyme variations in human RT lipoxygenases."; RL Redox Biol. 1:566-577(2013). RN [20] RP CATALYTIC ACTIVITY, AND FUNCTION. RX PubMed=25293588; DOI=10.1194/jlr.m054072; RA Teder T., Boeglin W.E., Brash A.R.; RT "Lipoxygenase-catalyzed transformation of epoxy fatty acids to hydroxy- RT endoperoxides: a potential P450 and lipoxygenase interaction."; RL J. Lipid Res. 55:2587-2596(2014). RN [21] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=32404334; DOI=10.1194/jlr.ra120000777; RA Perry S.C., Kalyanaraman C., Tourdot B.E., Conrad W.S., Akinkugbe O., RA Freedman J.C., Holinstat M., Jacobson M.P., Holman T.R.; RT "15-Lipoxygenase-1 biosynthesis of 7S,14S-diHDHA implicates 15- RT lipoxygenase-2 in biosynthesis of resolvin D5."; RL J. Lipid Res. 61:1087-1103(2020). RN [22] RP VARIANT MET-560, CHARACTERIZATION OF VARIANT MET-560, AND INVOLVEMENT IN RP CORONARY ARTERY DISEASE. RX PubMed=17959182; DOI=10.1016/j.atherosclerosis.2007.09.003; RA Assimes T.L., Knowles J.W., Priest J.R., Basu A., Borchert A., Volcik K.A., RA Grove M.L., Tabor H.K., Southwick A., Tabibiazar R., Sidney S., RA Boerwinkle E., Go A.S., Iribarren C., Hlatky M.A., Fortmann S.P., RA Myers R.M., Kuhn H., Risch N., Quertermous T.; RT "A near null variant of 12/15-LOX encoded by a novel SNP in ALOX15 and the RT risk of coronary artery disease."; RL Atherosclerosis 198:136-144(2008). CC -!- FUNCTION: Non-heme iron-containing dioxygenase that catalyzes the CC stereo-specific peroxidation of free and esterified polyunsaturated CC fatty acids generating a spectrum of bioactive lipid mediators CC (PubMed:1944593, PubMed:8334154, PubMed:17052953, PubMed:24282679, CC PubMed:25293588, PubMed:32404334). It inserts peroxyl groups at C12 or CC C15 of arachidonate ((5Z,8Z,11Z,14Z)-eicosatetraenoate) producing both CC 12-hydroperoxyeicosatetraenoate/12-HPETE and 15- CC hydroperoxyeicosatetraenoate/15-HPETE (PubMed:1944593, PubMed:8334154, CC PubMed:17052953, PubMed:24282679). It may then act on 12-HPETE to CC produce hepoxilins, which may show pro-inflammatory properties (By CC similarity). Can also peroxidize linoleate ((9Z,12Z)-octadecadienoate) CC to 13-hydroperoxyoctadecadienoate/13-HPODE (PubMed:8334154). May CC participate in the sequential oxidations of DHA CC ((4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate) to generate specialized pro- CC resolving mediators (SPMs)like resolvin D5 ((7S,17S)-diHPDHA) and CC (7S,14S)-diHPDHA, that actively down-regulate the immune response and CC have anti-aggregation properties with platelets (PubMed:32404334). Can CC convert epoxy fatty acids to hydroperoxy-epoxides derivatives followed CC by an intramolecular nucleophilic substitution leading to the formation CC of monocyclic endoperoxides (PubMed:25293588). Plays an important role CC during the maintenance of self-tolerance by peroxidizing membrane-bound CC phosphatidylethanolamine which can then signal the sorting process for CC clearance of apoptotic cells during inflammation and prevent an CC autoimmune response. In addition to its role in the immune and CC inflammatory responses, this enzyme may play a role in epithelial wound CC healing in the cornea through production of lipoxin A4 (LXA(4)) and CC docosahexaenoic acid-derived neuroprotectin D1 (NPD1; 10R,17S-HDHA), CC both lipid autacoids exhibit anti-inflammatory and neuroprotective CC properties. Furthermore, it may regulate actin polymerization which is CC crucial for several biological processes such as the phagocytosis of CC apoptotic cells. It is also implicated in the generation of endogenous CC ligands for peroxisome proliferator activated receptor (PPAR-gamma), CC hence modulating macrophage development and function. It may also exert CC a negative effect on skeletal development by regulating bone mass CC through this pathway. As well as participates in ER stress and CC downstream inflammation in adipocytes, pancreatic islets, and liver (By CC similarity). Finally, it is also involved in the cellular response to CC IL13/interleukin-13 (PubMed:21831839). {ECO:0000250|UniProtKB:P39654, CC ECO:0000250|UniProtKB:Q02759, ECO:0000269|PubMed:17052953, CC ECO:0000269|PubMed:1944593, ECO:0000269|PubMed:21831839, CC ECO:0000269|PubMed:24282679, ECO:0000269|PubMed:25293588, CC ECO:0000269|PubMed:32404334, ECO:0000269|PubMed:8334154}. CC -!- CATALYTIC ACTIVITY: CC Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 = (12S)-hydroperoxy- CC (5Z,8Z,10E,14Z)-eicosatetraenoate; Xref=Rhea:RHEA:10428, CC ChEBI:CHEBI:15379, ChEBI:CHEBI:32395, ChEBI:CHEBI:57444; CC EC=1.13.11.31; Evidence={ECO:0000269|PubMed:1944593}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:10429; CC Evidence={ECO:0000305|PubMed:1944593}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 = (15S)-hydroperoxy- CC (5Z,8Z,11Z,13E)-eicosatetraenoate; Xref=Rhea:RHEA:16869, CC ChEBI:CHEBI:15379, ChEBI:CHEBI:32395, ChEBI:CHEBI:57446; CC EC=1.13.11.33; Evidence={ECO:0000269|PubMed:17052953, CC ECO:0000269|PubMed:1944593, ECO:0000269|PubMed:24282679, CC ECO:0000269|PubMed:8334154}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16870; CC Evidence={ECO:0000305|PubMed:8334154}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(9Z,12Z)-octadecadienoate + O2 = (13S)-hydroperoxy-(9Z,11E)- CC octadecadienoate; Xref=Rhea:RHEA:22780, ChEBI:CHEBI:15379, CC ChEBI:CHEBI:30245, ChEBI:CHEBI:57466; EC=1.13.11.12; CC Evidence={ECO:0000269|PubMed:8334154}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:22781; CC Evidence={ECO:0000305|PubMed:8334154}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + 2 O2 = (14R,15S)- CC dihydroperoxy-(5Z,8Z,10E,12E)-eicosatetraenoate; CC Xref=Rhea:RHEA:50928, ChEBI:CHEBI:15379, ChEBI:CHEBI:32395, CC ChEBI:CHEBI:133900; Evidence={ECO:0000269|PubMed:8334154}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50929; CC Evidence={ECO:0000305|PubMed:8334154}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + 2 O2 = (8S,15S)- CC dihydroperoxy-(5Z,9E,11Z,13E)-eicosatetraenoate; CC Xref=Rhea:RHEA:50924, ChEBI:CHEBI:15379, ChEBI:CHEBI:32395, CC ChEBI:CHEBI:133899; Evidence={ECO:0000269|PubMed:8334154}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50925; CC Evidence={ECO:0000305|PubMed:8334154}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(14S,15R)-epoxy-(5Z,8Z,11Z)-eicosatrienoate + O2 = (8S)- CC hydroperoxy-(14S,15R)-epoxy-(5Z,9E,11Z)-eicosatrienoate; CC Xref=Rhea:RHEA:50288, ChEBI:CHEBI:15379, ChEBI:CHEBI:131964, CC ChEBI:CHEBI:132068; Evidence={ECO:0000269|PubMed:25293588}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50289; CC Evidence={ECO:0000305|PubMed:25293588}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(14S,15R)-epoxy-(5Z,8Z,11Z)-eicosatrienoate + O2 = (12S)- CC hydroperoxy-(14S,15R)-epoxy-(5Z,8Z,10E)-eicosatrienoate; CC Xref=Rhea:RHEA:50284, ChEBI:CHEBI:15379, ChEBI:CHEBI:131964, CC ChEBI:CHEBI:132065; Evidence={ECO:0000269|PubMed:25293588}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50285; CC Evidence={ECO:0000305|PubMed:25293588}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(14R,15S)-epoxy-(5Z,8Z,11Z)-eicosatrienoate + O2 = (5S)- CC hydroperoxy-(14R,15S)-epoxy-(6E,8Z,11Z)-eicosatrienoate; CC Xref=Rhea:RHEA:50280, ChEBI:CHEBI:15379, ChEBI:CHEBI:131965, CC ChEBI:CHEBI:132067; Evidence={ECO:0000269|PubMed:25293588}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50281; CC Evidence={ECO:0000305|PubMed:25293588}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(14R,15S)-epoxy-(5Z,8Z,11Z)-eicosatrienoate + O2 = (12S)- CC hydroperoxy-(14R,15S)-epoxy-(5Z,8Z,10E)-eicosatrienoate; CC Xref=Rhea:RHEA:50276, ChEBI:CHEBI:15379, ChEBI:CHEBI:131965, CC ChEBI:CHEBI:132063; Evidence={ECO:0000269|PubMed:25293588}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50277; CC Evidence={ECO:0000305|PubMed:25293588}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(15R)-hydroperoxy-(5Z,8Z,11Z,13E)-eicosatetraenoate = 15-oxo- CC (5Z,8Z,11Z,13E)-eicosatetraenoate + H2O; Xref=Rhea:RHEA:50152, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:57410, ChEBI:CHEBI:82626; CC Evidence={ECO:0000269|PubMed:23242647}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50153; CC Evidence={ECO:0000305|PubMed:23242647}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(15S)-hydroperoxy-(5Z,8Z,11Z,13E)-eicosatetraenoate = CC (14S,15S)-epoxy-(5Z,8Z,10E,12E)-eicosatetraenoate + H2O; CC Xref=Rhea:RHEA:50140, ChEBI:CHEBI:15377, ChEBI:CHEBI:57446, CC ChEBI:CHEBI:132070; Evidence={ECO:0000269|PubMed:23242647}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50141; CC Evidence={ECO:0000305|PubMed:23242647}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(12S)-hydroperoxy-(5Z,8Z,10E,14Z)-eicosatetraenoate = (8S)- CC hydroxy-(11S,12S)-epoxy-(5Z,9E,14Z)-eicosatrienoate; CC Xref=Rhea:RHEA:50216, ChEBI:CHEBI:57444, ChEBI:CHEBI:132129; CC Evidence={ECO:0000250|UniProtKB:Q02759}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50217; CC Evidence={ECO:0000250|UniProtKB:Q02759}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate + O2 = (14S)- CC hydroperoxy-(4Z,7Z,10Z,12E,16Z,19Z)-docosahexaenoate; CC Xref=Rhea:RHEA:41332, ChEBI:CHEBI:15379, ChEBI:CHEBI:77016, CC ChEBI:CHEBI:78048; Evidence={ECO:0000269|PubMed:32404334}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41333; CC Evidence={ECO:0000305|PubMed:32404334}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate + O2 = (17S)- CC hydroperoxy-(4Z,7Z,10Z,13Z,15E,19Z)-docosahexaenoate; CC Xref=Rhea:RHEA:50840, ChEBI:CHEBI:15379, ChEBI:CHEBI:77016, CC ChEBI:CHEBI:133795; Evidence={ECO:0000269|PubMed:32404334}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50841; CC Evidence={ECO:0000305|PubMed:32404334}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(7S)-hydroperoxy-(4Z,8E,10Z,13Z,16Z,19Z)-docosahexaenoate + O2 CC = (7S,14S)-dihydroperoxy-(4Z,8E,10Z,12E,16Z,19Z)-docosahexaenoate; CC Xref=Rhea:RHEA:64724, ChEBI:CHEBI:15379, ChEBI:CHEBI:156049, CC ChEBI:CHEBI:156082; Evidence={ECO:0000269|PubMed:32404334}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64725; CC Evidence={ECO:0000305|PubMed:32404334}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(7S)-hydroperoxy-(4Z,8E,10Z,13Z,16Z,19Z)-docosahexaenoate + O2 CC = (7S,17S)-dihydroperoxy-(4Z,8E,10Z,13Z,15E,19Z)-docosahexaenoate; CC Xref=Rhea:RHEA:64728, ChEBI:CHEBI:15379, ChEBI:CHEBI:140349, CC ChEBI:CHEBI:156049; Evidence={ECO:0000269|PubMed:32404334}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64729; CC Evidence={ECO:0000305|PubMed:32404334}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate + O2 = (11S)- CC hydroperoxy-(4Z,7Z,9E,13Z,16Z,19Z)-docosahexaenoate; CC Xref=Rhea:RHEA:64732, ChEBI:CHEBI:15379, ChEBI:CHEBI:77016, CC ChEBI:CHEBI:156131; Evidence={ECO:0000269|PubMed:32404334}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64733; CC Evidence={ECO:0000305|PubMed:32404334}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(7Z,10Z,13Z,16Z,19Z)-docosapentaenoate + O2 = 14-hydroperoxy- CC (7Z,10Z,12E,16Z,19Z)-docosapentaenoate; Xref=Rhea:RHEA:50836, CC ChEBI:CHEBI:15379, ChEBI:CHEBI:77224, ChEBI:CHEBI:133798; CC Evidence={ECO:0000250|UniProtKB:P16469}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50837; CC Evidence={ECO:0000250|UniProtKB:P16469}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(4Z,7Z,10Z,13Z,16Z)-docosapentaenoate + O2 = 14-hydroperoxy- CC (4Z,7Z,10Z,12E,16Z)-docosapentaenoate; Xref=Rhea:RHEA:50824, CC ChEBI:CHEBI:15379, ChEBI:CHEBI:77226, ChEBI:CHEBI:133799; CC Evidence={ECO:0000250|UniProtKB:P16469}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50825; CC Evidence={ECO:0000250|UniProtKB:P16469}; CC -!- CATALYTIC ACTIVITY: CC Reaction=N-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-taurine + O2 = N-(12S)- CC hydroperoxy-(5Z,8Z,10E,14Z)-eicosatetraenoyl-taurine; CC Xref=Rhea:RHEA:50160, ChEBI:CHEBI:15379, ChEBI:CHEBI:132060, CC ChEBI:CHEBI:132061; Evidence={ECO:0000250|UniProtKB:P16469}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50161; CC Evidence={ECO:0000250|UniProtKB:P16469}; CC -!- CATALYTIC ACTIVITY: CC Reaction=N-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-gamma-aminobutanoate + O2 = CC N-(12S)-hydroperoxy-(5Z,8Z,10E,14Z)-eicosatetraenoyl-gamma- CC aminobutanoate; Xref=Rhea:RHEA:50176, ChEBI:CHEBI:15379, CC ChEBI:CHEBI:132072, ChEBI:CHEBI:132075; CC Evidence={ECO:0000250|UniProtKB:P16469}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50177; CC Evidence={ECO:0000250|UniProtKB:P16469}; CC -!- CATALYTIC ACTIVITY: CC Reaction=N-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-glycine + O2 = N-(12S)- CC hydroperoxy-(5Z,8Z,10E,14Z)-eicosatetraenoyl-glycine; CC Xref=Rhea:RHEA:50168, ChEBI:CHEBI:15379, ChEBI:CHEBI:59002, CC ChEBI:CHEBI:132073; Evidence={ECO:0000250|UniProtKB:P16469}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50169; CC Evidence={ECO:0000250|UniProtKB:P16469}; CC -!- CATALYTIC ACTIVITY: CC Reaction=N-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-alanine + O2 = N-(12S)- CC hydroperoxy-(5Z,8Z,10E,14Z)-eicosatetraenoyl-alanine; CC Xref=Rhea:RHEA:50172, ChEBI:CHEBI:15379, ChEBI:CHEBI:132071, CC ChEBI:CHEBI:132074; Evidence={ECO:0000250|UniProtKB:P16469}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50173; CC Evidence={ECO:0000250|UniProtKB:P16469}; CC -!- CATALYTIC ACTIVITY: CC Reaction=N-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-taurine + O2 = N-(15S)- CC hydroperoxy-(5Z,8Z,11Z,13E)-eicosatetraenoyl-taurine; CC Xref=Rhea:RHEA:50156, ChEBI:CHEBI:15379, ChEBI:CHEBI:132060, CC ChEBI:CHEBI:132062; Evidence={ECO:0000250|UniProtKB:P12530}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50157; CC Evidence={ECO:0000250|UniProtKB:P12530}; CC -!- CATALYTIC ACTIVITY: CC Reaction=N-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-gamma-aminobutanoate + O2 = CC N-(15S)-hydroperoxy-(5Z,8Z,11Z,13E)-eicosatetraenoyl-gamma- CC aminobutanoate; Xref=Rhea:RHEA:50180, ChEBI:CHEBI:15379, CC ChEBI:CHEBI:132072, ChEBI:CHEBI:132078; CC Evidence={ECO:0000250|UniProtKB:P12530}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50181; CC Evidence={ECO:0000250|UniProtKB:P12530}; CC -!- CATALYTIC ACTIVITY: CC Reaction=N-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-glycine + O2 = N-(15S)- CC hydroperoxy-(5Z,8Z,11Z,13E)-eicosatetraenoyl-glycine; CC Xref=Rhea:RHEA:50188, ChEBI:CHEBI:15379, ChEBI:CHEBI:59002, CC ChEBI:CHEBI:132076; Evidence={ECO:0000250|UniProtKB:P12530}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50189; CC Evidence={ECO:0000250|UniProtKB:P12530}; CC -!- CATALYTIC ACTIVITY: CC Reaction=N-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-alanine + O2 = N-(15S)- CC hydroperoxy-(5Z,8Z,11Z,13E)-eicosatetraenoyl-alanine; CC Xref=Rhea:RHEA:50184, ChEBI:CHEBI:15379, ChEBI:CHEBI:132071, CC ChEBI:CHEBI:132077; Evidence={ECO:0000250|UniProtKB:P12530}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50185; CC Evidence={ECO:0000250|UniProtKB:P12530}; CC -!- COFACTOR: CC Name=Fe cation; Xref=ChEBI:CHEBI:24875; CC Evidence={ECO:0000250|UniProtKB:P16469, ECO:0000255|PROSITE- CC ProRule:PRU00726}; CC Note=Binds 1 Fe cation per subunit. {ECO:0000250|UniProtKB:P16469, CC ECO:0000255|PROSITE-ProRule:PRU00726}; CC -!- ACTIVITY REGULATION: Activity is increased by binding CC phosphatidylinositol phosphates, especially phosphatidylinositol 3,4- CC bisphosphate and phosphatidylinositol 4,5-bisphosphate CC (PubMed:17052953). Inactivated at 37 degrees Celsius by (13S)- CC hydroperoxy-(9Z,11E)-octadecadienoate (PubMed:8334154). CC {ECO:0000269|PubMed:17052953, ECO:0000269|PubMed:8334154}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=3 uM for (9Z,12Z)-octadecadienoate {ECO:0000269|PubMed:8334154}; CC KM=12 uM for (5Z,8Z,11Z,14Z)-eicosatetraenoate CC {ECO:0000269|PubMed:8334154}; CC KM=3.8 uM for (9Z,12Z)-octadecadienoate CC {ECO:0000269|PubMed:24282679}; CC Vmax=10.6 umol/min/mg enzyme toward (9Z,12Z)-octadecadienoate CC {ECO:0000269|PubMed:8334154}; CC Vmax=5.6 umol/min/mg enzyme toward (5Z,8Z,11Z,14Z)-eicosatetraenoate CC {ECO:0000269|PubMed:8334154}; CC Note=kcat is 14.4 sec(-1) with (9Z,12Z)-octadecadienoate as CC substrate. {ECO:0000269|PubMed:24282679}; CC pH dependence: CC Optimum pH is 7 with (9Z,12Z)-octadecadienoate as substrate. CC {ECO:0000269|PubMed:8334154}; CC -!- PATHWAY: Lipid metabolism; hydroperoxy eicosatetraenoic acid CC biosynthesis. {ECO:0000269|PubMed:1944593}. CC -!- SUBUNIT: Interacts with PEBP1; in response to IL13/interleukin-13, CC prevents the interaction of PEBP1 with RAF1 to activate the ERK CC signaling cascade. {ECO:0000269|PubMed:21831839}. CC -!- INTERACTION: CC P16050; P30086: PEBP1; NbExp=3; IntAct=EBI-14035397, EBI-716384; CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:17052953, CC ECO:0000269|PubMed:21831839}. Cell membrane CC {ECO:0000269|PubMed:21831839}; Peripheral membrane protein CC {ECO:0000269|PubMed:17052953}. Lipid droplet CC {ECO:0000269|PubMed:19528634}. Note=Predominantly cytosolic; becomes CC enriched at membranes upon calcium binding (By similarity). CC Translocates from the cytosol to the plasma membrane when stimulated by CC IL13/interleukin-13 and in macrophages binding apoptotic cells (By CC similarity). {ECO:0000250|UniProtKB:P39654}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=P16050-1; Sequence=Displayed; CC Name=2; CC IsoId=P16050-2; Sequence=VSP_056681; CC -!- TISSUE SPECIFICITY: Detected in monocytes and eosinophils (at protein CC level). Expressed in airway epithelial cells. CC {ECO:0000269|PubMed:21831839, ECO:0000269|PubMed:9414270}. CC -!- INDUCTION: Up-regulated by UV-irradiation. CC {ECO:0000269|PubMed:18755188}. CC -!- DOMAIN: The PLAT domain can bind calcium ions; this promotes CC association with membranes. {ECO:0000250}. CC -!- DISEASE: Note=Disease susceptibility may be associated with variants CC affecting the gene represented in this entry. Met at position 560 may CC confer interindividual susceptibility to coronary artery disease (CAD) CC (PubMed:17959182). {ECO:0000269|PubMed:17959182}. CC -!- SIMILARITY: Belongs to the lipoxygenase family. {ECO:0000305}. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/42986/ALOX15"; CC -!- WEB RESOURCE: Name=SeattleSNPs; CC URL="http://pga.gs.washington.edu/data/alox15/"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; M23892; AAA36182.1; -; mRNA. DR EMBL; U88317; AAB49305.1; -; Genomic_DNA. DR EMBL; AK290309; BAF82998.1; -; mRNA. DR EMBL; AK316126; BAH14497.1; -; mRNA. DR EMBL; AY505111; AAR84235.1; -; Genomic_DNA. DR EMBL; AC118754; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC029032; AAH29032.1; -; mRNA. DR EMBL; U63384; AAC52118.1; -; Genomic_DNA. DR CCDS; CCDS11049.1; -. [P16050-1] DR PIR; A31349; A31349. DR RefSeq; NP_001131.3; NM_001140.3. [P16050-1] DR AlphaFoldDB; P16050; -. DR SMR; P16050; -. DR BioGRID; 106747; 24. DR DIP; DIP-60388N; -. DR IntAct; P16050; 4. DR STRING; 9606.ENSP00000293761; -. DR BindingDB; P16050; -. DR ChEMBL; CHEMBL2903; -. DR DrugBank; DB08492; (2E)-3-(2-OCT-1-YN-1-YLPHENYL)ACRYLIC ACID. DR DrugBank; DB09061; Cannabidiol. DR DrugBank; DB14009; Medical Cannabis. DR DrugBank; DB14011; Nabiximols. DR DrugBank; DB02709; Resveratrol. DR DrugCentral; P16050; -. DR GuidetoPHARMACOLOGY; 1388; -. DR SwissLipids; SLP:000000667; -. DR iPTMnet; P16050; -. DR MetOSite; P16050; -. DR PhosphoSitePlus; P16050; -. DR BioMuta; ALOX15; -. DR DMDM; 126396; -. DR jPOST; P16050; -. DR MassIVE; P16050; -. DR PaxDb; 9606-ENSP00000458832; -. DR PeptideAtlas; P16050; -. DR ProteomicsDB; 53264; -. [P16050-1] DR ProteomicsDB; 7049; -. DR Antibodypedia; 2761; 413 antibodies from 33 providers. DR DNASU; 246; -. DR Ensembl; ENST00000293761.8; ENSP00000293761.3; ENSG00000161905.13. [P16050-1] DR Ensembl; ENST00000570836.6; ENSP00000458832.1; ENSG00000161905.13. [P16050-1] DR Ensembl; ENST00000574640.1; ENSP00000460483.1; ENSG00000161905.13. [P16050-2] DR GeneID; 246; -. DR KEGG; hsa:246; -. DR MANE-Select; ENST00000293761.8; ENSP00000293761.3; NM_001140.5; NP_001131.3. DR UCSC; uc002fyh.4; human. [P16050-1] DR AGR; HGNC:433; -. DR CTD; 246; -. DR DisGeNET; 246; -. DR GeneCards; ALOX15; -. DR HGNC; HGNC:433; ALOX15. DR HPA; ENSG00000161905; Tissue enhanced (adipose tissue, fallopian tube). DR MIM; 152392; gene. DR neXtProt; NX_P16050; -. DR OpenTargets; ENSG00000161905; -. DR PharmGKB; PA48; -. DR VEuPathDB; HostDB:ENSG00000161905; -. DR eggNOG; ENOG502QQSP; Eukaryota. DR GeneTree; ENSGT00940000162807; -. DR HOGENOM; CLU_004282_3_3_1; -. DR InParanoid; P16050; -. DR OMA; SFCPPED; -. DR OrthoDB; 999249at2759; -. DR PhylomeDB; P16050; -. DR TreeFam; TF105320; -. DR BioCyc; MetaCyc:HS08621-MONOMER; -. DR BRENDA; 1.13.11.31; 2681. DR BRENDA; 1.13.11.33; 2681. DR PathwayCommons; P16050; -. DR Reactome; R-HSA-2142691; Synthesis of Leukotrienes (LT) and Eoxins (EX). DR Reactome; R-HSA-2142712; Synthesis of 12-eicosatetraenoic acid derivatives. DR Reactome; R-HSA-2142770; Synthesis of 15-eicosatetraenoic acid derivatives. DR Reactome; R-HSA-6785807; Interleukin-4 and Interleukin-13 signaling. DR Reactome; R-HSA-9018677; Biosynthesis of DHA-derived SPMs. DR Reactome; R-HSA-9018681; Biosynthesis of protectins. DR Reactome; R-HSA-9018896; Biosynthesis of E-series 18(S)-resolvins. DR Reactome; R-HSA-9023661; Biosynthesis of E-series 18(R)-resolvins. DR Reactome; R-HSA-9025106; Biosynthesis of DPAn-6 SPMs. DR Reactome; R-HSA-9026286; Biosynthesis of DPAn-3-derived protectins and resolvins. DR SABIO-RK; P16050; -. DR SignaLink; P16050; -. DR SIGNOR; P16050; -. DR UniPathway; UPA00881; -. DR BioGRID-ORCS; 246; 9 hits in 1151 CRISPR screens. DR GeneWiki; ALOX15; -. DR GenomeRNAi; 246; -. DR Pharos; P16050; Tchem. DR PRO; PR:P16050; -. DR Proteomes; UP000005640; Chromosome 17. DR RNAct; P16050; Protein. DR Bgee; ENSG00000161905; Expressed in olfactory segment of nasal mucosa and 109 other cell types or tissues. DR GO; GO:0009898; C:cytoplasmic side of plasma membrane; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:UniProtKB. DR GO; GO:0005811; C:lipid droplet; IDA:UniProtKB. DR GO; GO:0016020; C:membrane; IDA:UniProtKB. DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB. DR GO; GO:0004052; F:arachidonate 12(S)-lipoxygenase activity; IDA:UniProtKB. DR GO; GO:0050473; F:arachidonate 15-lipoxygenase activity; IDA:UniProtKB. DR GO; GO:0005506; F:iron ion binding; ISS:UniProtKB. DR GO; GO:0016165; F:linoleate 13S-lipoxygenase activity; IDA:UniProtKB. DR GO; GO:0005546; F:phosphatidylinositol-4,5-bisphosphate binding; IDA:UniProtKB. DR GO; GO:0043277; P:apoptotic cell clearance; ISS:UniProtKB. DR GO; GO:0019369; P:arachidonic acid metabolic process; IDA:UniProtKB. DR GO; GO:0030282; P:bone mineralization; ISS:UniProtKB. DR GO; GO:0071277; P:cellular response to calcium ion; IDA:UniProtKB. DR GO; GO:0035963; P:cellular response to interleukin-13; IMP:UniProtKB. DR GO; GO:0019395; P:fatty acid oxidation; ISS:UniProtKB. DR GO; GO:0051122; P:hepoxilin biosynthetic process; ISS:UniProtKB. DR GO; GO:0006954; P:inflammatory response; TAS:ProtInc. DR GO; GO:0043651; P:linoleic acid metabolic process; IDA:UniProtKB. DR GO; GO:0006629; P:lipid metabolic process; IDA:UniProtKB. DR GO; GO:0034440; P:lipid oxidation; IBA:GO_Central. DR GO; GO:2001303; P:lipoxin A4 biosynthetic process; ISS:UniProtKB. DR GO; GO:0019372; P:lipoxygenase pathway; IDA:UniProtKB. DR GO; GO:0042759; P:long-chain fatty acid biosynthetic process; TAS:Reactome. DR GO; GO:0002820; P:negative regulation of adaptive immune response; ISS:UniProtKB. DR GO; GO:0001503; P:ossification; ISS:UniProtKB. DR GO; GO:0006646; P:phosphatidylethanolamine biosynthetic process; ISS:UniProtKB. DR GO; GO:0030838; P:positive regulation of actin filament polymerization; ISS:UniProtKB. DR GO; GO:0010811; P:positive regulation of cell-substrate adhesion; IDA:UniProtKB. DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IMP:UniProtKB. DR GO; GO:1901074; P:regulation of engulfment of apoptotic cell; ISS:UniProtKB. DR GO; GO:0050727; P:regulation of inflammatory response; IDA:UniProtKB. DR GO; GO:0035358; P:regulation of peroxisome proliferator activated receptor signaling pathway; ISS:UniProtKB. DR GO; GO:0034976; P:response to endoplasmic reticulum stress; ISS:UniProtKB. DR GO; GO:0042060; P:wound healing; ISS:UniProtKB. DR CDD; cd01753; PLAT_LOX; 1. DR DisProt; DP02162; -. DR Gene3D; 3.10.450.60; -; 1. DR Gene3D; 2.60.60.20; PLAT/LH2 domain; 1. DR InterPro; IPR000907; LipOase. DR InterPro; IPR013819; LipOase_C. DR InterPro; IPR036226; LipOase_C_sf. DR InterPro; IPR020834; LipOase_CS. DR InterPro; IPR020833; LipOase_Fe_BS. DR InterPro; IPR001885; LipOase_mml. DR InterPro; IPR001024; PLAT/LH2_dom. DR InterPro; IPR036392; PLAT/LH2_dom_sf. DR InterPro; IPR042062; PLAT_LOX_verte. DR PANTHER; PTHR11771; LIPOXYGENASE; 1. DR PANTHER; PTHR11771:SF33; POLYUNSATURATED FATTY ACID LIPOXYGENASE ALOX15; 1. DR Pfam; PF00305; Lipoxygenase; 1. DR Pfam; PF01477; PLAT; 1. DR PRINTS; PR00087; LIPOXYGENASE. DR PRINTS; PR00467; MAMLPOXGNASE. DR SMART; SM00308; LH2; 1. DR SUPFAM; SSF49723; Lipase/lipooxygenase domain (PLAT/LH2 domain); 1. DR SUPFAM; SSF48484; Lipoxigenase; 1. DR PROSITE; PS00711; LIPOXYGENASE_1; 1. DR PROSITE; PS00081; LIPOXYGENASE_2; 1. DR PROSITE; PS51393; LIPOXYGENASE_3; 1. DR PROSITE; PS50095; PLAT; 1. DR Genevisible; P16050; HS. PE 1: Evidence at protein level; KW Alternative splicing; Calcium; Cell membrane; Cytoplasm; Dioxygenase; KW Direct protein sequencing; Fatty acid metabolism; Iron; Lipid droplet; KW Lipid metabolism; Lipid-binding; Membrane; Metal-binding; Oxidoreductase; KW Reference proteome. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000269|PubMed:1662607, FT ECO:0000269|PubMed:3356688" FT CHAIN 2..662 FT /note="Polyunsaturated fatty acid lipoxygenase ALOX15" FT /id="PRO_0000220697" FT DOMAIN 2..114 FT /note="PLAT" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00152" FT DOMAIN 115..662 FT /note="Lipoxygenase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00726" FT BINDING 360 FT /ligand="Fe cation" FT /ligand_id="ChEBI:CHEBI:24875" FT /ligand_note="catalytic" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00726" FT BINDING 365 FT /ligand="Fe cation" FT /ligand_id="ChEBI:CHEBI:24875" FT /ligand_note="catalytic" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00726" FT BINDING 540 FT /ligand="Fe cation" FT /ligand_id="ChEBI:CHEBI:24875" FT /ligand_note="catalytic" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00726" FT BINDING 544 FT /ligand="Fe cation" FT /ligand_id="ChEBI:CHEBI:24875" FT /ligand_note="catalytic" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00726" FT BINDING 662 FT /ligand="Fe cation" FT /ligand_id="ChEBI:CHEBI:24875" FT /ligand_note="catalytic" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00726" FT VAR_SEQ 46..84 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_056681" FT VARIANT 90 FT /note="D -> H (in dbSNP:rs11568142)" FT /evidence="ECO:0000269|Ref.4" FT /id="VAR_018746" FT VARIANT 102 FT /note="G -> V (in dbSNP:rs41439950)" FT /id="VAR_035036" FT VARIANT 103 FT /note="N -> K (in dbSNP:rs11568099)" FT /evidence="ECO:0000269|Ref.4" FT /id="VAR_018747" FT VARIANT 205 FT /note="R -> Q (does not affect arachidonate 15-lipoxygenase FT activity. Does not affect protein affinity for FT (9Z,12Z)-octadecadienoate.; dbSNP:rs11568101)" FT /evidence="ECO:0000269|PubMed:24282679, ECO:0000269|Ref.4" FT /id="VAR_018748" FT VARIANT 239 FT /note="V -> M (in dbSNP:rs3892408)" FT /id="VAR_035037" FT VARIANT 402 FT /note="R -> W (36% of arachidonate 15-lipoxygenase FT activity)" FT /evidence="ECO:0000269|PubMed:24282679" FT /id="VAR_083449" FT VARIANT 422 FT /note="G -> E (loss of arachidonate 15-lipoxygenase FT activity)" FT /evidence="ECO:0000269|PubMed:24282679" FT /id="VAR_083450" FT VARIANT 422 FT /note="G -> R (46% of arachidonate 15-lipoxygenase FT activity. Does not affect protein affinity for FT (9Z,12Z)-octadecadienoate)" FT /evidence="ECO:0000269|PubMed:24282679" FT /id="VAR_083451" FT VARIANT 461 FT /note="A -> P (in dbSNP:rs17852628)" FT /evidence="ECO:0000269|PubMed:15489334" FT /id="VAR_035038" FT VARIANT 560 FT /note="T -> M (loss of catalytic activity; Loss of FT arachidonate 15-lipoxygenase activity.; dbSNP:rs34210653)" FT /evidence="ECO:0000269|PubMed:17959182, FT ECO:0000269|PubMed:24282679" FT /id="VAR_035039" FT VARIANT 617 FT /note="P -> S (does not affect arachidonate 15-lipoxygenase FT activity. Does not affect protein affinity for FT (9Z,12Z)-octadecadienoate)" FT /evidence="ECO:0000269|PubMed:24282679" FT /id="VAR_083452" FT MUTAGEN 418 FT /note="M->V: Catalyzes 15- and 12-lipoxygenation." FT /evidence="ECO:0000269|PubMed:1944593" FT CONFLICT 46 FT /note="E -> V (in Ref. 7; AAC52118)" FT /evidence="ECO:0000305" SQ SEQUENCE 662 AA; 74804 MW; 9ACF7FE7863A045C CRC64; MGLYRIRVST GASLYAGSNN QVQLWLVGQH GEAALGKRLW PARGKETELK VEVPEYLGPL LFVKLRKRHL LKDDAWFCNW ISVQGPGAGD EVRFPCYRWV EGNGVLSLPE GTGRTVGEDP QGLFQKHREE ELEERRKLYR WGNWKDGLIL NMAGAKLYDL PVDERFLEDK RVDFEVSLAK GLADLAIKDS LNVLTCWKDL DDFNRIFWCG QSKLAERVRD SWKEDALFGY QFLNGANPVV LRRSAHLPAR LVFPPGMEEL QAQLEKELEG GTLFEADFSL LDGIKANVIL CSQQHLAAPL VMLKLQPDGK LLPMVIQLQL PRTGSPPPPL FLPTDPPMAW LLAKCWVRSS DFQLHELQSH LLRGHLMAEV IVVATMRCLP SIHPIFKLII PHLRYTLEIN VRARTGLVSD MGIFDQIMST GGGGHVQLLK QAGAFLTYSS FCPPDDLADR GLLGVKSSFY AQDALRLWEI IYRYVEGIVS LHYKTDVAVK DDPELQTWCR EITEIGLQGA QDRGFPVSLQ ARDQVCHFVT MCIFTCTGQH ASVHLGQLDW YSWVPNAPCT MRLPPPTTKD ATLETVMATL PNFHQASLQM SITWQLGRRQ PVMVAVGQHE EEYFSGPEPK AVLKKFREEL AALDKEIEIR NAKLDMPYEY LRPSVVENSV AI //