LOX15_HUMAN
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 03-AUG-2022, entry version 207.
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,
CC ECO:0000255|PROSITE-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="http://atlasgeneticsoncology.org/Genes/ALOX15ID42986ch17p13.html";
CC -!- WEB RESOURCE: Name=SeattleSNPs;
CC URL="http://pga.gs.washington.edu/data/alox15/";
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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; 23.
DR DIP; DIP-60388N; -.
DR IntAct; P16050; 4.
DR STRING; 9606.ENSP00000458832; -.
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; P16050; -.
DR PeptideAtlas; P16050; -.
DR PRIDE; P16050; -.
DR ProteomicsDB; 53264; -. [P16050-1]
DR ProteomicsDB; 7049; -.
DR Antibodypedia; 2761; 360 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 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; MVPLGQH; -.
DR OrthoDB; 385042at2759; -.
DR PhylomeDB; P16050; -.
DR TreeFam; TF105320; -.
DR BioCyc; MetaCyc:HS08621-MON; -.
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; 8 hits in 1071 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 107 other tissues.
DR Genevisible; P16050; HS.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0031234; C:extrinsic component of cytoplasmic side of plasma membrane; 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:0016702; F:oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen; IBA:GO_Central.
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 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; PTHR11771; 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; SSF48484; SSF48484; 1.
DR SUPFAM; SSF49723; SSF49723; 1.
DR PROSITE; PS00711; LIPOXYGENASE_1; 1.
DR PROSITE; PS00081; LIPOXYGENASE_2; 1.
DR PROSITE; PS51393; LIPOXYGENASE_3; 1.
DR PROSITE; PS50095; PLAT; 1.
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 (9Z,12Z)-
FT 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 (9Z,12Z)-
FT 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 (9Z,12Z)-
FT 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
