ID   LOX15_RAT               Reviewed;         663 AA.
AC   Q02759; F1MA51;
DT   01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
DT   16-OCT-2013, sequence version 3.
DT   24-JAN-2024, entry version 174.
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:0000303|PubMed:8117750};
DE            Short=12-LOX;
DE            EC=1.13.11.31 {ECO:0000269|PubMed:8117750, ECO:0000269|PubMed:8444196};
DE   AltName: Full=Arachidonate 15-lipoxygenase;
DE            Short=15-LOX;
DE            EC=1.13.11.33 {ECO:0000269|PubMed:8117750, ECO:0000269|PubMed:8444196};
DE   AltName: Full=Arachidonate omega-6 lipoxygenase {ECO:0000250|UniProtKB:P16050};
DE   AltName: Full=Hepoxilin A3 synthase Alox15 {ECO:0000303|PubMed:15123652};
DE            EC=1.13.11.- {ECO:0000269|PubMed:15057822};
DE   AltName: Full=Linoleate 13S-lipoxygenase {ECO:0000250|UniProtKB:P16050};
DE            EC=1.13.11.12 {ECO:0000250|UniProtKB:P16050};
GN   Name=Alox15 {ECO:0000312|RGD:70493}; Synonyms=Alox12l;
OS   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, AND TISSUE
RP   SPECIFICITY.
RC   STRAIN=Sprague-Dawley; TISSUE=Brain;
RX   PubMed=8444196; DOI=10.1111/j.1432-1033.1993.tb17699.x;
RA   Watanabe T., Medina J.F., Haeggstroem J.Z., Raadmark O.P., Samuelsson B.;
RT   "Molecular cloning of a 12-lipoxygenase cDNA from rat brain.";
RL   Eur. J. Biochem. 212:605-612(1993).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, AND SUBCELLULAR
RP   LOCATION.
RC   TISSUE=Pineal gland;
RX   PubMed=8117750; DOI=10.1016/0005-2760(94)90272-0;
RA   Hada T., Hagiya H., Suzuki H., Arakawa T., Nakamura M., Matsuda S.,
RA   Yoshimoto T., Yamamoto S., Azekawa T., Morita Y., Ishimura K., Kim H.Y.;
RT   "Arachidonate 12-lipoxygenase of rat pineal glands: catalytic properties
RT   and primary structure deduced from its cDNA.";
RL   Biochim. Biophys. Acta 1211:221-228(1994).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION IN HEPOXILIN A3 SYNTHESIS, CATALYTIC
RP   ACTIVITY, SUBCELLULAR LOCATION, AND MUTAGENESIS OF LEU-353; LYS-417 AND
RP   ALA-418.
RX   PubMed=15123652; DOI=10.1074/jbc.m307576200;
RA   Nigam S., Patabhiraman S., Ciccoli R., Ishdorj G., Schwarz K., Petrucev B.,
RA   Kuehn H., Haeggstroem J.Z.;
RT   "The rat leukocyte-type 12-lipoxygenase exhibits an intrinsic hepoxilin A3
RT   synthase activity.";
RL   J. Biol. Chem. 279:29023-29030(2004).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Brown Norway;
RX   PubMed=15057822; DOI=10.1038/nature02426;
RA   Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA   Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA   Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA   Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA   Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA   Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA   Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA   Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA   Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA   Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA   Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA   Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA   Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA   Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA   Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA   Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA   Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA   Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA   Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA   Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA   Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA   Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA   Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA   Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA   Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA   Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA   Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA   Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA   Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA   Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA   Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA   Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA   Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA   Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA   Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA   Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA   Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA   Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA   Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA   Mockrin S., Collins F.S.;
RT   "Genome sequence of the Brown Norway rat yields insights into mammalian
RT   evolution.";
RL   Nature 428:493-521(2004).
RN   [5]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-149, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=22673903; DOI=10.1038/ncomms1871;
RA   Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA   Olsen J.V.;
RT   "Quantitative maps of protein phosphorylation sites across 14 different rat
RT   organs and tissues.";
RL   Nat. Commun. 3:876-876(2012).
RN   [6]
RP   FUNCTION.
RX   PubMed=23382512; DOI=10.1096/fj.12-217414;
RA   Gregus A.M., Dumlao D.S., Wei S.C., Norris P.C., Catella L.C.,
RA   Meyerstein F.G., Buczynski M.W., Steinauer J.J., Fitzsimmons B.L.,
RA   Yaksh T.L., Dennis E.A.;
RT   "Systematic analysis of rat 12/15-lipoxygenase enzymes reveals critical
RT   role for spinal eLOX3 hepoxilin synthase activity in inflammatory
RT   hyperalgesia.";
RL   FASEB J. 27:1939-1949(2013).
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:8444196, PubMed:8117750, PubMed:15123652, PubMed:23382512). It
CC       inserts peroxyl groups at C12 or C15 of arachidonate ((5Z,8Z,11Z,14Z)-
CC       eicosatetraenoate) producing both 12-hydroperoxyeicosatetraenoate/12-
CC       HPETE and 15-hydroperoxyeicosatetraenoate/15-HPETE (PubMed:8444196,
CC       PubMed:8117750, PubMed:15123652, PubMed:23382512). It may then act on
CC       12-HPETE to produce hepoxilins, which may show pro-inflammatory
CC       properties (PubMed:15123652, PubMed:23382512). Can also peroxidize
CC       linoleate ((9Z,12Z)-octadecadienoate) to 13-
CC       hydroperoxyoctadecadienoate. May participate in the sequential
CC       oxidations of DHA ((4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate) to
CC       generate specialized pro-resolving mediators (SPMs)like resolvin D5
CC       ((7S,17S)-diHPDHA) and (7S,14S)-diHPDHA, that actively down-regulate
CC       the immune response and have anti-aggregation properties with
CC       platelets. Can convert epoxy fatty acids to hydroperoxy-epoxides
CC       derivatives followed by an intramolecular nucleophilic substitution
CC       leading to the formation of monocyclic endoperoxides (By similarity).
CC       Plays an important role during the maintenance of self-tolerance by
CC       peroxidizing membrane-bound phosphatidylethanolamine which can then
CC       signal the sorting process for clearance of apoptotic cells during
CC       inflammation and prevent an autoimmune response. In addition to its
CC       role in the immune and inflammatory responses, this enzyme may play a
CC       role in epithelial wound healing in the cornea through production of
CC       lipoxin A4 (LXA(4)) and docosahexaenoic acid-derived neuroprotectin D1
CC       (NPD1; 10R,17S-HDHA), both lipid autacoids exhibit anti-inflammatory
CC       and neuroprotective properties. Furthermore, it may regulate actin
CC       polymerization which is crucial for several biological processes such
CC       as the phagocytosis of apoptotic cells. It is also implicated in the
CC       generation of endogenous ligands for peroxisome proliferator activated
CC       receptor (PPAR-gamma), hence modulating macrophage development and
CC       function. It may also exert a negative effect on skeletal development
CC       by regulating bone mass through this pathway. As well as participates
CC       in ER stress and downstream inflammation in adipocytes, pancreatic
CC       islets, and liver (By similarity). Finally, it is also involved in the
CC       cellular response to IL13/interleukin-13 (By similarity).
CC       {ECO:0000250|UniProtKB:P16050, ECO:0000250|UniProtKB:P39654,
CC       ECO:0000269|PubMed:15123652, ECO:0000269|PubMed:23382512,
CC       ECO:0000269|PubMed:8117750, ECO:0000269|PubMed:8444196}.
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:15123652,
CC         ECO:0000269|PubMed:8117750, ECO:0000269|PubMed:8444196};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:10429;
CC         Evidence={ECO:0000305|PubMed:15123652};
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:8117750,
CC         ECO:0000269|PubMed:8444196};
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:0000250|UniProtKB:P16050};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:22781;
CC         Evidence={ECO:0000250|UniProtKB:P16050};
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:0000269|PubMed:15123652};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50217;
CC         Evidence={ECO:0000305|PubMed:15123652};
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:0000250|UniProtKB:P16050};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50929;
CC         Evidence={ECO:0000250|UniProtKB:P16050};
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:0000250|UniProtKB:P16050};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50925;
CC         Evidence={ECO:0000250|UniProtKB:P16050};
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:0000250|UniProtKB:P16050};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50289;
CC         Evidence={ECO:0000250|UniProtKB:P16050};
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:0000250|UniProtKB:P16050};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50285;
CC         Evidence={ECO:0000250|UniProtKB:P16050};
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:0000250|UniProtKB:P16050};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50281;
CC         Evidence={ECO:0000250|UniProtKB:P16050};
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:0000250|UniProtKB:P16050};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50277;
CC         Evidence={ECO:0000250|UniProtKB:P16050};
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:0000250|UniProtKB:P16050};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50153;
CC         Evidence={ECO:0000250|UniProtKB:P16050};
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:0000250|UniProtKB:P16050};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50141;
CC         Evidence={ECO:0000250|UniProtKB:P16050};
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=(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,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:0000250|UniProtKB:P16050};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41333;
CC         Evidence={ECO:0000250|UniProtKB:P16050};
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:0000250|UniProtKB:P16050};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50841;
CC         Evidence={ECO:0000250|UniProtKB:P16050};
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:0000250|UniProtKB:P16050};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64725;
CC         Evidence={ECO:0000250|UniProtKB:P16050};
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:0000250|UniProtKB:P16050};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64729;
CC         Evidence={ECO:0000250|UniProtKB:P16050};
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:0000250|UniProtKB:P16050};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64733;
CC         Evidence={ECO:0000250|UniProtKB:P16050};
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   -!- PATHWAY: Lipid metabolism; hydroperoxy eicosatetraenoic acid
CC       biosynthesis. {ECO:0000269|PubMed:15123652, ECO:0000269|PubMed:8117750,
CC       ECO:0000269|PubMed:8444196}.
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:0000250|UniProtKB:P16050}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:15123652,
CC       ECO:0000269|PubMed:8117750}. Cell membrane
CC       {ECO:0000250|UniProtKB:P16050}; Peripheral membrane protein
CC       {ECO:0000250|UniProtKB:P16050}. Lipid droplet
CC       {ECO:0000250|UniProtKB:P16050}. Note=Predominantly cytosolic; becomes
CC       enriched at membranes upon calcium binding. Translocates from the
CC       cytosol to the plasma membrane when stimulated by IL13/interleukin-13
CC       and in macrophages binding apoptotic cells.
CC       {ECO:0000250|UniProtKB:P39654}.
CC   -!- TISSUE SPECIFICITY: Detected in leukocytes, lung and aorta.
CC       {ECO:0000269|PubMed:8444196}.
CC   -!- DOMAIN: The PLAT domain can bind calcium ions; this promotes
CC       association with membranes. {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the lipoxygenase family. {ECO:0000305}.
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; L06040; AAA41532.1; -; mRNA.
DR   EMBL; S69383; AAB30132.1; -; mRNA.
DR   EMBL; AABR06064408; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   PIR; I52462; I52462.
DR   PIR; S30051; S30051.
DR   RefSeq; NP_112272.2; NM_031010.2.
DR   AlphaFoldDB; Q02759; -.
DR   SMR; Q02759; -.
DR   BioGRID; 249539; 1.
DR   IntAct; Q02759; 1.
DR   STRING; 10116.ENSRNOP00000026038; -.
DR   BindingDB; Q02759; -.
DR   ChEMBL; CHEMBL2741; -.
DR   SwissLipids; SLP:000001609; -.
DR   iPTMnet; Q02759; -.
DR   PhosphoSitePlus; Q02759; -.
DR   PaxDb; 10116-ENSRNOP00000026038; -.
DR   Ensembl; ENSRNOT00000026038.7; ENSRNOP00000026038.4; ENSRNOG00000019183.7.
DR   Ensembl; ENSRNOT00055056410; ENSRNOP00055046516; ENSRNOG00055032645.
DR   Ensembl; ENSRNOT00060050968; ENSRNOP00060042397; ENSRNOG00060029354.
DR   Ensembl; ENSRNOT00065048499; ENSRNOP00065039765; ENSRNOG00065028140.
DR   GeneID; 81639; -.
DR   KEGG; rno:81639; -.
DR   UCSC; RGD:70493; rat.
DR   AGR; RGD:70493; -.
DR   CTD; 246; -.
DR   RGD; 70493; Alox15.
DR   eggNOG; ENOG502QQSP; Eukaryota.
DR   GeneTree; ENSGT00940000162807; -.
DR   HOGENOM; CLU_004282_3_3_1; -.
DR   InParanoid; Q02759; -.
DR   OrthoDB; 999249at2759; -.
DR   TreeFam; TF105320; -.
DR   BRENDA; 1.13.11.31; 5301.
DR   BRENDA; 1.13.11.33; 5301.
DR   Reactome; R-RNO-2142691; Synthesis of Leukotrienes (LT) and Eoxins (EX).
DR   Reactome; R-RNO-2142712; Synthesis of 12-eicosatetraenoic acid derivatives.
DR   Reactome; R-RNO-2142770; Synthesis of 15-eicosatetraenoic acid derivatives.
DR   Reactome; R-RNO-9018677; Biosynthesis of DHA-derived SPMs.
DR   Reactome; R-RNO-9018681; Biosynthesis of protectins.
DR   Reactome; R-RNO-9018896; Biosynthesis of E-series 18(S)-resolvins.
DR   Reactome; R-RNO-9023661; Biosynthesis of E-series 18(R)-resolvins.
DR   Reactome; R-RNO-9025106; Biosynthesis of DPAn-6 SPMs.
DR   Reactome; R-RNO-9026286; Biosynthesis of DPAn-3-derived protectins and resolvins.
DR   UniPathway; UPA00881; -.
DR   PRO; PR:Q02759; -.
DR   Proteomes; UP000002494; Chromosome 10.
DR   Bgee; ENSRNOG00000019183; Expressed in spleen and 17 other cell types or tissues.
DR   GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR   GO; GO:0009898; C:cytoplasmic side of plasma membrane; ISS:UniProtKB.
DR   GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR   GO; GO:0005811; C:lipid droplet; ISS:UniProtKB.
DR   GO; GO:0016020; C:membrane; ISS:UniProtKB.
DR   GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR   GO; GO:0042383; C:sarcolemma; ISS:UniProtKB.
DR   GO; GO:0004052; F:arachidonate 12(S)-lipoxygenase activity; IDA:RGD.
DR   GO; GO:0050473; F:arachidonate 15-lipoxygenase activity; IDA:RGD.
DR   GO; GO:0051120; F:hepoxilin A3 synthase activity; IDA:RGD.
DR   GO; GO:0047977; F:hepoxilin-epoxide hydrolase activity; IDA:UniProtKB.
DR   GO; GO:0005506; F:iron ion binding; ISS:UniProtKB.
DR   GO; GO:0016165; F:linoleate 13S-lipoxygenase activity; ISS:UniProtKB.
DR   GO; GO:0005546; F:phosphatidylinositol-4,5-bisphosphate binding; ISS:UniProtKB.
DR   GO; GO:0019870; F:potassium channel inhibitor activity; TAS: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; ISS:UniProtKB.
DR   GO; GO:0035963; P:cellular response to interleukin-13; ISS:UniProtKB.
DR   GO; GO:0019395; P:fatty acid oxidation; ISS:UniProtKB.
DR   GO; GO:0051122; P:hepoxilin biosynthetic process; IDA:UniProtKB.
DR   GO; GO:0046456; P:icosanoid biosynthetic process; NAS:UniProtKB.
DR   GO; GO:0043651; P:linoleic acid metabolic process; ISS:UniProtKB.
DR   GO; GO:0006629; P:lipid metabolic process; ISO:RGD.
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:RGD.
DR   GO; GO:0002820; P:negative regulation of adaptive immune response; ISS:UniProtKB.
DR   GO; GO:0045794; P:negative regulation of cell volume; TAS: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; ISS:UniProtKB.
DR   GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISS:UniProtKB.
DR   GO; GO:0034116; P:positive regulation of heterotypic cell-cell adhesion; IMP:RGD.
DR   GO; GO:1901074; P:regulation of engulfment of apoptotic cell; ISS:UniProtKB.
DR   GO; GO:0050727; P:regulation of inflammatory response; ISS:UniProtKB.
DR   GO; GO:0042391; P:regulation of membrane potential; TAS: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   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; Q02759; RN.
PE   1: Evidence at protein level;
KW   Calcium; Cell membrane; Cytoplasm; Dioxygenase; Fatty acid metabolism;
KW   Iron; Lipid droplet; Lipid metabolism; Lipid-binding; Membrane;
KW   Metal-binding; Oxidoreductase; Phosphoprotein; Reference proteome.
FT   CHAIN           1..663
FT                   /note="Polyunsaturated fatty acid lipoxygenase ALOX15"
FT                   /id="PRO_0000220687"
FT   DOMAIN          2..115
FT                   /note="PLAT"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00152"
FT   DOMAIN          116..663
FT                   /note="Lipoxygenase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00726"
FT   BINDING         361
FT                   /ligand="Fe cation"
FT                   /ligand_id="ChEBI:CHEBI:24875"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00726"
FT   BINDING         366
FT                   /ligand="Fe cation"
FT                   /ligand_id="ChEBI:CHEBI:24875"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00726"
FT   BINDING         541
FT                   /ligand="Fe cation"
FT                   /ligand_id="ChEBI:CHEBI:24875"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00726"
FT   BINDING         545
FT                   /ligand="Fe cation"
FT                   /ligand_id="ChEBI:CHEBI:24875"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00726"
FT   BINDING         663
FT                   /ligand="Fe cation"
FT                   /ligand_id="ChEBI:CHEBI:24875"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00726"
FT   MOD_RES         149
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:22673903"
FT   MUTAGEN         353
FT                   /note="L->F: Decreases arachidonic acid 12 lipoxygenase.
FT                   Exhibits an arachidonic acid 15 lipoxygenase. Decreases
FT                   hepoxilin A3 synthase activity."
FT                   /evidence="ECO:0000269|PubMed:15123652"
FT   MUTAGEN         417
FT                   /note="K->Q: Does not affect arachidonic acid 12
FT                   lipoxygenase. Does not affect hepoxilin A3 synthase
FT                   activity."
FT                   /evidence="ECO:0000269|PubMed:15123652"
FT   MUTAGEN         418
FT                   /note="A->I: Does not affect arachidonic acid 12
FT                   lipoxygenase. Does not affect hepoxilin A3 synthase
FT                   activity."
FT                   /evidence="ECO:0000269|PubMed:15123652"
FT   CONFLICT        55
FT                   /note="E -> G (in Ref. 2; AAB30132)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        371
FT                   /note="V -> L (in Ref. 1; AAA41532)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   663 AA;  75378 MW;  C732D3EB22CA0411 CRC64;
     MGVYRIRVST GDSKYAGSNN EVYLWLVGQH GEASLGKLLR PCRDSEAEFK VDVSEYLGPL
     LFVRVQKWHY LTDDAWFCNW ISVKGPGDQG SEYMFPCYRW VQGRSILSLP EGTGCTVVED
     SQGLFRKHRE EELEERRSLY RWGNWKDGSI LNVAAASISD LPVDQRFRED KRIEFEASQV
     IGVMDTVVNF PINTVTCWKS LDDFNCVFKS GHTKMAERVR NSWKEDAFFG YQFLNGANPM
     VLKRSTCLPA RLVFPPGMEK LQAQLNKELQ KGTLFEADFF LLDGIKANVI LCSQQYLAAP
     LVMLKLMPDG QLLPIAIQLE LPKTGSTPPP IFTPSDPPMD WLLAKCWVRS SDLQLHELQA
     HLLRGHLMAE VFAVATMRCL PSVHPVFKLL VPHLLYTMEI NVRARSDLIS ERGFFDKAMS
     TGGGGHLDLL KQAGAFLTYC SLCPPDDLAE RGLLDIETCF YAKDALRLWQ IMNRYVVGMF
     NLHYKTDKAV QDDYELQSWC REITDIGLQG AQDRGFPTSL QSRAQACYFI TMCIFTCTAQ
     HSSVHLGQLD WFYWVPNAPC TMRLPPPTTK EATMEKLMAT LPNPNQSTLQ INVVWLLGRR
     QAVMVPLGQH SEEHFPNPEA KAVLKKFREE LAALDKEIEI RNKSLDIPYE YLRPSMVENS
     VAI
//