LOX15_RAT
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 03-AUG-2022, entry version 166.
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,
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 -!- 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}.
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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; Q02759; -.
DR Ensembl; ENSRNOT00000026038; ENSRNOP00000026038; ENSRNOG00000019183.
DR GeneID; 81639; -.
DR KEGG; rno:81639; -.
DR UCSC; RGD:70493; rat.
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 OMA; MVPLGQH; -.
DR OrthoDB; 385042at2759; -.
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 tissues.
DR Genevisible; Q02759; RN.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0031234; C:extrinsic component of cytoplasmic side of plasma membrane; ISS: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: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; 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 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 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 affects 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 affects 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
