LOX15_RABIT
ID LOX15_RABIT Reviewed; 663 AA.
AC P12530; O19043;
DT 01-OCT-1989, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 158.
DE RecName: Full=Polyunsaturated fatty acid lipoxygenase ALOX15 {ECO:0000250|UniProtKB:P16050};
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 Short=L-12LO;
DE EC=1.13.11.31 {ECO:0000269|PubMed:9600854};
DE AltName: Full=Arachidonate 15-lipoxygenase;
DE Short=15-LOX;
DE EC=1.13.11.33 {ECO:0000269|PubMed:9414270, ECO:0000269|PubMed:9600854};
DE AltName: Full=Arachidonate omega-6 lipoxygenase {ECO:0000250|UniProtKB:P16050};
DE AltName: Full=Erythroid cell-specific 15-lipoxygenase {ECO:0000303|PubMed:2612916};
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 {ECO:0000250|UniProtKB:P16050};
DE EC=1.13.11.12 {ECO:0000250|UniProtKB:P16050};
GN Name=ALOX15 {ECO:0000250|UniProtKB:P16050};
OS Oryctolagus cuniculus (Rabbit).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX NCBI_TaxID=9986;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2612916; DOI=10.1016/0378-1119(89)90526-x;
RA O'Prey J., Chester J., Thiele B.J., Janetzki S., Prehn S., Fleming J.,
RA Harrison P.R.;
RT "The promoter structure and complete sequence of the gene encoding the
RT rabbit erythroid cell-specific 15-lipoxygenase.";
RL Gene 84:493-499(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, PATHWAY, AND
RP MUTAGENESIS OF PHE-353.
RX PubMed=9600854; DOI=10.1006/jmbi.1998.1737;
RA Berger M., Schwarz K., Thiele H., Reimann I., Huth A., Borngraeber S.,
RA Kuehn H., Thiele B.-J.;
RT "Simultaneous expression of leukocyte-type 12-lipoxygenase and
RT reticulocyte-type 15-lipoxygenase in rabbits.";
RL J. Mol. Biol. 278:935-948(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PROTEIN SEQUENCE OF 2-31.
RX PubMed=2777088; DOI=10.1016/0378-1119(89)90103-0;
RA Fleming J., Thiele B.J., Chester J., O'Prey J., Janetzki S., Aitken A.,
RA Anton I.A., Rapoport S.M., Harrison P.R.;
RT "The complete sequence of the rabbit erythroid cell-specific 15-
RT lipoxygenase mRNA: comparison of the predicted amino acid sequence of the
RT erythrocyte lipoxygenase with other lipoxygenases.";
RL Gene 79:181-188(1989).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-31.
RX PubMed=3123326; DOI=10.1016/0378-1119(87)90182-x;
RA Thiele B.J., Fleming J., Kasturi K., O'Prey J., Black E., Chester J.,
RA Rapoport S.M., Harrison P.R.;
RT "Cloning of a rabbit erythroid-cell-specific lipoxygenase mRNA.";
RL Gene 57:111-119(1987).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA], AND GENE STRUCTURE.
RX PubMed=2386503;
RA Thiele B.J., Fleming J., Chester J., O'Prey J., Prehn S., Janetzki S.,
RA Rapoport S.M., Harrison P.R.;
RT "Structure of the mRNA and of the gene coding for the rabbit erythroid 15-
RT lipoxygenase.";
RL Biomed. Biochim. Acta 49:S17-S24(1990).
RN [6]
RP CATALYTIC ACTIVITY, FUNCTION, 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 [7]
RP FUNCTION, CATALYTIC ACTIVITY, MUTAGENESIS OF ILE-418, AND
RP BIOPHYSICOCHEMICAL PROPERTIES.
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 [8]
RP BIOPHYSICOCHEMICAL PROPERTIES, CATALYTIC ACTIVITY, AND FUNCTION.
RX PubMed=17493578; DOI=10.1016/j.abb.2007.04.007;
RA Prusakiewicz J.J., Turman M.V., Vila A., Ball H.L., Al-Mestarihi A.H.,
RA Di Marzo V., Marnett L.J.;
RT "Oxidative metabolism of lipoamino acids and vanilloids by lipoxygenases
RT and cyclooxygenases.";
RL Arch. Biochem. Biophys. 464:260-268(2007).
RN [9]
RP CATALYTIC ACTIVITY, AND FUNCTION.
RX PubMed=18311922; DOI=10.1021/bi702530z;
RA Turman M.V., Kingsley P.J., Rouzer C.A., Cravatt B.F., Marnett L.J.;
RT "Oxidative metabolism of a fatty acid amide hydrolase-regulated lipid,
RT arachidonoyltaurine.";
RL Biochemistry 47:3917-3925(2008).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) IN COMPLEX WITH IRON AND SUBSTRATE
RP ANALOG.
RX PubMed=9406550; DOI=10.1038/nsb1297-1003;
RA Gillmor S.A., Villasenor A., Fletterick R., Sigal E., Browner M.F.;
RT "The structure of mammalian 15-lipoxygenase reveals similarity to the
RT lipases and the determinants of substrate specificity.";
RL Nat. Struct. Biol. 4:1003-1009(1997).
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:9600854, PubMed:9414270, PubMed:15123652, PubMed:17493578,
CC PubMed:18311922). It inserts peroxyl groups at C12 or C15 of
CC arachidonate ((5Z,8Z,11Z,14Z)-eicosatetraenoate) producing both 12-
CC hydroperoxyeicosatetraenoate/12-HPETE and 15-
CC hydroperoxyeicosatetraenoate/15-HPETE (PubMed:9600854, PubMed:9414270,
CC PubMed:15123652, PubMed:17493578). It may then act on 12-HPETE to
CC produce hepoxilins, which may show pro-inflammatory properties
CC (PubMed:15123652). Can also peroxidize linoleate ((9Z,12Z)-
CC octadecadienoate) to 13-hydroperoxyoctadecadienoate. May participate in
CC the sequential oxidations of DHA ((4Z,7Z,10Z,13Z,16Z,19Z)-
CC docosahexaenoate) to generate specialized pro-resolving mediators
CC (SPMs)like resolvin D5 ((7S,17S)-diHPDHA) and (7S,14S)-diHPDHA, that
CC actively down-regulate the immune response and have anti-aggregation
CC properties with platelets. Can convert epoxy fatty acids to
CC hydroperoxy-epoxides derivatives followed by an intramolecular
CC nucleophilic substitution leading to the formation of monocyclic
CC endoperoxides (By similarity). Plays an important role during the
CC 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 (By similarity). {ECO:0000250|UniProtKB:P16050,
CC ECO:0000250|UniProtKB:P39654, ECO:0000269|PubMed:15123652,
CC ECO:0000269|PubMed:17493578, ECO:0000269|PubMed:18311922,
CC ECO:0000269|PubMed:9414270, ECO:0000269|PubMed:9600854}.
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:9600854};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:10429;
CC Evidence={ECO:0000305|PubMed:9600854};
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:15123652,
CC ECO:0000269|PubMed:17493578, ECO:0000269|PubMed:9414270,
CC ECO:0000269|PubMed:9600854};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16870;
CC Evidence={ECO:0000305|PubMed:17493578};
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=(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=(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)-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-(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:0000269|PubMed:18311922};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50157;
CC Evidence={ECO:0000305|PubMed:18311922};
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:0000269|PubMed:17493578};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50181;
CC Evidence={ECO:0000305|PubMed:17493578};
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:0000269|PubMed:17493578};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50189;
CC Evidence={ECO:0000305|PubMed:17493578};
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:0000269|PubMed:17493578};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50185;
CC Evidence={ECO:0000305|PubMed:17493578};
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 -!- 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 -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=20 uM for (5Z,8Z,11Z,14Z)-eicosatetraenoate
CC {ECO:0000269|PubMed:17493578};
CC KM=49 uM for N-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-glycine
CC {ECO:0000269|PubMed:17493578};
CC KM=98 uM for N-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-alanine
CC {ECO:0000269|PubMed:17493578};
CC KM=48 uM for N-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-gamma-aminobutanoate
CC {ECO:0000269|PubMed:17493578};
CC KM=20.5 uM for (5Z,8Z,11Z,14Z)-eicosatetraenoate
CC {ECO:0000269|PubMed:15123652};
CC KM=91.5 uM for (12S)-hydroperoxy-(5Z,8Z,10E,14Z)-eicosatetraenoate
CC {ECO:0000269|PubMed:15123652};
CC Note=kcat is 22.2 sec(-1) with (5Z,8Z,11Z,14Z)-eicosatetraenoate as
CC substrate (PubMed:15123652). kcat is 1.34 sec(-1) with (12S)-
CC hydroperoxy-(5Z,8Z,10E,14Z)-eicosatetraenoate as substrate
CC (PubMed:15123652). {ECO:0000269|PubMed:15123652};
CC -!- PATHWAY: Lipid metabolism; hydroperoxy eicosatetraenoic acid
CC biosynthesis. {ECO:0000269|PubMed:9600854}.
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:9414270}.
CC Cell membrane {ECO:0000269|PubMed:9414270}; Peripheral membrane protein
CC {ECO:0000269|PubMed:9414270}. 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 reticulocytes (at protein level).
CC {ECO:0000269|PubMed:9414270}.
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 -!- CAUTION: According to the authors the mRNA described in PubMed:9600854
CC may be encoded by a gene different from ALOX15. {ECO:0000305}.
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DR EMBL; M33291; AAA75014.1; -; Genomic_DNA.
DR EMBL; Z97654; CAB10746.1; -; mRNA.
DR EMBL; M27214; AAB86978.1; -; mRNA.
DR EMBL; M22617; AAA31385.1; -; mRNA.
DR PIR; JQ0018; JQ0018.
DR RefSeq; NP_001075751.1; NM_001082282.1.
DR RefSeq; NP_001139620.1; NM_001146148.1.
DR PDB; 1LOX; X-ray; 2.40 A; A=2-663.
DR PDB; 2P0M; X-ray; 2.40 A; A/B=2-663.
DR PDBsum; 1LOX; -.
DR PDBsum; 2P0M; -.
DR AlphaFoldDB; P12530; -.
DR SMR; P12530; -.
DR STRING; 9986.ENSOCUP00000017072; -.
DR BindingDB; P12530; -.
DR ChEMBL; CHEMBL4358; -.
DR DrugCentral; P12530; -.
DR SwissLipids; SLP:000001603; -.
DR MetOSite; P12530; -.
DR GeneID; 100009114; -.
DR GeneID; 100271999; -.
DR KEGG; ocu:100009114; -.
DR KEGG; ocu:100271999; -.
DR CTD; 239; -.
DR CTD; 246; -.
DR eggNOG; ENOG502QQSP; Eukaryota.
DR InParanoid; P12530; -.
DR OrthoDB; 385042at2759; -.
DR BRENDA; 1.13.11.31; 1749.
DR BRENDA; 1.13.11.33; 1749.
DR UniPathway; UPA00881; -.
DR EvolutionaryTrace; P12530; -.
DR PRO; PR:P12530; -.
DR Proteomes; UP000001811; Unplaced.
DR GO; GO:0005829; C:cytosol; ISS: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: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; ISS:UniProtKB.
DR GO; GO:0005546; F:phosphatidylinositol-4,5-bisphosphate binding; ISS: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; IDA:UniProtKB.
DR GO; GO:0051122; P:hepoxilin biosynthetic process; ISS:UniProtKB.
DR GO; GO:0043651; P:linoleic acid metabolic process; IDA:UniProtKB.
DR GO; GO:0006629; P:lipid metabolic process; IDA:UniProtKB.
DR GO; GO:2001303; P:lipoxin A4 biosynthetic process; ISS:UniProtKB.
DR GO; GO:0019372; P:lipoxygenase pathway; IDA:UniProtKB.
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; ISS:UniProtKB.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISS:UniProtKB.
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: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 3D-structure; 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:2777088"
FT CHAIN 2..663
FT /note="Polyunsaturated fatty acid lipoxygenase ALOX15"
FT /id="PRO_0000220699"
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 ECO:0000269|PubMed:9406550"
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 ECO:0000269|PubMed:9406550"
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 ECO:0000269|PubMed:9406550"
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 ECO:0000269|PubMed:9406550"
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 ECO:0000269|PubMed:9406550"
FT MUTAGEN 353
FT /note="F->L: Changes the stereoselectivity of the
FT oxygenation reaction to produce (12S)-HPETE instead of
FT (15S)-HPETE."
FT /evidence="ECO:0000269|PubMed:9600854"
FT MUTAGEN 418
FT /note="I->A: Decreases 15 lipoxygenase activity. Exhibits
FT hepoxilin A3 synthase activity."
FT /evidence="ECO:0000269|PubMed:15123652"
FT CONFLICT 42
FT /note="T -> S (in Ref. 2; CAB10746)"
FT /evidence="ECO:0000305"
FT CONFLICT 64
FT /note="R -> K (in Ref. 2; CAB10746)"
FT /evidence="ECO:0000305"
FT CONFLICT 190
FT /note="N -> D (in Ref. 3; AAB86978)"
FT /evidence="ECO:0000305"
FT CONFLICT 194
FT /note="I -> V (in Ref. 3; AAB86978)"
FT /evidence="ECO:0000305"
FT CONFLICT 353
FT /note="F -> L (in Ref. 2; CAB10746)"
FT /evidence="ECO:0000305"
FT STRAND 3..10
FT /evidence="ECO:0007829|PDB:1LOX"
FT STRAND 12..15
FT /evidence="ECO:0007829|PDB:2P0M"
FT STRAND 19..30
FT /evidence="ECO:0007829|PDB:1LOX"
FT STRAND 32..39
FT /evidence="ECO:0007829|PDB:1LOX"
FT STRAND 46..52
FT /evidence="ECO:0007829|PDB:1LOX"
FT STRAND 59..68
FT /evidence="ECO:0007829|PDB:1LOX"
FT STRAND 70..72
FT /evidence="ECO:0007829|PDB:1LOX"
FT STRAND 76..88
FT /evidence="ECO:0007829|PDB:1LOX"
FT STRAND 93..101
FT /evidence="ECO:0007829|PDB:1LOX"
FT STRAND 103..105
FT /evidence="ECO:0007829|PDB:2P0M"
FT STRAND 107..110
FT /evidence="ECO:0007829|PDB:1LOX"
FT HELIX 126..139
FT /evidence="ECO:0007829|PDB:1LOX"
FT STRAND 152..154
FT /evidence="ECO:0007829|PDB:1LOX"
FT HELIX 158..160
FT /evidence="ECO:0007829|PDB:1LOX"
FT HELIX 163..165
FT /evidence="ECO:0007829|PDB:1LOX"
FT HELIX 169..175
FT /evidence="ECO:0007829|PDB:1LOX"
FT HELIX 189..192
FT /evidence="ECO:0007829|PDB:1LOX"
FT HELIX 193..195
FT /evidence="ECO:0007829|PDB:1LOX"
FT HELIX 201..206
FT /evidence="ECO:0007829|PDB:1LOX"
FT HELIX 214..222
FT /evidence="ECO:0007829|PDB:1LOX"
FT HELIX 226..235
FT /evidence="ECO:0007829|PDB:1LOX"
FT HELIX 259..270
FT /evidence="ECO:0007829|PDB:1LOX"
FT STRAND 274..278
FT /evidence="ECO:0007829|PDB:1LOX"
FT HELIX 280..282
FT /evidence="ECO:0007829|PDB:1LOX"
FT STRAND 301..306
FT /evidence="ECO:0007829|PDB:1LOX"
FT TURN 308..310
FT /evidence="ECO:0007829|PDB:2P0M"
FT STRAND 312..318
FT /evidence="ECO:0007829|PDB:1LOX"
FT HELIX 338..358
FT /evidence="ECO:0007829|PDB:1LOX"
FT HELIX 359..365
FT /evidence="ECO:0007829|PDB:1LOX"
FT HELIX 366..379
FT /evidence="ECO:0007829|PDB:1LOX"
FT HELIX 385..390
FT /evidence="ECO:0007829|PDB:1LOX"
FT HELIX 391..394
FT /evidence="ECO:0007829|PDB:1LOX"
FT HELIX 397..404
FT /evidence="ECO:0007829|PDB:1LOX"
FT TURN 405..408
FT /evidence="ECO:0007829|PDB:1LOX"
FT HELIX 414..418
FT /evidence="ECO:0007829|PDB:1LOX"
FT TURN 420..424
FT /evidence="ECO:0007829|PDB:1LOX"
FT HELIX 425..434
FT /evidence="ECO:0007829|PDB:1LOX"
FT HELIX 439..442
FT /evidence="ECO:0007829|PDB:1LOX"
FT HELIX 444..450
FT /evidence="ECO:0007829|PDB:1LOX"
FT HELIX 460..480
FT /evidence="ECO:0007829|PDB:1LOX"
FT TURN 481..483
FT /evidence="ECO:0007829|PDB:1LOX"
FT HELIX 487..491
FT /evidence="ECO:0007829|PDB:1LOX"
FT HELIX 494..504
FT /evidence="ECO:0007829|PDB:1LOX"
FT TURN 505..509
FT /evidence="ECO:0007829|PDB:1LOX"
FT HELIX 511..514
FT /evidence="ECO:0007829|PDB:1LOX"
FT HELIX 523..536
FT /evidence="ECO:0007829|PDB:1LOX"
FT HELIX 539..545
FT /evidence="ECO:0007829|PDB:1LOX"
FT HELIX 548..551
FT /evidence="ECO:0007829|PDB:1LOX"
FT STRAND 552..554
FT /evidence="ECO:0007829|PDB:1LOX"
FT HELIX 555..557
FT /evidence="ECO:0007829|PDB:1LOX"
FT STRAND 568..570
FT /evidence="ECO:0007829|PDB:1LOX"
FT HELIX 574..580
FT /evidence="ECO:0007829|PDB:1LOX"
FT HELIX 584..596
FT /evidence="ECO:0007829|PDB:1LOX"
FT HELIX 618..643
FT /evidence="ECO:0007829|PDB:1LOX"
FT STRAND 645..647
FT /evidence="ECO:0007829|PDB:1LOX"
FT TURN 654..656
FT /evidence="ECO:0007829|PDB:1LOX"
FT STRAND 657..660
FT /evidence="ECO:0007829|PDB:1LOX"
SQ SEQUENCE 663 AA; 75310 MW; C3391E1E6E7930BF CRC64;
MGVYRVCVST GASIYAGSKN KVELWLVGQH GEVELGSCLR PTRNKEEEFK VNVSKYLGSL
LFVRLRKKHF LKEDAWFCNW ISVQALGAAE DKYWFPCYRW VVGDGVQSLP VGTGCTTVGD
PQGLFQKHRE QELEERRKLY QWGSWKEGLI LNVAGSKLTD LPVDERFLED KKIDFEASLA
WGLAELALKN SLNILAPWKT LDDFNRIFWC GRSKLARRVR DSWQEDSLFG YQFLNGANPM
LLRRSVQLPA RLVFPPGMEE LQAQLEKELK AGTLFEADFA LLDNIKANVI LYCQQYLAAP
LVMLKLQPDG KLMPMVIQLH LPKIGSSPPP LFLPTDPPMV WLLAKCWVRS SDFQVHELNS
HLLRGHLMAE VFTVATMRCL PSIHPVFKLI VPHLRYTLEI NVRARNGLVS DFGIFDQIMS
TGGGGHVQLL QQAGAFLTYR SFCPPDDLAD RGLLGVESSF YAQDALRLWE IISRYVQGIM
GLYYKTDEAV RDDLELQSWC REITEIGLQG AQKQGFPTSL QSVAQACHFV TMCIFTCTGQ
HSSIHLGQLD WFTWVPNAPC TMRLPPPTTK DATLETVMAT LPNLHQSSLQ MSIVWQLGRD
QPIMVPLGQH QEEYFSGPEP RAVLEKFREE LAIMDKEIEV RNEKLDIPYE YLRPSIVENS
VAI
