LOX15_PIG
ID LOX15_PIG Reviewed; 663 AA.
AC P16469; F1RFT4;
DT 01-AUG-1990, integrated into UniProtKB/Swiss-Prot.
DT 16-OCT-2013, sequence version 3.
DT 03-AUG-2022, entry version 164.
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 EC=1.13.11.31 {ECO:0000269|PubMed:8305485};
DE AltName: Full=Arachidonate 15-lipoxygenase;
DE Short=15-LOX;
DE EC=1.13.11.33 {ECO:0000269|PubMed:8305485};
DE AltName: Full=Arachidonate omega-6 lipoxygenase {ECO:0000250|UniProtKB:P16050};
DE AltName: Full=Erythroid cell-specific 15-lipoxygenase {ECO:0000250|UniProtKB:P12530};
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 Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PARTIAL PROTEIN SEQUENCE.
RC TISSUE=Leukocyte;
RX PubMed=2315307; DOI=10.1073/pnas.87.6.2142;
RA Yoshimoto T., Suzuki H., Yamamoto S., Takai T., Yokoyama C., Tanabe T.;
RT "Cloning and sequence analysis of the cDNA for arachidonate 12-lipoxygenase
RT of porcine leukocytes.";
RL Proc. Natl. Acad. Sci. U.S.A. 87:2142-2146(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=1601885; DOI=10.1016/s0021-9258(19)49822-0;
RA Arakawa T., Oshima T., Kishimoto K., Yoshimoto T., Yamamoto S.;
RT "Molecular structure and function of the porcine arachidonate 12-
RT lipoxygenase gene.";
RL J. Biol. Chem. 267:12188-12191(1992).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RG Porcine genome sequencing project;
RL Submitted (NOV-2009) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, PATHWAY, IRON-BINDING, AND
RP MUTAGENESIS OF ILE-106; HIS-128; HIS-356; HIS-361; HIS-366; HIS-384;
RP HIS-393; MET-398; VAL-418; VAL-419; HIS-426; CYS-533 AND HIS-541.
RX PubMed=8305485; DOI=10.1016/0005-2760(94)90234-8;
RA Suzuki H., Kishimoto K., Yoshimoto T., Yamamoto S., Kanai F., Ebina Y.,
RA Miyatake A., Tanabe T.;
RT "Site-directed mutagenesis studies on the iron-binding domain and the
RT determinant for the substrate oxygenation site of porcine leukocyte
RT arachidonate 12-lipoxygenase.";
RL Biochim. Biophys. Acta 1210:308-316(1994).
RN [5]
RP 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 [6]
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 [7]
RP CATALYTIC ACTIVITY, AND FUNCTION.
RX PubMed=19324874; DOI=10.1074/jbc.m809014200;
RA Dangi B., Obeng M., Nauroth J.M., Teymourlouei M., Needham M., Raman K.,
RA Arterburn L.M.;
RT "Biogenic synthesis, purification, and chemical characterization of anti-
RT inflammatory resolvins derived from docosapentaenoic acid (DPAn-6).";
RL J. Biol. Chem. 284:14744-14759(2009).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (1.89 ANGSTROMS) OF 112-663 IN COMPLEX WITH
RP INHIBITOR, AND IRON-BINDING.
RX PubMed=22795085; DOI=10.1016/j.str.2012.06.003;
RA Xu S., Mueser T.C., Marnett L.J., Funk M.O. Jr.;
RT "Crystal structure of 12-lipoxygenase catalytic-domain-inhibitor complex
RT identifies a substrate-binding channel for catalysis.";
RL Structure 20:1490-1497(2012).
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:8305485, PubMed:17493578, PubMed:18311922, PubMed:19324874). 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:8305485,
CC PubMed:17493578). It may then act on 12-HPETE to produce hepoxilins,
CC which may show pro-inflammatory properties (By similarity). Can also
CC peroxidize 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:0000250|UniProtKB:Q02759, ECO:0000269|PubMed:17493578,
CC ECO:0000269|PubMed:18311922, ECO:0000269|PubMed:19324874,
CC ECO:0000269|PubMed:8305485}.
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:17493578,
CC ECO:0000269|PubMed:8305485};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:10429;
CC Evidence={ECO:0000305|PubMed:17493578};
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:8305485};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16870;
CC Evidence={ECO:0000305|PubMed:8305485};
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,19Z)-docosahexaenoate + O2 = 14-
CC hydroperoxy-(4Z,7Z,10Z,12E,16Z,19Z)-docosahexaenoate;
CC Xref=Rhea:RHEA:43472, ChEBI:CHEBI:15379, ChEBI:CHEBI:77016,
CC ChEBI:CHEBI:83336; Evidence={ECO:0000269|PubMed:19324874};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43473;
CC Evidence={ECO:0000305|PubMed:19324874};
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:0000269|PubMed:19324874};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50825;
CC Evidence={ECO:0000305|PubMed:19324874};
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:0000269|PubMed:19324874};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50837;
CC Evidence={ECO:0000305|PubMed:19324874};
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:0000269|PubMed:18311922};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50161;
CC Evidence={ECO:0000305|PubMed:18311922};
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:0000269|PubMed:17493578};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50177;
CC Evidence={ECO:0000305|PubMed:17493578};
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:0000269|PubMed:17493578};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50169;
CC Evidence={ECO:0000305|PubMed:17493578};
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:0000269|PubMed:17493578};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50173;
CC Evidence={ECO:0000305|PubMed:17493578};
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:0000255|PROSITE-ProRule:PRU00726,
CC ECO:0000269|PubMed:8305485};
CC Note=Binds 1 Fe cation per subunit. {ECO:0000255|PROSITE-
CC ProRule:PRU00726, ECO:0000269|PubMed:8305485};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=7.8 uM for (5Z,8Z,11Z,14Z)-eicosatetraenoate
CC {ECO:0000269|PubMed:17493578};
CC KM=8 uM for N-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-glycine
CC {ECO:0000269|PubMed:17493578};
CC KM=9 uM for N-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-alanine
CC {ECO:0000269|PubMed:17493578};
CC KM=7.8 uM for N-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-gamma-aminobutanoate
CC {ECO:0000269|PubMed:17493578};
CC Vmax=13.1 umol/sec/ug enzyme towards (5Z,8Z,11Z,14Z)-
CC eicosatetraenoate {ECO:0000269|PubMed:17493578};
CC Vmax=9.9 umol/sec/ug enzyme towards N-(5Z,8Z,11Z,14Z)-
CC eicosatetraenoyl-glycine {ECO:0000269|PubMed:17493578};
CC Vmax=7.6 umol/sec/ug enzyme towards N-(5Z,8Z,11Z,14Z)-
CC eicosatetraenoyl-alanine {ECO:0000269|PubMed:17493578};
CC Vmax=10.4 umol/sec/ug enzyme towards N-(5Z,8Z,11Z,14Z)-
CC eicosatetraenoyl-gamma-aminobutanoate {ECO:0000269|PubMed:17493578};
CC -!- PATHWAY: Lipid metabolism; hydroperoxy eicosatetraenoic acid
CC biosynthesis. {ECO:0000269|PubMed:8305485}.
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
CC {ECO:0000250|UniProtKB:P16050}. 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 -!- 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; M31417; AAA31068.1; -; mRNA.
DR EMBL; D10621; BAA01471.1; -; Genomic_DNA.
DR EMBL; CU972403; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR PIR; A35087; A35087.
DR RefSeq; NP_999096.1; NM_213931.1.
DR PDB; 3RDE; X-ray; 1.89 A; A/B/C/D=112-663.
DR PDBsum; 3RDE; -.
DR AlphaFoldDB; P16469; -.
DR SMR; P16469; -.
DR STRING; 9823.ENSSSCP00000018988; -.
DR BindingDB; P16469; -.
DR ChEMBL; CHEMBL2381; -.
DR SwissLipids; SLP:000001604; -.
DR PaxDb; P16469; -.
DR PeptideAtlas; P16469; -.
DR Ensembl; ENSSSCT00025067401; ENSSSCP00025028851; ENSSSCG00025049493.
DR Ensembl; ENSSSCT00070040554; ENSSSCP00070034023; ENSSSCG00070020395.
DR GeneID; 396971; -.
DR KEGG; ssc:396971; -.
DR CTD; 246; -.
DR eggNOG; ENOG502QQSP; Eukaryota.
DR HOGENOM; CLU_004282_3_3_1; -.
DR InParanoid; P16469; -.
DR OrthoDB; 385042at2759; -.
DR TreeFam; TF105320; -.
DR BRENDA; 1.13.11.31; 6170.
DR Reactome; R-SSC-2142691; Synthesis of Leukotrienes (LT) and Eoxins (EX).
DR Reactome; R-SSC-2142712; Synthesis of 12-eicosatetraenoic acid derivatives.
DR Reactome; R-SSC-2142770; Synthesis of 15-eicosatetraenoic acid derivatives.
DR Reactome; R-SSC-9018677; Biosynthesis of DHA-derived SPMs.
DR Reactome; R-SSC-9018681; Biosynthesis of protectins.
DR Reactome; R-SSC-9018896; Biosynthesis of E-series 18(S)-resolvins.
DR Reactome; R-SSC-9023661; Biosynthesis of E-series 18(R)-resolvins.
DR Reactome; R-SSC-9025106; Biosynthesis of DPAn-6 SPMs.
DR Reactome; R-SSC-9026286; Biosynthesis of DPAn-3-derived protectins and resolvins.
DR SABIO-RK; P16469; -.
DR UniPathway; UPA00881; -.
DR Proteomes; UP000008227; Unplaced.
DR Proteomes; UP000314985; Chromosome 12.
DR Genevisible; P16469; SS.
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; ISS:UniProtKB.
DR GO; GO:0005506; F:iron ion binding; IDA: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: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; IBA:GO_Central.
DR GO; GO:0043651; P:linoleic acid metabolic process; IDA:UniProtKB.
DR GO; GO:0006629; P:lipid metabolic process; IDA:UniProtKB.
DR GO; GO:0034440; P:lipid oxidation; IBA:GO_Central.
DR GO; GO:2001303; P:lipoxin A4 biosynthetic process; ISS:UniProtKB.
DR GO; GO:0019372; P:lipoxygenase pathway; IDA:UniProtKB.
DR GO; GO: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 CHAIN 1..663
FT /note="Polyunsaturated fatty acid lipoxygenase ALOX15"
FT /id="PRO_0000220684"
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 BINDING 366
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT BINDING 541
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT BINDING 545
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
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 MUTAGEN 106
FT /note="I->V: No effect on the stereoselectivity of the
FT oxygenation reaction."
FT /evidence="ECO:0000269|PubMed:8305485"
FT MUTAGEN 128
FT /note="H->L: No specific effect on enzymatic activity and
FT iron-binding."
FT /evidence="ECO:0000269|PubMed:8305485"
FT MUTAGEN 356
FT /note="H->L: No specific effect on enzymatic activity and
FT iron-binding."
FT /evidence="ECO:0000269|PubMed:8305485"
FT MUTAGEN 361
FT /note="H->L,Q: Loss of enzymatic activity and iron-
FT binding."
FT /evidence="ECO:0000269|PubMed:8305485"
FT MUTAGEN 366
FT /note="H->L: Loss of enzymatic activity and iron-binding."
FT /evidence="ECO:0000269|PubMed:8305485"
FT MUTAGEN 384
FT /note="H->L: Labile enzyme with normal enzymatic activity."
FT /evidence="ECO:0000269|PubMed:8305485"
FT MUTAGEN 393
FT /note="H->L: Labile enzyme with loss of enzymatic
FT activity."
FT /evidence="ECO:0000269|PubMed:8305485"
FT MUTAGEN 398
FT /note="M->L: No effect on the stereoselectivity of the
FT oxygenation reaction."
FT /evidence="ECO:0000269|PubMed:8305485"
FT MUTAGEN 418
FT /note="V->I: Alters the stereoselectivity of the
FT oxygenation reaction. Changes the stereoselectivity of the
FT oxygenation toward the production of (15S)-HPETE; when
FT associated with M-419."
FT /evidence="ECO:0000269|PubMed:8305485"
FT MUTAGEN 419
FT /note="V->M: Alters the stereoselectivity of the
FT oxygenation reaction. Changes the stereoselectivity of the
FT oxygenation toward the production of (15S)-HPETE; when
FT associated with I-418."
FT /evidence="ECO:0000269|PubMed:8305485"
FT MUTAGEN 426
FT /note="H->L: Decreased enzymatic activity without effect on
FT iron-binding."
FT /evidence="ECO:0000269|PubMed:8305485"
FT MUTAGEN 533
FT /note="C->S: No specific effect on enzymatic activity and
FT iron-binding."
FT /evidence="ECO:0000269|PubMed:8305485"
FT MUTAGEN 541
FT /note="H->L: Loss of enzymatic activity and iron-binding."
FT /evidence="ECO:0000269|PubMed:8305485"
FT CONFLICT 218
FT /note="R -> Q (in Ref. 1; AAA31068/BAA01471)"
FT /evidence="ECO:0000305"
FT CONFLICT 323
FT /note="H -> R (in Ref. 1; AAA31068/BAA01471)"
FT /evidence="ECO:0000305"
FT CONFLICT 494
FT /note="L -> F (in Ref. 1; AAA31068/BAA01471)"
FT /evidence="ECO:0000305"
FT CONFLICT 553
FT /note="S -> T (in Ref. 1; AAA31068/BAA01471)"
FT /evidence="ECO:0000305"
FT CONFLICT 623
FT /note="V -> G (in Ref. 1; BAA01471)"
FT /evidence="ECO:0000305"
FT HELIX 126..139
FT /evidence="ECO:0007829|PDB:3RDE"
FT HELIX 158..160
FT /evidence="ECO:0007829|PDB:3RDE"
FT HELIX 163..165
FT /evidence="ECO:0007829|PDB:3RDE"
FT HELIX 169..193
FT /evidence="ECO:0007829|PDB:3RDE"
FT HELIX 201..207
FT /evidence="ECO:0007829|PDB:3RDE"
FT HELIX 214..222
FT /evidence="ECO:0007829|PDB:3RDE"
FT HELIX 226..235
FT /evidence="ECO:0007829|PDB:3RDE"
FT HELIX 259..270
FT /evidence="ECO:0007829|PDB:3RDE"
FT STRAND 274..278
FT /evidence="ECO:0007829|PDB:3RDE"
FT HELIX 280..282
FT /evidence="ECO:0007829|PDB:3RDE"
FT STRAND 301..306
FT /evidence="ECO:0007829|PDB:3RDE"
FT STRAND 312..318
FT /evidence="ECO:0007829|PDB:3RDE"
FT HELIX 338..358
FT /evidence="ECO:0007829|PDB:3RDE"
FT HELIX 359..365
FT /evidence="ECO:0007829|PDB:3RDE"
FT HELIX 366..379
FT /evidence="ECO:0007829|PDB:3RDE"
FT HELIX 385..390
FT /evidence="ECO:0007829|PDB:3RDE"
FT HELIX 391..394
FT /evidence="ECO:0007829|PDB:3RDE"
FT HELIX 397..407
FT /evidence="ECO:0007829|PDB:3RDE"
FT HELIX 414..418
FT /evidence="ECO:0007829|PDB:3RDE"
FT TURN 420..424
FT /evidence="ECO:0007829|PDB:3RDE"
FT HELIX 425..436
FT /evidence="ECO:0007829|PDB:3RDE"
FT HELIX 440..442
FT /evidence="ECO:0007829|PDB:3RDE"
FT HELIX 444..450
FT /evidence="ECO:0007829|PDB:3RDE"
FT HELIX 460..483
FT /evidence="ECO:0007829|PDB:3RDE"
FT HELIX 487..491
FT /evidence="ECO:0007829|PDB:3RDE"
FT HELIX 494..505
FT /evidence="ECO:0007829|PDB:3RDE"
FT TURN 506..509
FT /evidence="ECO:0007829|PDB:3RDE"
FT HELIX 512..514
FT /evidence="ECO:0007829|PDB:3RDE"
FT HELIX 523..537
FT /evidence="ECO:0007829|PDB:3RDE"
FT HELIX 539..545
FT /evidence="ECO:0007829|PDB:3RDE"
FT HELIX 548..551
FT /evidence="ECO:0007829|PDB:3RDE"
FT STRAND 552..554
FT /evidence="ECO:0007829|PDB:3RDE"
FT HELIX 555..557
FT /evidence="ECO:0007829|PDB:3RDE"
FT STRAND 568..570
FT /evidence="ECO:0007829|PDB:3RDE"
FT HELIX 574..580
FT /evidence="ECO:0007829|PDB:3RDE"
FT HELIX 584..598
FT /evidence="ECO:0007829|PDB:3RDE"
FT HELIX 618..643
FT /evidence="ECO:0007829|PDB:3RDE"
FT STRAND 645..647
FT /evidence="ECO:0007829|PDB:3RDE"
FT TURN 654..656
FT /evidence="ECO:0007829|PDB:3RDE"
FT STRAND 657..660
FT /evidence="ECO:0007829|PDB:3RDE"
SQ SEQUENCE 663 AA; 75004 MW; 5E3864A7A3FDEF71 CRC64;
MGLYRVRVST GSSFYAGSQN QVQLWLVGQH GEAALGWCLR PARGKETEFS VDVSEYLGPL
LFVKLRKRHL LQDDAWFCNW ISVQGPGANG DEFRFPCYRW VEGDRILSLP EGTARTVVDD
PQGLFKKHRE EELAERRKLY RWGNWKDGLI LNIASTGIHD LPVDERFLED KRIDFEASLA
KGLADLAVKD SLNVLMSWNS LDSFNRIFWC GQSKLAERVR DSWKEDALFG YQFLNGTNPM
LLRHSVELPA RLKFPPGMEE LQAQLEKELQ GGTLFEADFS LLDGIKANVI LCSQQYLAVP
LVMLKLQPDG KLLPMVIQLQ LPHEGSPLPP LFLPTDPPMV WLLAKCWVRS SDFQLHELHS
HLLRGHLMAE VIAVATMRCL PSIHPIFKLL IPHFRYTMEI NVRARNGLVS DLGIFDQVVS
TGGGGHVELL RRAAALLTYS SFCPPDDLAD RGLLGVESSF YAQDALRLWE VISRYVEGIV
SLHYKTDESV KEDLELQAWC REFTEIGLLG AQDRGFPVSL QSKEQLCHFV TMCIFTCTGQ
HSSNHLGQLD WYSWVPNAPC TMRLPPPTTK DATLETVMAT LPNFHQASLQ MSITWQLGRC
QPTMVALGQH EEEYFSGPGP KAVLTKFREE LAALDKDIEV RNAKLALPYE YLRPSRVENS
VAI
