ID LX15B_HUMAN Reviewed; 676 AA.
AC O15296; D3DTR2; Q8IYQ2; Q8TEV3; Q8TEV4; Q8TEV5; Q8TEV6; Q9UKM4;
DT 11-JAN-2001, integrated into UniProtKB/Swiss-Prot.
DT 11-JAN-2011, sequence version 3.
DT 24-JAN-2024, entry version 205.
DE RecName: Full=Polyunsaturated fatty acid lipoxygenase ALOX15B {ECO:0000305};
DE AltName: Full=15-lipoxygenase 2 {ECO:0000303|PubMed:11839751};
DE Short=15-LOX-2 {ECO:0000303|PubMed:27435673};
DE AltName: Full=Arachidonate 15-lipoxygenase B;
DE Short=15-LOX-B;
DE EC=1.13.11.33 {ECO:0000269|PubMed:10625675, ECO:0000269|PubMed:11956198, ECO:0000269|PubMed:12704195, ECO:0000269|PubMed:17493578, ECO:0000269|PubMed:24282679, ECO:0000269|PubMed:24497644, ECO:0000269|PubMed:9177185};
DE AltName: Full=Arachidonate 15-lipoxygenase type II;
DE AltName: Full=Linoleate 13-lipoxygenase 15-LOb;
DE EC=1.13.11.- {ECO:0000269|PubMed:27435673, ECO:0000305|PubMed:10542053};
GN Name=ALOX15B {ECO:0000312|HGNC:HGNC:434};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A), VARIANT ARG-656, CATALYTIC
RP ACTIVITY, TISSUE SPECIFICITY, AND FUNCTION.
RC TISSUE=Skin;
RX PubMed=9177185; DOI=10.1073/pnas.94.12.6148;
RA Brash A.R., Boeglin W.E., Chang M.S.;
RT "Discovery of a second 15S-lipoxygenase in humans.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:6148-6152(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT ARG-656, AND TISSUE SPECIFICITY.
RX PubMed=11350124; DOI=10.1006/geno.2001.6519;
RA Krieg P., Marks F., Fuerstenberger G.;
RT "A gene cluster encoding human epidermis-type lipoxygenases at chromosome
RT 17p13.1: cloning, physical mapping, and expression.";
RL Genomics 73:323-330(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A; B; C AND D), VARIANTS HIS-486 AND
RP ARG-656, AND FUNCTION IN CELL CYCLE PROGRESSION.
RX PubMed=11839751; DOI=10.1074/jbc.m111936200;
RA Tang S., Bhatia B., Maldonado C.J., Yang P., Newman R.A., Liu J.,
RA Chandra D., Traag J., Klein R.D., Fischer S.M., Chopra D., Shen J.,
RA Zhau H.E., Chung L.W.K., Tang D.G.;
RT "Evidence that arachidonate 15-lipoxygenase 2 is a negative cell cycle
RT regulator in normal prostate epithelial cells.";
RL J. Biol. Chem. 277:16189-16201(2002).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S.,
RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the
RT human lineage.";
RL Nature 440:1045-1049(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM A), AND VARIANT ARG-656.
RC TISSUE=Skin;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 337-484, ALTERNATIVE SPLICING
RP (ISOFORMS A AND D), CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES,
RP KINETIC PARAMETERS, PATHWAY, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=10542053; DOI=10.1046/j.1432-1327.1999.00818.x;
RA Kilty I., Logan A., Vickers P.J.;
RT "Differential characteristics of human 15-lipoxygenase isozymes and a novel
RT splice variant of 15S-lipoxygenase.";
RL Eur. J. Biochem. 266:83-93(1999).
RN [8]
RP FUNCTION AS A 15S-LIPOXYGENASE, CATALYTIC ACTIVITY, AND MUTAGENESIS OF
RP ASP-602 AND VAL-603.
RX PubMed=10625675; DOI=10.1074/jbc.275.2.1287;
RA Jisaka M., Kim R.B., Boeglin W.E., Brash A.R.;
RT "Identification of amino acid determinants of the positional specificity of
RT mouse 8S-lipoxygenase and human 15S-lipoxygenase-2.";
RL J. Biol. Chem. 275:1287-1293(2000).
RN [9]
RP CATALYTIC ACTIVITY, FUNCTION, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=11956198; DOI=10.1074/jbc.m201084200;
RA Kozak K.R., Gupta R.A., Moody J.S., Ji C., Boeglin W.E., DuBois R.N.,
RA Brash A.R., Marnett L.J.;
RT "15-Lipoxygenase metabolism of 2-arachidonylglycerol. Generation of a
RT peroxisome proliferator-activated receptor alpha agonist.";
RL J. Biol. Chem. 277:23278-23286(2002).
RN [10]
RP FUNCTION IN CELL PROLIFERATION, SUBCELLULAR LOCATION, AND CATALYTIC
RP ACTIVITY.
RX PubMed=12704195; DOI=10.1074/jbc.m301920200;
RA Bhatia B., Maldonado C.J., Tang S., Chandra D., Klein R.D., Chopra D.,
RA Shappell S.B., Yang P., Newman R.A., Tang D.G.;
RT "Subcellular localization and tumor-suppressive functions of 15-
RT lipoxygenase 2 (15-LOX2) and its splice variants.";
RL J. Biol. Chem. 278:25091-25100(2003).
RN [11]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=16112079; DOI=10.1016/j.bbrc.2005.08.029;
RA Jisaka M., Iwanaga C., Takahashi N., Goto T., Kawada T., Yamamoto T.,
RA Ikeda I., Nishimura K., Nagaya T., Fushiki T., Yokota K.;
RT "Double dioxygenation by mouse 8S-lipoxygenase: specific formation of a
RT potent peroxisome proliferator-activated receptor alpha agonist.";
RL Biochem. Biophys. Res. Commun. 338:136-143(2005).
RN [12]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
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 [13]
RP FUNCTION IN CYTOKINE SECRETION.
RX PubMed=18067895; DOI=10.1016/j.atherosclerosis.2007.10.027;
RA Danielsson K.N., Rydberg E.K., Ingelsten M., Akyuerek L.M., Jirholt P.,
RA Ullstroem C., Forsberg G.B., Boren J., Wiklund O., Hulten L.M.;
RT "15-Lipoxygenase-2 expression in human macrophages induces chemokine
RT secretion and T cell migration.";
RL Atherosclerosis 199:34-40(2008).
RN [14]
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 [15]
RP INDUCTION BY UV.
RX PubMed=18755188; DOI=10.1016/j.febslet.2008.08.017;
RA Yoo H., Jeon B., Jeon M.S., Lee H., Kim T.Y.;
RT "Reciprocal regulation of 12- and 15-lipoxygenases by UV-irradiation in
RT human keratinocytes.";
RL FEBS Lett. 582:3249-3253(2008).
RN [16]
RP FUNCTION.
RX PubMed=22912809; DOI=10.1371/journal.pone.0043142;
RA Magnusson L.U., Lundqvist A., Karlsson M.N., Skalen K., Levin M.,
RA Wiklund O., Boren J., Hulten L.M.;
RT "Arachidonate 15-lipoxygenase type B knockdown leads to reduced lipid
RT accumulation and inflammation in atherosclerosis.";
RL PLoS ONE 7:E43142-E43142(2012).
RN [17]
RP CATALYTIC ACTIVITY, FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, VARIANTS
RP ASP-416; HIS-486; ARG-656 AND VAL-676, AND CHARACTERIZATION OF VARIANTS
RP ASP-416; HIS-486; ARG-656 AND VAL-676.
RX PubMed=24282679; DOI=10.1016/j.redox.2013.11.001;
RA Horn T., Reddy Kakularam K., Anton M., Richter C., Reddanna P., Kuhn H.;
RT "Functional characterization of genetic enzyme variations in human
RT lipoxygenases.";
RL Redox Biol. 1:566-577(2013).
RN [18]
RP CATALYTIC ACTIVITY, FUNCTION, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=27145229; DOI=10.1021/acs.biochem.5b01339;
RA Green A.R., Barbour S., Horn T., Carlos J., Raskatov J.A., Holman T.R.;
RT "Strict Regiospecificity of Human Epithelial 15-Lipoxygenase-2 Delineates
RT Its Transcellular Synthesis Potential.";
RL Biochemistry 55:2832-2840(2016).
RN [19]
RP BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR LOCATION, CATALYTIC ACTIVITY,
RP AND FUNCTION.
RX PubMed=27435673; DOI=10.1074/jbc.m116.741454;
RA Bender G., Schexnaydre E.E., Murphy R.C., Uhlson C., Newcomer M.E.;
RT "Membrane-dependent Activities of Human 15-LOX-2 and Its Murine
RT Counterpart: IMPLICATIONS FOR MURINE MODELS OF ATHEROSCLEROSIS.";
RL J. Biol. Chem. 291:19413-19424(2016).
RN [20]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=32404334; DOI=10.1194/jlr.ra120000777;
RA Perry S.C., Kalyanaraman C., Tourdot B.E., Conrad W.S., Akinkugbe O.,
RA Freedman J.C., Holinstat M., Jacobson M.P., Holman T.R.;
RT "15-Lipoxygenase-1 biosynthesis of 7S,14S-diHDHA implicates 15-
RT lipoxygenase-2 in biosynthesis of resolvin D5.";
RL J. Lipid Res. 61:1087-1103(2020).
RN [21]
RP X-RAY CRYSTALLOGRAPHY (2.63 ANGSTROMS) IN COMPLEX WITH CALCIUM AND IRON,
RP CATALYTIC ACTIVITY, COFACTOR, FUNCTION, SUBCELLULAR LOCATION, AND
RP MUTAGENESIS OF ASP-39; GLU-44 AND ASP-85.
RX PubMed=24497644; DOI=10.1074/jbc.m113.543777;
RA Kobe M.J., Neau D.B., Mitchell C.E., Bartlett S.G., Newcomer M.E.;
RT "The structure of human 15-lipoxygenase-2 with a substrate mimic.";
RL J. Biol. Chem. 289:8562-8569(2014).
CC -!- FUNCTION: [Isoform A]: Non-heme iron-containing dioxygenase that
CC catalyzes the stereo-specific peroxidation of free and esterified
CC polyunsaturated fatty acids (PUFAs) generating a spectrum of bioactive
CC lipid mediators (PubMed:9177185, PubMed:10625675, PubMed:12704195,
CC PubMed:17493578, PubMed:18311922, PubMed:24282679, PubMed:10542053,
CC PubMed:24497644, PubMed:32404334) (Probable). It inserts peroxyl groups
CC at C15 of arachidonate ((5Z,8Z,11Z,14Z)-eicosatetraenoate) producing
CC (15S)-hydroperoxyeicosatetraenoate/(15S)-HPETE (PubMed:17493578,
CC PubMed:12704195, PubMed:24282679, PubMed:9177185, PubMed:11956198,
CC PubMed:10625675, PubMed:24497644) (Probable). Also peroxidizes
CC linoleate ((9Z,12Z)-octadecadienoate) to 13-
CC hydroperoxyoctadecadienoate/13-HPODE (Probable) (PubMed:10542053,
CC PubMed:27435673). Oxygenates arachidonyl derivatives such as 2-
CC arachidonoylglycerol (2-AG) leading to the production and extracellular
CC release of 15-hydroxyeicosatetraenoyl glycerol (15-HETE-G) that acts as
CC a peroxisome proliferator-activated receptor alpha agonist
CC (PubMed:18311922, PubMed:17493578, PubMed:11956198). Has the ability to
CC efficiently class-switch ALOX5 pro-inflammatory mediators into anti-
CC inflammatory intermediates (PubMed:27145229). Participates in the
CC sequential oxidations of DHA ((4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate)
CC to generate specialized pro-resolving mediators (SPMs) resolvin D5
CC ((7S,17S)-diHPDHA), which can actively down-regulate the immune
CC response and have anti-aggregation properties with platelets
CC (PubMed:32404334). In addition to free PUFAs hydrolyzed from
CC phospholipids, it directly oxidizes PUFAs esterified to membrane-bound
CC phospholipids (PubMed:27435673). Has no detectable 8S-lipoxygenase
CC activity on arachidonate but reacts with (8S)-HPETE to produce
CC (8S,15S)-diHPETE (Probable). May regulate progression through the cell
CC cycle and cell proliferation (PubMed:12704195, PubMed:11839751). May
CC also regulate cytokine secretion by macrophages and therefore play a
CC role in the immune response (PubMed:18067895). May also regulate
CC macrophage differentiation into proatherogenic foam cells
CC (PubMed:22912809). {ECO:0000269|PubMed:10542053,
CC ECO:0000269|PubMed:10625675, ECO:0000269|PubMed:11839751,
CC ECO:0000269|PubMed:11956198, ECO:0000269|PubMed:12704195,
CC ECO:0000269|PubMed:17493578, ECO:0000269|PubMed:18067895,
CC ECO:0000269|PubMed:18311922, ECO:0000269|PubMed:22912809,
CC ECO:0000269|PubMed:24282679, ECO:0000269|PubMed:24497644,
CC ECO:0000269|PubMed:27145229, ECO:0000269|PubMed:27435673,
CC ECO:0000269|PubMed:32404334, ECO:0000269|PubMed:9177185,
CC ECO:0000305|PubMed:10542053, ECO:0000305|PubMed:16112079,
CC ECO:0000305|PubMed:27145229, ECO:0000305|PubMed:27435673}.
CC -!- FUNCTION: [Isoform B]: Does not convert arachidonic acid to 15S-
CC hydroperoxyeicosatetraenoic acid/(15S)-HPETE.
CC {ECO:0000269|PubMed:12704195}.
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:10625675,
CC ECO:0000269|PubMed:11956198, ECO:0000269|PubMed:12704195,
CC ECO:0000269|PubMed:17493578, ECO:0000269|PubMed:24282679,
CC ECO:0000269|PubMed:24497644, ECO:0000269|PubMed:9177185,
CC ECO:0000305|PubMed:10542053, ECO:0000305|PubMed:27145229,
CC ECO:0000305|PubMed:27435673};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16870;
CC Evidence={ECO:0000269|PubMed:12704195};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(9Z,12Z)-octadecadienoate + O2 = 13-hydroperoxy-(9Z,11E)-
CC octadecadienoate; Xref=Rhea:RHEA:48848, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:30245, ChEBI:CHEBI:90823;
CC Evidence={ECO:0000269|PubMed:27435673, ECO:0000305|PubMed:10542053};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48849;
CC Evidence={ECO:0000269|PubMed:27435673};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5S)-hydroxy-(6E,8Z,11Z,14Z)-eicosatetraenoate + O2 = (5S)-
CC hydroxy-(15S)-hydroperoxy-(6E,8Z,11Z,13E)-eicosatetraenoate;
CC Xref=Rhea:RHEA:53660, ChEBI:CHEBI:15379, ChEBI:CHEBI:90632,
CC ChEBI:CHEBI:137546; Evidence={ECO:0000269|PubMed:27145229};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53661;
CC Evidence={ECO:0000305|PubMed:27145229};
CC -!- CATALYTIC ACTIVITY: [Isoform D]:
CC Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 = 5-hydroperoxy-
CC (6E,8Z,11Z,14Z)-eicosatetraenoate; Xref=Rhea:RHEA:48844,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:32395, ChEBI:CHEBI:90822;
CC Evidence={ECO:0000269|PubMed:10542053};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48845;
CC Evidence={ECO:0000305|PubMed:10542053};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5S,6R)-dihydroxy-(7E,9E,11Z,14Z)-eicosatetraenoate + O2 =
CC (5S,6R)-dihydroxy-(15S)-hydroperoxy-(7E,9E,11Z,13E)-
CC eicosatetraenoate; Xref=Rhea:RHEA:53656, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:137542, ChEBI:CHEBI:137547;
CC Evidence={ECO:0000269|PubMed:27145229};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53657;
CC Evidence={ECO:0000305|PubMed:27145229};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5S)-hydroperoxy-(6E,8Z,11Z,14Z)-eicosatetraenoate + O2 =
CC (5S,15S)-dihydroperoxy-(6E,8Z,11Z,13E)-eicosatetraenoate;
CC Xref=Rhea:RHEA:53652, ChEBI:CHEBI:15379, ChEBI:CHEBI:57450,
CC ChEBI:CHEBI:137543; Evidence={ECO:0000269|PubMed:27145229};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53653;
CC Evidence={ECO:0000305|PubMed:27145229};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-glycerol + O2 = 2-[15(S)-
CC hydroperoxy-(5Z,8Z,11Z,13E)-eicosatetraenoyl]-glycerol;
CC Xref=Rhea:RHEA:53332, ChEBI:CHEBI:15379, ChEBI:CHEBI:52392,
CC ChEBI:CHEBI:137187; Evidence={ECO:0000269|PubMed:11956198};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53333;
CC Evidence={ECO:0000269|PubMed:11956198};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(8S)-hydroperoxy-(5Z,9E,11Z,14Z)-eicosatetraenoate + O2 =
CC (8S,15S)-dihydroperoxy-(5Z,9E,11Z,13E)-eicosatetraenoate;
CC Xref=Rhea:RHEA:50932, ChEBI:CHEBI:15379, ChEBI:CHEBI:75322,
CC ChEBI:CHEBI:133899; Evidence={ECO:0000305|PubMed:16112079};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50933;
CC Evidence={ECO:0000305|PubMed:16112079};
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-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:0000269|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:0000269|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:0000269|PubMed:18311922};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50157;
CC Evidence={ECO:0000305|PubMed:18311922};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-glycerol + O2 = 2-[12-
CC hydroperoxy-(5Z,8Z,10E,14Z)-eicosatetraenoyl]-glycerol;
CC Xref=Rhea:RHEA:63224, ChEBI:CHEBI:15379, ChEBI:CHEBI:52392,
CC ChEBI:CHEBI:146254; Evidence={ECO:0000269|PubMed:11956198};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63225;
CC Evidence={ECO:0000269|PubMed:11956198};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-octadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-
CC 3-phosphocholine + O2 = 1-octadecanoyl-2-(15-hydroperoxy-
CC 5Z,8Z,11Z,13E-eicosatetraenoyl)-sn-glycero-3-phosphocholine;
CC Xref=Rhea:RHEA:63264, ChEBI:CHEBI:15379, ChEBI:CHEBI:74965,
CC ChEBI:CHEBI:146283; Evidence={ECO:0000269|PubMed:27435673};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63265;
CC Evidence={ECO:0000305|PubMed:27435673};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1-acyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-
CC phospho-(1D-myo-inositol) + O2 = a 1-acyl-2-(15-hydroperoxy-
CC 5Z,8Z,11Z,13E-eicosatetraenoyl)-sn-glycero-3-phospho-(1D-myo-
CC inositol); Xref=Rhea:RHEA:63276, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:75243, ChEBI:CHEBI:146285;
CC Evidence={ECO:0000269|PubMed:27435673};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63277;
CC Evidence={ECO:0000305|PubMed:27435673};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1-acyl-2-(8Z,11Z,14Z-eicosatrienoyl)-sn-glycero-3-phospho-
CC (1D-myo-inositol) + O2 = a 1-acyl-2-(15-hydroperoxy-8Z,11Z,13E-
CC eicosatrienoyl)-sn-glycero-3-phospho-(1D-myo-inositol);
CC Xref=Rhea:RHEA:63280, ChEBI:CHEBI:15379, ChEBI:CHEBI:146286,
CC ChEBI:CHEBI:146287; Evidence={ECO:0000269|PubMed:27435673};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63281;
CC Evidence={ECO:0000305|PubMed:27435673};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-octadecanoyl-2-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-sn-glycero-
CC 3-phosphoethanolamine + O2 = 1-octadecanoyl-2-(15-hydroperoxy-
CC 5Z,8Z,11Z,13E-eicosatetraenoyl)-sn-glycero-3-phosphoethanolamine;
CC Xref=Rhea:RHEA:63268, ChEBI:CHEBI:15379, ChEBI:CHEBI:78268,
CC ChEBI:CHEBI:146282; Evidence={ECO:0000269|PubMed:27435673};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63269;
CC Evidence={ECO:0000305|PubMed:27435673};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-octadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-
CC 3-phospho-(1D-myo-inositol) + O2 = 1-octadecanoyl-2-(15-hydroperoxy-
CC 5Z,8Z,11Z,13E-eicosatetraenoyl)-sn-glycero-3-phospho-(1D-myo-
CC inositol); Xref=Rhea:RHEA:63272, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:133606, ChEBI:CHEBI:146284;
CC Evidence={ECO:0000269|PubMed:27435673};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63273;
CC Evidence={ECO:0000305|PubMed:27435673};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(8Z,11Z,14Z)-eicosatrienoate + O2 = 15-hydroperoxy-
CC (8Z,11Z,13E)-eicosatrienoate; Xref=Rhea:RHEA:63312,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:71589, ChEBI:CHEBI:146292;
CC Evidence={ECO:0000269|PubMed:27435673};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63313;
CC Evidence={ECO:0000269|PubMed:27435673};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(7S)-hydroperoxy-(4Z,8E,10Z,13Z,16Z,19Z)-docosahexaenoate + O2
CC = (7S,17S)-dihydroperoxy-(4Z,8E,10Z,13Z,15E,19Z)-docosahexaenoate;
CC Xref=Rhea:RHEA:64728, ChEBI:CHEBI:15379, ChEBI:CHEBI:140349,
CC ChEBI:CHEBI:156049; Evidence={ECO:0000269|PubMed:32404334};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64729;
CC Evidence={ECO:0000305|PubMed:32404334};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 = 15-hydroperoxy-
CC (5Z,8Z,11Z,13E)-eicosatetraenoate; Xref=Rhea:RHEA:48832,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:32395, ChEBI:CHEBI:90821;
CC Evidence={ECO:0000269|PubMed:10542053};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48833;
CC Evidence={ECO:0000305|PubMed:10542053};
CC -!- COFACTOR:
CC Name=Fe cation; Xref=ChEBI:CHEBI:24875;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00726,
CC ECO:0000269|PubMed:24497644};
CC Note=Binds 1 Fe cation per subunit. {ECO:0000255|PROSITE-
CC ProRule:PRU00726, ECO:0000269|PubMed:24497644};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=1100 uM for arachidonate (isoform D at pH 7.4 and 20 degrees
CC Celsius) {ECO:0000269|PubMed:10542053};
CC KM=10 uM for linoleate (isoform A at pH 7.4 and 20 degrees Celsius)
CC {ECO:0000269|PubMed:10542053};
CC KM=25 uM for (5Z,8Z,11Z,14Z)-eicosatetraenoate (isoform A at pH 7.4
CC and 20 degrees Celsius) {ECO:0000269|PubMed:10542053};
CC KM=23 uM for (5Z,8Z,11Z,14Z)-eicosatetraenoate (Sf9-expressed enzyme)
CC {ECO:0000269|PubMed:11956198};
CC KM=15 uM for (5Z,8Z,11Z,14Z)-eicosatetraenoate (E.coli-expressed
CC enzyme) {ECO:0000269|PubMed:11956198};
CC KM=9 uM for 2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-glycerol (Sf9-
CC expressed enzyme) {ECO:0000269|PubMed:11956198};
CC KM=8 uM for 2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-glycerol (E.coli-
CC expressed enzyme) {ECO:0000269|PubMed:11956198};
CC KM=14 uM for anandamide (Sf9-expressed enzyme)
CC {ECO:0000269|PubMed:11956198};
CC KM=11 uM for anandamide (E. Coli-expressed enzyme)
CC {ECO:0000269|PubMed:11956198};
CC KM=8 uM for (5Z,8Z,11Z,14Z)-eicosatetraenoate
CC {ECO:0000269|PubMed:17493578};
CC KM=11 uM for N-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-glycine
CC {ECO:0000269|PubMed:17493578};
CC KM=6 uM for N-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-alanine
CC {ECO:0000269|PubMed:17493578};
CC KM=8 uM for N-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-gamma-aminobutanoate
CC {ECO:0000269|PubMed:17493578};
CC KM=1.2 uM for (5Z,8Z,11Z,14Z)-eicosatetraenoate
CC {ECO:0000269|PubMed:24282679};
CC KM=4 uM for (5Z,8Z,11Z,14Z)-eicosatetraenoate
CC {ECO:0000269|PubMed:27145229};
CC KM=3.3 uM for (5S)-hydroxy-(6E,8Z,11Z,14Z)-eicosatetraenoate
CC {ECO:0000269|PubMed:27145229};
CC KM=19 uM for (5S)-hydroperoxy-(6E,8Z,11Z,14Z)-eicosatetraenoate
CC {ECO:0000269|PubMed:27145229};
CC KM=1.74 uM for (5Z,8Z,11Z,14Z)-eicosatetraenoate
CC {ECO:0000269|PubMed:27435673};
CC KM=3.46 uM for (8Z,11Z,14Z)-eicosatrienoate
CC {ECO:0000269|PubMed:27435673};
CC Vmax=4 umol/min/mg enzyme with arachidonate as substrate (isoform A
CC at pH 7.4 and 20 degrees Celsius) {ECO:0000269|PubMed:10542053};
CC Vmax=2 umol/min/mg enzyme with arachidonate as substrate (isoform D
CC at pH 7.4 and 20 degrees Celsius) {ECO:0000269|PubMed:10542053};
CC Vmax=4 umol/min/mg enzyme with linoleate as substrate (isoform A at
CC pH 7.4 and 20 degrees Celsius) {ECO:0000269|PubMed:10542053};
CC Vmax=0.82 nmol/sec/mg enzyme with (5Z,8Z,11Z,14Z)-eicosatetraenoate
CC (Sf9-expressed enzyme) {ECO:0000269|PubMed:11956198};
CC Vmax=4.3 nmol/sec/mg enzyme with (5Z,8Z,11Z,14Z)-eicosatetraenoate
CC (E.coli-expressed enzyme) {ECO:0000269|PubMed:11956198};
CC Vmax=9 nmol/sec/mg enzyme with 2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-
CC glycerol (Sf9-expressed enzyme) {ECO:0000269|PubMed:11956198};
CC Vmax=8 nmol/sec/mg enzyme with 2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-
CC glycerol (E.coli-expressed enzyme) {ECO:0000269|PubMed:11956198};
CC Vmax=14 nmol/sec/mg enzyme with anandamide (Sf9-expressed enzyme)
CC {ECO:0000269|PubMed:11956198};
CC Vmax=11 nmol/sec/mg enzyme with anandamide (E.coli-expressed enzyme)
CC {ECO:0000269|PubMed:11956198};
CC Note=kcat is 2 sec(-1) for (5Z,8Z,11Z,14Z)-eicosatetraenoate. kcat is
CC 2.1 sec(-1) for N-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-glycine. kcat is 2
CC sec(-1) for N-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-alanine. kcat is 2
CC sec(-1) for N-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-gamma-aminobutanoate
CC (PubMed:17493578). kcat is 0.18 sec(-1) for (5Z,8Z,11Z,14Z)-
CC eicosatetraenoate (PubMed:24282679). kcat is 1 sec(-1) for
CC (5Z,8Z,11Z,14Z)-eicosatetraenoate. kcat is 2.1 sec(-1) for (5S)-
CC hydroxy-(6E,8Z,11Z,14Z)-eicosatetraenoate. kcat is 1.5 sec(-1) for
CC (5S)-hydroperoxy-(6E,8Z,11Z,14Z)-eicosatetraenoate (PubMed:27145229).
CC kcat is 0.46 sec(-1) for (5Z,8Z,11Z,14Z)-eicosatetraenoate. kcat is
CC 0.31 sec(-1) for (8Z,11Z,14Z)-eicosatrienoate (PubMed:27435673).
CC {ECO:0000269|PubMed:17493578, ECO:0000269|PubMed:24282679,
CC ECO:0000269|PubMed:27145229, ECO:0000269|PubMed:27435673};
CC -!- PATHWAY: Lipid metabolism; hydroperoxy eicosatetraenoic acid
CC biosynthesis. {ECO:0000269|PubMed:10542053}.
CC -!- INTERACTION:
CC O15296; Q96NT0: CCDC115; NbExp=3; IntAct=EBI-12150557, EBI-2810325;
CC O15296; P78358: CTAG1B; NbExp=3; IntAct=EBI-12150557, EBI-1188472;
CC O15296; Q9H3M0: KCNF1; NbExp=3; IntAct=EBI-12150557, EBI-6918743;
CC O15296; P10276: RARA; NbExp=3; IntAct=EBI-12150557, EBI-413374;
CC O15296; Q9BWF2: TRAIP; NbExp=3; IntAct=EBI-12150557, EBI-1756205;
CC O15296; P19474: TRIM21; NbExp=3; IntAct=EBI-12150557, EBI-81290;
CC -!- SUBCELLULAR LOCATION: [Isoform A]: Nucleus
CC {ECO:0000269|PubMed:12704195}. Note=Other isoforms are excluded from
CC the nucleus. {ECO:0000269|PubMed:12704195}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:12704195}.
CC Cell membrane {ECO:0000269|PubMed:12704195,
CC ECO:0000269|PubMed:27435673}. Cytoplasm, cytoskeleton
CC {ECO:0000269|PubMed:12704195}. Membrane {ECO:0000269|PubMed:10542053,
CC ECO:0000269|PubMed:24497644}; Peripheral membrane protein
CC {ECO:0000269|PubMed:24497644}. Cell junction, adherens junction
CC {ECO:0000269|PubMed:12704195}. Cell junction, focal adhesion
CC {ECO:0000269|PubMed:12704195}. Note=Predominantly cytosolic; becomes
CC enriched at membranes upon calcium binding.
CC {ECO:0000269|PubMed:10542053, ECO:0000269|PubMed:12704195,
CC ECO:0000269|PubMed:24497644, ECO:0000269|PubMed:27435673}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=A; Synonyms=15-LOb1;
CC IsoId=O15296-1; Sequence=Displayed;
CC Name=B; Synonyms=15-LOX2sv-b;
CC IsoId=O15296-2; Sequence=VSP_003142, VSP_003143;
CC Name=C; Synonyms=15-LOX2sv-c;
CC IsoId=O15296-3; Sequence=VSP_003144, VSP_003145;
CC Name=D; Synonyms=15-LOX2sv-a, 15-LOb2;
CC IsoId=O15296-4; Sequence=VSP_003142;
CC -!- TISSUE SPECIFICITY: Expressed in hair, prostate, lung, ovary, lymph
CC node, spinal cord and cornea. {ECO:0000269|PubMed:10542053,
CC ECO:0000269|PubMed:11350124, ECO:0000269|PubMed:9177185}.
CC -!- INDUCTION: Up-regulated by UV-irradiation.
CC {ECO:0000269|PubMed:18755188}.
CC -!- DOMAIN: The PLAT domain can bind calcium ions; this promotes
CC association with membranes.
CC -!- SIMILARITY: Belongs to the lipoxygenase family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAD37786.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; U78294; AAB61706.1; -; mRNA.
DR EMBL; AJ305028; CAC34521.1; -; Genomic_DNA.
DR EMBL; AJ305029; CAC34521.1; JOINED; Genomic_DNA.
DR EMBL; AJ305030; CAC34521.1; JOINED; Genomic_DNA.
DR EMBL; AJ305031; CAC34521.1; JOINED; Genomic_DNA.
DR EMBL; AF468051; AAL76274.1; -; mRNA.
DR EMBL; AF468052; AAL76275.1; -; mRNA.
DR EMBL; AF468053; AAL76276.1; -; mRNA.
DR EMBL; AF468054; AAL76277.1; -; mRNA.
DR EMBL; AC129492; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471108; EAW90098.1; -; Genomic_DNA.
DR EMBL; CH471108; EAW90100.1; -; Genomic_DNA.
DR EMBL; BC035217; AAH35217.1; -; mRNA.
DR EMBL; BC063647; AAH63647.1; -; mRNA.
DR EMBL; AF149095; AAD37786.1; ALT_SEQ; Genomic_DNA.
DR CCDS; CCDS11128.1; -. [O15296-1]
DR CCDS; CCDS32558.1; -. [O15296-4]
DR CCDS; CCDS32559.1; -. [O15296-2]
DR RefSeq; NP_001034219.1; NM_001039130.1. [O15296-4]
DR RefSeq; NP_001034220.1; NM_001039131.1. [O15296-2]
DR RefSeq; NP_001132.2; NM_001141.2. [O15296-1]
DR PDB; 4NRE; X-ray; 2.63 A; A=1-676.
DR PDB; 7LAF; X-ray; 2.44 A; A/B=1-676.
DR PDBsum; 4NRE; -.
DR PDBsum; 7LAF; -.
DR AlphaFoldDB; O15296; -.
DR SMR; O15296; -.
DR BioGRID; 106748; 29.
DR IntAct; O15296; 11.
DR STRING; 9606.ENSP00000369530; -.
DR BindingDB; O15296; -.
DR ChEMBL; CHEMBL2457; -.
DR DrugCentral; O15296; -.
DR GuidetoPHARMACOLOGY; 1389; -.
DR SwissLipids; SLP:000000651; -.
DR SwissLipids; SLP:000001469; -. [O15296-1]
DR SwissLipids; SLP:000001470; -. [O15296-4]
DR iPTMnet; O15296; -.
DR PhosphoSitePlus; O15296; -.
DR BioMuta; ALOX15B; -.
DR EPD; O15296; -.
DR jPOST; O15296; -.
DR MassIVE; O15296; -.
DR PaxDb; 9606-ENSP00000369530; -.
DR PeptideAtlas; O15296; -.
DR ProteomicsDB; 48566; -. [O15296-1]
DR ProteomicsDB; 48567; -. [O15296-2]
DR ProteomicsDB; 48568; -. [O15296-3]
DR ProteomicsDB; 48569; -. [O15296-4]
DR Antibodypedia; 12373; 318 antibodies from 31 providers.
DR DNASU; 247; -.
DR Ensembl; ENST00000380173.6; ENSP00000369520.2; ENSG00000179593.16. [O15296-4]
DR Ensembl; ENST00000380183.9; ENSP00000369530.4; ENSG00000179593.16. [O15296-1]
DR Ensembl; ENST00000573359.1; ENSP00000460332.2; ENSG00000179593.16. [O15296-2]
DR GeneID; 247; -.
DR KEGG; hsa:247; -.
DR MANE-Select; ENST00000380183.9; ENSP00000369530.4; NM_001141.3; NP_001132.2.
DR UCSC; uc002gju.4; human. [O15296-1]
DR AGR; HGNC:434; -.
DR CTD; 247; -.
DR DisGeNET; 247; -.
DR GeneCards; ALOX15B; -.
DR HGNC; HGNC:434; ALOX15B.
DR HPA; ENSG00000179593; Tissue enhanced (breast, prostate).
DR MIM; 603697; gene.
DR neXtProt; NX_O15296; -.
DR OpenTargets; ENSG00000179593; -.
DR PharmGKB; PA24725; -.
DR VEuPathDB; HostDB:ENSG00000179593; -.
DR eggNOG; ENOG502QVKD; Eukaryota.
DR GeneTree; ENSGT00940000161510; -.
DR HOGENOM; CLU_004282_3_3_1; -.
DR InParanoid; O15296; -.
DR OMA; LHINMLA; -.
DR OrthoDB; 999249at2759; -.
DR PhylomeDB; O15296; -.
DR TreeFam; TF105320; -.
DR BRENDA; 1.13.11.33; 2681.
DR PathwayCommons; O15296; -.
DR Reactome; R-HSA-2142770; Synthesis of 15-eicosatetraenoic acid derivatives.
DR SABIO-RK; O15296; -.
DR SignaLink; O15296; -.
DR UniPathway; UPA00881; -.
DR BioGRID-ORCS; 247; 11 hits in 1142 CRISPR screens.
DR ChiTaRS; ALOX15B; human.
DR GeneWiki; ALOX15B; -.
DR GenomeRNAi; 247; -.
DR Pharos; O15296; Tchem.
DR PRO; PR:O15296; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; O15296; Protein.
DR Bgee; ENSG00000179593; Expressed in upper leg skin and 115 other cell types or tissues.
DR ExpressionAtlas; O15296; baseline and differential.
DR Genevisible; O15296; HS.
DR GO; GO:0005912; C:adherens junction; IDA:UniProtKB.
DR GO; GO:0005856; C:cytoskeleton; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005925; C:focal adhesion; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0050473; F:arachidonate 15-lipoxygenase activity; IDA:UniProtKB.
DR GO; GO:0036403; F:arachidonate 8(S)-lipoxygenase activity; IEA:Ensembl.
DR GO; GO:0005509; F:calcium ion binding; IDA:UniProtKB.
DR GO; GO:0005506; F:iron ion binding; IDA:UniProtKB.
DR GO; GO:0016165; F:linoleate 13S-lipoxygenase activity; IDA:UniProtKB.
DR GO; GO:1990136; F:linoleate 9S-lipoxygenase activity; IEA:Ensembl.
DR GO; GO:0008289; F:lipid binding; IEA:UniProtKB-KW.
DR GO; GO:0006915; P:apoptotic process; TAS:UniProtKB.
DR GO; GO:0019369; P:arachidonic acid metabolic process; IDA:UniProtKB.
DR GO; GO:1901696; P:cannabinoid biosynthetic process; IDA:UniProtKB.
DR GO; GO:0071926; P:endocannabinoid signaling pathway; IDA:UniProtKB.
DR GO; GO:0051122; P:hepoxilin biosynthetic process; ISS:UniProtKB.
DR GO; GO:0043651; P:linoleic acid metabolic process; IBA:GO_Central.
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; IDA:UniProtKB.
DR GO; GO:0019372; P:lipoxygenase pathway; IBA:GO_Central.
DR GO; GO:0045786; P:negative regulation of cell cycle; IDA:UniProtKB.
DR GO; GO:0030336; P:negative regulation of cell migration; TAS:UniProtKB.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IDA:UniProtKB.
DR GO; GO:0045926; P:negative regulation of growth; IDA:UniProtKB.
DR GO; GO:0006644; P:phospholipid metabolic process; IDA:UniProtKB.
DR GO; GO:0032722; P:positive regulation of chemokine production; IMP:UniProtKB.
DR GO; GO:0045618; P:positive regulation of keratinocyte differentiation; IEA:Ensembl.
DR GO; GO:0010744; P:positive regulation of macrophage derived foam cell differentiation; IMP:UniProtKB.
DR GO; GO:0035360; P:positive regulation of peroxisome proliferator activated receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0030850; P:prostate gland development; NAS:UniProtKB.
DR GO; GO:0030856; P:regulation of epithelial cell differentiation; NAS: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:SF161; POLYUNSATURATED FATTY ACID LIPOXYGENASE ALOX15B; 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.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Calcium; Cell junction; Cell membrane;
KW Cytoplasm; Cytoskeleton; Dioxygenase; Iron; Lipid metabolism;
KW Lipid-binding; Membrane; Metal-binding; Nucleus; Oxidoreductase;
KW Reference proteome.
FT CHAIN 1..676
FT /note="Polyunsaturated fatty acid lipoxygenase ALOX15B"
FT /id="PRO_0000220700"
FT DOMAIN 2..124
FT /note="PLAT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00152"
FT DOMAIN 125..676
FT /note="Lipoxygenase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00726"
FT BINDING 15
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:24497644"
FT BINDING 17
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:24497644"
FT BINDING 39
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:24497644"
FT BINDING 40
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:24497644"
FT BINDING 42
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:24497644"
FT BINDING 44
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:24497644"
FT BINDING 85
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:24497644"
FT BINDING 86
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:24497644"
FT BINDING 373
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:24497644"
FT BINDING 378
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:24497644"
FT BINDING 553
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:24497644"
FT BINDING 676
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:24497644"
FT VAR_SEQ 401..429
FT /note="Missing (in isoform B and isoform D)"
FT /evidence="ECO:0000303|PubMed:11839751"
FT /id="VSP_003142"
FT VAR_SEQ 483..527
FT /note="Missing (in isoform B)"
FT /evidence="ECO:0000303|PubMed:11839751"
FT /id="VSP_003143"
FT VAR_SEQ 561..617
FT /note="FDSCAWMPNLPPSMQLPPPTSKGLATCEGFIATLPPVNATCDVILALWLLSK
FT EPGDQ -> VRKGQRPRWQAGGDPAPQPHSALSAFSLTPVLGCPTCHPACSCHHPPPKA
FT WQHARAS (in isoform C)"
FT /evidence="ECO:0000303|PubMed:11839751"
FT /id="VSP_003144"
FT VAR_SEQ 618..676
FT /note="Missing (in isoform C)"
FT /evidence="ECO:0000303|PubMed:11839751"
FT /id="VSP_003145"
FT VARIANT 416
FT /note="A -> D (loss of 15-lipoxygenase activity;
FT dbSNP:rs140152561)"
FT /evidence="ECO:0000269|PubMed:24282679"
FT /id="VAR_083544"
FT VARIANT 486
FT /note="R -> H (does not affect arachidonate 15-lipoxygenase
FT activity; does not impact enzyme structure;
FT dbSNP:rs9895916)"
FT /evidence="ECO:0000269|PubMed:11839751,
FT ECO:0000269|PubMed:24282679"
FT /id="VAR_061334"
FT VARIANT 656
FT /note="Q -> R (does not affect arachidonate 15-lipoxygenase
FT activity; does not impact enzyme structure;
FT dbSNP:rs4792147)"
FT /evidence="ECO:0000269|PubMed:11350124,
FT ECO:0000269|PubMed:11839751, ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:24282679, ECO:0000269|PubMed:9177185"
FT /id="VAR_024524"
FT VARIANT 676
FT /note="I -> V (does not affect arachidonate 15-lipoxygenase
FT activity; destabilizes the enzyme structure;
FT dbSNP:rs7225107)"
FT /evidence="ECO:0000269|PubMed:24282679"
FT /id="VAR_024525"
FT MUTAGEN 39
FT /note="D->A: Abolishes calcium-dependent association with
FT membranes; when associated with A-44 and A-85."
FT /evidence="ECO:0000269|PubMed:24497644"
FT MUTAGEN 44
FT /note="E->A: Abolishes calcium-dependent association with
FT membranes; when associated with A-39 and A-85."
FT /evidence="ECO:0000269|PubMed:24497644"
FT MUTAGEN 85
FT /note="D->A: Abolishes calcium-dependent association with
FT membranes; when associated with A-39 and A-44."
FT /evidence="ECO:0000269|PubMed:24497644"
FT MUTAGEN 602
FT /note="D->Y: No effect on the stereoselectivity of the
FT oxygenation reaction. Completely changes the
FT stereoselectivity of the oxygenation reaction to produce
FT (8S)-HPETE instead of (15S)-HPETE; when associated with H-
FT 603."
FT /evidence="ECO:0000269|PubMed:10625675"
FT MUTAGEN 603
FT /note="V->H: Changes the stereoselectivity of the
FT oxygenation reaction. Completely changes the
FT stereoselectivity of the oxygenation reaction to produce
FT (8S)-HPETE instead of (15S)-HPETE; when associated with Y-
FT 602."
FT /evidence="ECO:0000269|PubMed:10625675"
FT CONFLICT 271
FT /note="V -> L (in Ref. 1; AAB61706 and 2; CAC34521)"
FT /evidence="ECO:0000305"
FT CONFLICT 338
FT /note="G -> C (in Ref. 6; AAD37786)"
FT /evidence="ECO:0000305"
FT STRAND 2..10
FT /evidence="ECO:0007829|PDB:7LAF"
FT STRAND 22..28
FT /evidence="ECO:0007829|PDB:7LAF"
FT STRAND 50..59
FT /evidence="ECO:0007829|PDB:7LAF"
FT STRAND 63..71
FT /evidence="ECO:0007829|PDB:7LAF"
FT TURN 77..79
FT /evidence="ECO:0007829|PDB:4NRE"
FT STRAND 86..95
FT /evidence="ECO:0007829|PDB:7LAF"
FT STRAND 97..99
FT /evidence="ECO:0007829|PDB:7LAF"
FT STRAND 102..113
FT /evidence="ECO:0007829|PDB:7LAF"
FT STRAND 115..119
FT /evidence="ECO:0007829|PDB:7LAF"
FT TURN 126..128
FT /evidence="ECO:0007829|PDB:7LAF"
FT HELIX 132..148
FT /evidence="ECO:0007829|PDB:7LAF"
FT STRAND 161..163
FT /evidence="ECO:0007829|PDB:4NRE"
FT HELIX 167..169
FT /evidence="ECO:0007829|PDB:7LAF"
FT TURN 172..174
FT /evidence="ECO:0007829|PDB:7LAF"
FT HELIX 178..198
FT /evidence="ECO:0007829|PDB:7LAF"
FT TURN 199..202
FT /evidence="ECO:0007829|PDB:7LAF"
FT HELIX 212..215
FT /evidence="ECO:0007829|PDB:7LAF"
FT HELIX 216..219
FT /evidence="ECO:0007829|PDB:7LAF"
FT HELIX 223..230
FT /evidence="ECO:0007829|PDB:7LAF"
FT TURN 231..233
FT /evidence="ECO:0007829|PDB:7LAF"
FT HELIX 235..244
FT /evidence="ECO:0007829|PDB:7LAF"
FT HELIX 265..272
FT /evidence="ECO:0007829|PDB:7LAF"
FT HELIX 278..283
FT /evidence="ECO:0007829|PDB:7LAF"
FT STRAND 287..291
FT /evidence="ECO:0007829|PDB:7LAF"
FT HELIX 293..295
FT /evidence="ECO:0007829|PDB:7LAF"
FT STRAND 314..319
FT /evidence="ECO:0007829|PDB:7LAF"
FT TURN 321..323
FT /evidence="ECO:0007829|PDB:7LAF"
FT STRAND 326..332
FT /evidence="ECO:0007829|PDB:7LAF"
FT STRAND 334..336
FT /evidence="ECO:0007829|PDB:7LAF"
FT HELIX 350..370
FT /evidence="ECO:0007829|PDB:7LAF"
FT HELIX 371..378
FT /evidence="ECO:0007829|PDB:7LAF"
FT HELIX 379..391
FT /evidence="ECO:0007829|PDB:7LAF"
FT HELIX 397..402
FT /evidence="ECO:0007829|PDB:7LAF"
FT HELIX 403..406
FT /evidence="ECO:0007829|PDB:7LAF"
FT HELIX 409..419
FT /evidence="ECO:0007829|PDB:7LAF"
FT HELIX 426..430
FT /evidence="ECO:0007829|PDB:7LAF"
FT HELIX 434..448
FT /evidence="ECO:0007829|PDB:7LAF"
FT HELIX 451..453
FT /evidence="ECO:0007829|PDB:7LAF"
FT HELIX 456..462
FT /evidence="ECO:0007829|PDB:7LAF"
FT HELIX 472..495
FT /evidence="ECO:0007829|PDB:7LAF"
FT HELIX 499..504
FT /evidence="ECO:0007829|PDB:7LAF"
FT HELIX 506..518
FT /evidence="ECO:0007829|PDB:7LAF"
FT TURN 519..522
FT /evidence="ECO:0007829|PDB:7LAF"
FT HELIX 524..526
FT /evidence="ECO:0007829|PDB:7LAF"
FT HELIX 535..549
FT /evidence="ECO:0007829|PDB:7LAF"
FT HELIX 551..557
FT /evidence="ECO:0007829|PDB:7LAF"
FT HELIX 560..564
FT /evidence="ECO:0007829|PDB:7LAF"
FT TURN 567..569
FT /evidence="ECO:0007829|PDB:7LAF"
FT STRAND 574..576
FT /evidence="ECO:0007829|PDB:7LAF"
FT STRAND 580..583
FT /evidence="ECO:0007829|PDB:4NRE"
FT HELIX 587..593
FT /evidence="ECO:0007829|PDB:7LAF"
FT HELIX 597..610
FT /evidence="ECO:0007829|PDB:7LAF"
FT HELIX 631..655
FT /evidence="ECO:0007829|PDB:7LAF"
FT HELIX 667..669
FT /evidence="ECO:0007829|PDB:7LAF"
FT STRAND 670..673
FT /evidence="ECO:0007829|PDB:7LAF"
SQ SEQUENCE 676 AA; 75857 MW; 4F641DF2F9D492C6 CRC64;
MAEFRVRVST GEAFGAGTWD KVSVSIVGTR GESPPLPLDN LGKEFTAGAE EDFQVTLPED
VGRVLLLRVH KAPPVLPLLG PLAPDAWFCR WFQLTPPRGG HLLFPCYQWL EGAGTLVLQE
GTAKVSWADH HPVLQQQRQE ELQARQEMYQ WKAYNPGWPH CLDEKTVEDL ELNIKYSTAK
NANFYLQAGS AFAEMKIKGL LDRKGLWRSL NEMKRIFNFR RTPAAEHAFE HWQEDAFFAS
QFLNGLNPVL IRRCHYLPKN FPVTDAMVAS VLGPGTSLQA ELEKGSLFLV DHGILSGIQT
NVINGKPQFS AAPMTLLYQS PGCGPLLPLA IQLSQTPGPN SPIFLPTDDK WDWLLAKTWV
RNAEFSFHEA LTHLLHSHLL PEVFTLATLR QLPHCHPLFK LLIPHTRYTL HINTLARELL
IVPGQVVDRS TGIGIEGFSE LIQRNMKQLN YSLLCLPEDI RTRGVEDIPG YYYRDDGMQI
WGAVERFVSE IIGIYYPSDE SVQDDRELQA WVREIFSKGF LNQESSGIPS SLETREALVQ
YVTMVIFTCS AKHAAVSAGQ FDSCAWMPNL PPSMQLPPPT SKGLATCEGF IATLPPVNAT
CDVILALWLL SKEPGDQRPL GTYPDEHFTE EAPRRSIATF QSRLAQISRG IQERNQGLVL
PYTYLDPPLI ENSVSI
//
