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; Evidence={ECO:0000255|PROSITE- CC ProRule:PRU00726, 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 CC (Sf9-expressed enzyme) {ECO:0000269|PubMed:11956198}; CC KM=8 uM for 2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-glycerol CC (E.coli-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 CC 2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-glycerol (Sf9-expressed enzyme) CC {ECO:0000269|PubMed:11956198}; CC Vmax=8 nmol/sec/mg enzyme with CC 2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-glycerol (E.coli-expressed enzyme) CC {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 CC (5Z,8Z,11Z,14Z)-eicosatetraenoate (PubMed:24282679). kcat is 1 CC sec(-1) for (5Z,8Z,11Z,14Z)-eicosatetraenoate. kcat is 2.1 sec(-1) CC for (5S)-hydroxy-(6E,8Z,11Z,14Z)-eicosatetraenoate. kcat is 1.5 CC sec(-1) for (5S)-hydroperoxy-(6E,8Z,11Z,14Z)-eicosatetraenoate CC (PubMed:27145229). kcat is 0.46 sec(-1) for CC (5Z,8Z,11Z,14Z)-eicosatetraenoate. kcat is 0.31 sec(-1) for CC (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}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; 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 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. DR Genevisible; O15296; HS. 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 FT H-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 FT Y-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 //