ID LOX5_MOUSE Reviewed; 674 AA. AC P48999; Q3TB75; DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot. DT 27-JUL-2011, sequence version 3. DT 27-MAR-2024, entry version 179. DE RecName: Full=Polyunsaturated fatty acid 5-lipoxygenase {ECO:0000305}; DE EC=1.13.11.- {ECO:0000250|UniProtKB:P09917}; DE AltName: Full=Arachidonate 5-lipoxygenase; DE Short=5-LO {ECO:0000250|UniProtKB:P09917}; DE Short=5-lipoxygenase {ECO:0000303|PubMed:7629107}; DE EC=1.13.11.34 {ECO:0000269|PubMed:31642348}; GN Name=Alox5 {ECO:0000312|MGI:MGI:87999}; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS RP OF VAL-672. RC STRAIN=C57BL/6 X 129/Sv; TISSUE=Peritoneal cavity; RX PubMed=7629107; DOI=10.1074/jbc.270.30.17993; RA Chen X.-S., Naumann T.A., Kurre U., Jenkins N.A., Copeland N.G., Funk C.D.; RT "cDNA cloning, expression, mutagenesis, intracellular localization, and RT gene chromosomal assignment of mouse 5-lipoxygenase."; RL J. Biol. Chem. 270:17993-17999(1995). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=C57BL/6J; TISSUE=Bone; RX PubMed=16141072; DOI=10.1126/science.1112014; RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J., RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.; RT "The transcriptional landscape of the mammalian genome."; RL Science 309:1559-1563(2005). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Testis; 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 [4] RP DISRUPTION PHENOTYPE, AND FUNCTION. RX PubMed=7809134; DOI=10.1073/pnas.91.26.12852; RA Goulet J.L., Snouwaert J.N., Latour A.M., Coffman T.M., Koller B.H.; RT "Altered inflammatory responses in leukotriene-deficient mice."; RL Proc. Natl. Acad. Sci. U.S.A. 91:12852-12856(1994). RN [5] RP DISRUPTION PHENOTYPE, AND FUNCTION. RX PubMed=7969451; DOI=10.1038/372179a0; RA Chen X.S., Sheller J.R., Johnson E.N., Funk C.D.; RT "Role of leukotrienes revealed by targeted disruption of the 5-lipoxygenase RT gene."; RL Nature 372:179-182(1994). RN [6] RP TISSUE SPECIFICITY, AND FUNCTION. RX PubMed=17392829; DOI=10.1038/sj.jid.5700796; RA Doepping S., Funk C.D., Habenicht A.J., Spanbroek R.; RT "Selective 5-lipoxygenase expression in Langerhans cells and impaired RT dendritic cell migration in 5-LO-deficient mice reveal leukotriene action RT in skin."; RL J. Invest. Dermatol. 127:1692-1700(2007). RN [7] RP FUNCTION. RX PubMed=18421434; DOI=10.1007/s00125-008-1002-3; RA Mehrabian M., Schulthess F.T., Nebohacova M., Castellani L.W., Zhou Z., RA Hartiala J., Oberholzer J., Lusis A.J., Maedler K., Allayee H.; RT "Identification of ALOX5 as a gene regulating adiposity and pancreatic RT function."; RL Diabetologia 51:978-988(2008). RN [8] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Lung; RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001; RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R., RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.; RT "A tissue-specific atlas of mouse protein phosphorylation and expression."; RL Cell 143:1174-1189(2010). RN [9] RP FUNCTION. RX PubMed=21224059; DOI=10.1016/j.ajpath.2010.11.033; RA Nagashima T., Ichimiya S., Kikuchi T., Saito Y., Matsumiya H., Ara S., RA Koshiba S., Zhang J., Hatate C., Tonooka A., Kubo T., Ye R.C., Hirose B., RA Shirasaki H., Izumi T., Takami T., Himi T., Sato N.; RT "Arachidonate 5-lipoxygenase establishes adaptive humoral immunity by RT controlling primary B cells and their cognate T-cell help."; RL Am. J. Pathol. 178:222-232(2011). RN [10] RP TISSUE SPECIFICITY, AND FUNCTION. RX PubMed=21307302; DOI=10.1126/scitranslmed.3001571; RA Sapieha P., Stahl A., Chen J., Seaward M.R., Willett K.L., Krah N.M., RA Dennison R.J., Connor K.M., Aderman C.M., Liclican E., Carughi A., RA Perelman D., Kanaoka Y., Sangiovanni J.P., Gronert K., Smith L.E.; RT "5-Lipoxygenase metabolite 4-HDHA is a mediator of the antiangiogenic RT effect of omega-3 polyunsaturated fatty acids."; RL Sci. Transl. Med. 3:69RA12-69RA12(2011). RN [11] RP CATALYTIC ACTIVITY, FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, AND RP MUTAGENESIS OF PHE-360; ALA-411; ALA-425; ASN-426 AND ALA-604. RX PubMed=23246375; DOI=10.1016/j.abb.2012.11.015; RA Hofheinz K., Kakularam K.R., Adel S., Anton M., Polymarasetty A., RA Reddanna P., Kuhn H., Horn T.; RT "Conversion of pro-inflammatory murine Alox5 into an anti-inflammatory 15S- RT lipoxygenating enzyme by multiple mutations of sequence determinants."; RL Arch. Biochem. Biophys. 530:40-47(2013). RN [12] RP FUNCTION, AND INDUCTION. RX PubMed=23720274; DOI=10.1093/cvr/cvt135; RA Lee S.J., Choi E.K., Seo K.W., Bae J.U., Kim Y.H., Park S.Y., Oh S.O., RA Kim C.D.; RT "5-Lipoxygenase plays a pivotal role in endothelial adhesion of monocytes RT via an increased expression of Mac-1."; RL Cardiovasc. Res. 99:724-733(2013). RN [13] RP FUNCTION. RX PubMed=24906289; DOI=10.1007/s00441-014-1920-y; RA Wu Y., Sun H., Song F., Huang C., Wang J.; RT "Deletion of Alox5 gene decreases osteogenic differentiation but increases RT adipogenic differentiation of mouse induced pluripotent stem cells."; RL Cell Tissue Res. 358:135-147(2014). RN [14] RP FUNCTION. RX PubMed=24226420; DOI=10.1038/jid.2013.493; RA Brogliato A.R., Moor A.N., Kesl S.L., Guilherme R.F., Georgii J.L., RA Peters-Golden M., Canetti C., Gould L.J., Benjamim C.F.; RT "Critical role of 5-lipoxygenase and heme oxygenase-1 in wound healing."; RL J. Invest. Dermatol. 134:1436-1445(2014). RN [15] RP FUNCTION. RX PubMed=28694473; DOI=10.1038/s41598-017-05346-5; RA Kwak H.J., Choi H.E., Cheon H.G.; RT "5-LO inhibition ameliorates palmitic acid-induced ER stress, oxidative RT stress and insulin resistance via AMPK activation in murine myotubes."; RL Sci. Rep. 7:5025-5025(2017). RN [16] RP FUNCTION. RX PubMed=28965882; DOI=10.1016/j.clim.2017.08.022; RA Guimaraes F.R., Sales-Campos H., Nardini V., da Costa T.A., Fonseca M.T.C., RA Junior V.R., Sorgi C.A., da Silva J.S., Chica J.E.L., Faccioli L.H., RA de Barros Cardoso C.R.; RT "The inhibition of 5-Lipoxygenase (5-LO) products leukotriene B4 (LTB4) and RT cysteinyl leukotrienes (cysLTs) modulates the inflammatory response and RT improves cutaneous wound healing."; RL Clin. Immunol. 190:74-83(2018). RN [17] RP MUTAGENESIS OF PHE-360; ALA-425 AND ASN-426, CATALYTIC ACTIVITY, AND RP FUNCTION. RX PubMed=31642348; DOI=10.1089/ars.2019.7751; RA Marbach-Breitrueck E., Kutzner L., Rothe M., Gurke R., Schreiber Y., RA Reddanna P., Schebb N.H., Stehling S., Wieler L.H., Heydeck D., Kuhn H.; RT "Functional Characterization of Knock-In Mice Expressing a 12/15- RT Lipoxygenating Alox5 Mutant Instead of the 5-Lipoxygenating Wild-Type RT Enzyme."; RL Antioxid. Redox Signal. 32:1-17(2020). CC -!- FUNCTION: Catalyzes the oxygenation of arachidonate to 5- CC hydroperoxyeicosatetraenoate (5-HPETE) followed by the dehydration to CC 5,6- epoxyeicosatetraenoate (Leukotriene A4/LTA4), the first two steps CC in the biosynthesis of leukotrienes, which are potent mediators of CC inflammation (PubMed:7629107, PubMed:7809134, PubMed:7969451, CC PubMed:23246375, PubMed:31642348). Also catalyzes the oxygenation of CC arachidonic acid into 8-hydroperoxyicosatetraenoic acid (8-HPETE) and CC 12-hydroperoxyicosatetraenoic acid (12-HPETE) (PubMed:23246375). CC Displays lipoxin synthase activity being able to convert (15S)-HETE CC into a conjugate tetraene (By similarity). Although arachidonate is the CC preferred substrate, this enzyme can also metabolize oxidized fatty CC acids derived from arachidonate such as (15S)-HETE, eicosapentaenoate CC (EPA) such as (18R)- and (18S)-HEPE or docosahexaenoate (DHA) which CC lead to the formation of specialized pro-resolving mediators (SPM) CC lipoxin and resolvins E and D respectively, therefore it participates CC in anti-inflammatory responses (PubMed:31642348). Oxidation of DHA CC directly inhibits endothelial cell proliferation and sprouting CC angiogenesis via peroxisome proliferator-activated receptor gamma CC (PPARgamma)(PubMed:21307302). It does not catalyze the oxygenation of CC linoleic acid and does not convert (5S)-HETE to lipoxin isomers CC (PubMed:31642348). In addition to inflammatory processes, participates CC in dendritic cell migration, wound healing through an antioxidant CC mechanism based on heme oxygenase-1 (HO-1) regulation expression, CC monocyte adhesion to the endothelium via ITGAM expression on monocytes CC (PubMed:24226420, PubMed:23720274, PubMed:17392829, PubMed:28965882). CC Moreover, it helps establish an adaptive humoral immunity by regulating CC primary resting B cells and follicular helper T cells and participates CC in the CD40-induced production of reactive oxygen species (ROS) after CC CD40 ligation in B cells through interaction with PIK3R1 that bridges CC ALOX5 with CD40 (PubMed:21224059). May also play a role in glucose CC homeostasis, regulation of insulin secretion and palmitic acid-induced CC insulin resistance via AMPK (PubMed:28694473, PubMed:18421434). Can CC regulate bone mineralization and fat cell differentiation increases in CC induced pluripotent stem cells (PubMed:24906289). CC {ECO:0000250|UniProtKB:P09917, ECO:0000269|PubMed:17392829, CC ECO:0000269|PubMed:18421434, ECO:0000269|PubMed:21224059, CC ECO:0000269|PubMed:21307302, ECO:0000269|PubMed:23246375, CC ECO:0000269|PubMed:23720274, ECO:0000269|PubMed:24226420, CC ECO:0000269|PubMed:24906289, ECO:0000269|PubMed:28694473, CC ECO:0000269|PubMed:28965882, ECO:0000269|PubMed:31642348, CC ECO:0000269|PubMed:7629107, ECO:0000269|PubMed:7809134, CC ECO:0000269|PubMed:7969451}. CC -!- CATALYTIC ACTIVITY: CC Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 = (5S)-hydroperoxy- CC (6E,8Z,11Z,14Z)-eicosatetraenoate; Xref=Rhea:RHEA:17485, CC ChEBI:CHEBI:15379, ChEBI:CHEBI:32395, ChEBI:CHEBI:57450; CC Evidence={ECO:0000269|PubMed:23246375, ECO:0000269|PubMed:31642348}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17486; CC Evidence={ECO:0000269|PubMed:31642348}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 = H2O + leukotriene A4; CC Xref=Rhea:RHEA:32307, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, CC ChEBI:CHEBI:32395, ChEBI:CHEBI:57463; EC=1.13.11.34; CC Evidence={ECO:0000269|PubMed:31642348}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:32308; CC Evidence={ECO:0000269|PubMed:31642348}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 = (8S)-hydroperoxy- CC (5Z,9E,11Z,14Z)-eicosatetraenoate; Xref=Rhea:RHEA:38675, CC ChEBI:CHEBI:15379, ChEBI:CHEBI:32395, ChEBI:CHEBI:75322; CC Evidence={ECO:0000269|PubMed:23246375}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38676; CC Evidence={ECO:0000305|PubMed:23246375}; 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 Evidence={ECO:0000269|PubMed:23246375}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:10429; CC Evidence={ECO:0000305|PubMed:23246375}; CC -!- CATALYTIC ACTIVITY: CC Reaction=18-HEPE + O2 = (5S)-hydroperoxy-18-hydroxy- CC (7E,9E,11Z,14Z,16E)-eicosapentaenoate; Xref=Rhea:RHEA:48860, CC ChEBI:CHEBI:15379, ChEBI:CHEBI:90825, ChEBI:CHEBI:90826; CC Evidence={ECO:0000250|UniProtKB:P09917}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48861; CC Evidence={ECO:0000250|UniProtKB:P09917}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(18R)-hydroxy-(5Z,8Z,11Z,14Z,16E)-eicosapentaenoate + O2 = CC (5S)-hydroperoxy-(18R)-hydroxy-(6E,8Z,11Z,14Z,16E)-eicosapentaenoate; CC Xref=Rhea:RHEA:51968, ChEBI:CHEBI:15379, ChEBI:CHEBI:90818, CC ChEBI:CHEBI:132218; Evidence={ECO:0000250|UniProtKB:P09917}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:51969; CC Evidence={ECO:0000250|UniProtKB:P09917}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(18S)-hydroxy-(5Z,8Z,11Z,14Z,16E)-eicosapentaenoate + O2 = CC (5S)-hydroperoxy-(18S)-hydroxy-(6E,8Z,11Z,14Z,16E)-eicosapentaenoate; CC Xref=Rhea:RHEA:50204, ChEBI:CHEBI:15379, ChEBI:CHEBI:132083, CC ChEBI:CHEBI:132091; Evidence={ECO:0000250|UniProtKB:P09917}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50205; CC Evidence={ECO:0000250|UniProtKB:P09917}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(5S)-hydroperoxy-(18S)-hydroxy-(6E,8Z,11Z,14Z,16E)- CC eicosapentaenoate = (5S,6S)-epoxy-(18S)-hydroxy-(7E,9E,11Z,14Z,16E)- CC eicosapentaenoate + H2O; Xref=Rhea:RHEA:39107, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:132091, ChEBI:CHEBI:134661; CC Evidence={ECO:0000250|UniProtKB:P09917}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39108; CC Evidence={ECO:0000250|UniProtKB:P09917}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(5S)-hydroperoxy-(18R)-hydroxy-(6E,8Z,11Z,14Z,16E)- CC eicosapentaenoate = (5S,6S)-epoxy-(18R)-hydroxy-(7E,9E,11Z,14Z,16E)- CC eicosapentaenoate + H2O; Xref=Rhea:RHEA:50268, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:132218, ChEBI:CHEBI:132219; CC Evidence={ECO:0000250|UniProtKB:P09917}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50269; CC Evidence={ECO:0000250|UniProtKB:P09917}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(5S)-hydroperoxy-18-hydroxy-(7E,9E,11Z,14Z,16E)- CC eicosapentaenoate = (5S,6S)-epoxy-18-hydroxy-(7E,9E,11Z,14Z,16E)- CC eicosapentaenoate + H2O; Xref=Rhea:RHEA:50844, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:90826, ChEBI:CHEBI:133812; CC Evidence={ECO:0000250|UniProtKB:P09917}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50845; CC Evidence={ECO:0000250|UniProtKB:P09917}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(15S)-hydroxy-(5Z,8Z,11Z,13E)-eicosatetraenoate + O2 = (5S)- CC hydroperoxy-(15S)-hydroxy-(6E,8Z,11Z,13E)-eicosatetraenoate; CC Xref=Rhea:RHEA:48624, ChEBI:CHEBI:15379, ChEBI:CHEBI:57409, CC ChEBI:CHEBI:131564; Evidence={ECO:0000250|UniProtKB:P09917}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48625; CC Evidence={ECO:0000250|UniProtKB:P09917}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(5S)-hydroperoxy-(6E,8Z,11Z,14Z)-eicosatetraenoate = H2O + CC leukotriene A4; Xref=Rhea:RHEA:17961, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:57450, ChEBI:CHEBI:57463; CC Evidence={ECO:0000250|UniProtKB:P09917}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17962; CC Evidence={ECO:0000250|UniProtKB:P09917}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(5Z,8Z)-eicosadienoate + O2 = (5S)-hydroperoxy-(6E,8Z)- CC eicosadienoate; Xref=Rhea:RHEA:62644, ChEBI:CHEBI:15379, CC ChEBI:CHEBI:145835, ChEBI:CHEBI:145836; CC Evidence={ECO:0000250|UniProtKB:P09917}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(12S)-hydroxy-(5Z,8Z,10E,14Z)-eicosatetraenoate + O2 = (5S)- CC hydroperoxy-(12S)-hydroxy-(6E,8Z,10E,14Z)-eicosatetraenoate; CC Xref=Rhea:RHEA:62648, ChEBI:CHEBI:15379, ChEBI:CHEBI:90680, CC ChEBI:CHEBI:145837; Evidence={ECO:0000250|UniProtKB:P09917}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(5Z,8Z,11Z,14Z,17Z)-eicosapentaenoate + O2 = 5-hydroperoxy- CC (6E,8Z,11Z,14Z,17Z)-eicosapentaenoate; Xref=Rhea:RHEA:62600, CC ChEBI:CHEBI:15379, ChEBI:CHEBI:58562, ChEBI:CHEBI:145815; CC Evidence={ECO:0000250|UniProtKB:P09917}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62601; CC Evidence={ECO:0000250|UniProtKB:P09917}; 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:P09917}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41333; CC Evidence={ECO:0000250|UniProtKB:P09917}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate + O2 = (7S)- CC hydroperoxy-(4Z,8E,10Z,13Z,16Z,19Z)-docosahexaenoate; CC Xref=Rhea:RHEA:64668, ChEBI:CHEBI:15379, ChEBI:CHEBI:77016, CC ChEBI:CHEBI:156049; Evidence={ECO:0000250|UniProtKB:P09917}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64669; CC Evidence={ECO:0000250|UniProtKB:P09917}; 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:P09917}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50841; CC Evidence={ECO:0000250|UniProtKB:P09917}; CC -!- COFACTOR: CC Name=Fe cation; Xref=ChEBI:CHEBI:24875; CC Evidence={ECO:0000250|UniProtKB:P09917, ECO:0000255|PROSITE- CC ProRule:PRU00726}; CC Note=Binds 1 Fe cation per subunit. {ECO:0000250|UniProtKB:P09917, CC ECO:0000255|PROSITE-ProRule:PRU00726}; CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=44.7 uM for arachidonic acid {ECO:0000269|PubMed:23246375}; CC -!- PATHWAY: Lipid metabolism; leukotriene A4 biosynthesis. CC {ECO:0000269|PubMed:31642348}. CC -!- SUBUNIT: Homodimer. Interacts with ALOX5AP and LTC4S. Interacts with CC COTL1, the interaction is required for stability and efficient CC catalytic activity. Interacts with PIK3R1; this interaction bridges CC ALOX5 with CD40 after CD40 ligation in B cells and leads to the CC production of reactive oxygen species (ROS). Interacts (via PLAT CC domain) with DICER1 (via Dicer dsRNA-binding fold domain); this CC interaction enhances arachidonate 5-lipoxygenase activity and modifies CC the miRNA precursor processing activity of DICER1. CC {ECO:0000250|UniProtKB:P09917}. CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P09917, CC ECO:0000255|PROSITE-ProRule:PRU00726, ECO:0000269|PubMed:7629107}. CC Nucleus matrix {ECO:0000269|PubMed:7629107}. Nucleus membrane CC {ECO:0000250|UniProtKB:P09917}; Peripheral membrane protein CC {ECO:0000250|UniProtKB:P09917}. Cytoplasm, perinuclear region CC {ECO:0000250|UniProtKB:P09917}. Cytoplasm, cytosol CC {ECO:0000250|UniProtKB:P09917}. Nucleus envelope CC {ECO:0000250|UniProtKB:P09917}. Nucleus intermembrane space CC {ECO:0000250|UniProtKB:P09917}. Note=Shuttles between cytoplasm and CC nucleus. Found exclusively in the nucleus, when phosphorylated on Ser- CC 272. Calcium binding promotes translocation from the cytosol and the CC nuclear matrix to the nuclear envelope and membrane association. CC {ECO:0000250|UniProtKB:P09917}. CC -!- TISSUE SPECIFICITY: Expressed in skin Langerhans cells and their CC emigrated counterparts in draining lymph nodes (PubMed:17392829). CC Highly expressed in circulating leukocytes (PubMed:21307302). CC {ECO:0000269|PubMed:17392829, ECO:0000269|PubMed:21307302}. CC -!- INDUCTION: IncreaseD by both NF-kappa-B and SP1 in LPS-treated CC monocytes. {ECO:0000269|PubMed:23720274}. CC -!- PTM: Serine phosphorylation by MAPKAPK2 is stimulated by arachidonic CC acid. Phosphorylation on Ser-524 by PKA has an inhibitory effect. CC Phosphorylation on Ser-272 prevents export from the nucleus. CC Phosphorylation at Ser-524 is stimulated by 8-bromo-3',5'-cyclic AMP or CC prostaglandin E2. {ECO:0000250|UniProtKB:P09917}. CC -!- DISRUPTION PHENOTYPE: Homozygous mice for ALOX5 are also present in the CC expected ratios. Mice are indistinguishable in growth and size from CC wild type littermates (PubMed:7809134). Homozygous mice for ALOX5 show CC no apparent abnormalities up to ten months of age under normal CC physiological conditions, except that the spleen is usually smaller for CC 8-week-old mice (PubMed:7969451). {ECO:0000269|PubMed:7809134, CC ECO:0000269|PubMed:7969451}. CC -!- MISCELLANEOUS: Can be converted from pro-inflammatory 5-lipoxygenase to CC anti-inflammatory 15-lipoxygenase by reducing the volume of the CC substrate-binding pocket. {ECO:0000269|PubMed:23246375}. CC -!- SIMILARITY: Belongs to the lipoxygenase family. {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; L42198; AAC37673.1; -; mRNA. DR EMBL; AK137481; BAE23373.1; -; mRNA. DR EMBL; AK171413; BAE42439.1; -; mRNA. DR EMBL; BC139102; AAI39103.1; -; mRNA. DR EMBL; BC141213; AAI41214.1; -; mRNA. DR CCDS; CCDS20452.1; -. DR PIR; I49479; I49479. DR RefSeq; NP_033792.1; NM_009662.2. DR AlphaFoldDB; P48999; -. DR SMR; P48999; -. DR BioGRID; 198076; 4. DR STRING; 10090.ENSMUSP00000026795; -. DR BindingDB; P48999; -. DR ChEMBL; CHEMBL5211; -. DR DrugCentral; P48999; -. DR iPTMnet; P48999; -. DR PhosphoSitePlus; P48999; -. DR MaxQB; P48999; -. DR PaxDb; 10090-ENSMUSP00000026795; -. DR PeptideAtlas; P48999; -. DR ProteomicsDB; 252484; -. DR Antibodypedia; 3906; 884 antibodies from 45 providers. DR Ensembl; ENSMUST00000026795.13; ENSMUSP00000026795.7; ENSMUSG00000025701.13. DR GeneID; 11689; -. DR KEGG; mmu:11689; -. DR UCSC; uc009dkd.1; mouse. DR AGR; MGI:87999; -. DR CTD; 240; -. DR MGI; MGI:87999; Alox5. DR VEuPathDB; HostDB:ENSMUSG00000025701; -. DR eggNOG; ENOG502QQSP; Eukaryota. DR GeneTree; ENSGT00940000156111; -. DR InParanoid; P48999; -. DR OMA; MMFNAND; -. DR OrthoDB; 999249at2759; -. DR PhylomeDB; P48999; -. DR TreeFam; TF105320; -. DR BRENDA; 1.13.11.34; 3474. DR Reactome; R-MMU-2142688; Synthesis of 5-eicosatetraenoic acids. DR Reactome; R-MMU-2142691; Synthesis of Leukotrienes (LT) and Eoxins (EX). DR Reactome; R-MMU-2142700; Synthesis of Lipoxins (LX). DR Reactome; R-MMU-6798695; Neutrophil degranulation. DR Reactome; R-MMU-9018676; Biosynthesis of D-series resolvins. DR Reactome; R-MMU-9018682; Biosynthesis of maresins. DR Reactome; R-MMU-9018896; Biosynthesis of E-series 18(S)-resolvins. DR Reactome; R-MMU-9020265; Biosynthesis of aspirin-triggered D-series resolvins. DR Reactome; R-MMU-9023661; Biosynthesis of E-series 18(R)-resolvins. DR Reactome; R-MMU-9026286; Biosynthesis of DPAn-3-derived protectins and resolvins. DR Reactome; R-MMU-9026290; Biosynthesis of DPAn-3-derived maresins. DR Reactome; R-MMU-9026403; Biosynthesis of DPAn-3-derived 13-series resolvins. DR Reactome; R-MMU-9027604; Biosynthesis of electrophilic Omega-3 PUFA oxo-derivatives. DR UniPathway; UPA00877; -. DR BioGRID-ORCS; 11689; 3 hits in 81 CRISPR screens. DR ChiTaRS; Alox5; mouse. DR PRO; PR:P48999; -. DR Proteomes; UP000000589; Chromosome 6. DR RNAct; P48999; Protein. DR Bgee; ENSMUSG00000025701; Expressed in granulocyte and 99 other cell types or tissues. DR ExpressionAtlas; P48999; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IDA:MGI. DR GO; GO:0005829; C:cytosol; ISS:UniProtKB. DR GO; GO:0030425; C:dendrite; ISO:MGI. DR GO; GO:0005635; C:nuclear envelope; ISO:MGI. DR GO; GO:0005641; C:nuclear envelope lumen; ISS:UniProtKB. DR GO; GO:0016363; C:nuclear matrix; ISO:MGI. DR GO; GO:0031965; C:nuclear membrane; ISS:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; ISO:MGI. DR GO; GO:0005634; C:nucleus; IDA:MGI. DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISS:UniProtKB. DR GO; GO:0042383; C:sarcolemma; ISO:MGI. DR GO; GO:0004052; F:arachidonate 12(S)-lipoxygenase activity; IEA:RHEA. DR GO; GO:0004051; F:arachidonate 5-lipoxygenase activity; IDA:UniProtKB. DR GO; GO:0036403; F:arachidonate 8(S)-lipoxygenase activity; IEA:RHEA. DR GO; GO:0016787; F:hydrolase activity; IEA:UniProtKB-KW. DR GO; GO:0005506; F:iron ion binding; ISS:UniProtKB. DR GO; GO:0019369; P:arachidonic acid metabolic process; IBA:GO_Central. DR GO; GO:0036336; P:dendritic cell migration; IMP:UniProtKB. DR GO; GO:0042593; P:glucose homeostasis; IMP:UniProtKB. DR GO; GO:0051122; P:hepoxilin biosynthetic process; IBA:GO_Central. DR GO; GO:0006959; P:humoral immune response; IMP:UniProtKB. DR GO; GO:0006954; P:inflammatory response; IMP:MGI. DR GO; GO:0002232; P:leukocyte chemotaxis involved in inflammatory response; ISS:UniProtKB. DR GO; GO:0002523; P:leukocyte migration involved in inflammatory response; IMP:UniProtKB. DR GO; GO:1901753; P:leukotriene A4 biosynthetic process; IMP:UniProtKB. DR GO; GO:0019370; P:leukotriene biosynthetic process; IDA:MGI. DR GO; GO:0006691; P:leukotriene metabolic process; IMP:MGI. DR GO; GO:0002540; P:leukotriene production involved in inflammatory response; IMP:MGI. DR GO; GO:0043651; P:linoleic acid metabolic process; IBA:GO_Central. DR GO; GO:0034440; P:lipid oxidation; IBA:GO_Central. DR GO; GO:2001301; P:lipoxin biosynthetic process; ISS:UniProtKB. DR GO; GO:0019372; P:lipoxygenase pathway; IBA:GO_Central. DR GO; GO:0016525; P:negative regulation of angiogenesis; IMP:UniProtKB. DR GO; GO:0001937; P:negative regulation of endothelial cell proliferation; IMP:UniProtKB. DR GO; GO:0050728; P:negative regulation of inflammatory response; ISS:UniProtKB. DR GO; GO:1903573; P:negative regulation of response to endoplasmic reticulum stress; IMP:UniProtKB. DR GO; GO:1903671; P:negative regulation of sprouting angiogenesis; IMP:UniProtKB. DR GO; GO:0061044; P:negative regulation of vascular wound healing; IMP:UniProtKB. DR GO; GO:0061045; P:negative regulation of wound healing; IMP:UniProtKB. DR GO; GO:0030501; P:positive regulation of bone mineralization; IMP:UniProtKB. DR GO; GO:1904999; P:positive regulation of leukocyte adhesion to arterial endothelial cell; IMP:UniProtKB. DR GO; GO:0045907; P:positive regulation of vasoconstriction; ISO:MGI. DR GO; GO:1900407; P:regulation of cellular response to oxidative stress; IMP:UniProtKB. DR GO; GO:1900015; P:regulation of cytokine production involved in inflammatory response; IMP:UniProtKB. DR GO; GO:0045598; P:regulation of fat cell differentiation; IMP:UniProtKB. DR GO; GO:0050727; P:regulation of inflammatory response; IMP:UniProtKB. DR GO; GO:0106014; P:regulation of inflammatory response to wounding; IMP:UniProtKB. DR GO; GO:0050796; P:regulation of insulin secretion; IMP:UniProtKB. DR GO; GO:1903426; P:regulation of reactive oxygen species biosynthetic process; ISS: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:SF5; POLYUNSATURATED FATTY ACID 5-LIPOXYGENASE; 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; P48999; MM. PE 1: Evidence at protein level; KW Calcium; Cytoplasm; Dioxygenase; Hydrolase; Iron; Leukotriene biosynthesis; KW Lipid metabolism; Membrane; Metal-binding; Nucleus; Oxidoreductase; KW Phosphoprotein; Reference proteome. FT CHAIN 1..674 FT /note="Polyunsaturated fatty acid 5-lipoxygenase" FT /id="PRO_0000220695" FT DOMAIN 2..118 FT /note="PLAT" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00152" FT DOMAIN 119..674 FT /note="Lipoxygenase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00726" FT BINDING 17 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /ligand_note="structural" FT /evidence="ECO:0000250" FT BINDING 18 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /ligand_note="structural" FT /evidence="ECO:0000250" FT BINDING 19 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /ligand_note="structural" FT /evidence="ECO:0000250" FT BINDING 44 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /ligand_note="structural" FT /evidence="ECO:0000250" FT BINDING 45 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /ligand_note="structural" FT /evidence="ECO:0000250" FT BINDING 47 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /ligand_note="structural" FT /evidence="ECO:0000250" FT BINDING 79 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /ligand_note="structural" FT /evidence="ECO:0000250" FT BINDING 80 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /ligand_note="structural" FT /evidence="ECO:0000250" FT BINDING 368 FT /ligand="Fe cation" FT /ligand_id="ChEBI:CHEBI:24875" FT /ligand_note="catalytic" FT /evidence="ECO:0000250|UniProtKB:P09917, FT ECO:0000255|PROSITE-ProRule:PRU00726" FT BINDING 373 FT /ligand="Fe cation" FT /ligand_id="ChEBI:CHEBI:24875" FT /ligand_note="catalytic" FT /evidence="ECO:0000250|UniProtKB:P09917, FT ECO:0000255|PROSITE-ProRule:PRU00726" FT BINDING 551 FT /ligand="Fe cation" FT /ligand_id="ChEBI:CHEBI:24875" FT /ligand_note="catalytic" FT /evidence="ECO:0000250|UniProtKB:P09917, FT ECO:0000255|PROSITE-ProRule:PRU00726" FT BINDING 555 FT /ligand="Fe cation" FT /ligand_id="ChEBI:CHEBI:24875" FT /ligand_note="catalytic" FT /evidence="ECO:0000250|UniProtKB:P09917, FT ECO:0000255|PROSITE-ProRule:PRU00726" FT BINDING 674 FT /ligand="Fe cation" FT /ligand_id="ChEBI:CHEBI:24875" FT /ligand_note="catalytic" FT /evidence="ECO:0000250|UniProtKB:P09917, FT ECO:0000255|PROSITE-ProRule:PRU00726" FT SITE 103 FT /note="Essential for stabilizing binding to COTL1" FT /evidence="ECO:0000250" FT MOD_RES 272 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P09917" FT MOD_RES 524 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P09917" FT MUTAGEN 360 FT /note="F->W: Increases formation of FT (8S)-hydroperoxyicosatetraenoic acid ((8S)-HPETE). Exhibits FT a (8S)-lipoxygenase activity; when associated with I-425. FT Exhibits a (15S)-lipoxygenase activity; when associated FT with I-425 and M-426. Loss of arachidonate FT (5S)-lipoxygenase activity; when associated with G-411; FT I-425 and M-426. Forms 11(R)-hydroperoxyicosatetraenoic FT acid (11(R)-HPETE) as the major arachidonic acid FT oxygenation product; when associated with G-411; I-425 and FT M-426. Does not oxygenate arachidonic acid into 5-HETE; FT when associated with I-425 and M-426. Catalyzes oxygenation FT of arachidonic acid into a major product (15S)-HETE FT followed by 12-HETE and 8-HETE;when associated with I-425 FT and M-426. Catalyzes oxygenation of linoleic acid, FT gamma-linolenic acid, arachidonic acid, eicosapentaenoic FT acid and docosahexaenoic acid; when associated with I-425 FT and M-426. Catalyzes oxygenation of anandamide to FT 15-OH-ANA. Knockin mice are viable, fertile, and develop FT normally; when associated with I-425 and M-426. Mice FT convert arachidonic to 15-HETE, 12-HETE, and 8-HETE; when FT associated with I-425 and M-426. Mice cannot synthesize FT pro-inflammatory leukotrienes but show significantly FT attenuated plasma levels of lipolytic endocannabinoids; FT when associated with I-425 and M-426. When aging, animals FT gain significantly more body weight probably due to higher FT levels of 13-HODE in the adipose tissue; when associated FT with I-425 and M-426." FT /evidence="ECO:0000269|PubMed:23246375, FT ECO:0000269|PubMed:31642348" FT MUTAGEN 411 FT /note="A->G: Decreases (5S)-lipoxygenase activity. Forms FT 9-hydroperoxyicosatetraenoic acid (9-HPETE) as the major FT arachidonic acid oxygenation product. Loss of arachidonate FT (5S)-lipoxygenase activity; when associated with W-360; FT I-425 and M-426. Forms 11(R)-hydroperoxyicosatetraenoic FT acid (11(R)-HPETE) as the major arachidonic acid FT oxygenation product; when associated with W-360; I-425 and FT M-426." FT /evidence="ECO:0000269|PubMed:23246375" FT MUTAGEN 425 FT /note="A->I: Decreases arachidonate (5S)-lipoxygenase FT activity. Decreases arachidonate 5 lipoxygenase activity; FT when associated with A-604. Exhibits a (8S)-lipoxygenase FT activity; when associated with W-360. Exhibits a FT (15S)-lipoxygenase activity; when associated with W-360 and FT M-426. Loss of arachidonate (5S)-lipoxygenase activity; FT when associated with W-360; G-411 and M-426. Forms FT 11(R)-hydroperoxyicosatetraenoic acid (11(R)-HPETE) as the FT major arachidonic acid oxygenation product; when associated FT with W-360; G-411 and M-426. Does not oxygenate arachidonic FT acid into 5-HETE; when associated with I-425 and M-426. FT Catalyzes oxygenation of arachidonic acid into a major FT product (15S)-HETE followed by 12-HETE and 8-HETE; when FT associated with I-425 and M-426. Catalyzes oxygenation of FT linoleic acid, gamma-linolenic acid, arachidonic acid, FT eicosapentaenoic acid and docosahexaenoic acid; when FT associated with I-425 and M-426. Catalyzes oxygenation of FT anandamide to 15-OH-ANA. Knockin mice are viable, fertile, FT and develop normally; when associated with I-425 and M-426. FT Mice convert arachidonic to 15-HETE, 12-HETE, and 8-HETE; FT when associated with I-425 and M-426. Mice cannot FT synthesize pro-inflammatory leukotrienes but show FT significantly attenuated plasma levels of lipolytic FT endocannabinoids; when associated with I-425 and M-426. FT When aging, animals gain significantly more body weight FT probably due to higher levels of 13-HODE in the adipose FT tissue; when associated with I-425 and M-426." FT /evidence="ECO:0000269|PubMed:23246375, FT ECO:0000269|PubMed:31642348" FT MUTAGEN 426 FT /note="N->M: Increases formation of FT (8S)-hydroperoxyicosatetraenoic acid ((8S)-HPETE) and FT (12S)-hydroperoxyicosatetraenoic acid ((12S)-HPETE). FT Exhibits a (15S)-lipoxygenase activity; when associated FT with W-360 and I-425. Loss of arachidonate FT (5S)-lipoxygenase activity; when associated with W-360; FT G-411 and I-425. Forms 11(R)-hydroperoxyicosatetraenoic FT acid (11(R)-HPETE) as the major arachidonic acid FT oxygenation product; when associated with W-360; G-411 and FT I-425." FT /evidence="ECO:0000269|PubMed:23246375, FT ECO:0000269|PubMed:31642348" FT MUTAGEN 604 FT /note="A->I: Decreases arachidonate (5S)-lipoxygenase FT activity." FT /evidence="ECO:0000269|PubMed:23246375" FT MUTAGEN 672 FT /note="V->M: Loss of activity." FT /evidence="ECO:0000269|PubMed:7629107" FT CONFLICT 466 FT /note="I -> M (in Ref. 1; AAC37673)" FT /evidence="ECO:0000305" FT CONFLICT 646 FT /note="V -> I (in Ref. 1; AAC37673)" FT /evidence="ECO:0000305" SQ SEQUENCE 674 AA; 77967 MW; 130F27F9A77A3D88 CRC64; MPSYTVTVAT GSQWFAGTDD YIYLSLIGSA GCSEKHLLDK AFYNDFERGA VDSYDVTVDE ELGEIYLVKI EKRKYWLHDD WYLKYITLKT PHGDYIEFPC YRWITGEGEI VLRDGRAKLA RDDQIHILKQ HRRKELEARQ KQYRWMEWNP GFPLSIDAKC HKDLPRDIQF DSEKGVDFVL NYSKAMENLF INRFMHMFQS SWHDFADFEK IFVKISNTIS ERVKNHWQED LMFGYQFLNG CNPVLIKRCT ALPPKLPVTT EMVECSLERQ LSLEQEVQEG NIFIVDYELL DGIDANKTDP CTHQFLAAPI CLLYKNLANK IVPIAIQLNQ TPGESNPIFL PTDSKYDWLL AKIWVRSSDF HVHQTITHLL RTHLVSEVFG IAMYRQLPAV HPLFKLLVAH VRFTIAINTK AREQLICEYG LFDKANATGG GGHVQMVQRA VQDLTYSSLC FPEAIKARGM DSTEDIPFYF YRDDGLLVWE AIQSFTMEVV SIYYENDQVV EEDQELQDFV KDVYVYGMRG KKASGFPKSI KSREKLSEYL TVVIFTASAQ HAAVNFGQYD WCSWIPNAPP TMRAPPPTAK GVVTIEQIVD TLPDRGRSCW HLGAVWALSQ FQENELFLGM YPEEHFIEKP VKEAMIRFRK NLEAIVSVIA ERNKNKKLPY YYLSPDRIPN SVAI //