LOX5_MOUSE
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 03-AUG-2022, entry version 170.
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=(5Z,8Z,11Z,13E,15S)-hydroxyeicosatetraenoate + 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,
CC ECO:0000255|PROSITE-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 ---------------------------------------------------------------------------
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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; P48999; -.
DR PeptideAtlas; P48999; -.
DR PRIDE; P48999; -.
DR ProteomicsDB; 252484; -.
DR Antibodypedia; 3906; 803 antibodies from 45 providers.
DR Ensembl; ENSMUST00000026795; ENSMUSP00000026795; ENSMUSG00000025701.
DR GeneID; 11689; -.
DR KEGG; mmu:11689; -.
DR UCSC; uc009dkd.1; mouse.
DR CTD; 240; -.
DR MGI; MGI:87999; Alox5.
DR VEuPathDB; HostDB:ENSMUSG00000025701; -.
DR eggNOG; ENOG502QQSP; Eukaryota.
DR GeneTree; ENSGT00940000156111; -.
DR InParanoid; P48999; -.
DR OMA; DFHMHQT; -.
DR OrthoDB; 385042at2759; -.
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 76 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 97 other tissues.
DR ExpressionAtlas; P48999; baseline and differential.
DR Genevisible; P48999; MM.
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:0016702; F:oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen; IBA:GO_Central.
DR GO; GO:0002526; P:acute inflammatory response; ISO:MGI.
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:1904960; P:positive regulation of cytochrome-c oxidase activity; ISO:MGI.
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 GO; GO:0019233; P:sensory perception of pain; ISO:MGI.
DR CDD; cd01753; PLAT_LOX; 1.
DR InterPro; IPR000907; LipOase.
DR InterPro; IPR013819; LipOase_C.
DR InterPro; IPR036226; LipOase_C_sf.
DR InterPro; IPR020834; LipOase_CS.
DR InterPro; IPR020833; LipOase_Fe_BS.
DR InterPro; IPR001885; LipOase_mml.
DR InterPro; IPR001024; PLAT/LH2_dom.
DR InterPro; IPR036392; PLAT/LH2_dom_sf.
DR InterPro; IPR042062; PLAT_LOX_verte.
DR PANTHER; PTHR11771; PTHR11771; 1.
DR Pfam; PF00305; Lipoxygenase; 1.
DR Pfam; PF01477; PLAT; 1.
DR PRINTS; PR00087; LIPOXYGENASE.
DR PRINTS; PR00467; MAMLPOXGNASE.
DR SMART; SM00308; LH2; 1.
DR SUPFAM; SSF48484; SSF48484; 1.
DR SUPFAM; SSF49723; SSF49723; 1.
DR PROSITE; PS00711; LIPOXYGENASE_1; 1.
DR PROSITE; PS00081; LIPOXYGENASE_2; 1.
DR PROSITE; PS51393; LIPOXYGENASE_3; 1.
DR PROSITE; PS50095; PLAT; 1.
PE 1: Evidence at protein level;
KW 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 (8S)-
FT hydroperoxyicosatetraenoic acid ((8S)-HPETE). Exhibits a
FT (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 (5S)-
FT lipoxygenase activity; when associated with G-411; I-425
FT and M-426. Forms 11(R)-hydroperoxyicosatetraenoic acid
FT (11(R)-HPETE) as the major arachidonic acid oxygenation
FT product; when associated with G-411; I-425 and M-426. Does
FT not oxygenate arachidonic acid into 5-HETE; when associated
FT with I-425 and M-426. Catalyzes oxygenation of arachidonic
FT acid into a major product (15S)-HETE followed by 12-HETE
FT and 8-HETE;when associated with I-425 and M-426. Catalyzes
FT oxygenation of linoleic acid, gamma-linolenic acid,
FT arachidonic acid, eicosapentaenoic acid and docosahexaenoic
FT acid; when associated with I-425 and M-426. Catalyzes
FT oxygenation of anandamide to 15-OH-ANA. Knockin mice are
FT viable, fertile, and develop normally; when associated with
FT I-425 and M-426. Mice convert arachidonic to 15-HETE, 12-
FT HETE, and 8-HETE; when associated with I-425 and M-426.
FT Mice cannot synthesize pro-inflammatory leukotrienes but
FT show 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 411
FT /note="A->G: Decreases (5S)-lipoxygenase activity. Forms 9-
FT hydroperoxyicosatetraenoic acid (9-HPETE) as the major
FT arachidonic acid oxygenation product. Loss of arachidonate
FT (5S)-lipoxygenase activity; when associated with W-360; I-
FT 425 and M-426. Forms 11(R)-hydroperoxyicosatetraenoic acid
FT (11(R)-HPETE) as the major arachidonic acid oxygenation
FT product; when associated with W-360; I-425 and 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 (15S)-
FT lipoxygenase activity; when associated with W-360 and M-
FT 426. Loss of arachidonate (5S)-lipoxygenase activity; when
FT associated with W-360; G-411 and M-426. Forms 11(R)-
FT hydroperoxyicosatetraenoic acid (11(R)-HPETE) as the major
FT arachidonic acid oxygenation product; when associated with
FT W-360; G-411 and M-426. Does not oxygenate arachidonic acid
FT 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 (8S)-
FT hydroperoxyicosatetraenoic acid ((8S)-HPETE) and (12S)-
FT hydroperoxyicosatetraenoic acid ((12S)-HPETE). Exhibits a
FT (15S)-lipoxygenase activity; when associated with W-360 and
FT I-425. Loss of arachidonate (5S)-lipoxygenase activity;
FT when associated with W-360; G-411 and I-425. Forms 11(R)-
FT hydroperoxyicosatetraenoic acid (11(R)-HPETE) as the major
FT arachidonic acid oxygenation product; when associated with
FT W-360; G-411 and 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
