LOX15_MOUSE
ID LOX15_MOUSE Reviewed; 663 AA.
AC P39654; Q4FJY9; Q5F2E3; Q6PHB2;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT 11-SEP-2007, sequence version 4.
DT 03-AUG-2022, entry version 175.
DE RecName: Full=Polyunsaturated fatty acid lipoxygenase ALOX15 {ECO:0000305};
DE AltName: Full=12/15-lipoxygenase {ECO:0000303|PubMed:8798642};
DE Short=12/15-LO;
DE AltName: Full=Arachidonate 12-lipoxygenase, leukocyte-type {ECO:0000250|UniProtKB:Q02759};
DE Short=12-LOX;
DE Short=L-12LO {ECO:0000303|PubMed:8798642};
DE EC=1.13.11.31 {ECO:0000269|PubMed:8188678};
DE AltName: Full=Arachidonate 15-lipoxygenase;
DE Short=15-LOX;
DE EC=1.13.11.33 {ECO:0000269|PubMed:8188678};
DE AltName: Full=Arachidonate omega-6 lipoxygenase {ECO:0000250|UniProtKB:P16050};
DE AltName: Full=Hepoxilin A3 synthase Alox15 {ECO:0000250|UniProtKB:Q02759};
DE EC=1.13.11.- {ECO:0000250|UniProtKB:Q02759};
DE AltName: Full=Linoleate 13S-lipoxygenase;
DE EC=1.13.11.12 {ECO:0000269|PubMed:8188678};
GN Name=Alox15 {ECO:0000312|MGI:MGI:87997}; Synonyms=Alox12l;
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], CATALYTIC ACTIVITY, TISSUE SPECIFICITY,
RP FUNCTION, AND MUTAGENESIS OF ILE-663.
RC STRAIN=C57BL/6J, and ICR; TISSUE=Spleen;
RX PubMed=8188678; DOI=10.1016/s0021-9258(17)36743-1;
RA Chen X.-S., Kurre U., Jenkins N.A., Copeland N.G., Funk C.D.;
RT "cDNA cloning, expression, mutagenesis of C-terminal isoleucine, genomic
RT structure, and chromosomal localizations of murine 12-lipoxygenases.";
RL J. Biol. Chem. 269:13979-13987(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Macrophage;
RX PubMed=7811740; DOI=10.1016/0005-2760(94)00199-9;
RA Freire-Moar J., Alavi-Nassab A., Ng M., Mulkins M., Sigal E.;
RT "Cloning and characterization of a murine macrophage lipoxygenase.";
RL Biochim. Biophys. Acta 1254:112-116(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Lung;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Muenstermann E., Schatten R., Henze S., Bohn E., Mollenhauer J.,
RA Wiemann S., Schick M., Korn B.;
RT "Cloning of mouse full open reading frames in Gateway(R) system entry
RT vector (pDONR201).";
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N, and FVB/N-3; TISSUE=Mammary tumor;
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 DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY.
RX PubMed=8798642; DOI=10.1074/jbc.271.39.24278;
RA Sun D., Funk C.D.;
RT "Disruption of 12/15-lipoxygenase expression in peritoneal macrophages.
RT Enhanced utilization of the 5-lipoxygenase pathway and diminished oxidation
RT of low density lipoprotein.";
RL J. Biol. Chem. 271:24055-24062(1996).
RN [8]
RP FUNCTION IN MACROPHAGE.
RX PubMed=10432118; DOI=10.1038/22572;
RA Huang J.T., Welch J.S., Ricote M., Binder C.J., Willson T.M., Kelly C.,
RA Witztum J.L., Funk C.D., Conrad D., Glass C.K.;
RT "Interleukin-4-dependent production of PPAR-gamma ligands in macrophages by
RT 12/15-lipoxygenase.";
RL Nature 400:378-382(1999).
RN [9]
RP FUNCTION IN ACTIN REGULATION, AND SUBCELLULAR LOCATION.
RX PubMed=11278875; DOI=10.1074/jbc.m011276200;
RA Miller Y.I., Chang M.K., Funk C.D., Feramisco J.R., Witztum J.L.;
RT "12/15-lipoxygenase translocation enhances site-specific actin
RT polymerization in macrophages phagocytosing apoptotic cells.";
RL J. Biol. Chem. 276:19431-19439(2001).
RN [10]
RP FUNCTION IN BONE DEVELOPMENT, AND DISRUPTION PHENOTYPE.
RX PubMed=14716014; DOI=10.1126/science.1090985;
RA Klein R.F., Allard J., Avnur Z., Nikolcheva T., Rotstein D., Carlos A.S.,
RA Shea M., Waters R.V., Belknap J.K., Peltz G., Orwoll E.S.;
RT "Regulation of bone mass in mice by the lipoxygenase gene Alox15.";
RL Science 303:229-232(2004).
RN [11]
RP FUNCTION IN HEALING, AND TISSUE SPECIFICITY.
RX PubMed=15708862; DOI=10.1074/jbc.m410638200;
RA Gronert K., Maheshwari N., Khan N., Hassan I.R., Dunn M.,
RA Laniado Schwartzman M.;
RT "A role for the mouse 12/15-lipoxygenase pathway in promoting epithelial
RT wound healing and host defense.";
RL J. Biol. Chem. 280:15267-15278(2005).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Lung, and Spleen;
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 [13]
RP FUNCTION IN ER STRESS RESPONSE, DISRUPTION PHENOTYPE, AND INDUCTION.
RX PubMed=22215650; DOI=10.1152/ajpendo.00373.2011;
RA Cole B.K., Kuhn N.S., Green-Mitchell S.M., Leone K.A., Raab R.M.,
RA Nadler J.L., Chakrabarti S.K.;
RT "12/15-Lipoxygenase signaling in the endoplasmic reticulum stress
RT response.";
RL Am. J. Physiol. 302:E654-E665(2012).
RN [14]
RP FUNCTION IN APOPTOTIC CELL CLEARANCE, DISRUPTION PHENOTYPE, AND TISSUE
RP SPECIFICITY.
RX PubMed=22503541; DOI=10.1016/j.immuni.2012.03.010;
RA Uderhardt S., Herrmann M., Oskolkova O.V., Aschermann S., Bicker W.,
RA Ipseiz N., Sarter K., Frey B., Rothe T., Voll R., Nimmerjahn F.,
RA Bochkov V.N., Schett G., Kroenke G.;
RT "12/15-lipoxygenase orchestrates the clearance of apoptotic cells and
RT maintains immunologic tolerance.";
RL Immunity 36:834-846(2012).
CC -!- FUNCTION: Non-heme iron-containing dioxygenase that catalyzes the
CC stereo-specific peroxidation of free and esterified polyunsaturated
CC fatty acids generating a spectrum of bioactive lipid mediators
CC (PubMed:8188678). It inserts peroxyl groups at C12 or C15 of
CC arachidonate ((5Z,8Z,11Z,14Z)-eicosatetraenoate) producing both 12-
CC hydroperoxyeicosatetraenoate/12-HPETE and 15-
CC hydroperoxyeicosatetraenoate/15-HPETE (PubMed:8188678). It may then act
CC on 12-HPETE to produce hepoxilins, which may show pro-inflammatory
CC properties (By similarity). Can also peroxidize linoleate ((9Z,12Z)-
CC octadecadienoate) to 13-hydroperoxyoctadecadienoate. May participate in
CC the sequential oxidations of DHA ((4Z,7Z,10Z,13Z,16Z,19Z)-
CC docosahexaenoate) to generate specialized pro-resolving mediators
CC (SPMs)like resolvin D5 ((7S,17S)-diHPDHA) and (7S,14S)-diHPDHA, that
CC actively down-regulate the immune response and have anti-aggregation
CC properties with platelets. Can convert epoxy fatty acids to
CC hydroperoxy-epoxides derivatives followed by an intramolecular
CC nucleophilic substitution leading to the formation of monocyclic
CC endoperoxides (By similarity). Plays an important role during the
CC maintenance of self-tolerance by peroxidizing membrane-bound
CC phosphatidylethanolamine which can then signal the sorting process for
CC clearance of apoptotic cells during inflammation and prevent an
CC autoimmune response (PubMed:22503541). In addition to its role in the
CC immune and inflammatory responses, this enzyme may play a role in
CC epithelial wound healing in the cornea through production of lipoxin A4
CC (LXA(4)) and docosahexaenoic acid-derived neuroprotectin D1 (NPD1;
CC 10R,17S-HDHA), both lipid autacoids exhibit anti-inflammatory and
CC neuroprotective properties (PubMed:15708862). Furthermore, it may
CC regulate actin polymerization which is crucial for several biological
CC processes such as the phagocytosis of apoptotic cells
CC (PubMed:11278875). It is also implicated in the generation of
CC endogenous ligands for peroxisome proliferator activated receptor
CC (PPAR-gamma), hence modulating macrophage development and function
CC (PubMed:10432118). It may also exert a negative effect on skeletal
CC development by regulating bone mass through this pathway
CC (PubMed:14716014). As well as participates in ER stress and downstream
CC inflammation in adipocytes, pancreatic islets, and liver
CC (PubMed:22215650). Finally, it is also involved in the cellular
CC response to IL13/interleukin-13 (By similarity).
CC {ECO:0000250|UniProtKB:P16050, ECO:0000250|UniProtKB:Q02759,
CC ECO:0000269|PubMed:10432118, ECO:0000269|PubMed:11278875,
CC ECO:0000269|PubMed:14716014, ECO:0000269|PubMed:15708862,
CC ECO:0000269|PubMed:22215650, ECO:0000269|PubMed:22503541,
CC ECO:0000269|PubMed:8188678}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 = (12S)-hydroperoxy-
CC (5Z,8Z,10E,14Z)-eicosatetraenoate; Xref=Rhea:RHEA:10428,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:32395, ChEBI:CHEBI:57444;
CC EC=1.13.11.31; Evidence={ECO:0000269|PubMed:8188678};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:10429;
CC Evidence={ECO:0000305|PubMed:8188678};
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:8188678};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16870;
CC Evidence={ECO:0000305|PubMed:8188678};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(9Z,12Z)-octadecadienoate + O2 = (13S)-hydroperoxy-(9Z,11E)-
CC octadecadienoate; Xref=Rhea:RHEA:22780, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:30245, ChEBI:CHEBI:57466; EC=1.13.11.12;
CC Evidence={ECO:0000269|PubMed:8188678};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:22781;
CC Evidence={ECO:0000305|PubMed:8188678};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + 2 O2 = (14R,15S)-
CC dihydroperoxy-(5Z,8Z,10E,12E)-eicosatetraenoate;
CC Xref=Rhea:RHEA:50928, ChEBI:CHEBI:15379, ChEBI:CHEBI:32395,
CC ChEBI:CHEBI:133900; Evidence={ECO:0000250|UniProtKB:P16050};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50929;
CC Evidence={ECO:0000250|UniProtKB:P16050};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5Z,8Z,11Z,14Z)-eicosatetraenoate + 2 O2 = (8S,15S)-
CC dihydroperoxy-(5Z,9E,11Z,13E)-eicosatetraenoate;
CC Xref=Rhea:RHEA:50924, ChEBI:CHEBI:15379, ChEBI:CHEBI:32395,
CC ChEBI:CHEBI:133899; Evidence={ECO:0000250|UniProtKB:P16050};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50925;
CC Evidence={ECO:0000250|UniProtKB:P16050};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(14S,15R)-epoxy-(5Z,8Z,11Z)-eicosatrienoate + O2 = (8S)-
CC hydroperoxy-(14S,15R)-epoxy-(5Z,9E,11Z)-eicosatrienoate;
CC Xref=Rhea:RHEA:50288, ChEBI:CHEBI:15379, ChEBI:CHEBI:131964,
CC ChEBI:CHEBI:132068; Evidence={ECO:0000250|UniProtKB:P16050};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50289;
CC Evidence={ECO:0000250|UniProtKB:P16050};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(14S,15R)-epoxy-(5Z,8Z,11Z)-eicosatrienoate + O2 = (12S)-
CC hydroperoxy-(14S,15R)-epoxy-(5Z,8Z,10E)-eicosatrienoate;
CC Xref=Rhea:RHEA:50284, ChEBI:CHEBI:15379, ChEBI:CHEBI:131964,
CC ChEBI:CHEBI:132065; Evidence={ECO:0000250|UniProtKB:P16050};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50285;
CC Evidence={ECO:0000250|UniProtKB:P16050};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(14R,15S)-epoxy-(5Z,8Z,11Z)-eicosatrienoate + O2 = (5S)-
CC hydroperoxy-(14R,15S)-epoxy-(6E,8Z,11Z)-eicosatrienoate;
CC Xref=Rhea:RHEA:50280, ChEBI:CHEBI:15379, ChEBI:CHEBI:131965,
CC ChEBI:CHEBI:132067; Evidence={ECO:0000250|UniProtKB:P16050};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50281;
CC Evidence={ECO:0000250|UniProtKB:P16050};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(14R,15S)-epoxy-(5Z,8Z,11Z)-eicosatrienoate + O2 = (12S)-
CC hydroperoxy-(14R,15S)-epoxy-(5Z,8Z,10E)-eicosatrienoate;
CC Xref=Rhea:RHEA:50276, ChEBI:CHEBI:15379, ChEBI:CHEBI:131965,
CC ChEBI:CHEBI:132063; Evidence={ECO:0000250|UniProtKB:P16050};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50277;
CC Evidence={ECO:0000250|UniProtKB:P16050};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(15R)-hydroperoxy-(5Z,8Z,11Z,13E)-eicosatetraenoate = 15-oxo-
CC (5Z,8Z,11Z,13E)-eicosatetraenoate + H2O; Xref=Rhea:RHEA:50152,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:57410, ChEBI:CHEBI:82626;
CC Evidence={ECO:0000250|UniProtKB:P16050};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50153;
CC Evidence={ECO:0000250|UniProtKB:P16050};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(15S)-hydroperoxy-(5Z,8Z,11Z,13E)-eicosatetraenoate =
CC (14S,15S)-epoxy-(5Z,8Z,10E,12E)-eicosatetraenoate + H2O;
CC Xref=Rhea:RHEA:50140, ChEBI:CHEBI:15377, ChEBI:CHEBI:57446,
CC ChEBI:CHEBI:132070; Evidence={ECO:0000250|UniProtKB:P16050};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50141;
CC Evidence={ECO:0000250|UniProtKB:P16050};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(12S)-hydroperoxy-(5Z,8Z,10E,14Z)-eicosatetraenoate = (8S)-
CC hydroxy-(11S,12S)-epoxy-(5Z,9E,14Z)-eicosatrienoate;
CC Xref=Rhea:RHEA:50216, ChEBI:CHEBI:57444, ChEBI:CHEBI:132129;
CC Evidence={ECO:0000250|UniProtKB:Q02759};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50217;
CC Evidence={ECO:0000250|UniProtKB:Q02759};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(4Z,7Z,10Z,13Z,16Z)-docosapentaenoate + O2 = 14-hydroperoxy-
CC (4Z,7Z,10Z,12E,16Z)-docosapentaenoate; Xref=Rhea:RHEA:50824,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:77226, ChEBI:CHEBI:133799;
CC Evidence={ECO:0000250|UniProtKB:P16469};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50825;
CC Evidence={ECO:0000250|UniProtKB:P16469};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(7Z,10Z,13Z,16Z,19Z)-docosapentaenoate + O2 = 14-hydroperoxy-
CC (7Z,10Z,12E,16Z,19Z)-docosapentaenoate; Xref=Rhea:RHEA:50836,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:77224, ChEBI:CHEBI:133798;
CC Evidence={ECO:0000250|UniProtKB:P16469};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50837;
CC Evidence={ECO:0000250|UniProtKB:P16469};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate + O2 = (14S)-
CC hydroperoxy-(4Z,7Z,10Z,12E,16Z,19Z)-docosahexaenoate;
CC Xref=Rhea:RHEA:41332, ChEBI:CHEBI:15379, ChEBI:CHEBI:77016,
CC ChEBI:CHEBI:78048; Evidence={ECO:0000250|UniProtKB:P16050};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41333;
CC Evidence={ECO:0000250|UniProtKB:P16050};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate + O2 = (17S)-
CC hydroperoxy-(4Z,7Z,10Z,13Z,15E,19Z)-docosahexaenoate;
CC Xref=Rhea:RHEA:50840, ChEBI:CHEBI:15379, ChEBI:CHEBI:77016,
CC ChEBI:CHEBI:133795; Evidence={ECO:0000250|UniProtKB:P16050};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50841;
CC Evidence={ECO:0000250|UniProtKB:P16050};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(7S)-hydroperoxy-(4Z,8E,10Z,13Z,16Z,19Z)-docosahexaenoate + O2
CC = (7S,14S)-dihydroperoxy-(4Z,8E,10Z,12E,16Z,19Z)-docosahexaenoate;
CC Xref=Rhea:RHEA:64724, ChEBI:CHEBI:15379, ChEBI:CHEBI:156049,
CC ChEBI:CHEBI:156082; Evidence={ECO:0000250|UniProtKB:P16050};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64725;
CC Evidence={ECO:0000250|UniProtKB:P16050};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(7S)-hydroperoxy-(4Z,8E,10Z,13Z,16Z,19Z)-docosahexaenoate + O2
CC = (7S,17S)-dihydroperoxy-(4Z,8E,10Z,13Z,15E,19Z)-docosahexaenoate;
CC Xref=Rhea:RHEA:64728, ChEBI:CHEBI:15379, ChEBI:CHEBI:140349,
CC ChEBI:CHEBI:156049; Evidence={ECO:0000250|UniProtKB:P16050};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64729;
CC Evidence={ECO:0000250|UniProtKB:P16050};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate + O2 = (11S)-
CC hydroperoxy-(4Z,7Z,9E,13Z,16Z,19Z)-docosahexaenoate;
CC Xref=Rhea:RHEA:64732, ChEBI:CHEBI:15379, ChEBI:CHEBI:77016,
CC ChEBI:CHEBI:156131; Evidence={ECO:0000250|UniProtKB:P16050};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64733;
CC Evidence={ECO:0000250|UniProtKB:P16050};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=N-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-taurine + O2 = N-(12S)-
CC hydroperoxy-(5Z,8Z,10E,14Z)-eicosatetraenoyl-taurine;
CC Xref=Rhea:RHEA:50160, ChEBI:CHEBI:15379, ChEBI:CHEBI:132060,
CC ChEBI:CHEBI:132061; Evidence={ECO:0000250|UniProtKB:P16469};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50161;
CC Evidence={ECO:0000250|UniProtKB:P16469};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=N-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-gamma-aminobutanoate + O2 =
CC N-(12S)-hydroperoxy-(5Z,8Z,10E,14Z)-eicosatetraenoyl-gamma-
CC aminobutanoate; Xref=Rhea:RHEA:50176, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:132072, ChEBI:CHEBI:132075;
CC Evidence={ECO:0000250|UniProtKB:P16469};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50177;
CC Evidence={ECO:0000250|UniProtKB:P16469};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=N-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-glycine + O2 = N-(12S)-
CC hydroperoxy-(5Z,8Z,10E,14Z)-eicosatetraenoyl-glycine;
CC Xref=Rhea:RHEA:50168, ChEBI:CHEBI:15379, ChEBI:CHEBI:59002,
CC ChEBI:CHEBI:132073; Evidence={ECO:0000250|UniProtKB:P16469};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50169;
CC Evidence={ECO:0000250|UniProtKB:P16469};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=N-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-alanine + O2 = N-(12S)-
CC hydroperoxy-(5Z,8Z,10E,14Z)-eicosatetraenoyl-alanine;
CC Xref=Rhea:RHEA:50172, ChEBI:CHEBI:15379, ChEBI:CHEBI:132071,
CC ChEBI:CHEBI:132074; Evidence={ECO:0000250|UniProtKB:P16469};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50173;
CC Evidence={ECO:0000250|UniProtKB:P16469};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=N-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-taurine + O2 = N-(15S)-
CC hydroperoxy-(5Z,8Z,11Z,13E)-eicosatetraenoyl-taurine;
CC Xref=Rhea:RHEA:50156, ChEBI:CHEBI:15379, ChEBI:CHEBI:132060,
CC ChEBI:CHEBI:132062; Evidence={ECO:0000250|UniProtKB:P12530};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50157;
CC Evidence={ECO:0000250|UniProtKB:P12530};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=N-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-gamma-aminobutanoate + O2 =
CC N-(15S)-hydroperoxy-(5Z,8Z,11Z,13E)-eicosatetraenoyl-gamma-
CC aminobutanoate; Xref=Rhea:RHEA:50180, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:132072, ChEBI:CHEBI:132078;
CC Evidence={ECO:0000250|UniProtKB:P12530};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50181;
CC Evidence={ECO:0000250|UniProtKB:P12530};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=N-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-glycine + O2 = N-(15S)-
CC hydroperoxy-(5Z,8Z,11Z,13E)-eicosatetraenoyl-glycine;
CC Xref=Rhea:RHEA:50188, ChEBI:CHEBI:15379, ChEBI:CHEBI:59002,
CC ChEBI:CHEBI:132076; Evidence={ECO:0000250|UniProtKB:P12530};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50189;
CC Evidence={ECO:0000250|UniProtKB:P12530};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=N-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-alanine + O2 = N-(15S)-
CC hydroperoxy-(5Z,8Z,11Z,13E)-eicosatetraenoyl-alanine;
CC Xref=Rhea:RHEA:50184, ChEBI:CHEBI:15379, ChEBI:CHEBI:132071,
CC ChEBI:CHEBI:132077; Evidence={ECO:0000250|UniProtKB:P12530};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50185;
CC Evidence={ECO:0000250|UniProtKB:P12530};
CC -!- COFACTOR:
CC Name=Fe cation; Xref=ChEBI:CHEBI:24875;
CC Evidence={ECO:0000250|UniProtKB:P16469,
CC ECO:0000255|PROSITE-ProRule:PRU00726};
CC Note=Binds 1 Fe cation per subunit. {ECO:0000250|UniProtKB:P16469,
CC ECO:0000255|PROSITE-ProRule:PRU00726};
CC -!- PATHWAY: Lipid metabolism; hydroperoxy eicosatetraenoic acid
CC biosynthesis. {ECO:0000269|PubMed:8188678}.
CC -!- SUBUNIT: Interacts with PEBP1; in response to IL13/interleukin-13,
CC prevents the interaction of PEBP1 with RAF1 to activate the ERK
CC signaling cascade. {ECO:0000250|UniProtKB:P16050}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:11278875}.
CC Cell membrane {ECO:0000269|PubMed:11278875}; Peripheral membrane
CC protein {ECO:0000250|UniProtKB:P16050}. Lipid droplet
CC {ECO:0000250|UniProtKB:P16050}. Note=Predominantly cytosolic; becomes
CC enriched at membranes upon calcium binding (PubMed:11278875).
CC Translocates from the cytosol to the plasma membrane when stimulated by
CC IL13/interleukin-13 and in macrophages binding apoptotic cells
CC (PubMed:11278875). {ECO:0000269|PubMed:11278875}.
CC -!- TISSUE SPECIFICITY: Found in pituitary and pineal glands as well as
CC leukocytes, kidney, aorta, small intestine and cornea (PubMed:15708862,
CC PubMed:22503541, PubMed:8188678). Also expressed by resident peritoneal
CC macrophages (at protein level) (PubMed:8798642).
CC {ECO:0000269|PubMed:15708862, ECO:0000269|PubMed:22503541,
CC ECO:0000269|PubMed:8188678, ECO:0000269|PubMed:8798642}.
CC -!- INDUCTION: Up-regulated in response to endoplasmic reticulum stress (at
CC protein level). {ECO:0000269|PubMed:22215650}.
CC -!- DOMAIN: The PLAT domain can bind calcium ions; this promotes
CC association with membranes. {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: Mice are fertile and do not display overt
CC phenotype. However, reduced endoplasmic reticulum stress response to
CC high-fat diet is observed. Aged mice also display systemic
CC autoimmunity, a significant and spontaneous production of several forms
CC of autoantibodies being detected and glomerulonephritis and deposits of
CC complement and immunoglobulins within their glomeruli being observed.
CC They also display reduced bone mass. {ECO:0000269|PubMed:14716014,
CC ECO:0000269|PubMed:22215650, ECO:0000269|PubMed:22503541,
CC ECO:0000269|PubMed:8798642}.
CC -!- SIMILARITY: Belongs to the lipoxygenase family. {ECO:0000305}.
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DR EMBL; U04331; AAA20658.1; -; mRNA.
DR EMBL; L34570; AAA64930.1; -; mRNA.
DR EMBL; AK142371; BAE25045.1; -; mRNA.
DR EMBL; CT010263; CAJ18471.1; -; mRNA.
DR EMBL; AL596096; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC056625; AAH56625.1; -; mRNA.
DR EMBL; BC081546; AAH81546.1; -; mRNA.
DR CCDS; CCDS24944.1; -.
DR PIR; B54075; B54075.
DR RefSeq; NP_033790.3; NM_009660.3.
DR AlphaFoldDB; P39654; -.
DR SMR; P39654; -.
DR BioGRID; 198074; 2.
DR IntAct; P39654; 1.
DR STRING; 10090.ENSMUSP00000019068; -.
DR BindingDB; P39654; -.
DR ChEMBL; CHEMBL3259476; -.
DR SwissLipids; SLP:000001638; -.
DR PhosphoSitePlus; P39654; -.
DR MaxQB; P39654; -.
DR PaxDb; P39654; -.
DR PRIDE; P39654; -.
DR ProteomicsDB; 292351; -.
DR Antibodypedia; 2761; 360 antibodies from 33 providers.
DR DNASU; 11687; -.
DR Ensembl; ENSMUST00000019068; ENSMUSP00000019068; ENSMUSG00000018924.
DR GeneID; 11687; -.
DR KEGG; mmu:11687; -.
DR UCSC; uc007juo.1; mouse.
DR CTD; 246; -.
DR MGI; MGI:87997; Alox15.
DR VEuPathDB; HostDB:ENSMUSG00000018924; -.
DR eggNOG; ENOG502QQSP; Eukaryota.
DR GeneTree; ENSGT00940000162807; -.
DR HOGENOM; CLU_004282_3_3_1; -.
DR InParanoid; P39654; -.
DR OMA; MVPLGQH; -.
DR OrthoDB; 385042at2759; -.
DR PhylomeDB; P39654; -.
DR TreeFam; TF105320; -.
DR BRENDA; 1.13.11.31; 3474.
DR BRENDA; 1.13.11.33; 3474.
DR Reactome; R-MMU-2142691; Synthesis of Leukotrienes (LT) and Eoxins (EX).
DR Reactome; R-MMU-2142712; Synthesis of 12-eicosatetraenoic acid derivatives.
DR Reactome; R-MMU-2142770; Synthesis of 15-eicosatetraenoic acid derivatives.
DR Reactome; R-MMU-9018677; Biosynthesis of DHA-derived SPMs.
DR Reactome; R-MMU-9018681; Biosynthesis of protectins.
DR Reactome; R-MMU-9018896; Biosynthesis of E-series 18(S)-resolvins.
DR Reactome; R-MMU-9023661; Biosynthesis of E-series 18(R)-resolvins.
DR Reactome; R-MMU-9025106; Biosynthesis of DPAn-6 SPMs.
DR Reactome; R-MMU-9026286; Biosynthesis of DPAn-3-derived protectins and resolvins.
DR UniPathway; UPA00881; -.
DR BioGRID-ORCS; 11687; 2 hits in 75 CRISPR screens.
DR ChiTaRS; Alox15; mouse.
DR PRO; PR:P39654; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; P39654; protein.
DR Bgee; ENSMUSG00000018924; Expressed in olfactory system and 51 other tissues.
DR ExpressionAtlas; P39654; baseline and differential.
DR Genevisible; P39654; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0031234; C:extrinsic component of cytoplasmic side of plasma membrane; ISS:UniProtKB.
DR GO; GO:0005811; C:lipid droplet; ISS:UniProtKB.
DR GO; GO:0016020; C:membrane; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0004052; F:arachidonate 12(S)-lipoxygenase activity; IDA:UniProtKB.
DR GO; GO:0050473; F:arachidonate 15-lipoxygenase activity; IDA:UniProtKB.
DR GO; GO:0051120; F:hepoxilin A3 synthase activity; ISO:MGI.
DR GO; GO:0047977; F:hepoxilin-epoxide hydrolase activity; ISO:MGI.
DR GO; GO:0005506; F:iron ion binding; ISS:UniProtKB.
DR GO; GO:0016165; F:linoleate 13S-lipoxygenase activity; ISS:UniProtKB.
DR GO; GO:0016702; F:oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen; IBA:GO_Central.
DR GO; GO:0005546; F:phosphatidylinositol-4,5-bisphosphate binding; ISS:UniProtKB.
DR GO; GO:0043277; P:apoptotic cell clearance; IMP:UniProtKB.
DR GO; GO:0019369; P:arachidonic acid metabolic process; IDA:UniProtKB.
DR GO; GO:0030282; P:bone mineralization; IMP:MGI.
DR GO; GO:0071277; P:cellular response to calcium ion; ISS:UniProtKB.
DR GO; GO:0035963; P:cellular response to interleukin-13; ISS:UniProtKB.
DR GO; GO:0019395; P:fatty acid oxidation; ISS:UniProtKB.
DR GO; GO:0051122; P:hepoxilin biosynthetic process; ISS:UniProtKB.
DR GO; GO:0043651; P:linoleic acid metabolic process; ISS:UniProtKB.
DR GO; GO:0006629; P:lipid metabolic process; ISO:MGI.
DR GO; GO:0034440; P:lipid oxidation; IBA:GO_Central.
DR GO; GO:2001303; P:lipoxin A4 biosynthetic process; IMP:UniProtKB.
DR GO; GO:0019372; P:lipoxygenase pathway; IDA:UniProtKB.
DR GO; GO:0002820; P:negative regulation of adaptive immune response; IMP:UniProtKB.
DR GO; GO:0001503; P:ossification; IMP:MGI.
DR GO; GO:0006646; P:phosphatidylethanolamine biosynthetic process; IMP:UniProtKB.
DR GO; GO:0030838; P:positive regulation of actin filament polymerization; IMP:UniProtKB.
DR GO; GO:0010811; P:positive regulation of cell-substrate adhesion; ISS:UniProtKB.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISS:UniProtKB.
DR GO; GO:0034116; P:positive regulation of heterotypic cell-cell adhesion; ISO:MGI.
DR GO; GO:1901074; P:regulation of engulfment of apoptotic cell; IMP:UniProtKB.
DR GO; GO:0050727; P:regulation of inflammatory response; ISS:UniProtKB.
DR GO; GO:0035358; P:regulation of peroxisome proliferator activated receptor signaling pathway; IMP:UniProtKB.
DR GO; GO:0034976; P:response to endoplasmic reticulum stress; IMP:UniProtKB.
DR GO; GO:0042060; P:wound healing; IMP:UniProtKB.
DR CDD; cd01753; PLAT_LOX; 1.
DR InterPro; IPR000907; LipOase.
DR InterPro; IPR013819; LipOase_C.
DR InterPro; IPR036226; LipOase_C_sf.
DR InterPro; IPR020834; LipOase_CS.
DR InterPro; IPR020833; LipOase_Fe_BS.
DR InterPro; IPR001885; LipOase_mml.
DR InterPro; IPR001024; PLAT/LH2_dom.
DR InterPro; IPR036392; PLAT/LH2_dom_sf.
DR InterPro; IPR042062; PLAT_LOX_verte.
DR PANTHER; PTHR11771; PTHR11771; 1.
DR Pfam; PF00305; Lipoxygenase; 1.
DR Pfam; PF01477; PLAT; 1.
DR PRINTS; PR00087; LIPOXYGENASE.
DR PRINTS; PR00467; MAMLPOXGNASE.
DR SMART; SM00308; LH2; 1.
DR SUPFAM; SSF48484; SSF48484; 1.
DR SUPFAM; SSF49723; SSF49723; 1.
DR PROSITE; PS00711; LIPOXYGENASE_1; 1.
DR PROSITE; PS00081; LIPOXYGENASE_2; 1.
DR PROSITE; PS51393; LIPOXYGENASE_3; 1.
DR PROSITE; PS50095; PLAT; 1.
PE 1: Evidence at protein level;
KW Calcium; Cell membrane; Cytoplasm; Dioxygenase; Fatty acid metabolism;
KW Iron; Lipid droplet; Lipid metabolism; Lipid-binding; Membrane;
KW Metal-binding; Oxidoreductase; Reference proteome.
FT CHAIN 1..663
FT /note="Polyunsaturated fatty acid lipoxygenase ALOX15"
FT /id="PRO_0000220686"
FT DOMAIN 2..115
FT /note="PLAT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00152"
FT DOMAIN 116..663
FT /note="Lipoxygenase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00726"
FT BINDING 361
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00726"
FT BINDING 366
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00726"
FT BINDING 541
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00726"
FT BINDING 545
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00726"
FT BINDING 663
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00726"
FT MUTAGEN 663
FT /note="Missing: Abolishes arachidonate 15-lipoxygenase
FT activity. Abolishes arachidonate 12-lipoxygenase activity.
FT Abolishes linoleate 13-lipoxygenase activity."
FT /evidence="ECO:0000269|PubMed:8188678"
FT CONFLICT 37
FT /note="K -> N (in Ref. 2; AAA64930)"
FT /evidence="ECO:0000305"
FT CONFLICT 119
FT /note="E -> Q (in Ref. 2; AAA64930)"
FT /evidence="ECO:0000305"
FT CONFLICT 397
FT /note="T -> N (in Ref. 2; AAA64930)"
FT /evidence="ECO:0000305"
FT CONFLICT 568
FT /note="K -> T (in Ref. 4; CAJ18471 and 6; AAH56625/
FT AAH81546)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 663 AA; 75445 MW; 0D5412B4502B5799 CRC64;
MGVYRIRVST GDSVYAGSNN EVYLWLIGQH GEASLGKLFR PCRNSEAEFK VDVSEYLGPL
LFVRVQKWHY LKEDAWFCNW ISVKGPGDQG SEYTFPCYRW VQGTSILNLP EGTGCTVVED
SQGLFRNHRE EELEERRSLY RWGNWKDGTI LNVAATSISD LPVDQRFRED KRLEFEASQV
LGTMDTVINF PKNTVTCWKS LDDFNYVFKS GHTKMAERVR NSWKEDAFFG YQFLNGANPM
VLKRSTCLPA RLVFPPGMEK LQAQLDEELK KGTLFEADFF LLDGIKANVI LCSQQYLAAP
LVMLKLQPDG QLLPIAIQLE LPKTGSTPPP IFTPLDPPMD WLLAKCWVRS SDLQLHELQA
HLLRGHLVAE VFAVATMRCL PSVHPVFKLL VPHLLYTMEI NVRARSDLIS ERGFFDKVMS
TGGGGHLDLL KQAGAFLTYS SLCPPDDLAE RGLLDIDTCF YAKDALQLWQ VMNRYVVGMF
DLYYKTDQAV QDDYELQSWC QEITEIGLQG AQDRGFPTSL QSRAQACHFI TMCIFTCTAQ
HSSIHLGQLD WFYWVPNAPC TMRLPPPKTK DATMEKLMAT LPNPNQSTLQ INVVWLLGRR
QAVMVPLGQH SEEHFPNPEA KAVLKKFREE LAALDKEIEI RNKSLDIPYE YLRPSLVENS
VAI
