PTGES_MOUSE
ID PTGES_MOUSE Reviewed; 153 AA.
AC Q9JM51; Q3T9C5;
DT 10-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 133.
DE RecName: Full=Prostaglandin E synthase;
DE Short=mPGES-1;
DE EC=5.3.99.3 {ECO:0000269|PubMed:10869354, ECO:0000269|PubMed:11795891};
DE AltName: Full=Glutathione peroxidase PTGES;
DE EC=1.11.1.- {ECO:0000250|UniProtKB:O14684};
DE AltName: Full=Glutathione transferase PTGES;
DE EC=2.5.1.18 {ECO:0000250|UniProtKB:O14684};
DE AltName: Full=Microsomal prostaglandin E synthase 1;
GN Name=Ptges; Synonyms=Pges;
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, FUNCTION, AND PATHWAY.
RC STRAIN=C57BL/6J;
RX PubMed=10869354; DOI=10.1074/jbc.m003505200;
RA Murakami M., Naraba H., Tanioka T., Semmyo N., Nakatani Y., Kojima F.,
RA Ikeda T., Fueki M., Ueno A., Oh S., Kudo I.;
RT "Regulation of prostaglandin E2 biosynthesis by inducible membrane-
RT associated prostaglandin E2 synthase that acts in concert with
RT cyclooxygenase-2.";
RL J. Biol. Chem. 275:32783-32792(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL
RP PROPERTIES, INDUCTION, FUNCTION, AND SUBCELLULAR LOCATION.
RC TISSUE=Spleen;
RX PubMed=11795891; DOI=10.1006/abbi.2001.2614;
RA Lazarus M., Kubata B.K., Eguchi N., Fujitani Y., Urade Y., Hayaishi O.;
RT "Biochemical characterization of mouse microsomal prostaglandin E synthase-
RT 1 and its colocalization with cyclooxygenase-2 in peritoneal macrophages.";
RL Arch. Biochem. Biophys. 397:336-341(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J, and NOD;
RC TISSUE=Embryonic stem cell, Epididymis, and Spleen;
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].
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 [5]
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 [6]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=12835414; DOI=10.1073/pnas.1332766100;
RA Trebino C.E., Stock J.L., Gibbons C.P., Naiman B.M., Wachtmann T.S.,
RA Umland J.P., Pandher K., Lapointe J.M., Saha S., Roach M.L., Carter D.,
RA Thomas N.A., Durtschi B.A., McNeish J.D., Hambor J.E., Jakobsson P.J.,
RA Carty T.J., Perez J.R., Audoly L.P.;
RT "Impaired inflammatory and pain responses in mice lacking an inducible
RT prostaglandin E synthase.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:9044-9049(2003).
RN [7]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=14566340; DOI=10.1038/nn1137;
RA Engblom D., Saha S., Engstroem L., Westman M., Audoly L.P., Jakobsson P.J.,
RA Blomqvist A.;
RT "Microsomal prostaglandin E synthase-1 is the central switch during immune-
RT induced pyresis.";
RL Nat. Neurosci. 6:1137-1138(2003).
CC -!- FUNCTION: Terminal enzyme of the cyclooxygenase (COX)-2-mediated
CC prostaglandin E2 (PGE2) biosynthetic pathway (PubMed:10869354,
CC PubMed:11795891). Catalyzes the glutathione-dependent oxidoreduction of
CC prostaglandin endoperoxide H2 (PGH2) to prostaglandin E2 (PGE2) in
CC response to inflammatory stimuli (PubMed:11795891, PubMed:10869354).
CC Plays a key role in inflammation response, fever and pain
CC (PubMed:12835414, PubMed:14566340). Catalyzes also the oxidoreduction
CC of endocannabinoids into prostaglandin glycerol esters and PGG2 into
CC 15-hydroperoxy-PGE2. In addition, displays low glutathione transferase
CC and glutathione-dependent peroxidase activities, toward 1-chloro-2,4-
CC dinitrobenzene and 5-hydroperoxyicosatetraenoic acid (5-HPETE),
CC respectively (By similarity). {ECO:0000250|UniProtKB:O14684,
CC ECO:0000269|PubMed:10869354, ECO:0000269|PubMed:11795891,
CC ECO:0000269|PubMed:12835414, ECO:0000269|PubMed:14566340}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=prostaglandin H2 = prostaglandin E2; Xref=Rhea:RHEA:12893,
CC ChEBI:CHEBI:57405, ChEBI:CHEBI:606564; EC=5.3.99.3;
CC Evidence={ECO:0000269|PubMed:10869354, ECO:0000269|PubMed:11795891};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12894;
CC Evidence={ECO:0000250|UniProtKB:O14684};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-glyceryl-prostaglandin H2 = 2-glyceryl-prostaglandin E2;
CC Xref=Rhea:RHEA:53324, ChEBI:CHEBI:85166, ChEBI:CHEBI:137172;
CC Evidence={ECO:0000250|UniProtKB:O14684};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53325;
CC Evidence={ECO:0000250|UniProtKB:O14684};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=prostaglandin G2 = (15S)-15-hydroperoxy-prostaglandin E2;
CC Xref=Rhea:RHEA:64364, ChEBI:CHEBI:82629, ChEBI:CHEBI:152564;
CC Evidence={ECO:0000250|UniProtKB:O14684};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64365;
CC Evidence={ECO:0000250|UniProtKB:O14684};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-chloro-2,4-dinitrobenzene + glutathione = 2,4-dinitrophenyl-
CC S-glutathione + chloride + H(+); Xref=Rhea:RHEA:51220,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:17996, ChEBI:CHEBI:34718,
CC ChEBI:CHEBI:57925, ChEBI:CHEBI:133977; EC=2.5.1.18;
CC Evidence={ECO:0000250|UniProtKB:O14684};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(5S)-hydroperoxy-(6E,8Z,11Z,14Z)-eicosatetraenoate + 2
CC glutathione = (5S)-hydroxy-(6E,8Z,11Z,14Z)-eicosatetraenoate +
CC glutathione disulfide + H2O; Xref=Rhea:RHEA:48620, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:57450, ChEBI:CHEBI:57925, ChEBI:CHEBI:58297,
CC ChEBI:CHEBI:90632; Evidence={ECO:0000250|UniProtKB:O14684};
CC -!- COFACTOR:
CC Name=glutathione; Xref=ChEBI:CHEBI:57925;
CC Evidence={ECO:0000269|PubMed:11795891};
CC -!- ACTIVITY REGULATION: Activity is increased markedly in macrophages and
CC osteoblasts following pro-inflammatory stimuli.
CC {ECO:0000269|PubMed:11795891}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=37 uM for prostaglandin H2 {ECO:0000269|PubMed:11795891};
CC KM=130 uM for glutathione {ECO:0000269|PubMed:11795891};
CC pH dependence:
CC Optimum pH is 8. {ECO:0000269|PubMed:11795891};
CC -!- PATHWAY: Lipid metabolism; prostaglandin biosynthesis.
CC {ECO:0000269|PubMed:10869354}.
CC -!- SUBUNIT: Homotrimer. {ECO:0000250|UniProtKB:O14684}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000269|PubMed:11795891}; Multi-
CC pass membrane protein {ECO:0000250|UniProtKB:O14684}. Cytoplasm,
CC perinuclear region {ECO:0000250|UniProtKB:O14684}. Note=Colocalizes
CC with PTGS1/COX-1 and PTGS2/COX-2 in the perinuclear compartment.
CC {ECO:0000250|UniProtKB:O14684}.
CC -!- INDUCTION: Induced by pro-inflammatory stimuli and down-regulated by
CC anti-inflammatory glucocorticoid. {ECO:0000269|PubMed:10869354,
CC ECO:0000269|PubMed:11795891}.
CC -!- DISRUPTION PHENOTYPE: Deficient mice are viable and fertile and develop
CC normally (PubMed:12835414, PubMed:14566340). However mice display a
CC marked reduction in inflammatory responses and reduced pain sensitivity
CC (PubMed:12835414). PTGES deletion results in a reduction of PGE2 levels
CC in the central nervous system in association with the impaired LPS-
CC induced febrile response (PubMed:14566340).
CC {ECO:0000269|PubMed:12835414, ECO:0000269|PubMed:14566340}.
CC -!- SIMILARITY: Belongs to the MAPEG family. {ECO:0000305}.
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DR EMBL; AB041997; BAA96083.1; -; mRNA.
DR EMBL; AB035323; BAB71813.1; -; mRNA.
DR EMBL; AK010757; BAB27163.1; -; mRNA.
DR EMBL; AK033752; BAC28463.1; -; mRNA.
DR EMBL; AK172621; BAE43099.1; -; mRNA.
DR EMBL; BC024960; AAH24960.1; -; mRNA.
DR CCDS; CCDS15889.1; -.
DR RefSeq; NP_071860.1; NM_022415.3.
DR AlphaFoldDB; Q9JM51; -.
DR SMR; Q9JM51; -.
DR BioGRID; 211054; 1.
DR STRING; 10090.ENSMUSP00000099916; -.
DR BindingDB; Q9JM51; -.
DR ChEMBL; CHEMBL2046261; -.
DR iPTMnet; Q9JM51; -.
DR PhosphoSitePlus; Q9JM51; -.
DR MaxQB; Q9JM51; -.
DR PaxDb; Q9JM51; -.
DR PRIDE; Q9JM51; -.
DR ProteomicsDB; 291618; -.
DR Antibodypedia; 17900; 221 antibodies from 34 providers.
DR DNASU; 64292; -.
DR Ensembl; ENSMUST00000102852; ENSMUSP00000099916; ENSMUSG00000050737.
DR GeneID; 64292; -.
DR KEGG; mmu:64292; -.
DR UCSC; uc008jcz.1; mouse.
DR CTD; 9536; -.
DR MGI; MGI:1927593; Ptges.
DR VEuPathDB; HostDB:ENSMUSG00000050737; -.
DR eggNOG; ENOG502RZBK; Eukaryota.
DR GeneTree; ENSGT00390000011980; -.
DR HOGENOM; CLU_105467_1_1_1; -.
DR InParanoid; Q9JM51; -.
DR OMA; TIAQIPC; -.
DR OrthoDB; 1591261at2759; -.
DR PhylomeDB; Q9JM51; -.
DR TreeFam; TF105327; -.
DR BRENDA; 5.3.99.3; 3474.
DR Reactome; R-MMU-2162123; Synthesis of Prostaglandins (PG) and Thromboxanes (TX).
DR UniPathway; UPA00662; -.
DR BioGRID-ORCS; 64292; 0 hits in 74 CRISPR screens.
DR ChiTaRS; Ptges; mouse.
DR PRO; PR:Q9JM51; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; Q9JM51; protein.
DR Bgee; ENSMUSG00000050737; Expressed in gastrula and 135 other tissues.
DR Genevisible; Q9JM51; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0016021; C:integral component of membrane; ISS:UniProtKB.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0005641; C:nuclear envelope lumen; IDA:MGI.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:MGI.
DR GO; GO:0043295; F:glutathione binding; ISS:UniProtKB.
DR GO; GO:0004602; F:glutathione peroxidase activity; ISS:UniProtKB.
DR GO; GO:0004364; F:glutathione transferase activity; ISS:UniProtKB.
DR GO; GO:0004667; F:prostaglandin-D synthase activity; IDA:UniProtKB.
DR GO; GO:0050220; F:prostaglandin-E synthase activity; ISS:UniProtKB.
DR GO; GO:0008283; P:cell population proliferation; IGI:MGI.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IGI:MGI.
DR GO; GO:0032308; P:positive regulation of prostaglandin secretion; IMP:MGI.
DR GO; GO:0001516; P:prostaglandin biosynthetic process; IDA:UniProtKB.
DR GO; GO:0006693; P:prostaglandin metabolic process; IDA:MGI.
DR GO; GO:0031620; P:regulation of fever generation; IMP:UniProtKB.
DR GO; GO:0050727; P:regulation of inflammatory response; IMP:UniProtKB.
DR GO; GO:0019233; P:sensory perception of pain; IMP:UniProtKB.
DR Gene3D; 1.20.120.550; -; 1.
DR InterPro; IPR023352; MAPEG-like_dom_sf.
DR InterPro; IPR001129; Membr-assoc_MAPEG.
DR InterPro; IPR040162; MGST1-like.
DR PANTHER; PTHR10689; PTHR10689; 1.
DR Pfam; PF01124; MAPEG; 1.
DR SUPFAM; SSF161084; SSF161084; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Fatty acid biosynthesis; Fatty acid metabolism; Isomerase;
KW Lipid biosynthesis; Lipid metabolism; Membrane; Oxidoreductase;
KW Prostaglandin biosynthesis; Prostaglandin metabolism; Reference proteome;
KW Transferase; Transmembrane; Transmembrane helix.
FT CHAIN 1..153
FT /note="Prostaglandin E synthase"
FT /id="PRO_0000217747"
FT TOPO_DOM 1..13
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:O14684"
FT TRANSMEM 14..42
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:O14684"
FT TOPO_DOM 43..61
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:O14684"
FT TRANSMEM 62..91
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:O14684"
FT TOPO_DOM 92..96
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:O14684"
FT TRANSMEM 97..120
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:O14684"
FT TOPO_DOM 121..124
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:O14684"
FT TRANSMEM 125..153
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:O14684"
FT BINDING 39
FT /ligand="glutathione"
FT /ligand_id="ChEBI:CHEBI:57925"
FT /evidence="ECO:0000250|UniProtKB:O14684"
FT BINDING 74..78
FT /ligand="glutathione"
FT /ligand_id="ChEBI:CHEBI:57925"
FT /evidence="ECO:0000250|UniProtKB:O14684"
FT BINDING 114
FT /ligand="glutathione"
FT /ligand_id="ChEBI:CHEBI:57925"
FT /evidence="ECO:0000250|UniProtKB:O14684"
FT BINDING 118
FT /ligand="glutathione"
FT /ligand_id="ChEBI:CHEBI:57925"
FT /evidence="ECO:0000250|UniProtKB:O14684"
FT BINDING 127..131
FT /ligand="glutathione"
FT /ligand_id="ChEBI:CHEBI:57925"
FT /evidence="ECO:0000250|UniProtKB:O14684"
FT SITE 50
FT /note="Essential for protaglandin-E synthase activity"
FT /evidence="ECO:0000250|UniProtKB:O14684"
FT SITE 127
FT /note="Essential for protaglandin-E synthase activity"
FT /evidence="ECO:0000250|UniProtKB:O14684"
SQ SEQUENCE 153 AA; 17286 MW; 08A1AF2D288D53F2 CRC64;
MPSPGLVMES GQVLPAFLLC STLLVIKMYA VAVITGQMRL RKKAFANPED ALKRGGLQYY
RSDPDVERCL RAHRNDMETI YPFLFLGFVY SFLGPNPLIA WIHFLVVLTG RVVHTVAYLG
KLNPRLRSGA YVLAQFSCFS MALQILWEVA HHL
