PTGES_RAT
ID PTGES_RAT Reviewed; 153 AA.
AC Q9JHF3;
DT 07-OCT-2020, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 124.
DE RecName: Full=Prostaglandin E synthase;
DE Short=mPGES-1;
DE EC=5.3.99.3 {ECO:0000269|PubMed:10869354, ECO:0000269|PubMed:11067848};
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=Inducible prostaglandin E synthase {ECO:0000303|Ref.3};
DE AltName: Full=Microsomal prostaglandin E synthase 1;
GN Name=Ptges;
GN Synonyms=Pges {ECO:0000303|PubMed:10869354},
GN Pig12 {ECO:0000303|PubMed:10754227};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], CATALYTIC ACTIVITY, FUNCTION, INDUCTION,
RP ACTIVITY REGULATION, AND PATHWAY.
RC STRAIN=Sprague-Dawley;
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].
RC STRAIN=Wistar; TISSUE=Brain;
RX PubMed=10754227; DOI=10.1016/s0304-3940(00)00926-5;
RA Satoh K., Nagano Y., Shimomura C., Suzuki N., Saeki Y., Yokota H.;
RT "Expression of prostaglandin E synthase mRNA is induced in beta-amyloid
RT treated rat astrocytes.";
RL Neurosci. Lett. 283:221-223(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley; TISSUE=Testis;
RA Yamagata K.;
RT "inducible prostaglandin E synthase mRNA.";
RL Submitted (SEP-2000) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA], CATALYTIC ACTIVITY, FUNCTION, INDUCTION, AND
RP SUBCELLULAR LOCATION.
RX PubMed=11067848; DOI=10.1074/jbc.m006865200;
RA Mancini J.A., Blood K., Guay J., Gordon R., Claveau D., Chan C.C.,
RA Riendeau D.;
RT "Cloning, expression, and up-regulation of inducible rat prostaglandine
RT synthase during lipopolysaccharide-induced pyresis and adjuvant-induced
RT arthritis.";
RL J. Biol. Chem. 276:4469-4475(2001).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
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).
CC -!- FUNCTION: Terminal enzyme of the cyclooxygenase (COX)-2-mediated
CC prostaglandin E2 (PGE2) biosynthetic pathway. Catalyzes the
CC glutathione-dependent oxidoreduction of prostaglandin endoperoxide H2
CC (PGH2) to prostaglandin E2 (PGE2) in response to inflammatory stimuli
CC (PubMed:10869354, PubMed:11067848). Plays a key role in inflammation
CC response, fever and pain (By similarity). Catalyzes also the
CC oxidoreduction of endocannabinoids into prostaglandin glycerol esters
CC and PGG2 into 15-hydroperoxy-PGE2. In addition, displays low
CC glutathione transferase and glutathione-dependent peroxidase
CC activities, toward 1-chloro-2,4-dinitrobenzene and 5-
CC hydroperoxyicosatetraenoic acid (5-HPETE), respectively (By
CC similarity). {ECO:0000250|UniProtKB:O14684,
CC ECO:0000250|UniProtKB:Q9JM51, ECO:0000269|PubMed:10869354,
CC ECO:0000269|PubMed:11067848}.
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:11067848};
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:0000250|UniProtKB:O14684};
CC -!- ACTIVITY REGULATION: Activity is increased following LPS stimulation
CC and down-regulated by the anti-inflammatory glucocorticoid
CC dexamethasone. {ECO:0000269|PubMed:10869354}.
CC -!- PATHWAY: Lipid metabolism; prostaglandin biosynthesis.
CC {ECO:0000269|PubMed:10869354}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000269|PubMed:11067848}; 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: Up-regulated after treatment with LPS or in a rat model of
CC adjuvant-induced arthritis (PubMed:10869354, PubMed:11067848). Down-
CC regulated by the anti-inflammatory glucocorticoid dexamethasone
CC (PubMed:10869354). {ECO:0000269|PubMed:10869354,
CC ECO:0000269|PubMed:11067848}.
CC -!- SIMILARITY: Belongs to the MAPEG family. {ECO:0000305}.
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DR EMBL; AB041998; BAA96084.1; -; mRNA.
DR EMBL; AB035145; BAA95808.1; -; mRNA.
DR EMBL; AB048730; BAB20597.1; -; mRNA.
DR EMBL; AF280967; AAG24803.1; -; mRNA.
DR EMBL; AC125306; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH474001; EDL93288.1; -; Genomic_DNA.
DR EMBL; BC105858; AAI05859.1; -; mRNA.
DR RefSeq; NP_067594.1; NM_021583.3.
DR AlphaFoldDB; Q9JHF3; -.
DR SMR; Q9JHF3; -.
DR STRING; 10116.ENSRNOP00000044191; -.
DR PaxDb; Q9JHF3; -.
DR GeneID; 59103; -.
DR KEGG; rno:59103; -.
DR UCSC; RGD:62076; rat.
DR CTD; 9536; -.
DR RGD; 62076; Ptges.
DR eggNOG; ENOG502RZBK; Eukaryota.
DR HOGENOM; CLU_105467_1_1_1; -.
DR InParanoid; Q9JHF3; -.
DR OMA; TIAQIPC; -.
DR OrthoDB; 1591261at2759; -.
DR PhylomeDB; Q9JHF3; -.
DR Reactome; R-RNO-2162123; Synthesis of Prostaglandins (PG) and Thromboxanes (TX).
DR UniPathway; UPA00662; -.
DR Proteomes; UP000002494; Chromosome 3.
DR Proteomes; UP000234681; Chromosome 3.
DR Bgee; ENSRNOG00000006320; Expressed in ovary and 17 other tissues.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0016021; C:integral component of membrane; ISO:RGD.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:RGD.
DR GO; GO:0005641; C:nuclear envelope lumen; ISO:RGD.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:RGD.
DR GO; GO:0043295; F:glutathione binding; ISO:RGD.
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; IDA:RGD.
DR GO; GO:0002526; P:acute inflammatory response; IEP:RGD.
DR GO; GO:0002544; P:chronic inflammatory response; IEP:RGD.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISO:RGD.
DR GO; GO:0032308; P:positive regulation of prostaglandin secretion; ISO:RGD.
DR GO; GO:0001516; P:prostaglandin biosynthetic process; IDA:RGD.
DR GO; GO:0006693; P:prostaglandin metabolic process; ISO:RGD.
DR GO; GO:0031620; P:regulation of fever generation; ISS:UniProtKB.
DR GO; GO:0050727; P:regulation of inflammatory response; ISS:UniProtKB.
DR GO; GO:0051592; P:response to calcium ion; IEP:RGD.
DR GO; GO:0034097; P:response to cytokine; IEP:RGD.
DR GO; GO:0032496; P:response to lipopolysaccharide; IEP:RGD.
DR GO; GO:0014070; P:response to organic cyclic compound; IEP:RGD.
DR GO; GO:0032526; P:response to retinoic acid; IEP:RGD.
DR GO; GO:0019233; P:sensory perception of pain; ISS: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_0000451029"
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..98
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:O14684"
FT TRANSMEM 99..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; 17273 MW; EA2E91E143CD7886 CRC64;
MTSLGLVMEN SQVLPAFLLC STLLVIKMYA VAVITGQVRL RKKAFANPED ALKRGGLQYC
RSDPDVERCL RAHRNDMETI YPFLFLGFVY SFLGPNPLIA WIHFLVVLTG RVVHTVAYLG
KMNPRIRSGA YVLAQFACFS MALQILWEVA HHL
