ID PTGES_HUMAN Reviewed; 152 AA.
AC O14684; O14900; Q5SZC0;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 30-MAY-2000, sequence version 2.
DT 27-MAR-2024, entry version 176.
DE RecName: Full=Prostaglandin E synthase;
DE EC=5.3.99.3 {ECO:0000269|PubMed:10377395, ECO:0000269|PubMed:10869354, ECO:0000269|PubMed:12244105, ECO:0000269|PubMed:12672824, ECO:0000269|PubMed:16439136, ECO:0000269|PubMed:18682561, ECO:0000269|PubMed:27684486};
DE AltName: Full=Glutathione peroxidase PTGES;
DE EC=1.11.1.- {ECO:0000269|PubMed:12244105};
DE AltName: Full=Glutathione transferase PTGES;
DE EC=2.5.1.18 {ECO:0000269|PubMed:12672824, ECO:0000269|PubMed:27684486};
DE AltName: Full=Microsomal glutathione S-transferase 1-like 1 {ECO:0000303|PubMed:10377395};
DE Short=MGST1-L1 {ECO:0000303|PubMed:10377395};
DE AltName: Full=Microsomal prostaglandin E synthase 1 {ECO:0000303|PubMed:12672824};
DE Short=MPGES-1 {ECO:0000303|PubMed:12672824};
DE AltName: Full=p53-induced gene 12 protein {ECO:0000303|PubMed:9305847};
GN Name=PTGES;
GN Synonyms=MGST1L1 {ECO:0000303|PubMed:10377395}, MPGES1, PGES,
GN PIG12 {ECO:0000303|PubMed:9305847};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND INDUCTION BY TP53.
RC TISSUE=Colon cancer;
RX PubMed=9305847; DOI=10.1038/38525;
RA Polyak K., Xia Y., Zweier J.L., Kinzler K.W., Vogelstein B.;
RT "A model for p53-induced apoptosis.";
RL Nature 389:300-306(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], CATALYTIC ACTIVITY, FUNCTION, INDUCTION, AND
RP SUBCELLULAR LOCATION.
RX PubMed=10377395; DOI=10.1073/pnas.96.13.7220;
RA Jakobsson P.-J., Thoren S., Morgenstern R., Samuelsson B.;
RT "Identification of human prostaglandin E synthase: a microsomal,
RT glutathione-dependent, inducible enzyme, constituting a potential novel
RT drug target.";
RL Proc. Natl. Acad. Sci. U.S.A. 96:7220-7225(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], INDUCTION, AND ACTIVITY REGULATION.
RX PubMed=10760517; DOI=10.1016/s0014-5793(00)01367-3;
RA Forsberg L., Leeb L., Thoren S., Morgenstern R., Jakobsson P.J.;
RT "Human glutathione dependent prostaglandin E synthase: gene structure and
RT regulation.";
RL FEBS Lett. 471:78-82(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Mammary gland;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG SeattleSNPs variation discovery resource;
RL Submitted (APR-2007) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L.,
RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S.,
RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J.,
RA Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Pancreas;
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 [8]
RP MUTAGENESIS OF ARG-70; ARG-110 AND TYR-117, CATALYTIC ACTIVITY, FUNCTION,
RP SUBCELLULAR LOCATION, COFACTOR, AND PATHWAY.
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 [9]
RP CATALYTIC ACTIVITY, AND FUNCTION.
RX PubMed=12244105; DOI=10.1074/jbc.m206788200;
RA Kozak K.R., Crews B.C., Morrow J.D., Wang L.H., Ma Y.H., Weinander R.,
RA Jakobsson P.J., Marnett L.J.;
RT "Metabolism of the endocannabinoids, 2-arachidonylglycerol and anandamide,
RT into prostaglandin, thromboxane, and prostacyclin glycerol esters and
RT ethanolamides.";
RL J. Biol. Chem. 277:44877-44885(2002).
RN [10]
RP CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, COFACTOR, AND FUNCTION.
RX PubMed=12460774; DOI=10.1016/s1046-5928(02)00566-1;
RA Ouellet M., Falgueyret J.-P., Ear P.H., Pen A., Mancini J.A., Riendeau D.,
RA Percival M.D.;
RT "Purification and characterization of recombinant microsomal prostaglandin
RT E synthase-1.";
RL Protein Expr. Purif. 26:489-495(2002).
RN [11]
RP CATALYTIC ACTIVITY, FUNCTION, MUTAGENESIS OF GLN-36; ARG-110; THR-114;
RP TYR-130 AND GLN-134, SUBCELLULAR LOCATION, AND BIOPHYSICOCHEMICAL
RP PROPERTIES.
RX PubMed=16439136; DOI=10.1016/j.bmc.2006.01.010;
RA Huang X., Yan W., Gao D., Tong M., Tai H.H., Zhan C.G.;
RT "Structural and functional characterization of human microsomal
RT prostaglandin E synthase-1 by computational modeling and site-directed
RT mutagenesis.";
RL Bioorg. Med. Chem. 14:3553-3562(2006).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [13]
RP CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, FUNCTION, AND
RP COFACTOR.
RX PubMed=12672824; DOI=10.1074/jbc.m303227200;
RA Thoren S., Weinander R., Saha S., Jegerschold C., Pettersson P.L.,
RA Samuelsson B., Hebert H., Hamberg M., Morgenstern R., Jakobsson P.-J.;
RT "Human microsomal prostaglandin E synthase-1: purification, functional
RT characterization, and projection structure determination.";
RL J. Biol. Chem. 278:22199-22209(2003).
RN [14]
RP FUNCTION, CATALYTIC ACTIVITY, MUTAGENESIS OF ASP-49; ARG-73; ARG-126 AND
RP SER-127, AND COFACTOR.
RX PubMed=27684486; DOI=10.1371/journal.pone.0163600;
RA Raouf J., Rafique N., Goodman M.C., Idborg H., Bergqvist F.,
RA Armstrong R.N., Jakobsson P.J., Morgenstern R., Spahiu L.;
RT "Arg126 and Asp49 Are Essential for the Catalytic Function of Microsomal
RT Prostaglandin E2 Synthase 1 and Ser127 Is Not.";
RL PLoS ONE 11:e0163600-e0163600(2016).
RN [15]
RP CATALYTIC ACTIVITY, FUNCTION, MUTAGENESIS OF ASP-49; ARG-126 AND SER-127,
RP AND COFACTOR.
RX PubMed=26755582; DOI=10.1073/pnas.1522891113;
RA Brock J.S., Hamberg M., Balagunaseelan N., Goodman M., Morgenstern R.,
RA Strandback E., Samuelsson B., Rinaldo-Matthis A., Haeggstroem J.Z.;
RT "A dynamic Asp-Arg interaction is essential for catalysis in microsomal
RT prostaglandin E2 synthase.";
RL Proc. Natl. Acad. Sci. U.S.A. 113:972-977(2016).
RN [16]
RP STRUCTURE BY ELECTRON MICROSCOPY (3.5 ANGSTROMS) IN COMPLEX WITH
RP GLUTATHIONE, FUNCTION, CATALYTIC ACTIVITY, COFACTOR, SUBCELLULAR LOCATION,
RP TRANSMEMBRANE TOPOLOGY, AND MUTAGENESIS OF GLU-66; ARG-67; ARG-70; HIS-72;
RP ARG-110 AND TYR-117.
RX PubMed=18682561; DOI=10.1073/pnas.0802894105;
RA Jegerschold C., Pawelzik S.C., Purhonen P., Bhakat P., Gheorghe K.R.,
RA Gyobu N., Mitsuoka K., Morgenstern R., Jakobsson P.J., Hebert H.;
RT "Structural basis for induced formation of the inflammatory mediator
RT prostaglandin E2.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:11110-11115(2008).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (1.16 ANGSTROMS) IN COMPLEXES WITH GLUTATIONE,
RP SUBUNIT, AND PROBABLE TOPOLOGY.
RX PubMed=23431194; DOI=10.1073/pnas.1218504110;
RA Sjogren T., Nord J., Ek M., Johansson P., Liu G., Geschwindner S.;
RT "Crystal structure of microsomal prostaglandin E2 synthase provides insight
RT into diversity in the MAPEG superfamily.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:3806-3811(2013).
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:18682561, PubMed:10377395, PubMed:12672824, PubMed:12460774,
CC PubMed:10869354, PubMed:12244105). 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 (PubMed:12244105, PubMed:12672824).
CC In addition, displays low glutathione transferase and glutathione-
CC dependent peroxidase activities, toward 1-chloro-2,4-dinitrobenzene and
CC 5-hydroperoxyicosatetraenoic acid (5-HPETE), respectively
CC (PubMed:12672824). {ECO:0000250|UniProtKB:Q9JM51,
CC ECO:0000269|PubMed:10377395, ECO:0000269|PubMed:10869354,
CC ECO:0000269|PubMed:12244105, ECO:0000269|PubMed:12460774,
CC ECO:0000269|PubMed:12672824, ECO:0000269|PubMed:18682561}.
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:10377395, ECO:0000269|PubMed:10869354,
CC ECO:0000269|PubMed:12244105, ECO:0000269|PubMed:12460774,
CC ECO:0000269|PubMed:12672824, ECO:0000269|PubMed:16439136,
CC ECO:0000269|PubMed:18682561, ECO:0000269|PubMed:26755582,
CC ECO:0000269|PubMed:27684486};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12894;
CC Evidence={ECO:0000305|PubMed:10377395, ECO:0000305|PubMed:12460774,
CC ECO:0000305|PubMed:12672824, ECO:0000305|PubMed:16439136};
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:0000269|PubMed:12244105};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:53325;
CC Evidence={ECO:0000305|PubMed:12244105};
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:0000269|PubMed:12672824};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64365;
CC Evidence={ECO:0000305|PubMed:12672824};
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:0000269|PubMed:12672824, ECO:0000269|PubMed:27684486};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:51221;
CC Evidence={ECO:0000305|PubMed:27684486};
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:0000269|PubMed:12244105};
CC -!- COFACTOR:
CC Name=glutathione; Xref=ChEBI:CHEBI:57925;
CC Evidence={ECO:0000269|PubMed:10869354, ECO:0000269|PubMed:12460774,
CC ECO:0000269|PubMed:12672824, ECO:0000269|PubMed:18682561,
CC ECO:0000269|PubMed:27684486};
CC -!- ACTIVITY REGULATION: Induced by interleukin IL1B.
CC {ECO:0000269|PubMed:10760517}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=75 uM for glutathione {ECO:0000269|PubMed:12460774};
CC KM=160 uM for prostaglandin H2 (at 37 degrees)
CC {ECO:0000269|PubMed:12672824};
CC KM=71 uM for glutathione (at 37 degrees)
CC {ECO:0000269|PubMed:12672824};
CC KM=160 uM for prostaglandin G2 (at 37 degrees)
CC {ECO:0000269|PubMed:12672824};
CC KM=14 uM for prostaglandin H2 {ECO:0000269|PubMed:12460774};
CC KM=130 uM for prostaglandin H2 {ECO:0000269|PubMed:16439136};
CC Vmax=170 umol/min/mg enzyme with prostaglandin H2 as substrate
CC {ECO:0000269|PubMed:12672824};
CC Note=kcat is 50 sec(-1) for prostaglandin H2 as substrate
CC (PubMed:12672824). kcat is 75 sec(-1) for prostaglandin H2 as
CC substrate (PubMed:12672824). kcat is 21 sec(-1) for glutathione as
CC substrate (PubMed:12672824). {ECO:0000269|PubMed:12672824};
CC -!- PATHWAY: Lipid metabolism; prostaglandin biosynthesis.
CC {ECO:0000269|PubMed:10869354}.
CC -!- SUBUNIT: Homotrimer. {ECO:0000269|PubMed:12672824,
CC ECO:0000269|PubMed:23431194}.
CC -!- INTERACTION:
CC O14684; O15155: BET1; NbExp=3; IntAct=EBI-11161398, EBI-749204;
CC O14684; Q8WVX3-2: C4orf3; NbExp=3; IntAct=EBI-11161398, EBI-12003442;
CC O14684; Q08426: EHHADH; NbExp=3; IntAct=EBI-11161398, EBI-2339219;
CC O14684; Q8WWP7: GIMAP1; NbExp=3; IntAct=EBI-11161398, EBI-11991950;
CC O14684; Q96F15: GIMAP5; NbExp=3; IntAct=EBI-11161398, EBI-6166686;
CC O14684; Q04941: PLP2; NbExp=3; IntAct=EBI-11161398, EBI-608347;
CC O14684; Q96IW7: SEC22A; NbExp=3; IntAct=EBI-11161398, EBI-8652744;
CC O14684; Q8N6R1: SERP2; NbExp=3; IntAct=EBI-11161398, EBI-749270;
CC O14684; Q9NRQ5: SMCO4; NbExp=3; IntAct=EBI-11161398, EBI-8640191;
CC O14684; Q96HH6: TMEM19; NbExp=3; IntAct=EBI-11161398, EBI-741829;
CC O14684; Q9H0R3: TMEM222; NbExp=3; IntAct=EBI-11161398, EBI-347385;
CC O14684; Q6PI78: TMEM65; NbExp=3; IntAct=EBI-11161398, EBI-6656213;
CC O14684; Q15836: VAMP3; NbExp=3; IntAct=EBI-11161398, EBI-722343;
CC O14684; O75379: VAMP4; NbExp=3; IntAct=EBI-11161398, EBI-744953;
CC O14684; O95292: VAPB; NbExp=3; IntAct=EBI-11161398, EBI-1188298;
CC O14684; O95070: YIF1A; NbExp=3; IntAct=EBI-11161398, EBI-2799703;
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000269|PubMed:10377395,
CC ECO:0000269|PubMed:16439136, ECO:0000269|PubMed:18682561,
CC ECO:0000269|PubMed:27684486}; Multi-pass membrane protein
CC {ECO:0000303|PubMed:18682561}. Cytoplasm, perinuclear region
CC {ECO:0000269|PubMed:10869354}. Note=Colocalizes with PTGS1/COX-1 and
CC PTGS2/COX-2 in the perinuclear compartment.
CC {ECO:0000269|PubMed:10869354}.
CC -!- INDUCTION: Induced by the interleukin IL1B (PubMed:10377395,
CC PubMed:10760517). Induced By p53/TP53 (PubMed:9305847).
CC {ECO:0000269|PubMed:10377395, ECO:0000269|PubMed:10760517,
CC ECO:0000269|PubMed:9305847}.
CC -!- SIMILARITY: Belongs to the MAPEG family. {ECO:0000305}.
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DR EMBL; AF010316; AAC39534.1; -; mRNA.
DR EMBL; AF027740; AAB82299.1; -; mRNA.
DR EMBL; AJ271802; CAB72099.1; -; Genomic_DNA.
DR EMBL; AJ271803; CAB72099.1; JOINED; Genomic_DNA.
DR EMBL; AJ271804; CAB72099.1; JOINED; Genomic_DNA.
DR EMBL; AK311947; BAG34888.1; -; mRNA.
DR EMBL; EF543149; ABQ01233.1; -; Genomic_DNA.
DR EMBL; AL590369; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL592219; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC008280; AAH08280.1; -; mRNA.
DR CCDS; CCDS6927.1; -.
DR RefSeq; NP_004869.1; NM_004878.4.
DR PDB; 3DWW; EM; 3.50 A; A/B/C=1-152.
DR PDB; 4AL0; X-ray; 1.16 A; A=1-152.
DR PDB; 4AL1; X-ray; 1.95 A; A=1-152.
DR PDB; 4BPM; X-ray; 2.08 A; A=10-152.
DR PDB; 4WAB; X-ray; 2.70 A; A=10-151.
DR PDB; 4YK5; X-ray; 1.42 A; A=2-152.
DR PDB; 4YL0; X-ray; 1.52 A; A=5-152.
DR PDB; 4YL1; X-ray; 1.41 A; A=5-152.
DR PDB; 4YL3; X-ray; 1.41 A; A=5-152.
DR PDB; 5BQG; X-ray; 1.44 A; A=2-152.
DR PDB; 5BQH; X-ray; 1.60 A; A=2-152.
DR PDB; 5BQI; X-ray; 1.88 A; A=2-152.
DR PDB; 5K0I; X-ray; 1.30 A; A=2-152.
DR PDB; 5T36; X-ray; 1.40 A; A=2-152.
DR PDB; 5T37; X-ray; 1.76 A; A=2-152.
DR PDB; 5TL9; X-ray; 1.20 A; A=2-152.
DR PDB; 6VL4; X-ray; 1.40 A; A=2-152.
DR PDB; 8PYV; X-ray; 1.77 A; A=1-152.
DR PDBsum; 3DWW; -.
DR PDBsum; 4AL0; -.
DR PDBsum; 4AL1; -.
DR PDBsum; 4BPM; -.
DR PDBsum; 4WAB; -.
DR PDBsum; 4YK5; -.
DR PDBsum; 4YL0; -.
DR PDBsum; 4YL1; -.
DR PDBsum; 4YL3; -.
DR PDBsum; 5BQG; -.
DR PDBsum; 5BQH; -.
DR PDBsum; 5BQI; -.
DR PDBsum; 5K0I; -.
DR PDBsum; 5T36; -.
DR PDBsum; 5T37; -.
DR PDBsum; 5TL9; -.
DR PDBsum; 6VL4; -.
DR PDBsum; 8PYV; -.
DR AlphaFoldDB; O14684; -.
DR SMR; O14684; -.
DR BioGRID; 114912; 25.
DR IntAct; O14684; 20.
DR STRING; 9606.ENSP00000342385; -.
DR BindingDB; O14684; -.
DR ChEMBL; CHEMBL5658; -.
DR DrugCentral; O14684; -.
DR GuidetoPHARMACOLOGY; 1377; -.
DR SwissLipids; SLP:000001631; -.
DR GlyGen; O14684; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; O14684; -.
DR PhosphoSitePlus; O14684; -.
DR SwissPalm; O14684; -.
DR BioMuta; PTGES; -.
DR EPD; O14684; -.
DR jPOST; O14684; -.
DR MassIVE; O14684; -.
DR MaxQB; O14684; -.
DR PaxDb; 9606-ENSP00000342385; -.
DR PeptideAtlas; O14684; -.
DR ProteomicsDB; 48167; -.
DR Pumba; O14684; -.
DR TopDownProteomics; O14684; -.
DR Antibodypedia; 17900; 249 antibodies from 34 providers.
DR DNASU; 9536; -.
DR Ensembl; ENST00000340607.5; ENSP00000342385.4; ENSG00000148344.11.
DR GeneID; 9536; -.
DR KEGG; hsa:9536; -.
DR MANE-Select; ENST00000340607.5; ENSP00000342385.4; NM_004878.5; NP_004869.1.
DR UCSC; uc004byi.4; human.
DR AGR; HGNC:9599; -.
DR CTD; 9536; -.
DR DisGeNET; 9536; -.
DR GeneCards; PTGES; -.
DR HGNC; HGNC:9599; PTGES.
DR HPA; ENSG00000148344; Tissue enhanced (seminal vesicle, urinary bladder).
DR MIM; 605172; gene.
DR neXtProt; NX_O14684; -.
DR OpenTargets; ENSG00000148344; -.
DR PharmGKB; PA33948; -.
DR VEuPathDB; HostDB:ENSG00000148344; -.
DR eggNOG; ENOG502RZBK; Eukaryota.
DR GeneTree; ENSGT00390000011980; -.
DR HOGENOM; CLU_105467_1_1_1; -.
DR InParanoid; O14684; -.
DR OMA; TIAQIPC; -.
DR OrthoDB; 5347993at2759; -.
DR PhylomeDB; O14684; -.
DR TreeFam; TF105327; -.
DR BioCyc; MetaCyc:HS07518-MONOMER; -.
DR BRENDA; 5.3.99.3; 2681.
DR PathwayCommons; O14684; -.
DR Reactome; R-HSA-2162123; Synthesis of Prostaglandins (PG) and Thromboxanes (TX).
DR SABIO-RK; O14684; -.
DR SignaLink; O14684; -.
DR SIGNOR; O14684; -.
DR UniPathway; UPA00662; -.
DR BioGRID-ORCS; 9536; 9 hits in 1149 CRISPR screens.
DR ChiTaRS; PTGES; human.
DR EvolutionaryTrace; O14684; -.
DR GeneWiki; PTGES; -.
DR GenomeRNAi; 9536; -.
DR Pharos; O14684; Tchem.
DR PRO; PR:O14684; -.
DR Proteomes; UP000005640; Chromosome 9.
DR RNAct; O14684; Protein.
DR Bgee; ENSG00000148344; Expressed in palpebral conjunctiva and 159 other cell types or tissues.
DR Genevisible; O14684; HS.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0016020; C:membrane; IDA:UniProtKB.
DR GO; GO:0005641; C:nuclear envelope lumen; IEA:Ensembl.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0043295; F:glutathione binding; IDA:UniProtKB.
DR GO; GO:0004602; F:glutathione peroxidase activity; IDA:UniProtKB.
DR GO; GO:0004364; F:glutathione transferase activity; IDA:UniProtKB.
DR GO; GO:0004667; F:prostaglandin-D synthase activity; IEA:Ensembl.
DR GO; GO:0050220; F:prostaglandin-E synthase activity; IDA:UniProtKB.
DR GO; GO:0008283; P:cell population proliferation; IEA:Ensembl.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IEA:Ensembl.
DR GO; GO:0032308; P:positive regulation of prostaglandin secretion; IEA:Ensembl.
DR GO; GO:0001516; P:prostaglandin biosynthetic process; IDA:UniProtKB.
DR GO; GO:0006693; P:prostaglandin metabolic process; TAS:ProtInc.
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:0019233; P:sensory perception of pain; ISS:UniProtKB.
DR GO; GO:0007165; P:signal transduction; NAS:ProtInc.
DR Gene3D; 1.20.120.550; Membrane associated eicosanoid/glutathione metabolism-like domain; 1.
DR InterPro; IPR023352; MAPEG-like_dom_sf.
DR InterPro; IPR001129; Membr-assoc_MAPEG.
DR InterPro; IPR040162; MGST1-like.
DR PANTHER; PTHR10689; MICROSOMAL GLUTATHIONE S-TRANSFERASE 1; 1.
DR PANTHER; PTHR10689:SF9; PROSTAGLANDIN E SYNTHASE; 1.
DR Pfam; PF01124; MAPEG; 1.
DR SUPFAM; SSF161084; MAPEG domain-like; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cytoplasm; Fatty acid biosynthesis; Fatty acid metabolism;
KW Isomerase; Lipid biosynthesis; Lipid metabolism; Membrane; Oxidoreductase;
KW Prostaglandin biosynthesis; Prostaglandin metabolism; Reference proteome;
KW Transferase; Transmembrane; Transmembrane helix.
FT CHAIN 1..152
FT /note="Prostaglandin E synthase"
FT /id="PRO_0000217745"
FT TOPO_DOM 1..12
FT /note="Lumenal"
FT /evidence="ECO:0000305|PubMed:23431194"
FT TRANSMEM 13..41
FT /note="Helical"
FT /evidence="ECO:0000305|PubMed:23431194"
FT TOPO_DOM 42..60
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:23431194"
FT TRANSMEM 61..90
FT /note="Helical"
FT /evidence="ECO:0000305|PubMed:23431194"
FT TOPO_DOM 91..95
FT /note="Lumenal"
FT /evidence="ECO:0000305|PubMed:23431194"
FT TRANSMEM 96..119
FT /note="Helical"
FT /evidence="ECO:0000305|PubMed:23431194"
FT TOPO_DOM 120..123
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:23431194"
FT TRANSMEM 124..152
FT /note="Helical"
FT /evidence="ECO:0000305|PubMed:23431194"
FT BINDING 38
FT /ligand="glutathione"
FT /ligand_id="ChEBI:CHEBI:57925"
FT /evidence="ECO:0000269|PubMed:18682561,
FT ECO:0000269|PubMed:23431194, ECO:0007744|PDB:4AL0,
FT ECO:0007744|PDB:4BPM, ECO:0007744|PDB:4WAB,
FT ECO:0007744|PDB:4YK5, ECO:0007744|PDB:4YL0,
FT ECO:0007744|PDB:4YL1, ECO:0007744|PDB:4YL3,
FT ECO:0007744|PDB:5BQG, ECO:0007744|PDB:5BQH,
FT ECO:0007744|PDB:5BQI, ECO:0007744|PDB:5K0I,
FT ECO:0007744|PDB:5T36, ECO:0007744|PDB:5T37,
FT ECO:0007744|PDB:5TL9"
FT BINDING 73..77
FT /ligand="glutathione"
FT /ligand_id="ChEBI:CHEBI:57925"
FT /evidence="ECO:0000269|PubMed:18682561,
FT ECO:0000269|PubMed:23431194, ECO:0007744|PDB:4AL0,
FT ECO:0007744|PDB:4BPM, ECO:0007744|PDB:4WAB,
FT ECO:0007744|PDB:4YK5, ECO:0007744|PDB:4YL0,
FT ECO:0007744|PDB:4YL1, ECO:0007744|PDB:4YL3,
FT ECO:0007744|PDB:5BQG, ECO:0007744|PDB:5BQH,
FT ECO:0007744|PDB:5BQI, ECO:0007744|PDB:5K0I,
FT ECO:0007744|PDB:5T36, ECO:0007744|PDB:5T37,
FT ECO:0007744|PDB:5TL9"
FT BINDING 113
FT /ligand="glutathione"
FT /ligand_id="ChEBI:CHEBI:57925"
FT /evidence="ECO:0000269|PubMed:18682561,
FT ECO:0000269|PubMed:23431194, ECO:0007744|PDB:4AL0,
FT ECO:0007744|PDB:4BPM, ECO:0007744|PDB:4WAB,
FT ECO:0007744|PDB:4YK5, ECO:0007744|PDB:4YL0,
FT ECO:0007744|PDB:4YL1, ECO:0007744|PDB:4YL3,
FT ECO:0007744|PDB:5BQG, ECO:0007744|PDB:5BQH,
FT ECO:0007744|PDB:5BQI, ECO:0007744|PDB:5K0I,
FT ECO:0007744|PDB:5T36, ECO:0007744|PDB:5T37,
FT ECO:0007744|PDB:5TL9"
FT BINDING 117
FT /ligand="glutathione"
FT /ligand_id="ChEBI:CHEBI:57925"
FT /evidence="ECO:0000269|PubMed:18682561,
FT ECO:0000269|PubMed:23431194, ECO:0007744|PDB:4AL0,
FT ECO:0007744|PDB:4BPM, ECO:0007744|PDB:4WAB,
FT ECO:0007744|PDB:4YK5, ECO:0007744|PDB:4YL0,
FT ECO:0007744|PDB:4YL1, ECO:0007744|PDB:4YL3,
FT ECO:0007744|PDB:5BQG, ECO:0007744|PDB:5BQH,
FT ECO:0007744|PDB:5BQI, ECO:0007744|PDB:5K0I,
FT ECO:0007744|PDB:5T36, ECO:0007744|PDB:5T37,
FT ECO:0007744|PDB:5TL9"
FT BINDING 126..130
FT /ligand="glutathione"
FT /ligand_id="ChEBI:CHEBI:57925"
FT /evidence="ECO:0000269|PubMed:18682561,
FT ECO:0000269|PubMed:23431194, ECO:0007744|PDB:4AL0,
FT ECO:0007744|PDB:4BPM, ECO:0007744|PDB:4WAB,
FT ECO:0007744|PDB:4YK5, ECO:0007744|PDB:4YL0,
FT ECO:0007744|PDB:4YL1, ECO:0007744|PDB:4YL3,
FT ECO:0007744|PDB:5BQG, ECO:0007744|PDB:5BQH,
FT ECO:0007744|PDB:5BQI, ECO:0007744|PDB:5K0I,
FT ECO:0007744|PDB:5T36, ECO:0007744|PDB:5T37,
FT ECO:0007744|PDB:5TL9"
FT SITE 49
FT /note="Essential for protaglandin-E synthase activity"
FT /evidence="ECO:0000269|PubMed:26755582,
FT ECO:0000269|PubMed:27684486"
FT SITE 126
FT /note="Essential for protaglandin-E synthase activity"
FT /evidence="ECO:0000269|PubMed:26755582,
FT ECO:0000269|PubMed:27684486"
FT MUTAGEN 36
FT /note="Q->E: Keeps about 40-50% of prostaglandin-E synthase
FT activity."
FT /evidence="ECO:0000269|PubMed:16439136"
FT MUTAGEN 49
FT /note="D->A: Loss of prostaglandin-E synthase activity."
FT /evidence="ECO:0000269|PubMed:27684486"
FT MUTAGEN 49
FT /note="D->N: Loss of prostaglandin-E synthase activity."
FT /evidence="ECO:0000269|PubMed:26755582"
FT MUTAGEN 66
FT /note="E->A: Reduces protaglandin-E synthase activity by
FT 50%."
FT /evidence="ECO:0000269|PubMed:18682561"
FT MUTAGEN 67
FT /note="R->A: Loss of prostaglandin-E synthase activity."
FT /evidence="ECO:0000269|PubMed:18682561"
FT MUTAGEN 70
FT /note="R->A: Slightly reduced protaglandin-E synthase
FT activity."
FT /evidence="ECO:0000269|PubMed:18682561"
FT MUTAGEN 70
FT /note="R->S: No effect on protaglandin-E synthase
FT activity."
FT /evidence="ECO:0000269|PubMed:10869354"
FT MUTAGEN 72
FT /note="H->A: Reduces protaglandin-E synthase activity by
FT 70%."
FT /evidence="ECO:0000269|PubMed:18682561"
FT MUTAGEN 73
FT /note="R->A: Retains partial of protaglandin-E synthase
FT activity."
FT /evidence="ECO:0000269|PubMed:27684486"
FT MUTAGEN 73
FT /note="R->L: Loss of protaglandin-E synthase activity."
FT /evidence="ECO:0000269|PubMed:27684486"
FT MUTAGEN 110
FT /note="R->A,S: Loss of protaglandin-E synthase activity."
FT /evidence="ECO:0000269|PubMed:10869354,
FT ECO:0000269|PubMed:18682561"
FT MUTAGEN 110
FT /note="R->T: Retains 17.8% of protaglandin-E synthase
FT activity."
FT /evidence="ECO:0000269|PubMed:16439136"
FT MUTAGEN 114
FT /note="T->V: Retains 21.3% activity of protaglandin-E
FT synthase activity."
FT /evidence="ECO:0000269|PubMed:16439136"
FT MUTAGEN 117
FT /note="Y->A: Loss of protaglandin-E synthase activity."
FT /evidence="ECO:0000269|PubMed:18682561"
FT MUTAGEN 117
FT /note="Y->F: No effect on protaglandin-E synthase
FT activity."
FT /evidence="ECO:0000269|PubMed:10869354,
FT ECO:0000269|PubMed:18682561"
FT MUTAGEN 126
FT /note="R->A,L: Loss of prostaglandin-E synthase activity."
FT /evidence="ECO:0000269|PubMed:27684486"
FT MUTAGEN 126
FT /note="R->K: Loss of prostaglandin-E synthase activity.
FT Transforms prostaglandin-E synthase activity to
FT prostaglandin-F(2alpha)synthase activity."
FT /evidence="ECO:0000269|PubMed:26755582"
FT MUTAGEN 126
FT /note="R->Q: Loss of prostaglandin-E synthase activity."
FT /evidence="ECO:0000269|PubMed:26755582"
FT MUTAGEN 127
FT /note="S->A: No effect on protaglandin-E synthase
FT activity."
FT /evidence="ECO:0000269|PubMed:26755582,
FT ECO:0000269|PubMed:27684486"
FT MUTAGEN 130
FT /note="Y->I: Loss of protaglandin-E synthase activity."
FT /evidence="ECO:0000269|PubMed:16439136"
FT MUTAGEN 134
FT /note="Q->E: Keeps about 40-50% of prostaglandin-E synthase
FT activity."
FT /evidence="ECO:0000269|PubMed:16439136"
FT CONFLICT 55
FT /note="G -> GG (in Ref. 1; AAC39534)"
FT /evidence="ECO:0000305"
FT HELIX 6..9
FT /evidence="ECO:0007829|PDB:5TL9"
FT HELIX 13..41
FT /evidence="ECO:0007829|PDB:4AL0"
FT STRAND 44..46
FT /evidence="ECO:0007829|PDB:4AL0"
FT HELIX 47..52
FT /evidence="ECO:0007829|PDB:4AL0"
FT HELIX 56..58
FT /evidence="ECO:0007829|PDB:4AL0"
FT HELIX 63..90
FT /evidence="ECO:0007829|PDB:4AL0"
FT HELIX 96..118
FT /evidence="ECO:0007829|PDB:4AL0"
FT HELIX 125..150
FT /evidence="ECO:0007829|PDB:4AL0"
SQ SEQUENCE 152 AA; 17102 MW; BF9B9ED81CA67A3D CRC64;
MPAHSLVMSS PALPAFLLCS TLLVIKMYVV AIITGQVRLR KKAFANPEDA LRHGGPQYCR
SDPDVERCLR AHRNDMETIY PFLFLGFVYS FLGPNPFVAW MHFLVFLVGR VAHTVAYLGK
LRAPIRSVTY TLAQLPCASM ALQILWEAAR HL
//
