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PTGES_HUMAN
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   03-AUG-2022, entry version 168.
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   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   AlphaFoldDB; O14684; -.
DR   SMR; O14684; -.
DR   BioGRID; 114912; 22.
DR   IntAct; O14684; 19.
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; O14684; -.
DR   PeptideAtlas; O14684; -.
DR   PRIDE; O14684; -.
DR   ProteomicsDB; 48167; -.
DR   TopDownProteomics; O14684; -.
DR   Antibodypedia; 17900; 221 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   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   PhylomeDB; O14684; -.
DR   TreeFam; TF105327; -.
DR   BioCyc; MetaCyc:HS07518-MON; -.
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; 8 hits in 1071 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 158 other tissues.
DR   Genevisible; O14684; HS.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR   GO; GO:0016021; C:integral component of membrane; IDA:UniProtKB.
DR   GO; GO:0016020; C:membrane; TAS:ProtInc.
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; -; 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   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
 
 
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