Any feedback?
Information on EC 5.3.99.3 - prostaglandin-E synthase and Organism(s) Mus musculus and UniProt Accession Q9JM51
for references in articles please use BRENDA:EC5.3.99.3Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
EC Tree
5.3.99.3 prostaglandin-E synthaseIUBMB Comments
Brings about the opening of the epidioxy bridge. Requires glutathione.
Specify your search results
Word Map
- 5.3.99.3
- cox-2
-
cyclooxygenase
-
arachidonic
- synthases
-
prostanoids
- lipopolysaccharide
- tnf
- lps
- phospholipase
-
eicosanoids
-
lps-induced
- pain
- endometrium
-
leukotriene
- prostacyclin
-
thromboxane
-
nsaids
- indomethacin
-
pgf2alpha
-
5-lipoxygenase
- il-1beta
- celecoxib
-
nonsteroidal
- interleukin-1beta
-
luteolysis
- luteal
- platinum
- 15-pgdh
-
estrous
-
postictal
- medicine
-
rhodium
-
pencil
- palladium
- drug development
-
6-keto-pgf1alpha
-
automobile
- pghs-2
-
prostaglandin-endoperoxide
-
e-prostanoid
-
ictal
-
pge2-dependent
- l-pgds
- 15-hydroxyprostaglandin
-
lipocalin-type
- akr1b1
-
cox-2-dependent
-
6-keto
-
coxibs
-
6-keto-pgf1
- ptgds
-
cox-derived
The taxonomic range for the selected organisms is: Mus musculus
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
Reaction Schemes
=
Synonyms
mpges-1, pges, microsomal prostaglandin e synthase-1, mpges, pge synthase, ptges, prostaglandin e synthase, mpges-2, cpges, mpges1, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
endoperoxide isomerase
-
-
-
-
Isomerase, prostaglandin R2 E-
-
-
-
-
microsomal prostaglandin E synthase-1
-
-
mPGES-1
-
-
PGE isomerase
-
-
-
-
PGE2 isomerase
-
-
-
-
PGH-PGE isomerase
-
-
-
-
PGH2/PGE2 isomerase
-
-
-
-
prostagandin-E synthetase
-
-
-
-
Prostaglandin E synthase
Prostaglandin E2 isomerase
-
-
-
-
Prostaglandin endoperoxide E isomerase
-
-
-
-
Prostaglandin endoperoxide E2 isomerase
-
-
-
-
Prostaglandin endoperoxide-E isomerase
-
-
-
-
Prostaglandin H-E isomerase
-
-
-
-
Prostaglandin H-prostaglandin E isomerase
-
-
-
-
Prostaglandin R-prostaglandin E isomerase
-
-
-
-
Prostaglandin-H2 E-isomerase
-
-
-
-
Prostaglandin E synthase
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
isomerization
intramolecular oxidation
-
-
-
-
isomerization
-
-
-
-
PATHWAY SOURCE
PATHWAYS
BRENDA
-
-, -, -, -
SYSTEMATIC NAME
IUBMB Comments
(5Z,13E)-(15S)-9alpha,11alpha-Epidioxy-15-hydroxyprosta-5,13-dienoate E-isomerase
Brings about the opening of the epidioxy bridge. Requires glutathione.
CAS REGISTRY NUMBER
COMMENTARY
52227-79-9
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
(5Z,13E)-(15S)-9alpha,11alpha-epidioxy-15-hydroxyprosta-5,13-dienoate
(5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprosta-5,13-dienoate
-
-
-
?
(5Z,13E)-(15S)-9alpha,11alpha-epidioxy-15-hydroxyprosta-5,13-dienoate
(5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprosta-5,13-dienoate
-
-
-
-
?
Prostaglandin H2
Prostaglandin E2
-
-
662071, 667830, 702146, 702949, 703978, 705284, 706576, 713719, 714401, 714944, 716081, 716814, 746707, 747229, 748296
-
-
?
Prostaglandin H2
Prostaglandin E2
-
isozyme mPEGS-2 has an important role in urogenital function
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
(5Z,13E)-(15S)-9alpha,11alpha-epidioxy-15-hydroxyprosta-5,13-dienoate
(5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprosta-5,13-dienoate
-
-
-
?
(5Z,13E)-(15S)-9alpha,11alpha-epidioxy-15-hydroxyprosta-5,13-dienoate
(5Z,13E)-(15S)-11alpha,15-dihydroxy-9-oxoprosta-5,13-dienoate
-
-
-
-
?
Prostaglandin H2
Prostaglandin E2
-
-
-
-
?
Prostaglandin H2
Prostaglandin E2
-
isozyme mPEGS-2 has an important role in urogenital function
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
5-hydroxy-3-naphthalen-2-yl-4-(3-naphthalen-2-yl-phenyl)-5H-furan-2-one
-
MK-886
-
glutamate-induced PGE2 production is suppressed almost completely by MK-886 at a concentration of 0.003 mM or higher
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
angiotensin II
-
angiotension II infusion induces mRNA expression of mPGES-1, mPGES-2 and cytosolic PGE synthase
lipopolysaccharide
-
lipopolysaccharide binds to receptor TLR4 on osteoblasts that directly induces isoform mPGES-1 expression for prostaglandin E2 synthesis, leading to subsequent bone resorption
additional information
-
IL-1 administration into the mouse cortex leads to elevated expression of cPGES and an increase in prostaglandin E2
-
additional information
-
mPGES-1 expression is upregulated in COX-1 and COX-2 knock-out cells
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00323
3,4-bis-(3-benzo[b]thiophen-3-yl-phenyl)-5-hydroxy-5H-furan-2-one
Mus musculus
-
0.00459
4-(4'-butyl-biphenyl-4-yl)-3-(4-butyl-phenyl)-5-hydroxy-5H-furan-2-one
Mus musculus
-
0.00084
5-hydroxy-3-naphthalen-2-yl-4-(3-naphthalen-2-yl-phenyl)-5H-furan-2-one
Mus musculus
-
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
both microsomal enzyme immunostaining and mRNA, enzyme is induced by equine and human chorionic gonadotropin treatment
exclusive localization of cytosolic enzyme, no obvious effect of treatment with equine chorionic gonadotropin on mRNA or protein level
additional information
additional information
no microsomal enzyme immunostaining or mRNA in thecal cell or oocyte
additional information
-
no microsomal enzyme immunostaining or mRNA in thecal cell or oocyte
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
-
-
additional information
-
cPGES is directly associated with and phosphorylated by casein kinase 2, cPGES, casein kinase 2 and Hsp90 form a stoichiometric complex of 1:1:1 immediately after cell activation, Hsp90 acts as an essential scaffold protein that brings cPGES and casein kinase 2 in proximity, thereby allowing their efficient functional interaction under physiological condition
-
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
metabolism
physiological function
malfunction
-
baseline blood pressures are significantly higher in mPGES1-deficientanimals than wild type controls
malfunction
-
mPGES-1-deficient mice exhibit significantly less neuronal loss induced by kainic acid
malfunction
-
small interfering RNA silencing of mPGES-1 in Lewis lung carcinoma cells decreases prostaglandin E2 synthesis markedly, accompanied by reduced cell proliferation, attenuated Matrigel invasiveness and increased extracellular matrix adhesion, while mPGES-1-overexpression shows increased proliferating and invasive capacities
malfunction
-
the deletion of mPGES-1 in mice results in increased prostacyclin I2 formation and marginal effects on the circulatory prostaglandin E2 level. Loss of mPGES-1 results in increased prostacyclin I2 formation, and in contrast to inhibition of prostacyclin I2, without worsening acute cardiac ischemic injury
malfunction
-
embryonic fibroblasts deficient in cPGES/p23 decrease the expression of the prostaglandin E2 degrading enzyme, 15-hydroxyprostaglandin dehydrogenase, which catalyzes the inactivating conversion of the PGE2 15-OH to a 15-keto group
malfunction
-
PGES-1-deficient mice exhibit reduced tumor growth in bone marrow and significantly fewer spontaneous flinches and their onset is several days later compared to wild type mice
malfunction
-
the expression of vascular endothelial growth factor A is significantly reduced in mPGES-1-deficient endometrial tissues implanted into mPGES-1-deficient mice at days 14 and 28
malfunction
-
the healing of acetic acid-induced gastric ulcers is significantly delayed in mPGES-1 knockout mice compared with wild type. This is accompanied with reduced angiogenesis in ulcer granulation tissues. The mRNA levels of proangiogenic growth factors, such as transforming growth factor-beta, basic fibroblast growth factor, and connective tissue growth factor are reduced in mPGES-1 knockout mice compared with wild type
metabolism
-
the prostaglandin E2-inactivating pathway is controlled by cPGES/p23
metabolism
-
the enzyme is involved in the activation of extracellular signal regulated kinase to promote c-Fos expression
physiological function
-
microsomal prostaglandin E synthase-1 and cyclooxygenase-2 are co-induced by excess glutamate in ischaemic brain. mPGES-1 activity is required for cyclooxygenase-2 to cause neuronal damage in ischaemic injury
physiological function
-
microsomal prostaglandin E synthase-1 enhances bone cancer growth and bone cancer-related pain behaviors in mice
physiological function
-
mPGES-1 enhances the gastric ulcer-healing processes and the angiogenesis indispensable to gastric ulcer healing
physiological function
-
mPGES-1 regulates growth of endometrial tissues and angiogenesis
physiological function
-
microsomal prostaglandin E synthase-1 protects against Fas-induced liver injury and enhances epidermal growth factor receptor/Akt signaling
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). PTGES_MOUSE
153
2
17286
Swiss-Prot
Secretory Pathway (Reliability: 1)
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
-
in enzyme knock-out mice, the infarction, edema, apoptotic cell death, and caspase-3 activation in the cortex ischemia cell are all reduced. the behavioral neurological dysfunctions observed after ischemia in wild-type animals are significantly ameliorated in knock-out animals
additional information
-
in mice with targeted disruption of isoform mPGES-1 gene, basal excretion of prostaglandin E2 in urine is decreased by 50%. In female enzyme-deficient mice, there is a reciprocal increase in basal excretion of other prostanoids. Urinary osmolalities are similar in wild-type and enzyme deficient animals at baseline and after 12 h of water deprivation, and there are no differences in blood pressure on control or high- or low-salt diet. Furesemide-associated diuresis is reduced in male enzyme-deficient animals
additional information
-
isoform mPGES-1 knockout mice. Contrary to wild-type, in knock-out animals no prostaglandin E2 production is found in osteoblast after administration of LPS. While in wild-type, LPS reduces the bone volume in femur associated with an increased number of osteoclasts, this loss is reduced in knock-out mice. LPS induces the loss of alveolar bone in wild-type, but not in the mutants
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
1 mM glutamate up-regulates the expression of mPGES-1 to about 3fold that in the controls
-
inhibition of NADPH-oxidase negatively modulates mPGES-1 expression induced by tobacco smoke/interleukin-1beta. The activation of mPGES-1 is negatively regulated by prostaglandin I2
-
microinjection of kainic acid induces mPGES-1 in venous endothelial cells but not in neurons or astrocytes
-
the expression of mPGES-1 in wild type mice is markedly upregulated in the gastric ulcer tissues compared with normal gastric tissues without ulcers
-
tobacco smoke (EC50 about 5 puffs/l) interacting with IL-1beta (0.002 mg/l) upregulates PGE2 production and mPGES-1 expression, reaching a plateau at 4-6 h
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
medicine
-
in enzyme knock-out mice, the infarction, edema, apoptotic cell death, and caspase-3 activation in the cortex ischemia cell are all reduced. the behavioral neurological dysfunctions observed after ischemia in wild-type animals are significantly ameliorated in knock-out animals. Microsomal enzyme mPGES-1 may be a critical determinant of postischemic neurological dysfunctions and a therapeutic target for treatment of stroke
medicine
-
use of isoform mPGES-1 as a target for the treatment of inflammatory bone disease
medicine
-
induction of various inflammatory cytokines in addition to overexpression of COX-2 and mPGES-1 could be risk factors of gastric carcinogenesis and may serve as a better gastric carcinogenesis model
medicine
-
mPGES-1 could be a potential therapeutic target of novel inhibitors for treatment of inflammatory diseases
medicine
-
mPGES-1 inhibitors have therapeutic potential in syndromes of cardiovascular inflammation, cancer and perhaps neurodegenerative disease
medicine
-
inhibition of mPGES-1 may have clinical utility in the management of bone cancer pain
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Shalinsky, D.R.; McNamara, D.B.; Agrawal, K.C.
Inhibition of GSH-dependent PGH2 isomerase in mammary adenocarcinoma cells by allicin
Prostaglandins
37
135-148
1989
Mus musculus
Kudo, I.; Murakami, M.
Prostaglandin E synthase, a terminal enzyme for prostaglandin E2 biosynthesis
J. Biochem. Mol. Biol.
38
633-638
2005
Homo sapiens, Mus musculus, Rattus norvegicus
Yang, G.; Chen, L.; Zhang, Y.; Zhang, X.; Wu, J.; Li, S.; Wei, M.; Zhang, Z.; Breyer, M.D.; Guan, Y.
Expression of mouse membrane-associated prostaglandin E(2) synthase-2 (mPGES-2) along the urogenital tract
Biochim. Biophys. Acta
1761
1459-1468
2006
Mus musculus
Francois, H.; Facemire, C.; Kumar, A.; Audoly, L.; Koller, B.; Coffman, T.
Role of microsomal prostaglandin E synthase 1 in the kidney
J. Am. Soc. Nephrol.
18
1466-1475
2007
Mus musculus
Sun, T.; Deng, W.B.; Diao, H.L.; Ni, H.; Bai, Y.Y.; Ma, X.H.; Xu, L.B.; Yang, Z.M.
Differential expression and regulation of prostaglandin E synthases in the mouse ovary during sexual maturation and luteal development
J. Endocrinol.
189
89-101
2006
Mus musculus (Q9JM51), Mus musculus
Inada, M.; Matsumoto, C.; Uematsu, S.; Akira, S.; Miyaura, C.
Membrane-bound prostaglandin E synthase-1-mediated prostaglandin E2 production by osteoblast plays a critical role in lipopolysaccharide-induced bone loss associated with inflammation
J. Immunol.
177
1879-1885
2006
Mus musculus
Ikeda-Matsuo, Y.; Ota, A.; Fukada, T.; Uematsu, S.; Akira, S.; Sasaki, Y.
Microsomal prostaglandin E synthase-1 is a critical factor of stroke-reperfusion injury
Proc. Natl. Acad. Sci. USA
103
11790-11795
2006
Mus musculus
Aquino, M.; Guerrero, M.D.; Bruno, I.; Terencio, M.C.; Paya, M.; Riccio, R.
Development of a second generation of inhibitors of microsomal prostaglandin E synthase 1 expression bearing the gamma-hydroxybutenolide scaffold
Bioorg. Med. Chem.
16
9056-9064
2008
Mus musculus (Q9JM51)
Takasu, S.; Tsukamoto, T.; Cao, X.Y.; Toyoda, T.; Hirata, A.; Ban, H.; Yamamoto, M.; Sakai, H.; Yanai, T.; Masegi, T.; Oshima, M.; Tatematsu, M.
Roles of cyclooxygenase-2 and microsomal prostaglandin E synthase-1 expression and beta-catenin activation in gastric carcinogenesis in N-methyl-N-nitrosourea-treated K19-C2mE transgenic mice
Cancer Sci.
99
2356-2364
2008
Mus musculus
Jia, Z.; Guo, X.; Zhang, H.; Wang, M.H.; Dong, Z.; Yang, T.
Microsomal prostaglandin synthase-1-derived prostaglandin E2 protects against angiotensin II-induced hypertension via inhibition of oxidative stress
Hypertension
52
952-959
2008
Mus musculus
Wang, M.; Song, W.L.; Cheng, Y.; Fitzgerald, G.A.
Microsomal prostaglandin E synthase-1 inhibition in cardiovascular inflammatory disease
J. Intern. Med.
263
500-505
2008
Mus musculus
Sandee, D.; Sivanuntakorn, S.; Vichai, V.; Kramyu, J.; Kirtikara, K.
Up-regulation of microsomal prostaglandin E synthase-1 in COX-1 and COX-2 knock-out mouse fibroblast cell lines
Prostaglandins Other Lipid Mediat.
88
111-116
2009
Mus musculus
Jania, L.A.; Chandrasekharan, S.; Backlund, M.G.; Foley, N.A.; Snouwaert, J.; Wang, I.M.; Clark, P.; Audoly, L.P.; Koller, B.H.
Microsomal prostaglandin E synthase-2 is not essential for in vivo prostaglandin E(2) biosynthesis
Prostaglandins Other Lipid Mediat.
88
73-81
2009
Mus musculus
Kamei, D.; Murakami, M.; Sasaki, Y.; Nakatani, Y.; Majima, M.; Ishikawa, Y.; Ishii, T.; Uematsu, S.; Akira, S.; Hara, S.; Kudo, I.
Microsomal prostaglandin E synthase-1 in both cancer cells and hosts contributes to tumour growth, invasion and metastasis
Biochem. J.
425
361-371
2010
Mus musculus
Ikeda-Matsuo, Y.; Hirayama, Y.; Ota, A.; Uematsu, S.; Akira, S.; Sasaki, Y.
Microsomal prostaglandin E synthase-1 and cyclooxygenase-2 are both required for ischaemic excitotoxicity
Br. J. Pharmacol.
159
1174-1186
2010
Mus musculus, Rattus norvegicus
Facemire, C.S.; Griffiths, R.; Audoly, L.P.; Koller, B.H.; Coffman, T.M.
The impact of microsomal prostaglandin E synthase 1 on blood pressure is determined by genetic background
Hypertension
55
531-538
2010
Mus musculus
Takemiya, T.; Matsumura, K.; Sugiura, H.; Maehara, M.; Yasuda, S.; Uematsu, S.; Akira, S.; Yamagata, K.
Endothelial microsomal prostaglandin E synthase-1 exacerbates neuronal loss induced by kainate
J. Neurosci. Res.
88
381-390
2010
Mus musculus, Rattus norvegicus
Wu, D.; Mennerich, D.; Arndt, K.; Sugiyama, K.; Ozaki, N.; Schwarz, K.; Wei, J.; Wu, H.; Bishopric, N.H.; Doods, H.
The effects of microsomal prostaglandin E synthase-1 deletion in acute cardiac ischemia in mice
Prostaglandins Leukot. Essent. Fatty Acids
81
31-33
2009
Mus musculus
Ae, T.; Ohno, T.; Hattori, Y.; Suzuki, T.; Hosono, K.; Minamino, T.; Sato, T.; Uematsu, S.; Akira, S.; Koizumi, W.; Majima, M.
Role of microsomal prostaglandin E synthase-1 in the facilitation of angiogenesis and the healing of gastric ulcers
Am. J. Physiol. Gastrointest. Liver Physiol.
299
G1139-G1146
2010
Mus musculus
Numao, A.; Hosono, K.; Suzuki, T.; Hayashi, I.; Uematsu, S.; Akira, S.; Ogino, Y.; Kawauchi, H.; Unno, N.; Majima, M.
The inducible prostaglandin E synthase mPGES-1 regulates growth of endometrial tissues and angiogenesis in a mouse implantation model
Biomed. Pharmacother.
65
77-84
2011
Mus musculus
Barbieri, S.S.; Amadio, P.; Gianellini, S.; Zacchi, E.; Weksler, B.B.; Tremoli, E.
Tobacco smoke regulates the expression and activity of microsomal prostaglandin E synthase-1: role of prostacyclin and NADPH-oxidase
FASEB J.
25
3731-3740
2011
Mus musculus
Isono, M.; Suzuki, T.; Hosono, K.; Hayashi, I.; Sakagami, H.; Uematsu, S.; Akira, S.; DeClerck, Y.A.; Okamoto, H.; Majima, M.
Microsomal prostaglandin E synthase-1 enhances bone cancer growth and bone cancer-related pain behaviors in mice
Life Sci.
88
693-700
2011
Mus musculus
Nakatani, Y.; Hokonohara, Y.; Tajima, Y.; Kudo, I.; Hara, S.
Involvement of the constitutive prostaglandin E synthase cPGES/p23 in expression of an initial prostaglandin E2 inactivating enzyme, 15-PGDH
Prostaglandins Other Lipid Mediat.
94
112-117
2011
Mus musculus, Rattus norvegicus
Yao, L.; Chen, W.; Han, C.; Wu, T.
Microsomal prostaglandin E synthase-1 protects against Fas-induced liver injury
Am. J. Physiol. Gastrointest. Liver Physiol.
310
G1071-G1080
2016
Mus musculus
Nakatani, Y.; Miyazaki, Y.; Hara, S.
Cytosolic prostaglandin E synthase is involved in c-Fos expression in rat fibroblastic 3Y1 cells
Biol. Pharm. Bull.
40
1963-1967
2017
Mus musculus, Rattus norvegicus
EXTERNAL LINKS (specific for EC-Number 5.3.99.3)
Use of this online version of BRENDA is free under the CC BY 4.0 license. See terms of use for full details.
Release 2023.1 (January 2023)
Legal
Curated at
Member of
