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Information on EC 1.1.1.188 - prostaglandin-F synthase and Organism(s) Homo sapiens and UniProt Accession P15121
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1.1.1.188 prostaglandin-F synthaseIUBMB Comments
Reduces prostaglandin D2 and prostaglandin H2 to prostaglandin F2; prostaglandin D2 is not an intermediate in the reduction of prostaglandin H2. Also catalyses the reduction of a number of carbonyl compounds, such as 9,10-phenanthroquinone and 4-nitroacetophenone.
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Word Map
- 1.1.1.188
- aldose
- endometrium
-
estrous
- mpges-1
-
reductase-like
- akr1b3
- synthase-2
-
rho-crystallins
-
ptgfr
-
luteotropic
-
9-ketoreductase
-
alpha-hsds
-
bitch
- medicine
- chlordecone
- synthesis
- drug development
- pharmacology
- molecular biology
The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota
Reaction Schemes
Synonyms
pgfs, akr1b7, prostaglandin f synthase, pgf synthase, vas deferens protein, prostaglandin f synthetase, prostamide/pgf synthase, p100/11e, akr1cl, pgd2 11-ketoreductase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
AKR1C3
NADPH-dependent prostaglandin D2 11-keto reductase
-
-
-
-
PGD2 11-ketoreductase
PGF synthase
PGF2alpha synthase
-
-
-
-
PGFS
PGFSI
-
-
-
-
PGFSII
-
-
-
-
prostaglandin 11-keto reductase
-
-
-
-
prostaglandin 11-ketoreductase
-
-
-
-
prostaglandin D2-ketoreductase
-
-
-
-
prostaglandin F synthase
prostaglandin F synthetase
-
-
-
-
prostaglandin F2alpha synthase
prostaglandin-D2 11-reductase
-
-
-
-
reductase, 15-hydroxy-11-oxoprostaglandin
-
-
-
-
synthetase, prostaglandin F2alpha
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-
-
-
additional information
PGD2 11-ketoreductase
-
-
-
-
PGF synthase
-
-
-
-
prostaglandin F synthase
-
-
-
-
additional information
-
enzyme belongs to the AKR aldo-keto-reductase superfamily
additional information
enzyme also shows 3alpha-hydroxysteroid dehydrogenase type II activity, i.e. 3alpha-HSD
additional information
enzyme belongs to the aldo-keto reductase AKR family, enzyme also shows 3alpha-hydroxysteroid dehydrogenase type II activity, i.e. 3alpha-HSD
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
(5Z,13E)-(15S)-9alpha,11alpha,15-trihydroxyprosta-5,13-dienoate + NADP+ = (5Z,13E)-(15S)-9alpha,15-dihydroxy-11-oxoprosta-5,13-dienoate + NADPH + H+
(5Z,13E)-(15S)-9alpha,11alpha,15-trihydroxyprosta-5,13-dienoate + NADP+ = (5Z,13E)-(15S)-9alpha,15-dihydroxy-11-oxoprosta-5,13-dienoate + NADPH + H+
active site structure, enzyme also shows 3alpha-hydroxysteroid dehydrogenase type II activity, i.e. 3alpha-HSD
(5Z,13E)-(15S)-9alpha,11alpha,15-trihydroxyprosta-5,13-dienoate + NADP+ = (5Z,13E)-(15S)-9alpha,15-dihydroxy-11-oxoprosta-5,13-dienoate + NADPH + H+
substrate binding and catalytic mechanism, catalytic site residues are Y55 and H117, enzyme also shows 3alpha-hydroxysteroid dehydrogenase type II activity, i.e. 3alpha-HSD
(5Z,13E)-(15S)-9alpha,11alpha,15-trihydroxyprosta-5,13-dienoate + NADP+ = (5Z,13E)-(15S)-9alpha,15-dihydroxy-11-oxoprosta-5,13-dienoate + NADPH + H+
catalytic mechanisms, the catalytic sites for PGD2 11-ketoreductase and PGH2 9,11-endoperoxide reductase activities are located differently in the active site cavity, residue Y55 is important for the PGD2 11-ketoreductase activity, but not for the PGH2 9,11-endoperoxide reductase activity, involved structural features, overview
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
redox reaction
-
-
-
-
oxidation
-
-
-
-
reduction
reduction
-
-
-
-
SYSTEMATIC NAME
IUBMB Comments
(5Z,13E)-(15S)-9alpha,11alpha,15-trihydroxyprosta-5,13-dienoate:NADP+ 11-oxidoreductase
Reduces prostaglandin D2 and prostaglandin H2 to prostaglandin F2; prostaglandin D2 is not an intermediate in the reduction of prostaglandin H2. Also catalyses the reduction of a number of carbonyl compounds, such as 9,10-phenanthroquinone and 4-nitroacetophenone.
CAS REGISTRY NUMBER
COMMENTARY
55976-95-9
-
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,15-trihydroxyprosta-5,13-dienoate + NADP+
(5Z,13E)-(15S)-9alpha,15-dihydroxy-11-oxoprosta-5,13-dienoate + NADPH + H+
prostaglandin H2 + NADPH + H+
(5Z,13E)-(15S)-9alpha,11alpha,15-trihydroxyprosta-5,13-dienoate + NADP+
aldo-keto reductase has prostaglandin F2alpha synthase activity. AKR1B1 is a more efficient prostaglandin F2alpha synthase than AKR1C3
-
-
?
prostaglandin H2 + NADPH + H+
9alpha,11beta-prostaglandin F2 + NADP+
-
-
-
?
(5Z,13E)-(15S)-9alpha,11alpha,15-trihydroxyprosta-5,13-dienoate + NADP+
(5Z,13E)-(15S)-9alpha,15-dihydroxy-11-oxoprosta-5,13-dienoate + NADPH + H+
-
-
-
?
(5Z,13E)-(15S)-9alpha,11beta,15-trihydroxyprosta-5,13-dienoate + NADP+
(5Z,13E)-(15S)-9alpha,15-dihydroxy-11-oxoprosta-5,13-dienoate + NADPH + H+
-
-
-
?
(5Z,13E)-(15S)-9alpha,15-dihydroxy-11-oxoprosta-5,13-dienoate + NADPH
(5Z,13E)-(15S)-9alpha,11alpha,15-trihydroxyprosta-5,13-dienoate + NADP+
-
-
-
-
?
(5Z,13E)-(15S)-9alpha,15-dihydroxy-11-oxoprosta-5,13-dienoate + NADPH
(5Z,13E)-(15S)-9alpha,11beta,15-trihydroxyprosta-5,13-dienoate + NADP+
-
-
-
-
?
5beta-androstane-3,17-dione + NADPH
5beta-androstan-3alpha-ol-17-one + NADP+
-
-
-
-
r
prostaglandin D2 + NADPH + H+
9-alpha,11-beta-prostaglandin F2 + NADP+
-
-
-
-
?
prostaglandin D2 + NADPH + H+
9alpha,11alpha-prostaglandin F2alpha + NADP+
-
reaction via formation of the endoperoxide ethanolamide intermediate prostaglandin H2
-
-
?
prostaglandin D2 + NADPH + H+
9alpha,11beta-prostaglandin F2alpha + NADP+
-
-
-
r
prostaglandin D2 + NADPH + H+
9alpha,11beta-prostaglandin F2alphabeta + NADP+
-
-
-
?
prostaglandin D2 ethanolamide + NADPH
prostaglandin 9alpha,11beta-F2 ethanolamide + NADP+
i.e. prostamide D2
i.e. 91lpha,11beta-prostamide F2
-
?
prostaglandin H2 + NADPH + H+
(5Z,13E)-(15S)-9alpha,11alpha,15-trihydroxyprosta-5,13-dienoate + NADP+
prostaglandin H2 + NADPH + H+
9alpha,11alpha-prostaglandin F2alpha + NADP+
-
-
-
?
prostaglandin H2 + NADPH + H+
prostaglandin 9alpha,11beta-F2 + NADP+
-
-
-
?
prostamide H2 + NADPH + H+
prostamide F2alpha + NADP+
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about 70% of prostamide H2 is converted to prostamide F2alpha after 2 min at 37°C
-
-
?
(5Z,13E)-(15S)-9alpha,11alpha,15-trihydroxyprosta-5,13-dienoate + NADP+
(5Z,13E)-(15S)-9alpha,15-dihydroxy-11-oxoprosta-5,13-dienoate + NADPH + H+
-
-
-
?
(5Z,13E)-(15S)-9alpha,11alpha,15-trihydroxyprosta-5,13-dienoate + NADP+
(5Z,13E)-(15S)-9alpha,15-dihydroxy-11-oxoprosta-5,13-dienoate + NADPH + H+
-
-
-
?
prostaglandin H2 + NADP+
prostaglandin F2alpha + NADPH + H+
-
-
-
?
prostaglandin D2 + NADPH + H+
9alpha,11beta-prostaglandin F2 + NADP+
-
-
-
?
prostaglandin D2 + NADPH + H+
9alpha,11beta-prostaglandin F2 + NADP+
-
-
-
?
prostaglandin D2 + NADPH + H+
prostaglandin 9alpha,11beta-F2 + NADP+
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-
-
?
prostaglandin D2 + NADPH + H+
prostaglandin 9alpha,11beta-F2 + NADP+
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-
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?
prostaglandin D2 + NADPH + H+
prostaglandin 9alpha,11beta-F2 + NADP+
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-
product is involved in bronchial, vascular, and arterial smooth muscle contraction, product inhibits platelet aggregation and activates urinary excretion, i.e. 11-epi PGF2alpha
-
?
prostaglandin H2 + NADPH + H+
(5Z,13E)-(15S)-9alpha,11alpha,15-trihydroxyprosta-5,13-dienoate + NADP+
-
-
-
-
?
prostaglandin H2 + NADPH + H+
(5Z,13E)-(15S)-9alpha,11alpha,15-trihydroxyprosta-5,13-dienoate + NADP+
aldo-keto reductase has prostaglandin F2alpha synthase activity. AKR1B1 is a more efficient prostaglandin F2alpha synthase than AKR1C3
-
-
?
prostaglandin H2 + NADPH + H+
prostaglandin F2alpha + NADP+
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-
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?
prostaglandin H2 + NADPH + H+
prostaglandin F2alpha + NADP+
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enzyme also shows PGH2 9-,11-endoperoxide reductase activity
-
-
?
additional information
?
-
in the absence of NADPH or NADP+, enzyme catalyzes the isomerization of prostaglandin H2 to prostaglandin D2 with a Km value of 0.023 mM. This activity of AKR1B1 increases with increasing pH, with an optimum of pH 8.5. Residue His110 acts as a base in concert with Asp43 and Lys77 and as an acid to generate PGD2 and PGF2a in the absence of NADPH or NADP+ and in the presence of NADPH, respectively
-
-
?
additional information
?
-
-
in the absence of NADPH or NADP+, enzyme catalyzes the isomerization of prostaglandin H2 to prostaglandin D2 with a Km value of 0.023 mM. This activity of AKR1B1 increases with increasing pH, with an optimum of pH 8.5. Residue His110 acts as a base in concert with Asp43 and Lys77 and as an acid to generate PGD2 and PGF2a in the absence of NADPH or NADP+ and in the presence of NADPH, respectively
-
-
?
additional information
?
-
PGFS activity of the recombinant proteins is evaluated using an assay based on in situ generation of the precursor of prostaglandin PGH2 biosynthesis. PGF2alpha is measured by ELISA. Comparisons of PGFS activity of recombinant bovine and human endometrial AKRs, overview
-
-
?
additional information
?
-
-
PGFS activity of the recombinant proteins is evaluated using an assay based on in situ generation of the precursor of prostaglandin PGH2 biosynthesis. PGF2alpha is measured by ELISA. Comparisons of PGFS activity of recombinant bovine and human endometrial AKRs, overview
-
-
?
additional information
?
-
-
the cytosolic enzyme synergistically interacts with cyclooxygenase 1 and 2, coupling, isozyme PGFS-I interacts predominantly with cyclooxygenase 2, i.e. COX-2
-
-
?
additional information
?
-
acive site structure, enzyme also shows 3alpha-hydroxysteroid dehydrogenase type II activity
-
-
?
additional information
?
-
-
substrate and product detection by liquid chromatographic-electrospray ionization-mass spectrometry
-
-
?
additional information
?
-
substrate and product detection by liquid chromatographic-electrospray ionization-mass spectrometry
-
-
?
additional information
?
-
Y55 and H117 are involved in catalysis, enzyme also shows 3alpha-hydroxysteroid dehydrogenase type II activity
-
-
?
additional information
?
-
-
Y55 and H117 are involved in catalysis, enzyme also shows 3alpha-hydroxysteroid dehydrogenase type II activity
-
-
?
additional information
?
-
-
the enzyme has dual activity as PGD2 11-ketoreductase and PGH2 9,11-endoperoxide reductase
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-
?
additional information
?
-
the enzyme has dual activity as PGD2 11-ketoreductase and PGH2 9,11-endoperoxide reductase
-
-
?
additional information
?
-
-
PGFS does not catalyze the reduction of prostaglandin E2
-
-
?
additional information
?
-
PGFS does not catalyze the reduction of prostaglandin E2
-
-
?
additional information
?
-
AKR1C3 is overexpressed in keloids and mediates the conversion of PGD2 to 9alpha,11beta-PGF2 in keloid and normal fibroblasts
-
-
?
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,15-trihydroxyprosta-5,13-dienoate + NADP+
(5Z,13E)-(15S)-9alpha,15-dihydroxy-11-oxoprosta-5,13-dienoate + NADPH + H+
(5Z,13E)-(15S)-9alpha,11alpha,15-trihydroxyprosta-5,13-dienoate + NADP+
(5Z,13E)-(15S)-9alpha,15-dihydroxy-11-oxoprosta-5,13-dienoate + NADPH + H+
-
-
-
?
(5Z,13E)-(15S)-9alpha,11beta,15-trihydroxyprosta-5,13-dienoate + NADP+
(5Z,13E)-(15S)-9alpha,15-dihydroxy-11-oxoprosta-5,13-dienoate + NADPH + H+
-
-
-
?
prostaglandin D2 + NADPH + H+
9-alpha,11-beta-prostaglandin F2 + NADP+
-
-
-
-
?
prostaglandin D2 + NADPH + H+
9alpha,11beta-prostaglandin F2alphabeta + NADP+
-
-
-
?
prostaglandin D2 + NADPH + H+
prostaglandin 9alpha,11beta-F2 + NADP+
-
-
product is involved in bronchial, vascular, and arterial smooth muscle contraction, product inhibits platelet aggregation and activates urinary excretion
-
?
prostaglandin H2 + NADPH + H+
9alpha,11alpha-prostaglandin F2alpha + NADP+
-
-
-
?
(5Z,13E)-(15S)-9alpha,11alpha,15-trihydroxyprosta-5,13-dienoate + NADP+
(5Z,13E)-(15S)-9alpha,15-dihydroxy-11-oxoprosta-5,13-dienoate + NADPH + H+
-
-
-
?
(5Z,13E)-(15S)-9alpha,11alpha,15-trihydroxyprosta-5,13-dienoate + NADP+
(5Z,13E)-(15S)-9alpha,15-dihydroxy-11-oxoprosta-5,13-dienoate + NADPH + H+
-
-
-
?
prostaglandin H2 + NADP+
prostaglandin F2alpha + NADPH + H+
-
-
-
?
additional information
?
-
-
the cytosolic enzyme synergistically interacts with cyclooxygenase 1 and 2, coupling, isozyme PGFS-I interacts predominantly with cyclooxygenase 2, i.e. COX-2
-
-
?
additional information
?
-
-
the enzyme has dual activity as PGD2 11-ketoreductase and PGH2 9,11-endoperoxide reductase
-
-
?
additional information
?
-
the enzyme has dual activity as PGD2 11-ketoreductase and PGH2 9,11-endoperoxide reductase
-
-
?
additional information
?
-
AKR1C3 is overexpressed in keloids and mediates the conversion of PGD2 to 9alpha,11beta-PGF2 in keloid and normal fibroblasts
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
NADPH
binding structure at the active site, catalytic structure and mechanism involving the cofactor
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
ponalrestat
specific inhibitor developed to block AKR1B1 activity. Application reduces prostaglandin F2alpha production in response to interleukin IL-1beta in both cultured endometrial cells and endometrial explants
(5Z)-7-[(1R,2R,3R,5S)-3,5-dihydroxy-2-[(1E,3S)-3-hydroxy-5-phenylpent-1-en-1-yl]cyclopentyl]-N-ethylhept-5-enamide
bimatoprost
(5Z)-7-[(1R,4S,5S,6R)-6-[(1E)-oct-1-en-1-yl]-2-azabicyclo[2.2.1]hept-5-yl]hept-5-enoic acid
ONO1370
(5Z)-7-[(1R,4S,5S,6R)-6-[(1E,3S)-3-hydroxyoct-1-en-1-yl]-2-azabicyclo[2.2.1]hept-5-yl]hept-5-enoic acid
ONO1349
(5Z)-7-[(1S,4S,5S,6R)-2-methyl-6-[(1E)-oct-1-en-1-yl]-2-azabicyclo[2.2.1]hept-5-yl]hept-5-enoic acid
ONO1373
(Z)-7-[(1R,4S,5S,6R)-((E)-6-oct-1-enyl)-2-aza-bicyclo[2.2.1]hept-5-yl]-hept-5-enoic acid
inhibition of PGH2 9,11-endoperoxide reductase activity, slight inhibition of prostamide D2 11-ketoreductase and PGD2 11-ketoreductase activity
(Z)-7-[(1R,4S,5S,6R)-2-methyl-6-((E)-oct-1-enyl)-2-aza-bicyclo[2.2.1]hept-5-yl]-hept-5-enoic acid
inhibition of PGH2 9,11-endoperoxide reductase activity, slight inhibition of prostamide D2 11-ketoreductase and PGD2 11-ketoreductase activity, competitive, binds to the active site
(Z)-7-[(1R,4S,5S,6R)-6-((E)-(S)-3-hydroxy-oct-1-enyl)-2-aza-bicyclo[2.2.1]hept-5-yl]-hept-5-enoic acid
inhibition of PGH2 9,11-endoperoxide reductase activity, slight inhibition of prostamide D2 11-ketoreductase and PGD2 11-ketoreductase activity
15-deoxy-DELTA12,14-prostaglandin J2
15d-PGJ2, the enzyme inhibitor attenuates proliferation, inhibits collagen gel contraction and induces activation of the apoptotic marker, caspase-3, in CRL1762 keloid fibroblasts
2-(1-(4-chlorobenzoyl)-5-methoxy-1H-indol-3-yl)-N-((trifluoromethyl)sulfonyl)acetamide
257fold selectivity for isoform AKR1C3 over isoform AKR1C2
3-(1-(4-chlorobenzoyl)-3-ethyl-5-methoxy-1H-indol-2-yl)-propanoic acid
540fold selectivity for isoform AKR1C3 over isoform AKR1C2
3-(1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl)-propanoic acid
257fold selectivity for isoform AKR1C3 over isoform AKR1C2
9,10-phenanthrenequinone
the prostaglandin D2 11-ketoreductase activity of PGFS is competitively inhibited by 9,10-phenanthrenequinone
acetate
occupies the oxyanion hole of the active site, 2 complex structures
Flufenamic acid
nonsteroidal anti-inflammatory drug, binds to both the active site and the beta-hairpin loop at the opposite end of the central beta-barrel, complex structure
indomethacin methyl ester
specific inhibition of isoform AKR1C3 versus AKR1C1 and AKR1C3
bimatoprost
ethyl amide analogue of 17-phenyl-trinor PGF2alpha, inhibits all enzyme activities noncompetitively at low concentration, binds to a site different from the active site
bimatoprost
inhibits the prostaglandin D2 11-ketoreductase activity as well as the prostaglandin H2 9,11-endoperoxide reductase activity of PGFS
indomethacin
nonsteroidal anti-inflammatory drug, 1 molecule binds to the active site, complex structure
indomethacin
specific inhibition of isoform AKR1C3 versus AKR1C1 and AKR1C3
indomethacin
inhibits AKR1C3, but does not inhibit highly related AKR1C1 or AKR1C2
N-(4-chlorobenzoyl)-melatonin
specific inhibition of isoform AKR1C3 versus AKR1C1 and AKR1C3, not inhibitory to cyclooxygenases. Uncompetitive versus 9,10-phenynthrenequinone, competitive versus DELTA4-andostene-3,17-dione
N-(4-chlorobenzoyl)-melatonin
exhibits uncompetitive inhibition patterns for the reduction of 9,10-phenanthrenequinone but competitive inhibition patterns for the reduction of androstenedione by AKR1C3
Tolrestat
inhibition of all 3 enzyme activities, most effective inhibiting the PGD2 11-ketoreductase activity
additional information
heat treatment of AKR1B1 at 100°C for 5 min completely inactivates the prostaglandin F2alpha synthase activity, which is strictly dependent on the presence of NADPH
-
additional information
heat treatment of AKR1B1 at 100°C for 5 min completely inactivates the prostaglandin F2alpha synthase activity, which is strictly dependent on the presence of NADPH
-
additional information
-
heat treatment of AKR1B1 at 100°C for 5 min completely inactivates the prostaglandin F2alpha synthase activity, which is strictly dependent on the presence of NADPH
-
additional information
inhibitors such as alrestatin, ponalrestat, and EBPC exhibit distinct and characteristic inhibition of prostaglandin F2alpha production in different cell models
-
additional information
-
inhibitors such as alrestatin, ponalrestat, and EBPC exhibit distinct and characteristic inhibition of prostaglandin F2alpha production in different cell models
-
additional information
-
AKR1C3 is potently inhibited by non-steroidal anti-inflammatory drugs, which are protective against breast cancer
-
additional information
AKR1C3 is potently inhibited by non-steroidal anti-inflammatory drugs, which are protective against breast cancer
-
additional information
combination of indomethacin with tert-butyl hydroperoxide significantly inhibits the growth of radiation-resistant AKR1C3-over cells
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
-
PGF synthase I activity in HEK 293 cells is unaffected by interleukin-1beta
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
kinetics of 3alpha-hydroxysteroid dehydrogenase type II activity
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
Ki values for the nonsteroidal anti-inflammatory drug inhibitors with 3alpha-androstanediol as a substrate
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.005 - 0.06
(5Z)-7-[(1R,2R,3R,5S)-3,5-dihydroxy-2-[(1E,3S)-3-hydroxy-5-phenylpent-1-en-1-yl]cyclopentyl]-N-ethylhept-5-enamide
0.3 - 1
(5Z)-7-[(1R,4S,5S,6R)-6-[(1E)-oct-1-en-1-yl]-2-azabicyclo[2.2.1]hept-5-yl]hept-5-enoic acid
0.13 - 1
(5Z)-7-[(1R,4S,5S,6R)-6-[(1E,3S)-3-hydroxyoct-1-en-1-yl]-2-azabicyclo[2.2.1]hept-5-yl]hept-5-enoic acid
0.06 - 1
(5Z)-7-[(1S,4S,5S,6R)-2-methyl-6-[(1E)-oct-1-en-1-yl]-2-azabicyclo[2.2.1]hept-5-yl]hept-5-enoic acid
0.00021
2-(1-(4-chlorobenzoyl)-5-methoxy-1H-indol-3-yl )-N-((trifluoromethyl)sulfonyl)acetamide
Homo sapiens
pH not specified in the publication, temperature not specified in the publication
0.00009
3-(1-(4-chlorobenzoyl)-3-ethyl-5-methoxy-1H-indol-2-yl)-propanoic acid
Homo sapiens
pH not specified in the publication, temperature not specified in the publication
0.00022
3-(1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl)-propanoic acid
Homo sapiens
pH not specified in the publication, temperature not specified in the publication
0.005
(5Z)-7-[(1R,2R,3R,5S)-3,5-dihydroxy-2-[(1E,3S)-3-hydroxy-5-phenylpent-1-en-1-yl]cyclopentyl]-N-ethylhept-5-enamide
Homo sapiens
recombinant enzyme, using prostaglandin D2 as substrate, in 0.1 M potassium phosphate buffer, pH 6.5, at 37°C
0.006
(5Z)-7-[(1R,2R,3R,5S)-3,5-dihydroxy-2-[(1E,3S)-3-hydroxy-5-phenylpent-1-en-1-yl]cyclopentyl]-N-ethylhept-5-enamide
Homo sapiens
recombinant enzyme, using prostaglandin H2 as substrate, in 0.1 M potassium phosphate buffer, pH 6.5, at 37°C
0.06
(5Z)-7-[(1R,2R,3R,5S)-3,5-dihydroxy-2-[(1E,3S)-3-hydroxy-5-phenylpent-1-en-1-yl]cyclopentyl]-N-ethylhept-5-enamide
Homo sapiens
recombinant enzyme, using prostamide D2 as substrate, in 0.1 M potassium phosphate buffer, pH 6.5, at 37°C
0.3
(5Z)-7-[(1R,4S,5S,6R)-6-[(1E)-oct-1-en-1-yl]-2-azabicyclo[2.2.1]hept-5-yl]hept-5-enoic acid
Homo sapiens
recombinant enzyme, using prostaglandin H2 as substrate, in 0.1 M potassium phosphate buffer, pH 6.5, at 37°C
1
(5Z)-7-[(1R,4S,5S,6R)-6-[(1E)-oct-1-en-1-yl]-2-azabicyclo[2.2.1]hept-5-yl]hept-5-enoic acid
Homo sapiens
IC50 about 1 mM, recombinant enzyme, using prostaglandin D2 as substrate, in 0.1 M potassium phosphate buffer, pH 6.5, at 37°C
1
(5Z)-7-[(1R,4S,5S,6R)-6-[(1E)-oct-1-en-1-yl]-2-azabicyclo[2.2.1]hept-5-yl]hept-5-enoic acid
Homo sapiens
IC50 about 1 mM, recombinant enzyme, using prostamide D2 as substrate, in 0.1 M potassium phosphate buffer, pH 6.5, at 37°C
0.13
(5Z)-7-[(1R,4S,5S,6R)-6-[(1E,3S)-3-hydroxyoct-1-en-1-yl]-2-azabicyclo[2.2.1]hept-5-yl]hept-5-enoic acid
Homo sapiens
recombinant enzyme, using prostaglandin H2 as substrate, in 0.1 M potassium phosphate buffer, pH 6.5, at 37°C
1
(5Z)-7-[(1R,4S,5S,6R)-6-[(1E,3S)-3-hydroxyoct-1-en-1-yl]-2-azabicyclo[2.2.1]hept-5-yl]hept-5-enoic acid
Homo sapiens
IC50 about 1 mM, recombinant enzyme, using prostaglandin D2 as substrate, in 0.1 M potassium phosphate buffer, pH 6.5, at 37°C
1
(5Z)-7-[(1R,4S,5S,6R)-6-[(1E,3S)-3-hydroxyoct-1-en-1-yl]-2-azabicyclo[2.2.1]hept-5-yl]hept-5-enoic acid
Homo sapiens
IC50 about 1 mM, recombinant enzyme, using prostamide D2 as substrate, in 0.1 M potassium phosphate buffer, pH 6.5, at 37°C
0.06
(5Z)-7-[(1S,4S,5S,6R)-2-methyl-6-[(1E)-oct-1-en-1-yl]-2-azabicyclo[2.2.1]hept-5-yl]hept-5-enoic acid
Homo sapiens
recombinant enzyme, using prostaglandin H2 as substrate, in 0.1 M potassium phosphate buffer, pH 6.5, at 37°C
1
(5Z)-7-[(1S,4S,5S,6R)-2-methyl-6-[(1E)-oct-1-en-1-yl]-2-azabicyclo[2.2.1]hept-5-yl]hept-5-enoic acid
Homo sapiens
IC50 about 1 mM, recombinant enzyme, using prostaglandin D2 as substrate, in 0.1 M potassium phosphate buffer, pH 6.5, at 37°C
1
(5Z)-7-[(1S,4S,5S,6R)-2-methyl-6-[(1E)-oct-1-en-1-yl]-2-azabicyclo[2.2.1]hept-5-yl]hept-5-enoic acid
Homo sapiens
IC50 about 1 mM, recombinant enzyme, using prostamide D2 as substrate, in 0.1 M potassium phosphate buffer, pH 6.5, at 37°C
0.005
bimatoprost
Homo sapiens
recombinant enzyme, using prostaglandin D2 as substrate,in 0.1 M potassium phosphate buffer, pH 6.5, at 37°C
0.006
bimatoprost
Homo sapiens
recombinant enzyme, using prostaglandin H2 as substrate,in 0.1 M potassium phosphate buffer, pH 6.5, at 37°C
0.06
bimatoprost
Homo sapiens
recombinant enzyme, using prostamide D2 as substrate,in 0.1 M potassium phosphate buffer, pH 6.5, at 37°C
0.13
ONO1349
Homo sapiens
recombinant enzyme, using prostaglandin H2 as substrate,in 0.1 M potassium phosphate buffer, pH 6.5, at 37°C
1
ONO1349
Homo sapiens
recombinant enzyme, using prostaglandin D2 as substrate,in 0.1 M potassium phosphate buffer, pH 6.5, at 37°C
1
ONO1349
Homo sapiens
recombinant enzyme, using prostamide D2 as substrate,in 0.1 M potassium phosphate buffer, pH 6.5, at 37°C
0.3
ONO1370
Homo sapiens
recombinant enzyme, using prostaglandin H2 as substrate,in 0.1 M potassium phosphate buffer, pH 6.5, at 37°C
1
ONO1370
Homo sapiens
recombinant enzyme, using prostaglandin D2 as substrate,in 0.1 M potassium phosphate buffer, pH 6.5, at 37°C
1
ONO1370
Homo sapiens
recombinant enzyme, using prostamide D2 as substrate,in 0.1 M potassium phosphate buffer, pH 6.5, at 37°C
0.06
ONO1373
Homo sapiens
recombinant enzyme, using prostaglandin H2 2 as substrate,in 0.1 M potassium phosphate buffer, pH 6.5, at 37°C
1
ONO1373
Homo sapiens
recombinant enzyme, using prostaglandin D2 as substrate,in 0.1 M potassium phosphate buffer, pH 6.5, at 37°C
1
ONO1373
Homo sapiens
recombinant enzyme, using prostamide D2 2 as substrate,in 0.1 M potassium phosphate buffer, pH 6.5, at 37°C
0.1
Tolrestat
Homo sapiens
recombinant enzyme, using prostaglandin D2 as substrate,in 0.1 M potassium phosphate buffer, pH 6.5, at 37°C
0.3
Tolrestat
Homo sapiens
recombinant enzyme, using prostaglandin H2 as substrate,in 0.1 M potassium phosphate buffer, pH 6.5, at 37°C
0.45
Tolrestat
Homo sapiens
recombinant enzyme, using prostamide D2 as substrate,in 0.1 M potassium phosphate buffer, pH 6.5, at 37°C
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.078
purified recombinant enzyme, pH 7.0, 25°C, in presence of 0.05 mM 9,10-phenanthrenequinone
additional information
-
at 37°C in 100 mM Tris/HCl (pH 7.0), the reaction product, 9-alpha,11-beta-prostaglandin F2 is detected as well as the substrate prostaglandin D2 in the reaction solution after reaction for 1 h, the amount of the product increases linearly for 1 h and then gradually plateaues
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6.5
6.5
assay at, PGD2 11-ketoreductase activity and PGH2 9,11-endoperoxide reductase activity
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
25 - 37
-
the activity increases gradually as the temperature increases from 25 to 37°C, and then decreases significantly at 45°C compared with that at 37°C
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
of invasive ductal carcinoma of the breast, immunohistochemical analysis
isoform AKR1B1 is expressed at a high level during the menstrual cycle during the secretory phase and in both epithelial and stromal cells
isoform AKR1B1 is expressed at a high level during the menstrual cycle during the secretory phase and in both epithelial and stromal cells
the prostaglandin F synthase AKR1B1 is upregulated while prostaglandin transporter is downregulated during term labor. The amnion is more responsive than choriodecidua to stimulation with proinflammatory cytokines. The mechanisms of term and preterm labor are different, overview
-
expression of genes for PGE2 synthesis, with low levels of prostaglandin transporters and dehydrogenase
normal breast expresses very high levels of AKR1C3 relative to other tissues
-
production of PGE2, PGF2 and PGD2 and high prostaglandin turnover
both activities of enzymes AKR1C1/AKR1C2 and AKR1C3 are present in the periovuatory granulosa cell
-
proximal tubule, the enzyme is associated with the cyclooxygenase-I, COX-I
-
in pregnant myometrium, PGI2, PGD2 and PGF2 synthases are highly expressed while prostaglandin dehydrogenase is underexpressed. Myometrium from non-pregnant women has lower levels of prostaglandin synthases and higher levels of prostaglandin dehydrogenase than pregnant myometrium
-
the prostaglandin synthase expression profile favours production of PGD2, PGE2 and PGF2, with high levels of prostaglandin transporters and catabolic prostaglandin dehydrogenase suggesting rapid prostaglandin turnover
-
the enzyme is associated with the cyclooxygenase-II, COX-II
AKR1C3 is overexpressed in skin squamous cell carcinoma (SCC) and affects SCC growth via prostaglandin metabolism
additional information
18fold increase in the median AKR1C3 mRNA levels in breast cancer patients as compared to those without disease
of invasive ductal carcinoma of the breast, immunohistochemical analysis
AKR1C3 is overexpressed in the fibrotic area of keloids (scarfs) while relatively weak staining is detected in normal skin
additional information
AKR1B1 shows decreased expression in neoplastic disease, with decreased AKR1B1 immunoreactivity in carcinoma cells compared with nonneoplastic ductal cells, suggesting that AKR1B1 activity might be suppressed in tumor cells in breast cancer tissues
additional information
AKR1B1 shows decreased expression in neoplastic disease, with decreased AKR1B1 immunoreactivity in carcinoma cells compared with nonneoplastic ductal cells, suggesting that AKR1B1 activity might be suppressed in tumor cells in breast cancer tissues
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
metabolism
physiological function
malfunction
metabolism
AKR1C3 is an enzyme responsible for the metabolism of steroid hormones such as androgens, progesterones and estrogens in addition to the reduction of PGD2 to 11beta-PGF2alpha
physiological function
additional information
evolution
most prostaglandin F2alpha synthases (PGFS) identified to date are aldo-ketoreductases, AKRs
metabolism
AKR1B1 is involved in the synthesis of PGF2alpha. Pathways of prostaglandin F2alpha biosynthesis in human cells, overview
metabolism
AKR1C3 is able to produce PGF2alpha in the endometrium in addition to AKR1B1. The PGF synthase activity of AKR1B1 proves to be much higher than that of AKR1C3
metabolism
there are three different pathways for the synthesis of the uterotonic PGF2alpha: 1. from PGH2 by PGH 9-,11-endoperoxide reductase, 2. from PGD2 by PGD 11-ketoreductase, 3. from PGE2 by PGE 9-ketoreductase
physiological function
in breast cancer, the status of the 11alpha-PGF2alpha and 11beta-PGF2alpha cognate FP receptor is associated with adverse clinical outcome only in the AKR1C3 positive cases, while there are no significant correlations between FP receptor status and any of the clinicathological parameters in AKR1B1 positive cases. AKR1B1 does not induce Slug expression
physiological function
PGF2alpha plays important roles in the regulation of ocular pressure, renal absorption, cardiovascular function, adipocyte differentiation, and female reproductive function. Role of AKR1C3 in the formation of PGF2alpha from PGH2 in the bovine endometrium
physiological function
prostaglandins (PGs) are important regulators of female reproductive function. The primary PGs produced in the endometrium are PGE2 and PGF2alpha. Role of aldo-ketoreductase (AKR)1B1 in increased PGF2alpha production by human endometrial cells following stimulation with interleukin-1beta (IL-1beta)
malfunction
administration of an AKR1C3 inhibitor significantly decreases 11beta-PGF2alpha concentrations in culture media of breast cancer cells
malfunction
although attenuating AKR1C3 expression in squamous cell carcinoma cells by siRNA does not affect growth, treatment with PGD2 and its dehydration metabolite, 15delta-PGJ2, decreases squamous cell carcinoma, SCC, proliferation in a PPARgamma-dependent manner. In addition, treatment with the PPARgamma agonist pioglitazone profoundly inhibits squamous cell carcinoma proliferation. SCC-AKR1C3 metabolizes protaglandin D2, PGD2, to 9alpha,11beta-prostaglandin F2 12fold faster than the parent cell line and is protected from the antiproliferative effect mediated by PGD2. PGD2 and its metabolite 15delta-prostaglandin J2 attenuate SCC proliferation in a PPARgamma-dependent manner, therefore activation of PPARgamma by agonists such as pioglitazone may benefit those at high risk of SCC
malfunction
the enzyme inhibitor 15-deoxy-delta12,14-prostaglandin J2 attenuates proliferation, inhibits collagen gel contraction and induces activation of the apoptotic marker, caspase-3, in CRL1762 keloid fibroblasts, overview
physiological function
AKR1C3 is overexpressed in skin squamous cell carcinoma (SCC) and affects SCC growth via prostaglandin metabolism. AKR1C3 is overexpressed in various malignancies, suggesting a tumor promoting function. SCC-AKR1C3 metabolizes protaglandin D2, PGD2, to 9alpha,11beta prostaglandin F2. Unlike other AKR1C members, AKR1C3 can synthesize prostaglandin F2alpha from prostaglandin H2, an arachidonic acid derivative synthesized by cyclooxygenase
physiological function
in breast cancer, the status of the 11alpha-PGF2alpha and 11beta-PGF2alpha cognate FP receptor is associated with adverse clinical outcome only in the AKR1C3 positive cases, immunohistochemical analysis. FP receptor-mediated functions of 11beta-PGF2alpha using FP receptor expressed MCF-7 cell line shows that 11beta-PGF2alpha treatment phosphorylates ERK and CREB and induces Slug expression through FP receptor in MCF-FP, and MCF-FP cells demonstrate decreased chemosensitivity compared to parental controls. The actions of AKR1C3, but not of AKR1B1, can produce FP receptor ligands whose activation results in carcinoma cell survival in breast cancer. 11beta-PGF2alpha stimulates phosphorylation of ERK and CREB via FP receptor. AKR1C3-dependent signaling performs through 11beta-PGF2alpha and the FP receptor, overview
physiological function
the enzyme is involved in prostaglandins metabolism. The produced PGF2alpha can not only promote prostate cancer cell's proliferation but also enhance prostate cancer cells resistance to radition. Overexpression of AKR1C3 significantly enhances human prostate cancer cells PCa resistance to radiation (or tert-butyl hydroperoxide) through activation of MAPK pathway. AKR1C3 has a pivotal role in the radioresistance of esophageal cancer and non-small-cell lung cancer
physiological function
The major eicosanoid secreted by mast cells is prostaglandin D2 (PGD2), a relatively unstable pro-inflammatory mediator which can be spontaneously converted to 15-deoxy-(Delta12,14)-prostaglandin J2(15d-PGJ2) or enzymatically metabolized to 9alpha,11beta-PGF2 by aldo-keto reductase 1C3 (AKR1C3). Role of enzyme AKR1C3-mediated prostaglandin D2 (PGD2) metabolism in keloids, overview. Keloids are progressively expanding scars, mostly prevalent in individuals of African descent. Metabolism of PGD2 to 9a,11b-PGF2 by both, keloids and normal fibroblasts, is dependent on AKR1C3
additional information
comparisons of PGFS activity of recombinant bovine and human endometrial AKRs, overview
additional information
-
comparisons of PGFS activity of recombinant bovine and human endometrial AKRs, overview
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). MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37000
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
enzyme has a (alpha/beta)8 barrel structure, from crystal structure determination
additional information
-
enzyme has a (alpha/beta)8 barrel structure, from crystal structure determination
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
16 mg/ml purified enzyme complexed with inhibitors acetate, flufenamic acid or indomethacin, hanging drop vapour diffusion method in 0.006 ml drops, 1:1 mixture of protein solution containing 10 mM potassium phosphate, pH 7.0, 1 mM DTT, 1 mM EDTA, 2 mM NADP+, with reservoir solution containing 25% w/v PEG 4000, 100 mM sodium citrate, pH 6.0, 2.5% v/v 2-methyl-2,4-pentanediol, and 800 mM ammonium acetate, 6 days to maximum size, X-ray diffraction structure determination of the complexes and analysis at 1.2-2.1 A resolution
20 mg/ml purified recombinant enzyme in a solution containing 1.4 mM PGD2 or inhibitor rutin, 1.2 mM NADP+ and NADPH, 50 mM MES, pH 6.0, and 25% w/v PEG 8000, hanging drop vapour diffusion method, 2-3 days, thick plate-shaped crystals of enzyme with NADP+ and PGD2 and of enzyme with NADPH and rutin, X-ray diffraction structure determination and analysis at 1.69 A resolution
in complex with bimatoprost and NADPH, hanging drop vapor diffusion method, using 1.0 mM BMP, 1.0 mM NADPH, 0.14 M NaCl, 50 mM MES buffer (pH 7.0), and 26% (w/v) PEG 8000
purified recombinant enzyme in complex with NADPH and bimatoprost BMP, an ocular hypotensive agent bound near the PGD2 binding site located on the alpha- and omega-chains, hanging drop vapour diffusion method, from 50 mM MES, pH 7.0, containing 7 mg/ml protein, 0.14 M NaCl, 26% w/v PEG 8000, 1.0 mM NADPH, and 1.0 mM BMP, added in a 95% ethanol solution, 4°C, 14 days, thick plate-shaped crystals, X-ray diffraction structure determination and analysis at 2.0 A resolution
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Y48F
69% of wild-type activity in presence of NADPH, 138% of wild-type isomerization activity in absence of NADPH, 0.2% of wild-type activity reducing 4-nitrobenzaldehyde
Y55F
additional information
Y55F
site-directed mutagenesis, the mutant loses its PGD2 11-ketoreductase activity, but not the PGH2 9,11-endoperoxide reductase
Y55F
the mutated enzyme loses the prostaglandin D2 11-ketoreductase activity but retains the prostaglandin H2 9,-11-endoperoxide reductase activity
additional information
knockout of AKR1B1 gene expression in human endometrial cell lines using the CRISPR/Cas9 system. Clone 16-2 exhibits deletion of 68 and 2 nucleotides, respectively, on each of the alleles. Cells from this clone lose their ability to produce PGF2alpha but maintain their original human endometrial stromal cells-2 phenotype including the capacity to decidualize in the presence of progesterone (medroxyprogesterone acetate) and 8-bromo-cAMP. Knockout cells also maintain their ability to increase PGE2 production in response to interleukin-1beta
additional information
-
knockout of AKR1B1 gene expression in human endometrial cell lines using the CRISPR/Cas9 system. Clone 16-2 exhibits deletion of 68 and 2 nucleotides, respectively, on each of the alleles. Cells from this clone lose their ability to produce PGF2alpha but maintain their original human endometrial stromal cells-2 phenotype including the capacity to decidualize in the presence of progesterone (medroxyprogesterone acetate) and 8-bromo-cAMP. Knockout cells also maintain their ability to increase PGE2 production in response to interleukin-1beta
additional information
-
coexpression of COX-1 and COX-2 increases the endogenous cytosolic PGFS-I activity, but only slightly the membrane-bound activity, overview
additional information
AKR1C3 overexpressing skin squamous cell carcinoma, SCC, cells are protected from the antiproliferative effects of prostaglandin D2
additional information
establishment of a stable overexpressing AKR1C3 cell line (AKR1C3-over) derived from the prostate cell line DU145
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
gene AKR1B1, cloning from genomic DNA, DNA and amino acid sequence determination and analysis, recombinant expression in immortalized human endometrial stromal cells, HIESC-2 cells, expression analysis in clones 16-1, 16-2, and 16-4. Clones 16-1 and 16-2 present with a complete absence of AKR1B1 protein, while clone 16-4 is able to express the AKR1B1 protein. Following treatment of cells with interleukin-1beta, both wild-type and clone 16-4 cells exhibit a similar response, but clone 16-2 does not respond with increased production of eitherPGF2alpha or PGE2. At the protein level, IL-1beta induces an increase in mPGES-1 and COX-2 protein expression but in clone 16-2 the relative increase of Cox-2 protein is weaker
gene AKR1C3, recombinant expression of N-terminally His8-tagged enzyme in Escherichia coli strain BL21(DE3)pLysS
expressed in Escherichia coli HB101 cells
overexpression of AKR1C3 using a pLNCX retroviral vector in MCF-7 cell line
SCC cell line is infected with either AKR1C3 overexpressing retroviral construct (SCC-AKR1C3), quantitative AKR1C3 expression analysis in wild-type and mtransfected cells
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
AKR1B1 shows decreased expression in neoplastic disease, AKR1B1 activity might be suppressed in tumor cells in breast cancer tissues
AKR1C3 expression is induced by interleukin-1beta leading to a higher production of prostaglandin F2alpha
expression of AKR1B1 is upregulated in the fetal membranes in association with term labor, during labor tumor necrosis factor TNF upregulates the AKR1B1 protein expression
interleukin IL-1beta is able to upregulate COX-2 and AKR1B1 proteins as well as prostaglandin F2alpha production under normal glucose concentrations. The promoter activity of AKR1B1 gene is increased by IL-1beta particularly around the multiple stress response region
AKR1C3 is overexpressed in skin squamous cell carcinoma (SCC) and affects SCC growth via prostaglandin metabolism. It is upregulated by its substrate, prostaglandin D2
in cultured myometrial cells there is a dose-dependent stimulatory effect of interleukin 1beta and tumor necrosis factor alpha on PTGS2, PTGES and AKR1B1, i.e.PGF synthase expression
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
drug development
prostaglandin formation is a key component of PGaction and the specific target of non-steroidal anti-inflammatory drugs
molecular biology
genome editing of human cell lines can be used to complement mouse KO models to validate the function of genes in differentiated tissues and cells
medicine
AKR1C3 likely plays important roles in the development of hormone-dependent, and possibly hormone-independent, breast cancer. It is highly expressed in normal breast and upregulated in breast cancer, where its expression is associated with a worse prognosis
pharmacology
enzyme is a target for cyclooxygenase-independent antineoplastic actions of nonsteroidal anti-inflammatory drugs
synthesis
-
development of a coupled assay method for enzymatic formation of prostamide F2alpha from anandamide by the cyclooxygenase-II and the prostaglandin synthase F involving the intermediate metabolite, prostamide H2
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Suzuki-Yamamoto, T.; Nishizawa, M.; Fukui, M.; Okuda-Ashitaka, E.; Nakajima, T.; Ito, S.; Watanabe, K.
cDNA cloning, expression and characterization of human prostaglandin F synthase
FEBS Lett.
462
335-340
1999
Homo sapiens
Wolfe, L.S.; Rostworowski, K.; Pellerin, L.; Sherwin, A.
Metabolism of prostaglandin D2 by human cerebral cortex into 9alpha,11beta-prostaglandin F2 by an active NADPH-dependent 11-ketoreductase:Metabolism of prostaglandin D2 by human cerebral cortex into 9alpha,11beta-prostaglandin F2 by an active NADPH-dependent 11-ketoreductase
J. Neurochem.
53
64-70
1989
Homo sapiens
Koda, N.; Tsutsui, Y.; Niwa, H.; Ito, S.; Woodward, D.F.; Watanabe, K.
Synthesis of prostaglandin F ethanolamide by prostaglandin F synthase and identification of Bimatoprost as a potent inhibitor of the enzyme: new enzyme assay method using LC/ESI/MS
Arch. Biochem. Biophys.
424
128-136
2004
Homo sapiens, Homo sapiens (P42330)
Komoto, J.; Yamada, T.; Watanabe, K.; Takusagawa, F.
Crystal structure of human prostaglandin F synthase (AKR1C3)
Biochemistry
43
2188-2198
2004
Homo sapiens (P42330), Homo sapiens
Nakashima, K.; Ueno, N.; Kamei, D.; Tanioka, T.; Nakatani, Y.; Murakami, M.; Kudo, I.
Coupling between cyclooxygenases and prostaglandin F(2alpha) synthase. Detection of an inducible, glutathione-activated, membrane-bound prostaglandin F2alpha-synthetic activity
Biochim. Biophys. Acta
1633
96-105
2003
Homo sapiens, Mus musculus, Rattus norvegicus
Lovering, A.L.; Ride, J.P.; Bunce, C.M.; Desmond, J.C.; Cummings, S.M.; White, S.A.
Crystal structures of prostaglandin D(2) 11-ketoreductase (AKR1C3) in complex with the nonsteroidal anti-inflammatory drugs flufenamic acid and indomethacin
Cancer Res.
64
1802-1810
2004
Homo sapiens (P42330)
Watanabe, K.
Prostaglandin F synthase
Prostaglandins
68-69
401-407
2002
Bos taurus, Oryctolagus cuniculus, Ovis aries, Homo sapiens, Rattus norvegicus, Trypanosoma brucei
Sakurai, M.; Oishi, K.; Watanabe, K.
Localization of cyclooxygenases-1 and -2, and prostaglandin F synthase in human kidney and renal cell carcinoma
Biochem. Biophys. Res. Commun.
338
82-86
2005
Homo sapiens
Komoto, J.; Yamada, T.; Watanabe, K.; Woodward, D.F.; Takusagawa, F.
Prostaglandin F2alpha formation from prostaglandin H2 by prostaglandin F synthase (PGFS): crystal structure of PGFS containing bimatoprost
Biochemistry
45
1987-1996
2006
Homo sapiens, Homo sapiens (P42330)
Yang, W.; Ni, J.; Woodward, D.F.; Tang-Liu, D.D.; Ling, K.H.
Enzymatic formation of prostamide F2alpha from anandamide involves a newly identified intermediate metabolite, prostamide H2
J. Lipid Res.
46
2745-2751
2005
Homo sapiens
Byrns, M.C.; Steckelbroeck, S.; Penning, T.M.
An indomethacin analogue, N-(4-chlorobenzoyl)-melatonin, is a selective inhibitor of aldo-keto reductase 1C3 (type 2 3alpha-HSD, type 5 17beta-HSD, and prostaglandin F synthase), a potential target for the treatment of hormone dependent and hormone independent malignancies
Biochem. Pharmacol.
75
484-493
2008
Homo sapiens (P42330)
Dozier, B.L.; Watanabe, K.; Duffy, D.M.
Two pathways for prostaglandin F2 alpha synthesis by the primate periovulatory follicle
Reproduction
136
53-63
2008
Homo sapiens (P42330), Homo sapiens AKR1C3 (P42330), Macaca fascicularis, Macaca fascicularis AKR1C3
Byrns, M.; Penning, T.
Type 5 17beta-hydroxysteroid dehydrogenase/prostaglandin F synthase (AKR1C3): Role in breast cancer and inhibition by non-steroidal anti-inflammatory drug analogs
Chem. Biol. Interact.
178
221-227
2009
Homo sapiens, Homo sapiens (P42330)
Inagaki, S.; Esaka, Y.; Deyashiki, Y.; Uno, B.; Hara, A.; Toyooka, T.
Human liver dihydrodiol dehydrogenase 1-catalyzed reaction generating 9alpha,11beta-prostaglandin F2 from prostaglandin D2 followed by micellar electrokinetic chromatography
J. Sep. Sci.
31
735-740
2008
Homo sapiens
Kabututu, Z.; Manin, M.; Pointud, J.C.; Maruyama, T.; Nagata, N.; Lambert, S.; Lefrancois-Martinez, A.M.; Martinez, A.; Urade, Y.
Prostaglandin F2alpha synthase activities of aldo-keto reductase 1B1, 1B3 and 1B7
J. Biochem.
145
161-168
2009
Homo sapiens (P15121), Homo sapiens (P42330), Homo sapiens, Mus musculus
Phillips, R.J.; Al-Zamil, H.; Hunt, L.P.; Fortier, M.A.; Lopez Bernal, A.
Genes for prostaglandin synthesis, transport and inactivation are differentially expressed in human uterine tissues, and the prostaglandin F synthase AKR1B1 is induced in myometrial cells by inflammatory cytokines
Mol. Hum. Reprod.
17
1-13
2011
Homo sapiens
Nagata, N.; Kusakari, Y.; Fukunishi, Y.; Inoue, T.; Urade, Y.
Catalytic mechanism of the primary human prostaglandin F2alpha synthase, aldo-keto reductase 1B1 - prostaglandin D2 synthase activity in the absence of NADP(H)
FEBS J.
278
1288-1298
2011
Homo sapiens (P15121), Homo sapiens, Mus musculus
Bresson, E.; Lacroix-Pepin, N.; Boucher-Kovalik, S.; Chapdelaine, P.; Fortier, M.A.
The prostaglandin F synthase activity of the human aldose reductase AKR1B1 brings new lenses to look at pathologic conditions
Front. Pharmacol.
3
98
2012
Homo sapiens (P15121), Homo sapiens
Bresson, E.; Boucher-Kovalik, S.; Chapdelaine, P.; Madore, E.; Harvey, N.; Laberge, P.Y.; Leboeuf, M.; Fortier, M.A.
The human aldose reductase AKR1B1 qualifies as the primary prostaglandin F synthase in the endometrium
J. Clin. Endocrinol. Metab.
96
210-219
2011
Homo sapiens (P15121), Homo sapiens
Liedtke, A.J.; Adeniji, A.O.; Chen, M.; Byrns, M.C.; Jin, Y.; Christianson, D.W.; Marnett, L.J.; Penning, T.M.
Development of potent and selective indomethacin analogues for the inhibition of AKR1C3 (Type 5 17beta-hydroxysteroid dehydrogenase/prostaglandin F synthase) in castrate-resistant prostate cancer
J. Med. Chem.
56
2429-2446
2013
Homo sapiens (P42330)
Mantel, A.; Carpenter-Mendini, A.; VanBuskirk, J.; Pentland, A.P.
Aldo-keto reductase 1C3 is overexpressed in skin squamous cell carcinoma (SCC) and affects SCC growth via prostaglandin metabolism
Exp. Dermatol.
23
573-578
2014
Homo sapiens (P42330)
Mantel, A.; Newsome, A.; Thekkudan, T.; Frazier, R.; Katdare, M.
The role of aldo-keto reductase 1C3 (AKR1C3)-mediated prostaglandin D2 (PGD2) metabolism in keloids
Exp. Dermatol.
25
38-43
2016
Homo sapiens (P42330)
Alzamil, H.A.; Pawade, J.; Fortier, M.A.; Bernal, A.L.
Expression of the prostaglandin F synthase AKR1B1 and the prostaglandin transporter SLCO2A1 in human fetal membranes in relation to spontaneous term and preterm labor
Front. Physiol.
5
272
2014
Homo sapiens (P15121), Homo sapiens
Yoda, T.; Kikuchi, K.; Miki, Y.; Onodera, Y.; Hata, S.; Takagi, K.; Nakamura, Y.; Hirakawa, H.; Ishida, T.; Suzuki, T.; Ohuchi, N.; Sasano, H.; McNamara, K.M.
11beta-Prostaglandin F2alpha, a bioactive metabolite catalyzed by AKR1C3, stimulates prostaglandin F receptor and induces slug expression in breast cancer
Mol. Cell. Endocrinol.
413
236-247
2015
Homo sapiens (P15121), Homo sapiens (P42330)
Lacroix Pepin, N.; Chapdelaine, P.; Rodriguez, Y.; Tremblay, J.P.; Fortier, M.A.
Generation of human endometrial knockout cell lines with the CRISPR/Cas9 system confirms the prostaglandin F2alpha synthase activity of aldo-ketoreductase 1B1
Mol. Hum. Reprod.
20
650-663
2014
Homo sapiens (P15121), Homo sapiens
Sun, S.Q.; Gu, X.; Gao, X.S.; Li, Y.; Yu, H.; Xiong, W.; Yu, H.; Wang, W.; Li, Y.; Teng, Y.; Zhou, D.
Overexpression of AKR1C3 significantly enhances human prostate cancer cells resistance to radiation
Oncotarget
7
48050-48058
2016
Homo sapiens (P42330)
Lacroix Pepin, N.; Chapdelaine, P.; Fortier, M.A.
Evaluation of the prostaglandin F synthase activity of human and bovine aldo-keto reductases: AKR1A1s complement AKR1B1s as potent PGF synthases
Prostaglandins Other Lipid Mediat.
106
124-132
2013
Bos taurus (P16116), Bos taurus, Homo sapiens (P15121), Homo sapiens
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