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Information on EC 1.14.99.1 - prostaglandin-endoperoxide synthase and Organism(s) Homo sapiens and UniProt Accession P35354

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EC Tree
IUBMB Comments
This enzyme acts both as a dioxygenase and as a peroxidase.
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This record set is specific for:
Homo sapiens
UNIPROT: P35354
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Word Map
The taxonomic range for the selected organisms is: Homo sapiens
The enzyme appears in selected viruses and cellular organisms
Synonyms
cox-2, cyclooxygenase, cyclooxygenase-2, cox-1, cyclooxygenase 2, ptgs2, pghs-2, cyclooxygenase-1, prostaglandin synthetase, pghs-1, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
cyclooxygenase
-
cyclooxygenase 2
-
cyclooxygenase-2
-
PG H synthase
-
PGHS-1
isoform
PGHS-2
prostaglandin endoperoxide H synthase
-
prostaglandin endoperoxide H synthase 2
-
prostaglandin endoperoxide synthase 2
-
prostaglandin G/H synthase
-
prostaglandin H synthase
-
prostaglandin H synthase-2
-
prostaglandin-endoperoxide synthase 2
-
(PG)H synthase
-
-
-
-
COX-1
COX1
-
-
cyclooxygenase
cyclooxygenase-1
-
cyclooxygenase-1b
-
cyclooxygenase-1 splice variant
cyclooxygenase-2
-
-
cycloxigenase-2
-
-
fatty acid cyclooxygenase
-
-
-
-
hPGHS-2
-
-
PG H synthase
-
PG synthetase
-
-
-
-
PGHS-1
PGHS-2
prostaglandin endoperoxide H synthase
-
prostaglandin endoperoxide H synthase 1
-
prostaglandin endoperoxide H synthase-1
-
-
prostaglandin endoperoxide H2 synthase-2
-
-
prostaglandin endoperoxide synthase
-
-
prostaglandin endoperoxide synthetase
-
-
-
-
prostaglandin G/H synthase
-
-
-
-
prostaglandin H synthase
prostaglandin H synthase-1
-
prostaglandin H synthase-2
-
-
prostaglandin synthase
-
-
-
-
prostaglandin synthase-2
-
-
-
-
prostaglandin synthetase
-
-
-
-
prostaglandin-endoperoxide synthase 2
-
-
PTGS2
-
-
synthase, prostaglandin
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
oxidation
reduction
redox reaction
-
-
-
-
oxidation
reduction
PATHWAY SOURCE
PATHWAYS
-
-, -, -, -
SYSTEMATIC NAME
IUBMB Comments
(5Z,8Z,11Z,14Z)-icosa-5,8,11,14-tetraenoate,hydrogen-donor:oxygen oxidoreductase
This enzyme acts both as a dioxygenase and as a peroxidase.
CAS REGISTRY NUMBER
COMMENTARY hide
39391-18-9
-
9055-65-6
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
arachidonate + AH2 + 2 O2
prostaglandin G2 + A + ?
show the reaction diagram
-
-
-
?
arachidonate + AH2 + 2 O2
prostaglandin H2 + A + H2O
show the reaction diagram
arachidonate + AH2 + O2
prostaglandin H2 + A + H2O
show the reaction diagram
arachidonate + reduced N,N,N',N'-tetramethylphenylenediamine + 2 O2
prostaglandin H2 + oxidized N,N,N',N'-tetramethylphenylenediamine + H2O
show the reaction diagram
arachidonic acid + AH2 + 2 O2
prostaglandin E2 + A + H2O
show the reaction diagram
-
-
-
?
cis-8,11,14-eicosatrienoic acid + AH2 + O2
?
show the reaction diagram
-
-
-
?
linoleic acid + AH2 + O2
9-hydroxyoctadecadienoic acid + 13-hydroxyoctadecadienoic acid + ?
show the reaction diagram
-
-
-
?
arachidonate + AH2 + 2 O2
prostaglandin G2 + A + ?
show the reaction diagram
-
-
-
?
arachidonate + AH2 + 2 O2
prostaglandin H2 + A + H2O
show the reaction diagram
arachidonate + AH2 + O2
prostaglandin H2 + A + H2O
show the reaction diagram
arachidonate + electron donor + O2
prostaglandin H2 + oxidized electron donor + H2O
show the reaction diagram
arachidonate + reduced N,N,N',N'-tetramethylphenylenediamine + 2 O2
prostaglandin H2 + oxidized N,N,N',N'-tetramethylphenylenediamine + H2O
show the reaction diagram
arachidonic acid + AH2 + 2 O2
15(R)-hydroxy-eicosatetraenoic acid + A + H2O
show the reaction diagram
-
-
product of aspirin acetylated enzyme or S516M mutant
?
arachidonic acid + AH2 + 2 O2
6-keto-prostaglandin F1alpha + A + H2O
show the reaction diagram
-
activity assay
-
-
?
arachidonic acid + AH2 + 2 O2
prostaglandin E2 + A + H2O
show the reaction diagram
-
-
-
?
cis-11,14-eicosadienoic acid + AH2 + O2
?
show the reaction diagram
-
-
-
?
cis-4,7,10,13,16,19-docosahexaenoic acid + AH2 + O2
?
show the reaction diagram
-
-
-
?
cis-5,8,11,14,17-eicosapentaenoic acid + AH2 + O2
?
show the reaction diagram
-
-
-
?
cis-5,8,11,14-eicosatetraenoic acid + AH2 + O2
?
show the reaction diagram
-
-
-
?
cis-7,10,13,16-docosatetraenoic acid + AH2 + O2
?
show the reaction diagram
-
-
-
?
gamma-linolenic acid + AH2 + O2
?
show the reaction diagram
-
-
-
?
guaiacol + trans-5-phenyl-4-pentenyl-1-hydroperoxide
?
show the reaction diagram
-
-
-
-
?
H2O2 + guaiacol
?
show the reaction diagram
-
peroxidase activity
-
-
?
H2O2 + N,N,N',N'-tetramethyl-p-phenylenediamine
?
show the reaction diagram
-
peroxidase activity
-
-
?
linoleic acid + AH2 + O2
9-hydroxyoctadecadienoic acid + 13-hydroxyoctadecadienoic acid + ?
show the reaction diagram
-
-
-
?
linolenic acid + AH2 + O2
?
show the reaction diagram
-
-
-
?
additional information
?
-
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
arachidonate + AH2 + 2 O2
prostaglandin G2 + A + ?
show the reaction diagram
-
-
-
?
arachidonate + AH2 + 2 O2
prostaglandin H2 + A + H2O
show the reaction diagram
arachidonate + AH2 + O2
prostaglandin H2 + A + H2O
show the reaction diagram
arachidonate + AH2 + 2 O2
prostaglandin G2 + A + ?
show the reaction diagram
-
-
-
?
arachidonate + AH2 + 2 O2
prostaglandin H2 + A + H2O
show the reaction diagram
arachidonate + AH2 + O2
prostaglandin H2 + A + H2O
show the reaction diagram
additional information
?
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
iron-protoporphyrin IX
each subunit contains a molecule of Fe3+-protoporphyrin IX noncovalently attached to the enzyme, the heme group is essential for both enzyme activities
iron-protoporphyrin IX
each subunit contains a molecule of Fe3+-protoporphyrin IX noncovalently attached to the enzyme, the heme group is essential for both enzyme activities
additional information
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Iron
each subunit contains a molecule of Fe3+-protoporphyrin IX noncovalently attached to the enzyme, the heme group is essential for both enzyme activities, the cofactor is released by induction of inhibitor nitroarachidonic acid
Fe3+
-
-
Iron
each subunit contains a molecule of Fe3+-protoporphyrin IX noncovalently attached to the enzyme, the heme group is essential for both enzyme activities, the cofactor is released by induction of inhibitor nitroarachidonic acid
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
NS-398
inhibits PTGS2
PD-98059
MEK inhibitor, blocks specifically the activation of ERK1/2 and the PGHS-2 mRNA response to oxygen and glucose depivation, hence ERK is a mediator of PGHS-2 gene expression
quercetin 3-O-glucoside
-
SB203580
inhibitor of p38, reduces the PGHS-2 response to oxygen and glucose depivation by approximately 50%
U0126
MEK inhibitor, blocks specifically the activation of ERK1/2 and the PGHS-2 mRNA response to oxygen and glucose depivation, hence ERK is a mediator of PGHS-2 gene expression
12-nitroarachidonic acid
nitro-fatty acid inhibition is due to a slow, tightly binding mechanism, it inhibits oxygenase and peroxidase activity PGHS-1, kinetics, overview. Inactivation of PGHS by nitroarachidonic acid involves two sequential steps: an initial reversible binding event, followed by a practically irreversible event leading to an inactivated enzyme. Inactivation is associated with irreversible disruption of heme binding to the protein, the inhibitor induces heme release from Fe2+-protoporphyrin-PGHS-1. In activated human platelets, nitroarachidonic acid significantly decreases PGHS-1-dependent thromboxane B2 formation in parallel with a decrease in platelet aggregation
14-nitroarachidonic acid
nitro-fatty acid inhibition is due to a slow, tightly binding mechanism, it inhibits oxygenase and peroxidase activity PGHS-1, kinetics, overview. Inactivation of PGHS by nitroarachidonic acid involves two sequential steps: an initial reversible binding event, followed by a practically irreversible event leading to an inactivated enzyme. Inactivation is associated with irreversible disruption of heme binding to the protein, the inhibitor induces heme release from Fe2+-protoporphyrin-PGHS-1. In activated human platelets, nitroarachidonic acid significantly decreases PGHS-1-dependent thromboxane B2 formation in parallel with a decrease in platelet aggregation
15-nitroarachidonic acid
nitro-fatty acid inhibition is due to a slow, tightly binding mechanism, it inhibits oxygenase and peroxidase activity PGHS-1, kinetics, overview. Inactivation of PGHS by nitroarachidonic acid involves two sequential steps: an initial reversible binding event, followed by a practically irreversible event leading to an inactivated enzyme. Inactivation is associated with irreversible disruption of heme binding to the protein, the inhibitor induces heme release from Fe2+-protoporphyrin-PGHS-1. In activated human platelets, nitroarachidonic acid significantly decreases PGHS-1-dependent thromboxane B2 formation in parallel with a decrease in platelet aggregation
5-amino-2-hydroxy-N-(propan-2-yl)benzamide
-
5-aminosalicylic acid derivative, additionally inhibits lipoxygenase Lox-5. 7.6fold selectivity for isoform Cox-2 over Cox-1
-
5-amino-N-cyclohexyl-2-hydroxybenzamide
-
5-aminosalicylic acid derivative, additionally inhibits lipoxygenase Lox-5. 44fold selectivity for isoform Cox-2 over Cox-1
-
5-amino-N-hexyl-2-hydroxybenzamide
-
5-aminosalicylic acid derivative, additionally inhibits lipoxygenase Lox-5. 44fold selectivity for isoform Cox-2 over Cox-1
-
5-bromo-2-[4-fluorophenyl]-3-[4-methylsulfonylphenyl]-thiophene
5-[[(2,5-dihydroxyphenyl)methyl]amino]-2-hydroxy-N-(4-methylphenyl)benzamide
-
5-aminosalicylic acid derivative, additionally inhibits lipoxygenase Lox-5. 29.7fold selectivity for isoform Cox-2 over Cox-1
-
6-methylnaphthylacetic acid
-
recombinant protein, 50% inhibition at 0.08-0.1 mM
9-nitroarachidonic acid
nitro-fatty acid inhibition is due to a slow, tightly binding mechanism, it inhibits oxygenase activity and peroxidase activity of PGHS-1, kinetics, overview. Inactivation of PGHS by nitroarachidonic acid involves two sequential steps: an initial reversible binding event, followed by a practically irreversible event leading to an inactivated enzyme. Inactivation is associated with irreversible disruption of heme binding to the protein, the inhibitor induces heme release from Fe2+-protoporphyrin-PGHS-1. In activated human platelets, nitroarachidonic acid significantly decreases PGHS-1-dependent thromboxane B2 formation in parallel with a decrease in platelet aggregation
Acetylsalicylic acid
-
an irreversible inhibitor of both hPHS-1 and hPHS-2
anirolac
-
isozyme 1, 50% inhibition at 0.0007 mM, isozyme 2, 50% inhibition at 0.009 mM
BW 755C
-
recombinant protein, 50% inhibition at 0.01-0.02 mM
delta-tocopherol-13'-carboxychromanol
-
inhibits isoform Cox-1 and suppresses Cox-1 mediated formation of thromboxane in collagen-stimulated rat's platelets
-
delta-tocotrienol
-
inhibits isoform Cox-1 and suppresses Cox-1 mediated formation of thromboxane in collagen-stimulated rat's platelets
delta-tocotrienol-13'-carboxychromanol
-
inhibits isoform Cox-1 and suppresses Cox-1 mediated formation of thromboxane in collagen-stimulated rat's platelets
-
diclofenac
DUP-697
etodalac
-
recombinant protein, 50% inhibition at 0.06-0.07 mM
ETYA
-
recombinant protein, 50% inhibition at 0.015-0.025 mM
fenclofenac
-
isozyme 1, 50% inhibition at 0.007 mM, isozyme 2, 50% inhibition at 0.004 mM
flosulide
-
selective for isozyme 2, 50% inhibition at 130 nM
Flufenamic acid
-
50% inhibition at 0.02 mM
flurbiprofen
Ibuprofen
indomethacin
Ketoprofen
L-745
-
isozyme 1, 50% inhibition at 0.369 mM, isozyme 2, 50% inhibition at 0.002 mM
Mefenamic acid
-
isozyme 1, 50% inhibition at 0.01 mM, isozyme 2, 50% inhibition at 0.0003 mM
meloxicam
-
isozyme 1, 50% inhibition at 0.005 mM, isozyme 2, 50% inhibition at 0.0004 mM
N-butyl-5-[[(2,5-dihydroxyphenyl)methyl]amino]-2-hydroxybenzamide
-
5-aminosalicylic acid derivative, additionally inhibits lipoxygenase Lox-5. 135fold selectivity for isoform Cox-2 over Cox-1
-
N-cyclohexyl-5-[(E)-[(2,5-dihydroxyphenyl)methylidene]amino]-2-hydroxybenzamide
-
5-aminosalicylic acid derivative, additionally inhibits lipoxygenase Lox-5. 120fold selectivity for isoform Cox-2 over Cox-1
-
N-cyclohexyl-5-[[(2,5-dihydroxyphenyl)methyl]amino]-2-hydroxybenzamide
-
5-aminosalicylic acid derivative, additionally inhibits lipoxygenase Lox-5. 114fold selectivity for isoform Cox-2 over Cox-1
-
N-hexyl-5-[[(2,5-dihydroxyphenyl)methyl]amino]-2-hydroxybenzamide
-
5-aminosalicylic acid derivative, additionally inhibits lipoxygenase Lox-5. 145fold selectivity for isoform Cox-2 over Cox-1
-
N-[2-cyclohexyloxy-4-nitrophenyl]methanesulfonamide
naproxen
niflumic acid
-
isozyme 1, 50% inhibition at 0.016 mM, isozyme 2, 50% inhibition at 0.0001 mM
nimesulide
piroxicam
-
isozyme 1, 50% inhibition at 0.009-0.024 mM, isozyme 2, 50% inhibition at 0.070-0.240 mM
quercetin 3-O-glucoside
-
SC-560
SC58125
-
isozyme 1, 50% inhibition at 0.039 mM, isozyme 2, 50% inhibition at 0.0003 mM
suprofen
-
isozyme 1, 50% inhibition at 0.0005 mM, isozyme 2, 50% inhibition at 0.002mM
additional information
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
glutathione
promotes prostaglandin H synthase-dependent formation of oxidative stress biomarkers malondialdehyde and 15(S)-8-iso-prostaglandin F2alpha
arachidonate
-
-
arachidonic acid
-
exogenous, increases hPHS activity
glutathione
promotes prostaglandin H synthase-dependent formation of oxidative stress biomarkers malondialdehyde and 15(S)-8-iso-prostaglandin F2alpha
additional information
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0045 - 0.0102
arachidonate
0.002
cis-8,11,14-eicosatrienoic acid
-
0.0068
linoleic acid
isozyme PGHS-2, in 100 mM Tris-HCl buffer (pH 7.4), at 24°C
0.0031
alpha-linolenic acid
-
0.0009 - 0.01
arachidonate
0.001 - 0.015
arachidonic acid
0.0052
cis-11,14-eicosadienoic acid
-
0.0011
cis-4,7,10,13,16,19-docosahexaenoic acid
-
0.0012
cis-5,8,11,14,17-eicosapentaenoic acid
-
0.0017
cis-5,8,11,14-eicosatetraenoic acid
-
0.0027
cis-7,10,13,16-docosatetraenoic acid
-
0.0048
gamma-linolenic acid
-
0.08 - 0.29
guaiacol
1.3 - 5.5
H2O2
0.0055
linoleic acid
isozyme PGHS-1, in 100 mM Tris-HCl buffer (pH 7.4), at 24°C
0.0083 - 0.0854
N,N,N',N'-tetramethyl-p-phenylenediamine
0.02 - 0.437
trans-5-phenyl-4-pentenyl-1-hydroperoxide
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.00027 - 0.001
nimesulide
additional information
additional information
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.086
quercetin
Homo sapiens
isozyme PGHS-2, in 100 mM Tris-HCl buffer (pH 7.4), at 24°C
0.00039
5-amino-2-hydroxy-N-(propan-2-yl)benzamide
Homo sapiens
-
pH 7.4, temperature not specified in the publication
-
0.00019
5-amino-N-cyclohexyl-2-hydroxybenzamide
Homo sapiens
-
pH 7.4, temperature not specified in the publication
-
0.00022
5-amino-N-hexyl-2-hydroxybenzamide
Homo sapiens
-
pH 7.4, temperature not specified in the publication
-
0.00033
5-[[(2,5-dihydroxyphenyl)methyl]amino]-2-hydroxy-N-(4-methylphenyl)benzamide
Homo sapiens
-
pH 7.4, temperature not specified in the publication
-
0.00051
indomethacin
Homo sapiens
-
pH 7.4, temperature not specified in the publication
0.0001
N-butyl-5-[[(2,5-dihydroxyphenyl)methyl]amino]-2-hydroxybenzamide
Homo sapiens
-
pH 7.4, temperature not specified in the publication
-
0.00011
N-cyclohexyl-5-[(E)-[(2,5-dihydroxyphenyl)methylidene]amino]-2-hydroxybenzamide, N-cyclohexyl-5-[[(2,5-dihydroxyphenyl)methyl]amino]-2-hydroxybenzamide
Homo sapiens
-
pH 7.4, temperature not specified in the publication
-
0.0001
N-hexyl-5-[[(2,5-dihydroxyphenyl)methyl]amino]-2-hydroxybenzamide
Homo sapiens
-
pH 7.4, temperature not specified in the publication
-
0.018
quercetin
Homo sapiens
isozyme PGHS-1, in 100 mM Tris-HCl buffer (pH 7.4), at 24°C
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
4220
purified recombinant His6-tagged PGHS-2, pH 8.0, 37°C
0.0027
-
mutant Y348F, cyclooxygenase activity
0.0039
-
mutant Y504F, cyclooxygenase activity
0.0047
-
mutant Y348F/Y504F, cyclooxygenase activity
0.0058
-
wild-type, cyclooxygenase activity
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.2
cyclooxygenase activity assay
7.4
prostaglandin endoperoxide H synthase assay at
7.2
cyclooxygenase activity assay
7.8
-
enzyme-linked immunoassay for PGE2
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
23
room temperature, 22-23°C, lipoxygenase activity assay
25
cyclooxygenase activity assay using a standard electrode
30
cyclooxygenase activity assay using a high sensitivity electrode
22
-
lipoxygenase activity assay at room temperature
23
room temperature, 22-23°C, lipoxygenase activity assay
25
cyclooxygenase activity assay using a standard electrode
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
seminal plasma induces and potentiates the expression of PTGS2 in cervicovaginal cells and tissues
Manually annotated by BRENDA team
increased expression of PTGS2
Manually annotated by BRENDA team
human neuroblastoma cell
Manually annotated by BRENDA team
vaginal cell line, expression of prostaglandin-endoperoxide synthase 2, i.e. cyclooxygenase 2, in human vaginal cells in response to toll-like receptor ligands and other proinflammatory stimuli, such vaginal mucosal irritant nonoxynol-9, in a synergistic manner
Manually annotated by BRENDA team
-
isozyme 2
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
membrane associated glycoprotein
Manually annotated by BRENDA team
additional information
-
enzyme can be associated with endoplasmic reticulum, nuclear envelope and plasma membrane even within the same cell
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
metabolism
prostaglandin H synthase-2 catalyzes the first two steps in prostaglandin synthesis
physiological function
malfunction
PGHS-1 inhibition in activated human plateletts significantly decreases PGHS-1-dependent thromboxane B2 formation in parallel with a decrease in platelet aggregation
metabolism
prostaglandin H synthase-1 catalyzes the first two steps in prostaglandin synthesis
physiological function
additional information
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
PGH2_HUMAN
604
0
68996
Swiss-Prot
Secretory Pathway (Reliability: 2)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
72000
estimated by PAGE and Western blotting
68000
72000
-
human cyclooxygenase-1bdeltaG, estimated by SDS-PAGE and Western blotting, detected with a cyclooxygenase-1 and a FLAG-tag antibody
73000
-
determined by SDS-PAGE and immunoblotting
75000
-
x * 75000, SDS-PAGE, isozyme 1 and 2
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
homodimer
PGHS-2 is a homodimer of 70 kDa whose dimerization is required for structural integrity and catalytic activity
homodimer
PGHS-1 is a homodimer of 70 kDa whose dimerization is required for structural integrity and catalytic activity
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
glycoprotein
membrane associated glycoprotein
glycoprotein
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
C299S/C526S
-
mutant, relative activity: 70%
cyclooxygenase-1bdeltaG
-
mutant, in which the frame shift in the splice variant human cyclooxygenase-1b is corrected
E488G
-
site-directed mutagenesis, the mutant shows reduced sensitivity to the cyclooxygenase inhibitor nimesulide compared to the wild-type enzyme. The activity with eicosapentaenoate is altered
F59C
-
mutant, relative activity: 50%
F66C
-
mutant, relative activity: 50%
F84C
-
mutant, relative activity: 50%
G587R
-
site-directed mutagenesis, the mutant shows reduced sensitivity to the cyclooxygenase inhibitor nimesulide compared to the wild-type enzyme. The activity with eicosapentaenoate is not affected
G83C
-
mutant, relative activity: 35%
H75C
-
mutant, relative activity: 70%
I63C
-
mutant, relative activity: 70%
I77C
-
mutant, relative activity: 60%
K211A
-
complete abolition of activity
K211A/K215A
-
complete abolition of activity
K211A/K215A/K222A
-
complete abolition of activity
K211A/K222A
-
complete abolition of activity
K211E
-
complete abolition of activity
K211E/K215E
-
complete abolition of activity
K211E/K215E/K222E
-
complete abolition of activity
K211E/K222E
-
complete abolition of activity
K215A
-
does not impair PGHS activity
K215A/K222A
-
significant reduction of 27% of the activity
K215E
-
does not impair PGHS activity
K215E/K222E
-
significant reduction of 58% of the activity
K222A
-
no significant reduction of activity
K222E
-
no significant reduction of activity
K64C
-
mutant, relative activity: 70%
L60C
-
mutant, relative activity: 70%
L65C
-
mutant, relative activity: 70%
L67C
-
mutant, relative activity: 40%
L78C
-
mutant, relative activity: 30%
N382A
-
mutation has little effect on the cyclooxygenase specific activity or activation efficiency but almost doubles the cyclooxygenase catalytic output before self-inactivation
N382D
-
mutation has little effect on the cyclooxygenase specific activity or activation efficiency but almost doubles the cyclooxygenase catalytic output before self-inactivation
N382L
-
mutation has little effect on the cyclooxygenase specific activity or activation efficiency but almost doubles the cyclooxygenase catalytic output before self-inactivation
N72C
-
mutant, relative activity: 60%
N86C
-
mutant, relative activity: 50%
N89C
-
mutant, relative activity: 30%
N90C
-
mutant, relative activity: 20%
R228H
-
site-directed mutagenesis, the mutant shows reduced sensitivity to the cyclooxygenase inhibitor nimesulide compared to the wild-type enzyme. The activity with eicosapentaenoate is not affected
R62C
-
mutant, relative activity: 50%
S516M
-
mutation mimics acetylation of Ser516, mutant still sensitive to most inhibitors, not: diclofenac, meclofenamic acid
T61C
-
mutant, relative activity: 60%
T73C
-
mutant, relative activity: 40%
V511A
-
site-directed mutagenesis, the mutant shows reduced sensitivity to the cyclooxygenase inhibitor nimesulide compared to the wild-type enzyme. The activity with eicosapentaenoate altered
V74C
-
mutant, relative activity: 60%
V87C
-
mutant, relative activity: 30%
V88C
-
mutant, relative activity: 30%
W85C
-
mutant, relative activity: 10%
Y148F
-
mutant enzyme has cyclooxygenase activity comparable to that of the native enzyme
Y148F/Y348F/Y385F/Y404F/Y504F
-
no cyclooxygenase activity detected
Y148F/Y348F/Y404F/Y504F
-
mutant enzyme has specific cyclooxygenase activity approximately half that of native enzyme. Modest increase in cyclooxygenase self-inactivation rate, 2.3fold
Y348F
Y348F/Y504F
-
mutant
Y385F
-
no cyclooxygenase activity detected
Y404F
-
mutant enzyme has cyclooxygenase activity comparable to that of the native enzyme. Modest increase in cyclooxygenase self-inactivation rate, 2.3fold
Y504F
Y76C
-
mutant, relative activity: 70%
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant C-terminally or N-terminally His6-tagged PGHS-2 from Pichia pastoris strain GS115 microsomes by ultracentrifugation, nickel affinity and anion exchange chromatography, purification of the C-terminally His6 tagged hPGHS-2 is more efficient, relative efficiency of the detergents used for solubilization of the recombinant hPGHS-2, CHAPS is most effective, method evaluation, overview
recombinant protein expressed in Sf9 cells
recombinant enzyme, apoenzyme
-
recombinant protein expressed in Sf9 cells
using nickel affinity chromatography
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expressed in colon carcinoma cells COLO320DM
functional expression of C-terminally or N-terminally His6-tagged and non-tagged PGHS-2 in Pichia pastoris strain GS115, GS117 and KM71 using native or yeast signal sequences, method evaluation by enzyme activity, overview
quantitative real-time RT-PCR enzyme expression analysis
quantitative RT-PCR enzyme expression analysis
all mutants are overexpressed in the baculovirus system as detergent-soluble full-length proteins
-
expressed in colon carcinoma cells COLO320DM
expressed in COS-1 cells
-
expression of isozymes PHS-1 and PHS-2 in CHO-K1 cells
-
expression of mutant enzymes in Sf9 cells
-
for transfection of COS-7 cells
-
into a baculoviral vector for expression in Sf-21 cells
-
into the mammalian expression vector pcDNA3
-
into the pVL1393 vector
-
stable expression of PHS-1 and PHS-2 in CHO-K1 cells
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
seminal plasma induces prostaglandin-endoperoxide synthase 2 expression in immortalized human vaginal cells, involvement of semen prostaglandin E2 in PTGS2 upregulation. Expression of prostaglandin-endoperoxide synthase 2, i.e. cyclooxygenase 2, in human vaginal cells in response to toll-like receptor ligands and other proinflammatory stimuli. Seminal prostaglandin-E2 is one of the major factors in PTGS2 induction
when NCI-H292 cells are transfected with E2F1 siRNA, PTGS2 expression is attenuated
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Smith, W.L.
Prostaglandin biosynthesis and its compartmentation in vascular smooth muscle and endothelial cells
Annu. Rev. Physiol.
48
251-262
1986
Bos taurus, Homo sapiens, Sus scrofa
Manually annotated by BRENDA team
Miller, D.B.; Munster, D.; Wasvary, J.S.; Simke, J.P.; Peppard, J.V.; Bowen, B.R.; Marshall, P.J.
The heterologous expression and characterization of human prostaglandin G/H synthase-2 (COX-2)
Biochem. Biophys. Res. Commun.
201
356-362
1994
Homo sapiens
Manually annotated by BRENDA team
Kargman, S.; Wong, E.; Greig, G.M.; Falgueyret, J.P.; Cromlish, W.; Ethier, D.; Yergey, J.A.; Riendeau, D.; Evans, J.F.; Kennedy, B.; Tagari, P.; Francis, D.A.; O'Neill, G.P.
Mechanism of selective inhibition of human prostaglandin G/H synthase-1 and -2 in intact cells
Biochem. Pharmacol.
52
1113-1125
1996
Homo sapiens
Manually annotated by BRENDA team
Forghani, F.; Ouellet, M.; Keen, S.; Percival, M.D.; Tagari, P.
Analysis of prostaglandin G/H synthase-2 inhibition using peroxidase-induced luminol luminescence
Anal. Biochem.
264
216-221
1998
Homo sapiens
Manually annotated by BRENDA team
Mancini, J.A.; Vickers, P.J.; O'Neill, G.P.; Boily, C.; Falgueyret, J.P.; Riendeau, D.
Altered sensitivity of aspirin-acetylated prostaglandin G/H synthase-2 to inhibition by nonsteroidal anti-inflammatory drugs
Mol. Pharmacol.
51
52-60
1997
Homo sapiens
Manually annotated by BRENDA team
George, H.J.; Van Dyk, D.E.; Straney, R.A.; Trzaskos, J.M.; Copeland, R.A.
Expression purification and characterization of recombinant human inducible prostaglandin G/H synthase from baculovirus-infected insect cells
Protein Expr. Purif.
7
19-26
1996
Homo sapiens
Manually annotated by BRENDA team
Barnett, J.; Chow, J.; Ives, D.; Chiou, M.; Mackenzie, R.; Osen, E.; Nguyen, B.; Tsing, S.; Bach, C.; Freire, J.; et al.
Purification, characterization and selective inhibition of human prostaglandin G/H synthase 1 and 2 expressed in the baculovirus system
Biochim. Biophys. Acta
1209
130-139
1994
Homo sapiens
Manually annotated by BRENDA team
Kargman, S.; Charleson, S.; Cartwright, M.; Frank, J.; Riendeau, D.; Mancini, J.; Evans, J.; O'Neill, G.
Characterization of Prostaglandin G/H Synthase 1 and 2 in rat, dog, monkey, and human gastrointestinal tracts
Gastroenterology
111
445-454
1996
Canis lupus familiaris, Homo sapiens, Macaca mulatta, Rattus norvegicus, Saimiri sciureus
Manually annotated by BRENDA team
Patrignani, P.; Panara, M.R.; Sciulli, M.G.; Santini, G.; Renda, G.; Patrono, C.
Differential inhibition of human prostaglandin endoperoxide synthase-1 and -2 by nonsteroidal anti-inflammatory drugs
J. Physiol. Pharmacol.
48
623-631
1997
Homo sapiens
Manually annotated by BRENDA team
O'Neill, G.P.; Mancini, J.A.; Kargman, S.; Yergey, J.; Kwan, M.Y.; Falgueyret, J.P.; Abramovitz, M.; Kennedy, B.P.; Ouellet, M.; Cromlish, W.
Overexpression of human prostaglandin G/H synthase-1 and -2 by recombinant vaccinia virus: inhibition by nonsteroidal anti-inflammatory drugs and biosynthesis of 15-hydroxyeicosatetraenoic acid
Mol. Pharmacol.
45
245-254
1994
Homo sapiens
Manually annotated by BRENDA team
Rogge, C.E.; Liu, W.; Wu, G.; Wang, L.H.; Kulmacz, R.J.; Tsai, A.L.
Identification of Tyr504 as an alternative tyrosyl radical site in human prostaglandin H synthase-2
Biochemistry
43
1560-1568
2004
Homo sapiens
Manually annotated by BRENDA team
Bambai, B.; Rogge, C.E.; Stec, B.; Kulmacz, R.J.
Role of Asn-382 and Thr-383 in activation and inactivation of human prostaglandin H synthase cyclooxygenase catalysis
J. Biol. Chem.
279
4084-4092
2004
Homo sapiens
Manually annotated by BRENDA team
Rogge, C.E.; Ho, B.; Liu, W.; Kulmacz, R.J.; Tsai, A.L.
Role of Tyr348 in Tyr385 radical dynamics and cyclooxygenase inhibitor interactions in prostaglandin H synthase-2
Biochemistry
45
523-532
2006
Homo sapiens
Manually annotated by BRENDA team
Chubb, A.J.; Fitzgerald, D.J.; Nolan, K.B.; Moman, E.
The productive conformation of prostaglandin G2 at the peroxidase site of prostaglandin endoperoxide H synthase: docking, molecular dynamics, and site-directed mutagenesis studies
Biochemistry
45
811-820
2006
Homo sapiens
Manually annotated by BRENDA team
Zhang, D.; Wood, C.E.
Neuronal prostaglandin endoperoxide synthase 2 responses to oxygen and glucose deprivation are mediated by mitogen-activated protein kinase ERK1/2
Brain Res.
1060
100-107
2005
Homo sapiens (P35354)
Manually annotated by BRENDA team
Censarek, P.; Freidel, K.; Hohlfeld, T.; Schroer, K.; Weber, A.A.
Human cyclooxygenase-1b is not the elusive target of acetaminophen
Eur. J. Pharmacol.
551
50-53
2006
Homo sapiens
Manually annotated by BRENDA team
Liu, W.; Cao, D.; Oh, S.F.; Serhan, C.N.; Kulmacz, R.J.
Divergent cyclooxygenase responses to fatty acid structure and peroxide level in fish and mammalian prostaglandin H synthases
FASEB J.
20
1097-1108
2006
Ovis aries, Homo sapiens (P23219), Homo sapiens (P35354), Salvelinus fontinalis (Q9PTN3), Salvelinus fontinalis (Q9PW89), Salvelinus fontinalis
Manually annotated by BRENDA team
MirAfzali, Z.; Leipprandt, J.R.; McCracken, J.L.; DeWitt, D.L.
Topography of the prostaglandin endoperoxide H2 synthase-2 in membranes
J. Biol. Chem.
281
28354-28364
2006
Homo sapiens
Manually annotated by BRENDA team
Tsai, A.L.; Kulmacz, R.J.
Prostaglandin H synthase: Resolved and unresolved mechanistic issues
Arch. Biochem. Biophys.
493
103-124
2010
Ovis aries (P05979), Homo sapiens (P23219), Homo sapiens (P35354)
Manually annotated by BRENDA team
Kawakami, Y.; Nakamura, T.; Hosokawa, T.; Suzuki-Yamamoto, T.; Yamashita, H.; Kimoto, M.; Tsuji, H.; Yoshida, H.; Hada, T.; Takahashi, Y.
Antiproliferative activity of guava leaf extract via inhibition of prostaglandin endoperoxide H synthase isoforms
Prostaglandins Leukot. Essent. Fatty Acids
80
239-245
2009
Ovis aries (P05979), Ovis aries (P79208), Homo sapiens (P23219), Homo sapiens (P35354), Homo sapiens
Manually annotated by BRENDA team
Ramkissoon, A.; Wells, P.G.
Human prostaglandin H synthase (hPHS)-1- and hPHS-2-dependent bioactivation, oxidative macromolecular damage, and cytotoxicity of dopamine, its precursor, and its metabolites
Free Radic. Biol. Med.
50
295-304
2011
Homo sapiens
Manually annotated by BRENDA team
Liu, W.; Poole, E.M.; Ulrich, C.M.; Kulmacz, R.J.
Polymorphic human prostaglandin H synthase-2 proteins and their interactions with cyclooxygenase substrates and inhibitors
Pharmacogenomics J.
11
337-347
2010
Homo sapiens
Manually annotated by BRENDA team
Ramkissoon, A.; Wells, P.G.
Human prostaglandin H synthase (hPHS)-1 and hPHS-2 in amphetamine analog bioactivation, DNA oxidation, and cytotoxicity
Toxicol. Sci.
120
154-162
2011
Homo sapiens
Manually annotated by BRENDA team
Joseph, T.; Zalenskaya, I.A.; Sawyer, L.C.; Chandra, N.; Doncel, G.F.
Seminal plasma induces prostaglandin-endoperoxide synthase (PTGS) 2 expression in immortalized human vaginal cells: involvement of semen prostaglandin E2 in PTGS2 upregulation
Biol. Reprod.
88
13
2013
Homo sapiens (P35354), Homo sapiens
Manually annotated by BRENDA team
Tsikas, D.; Suchy, M.T.; Niemann, J.; Tossios, P.; Schneider, Y.; Rothmann, S.; Gutzki, F.M.; Froelich, J.C.; Stichtenoth, D.O.
Glutathione promotes prostaglandin H synthase (cyclooxygenase)-dependent formation of malondialdehyde and 15(S)-8-iso-prostaglandin F2?
FEBS Lett.
586
3723-3730
2012
Homo sapiens (P23219), Homo sapiens (P35354)
Manually annotated by BRENDA team
Trostchansky, A.; Bonilla, L.; Thomas, C.P.; ODonnell, V.B.; Marnett, L.J.; Radi, R.; Rubbo, H.
Nitroarachidonic acid, a novel peroxidase inhibitor of prostaglandin endoperoxide H synthases 1 and 2
J. Biol. Chem.
286
12891-12900
2011
Homo sapiens (P23219), Homo sapiens (P35354), Homo sapiens
Manually annotated by BRENDA team
Brant, K.A.; Leikauf, G.D.
Dysregulation of FURIN by prostaglandin-endoperoxide synthase 2 in lung epithelial NCI-H292 cells
Mol. Carcinog.
53
192-200
2012
Homo sapiens (P35354)
Manually annotated by BRENDA team
Kukk, K.; Jaerving, R.; Samel, N.
Purification and characterization of the recombinant human prostaglandin H synthase-2 expressed in Pichia pastoris
Protein Expr. Purif.
83
182-189
2012
Homo sapiens (P23219), Homo sapiens (P35354), Homo sapiens
Manually annotated by BRENDA team
Piranda, D.; Abreu, R.; Freitas-Alves, D.; de Carvalho, M.; Vianna-Jorge, R.
Modulation of the prostaglandin-endoperoxide synthase 2 gene expression by variant haplotypes Influence of the 3'-untranslated region
Braz. J. Med. Biol. Res.
51
e6546
2018
Homo sapiens
Manually annotated by BRENDA team
El-Nagar, M.K.S.; Abdu-Allah, H.H.M.; Salem, O.I.A.; Kafafy, A.N.; Farghaly, H.S.M.
Novel N-substituted 5-aminosalicylamides as dual inhibitors of cyclooxygenase and 5-lipoxygenase enzymes Synthesis, biological evaluation and docking study
Bioorg. Chem.
78
80-93
2018
Ovis aries, Homo sapiens
Manually annotated by BRENDA team
Park, N.Y.; Im, S.; Jiang, Q.
Different forms of vitamin E and metabolite 13-carboxychromanols inhibit cyclooxygenase-1 and its catalyzed thromboxane in platelets, and tocotrienols and 13-carboxychromanols are competitive inhibitors of 5-lipoxygenase
J. Nutr. Biochem.
100
108884
2022
Homo sapiens
Manually annotated by BRENDA team