Any feedback?
Please rate this page
(enzyme.php)
(0/150)

BRENDA support

BRENDA Home
show all | hide all No of entries

Information on EC 3.4.21.69 - Protein C (activated) and Organism(s) Homo sapiens

for references in articles please use BRENDA:EC3.4.21.69
Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
EC Tree
     3 Hydrolases
         3.4 Acting on peptide bonds (peptidases)
             3.4.21 Serine endopeptidases
                3.4.21.69 Protein C (activated)
Specify your search results
Select one or more organisms in this record: ?
This record set is specific for:
Homo sapiens
Show additional data
Do not include text mining results
Include (text mining) results
Include results (AMENDA + additional results, but less precise)
Word Map
hide
The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota
Reaction Schemes
hide
degradation of blood coagulation factors Va and VIIIa
Synonyms
activated protein c, rhapc, protein ca, anticoagulant activated protein c, autoprothrombin ii-a, anticoagulant-activated protein c, anticoagulant serine protease-activated protein c, ghrelin endopeptidase, protein c (activated), more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Activated blood coagulation factor XIV
-
-
-
-
Activated protein C
anticoagulant activated protein C
-
-
anticoagulant protein C/protein S system
-
-
anticoagulant serine protease-activated protein C
-
-
anticoagulant-activated protein C
-
Autoprothrombin II-A
-
-
-
-
Autoprothrombin IIA
-
-
-
-
Blood coagulation factor XIV
-
-
-
-
Blood-coagulation factor XIV, activated
-
-
-
-
Blood-coagulation factor XIVa
-
-
-
-
ghrelin endopeptidase
-
-
GSAPC
-
-
-
-
hAPC
-
-
Protein Ca
-
-
-
-
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
degradation of blood coagulation factors Va and VIIIa
show the reaction diagram
the catalytic triad is formed by His211, Asp257, and Ser360
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
hydrolysis of peptide bond
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY hide
42617-41-4
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
active factor Va + H2O
inactive factor V + ?
show the reaction diagram
active factor Va + H2O
inactive factor V + domain B
show the reaction diagram
active factor Va + H2O
inactive factor V heavy chain + peptide fragment 307-709
show the reaction diagram
active factor Va mutant R306Q + H2O
?
show the reaction diagram
-
proteolytic inactivation, cleavage at Arg506
-
-
?
active factor Va mutant R306Q + H2O
inactive factor V mutant R306Q + ?
show the reaction diagram
-
proteolytic inactivation, cleavage of the heavy chain at Arg506 and Arg679
-
-
?
active factor Va mutant R306Q/R679Q + H2O
inactive factor V mutant R306Q/R679Q + ?
show the reaction diagram
-
recombinant substrate expressed in COS-1 cells, proteolytic inactivation, cleavage of the heavy chain at Arg506, protected by factor Xa
-
-
?
active factor Va mutant R506Q + H2O
?
show the reaction diagram
-
proteolytic inactivation, cleavage at Arg306
-
-
?
active factor Va mutant R506Q + H2O
inactive factor V mutant R506Q + ?
show the reaction diagram
-
proteolytic inactivation, cleavage of the heavy chain at Arg306 and Arg679
-
-
?
active factor Va mutant R506Q/R679Q + H2O
inactive factor V mutant R506Q/R679Q + ?
show the reaction diagram
-
recombinant substrate expressed in COS-1 cells, proteolytic inactivation, cleavage of the heavy chain at Arg306, stimulated by factor Xa
-
-
?
active factor Va mutant R679Q + H2O
inactive factor V mutant R679Q + ?
show the reaction diagram
-
proteolytic inactivation, cleavage of the heavy chain at Arg306 and Arg506
-
-
?
active factor VIII + H2O
inactive factor VIII + domain B
show the reaction diagram
-
activated protein C and activated factor X play a role in proteolytic inactivation of activated coagulation factor VIII involving the B domain, the inactivated substrate factor VIII is less efficient on blood clotting, overview
-
-
?
active factor VIIIa + H2O
inactive factor VIII + domain B
show the reaction diagram
Benzyloxycarbonyl-Val-Gly-Arg + H2O
?
show the reaction diagram
-
-
-
-
?
bradykinin + H2O
?
show the reaction diagram
-
proteolytic inactivation
-
-
?
D-Ile-Pro-Arg + H2O
?
show the reaction diagram
-
-
-
-
?
D-Phe-Pip-Arg-4-nitroanilide + H2O
D-Phe-Pip-Arg + 4-nitroaniline
show the reaction diagram
-
S-2238
-
-
?
D-Phe-pipecolyl-Arg + H2O
?
show the reaction diagram
-
-
-
-
?
D-Pro-Phe-Arg + H2O
?
show the reaction diagram
-
-
-
-
?
D-Val-Arg-p-nitroanilide + H2O
?
show the reaction diagram
-
i.e. S-S2266
-
?
D-Val-cyclohexyl-Ala-Arg + H2O
?
show the reaction diagram
-
-
-
-
?
D-Val-Leu-Arg + H2O
?
show the reaction diagram
-
-
-
-
?
factor V + H2O
?
show the reaction diagram
Factor Va + H2O
?
show the reaction diagram
factor Va Leiden + H2O
?
show the reaction diagram
Factor VaR506Q + H2O
?
show the reaction diagram
factor VIII + H2O
?
show the reaction diagram
Factor VIIIa + H2O
?
show the reaction diagram
ghrelin + H2O
?
show the reaction diagram
-
ghrelin is converted into smaller fragments in blood plasma in circulation under thrombotic and inflammatory conditions
-
-
?
L-pGln-L-Pro-L-Arg-4-nitroanilide + H2O
L-pGln-L-Pro-L-Arg + 4-nitroaniline
show the reaction diagram
-
-
-
-
?
membrane-bound factor Va + H2O
?
show the reaction diagram
-
cleavage of Arg506 in membrane-bound factor Va
-
-
?
octanoyl-ghrelin + H2O
?
show the reaction diagram
-
-
-
-
?
octanoyl-truncated ghrelin + H2O
?
show the reaction diagram
-
preferred substrate, synthetic human substrate, octanoyl-truncated ghrelin(1-15) activates GHSR1a-dependent signaling similar to the full-length peptide
-
-
?
protease activated receptor 1 + H2O
?
show the reaction diagram
protease activated receptor 3 N-terminal peptide + H2O
?
show the reaction diagram
-
the enzyme cleaves a synthetic PAR3 N-terminal peptide at Arg41
-
-
?
protease activated receptor 3 zymogen H2O
active protease activated receptor 3 + ?
show the reaction diagram
protease-activated receptor 1 + H2O
?
show the reaction diagram
protease-activated receptor-1 + H2O
?
show the reaction diagram
-
-
-
-
?
pyroGlu-Pro-Arg-4-nitroanilide + H2O
pyroGlu-Pro-Arg + 4-nitroaniline
show the reaction diagram
S-2238 + H2O
?
show the reaction diagram
-
a chromogenic substrate
-
-
?
S-2288 + H2O
?
show the reaction diagram
-
i.e. D-Ile-L-Pro-L-Arg-p-nitroanilide
-
?
S-2366 + H2O
?
show the reaction diagram
S2238 + H2O
?
show the reaction diagram
-
a commercial chromogenic substrate
-
-
?
S2366 + H2O
?
show the reaction diagram
spectrozyme PCa + H2O
?
show the reaction diagram
-
-
?
SpPCa + H2O
?
show the reaction diagram
-
a commercial tripeptidyl chromogenic substrate
-
-
?
Tie2 + H2O
?
show the reaction diagram
Toluene-p-sulfonyl-Gly-Pro-Arg + H2O
?
show the reaction diagram
-
-
-
-
?
Toluene-p-sulfonyl-Gly-Pro-Lys + H2O
?
show the reaction diagram
-
-
-
-
?
Z-Gly-Gly-Arg-7-amido-4-methylcoumarin + H2O
?
show the reaction diagram
Z-Gly-Gly-Arg-aminomethylcoumarin + H2O
?
show the reaction diagram
-
a fluorogenic substrate, S-2366
-
-
?
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
active factor Va + H2O
inactive factor V + ?
show the reaction diagram
active factor Va + H2O
inactive factor V + domain B
show the reaction diagram
active factor Va + H2O
inactive factor V heavy chain + peptide fragment 307-709
show the reaction diagram
-
proteolytic inactivation
-
-
?
active factor VIII + H2O
inactive factor VIII + domain B
show the reaction diagram
-
activated protein C and activated factor X play a role in proteolytic inactivation of activated coagulation factor VIII involving the B domain, the inactivated substrate factor VIII is less efficient on blood clotting, overview
-
-
?
active factor VIIIa + H2O
inactive factor VIII + domain B
show the reaction diagram
factor V + H2O
?
show the reaction diagram
-
proteolytic inactivation
-
?
Factor Va + H2O
?
show the reaction diagram
factor VIII + H2O
?
show the reaction diagram
Factor VIIIa + H2O
?
show the reaction diagram
ghrelin + H2O
?
show the reaction diagram
-
ghrelin is converted into smaller fragments in blood plasma in circulation under thrombotic and inflammatory conditions
-
-
?
protease activated receptor 1 + H2O
?
show the reaction diagram
protease activated receptor 3 zymogen H2O
active protease activated receptor 3 + ?
show the reaction diagram
-
the enzyme cleaves the substrate PAR3 in transfected and endothelial cells in the presence of endothelial protein C receptor, as well as substrate mutant K38Q-PAR3, but fails to cleave the substrate mutant R41Q-PAR3
-
-
?
protease-activated receptor 1 + H2O
?
show the reaction diagram
protease-activated receptor-1 + H2O
?
show the reaction diagram
-
-
-
-
?
Tie2 + H2O
?
show the reaction diagram
activated protein C binds directly to and activates Tie2. Tie2 is a transmembrane endothelial tyrosine kinase receptor that not only regulates vessel maturation and remodeling angiogenesis, but also controls endothelial inflammation and permeability
-
-
?
additional information
?
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
chondroitin sulfate
-
anticoagulant cofactor for APC
dermatan sulfate
-
anticoagulant cofactor for APC, important physiological cofactor
heparan sulfate
-
anticoagulant cofactor for APC
protein S
-
vitamin K
additional information
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Mg2+
-
significantly increases recombinant activated protein C binding to the neutrophil surface
Zn2+
-
Zn2+ enhances the binding of protein C/activated protein C to endothelial cell protein C receptor on endothelial cells by increasing the binding affinities. Zn2+ binding induces conformational changes in protein C/APC. Zn2+ binding to APC inhibits the amidolytic activity of APC, but the inhibition is reversed by Ca2+. Zn2+ increases the rate of APC generation on endothelial cells in the presence of physiological concentrations of Ca2+, but does not further enhance increased APC generation obtained in the presence of physiological concentrations of Mg2+ with Ca2+. Zn2+ has no effect on the anticoagulant activity of APC. Zn2+ enhances APC-mediated activation of protease activated receptor 1 and p44/42 MAPK
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
4-Amino-D-Phe-Pro-Arg-CH2Cl
-
-
Ala-Phe-Arg-CH2Cl
-
-
alpha-2-Macroglobulin
-
-
-
alpha1-anti-trypsin
APC inhibition by its principal plasma inhibitor alpha1-anti-trypsin
-
alpha1-antitrypsin
-
antithrombin III
-
-
-
Aprotinin
-
-
Benzamidine hydrochloride
-
-
D-Phe-Pro-Arg-CH2Cl
-
-
D-Tyr-Pro-Arg-CH2Cl
-
-
DAN-Glu-Gly-Arg-CMK
-
dansyl-glutamyl-glycyl-arginyl-chloromethylketone, blocks the enzyme
diisopropyl fluorophosphate
-
-
factor Xa
-
stimulates factor Va cleavage at Arg306, but inhibits the cleavage at Arg506 20fold, which is counteracted by protein S, overview, factor Xa and protein S interact with distinct sites on factor Va
-
heparin
-
heparin forms a complex with enzyme and inhibits optimal docking at Arg506 of substrate factor Va, instead promoting association between factor Va and enzyme at position Arg306
I2-D-Phe-Pro-Arg-CH2Cl
-
-
Ile-Leu-Arg-CH2Cl
-
-
Ile-Pro-Arg-CH2Cl
-
-
Macromolecular inhibitor
-
conversion of glutamic acid 192 to glutamine in activated protein C increases the reactivity towards macromolecular inhibitors
-
Monoclonal antibodies to human protein C
-
positions of some monoclonal antibody-binding sites in the protein C molecule
-
Mutants of alpha1-antichymotrypsin with P1 arginine residue
-
-
-
N-(2-carboxyethyl)-3-cyclohexyl-L-alanyl-N-(4-carbamimidoylbenzyl)argininamide
-
-
N-(4-carbamimidoylbenzyl)-2-[(3-cyclohexyl-L-alanyl)amino]-4-(piperidin-4-yl)butanamide
-
-
N-(4-[2-[(4-carbamimidoylbenzyl)carbamoyl]-2,3-dihydro-1H-inden-2-yl]-2,2-dimethyl-4-oxobutyl)glycine
-
-
N-(4-[2-[(4-carbamimidoylbenzyl)carbamoyl]-2,3-dihydro-1H-inden-2-yl]-2-cyclohexyl-4-oxobutyl)glycine
-
-
N-(4-[2-[(4-carbamimidoylbenzyl)carbamoyl]-2,3-dihydro-1H-inden-2-yl]-4-oxobutyl)glycine
-
-
N-(carboxymethyl)-3-cyclohexyl-D-alanyl-4-(aminomethyl)-N-(4-carbamimidoylbenzyl)phenylalaninamide
-
-
N-(carboxymethyl)-3-cyclohexyl-D-alanyl-4-amino-N-(4-carbamimidoylbenzyl)-D-phenylalaninamide
-
-
N-(carboxymethyl)-3-cyclohexyl-D-alanyl-N-(4-carbamimidoylbenzyl)-4-cyanophenylalaninamide
-
-
N-(carboxymethyl)-3-cyclohexyl-D-alanyl-N-(4-carbamimidoylbenzyl)-D-phenylalaninamide
-
-
N-(carboxymethyl)-3-cyclohexyl-D-alanyl-N-(4-carbamimidoylbenzyl)-D-tyrosinamide
-
-
N-(carboxymethyl)-3-cyclohexyl-L-alanyl-N-(4-carbamimidoylbenzyl)-3-piperidin-4-ylalaninamide
-
-
N-(carboxymethyl)-3-cyclohexyl-L-alanyl-N-(4-carbamimidoylbenzyl)-3-pyrrolidin-2-yl-D-alaninamide
-
-
N-(carboxymethyl)-3-cyclohexyl-L-alanyl-N-(4-carbamimidoylbenzyl)-3-pyrrolidin-2-yl-L-alaninamide
-
-
N-(carboxymethyl)-3-cyclohexyl-L-alanyl-N-(4-carbamimidoylbenzyl)argininamide
-
-
N-[(1S)-2-([1-[(4-carbamimidoylbenzyl)amino]-1-oxo-4-(piperidin-4-yl)butan-2-yl]amino)-1-cyclohexyl-2-oxoethyl]glycine
-
-
N-[(1S)-2-([2-[(4-carbamimidoylbenzyl)carbamoyl]-2,3-dihydro-1H-inden-2-yl]amino)-1-cyclohexyl-2-oxoethyl]glycine
-
the compound shows a 21fold selectivity for activated protein C over thrombin
N-[(2R)-2-(2-[2-[(4-carbamimidoylbenzyl)carbamoyl]-2,3-dihydro-1H-inden-2-yl]-2-oxoethyl)-3-methylpentyl]glycine
-
-
N-[(2R)-2-(2-[2-[(4-carbamimidoylbenzyl)carbamoyl]-2,3-dihydro-1H-inden-2-yl]-2-oxoethyl)-4-methylpentyl]glycine
-
-
N-[(2R)-2-benzyl-4-[2-[(4-carbamimidoylbenzyl)carbamoyl]-2,3-dihydro-1H-inden-2-yl]-4-oxobutyl]glycine
-
-
N-[(2R)-4-[2-[(4-carbamimidoylbenzyl)carbamoyl]-2,3-dihydro-1H-inden-2-yl]-2-(cyclohexylmethyl)-4-oxobutyl]glycine
-
-
N-[(2R)-4-[2-[(4-carbamimidoylbenzyl)carbamoyl]-2,3-dihydro-1H-inden-2-yl]-2-ethyl-4-oxobutyl]glycine
-
-
N-[(2R)-4-[2-[(4-carbamimidoylbenzyl)carbamoyl]-2,3-dihydro-1H-inden-2-yl]-2-methyl-4-oxobutyl]glycine
-
-
N-[(2S)-1-([1-[(4-carbamimidoylbenzyl)amino]-1-oxo-4-(piperidin-4-yl)butan-2-yl]amino)-3-cyclohexyl-1-oxopropan-2-yl]glycine
-
the compound shows a 23fold selectivity for activated protein C over thrombin
N-[(2S)-1-[[(1S)-2-[(4-carbamimidoylbenzyl)amino]-2-oxo-1-(piperidin-4-yl)ethyl]amino]-3-cyclohexyl-1-oxopropan-2-yl]glycine
-
-
N-[(2S)-2-(2-[2-[(4-carbamimidoylbenzyl)carbamoyl]-2,3-dihydro-1H-inden-2-yl]-2-oxoethyl)-3,3-dimethylbutyl]glycine
-
-
N-[(2S)-2-([1-benzyl-2-[(4-carbamimidoylbenzyl)amino]-2-oxoethyl]carbamoyl)-3-methylbutyl]glycine
-
-
N-[(2S)-2-([2-[(4-carbamimidoylbenzyl)amino]-1-(2,3-dihydro-1H-inden-2-yl)-2-oxoethyl]carbamoyl)-3-methylbutyl]glycine
-
-
N-[(2S)-2-([2-[(4-carbamimidoylbenzyl)amino]-1-(diphenylmethyl)-2-oxoethyl]carbamoyl)-3-methylbutyl]glycine
-
-
N-[(2S)-2-([2-[(4-carbamimidoylbenzyl)carbamoyl]-2,3-dihydro-1H-cyclopenta[a]naphthalen-2-yl]carbamoyl)-3-methylbutyl]glycine
-
-
N-[(2S)-2-([2-[(4-carbamimidoylbenzyl)carbamoyl]-2,3-dihydro-1H-cyclopenta[b]naphthalen-2-yl]carbamoyl)-3-methylbutyl]glycine
-
-
N-[(2S)-2-([2-[(4-carbamimidoylbenzyl)carbamoyl]-2,3-dihydro-1H-phenalen-2-yl]carbamoyl)-3-methylbutyl]glycine
-
-
N-[(2S)-2-([2-[(4-carbamimidoylbenzyl)carbamoyl]-5,6-dimethoxy-2,3-dihydro-1H-inden-2-yl]carbamoyl)-3-methylbutyl]glycine
-
-
N-[(2S)-2-([6-[(4-carbamimidoylbenzyl)carbamoyl]-6,7-dihydro-5H-cyclopenta[b]pyridin-6-yl]carbamoyl)-3-methylbutyl]glycine
-
-
N-[(2S)-2-([6-[(4-carbamimidoylbenzyl)carbamoyl]-6,7-dihydro-5H-cyclopenta[c]pyridin-6-yl]carbamoyl)-3-methylbutyl]glycine
-
-
N-[(2S)-2-([6-[(4-carbamimidoylbenzyl)carbamoyl]-6,7-dihydro-5H-dibenzo[a,c][7]annulen-6-yl]carbamoyl)-3-methylbutyl]glycine
-
-
N-[(2S)-4-[2-[(4-carbamimidoylbenzyl)carbamoyl]-2,3-dihydro-1H-inden-2-yl]-2-(1-methylethyl)-4-oxobutyl]glycine
-
-
N-[(2S)-4-[2-[(4-carbamimidoylbenzyl)carbamoyl]-2,3-dihydro-1H-inden-2-yl]-2-cyclohexyl-4-oxobutyl]glycine
-
-
N-[[1-(2-[2-[(4-carbamimidoylbenzyl)carbamoyl]-2,3-dihydro-1H-inden-2-yl]-2-oxoethyl)cyclopentyl]methyl]glycine
-
-
N2-[(2S)-2-amino-2-cyclohexylacetyl]-N-(4-carbamimidoylbenzyl)argininamide
-
-
peptide VP311-325
-
a peptide comprising residues 311-325 in factor Va, potent inhibition of factor Va-dependent prothrombin activation by factor Xa in the absence of APC, the peptide also inhibits the inactivation of factor Va by APC by APC-dependent cleavage of both Arg506 and Arg306, thus inhibits cleavage of wild-type factor Va and of the mutant R306Q and R506Q, overview
-
Phe-Ala-Arg-CH2Cl
-
-
Phe-Phe-Arg-CH2Cl
-
-
Phe-Pro-Arg-chloromethylketone
phenylmethylsulfonyl fluoride
-
-
Platelet plasminogen activator inhibitor
-
reacts with the enzyme to yield both, an SDS-stable complex and a modified inhibitor
-
Protease nexin I
-
-
-
Protein C inhibitor
-
protein C inhibitor PCI
-
inhibition stimulated by heparin
-
protein S
-
the cofactor is active as free protein and in complex with C4b binding protein, the latter shows a less potent effect, activation up to 10fold, but the complex inhibits proteolysis at Arg506 by 3-4fold, overview
-
prothrombin
-
Tyr-Phe-Arg-CH2Cl
-
-
Val-Val-Arg-CH2Cl
-
-
Zn2+
-
Zn2+ enhances the binding of protein C/activated protein C to endothelial cell protein C receptor on endothelial cells by increasing the binding affinities. Zn2+ binding induces conformational changes in protein C/APC. Zn2+ binding to APC inhibits the amidolytic activity of APC, but the inhibition is reversed by Ca2+. Zn2+ increases the rate of APC generation on endothelial cells in the presence of physiological concentrations of Ca2+, but does not further enhance increased APC generation obtained in the presence of physiological concentrations of Mg2+ with Ca2+. Zn2+ has no effect on the anticoagulant activity of APC. Zn2+-mediated inhibition of APC amidolytic activity rather than the direct inhibition of protein C activation
[[(2R)-1-[[(2R)-1-[(4-carbamimidoylbenzyl)amino]-3-(naphthalen-1-yl)-1-oxopropan-2-yl]amino]-3-cyclohexyl-1-oxopropan-2-yl]amino]acetic acid
-
non-preferred name
[[(2R)-1-[[(2R)-1-[(4-carbamimidoylbenzyl)amino]-3-(naphthalen-2-yl)-1-oxopropan-2-yl]amino]-3-cyclohexyl-1-oxopropan-2-yl]amino]acetic acid
-
non-preferred name
additional information
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
certoparin
-
clinical LMWH enhances activity
-
cholesterol
-
in phosphatidylcholine/phosphatidylserine vesicles, cholesterol enhances Factor Va inactivation and the rate of cleavage by enzyme both at R506 and R306
dalteparin
-
clinical LMWH enhances activity
-
dermatan sulfate
endothelial cell protein C receptor
activation of protein C is potentiated by the presence of the endothelial cell protein C receptor (EPCR), which binds protein C with high affinity and increases the rate of protein C activation by about 20fold in vivo
-
enoxaparin
-
clinical LMWH enhances activity
factor Xa
-
stimulates factor Va cleavage at Arg306, but inhibits the cleavage at Arg506 20fold, overview, factor Xa and protein S interact with distinct sites on factor Va
-
glycosaminoglycan
-
enhances activity with factor V but not with factor Va as substrate
LMW heparin
-
enhances the anticoagulant action of activated protein C
-
nadroparin
-
clinical LMWH enhances activity
-
phosphatidylcholine
-
as phospholipid vesicles with 80% phosphatidylcholine and 20% phosphatidylserine, specific binding to the enzyme of anionic phospholipid vesicles passed over the protein C surface, defective phospholipid binding of mutant variants also resulted in severely impaired anticoagulant activity in protein C-deficient plasma
phosphatidylserine
-
as phospholipid vesicles with 80% phosphatidylcholine and 20% phosphatidylserine, specific binding to the enzyme of anionic phospholipid vesicles passed over the protein C surface, defective phospholipid binding of mutant variants also resulted in severely impaired anticoagulant activity in protein C-deficient plasma
Phospholipid
Phospholipids
-
-
polysulfated dermatan sulfate
-
more active than dermatan sulfate-derived oligosaccharide on basis of comparable molecular weight. Most active polysulfated dermatan sulfate has a molecular weight of 2749 and increases enzyme activity by about 230%
-
ProTac
-
a protein C-activating agent
-
protein S
-
tinzaparin
-
clinical LMWH enhances activity
-
vitamin K
additional information
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.528
Benzyloxycarbonyl-Val-Gly-Arg
-
-
0.606
D-Ile-Pro-Arg
-
-
0.373
D-Phe-pipecolyl-Arg
-
-
0.505
D-Pro-Phe-Arg
-
-
0.259
D-Val-cyclohexyl-Ala-Arg
-
-
0.345
D-Val-Leu-Arg
-
-
0.0000197
Factor Va
-
pH 7.4, 22°C
-
0.000196
Factor VaR506Q
-
-
-
0.0001 - 0.000102
Factor VIIIa
-
0.00002
membrane-bound factor Va
-
-
-
0.39 - 1.723
S-2288
0.0009 - 0.00098
S-2366
0.131 - 0.177
spectrozyme PCa
0.234 - 0.258
SpPCa
-
0.762
Toluene-p-sulfonyl-Gly-Pro-Arg
-
-
0.116
Toluene-p-sulfonyl-Gly-Pro-Lys
-
-
additional information
additional information
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.38
Benzyloxycarbonyl-Val-Gly-Arg
-
-
200
D-Ile-Pro-Arg
-
-
53
D-Phe-pipecolyl-Arg
-
-
31
D-Pro-Phe-Arg
-
-
1.9
D-Val-cyclohexyl-Ala-Arg
-
-
35
D-Val-Leu-Arg
-
-
0.395
Factor Va
-
pH 7.4, 22°C
-
0.37
Factor VaR506Q
-
-
-
0.96
membrane-bound factor Va
-
-
-
70 - 78
S-2366
44 - 48
spectrozyme PCa
33.1 - 35
SpPCa
-
87
Toluene-p-sulfonyl-Gly-Pro-Arg
-
-
0.81
Toluene-p-sulfonyl-Gly-Pro-Lys
-
-
additional information
additional information
-
-
-
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
20000
Factor Va
-
pH 7.4, 22°C
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0028
N-(2-carboxyethyl)-3-cyclohexyl-L-alanyl-N-(4-carbamimidoylbenzyl)argininamide
Homo sapiens
-
pH 7.4, 37°C
0.0031
N-(4-carbamimidoylbenzyl)-2-[(3-cyclohexyl-L-alanyl)amino]-4-(piperidin-4-yl)butanamide
Homo sapiens
-
pH 7.4, 37°C
0.044
N-(4-[2-[(4-carbamimidoylbenzyl)carbamoyl]-2,3-dihydro-1H-inden-2-yl]-2,2-dimethyl-4-oxobutyl)glycine
Homo sapiens
-
-
0.033
N-(4-[2-[(4-carbamimidoylbenzyl)carbamoyl]-2,3-dihydro-1H-inden-2-yl]-2-cyclohexyl-4-oxobutyl)glycine
Homo sapiens
-
above
0.033
N-(4-[2-[(4-carbamimidoylbenzyl)carbamoyl]-2,3-dihydro-1H-inden-2-yl]-4-oxobutyl)glycine
Homo sapiens
-
above
0.0011
N-(carboxymethyl)-3-cyclohexyl-D-alanyl-4-(aminomethyl)-N-(4-carbamimidoylbenzyl)phenylalaninamide
Homo sapiens
-
pH 7.4, 37°C
0.00013
N-(carboxymethyl)-3-cyclohexyl-D-alanyl-4-amino-N-(4-carbamimidoylbenzyl)-D-phenylalaninamide
Homo sapiens
-
pH 7.4, 37°C
0.0038
N-(carboxymethyl)-3-cyclohexyl-D-alanyl-N-(4-carbamimidoylbenzyl)-4-cyanophenylalaninamide
Homo sapiens
-
pH 7.4, 37°C
0.00067
N-(carboxymethyl)-3-cyclohexyl-D-alanyl-N-(4-carbamimidoylbenzyl)-D-phenylalaninamide
Homo sapiens
-
pH 7.4, 37°C
0.00026
N-(carboxymethyl)-3-cyclohexyl-D-alanyl-N-(4-carbamimidoylbenzyl)-D-tyrosinamide
Homo sapiens
-
pH 7.4, 37°C
0.0013
N-(carboxymethyl)-3-cyclohexyl-L-alanyl-N-(4-carbamimidoylbenzyl)-3-piperidin-4-ylalaninamide
Homo sapiens
-
pH 7.4, 37°C
0.044
N-(carboxymethyl)-3-cyclohexyl-L-alanyl-N-(4-carbamimidoylbenzyl)-3-pyrrolidin-2-yl-D-alaninamide
Homo sapiens
-
above, pH 7.4, 37°C
0.0056
N-(carboxymethyl)-3-cyclohexyl-L-alanyl-N-(4-carbamimidoylbenzyl)-3-pyrrolidin-2-yl-L-alaninamide
Homo sapiens
-
pH 7.4, 37°C
0.00047
N-(carboxymethyl)-3-cyclohexyl-L-alanyl-N-(4-carbamimidoylbenzyl)argininamide
Homo sapiens
-
pH 7.4, 37°C
0.044
N-[(1S)-2-([1-[(4-carbamimidoylbenzyl)amino]-1-oxo-4-(piperidin-4-yl)butan-2-yl]amino)-1-cyclohexyl-2-oxoethyl]glycine
Homo sapiens
-
above, pH 7.4, 37°C
0.0017
N-[(1S)-2-([2-[(4-carbamimidoylbenzyl)carbamoyl]-2,3-dihydro-1H-inden-2-yl]amino)-1-cyclohexyl-2-oxoethyl]glycine
Homo sapiens
-
pH 7.4, 37°C
0.00112
N-[(2R)-2-(2-[2-[(4-carbamimidoylbenzyl)carbamoyl]-2,3-dihydro-1H-inden-2-yl]-2-oxoethyl)-3-methylpentyl]glycine
Homo sapiens
-
-
0.00075
N-[(2R)-2-(2-[2-[(4-carbamimidoylbenzyl)carbamoyl]-2,3-dihydro-1H-inden-2-yl]-2-oxoethyl)-4-methylpentyl]glycine
Homo sapiens
-
-
0.01125
N-[(2R)-2-benzyl-4-[2-[(4-carbamimidoylbenzyl)carbamoyl]-2,3-dihydro-1H-inden-2-yl]-4-oxobutyl]glycine
Homo sapiens
-
-
0.0001
N-[(2R)-4-[2-[(4-carbamimidoylbenzyl)carbamoyl]-2,3-dihydro-1H-inden-2-yl]-2-(cyclohexylmethyl)-4-oxobutyl]glycine
Homo sapiens
-
-
0.00204
N-[(2R)-4-[2-[(4-carbamimidoylbenzyl)carbamoyl]-2,3-dihydro-1H-inden-2-yl]-2-ethyl-4-oxobutyl]glycine
Homo sapiens
-
-
0.00908
N-[(2R)-4-[2-[(4-carbamimidoylbenzyl)carbamoyl]-2,3-dihydro-1H-inden-2-yl]-2-methyl-4-oxobutyl]glycine
Homo sapiens
-
-
0.0092
N-[(2S)-1-([1-[(4-carbamimidoylbenzyl)amino]-1-oxo-4-(piperidin-4-yl)butan-2-yl]amino)-3-cyclohexyl-1-oxopropan-2-yl]glycine
Homo sapiens
-
pH 7.4, 37°C
0.0031
N-[(2S)-1-[[(1S)-2-[(4-carbamimidoylbenzyl)amino]-2-oxo-1-(piperidin-4-yl)ethyl]amino]-3-cyclohexyl-1-oxopropan-2-yl]glycine
Homo sapiens
-
pH 7.4, 37°C
0.00383
N-[(2S)-2-(2-[2-[(4-carbamimidoylbenzyl)carbamoyl]-2,3-dihydro-1H-inden-2-yl]-2-oxoethyl)-3,3-dimethylbutyl]glycine
Homo sapiens
-
-
0.00071
N-[(2S)-2-([1-benzyl-2-[(4-carbamimidoylbenzyl)amino]-2-oxoethyl]carbamoyl)-3-methylbutyl]glycine
Homo sapiens
-
-
0.00035
N-[(2S)-2-([2-[(4-carbamimidoylbenzyl)amino]-1-(2,3-dihydro-1H-inden-2-yl)-2-oxoethyl]carbamoyl)-3-methylbutyl]glycine
Homo sapiens
-
-
0.033
N-[(2S)-2-([2-[(4-carbamimidoylbenzyl)amino]-1-(diphenylmethyl)-2-oxoethyl]carbamoyl)-3-methylbutyl]glycine
Homo sapiens
-
above
0.00025
N-[(2S)-2-([2-[(4-carbamimidoylbenzyl)carbamoyl]-2,3-dihydro-1H-cyclopenta[a]naphthalen-2-yl]carbamoyl)-3-methylbutyl]glycine
Homo sapiens
-
-
0.00928
N-[(2S)-2-([2-[(4-carbamimidoylbenzyl)carbamoyl]-2,3-dihydro-1H-cyclopenta[b]naphthalen-2-yl]carbamoyl)-3-methylbutyl]glycine
Homo sapiens
-
-
0.00043
N-[(2S)-2-([2-[(4-carbamimidoylbenzyl)carbamoyl]-2,3-dihydro-1H-phenalen-2-yl]carbamoyl)-3-methylbutyl]glycine
Homo sapiens
-
-
0.01091
N-[(2S)-2-([2-[(4-carbamimidoylbenzyl)carbamoyl]-5,6-dimethoxy-2,3-dihydro-1H-inden-2-yl]carbamoyl)-3-methylbutyl]glycine
Homo sapiens
-
-
0.0011
N-[(2S)-2-([6-[(4-carbamimidoylbenzyl)carbamoyl]-6,7-dihydro-5H-cyclopenta[b]pyridin-6-yl]carbamoyl)-3-methylbutyl]glycine
Homo sapiens
-
-
0.0017
N-[(2S)-2-([6-[(4-carbamimidoylbenzyl)carbamoyl]-6,7-dihydro-5H-cyclopenta[c]pyridin-6-yl]carbamoyl)-3-methylbutyl]glycine
Homo sapiens
-
-
0.01265
N-[(2S)-2-([6-[(4-carbamimidoylbenzyl)carbamoyl]-6,7-dihydro-5H-dibenzo[a,c][7]annulen-6-yl]carbamoyl)-3-methylbutyl]glycine
Homo sapiens
-
-
0.0008
N-[(2S)-4-[2-[(4-carbamimidoylbenzyl)carbamoyl]-2,3-dihydro-1H-inden-2-yl]-2-(1-methylethyl)-4-oxobutyl]glycine
Homo sapiens
-
-
0.00082
N-[(2S)-4-[2-[(4-carbamimidoylbenzyl)carbamoyl]-2,3-dihydro-1H-inden-2-yl]-2-cyclohexyl-4-oxobutyl]glycine
Homo sapiens
-
-
0.053
N-[[1-(2-[2-[(4-carbamimidoylbenzyl)carbamoyl]-2,3-dihydro-1H-inden-2-yl]-2-oxoethyl)cyclopentyl]methyl]glycine
Homo sapiens
-
-
0.0016
N2-[(2S)-2-amino-2-cyclohexylacetyl]-N-(4-carbamimidoylbenzyl)argininamide
Homo sapiens
-
pH 7.4, 37°C
0.0011
[[(2R)-1-[[(2R)-1-[(4-carbamimidoylbenzyl)amino]-3-(naphthalen-1-yl)-1-oxopropan-2-yl]amino]-3-cyclohexyl-1-oxopropan-2-yl]amino]acetic acid
Homo sapiens
-
pH 7.4, 37°C
0.00098
[[(2R)-1-[[(2R)-1-[(4-carbamimidoylbenzyl)amino]-3-(naphthalen-2-yl)-1-oxopropan-2-yl]amino]-3-cyclohexyl-1-oxopropan-2-yl]amino]acetic acid
Homo sapiens
-
pH 7.4, 37°C
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.2
-
assay at
7.5
-
assay at
7.7
-
assay at
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
25
-
anticoagulation assay at
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
rheumatoid synovial fibroblasts
Manually annotated by BRENDA team
-
enzyme synthesis
Manually annotated by BRENDA team
-
breast cancer cells
Manually annotated by BRENDA team
-
an immortalized human monocytic cell line
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
metabolism
physiological function
additional information
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
PROC_HUMAN
461
0
52071
Swiss-Prot
Secretory Pathway (Reliability: 2)
I7BL31_HUMAN
46
0
4198
TrEMBL
Mitochondrion (Reliability: 2)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
55000
-
x * 55000, recombinant activated enzyme
56000
-
x * 56000, SDS-PAGE
62000
-
x * 62000
additional information
-
structure-function assessment of the role of the helical stack domain in the properties of human recombinant activated protein C
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
glycoprotein
proteolytic modification
side-chain modification
-
beta-hydroxylation of Asp71, and carboxylation of nine glutamic acid residues in the N-terminus
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
D167F/D172G
-
at saturating Ca2+ concentrations, the activation rates of the mutant and wild-type protein C by the thrombin-TM complex are comparable, but the mutant requires four-fold higher Ca2+ concentrations than wild-type APC to achieve half-maximal activation rates. When only thrombin is present, Ca2+ is not able to influence the activation of the D167F/D172G mutant, though Ca2+ effectively inhibits activation of wild-type protein C by thrombin
D222E
-
mutation of the Arg-Gly-Asp sequence abolishes both integrin binding and inhibition of neutrophil migration
D35T/D36A
-
site-directed mutagenesis, the mutant shows slightly increased factor Va proteolysis compared to the wild-type enzyme, the activation by protein S is reduced
D36A/L38D/A39V
E149A
-
the cytoprotective effects of the APC mutant are severely diminished, despite a normal cleavage of PAR-1 and normal binding to EPCR. E149A-APC expresses only 6% of the anti-apoptotic activity of wild-type APC in a staurosporine-induced apoptosis model in endothelial cells and was unable to down-regulate IL-6 release in lipopolysaccharide treated U937 monocytes
E167A
-
site-directed mutagenesis, the surface loop residue mutation eliminates the cytoprotective signaling properties of APC without affecting its anticoagulant activity, inability of E167A to exhibit significant protective activity in response to TNF-alpha-induced inflammatory events in endothelial cells
E16D
-
site-directed mutagenesis, the mutation causes aberrant Ca2+ binding and Gla domain misfolding
E170A
-
site-directed mutagenesis, the surface loop residue mutation eliminates the cytoprotective signaling properties of APC without affecting its anticoagulant activity, inability of E170A to exhibit significant protective activity in response to TNF-alpha-induced inflammatory events in endothelial cells
E20A/V34M
-
the mutation is associated with thrombotic complications, despite the fact that carriers of these mutations have normal protein C antigen levels and APC amidolytic activity
E357Q
-
E357 is involved in binding of macromolecular substrates. Engineered E357Q-APC shows two to threefold improved FVa inactivation, but slightly reduced anticoagulant activity in plasma compared to wild-type APC
E7D
-
the mutation is associated with thrombotic complications, despite the fact that carriers of these mutations have normal protein C antigen levels and APC amidolytic activity
E80K
-
GDPC derivative
G216D
-
a naturally occuring mutation, the mutant shows impaired protease activity, while preserving the overall protein fold. Superposition of the integrin binding motifs in wild-type and mutant forms suggests that the interaction with integrin can still occur and thus the mutant is likely to retain its antiseptic function related to the neutrophyl integrin binding
H10Q/S11G/S12N/D23S/Q32E/N33D/H44Y
-
naturally occuring Gla-domain mutant, the mutant enzyme shows a higher anticoagulant effect compared to the wild-type enzyme, the combination with the B148 mutation in the serine protease domain even enhances the effect, overview
K174E
-
site-directed mutagenesis, the activation rate of the mutant by thrombin is 12fold faster than that observed for wild-type protein C in the presence of Ca2+, and unchanged in the absence of Ca2+. Thrombin does not stimulate activation of the protein C variant
K191A
-
Km- and kcat-value similar to wild-type, minor contribution to interaction with thrombin-thrombomodulin
K191A/K192A/K193A
K192A
-
Km- and kcat-value similar to wild-type, major contribution to interaction with thrombin-thrombomodulin
K217A
-
Km- and kcat-value similar to wild-type, minor contribution to interaction with thrombin-thrombomodulin
K218A
-
Km- and kcat-value similar to wild-type, minor contribution to interaction with thrombin-thrombomodulin
K37S/K38Q/K39Q
-
created by site-directed in vitro mutagenesis
K37S/K38Q/K39Q/K62N/K63D
-
created by site-directed in vitro mutagenesis
K78A
prepared by PCR methods
L38D
site-directed mutagenesis, creation of an APC variant with individual amino acid substitutions within this region, L38D is the main source of lost anti-coagulant activity. Despite this, APC-L38D retains the ability to mediate PAR1-dependent signalling properties on endothelial cells
L8Q
-
mutant variants L8Q and R9H show reduced affinity for EPCR and can contribute to the reduced anticoagulant activity
N329Q
N33S/V34S/D35T/D36A/L38D/A39V
-
site-directed mutagenesis, the mutant shows slightly increased factor Va proteolysis compared to the wild-type enzyme, no activation by protein S
P168V
-
at saturating Ca2+ concentrations, the activation rates of the mutant and wild-type protein C by the thrombin-TM complex are comparable, but the mutant requires four-fold higher Ca2+ concentrations than wild-type APC to achieve half-maximal activation rates. When only thrombin is present, Ca2+ is not able to influence the activation of the P168V mutant, though Ca2+ effectively inhibits activation of wild-type protein C by thrombin
R15G
-
the mutation leads to increased thrombotic tendency
R15W
-
the mutation leads to increased thrombotic tendency
R177E
-
site-directed mutagenesis, the activation rate of the mutant by thrombin is 12fold faster than that observed for wild-type protein C in the presence of Ca2+, and unchanged in the absence of Ca2+. Thrombin does not stimulate activation of the protein C variant
R178E
-
site-directed mutagenesis, the activation rate of the mutant by thrombin is 12fold faster than that observed for wild-type protein C in the presence of Ca2+, and unchanged in the absence of Ca2+. Thrombin does not stimulate activation of the protein C variant
R222C/D237C
site-directed mutagenesis, manipulation of the APC serine protease domain via the introduction of a new disulfide bridge is found to disproportionately inhibit APC anti-coagulant activity compared with EPCR-PAR1 signalling function
R229A
-
Km- and kcat-value similar to wild-type, major contribution to interaction with thrombin-thrombomodulin
R229A/R230A
site-directed mutagenesis
R229A/R230A/K191A/K192A/K193A
-
site-directed mutagenesis, construction of an APC protease domain mutant, 5A-APC, the mutant has minimal anticoagulant activity but normal cytoprotective activities that are dependent on endothelial protein C receptor and protease-activated receptor-1 as compared to the wild-tpe enzyme, activation of thrombin activable fibrinolysis inhibitor is essentially unaffected by 5A-APC due to its low anticoagulant activity, a 1000fold higher concentration of 5A-APC is required to give a factor Va inactivation pattern similar to that of recombinant wild-type APC
R230A
-
Km- and kcat-value similar to wild-type, major contribution to interaction with thrombin-thrombomodulin
R312A
-
Km- and kcat-value similar to wild-type, minor contribution to interaction with thrombin-thrombomodulin
R67C/R82C
-
site-directed mutagenesis, construction of a protein C variant in which an engineered disulfide bond between two beta-sheets stabilizes the functionally critical Ca2+-binding 70-80 loop of the molecule. The 70-80 loop of this mutant no longer binds Ca2+, and the activation of the mutant by thrombin is enhanced 60-80fold independently of thrombomodulin, the anticoagulant activity of the activated protein C mutant is nearly eliminated. The endothelial protein C receptor- and protease activated receptor-1-dependent protective signaling properties of the mutant are minimally altered compared to the wild-type enzyme. The mutant loses its ability to interact with the procoagulant cofactors but not with the protective signaling molecules. The binding of EPCR is 2fold reduced compared to the wild-type enzyme
R74A
prepared by PCR methods
R74E/R75E/K78E
triple mutant, Gla-domainless form of APC
R74Q
-
created by site-directed in vitro mutagenesis
R75A
prepared by PCR methods
R9H
-
mutant variants L8Q and R9H show reduced affinity for EPCR and can contribute to the reduced anticoagulant activity
S11G/S12N
-
site-directed mutagenesis, the mutant shows slightly increased factor Va proteolysis compared to the wild-type enzyme
S190A
-
Km- and kcat-value similar to wild-type, minor contribution to interaction with thrombin-thrombomodulin
S195A
-
site-directed mutagenesis, inactive mutant
S360A
S360C
-
site-directed mutagenesis, the active site residue mutant shows no amidolytic activity
W231A
-
Km- and kcat-value similar to wild-type, minor contribution to interaction with thrombin-thrombomodulin
additional information
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
mutant
-
recombinant enzyme
recombinant wild-type and mutant enzymes from HEK-293 cell culture medium by anion exchange chromatography
-
use of the insolubilized inhibitor aprotinin for purification
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
APCTPTGla chimera, much more potent anticoagulant than wild-type APC in plasma
-
expression of Gla domainless Protein C GDPC andGDPC E80K by the RSV-PL4 expression/purification vector system in human 293 cells
-
expression of the mutant zymogen protein C(S360A) in HEK-293 cells
-
expression of wild-type an dmutant enzymes in HEK-293 cells
-
expression of wild-type and mutant enzymes in HEK-293 cells
-
expression of wild-type and mutant enzymes in HEK-293 cells, secretion to the medium
-
gene PROC, location on chromosome 1p13-14
-
gene PROC, location on on chromosome 2 (2q13–q14)
-
mutant cloned into pcDNA 3.1(+)/Hygro vector and expressed in HEK-293 cells
-
protein C mutants prepared by PCR methods expressed in HEK293 cells
recombinant coexpression of hEPCR and PAR1 linked to an N-terminal alkaline phosphatase (AP) cleavage reporter and treatment with recombinant APC-b (APCN329Q) or N-glycosidase PNGase F-treated APC (APCPNG), in which all N-linked glycans are excised, in HEK 293-T cells, detection of PAR1 proteolysis on HEK 293T cells
recombinant expression of the enzyme, co-expression with SEAP from a SEAP-protease activated receptor 3 fusion protein in HEK-293 cells with or without stable endothelial protein C receptor coexpression
-
stable, functional expression of wild-type and mutant enzymes in HEK-293 cells
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
presence of the APC cofactor, protein S, thrombomodulin, endothelial protein C receptor and a phospholipid surface are important for the expression of anticoagulant APC activity
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
diagnostics
endogenous protein C levels positively correlate with a positive outcome in patients with severe sepsis
drug development
-
at therapeutically relevant concentrations, activated protein C suppresses the release of interleukin-6 from stimulated human neutrophils and inhibited chemotaxis, without affecting the respiratory burst, apoptosis, and expression of other key cytokines. These effects are likely to be cell-type specific but may have implications for treatment of patients with activated protein C
medicine
pharmacology
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Esmon, C.T.
The roles of protein C and thrombomodulin in the regulation of blood coagulation
J. Biol. Chem.
264
4743-4746
1989
Bos taurus, Homo sapiens
Manually annotated by BRENDA team
Esmon, C.T.
The regulation of natural anticoagulant pathways
Science
235
1348-1352
1987
Homo sapiens
Manually annotated by BRENDA team
Kisiel, W.; Davie, E.W.
Protein C
Methods Enzymol.
80
320-332
1981
Bos taurus, Homo sapiens
-
Manually annotated by BRENDA team
Stone, S.R.; Hofsteenge, J.
Specificity of activated human protein C
Biochem. J.
230
497-502
1985
Homo sapiens
Manually annotated by BRENDA team
Nicolaes, G.A.F.; Tans, G.; Thomassen, C.L.G.D.; Hemker, H.C.; Pabinger, I.; Varadi, K.; Schwarz, H.P.; Rosing, J.
Peptide bond cleavages and loss of functional activity during inactivation of factor Va and factor VaR506Q by activated protein C
J. Biol. Chem.
270
21158-21166
1995
Homo sapiens
Manually annotated by BRENDA team
Rezaie, A.R.; Cooper, S.T.; Church, F.C.; Esmon, C.T.
Protein C inhibitor is a potent inhibitor of the thrombin-thrombomodulin complex
J. Biol. Chem.
270
25336-25339
1995
Homo sapiens
Manually annotated by BRENDA team
Regan, L.M.; O'Brien, L.M.; Beattie, T.L.; Sudhakar, K.; Walker, F.J.; Fay, P.J.
Activated protein C-catalyzed proteolysis of factor VIIIa alters its interactions within factor Xase
J. Biol. Chem.
271
3982-3987
1996
Homo sapiens
Manually annotated by BRENDA team
Fay, W.P.; Owen, W.G.
Platelet plasminogen activator inhibitor: purification and characterization of interaction with plasminogen activators and activated protein C
Biochemistry
28
5773-5778
1989
Homo sapiens
Manually annotated by BRENDA team
Heeb, M.J.; Griffin, J.H.
Physiologic inhibition of human activated protein C by alpha 1-antitrypsin
J. Biol. Chem.
263
11613-11616
1988
Homo sapiens
Manually annotated by BRENDA team
Suzuki, K.; Matsuda, Y.; Kusumoto, H.; Nishioka, J.; Terada, M.; Yamashita, T.; Hashimoto, S.
Monoclonal antibodies to human protein C: effects on the biological activity of activated protein C and the thrombin-catalyzed activation of protein C1
J. Biochem.
97
127-138
1985
Homo sapiens
Manually annotated by BRENDA team
Suzuki, K.; Nishioka, J.; Kusumoto, H.; Hashimoto, S.
Mechanism of inhibition of activated protein C by protein C inhibitor
J. Biochem.
95
187-195
1984
Homo sapiens
Manually annotated by BRENDA team
Suzuki, K.; Nishioka, J.; Hashimoto, S.
Protein C inhibitor. Purification from human plasma and characterization
J. Biol. Chem.
258
163-168
1983
Homo sapiens
Manually annotated by BRENDA team
Suzuki, K.; Kusumoto, H.; Nishioka, J.; Komiyama, Y.
Bovine plasma protein C inhibitor with structural and functional homologous properties to human plasma protein C inhibitor
J. Biochem.
107
381-388
1990
Bos taurus, Homo sapiens
Manually annotated by BRENDA team
Rezaie, A.R.; Esmon, C.T.
Conversion of glutamic acid 192 to glutamine in activated protein C changes the substrate specificity and increases reactivity toward macromolecular inhibitors
J. Biol. Chem.
268
19943-19948
1993
Homo sapiens
Manually annotated by BRENDA team
Hermans, J.M.; Stone, S.R.
Interaction of activated protein C with serpins
Biochem. J.
295
239-245
1993
Homo sapiens
Manually annotated by BRENDA team
Christiansen, W.T.; Geng, J.P.; Castellino, F.J.
Structure-function assessment of the role of the helical stack domain in the properties of human recombinant protein C and activated protein C
Biochemistry
34
8082-8090
1995
Homo sapiens
Manually annotated by BRENDA team
Gruber, A.; Griffin, J.H.
Direct detection of activated protein C in blood from human subjects
Blood
79
2340-2348
1992
Homo sapiens
Manually annotated by BRENDA team
Taby, O.; Chabbat, J.; Steinbuch, M.
Inhibition of activated protein C by aprotinin and the use of the insolubilized inhibitor for its purification
Thromb. Res.
59
27-35
1990
Homo sapiens
Manually annotated by BRENDA team
Pratt, C.W.; Macik, B.G.; Church, F.C.
Protein C inhibitor: purification and proteinase reactivity
Thromb. Res.
53
595-602
1989
Homo sapiens
Manually annotated by BRENDA team
Yang, L.; Manithody, C.; Rezaie, A.R.
Contribution of basic residues of the 70-80-loop to heparin binding and anticoagulant function of activated protein C
Biochemistry
41
6149-6157
2002
Homo sapiens (P04070)
Manually annotated by BRENDA team
Smirnov, M.D.; Safa, O.; Esmon, N.L.; Esmon, C.T.
Inhibition of activated protein C anticoagulant activity by prothrombin
Blood
94
3839-3846
1999
Homo sapiens
Manually annotated by BRENDA team
Colucci, M.; Stramaglia, A.M.; Mascolo, E.; Napoleone, E.; Lorenzet, R.; Semeraro, N.
Monocytes, but not endothelial cells, downregulate the anticoagulant activity of activated protein C
Br. J. Haematol.
112
519-526
2001
Homo sapiens
Manually annotated by BRENDA team
He, X.; Rezaie, A.R.
Identification and characterization of the sodium-binding site of activated protein C
J. Biol. Chem.
274
4970-4976
1999
Homo sapiens
Manually annotated by BRENDA team
Yegneswaran, S.; Smirnov, M.D.; Safa, O.; Esmon, N.L.; Esmon, C.T.; Johnson, A.E.
Relocating the active site of activated protein C eliminates the need for its protein S cofactor. A fluorescence resonance energy transfer study
J. Biol. Chem.
274
5462-5468
1999
Homo sapiens
Manually annotated by BRENDA team
Friedrich, U.; Blom, A.M.; Dahlbaeck, B.; Villoutreix, B.O.
Structural and energetic characteristics of the heparin-binding site in antithrombotic protein C
J. Biol. Chem.
276
24122-24128
2001
Homo sapiens
Manually annotated by BRENDA team
Schmidt, A.E.; Padmanabhan, K.; Underwood, M.C.; Bode, W.; Mather, T.; Bajaj, S.P.
Thermodynamic linkage between the S1 site, the Na+ site, and the Ca2+ site in the protease domain of human activated protein C (APC). Sodium ion in the APC crystal structure is coordinated to four carbonyl groups from two separate loops
J. Biol. Chem.
277
28987-28995
2002
Homo sapiens
Manually annotated by BRENDA team
Yegneswaran, S.; Deguchi, H.; Griffin, J.H.
Glucosylceramide, a neutral glycosphingolipid anticoagulant cofactor, enhances the interaction of human- and bovine-activated protein C with negatively charged phospholipid vesicles
J. Biol. Chem.
278
14614-14621
2003
Bos taurus, Homo sapiens
Manually annotated by BRENDA team
Fernandez, J.A.; Petaja, J.; Griffin, J.H.
Dermatan sulfate and LMW heparin enhance the anticoagulant action of activated protein C
Thromb. Haemost.
82
1462-1468
1999
Homo sapiens
Manually annotated by BRENDA team
Cvirn, G.; Gallistl, S.; Koestenberger, M.; Kutschera, J.; Leschnik, B.; Muntean, W.
Alpha 2-macroglobulin enhances prothrombin activation and thrombin potential by inhibiting the anticoagulant protein C/protein S system in cord and adult plasma
Thromb. Res.
105
433-439
2002
Homo sapiens
Manually annotated by BRENDA team
Varfaj, F.; Neuberg, J.; Jenkins, P.V.; Wakabayashi, H.; Fay, P.J.
Role of P1 residues Arg336 and Arg562 in the activated-Protein-C-catalysed inactivation of Factor VIIIa
Biochem. J.
396
355-362
2006
Homo sapiens
Manually annotated by BRENDA team
Nicolaes, G.A.F.; Sorensen, K.W.; Friedrich, U.; Tans, G.; Rosing, J.; Autin, L.; Dahlbaeck, B.; Villoutreix, B.O.
Altered inactivation pathway of factor Va by activated protein C in the presence of heparin
Eur. J. Biochem.
271
2724-2736
2004
Homo sapiens
Manually annotated by BRENDA team
Sun, Y.H.; Tran, S.; Norstrom, E.A.; Dahlbaeck, B.
Enhanced rate of cleavage at Arg-306 and Arg-506 in coagulation factor Va by Gla domain-mutated human-activated protein C
J. Biol. Chem.
279
47528-47535
2004
Homo sapiens
Manually annotated by BRENDA team
Pecheniuk, N.M.; Deguchi, H.; Griffin, J.H.
Cholesterol enhances phospholipid-dependent activated protein C anticoagulant activity
J. Thromb. Haemost.
3
340-345
2005
Homo sapiens
Manually annotated by BRENDA team
Gale, A.J.; Griffin, J.H.
Characterization of a thrombomodulin binding site on protein C and its comparison to an activated protein C binding site for factor Va
Proteins
54
433-441
2004
Homo sapiens
Manually annotated by BRENDA team
Brueckmann, M.; Horn, S.; Lang, S.; Fukudome, K.; Schulze Nahrup, A.; Hoffmann, U.; Kaden, J.J.; Borggrefe, M.; Haase, K.K.; Huhle, G.
Recombinant human activated protein C upregulates cyclooxygenase-2 expression in endothelial cells via binding to endothelial cell protein C receptor and activation of protease-activated receptor-1
Thromb. Haemost.
93
743-750
2005
Homo sapiens
Manually annotated by BRENDA team
Yang, L.; Manithody, C.; Rezaie, A.R.
The functional significance of the autolysis loop in protein C and activated protein C
Thromb. Haemost.
94
60-68
2005
Homo sapiens
Manually annotated by BRENDA team
Ji, S.L.; Du, H.Y.; Chi, Y.Q.; Cui, H.F.; Cao, J.C.; Geng, M.Y.; Guan, H.S.
Effects of dermatan sulfate derivatives on platelet surface P-selectin expression and protein C activity in blood of inflammatory bowel disease patients
World J. Gastroenterol.
10
3485-3489
2004
Homo sapiens
Manually annotated by BRENDA team
O'Brien, L.A.; Richardson, M.A.; Mehrbod, S.F.; Berg, D.T.; Gerlitz, B.; Gupta, A.; Grinnell, B.W.
Activated protein C decreases tumor necrosis factor-related apoptosis-inducing ligand by an EPCR-independent mechanism involving Egr-1/Erk-1/2 activation
Arterioscler. Thromb. Vasc. Biol.
27
2634-2641
2007
Homo sapiens
Manually annotated by BRENDA team
Qureshi, S.H.; Manithody, C.; Bae, J.S.; Yang, L.; Rezaie, A.R.
Autolysis loop restricts the specificity of activated protein C: analysis by FRET and functional assays
Biophys. Chem.
134
239-245
2008
Homo sapiens
Manually annotated by BRENDA team
Maurissen, L.F.; Thomassen, M.C.; Nicolaes, G.A.; Dahlbaeck, B.; Tans, G.; Rosing, J.; Hackeng, T.M.
Re-evaluation of the role of the protein S-C4b binding protein complex in activated protein C-catalyzed factor Va-inactivation
Blood
111
3034-3041
2008
Homo sapiens
Manually annotated by BRENDA team
Khrenov, A.V.; Ananyeva, N.M.; Saenko, E.L.
Role of the B domain in proteolytic inactivation of activated coagulation factor VIII by activated protein C and activated factor X
Blood Coagul. Fibrinolysis
17
379-388
2006
Homo sapiens
Manually annotated by BRENDA team
Brueckmann, M.; Nahrup, A.S.; Lang, S.; Bertsch, T.; Fukudome, K.; Liebe, V.; Kaden, J.J.; Hoffmann, U.; Borggrefe, M.; Huhle, G.
Recombinant human activated protein C upregulates the release of soluble fractalkine from human endothelial cells
Br. J. Haematol.
133
550-557
2006
Homo sapiens
Manually annotated by BRENDA team
Baillie, J.K.
Activated protein C: controversy and hope in the treatment of sepsis
Curr. Opin. Investig. Drugs
8
933-938
2007
Homo sapiens
Manually annotated by BRENDA team
Sakar, A.; Vatansever, S.; Sepit, L.; Ozbilgin, K.; Yorgancioglu, A.
Effect of recombinant human activated protein C on apoptosis-related proteins
Eur. J. Histochem.
51
103-109
2007
Homo sapiens
Manually annotated by BRENDA team
Beaulieu, L.M.; Church, F.C.
Activated protein C promotes breast cancer cell migration through interactions with EPCR and PAR-1
Exp. Cell Res.
313
677-687
2007
Homo sapiens
Manually annotated by BRENDA team
Hughes, M.
Recombinant human activated protein C
Int. J. Antimicrob. Agents
28
90-94
2006
Homo sapiens
Manually annotated by BRENDA team
Jackson, C.J.; Xue, M.
Activated protein C - an anticoagulant that does more than stop clots
Int. J. Biochem. Cell Biol.
40
2692-2697
2008
Homo sapiens
Manually annotated by BRENDA team
Baltch, A.L.; Bopp, L.H.; Ritz, W.J.; Michelsen, P.B.; Yan, S.B.; Um, S.; Smith, R.P.
Effect of recombinant human activated protein C on the bactericidal activity of human monocytes and modulation of pro-inflammatory cytokines in the presence of antimicrobial agents
J. Antimicrob. Chemother.
59
1177-1181
2007
Homo sapiens
Manually annotated by BRENDA team
Feistritzer, C.; Schuepbach, R.A.; Mosnier, L.O.; Bush, L.A.; Di Cera, E.; Griffin, J.H.; Riewald, M.
Protective signaling by activated protein C is mechanistically linked to protein C activation on endothelial cells
J. Biol. Chem.
281
20077-20084
2006
Homo sapiens
Manually annotated by BRENDA team
Preston, R.J.; Ajzner, E.; Razzari, C.; Karageorgi, S.; Dua, S.; Dahlbaeck, B.; Lane, D.A.
Multifunctional specificity of the protein C/activated protein C Gla domain
J. Biol. Chem.
281
28850-28857
2006
Homo sapiens
Manually annotated by BRENDA team
Norstrom, E.A.; Tran, S.; Steen, M.; Dahlbaeck, B.
Effects of factor Xa and protein S on the individual activated protein C-mediated cleavages of coagulation factor Va
J. Biol. Chem.
281
31486-31494
2006
Homo sapiens
Manually annotated by BRENDA team
Varfaj, F.; Wakabayashi, H.; Fay, P.J.
Residues surrounding Arg336 and Arg562 contribute to the disparate rates of proteolysis of factor VIIIa catalyzed by activated protein C
J. Biol. Chem.
282
20264-20272
2007
Homo sapiens
Manually annotated by BRENDA team
Yang, L.; Bae, J.S.; Manithody, C.; Rezaie, A.R.
Identification of a specific exosite on activated protein C for interaction with protease-activated receptor 1
J. Biol. Chem.
282
25493-25500
2007
Homo sapiens
Manually annotated by BRENDA team
Yegneswaran, S.; Kojima, Y.; Nguyen, P.M.; Gale, A.J.; Heeb, M.J.; Griffin, J.H.
Factor Va residues 311-325 represent an activated protein C binding region
J. Biol. Chem.
282
28353-28361
2007
Homo sapiens
Manually annotated by BRENDA team
Mosnier, L.O.; Yang, X.V.; Griffin, J.H.
Activated protein C mutant with minimal anticoagulant activity, normal cytoprotective activity, and preservation of thrombin activable fibrinolysis inhibitor-dependent cytoprotective functions
J. Biol. Chem.
282
33022-33033
2007
Homo sapiens
Manually annotated by BRENDA team
Bae, J.S.; Yang, L.; Manithody, C.; Rezaie, A.R.
Engineering a disulfide bond to stabilize the calcium-binding loop of activated protein C eliminates its anticoagulant but not its protective signaling properties
J. Biol. Chem.
282
9251-9259
2007
Homo sapiens
Manually annotated by BRENDA team
Tran, S.; Norstrom, E.; Dahlbaeck, B.
Effects of prothrombin on the individual activated protein C-mediated cleavages of coagulation factor Va
J. Biol. Chem.
283
6648-6655
2008
Homo sapiens
Manually annotated by BRENDA team
Stephenson, D.A.; Toltl, L.J.; Beaudin, S.; Liaw, P.C.
Modulation of monocyte function by activated protein C, a natural anticoagulant
J. Immunol.
177
2115-2122
2006
Homo sapiens
Manually annotated by BRENDA team
Hensley, L.E.; Stevens, E.L.; Yan, S.B.; Geisbert, J.B.; Macias, W.L.; Larsen, T.; Daddario-DiCaprio, K.M.; Cassell, G.H.; Jahrling, P.B.; Geisbert, T.W.
Recombinant human activated protein C for the postexposure treatment of Ebola hemorrhagic fever
J. Infect. Dis.
196 Suppl 2
S390-S399
2007
Homo sapiens
Manually annotated by BRENDA team
De Nanteuil, G.; Gloanec, P.; Beguin, S.; Giesen, P.L.; Hemker, H.C.; Mennecier, P.; Rupin, A.; Verbeuren, T.J.
Low molecular weight activated protein C inhibitors as a potential treatment for hemophilic disorders
J. Med. Chem.
49
5047-5050
2006
Homo sapiens
Manually annotated by BRENDA team
Griffin, J.H.; Fernandez, J.A.; Gale, A.J.; Mosnier, L.O.
Activated protein C
J. Thromb. Haemost.
5 Suppl 1
73-80
2007
Homo sapiens, Mus musculus
Manually annotated by BRENDA team
Cheng, T.; Petraglia, A.L.; Li, Z.; Thiyagarajan, M.; Zhong, Z.; Wu, Z.; Liu, D.; Maggirwar, S.B.; Deane, R.; Fernandez, J.A.; LaRue, B.; Griffin, J.H.; Chopp, M.; Zlokovic, B.V.
Activated protein C inhibits tissue plasminogen activator-induced brain hemorrhage
Nat. Med.
12
1278-1285
2006
Homo sapiens
Manually annotated by BRENDA team
Nold, M.F.; Nold-Petry, C.A.; Fischer, D.; Richter, B.; Blaheta, R.; Pfeilschifter, J.; Muhl, H.; Schranz, D.; Veldman, A.
Activated protein C downregulates p38 mitogen-activated protein kinase and improves clinical parameters in an in-vivo model of septic shock
Thromb. Haemost.
98
1118-1126
2007
Homo sapiens, Sus scrofa
Manually annotated by BRENDA team
Gennari, L.C.; Blanco, A.N.; Dominguez, M.P.; Grosso, S.H.; Lazzari, M.A.
Endogenous or exogenous coagulation factor level and the response to activated protein C
Thromb. Res.
118
269-273
2006
Homo sapiens
Manually annotated by BRENDA team
Cimenti, C.; Koestenberger, M.; Leschnik, B.; Haidl, H.; Muntean, W.
The respective and combined anticoagulant effects of recombinant human activated protein C, melagatran and heparins using CAT
Thromb. Res.
119
361-367
2007
Homo sapiens
Manually annotated by BRENDA team
Malm, K.; Arnljots, B.; Persson, I.M.; Dahlbaeck, B.
Antithrombotic and anticoagulant effects of wild type and Gla-domain mutated human activated protein C in rats
Thromb. Res.
120
531-539
2007
Homo sapiens
Manually annotated by BRENDA team
Slofstra, S.H.; ten Cate, H.; Spek, C.A.
Signal transduction induced by activated protein C: no role in protection against sepsis?
Trends Mol. Med.
12
374-381
2006
Homo sapiens
Manually annotated by BRENDA team
Bezuhly, M.; Cullen, R.; Esmon, C.T.; Morris, S.F.; West, K.A.; Johnston, B.; Liwski, R.S.
Role of activated protein C and its receptor in inhibition of tumor metastasis
Blood
113
3371-3374
2009
Homo sapiens
Manually annotated by BRENDA team
Elphick, G.F.; Sarangi, P.P.; Hyun, Y.M.; Hollenbaugh, J.A.; Ayala, A.; Biffl, W.L.; Chung, H.L.; Rezaie, A.R.; McGrath, J.L.; Topham, D.J.; Reichner, J.S.; Kim, M.
Recombinant human activated protein C inhibits integrin-mediated neutrophil migration
Blood
113
4078-4085
2009
Homo sapiens
Manually annotated by BRENDA team
Galley, H.F.; El Sakka, N.E.; Webster, N.R.; Lowes, D.A.; Cuthbertson, B.H.
Activated protein C inhibits chemotaxis and interleukin-6 release by human neutrophils without affecting other neutrophil functions
Br. J. Anaesth.
100
815-819
2008
Homo sapiens
Manually annotated by BRENDA team
Takeyama, M.; Nogami, K.; Saenko, E.L.; Soeda, T.; Nishiya, K.; Ogiwara, K.; Yoshioka, A.; Shima, M.
Protein S down-regulates factor Xase activity independent of activated protein C: specific binding of factor VIII(a) to protein S inhibits interactions with factor IXa
Br. J. Haematol.
143
409-420
2008
Homo sapiens
Manually annotated by BRENDA team
Toltl, L.J.; Beaudin, S.; Liaw, P.C.; Liaw, P.C.
Activated protein C up-regulates IL-10 and inhibits tissue factor in blood monocytes
J. Immunol.
181
2165-2173
2008
Homo sapiens
Manually annotated by BRENDA team
Bakoush, O.; Ohlin, A.K.; Strandberg, K.; Kurkus, J.
Low plasma activated protein C-protein C inhibitor complex concentration is associated with vascular access failure in hemodialysis patients
Nephron. Clin. Pract.
110
c151-c157
2008
Homo sapiens
Manually annotated by BRENDA team
Koelbel, T.; Strandberg, K.; Donath, T.; Mattiasson, I.; Stenflo, J.; Lindblad, B.
Activated protein C-protein C inhibitor complex in patients with abdominal aortic aneurysms: is it associated with diameter and growth rate?
Vasc. Endovascular. Surg.
42
135-140
2008
Homo sapiens
Manually annotated by BRENDA team
Guitton, C.; Cottereau, A.; Gerard, N.; Quillard, T.; Chauveau, A.; Devalliere, J.; Tonnerre, P.; Charreau, B.
Protective cross talk between activated protein C and TNF signaling in vascular endothelial cells: implication of EPCR, noncanonical NF-kappaB, and ERK1/2 MAP kinases
Am. J. Physiol. Cell Physiol.
300
C833-C842
2011
Homo sapiens
Manually annotated by BRENDA team
Barhoover, M.A.; Kalafatis, M.
Cleavage at both Arg306 and Arg506 is required and sufficient for timely and efficient inactivation of factor Va by activated protein C
Blood Coagul. Fibrinolysis
22
317-324
2011
Homo sapiens
Manually annotated by BRENDA team
Schuepbach, R.A.; Velez, K.; Riewald, M.
Activated protein C up-regulates procoagulant tissue factor activity on endothelial cells by shedding the TFPI Kunitz 1 domain
Blood
117
6338-6346
2011
Homo sapiens
Manually annotated by BRENDA team
Bae, J.S.; Rezaie, A.R.
Activated protein C inhibits high mobility group box 1 signaling in endothelial cells
Blood
118
3952-3959
2011
Homo sapiens
Manually annotated by BRENDA team
Gramling, M.; Beaulieu, L.; Church, F.
Activated protein C enhances cell motility of endothelial cells and MDA-MB-231 breast cancer cells by intracellular signal transduction
Exp. Cell Res.
316
314-328
2010
Homo sapiens
Manually annotated by BRENDA team
Seol, J.W.; Lee, Y.J.; Jackson, C.J.; Sambrook, P.N.; Park, S.Y.
Activated protein C inhibits bisphosphonate-induced endothelial cell death via the endothelial protein C receptor and nuclear factor-kappaB pathways
Int. J. Mol. Med.
27
835-840
2011
Homo sapiens
Manually annotated by BRENDA team
Du, Z.J.; Yamamoto, T.; Ueda, T.; Suzuki, M.; Tano, Y.; Kamei, M.
Activated protein C rescues the retina from ischemia-induced cell death
Invest. Ophthalmol. Vis. Sci.
52
987-993
2011
Homo sapiens
Manually annotated by BRENDA team
Sen, P.; Sahoo, S.; Pendurthi, U.R.; Rao, L.V.
Zinc modulates the interaction of protein C and activated protein C with endothelial cell protein C receptor
J. Biol. Chem.
285
20410-20420
2010
Homo sapiens
Manually annotated by BRENDA team
Nicolaes, G.A.; Bock, P.E.; Segers, K.; Wildhagen, K.C.; Dahlbaeck, B.; Rosing, J.
Inhibition of thrombin formation by active site mutated (S360A) activated protein C
J. Biol. Chem.
285
22890-22900
2010
Homo sapiens
Manually annotated by BRENDA team
Xue, M.; Chow, S.O.; Dervish, S.; Chan, Y.K.; Julovi, S.M.; Jackson, C.J.
Activated protein C enhances human keratinocyte barrier integrity via sequential activation of epidermal growth factor receptor and Tie2
J. Biol. Chem.
286
6742-6750
2011
Homo sapiens
Manually annotated by BRENDA team
Lichtnekert, J.; Rupanagudi, K.V.; Kulkarni, O.P.; Darisipudi, M.N.; Allam, R.; Anders, H.J.
Activated protein C attenuates systemic lupus erythematosus and lupus nephritis in MRL-Fas(lpr) mice
J. Immunol.
187
3413-3421
2011
Homo sapiens
Manually annotated by BRENDA team
Toltl, L.J.; Austin, R.C.; Liaw, P.C.
Activated protein C modulates inflammation, apoptosis and tissue factor procoagulant activity by regulating endoplasmic reticulum calcium depletion in blood monocytes
J. Thromb. Haemost.
9
582-592
2011
Homo sapiens
Manually annotated by BRENDA team
Keller, S.A.; Moore, C.C.; Clemens, M.G.; McKillop, I.H.; Huynh, T.
Activated protein C restores hepatic microcirculation during sepsis by modulating vasoregulator expression
Shock
36
361-369
2011
Homo sapiens
Manually annotated by BRENDA team
Kim, P.Y.; Nesheim, M.E.
Down regulation of prothrombinase by activated protein C during prothrombin activation
Thromb. Haemost.
104
61-70
2010
Homo sapiens
Manually annotated by BRENDA team
Wildhagen, K.C.; Lutgens, E.; Loubele, S.T.; Ten Cate, H.; Nicolaes, G.A.
The structure-function relationship of activated protein C. Lessons from natural and engineered mutations
Thromb. Haemost.
106
1034-1045
2011
Homo sapiens
Manually annotated by BRENDA team
Deangelis, J.P.; Varfaj, F.; Wakabayashi, H.; Fay, P.J.
The role of P4-P3 residues flanking Arg336 in facilitating activated protein C-catalyzed cleavage and inactivation of factor VIIIa
Thromb. Res.
128
470-476
2011
Homo sapiens
Manually annotated by BRENDA team
Hemmer, C.J.; Loebermann, M.; Unverricht, M.; Vogt, A.; Krause, R.; Reisinger, E.C.
Activated protein C protects vascular endothelial cells from apoptosis in malaria and in sepsis
Trop. Med. Int. Health
16
906-913
2011
Homo sapiens
Manually annotated by BRENDA team
Kowalska, M.A.; Zhao, G.; Zhai, L.; David, G.; Marcus, S.; Krishnaswamy, S.; Poncz, M.
Modulation of protein C activation by histones, platelet factor 4, and heparinoids: new insights into activated protein C formation
Arterioscler. Thromb. Vasc. Biol.
34
120-126
2014
Homo sapiens
Manually annotated by BRENDA team
Bach, P.; Knerr, L.; Fjellstroem, O.; Hansson, K.; Mattsson, C.; Gustafsson, D.
Design, synthesis, and SAR of a series of activated protein C (APC) inhibitors with selectivity against thrombin for the treatment of haemophilia
Bioorg. Med. Chem. Lett.
24
821-827
2014
Homo sapiens
Manually annotated by BRENDA team
Burnier, L.; Mosnier, L.O.
Novel mechanisms for activated protein C cytoprotective activities involving noncanonical activation of protease-activated receptor 3
Blood
122
807-816
2013
Homo sapiens
Manually annotated by BRENDA team
Li, B.; Yu, D.; Xu, Z.
Activated protein C inhibits amyloid beta production via promoting expression of ADAM-10
Brain Res.
1545
35-44
2014
Homo sapiens
Manually annotated by BRENDA team
Lee, Y.J.; Jeong, J.K.; Seol, J.W.; Xue, M.; Jackson, C.; Park, S.Y.
Activated protein C differentially regulates both viability and differentiation of osteoblasts mediated by bisphosphonates
Exp. Mol. Med.
45
e9
2013
Homo sapiens
Manually annotated by BRENDA team
Xue, M.; Dervish, S.; Harrison, L.C.; Fulcher, G.; Jackson, C.J.
Activated protein C inhibits pancreatic islet inflammation, stimulates T regulatory cells, and prevents diabetes in non-obese diabetic (NOD) mice
J. Biol. Chem.
287
16356-16364
2012
Homo sapiens
Manually annotated by BRENDA team
D'Ursi, P.; Orro, A.; Morra, G.; Moscatelli, M.; Trombetti, G.; Milanesi, L.; Rovida, E.
Molecular dynamics and docking simulation of a natural variant of Activated Protein C with impaired protease activity: implications for integrin-mediated antiseptic function
J. Biomol. Struct. Dyn.
33
85-92
2015
Homo sapiens
Manually annotated by BRENDA team
Satou, M.; Nishi, Y.; Hishinuma, A.; Hosoda, H.; Kangawa, K.; Sugimoto, H.
Identification of activated protein C as a ghrelin endopeptidase in bovine plasma
J. Endocrinol.
224
61-73
2015
Bos taurus, Homo sapiens, Mus musculus, Mus musculus C57/BL6J
Manually annotated by BRENDA team
Luo, L.; Lv, T.; Wang, Q.; Zhang, T.; Gu, X.; Xu, F.; Song, Y.
Activated protein C induces endoplasmic reticulum stress and attenuates lipopolysaccharide-induced apoptosis mediated by glycogen synthase kinase-3beta
Mediators Inflamm.
2012
485279
2012
Homo sapiens
Manually annotated by BRENDA team
Julovi, S.M.; Shen, K.; Mckelvey, K.; Minhas, N.; March, L.; Jackson, C.J.
Activated protein C inhibits proliferation and tumor necrosis factor alpha-stimulated activation of p38, c-Jun NH2-terminal kinase (JNK) and Akt in rheumatoid synovial fibroblasts
Mol. Med.
19
324-331
2013
Homo sapiens
Manually annotated by BRENDA team
Babu, B.I.; Genovese, T.; Mazzon, E.; Riccardi, L.; Paterniti, I.; Galuppo, M.; Crisafulli, C.; Siriwardena, A.K.; Cuzzocrea, S.
Recombinant human activated protein C (Xigris) attenuates murine cerulein-induced acute pancreatitis via regulation of nuclear factor kappaB and apoptotic pathways
Pancreas
41
619-628
2012
Homo sapiens
Manually annotated by BRENDA team
Puig, F.; Fuster, G.; Adda, M.; Blanch, L.; Farre, R.; Navajas, D.; Artigas, A.
Barrier-protective effects of activated protein C in human alveolar epithelial cells
PLoS ONE
8
e56965
2013
Homo sapiens
Manually annotated by BRENDA team
Quinn, L.M.; Drakeford, C.; O'Donnell, J.S.; Preston, R.J.
Engineering activated protein C to maximize therapeutic efficacy
Biochem. Soc. Trans.
43
691-695
2015
Bos taurus (P00745), Homo sapiens (P04070), Mus musculus (P33587)
Manually annotated by BRENDA team
Gleeson, E.M.; Dichiara, M.G.; Salicio, A.; Quinn, L.M.; Drakeford, C.; Russell, S.E.; Walsh, P.T.; Orbe, J.; Hermida, J.; Smith, O.P.; O'Donnell, J.S.; Montes, R.; Preston, R.J.
Activated protein C beta-glycoform promotes enhanced noncanonical PAR1 proteolysis and superior resistance to ischemic injury
Blood
126
915-919
2015
Homo sapiens (P04070), Mus musculus (P33587), Mus musculus
Manually annotated by BRENDA team
Griffin, J.H.; Zlokovic, B.V.; Mosnier, L.O.
Activated protein C, protease activated receptor 1, and neuroprotection
Blood
132
159-169
2018
Homo sapiens (P04070), Homo sapiens, Mus musculus (P33587), Mus musculus
Manually annotated by BRENDA team
Minhas, N.; Xue, M.; Jackson, C.J.
Activated protein C binds directly to Tie2 possible beneficial effects on endothelial barrier function
Cell. Mol. Life Sci.
74
1895-1906
2017
Homo sapiens (P04070)
Manually annotated by BRENDA team
Wang, Y.; Zhao, Z.; Rege, S.V.; Wang, M.; Si, G.; Zhou, Y.; Wang, S.; Griffin, J.H.; Goldman, S.A.; Zlokovic, B.V.
3K3A-activated protein C stimulates postischemic neuronal repair by human neural stem cells in mice
Nat. Med.
22
1050-1055
2016
Homo sapiens (P04070), Homo sapiens
Manually annotated by BRENDA team