3.4.21.69: Protein C (activated)
This is an abbreviated version!
For detailed information about Protein C (activated), go to the full flat file.
Word Map on EC 3.4.21.69
-
3.4.21.69
-
thrombosis
-
venous
-
leiden
-
sepsis
-
endothelial
-
antithrombin
-
thromboembolism
-
thrombophilia
-
clot
-
thrombomodulin
-
platelet
-
procoagulant
-
heparin
-
arterial
-
vein
-
bleeding
-
plasminogen
-
hypercoagulable
-
thromboplastin
-
lupus
-
fibrinogen
-
fibrinolysis
-
hemostatic
-
viiia
-
epcr
-
intravascular
-
contraceptive
-
antiphospholipid
-
antithrombotic
-
prothrombotic
-
fibrin
-
k-dependent
-
anticardiolipin
-
d-dimers
-
coagulopathy
-
embolism
-
prothrombinase
-
amidolytic
-
thrombin-antithrombin
-
haemostasis
-
par1
-
profibrinolytic
-
pharmacology
-
goal-directed
-
diagnostics
-
drug development
-
gamma-carboxyglutamic
-
deep-vein
-
time-based
-
tafi
-
hypofibrinolysis
-
thromboprophylaxis
-
medicine
-
protac
- 3.4.21.69
- thrombosis
- venous
- leiden
- sepsis
- endothelial
- antithrombin
- thromboembolism
- thrombophilia
- clot
- thrombomodulin
- platelet
-
procoagulant
- heparin
- arterial
- vein
-
bleeding
- plasminogen
-
hypercoagulable
- thromboplastin
-
lupus
- fibrinogen
-
fibrinolysis
-
hemostatic
- viiia
- epcr
-
intravascular
-
contraceptive
-
antiphospholipid
-
antithrombotic
-
prothrombotic
- fibrin
-
k-dependent
-
anticardiolipin
-
d-dimers
- coagulopathy
- embolism
- prothrombinase
-
amidolytic
-
thrombin-antithrombin
-
haemostasis
- par1
-
profibrinolytic
- pharmacology
-
goal-directed
- diagnostics
- drug development
-
gamma-carboxyglutamic
-
deep-vein
-
time-based
- tafi
-
hypofibrinolysis
-
thromboprophylaxis
- medicine
- protac
Reaction
degradation of blood coagulation factors Va and VIIIa =
Synonyms
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, APC, Autoprothrombin II-A, Autoprothrombin IIA, Blood coagulation factor XIV, Blood-coagulation factor XIV, activated, Blood-coagulation factor XIVa, ghrelin endopeptidase, GSAPC, hAPC, PROC, Protein Ca, rhAPC
ECTree
3.4.21.69 Protein C (activated)Advanced search results
results (
results (Substrates Products
Substrates Products on EC 3.4.21.69 - Protein C (activated)
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SUBSTRATE 
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
active factor Va mutant R306Q + H2O
?
-
proteolytic inactivation, cleavage at Arg506
-
-
?
active factor Va mutant R306Q + H2O
inactive factor V mutant R306Q + ?
-
proteolytic inactivation, cleavage of the heavy chain at Arg506 and Arg679
-
-
?
active factor Va mutant R306Q/R679Q + H2O
inactive factor V mutant R306Q/R679Q + ?
-
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
?
-
proteolytic inactivation, cleavage at Arg306
-
-
?
active factor Va mutant R506Q + H2O
inactive factor V mutant R506Q + ?
-
proteolytic inactivation, cleavage of the heavy chain at Arg306 and Arg679
-
-
?
active factor Va mutant R506Q/R679Q + H2O
inactive factor V mutant R506Q/R679Q + ?
-
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 + ?
-
proteolytic inactivation, cleavage of the heavy chain at Arg306 and Arg506
-
-
?
active factor VIII + H2O
inactive factor VIII + domain B
-
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
-
-
?
D-Phe-Pip-Arg-4-nitroanilide + H2O
D-Phe-Pip-Arg + 4-nitroaniline
-
S-2238
-
-
?
L-pGln-L-Pro-L-Arg-4-nitroanilide + H2O
L-pGln-L-Pro-L-Arg + 4-nitroaniline
-
-
-
-
?
membrane-bound factor Va + H2O
?
-
cleavage of Arg506 in membrane-bound factor Va
-
-
?
Nalpha-benzoyl-L-Arg 4-nitroanilide + H2O
Nalpha-benzoyl-L-Arg + 4-nitroaniline
-
amidase activity
-
-
?
protease activated receptor 3 N-terminal peptide + H2O
?
-
the enzyme cleaves a synthetic PAR3 N-terminal peptide at Arg41
-
-
?
Z-Gly-Gly-Arg-aminomethylcoumarin + H2O
?
-
a fluorogenic substrate, S-2366
-
-
?
active factor Va + H2O
inactive factor V + ?
-
proteolytic inactivation
-
-
?
active factor Va + H2O
inactive factor V + ?
-
proteolytic inactivation of the cofactor in the prothrombinase complex
-
-
?
active factor Va + H2O
inactive factor V + ?
-
proteolytic inactivation, cleavage of the heavy chain at Arg506, Arg306, and Arg679, factor Xa protects factor Va from inactivation by APC, interaction of factor Va and APC at residues 311-325 of the substrate
-
-
?
active factor Va + H2O
inactive factor V + ?
-
proteolytic inactivation, the autolysis loop of APC represents the active site, active site topology, the loop plays a critical role in restricting both the specificity and spatial environment of the active-site groove of APC, overview
-
-
?
active factor Va + H2O
inactive factor V + domain B
-
proteolytic inactivation
-
-
?
active factor Va + H2O
inactive factor V + domain B
-
activated protein C inhibits the procoagulant function of activated factor V through proteolytic cleavage
-
-
?
active factor Va + H2O
inactive factor V + domain B
-
proteolytic inactivation requires interactions with both EPCR and PAR-1
-
-
?
active factor Va + H2O
inactive factor V + domain B
-
proteolytic inactivation, cleavage at Arg306 and Arg506
-
-
?
active factor Va + H2O
inactive factor V + domain B
-
proteolytic inactivation, cleavages at Arg306, Arg506, and Arg679, the cleavage at Arg506 is kinetically favored but protected by factor Xa
-
-
?
active factor Va + H2O
inactive factor V + domain B
-
proteolytic inactivation, the basic residues of two surface loops including those on 39 and the Ca2+-binding 70-80 loops constitute interactive sites for both factors Va and VIIIa, thereby mediating the interaction of APC specifically with these procoagulant cofactors
-
-
?
active factor Va + H2O
inactive factor V heavy chain + peptide fragment 307-709
-
proteolytic inactivation
-
-
?
active factor Va + H2O
inactive factor V heavy chain + peptide fragment 307-709
-
proteolytic inactivation, cleavage at Arg306 and Arg506
-
-
?
active factor VIIIa + H2O
inactive factor VIII + domain B
-
proteolytic inactivation
-
-
?
active factor VIIIa + H2O
inactive factor VIII + domain B
-
the inactivation of factor VIIIa by the enzyme is responsible for its high anticoagulation effect, high factor VIII contents lead to increased resistance to activated protein C, while factor II and factor X are not correleted to active protein C resistance, mechanism, overview
-
-
?
active factor VIIIa + H2O
inactive factor VIII + domain B
-
proteolytic inactivation with cleavage at Arg336 within the factor VIIIa A1 subunit and Arg562 within the A2 subunit, reduced activity with three 336(P4-P3')562 fator VIII variants, possessing mutations surrounding Arg336, compared to wild-type fVIIIa, the rate of cleavage for the A1 subunit of the fully substituted P4-P3' mutant is reduced by 100fold relative to wild-type, cleavage of the A2 subunit for the 336(P4-P3')562 appear a few fold slower than that for wild-type, overview
-
-
?
active factor VIIIa + H2O
inactive factor VIII + domain B
-
proteolytic inactivation, cleavage at Arg336 and Arg572 in domains A1 and A2, respectively
-
-
?
active factor VIIIa + H2O
inactive factor VIII + domain B
-
proteolytic inactivation, the basic residues of two surface loops including those on 39 and the Ca2+-binding 70-80 loops constitute interactive sites for both factors Va and VIIIa, thereby mediating the interaction of APC specifically with these procoagulant cofactors
-
-
?
Boc-Leu-Ser-Thr-Arg-4-nitroanilide + H2O
Boc-Leu-Ser-Thr-Arg + 4-nitroaniline
-
amidolytic activity
-
-
?
Boc-Leu-Ser-Thr-Arg-4-nitroanilide + H2O
Boc-Leu-Ser-Thr-Arg + 4-nitroaniline
-
-
-
-
?
Boc-Leu-Ser-Thr-Arg-4-nitroanilide + H2O
Boc-Leu-Ser-Thr-Arg + 4-nitroaniline
-
-
-
-
?
Factor Va + H2O
?
-
in the membrane-bound factor Va cleavage occurs rapidly at Arg506 and is followed by a slower proteolysis at Arg306 and a final, very slow cleavage at Arg679
-
-
?
Factor Va + H2O
?
-
natural anticoagulant, inhibits thrombin generation by degrading factors Va and VIIIa
-
?
Factor Va + H2O
?
-
natural anticoagulant, inhibits thrombin generation by degrading factors Va and VIIIa
-
?
Factor Va + H2O
?
-
protein C anticoagulanat pathway, multi-domain vitamin K-dependent plasma serine protease zymogen, down-regulates the blood coagulation cascade upon activation by the thrombin-TM complex by selectively inactivating factors Va and VIII a
-
?
Factor Va + H2O
?
-
protein C anticoagulanat pathway, multi-domain vitamin K-dependent plasma serine protease zymogen, down-regulates the blood coagulation cascade upon activation by the thrombin-TM complex by selectively inactivating factors Va and VIII a
-
?
Factor Va + H2O
?
-
activated protein C downregulates thrombin formation through proteolytic inactivation of factor Va by cleavage at Arg506 and Arg306. Docking of APC to FVa and FVIIIa constitutes the first step in the inactivation of the cofactor
-
-
?
Factor Va + H2O
?
-
activated protein C inactivates membrane-bound factor Va following cleavages of the heavy chain at Arg306, Arg506, and Arg679. In the absence of the APC-cleavage sites at Arg306 and Arg506, the active cofactor is unable to be significantly inactivated by APC in the presence of a membrane surface
-
-
?
Factor Va + H2O
?
-
APC can inactivate FVa by proteolysis of three different peptide bonds at positions R306, R506 and R679. The cleavage at R506 is kinetically favoured, protein S-independent and yields a FVa intermediate with decreased factor Xa-cofactor activity. The slower cleavage at R306 is stimulated by protein S and completely inactivates FVa
-
-
?
Factor Va + H2O
?
-
cleavage at Arg306, Arg506, and Arg679 of the heavy chain
-
-
?
Factor Va + H2O
?
-
inactivation through cleavage at Arg306, Arg506, and Arg679
-
-
?
Factor Va + H2O
?
-
activated protein C inactivates membrane-bound factor Va following cleavages of the heavy chain at Arg306, Arg506, and Arg679. It is the first cleavage at Arg306 that is the inactivating cleavage. Cleavage at Arg306 leads to full loss of cofactor function and the dissociation of the A2 domain from the rest of the molecule. Complete inactivation of factor Va by APC requires the presence of a membrane surface, however, factor Va can be cleaved by APC in the absence of a membrane surface at Arg506 and Arg679, retaining approximately 80% of its cofactor activity
-
-
?
Factor Va + H2O
?
-
cleavage at Arg306, Arg506, and Arg679 of the heavy chain. FVa is protected by prothrombin about 7.6fold in the absence of FXa
-
-
?
factor Va Leiden + H2O
?
-
inactivation is much less sensitive to prothrombin inhibition
-
?
Factor VaR506Q + H2O
?
-
The substrate is derived from factor Va by replacing Arg506 by Gln. In the presence of phospholipids the substrate is hydrolyzed at Arg306, but in the absence of phospholipids hydrolysis occurs at Arg679, followed by cleavage at Arg306, suggesting that the binding of phospholipids alters the accessibility of Arg679
-
-
?
Factor VIIIa + H2O
?
-
cleavage at two sites: at Arg336 near the C-terminus of the A1 subunit, and at Arg562, bisecting the A2 subunit, the proteolysis abolishes the cofactor activity in the intrinsic factor Xase
-
-
?
Factor VIIIa + H2O
?
-
natural anticoagulant, inhibits thrombin generation by degrading factors Va and VIIIa
-
?
Factor VIIIa + H2O
?
-
natural anticoagulant, inhibits thrombin generation by degrading factors Va and VIIIa
-
?
Factor VIIIa + H2O
?
-
protein C anticoagulanat pathway, multi-domain vitamin K-dependent plasma serine protease zymogen, down-regulates the blood coagulation cascade upon activation by the thrombin-TM complex by selectively inactivating factors Va and VIII a
-
?
Factor VIIIa + H2O
?
-
protein C anticoagulanat pathway, multi-domain vitamin K-dependent plasma serine protease zymogen, down-regulates the blood coagulation cascade upon activation by the thrombin-TM complex by selectively inactivating factors Va and VIII a
-
?
Factor VIIIa + H2O
?
-
proteolytic inactivation by cleavage at Arg336 in A1 subunit and Arg562 in A2 subunit. Cleavage at A1 site is the dominant mechanism for factor VIIIa inactivation
-
-
?
Factor VIIIa + H2O
?
-
activated protein C downregulates thrombin formation through proteolytic inactivation of factor VIIIa by cleavage at Arg336 and Arg56. Docking of APC to FVa and FVIIIa constitutes the first step in the inactivation of the cofactor
-
-
?
Factor VIIIa + H2O
?
-
APC cleaves factor VIIIa at two peptide bonds, Arg336 and Arg562
-
-
?
Factor VIIIa + H2O
?
-
inactivation through cleavages at Arg336 in the A1 subunit and Arg562 in the A2 subunit
-
-
?
Factor VIIIa + H2O
?
-
inactivation through cleavages at Arg336 in the A1 subunit and Arg562 in the A2 subunit. Proteolysis at Arg336 occurs 25fold faster than at Arg562. Activities with substrate mutants, overview. The inactivation rates observed for point mutations at the P3 and P2 positions, Gln334Asp, Leu335Gln, and Leu335Arg, are reduced by about 2fold compared with wild-type factor VIIIa
-
-
?
ghrelin + H2O
?
-
ghrelin is converted into smaller fragments in blood plasma in circulation under thrombotic and inflammatory conditions
-
-
?
ghrelin + H2O
?
-
ghrelin is converted into smaller fragments in blood plasma in circulation under thrombotic and inflammatory conditions
-
-
?
ghrelin + H2O
?
-
ghrelin is converted into smaller fragments in blood plasma in circulation under thrombotic and inflammatory conditions
-
-
?
ghrelin + H2O
?
-
ghrelin is converted into smaller fragments in blood plasma in circulation under thrombotic and inflammatory conditions
-
-
?
octanoyl-ghrelin + H2O
octanoyl ghrelin(1-15) + ?
-
preferred substrate
-
-
?
octanoyl-truncated ghrelin + H2O
?
-
preferred substrate, synthetic human substrate, octanoyl-truncated ghrelin(1-15) activates GHSR1a-dependent signaling similar to the full-length peptide
-
-
?
octanoyl-truncated ghrelin + H2O
?
-
preferred substrate, synthetic human substrate, octanoyl-truncated ghrelin(1-15) activates GHSR1a-dependent signaling similar to the full-length peptide
-
-
?
octanoyl-truncated ghrelin + H2O
ghrelin(1-15) + ?
-
octanoyl-truncated ghrelin(1-15) activates GHSR1a-dependent signaling similar to the full-length peptide
-
-
?
octanoyl-truncated ghrelin + H2O
ghrelin(1-15) + ?
-
octanoyl-truncated ghrelin(1-15) activates GHSR1a-dependent signaling similar to the full-length peptide
-
-
?
protease activated receptor 1 + H2O
?
-
APC can also bind to endothelial protein C receptor to activate protease activated receptor 1, PAR-1, thereby eliciting antiinflammatory and cytoprotective signaling responses in endothelial cells
-
-
?
protease activated receptor 1 + H2O
?
-
APC exhibits cytoprotective and antiinflammatory activity through the endothelial protein C receptor-dependent cleavage of protease activated receptor 1, PAR-1, on endothelial cells
-
-
?
protease activated receptor 1 + H2O
?
-
activation, the basic residues of surface loops are indispensable for interaction with APC, also two acidic residues on helix-162, Glu167 and Glu170, on the protease domain of APC which are required for the protease interaction with PAR-1
-
-
?
protease activated receptor 1 + H2O
?
-
APC can also bind to endothelial protein C receptor to activate protease activated receptor 1, PAR-1, APC cleaves the PAR-1 exodomain with about 750fold lower catalytic efficiency than thrombin
-
-
?
protease activated receptor 3 zymogen H2O
active protease activated receptor 3 + ?
-
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 3 zymogen H2O
active protease activated receptor 3 + ?
-
enzyme-mediated cleavage of PAR3 is analyzed by the proteolytic release of SEAP from a SEAP-PAR3 fusion protein expressed in HEK-293 cells in the absence or presence of stable endothelial protein C receptor coexpression
-
-
?
protease-activated receptor 1 + H2O
?
PAR1, generation of unique tethered ligands by APC by cleavage at Arg46 on PAR1
-
-
?
pyroGlu-Pro-Arg-4-nitroanilide + H2O
pyroGlu-Pro-Arg + 4-nitroaniline
-
S-2366
-
-
?
pyroGlu-Pro-Arg-4-nitroanilide + H2O
pyroGlu-Pro-Arg + 4-nitroaniline
-
S-2366, APC is labeled with AF546
-
-
?
Tie2 + H2O
?
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
-
-
?
Z-Gly-Gly-Arg-7-amido-4-methylcoumarin + H2O
?
-
a fluorogenic substrate, S-2366
-
-
?
additional information
?
-
-
no effect on the coagulation activity of factor XII, factor XI, factor X, factor IX, factor VII or prothrombin
-
-
?
additional information
?
-
-
identification of the binding site for activated protein C on the light chains of factors V and VIII
-
-
?
additional information
?
-
-
role of protein C in the regulation of blood coagulation
-
-
?
additional information
?
-
-
activated protein C complexes with protein S on the surface of either platelets or the endothelium, these complexes catalyze the proteolytic inactivation of factors Va and VIIIa
-
-
?
additional information
?
-
-
potential role of the enzyme in blood coagulation and hemostasis
-
-
?
additional information
?
-
-
the enzyme is one of the gamma-carboxyglutamic acid-containing coagulation factors. It is formed by protein C, the proenzyme that circulates in plasma, by the action of a complex of thrombin with thrombomodulin or by serine endopeptidases present in several snake venoms
-
-
?
additional information
?
-
-
the enzyme is one of the gamma-carboxyglutamic acid-containing coagulation factors. It is formed by protein C, the proenzyme that circulates in plasma, by the action of a complex of thrombin with thrombomodulin or by serine endopeptidases present in several snake venoms
-
-
?
additional information
?
-
-
the enzyme is one of the gamma-carboxyglutamic acid-containing coagulation factors. It is formed by protein C, the proenzyme that circulates in plasma, by the action of a complex of thrombin with thrombomodulin or by serine endopeptidases present in several snake venoms
-
-
?
additional information
?
-
-
does not seem to be necessary for blood coagulation
-
-
?
additional information
?
-
-
bovine enzyme preferentially hydrolyzes the major form of octanoylated ghrelin(28), i.e. about twice as much hydrolysis as is observed for a longer acyl chain of decanoylated ghrelin(28). But both acyl and desacyl ghrelin are hydrolyzed at the peptidebond between Arg15 and Lys16, generating an N-terminal peptide consisting of the first 15 residues
-
-
?
additional information
?
-
-
the enzyme is able to accomodate large hydrophobic residues such as phenylalanine and leucine in the P2 position. In the P3 position, the enzyme prefers an apolar D-amino acid residue
-
-
?
additional information
?
-
-
conversion of glutamic acid 192 to glutamine in activated protein C changes the substrate specificity
-
-
?
additional information
?
-
-
specificity: substrates with arginine in the P1 position have the highest activity
-
-
?
additional information
?
-
-
role of protein C in the regulation of blood coagulation
-
-
?
additional information
?
-
-
activated protein C complexes with protein S on the surface of either platelets or the endothelium, these complexes catalyze the proteolytic inactivation of factors Va and VIIIa
-
-
?
additional information
?
-
-
physiological relevance of the protein C anticoagulant pathway
-
-
?
additional information
?
-
-
the enzyme is one of the gamma-carboxyglutamic acid-containing coagulation factors. It is formed by protein C, the proenzyme that circulates in plasma, by the action of a complex of thrombin with thrombomodulin or by serine endopeptidases present in several snake venoms
-
-
?
additional information
?
-
-
the enzyme is one of the gamma-carboxyglutamic acid-containing coagulation factors. It is formed by protein C, the proenzyme that circulates in plasma, by the action of a complex of thrombin with thrombomodulin or by serine endopeptidases present in several snake venoms
-
-
?
additional information
?
-
-
human umbilical vein endothelial cells respond to stimulation by enzyme with induction of COX-2-expression, enzyme promotes upregulation of prostanoid production in human endothelium
-
-
?
additional information
?
-
-
activated protein C acts as feedback inhibitor of thrombin production
-
-
?
additional information
?
-
-
activated protein C downregulates p38 mitogen-activated protein kinase p53 and improves clinical parameters in an in-vivo model of septic shock, overview, the activated enzyme prevents acidosis and tends to improve heart rate responses to endotoxia
-
-
?
additional information
?
-
-
activated protein C has endothelial barrier protective effects that require binding to endothelial protein C receptor, EPCR, and cleavage of protease activated receptor-1, PAR1, and that may play a role in the anti-inflammatory action of APC, thrombin does not exert directly barrier protective effects, overview
-
-
?
additional information
?
-
-
activated protein C has potent anticoagulant and antiinflammatory properties that are mediated in part by its interactions with its cofactor protein S and the endothelial cell protein C receptor, EPCR, the protein C/APC Gla domain is implicated in both interactions
-
-
?
additional information
?
-
-
activated protein C is a physiological anticoagulant, it also exerts anti-inflammatory and antiapoptotic effects, activated protein C inhibits the production of TNF, IL-1beta, IL-6, and IL-8 and inhibits camptothecin-induced apoptosis in a dose-dependent manner in the LPS-stimulated immortalized human monocytic cell line THP-1, activated protein C inhibited spontaneous apoptosis in primary blood monocytes from healthy individuals, activated protein C does not influence the phagocytic internalization of Gram-negative and Gram-positive bioparticles by THP-1 cells or by primary blood monocytes, it does not affect the expression of adhesion molecules by LPS-stimulated blood monocytes nor the ability of monocytes to adhere to LPS-stimulated endothelial cells
-
-
?
additional information
?
-
-
activated protein C is a plasma serine protease with systemic anticoagulant, anti-inflammatory and antiapoptotic activities, and direct vasculoprotective and neuroprotective activities, it blocks tissue plasminogen activator-mediated brain hemorrhage after transient brain ischemia and embolic stroke in mice, overview, APC inhibits a pro-hemorrhagic tissue plasminogen activator-induced, NF-kappaB-dependent matrix metalloproteinase-9 pathway in ischemic brain endothelium in vivo and in vitro by acting through protease-activated receptor 1, overview
-
-
?
additional information
?
-
-
activated protein C reduces mortality in severe sepsis patients and exhibits beneficial effects in multiple animal injury models. APC anticoagulant activity involves inactivation of factors Va and VIIIa, whereas APC cytoprotective activities involve the endothelial protein C receptor and protease-activated receptor-1, PAR-1, anticoagulantly active APC inhibits secondary extended thrombin generation and concomitant thrombin dependent activation of thrombin activable fibrinolysis inhibitor in plasma, both recombinant wild-type and mutant APCs inhibit staurosporine-induced endothelial cell apoptosis
-
-
?
additional information
?
-
-
in addition to an anticoagulant activity, activated protein C also exhibits anti-inflammatory and cytoprotective properties, but can cause bleeding because of its anticoagulant function, the cytoprotective activity of APC is mediated through inhibition of caspase-3 activity
-
-
?
additional information
?
-
-
protein C has antiinflammatory, anticoagulant and pro-fibrinolytic activities in humans, counteracting some of the main pro-inflammatory pathophysiological mechanisms in sepsis, overview, the antithrombotic effect is caused by irreversible inactivation of factors Va and VIIIa, the anti-inflammatory activity reduces formation of TNF, IL-8, IL-6 and thrombin and limits the rolling of monocytes and neutrophils on injured endothelium by binding selectins, it may reduce apoptosis, the pro-fibrinolytic activity occurs due to inhibition of PAI-1 and indirectly via reduced thrombin and thrombin-activatable fibrinolysis inhibitor
-
-
?
additional information
?
-
-
recombinant activated protein C enhances intracellular antibacterial activity, against Escherichia coli strain ATCC 25922, in presence of antibiotics, e.g. levofloxacin or ampicillin, but has no antibacterial effects without antibiotics, while it decreases the production of cytokines, such as TNF-alpha, IL-1beta and interleukin-6, but not interleukin-8, by monocytes
-
-
?
additional information
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the activated enzyme induces signal transduction in an endothelial protein C receptor- or PAR1-dependent manner involved in apoptosis, microcirculation, and vascular permeability, the activated enzyme plays an important role in sepsis, but does not protect against sepsis, effects of long time treatment, overview, the activated enzyme induces expression of monocyte chemoattractant protein-1, MCP-1, in endothelial cells, overview
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the activated protein C constitutes an important natural coagulation inhibitor and key regulator of both coagulation and inflammation
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the enzyme has anticoagulant, antiapoptotic, and cytoprotective activities, mechanisms, overview, severe homozygous enzyme-deficiency causes massive, usually lethal thrombotic complications that arise in infants, heterozygous adults show a risk for venous thrombosis
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the enzyme is a serine protease that regulates thrombin production through inactivation of blood coagulation factors Va and VIIIa, overview, treatment of breast cancer cells with exogenous active enzyme leads to increased invasion and chemotaxis, thereby not acting as a chemoattractant, but via endothelial protein C receptor and protease-activated receptor-1, PAR-1, receptor blocking b antibodies blocks the enzyme effects, overview, the enzyme does not increase cell division and proliferation
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the enzyme shows anticoagulation activity and can prolonge life of sepsis patients, but can also cause hemorrhage, mechanism of action and biological effects, detailed overview
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the protein C pathway plays a key role in the regulation of blood coagulation, APC inhibits thrombin generation, and functions as a physiological anticoagulant with cytoprotective, anti-inflammatory and anti-apoptotic properties, mechanisms, overview, APC exerts its protective effects via an intriguing mechanism requiring endothelial protein C receptor and the thrombin receptor, protease-activated receptor-1, but even though APC cleaves this receptor in an identical fashion to thrombin, it exerts opposing effects, overview, administration of APC leads to reduced mortality in a subset of patients with severe sepsis, APC improves cerebral blood flow in the ischemic hemisphere and markedly reduces the volume of brain injury caused by middle cerebral vein occlusion effects, APC dramatically inhibits NFkappa B activity and TNF-alpha in monocytes from rheumatoid arthritis patients, APC protects against diabetic nephropathy by inhibiting endothelial and podocyte apoptosis, APC may have beneficial effects in patients with inflammatory lung diseases, APC stimulates new blood vessel formation and ectodermal epithelial cells to grow across the top of the gelatin sponge in the chorio-allantoic membrane assay
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the recombinant enzyme shows antithrombotic and anticoagulant effects in a rat model of arterial thrombosis, overview
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the recombinant human activated protein C affects apoptosis-related proteins, e.g. Bcl-2, p21, and p53, in mice, and reduces mortality in patients with severe sepsis, mechanism, overview
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the serine protease has antithrombotic and antiinflammatory activities, that play an important role in vascular function, APC inhibits TNF-related apoptosis-inducing ligand expression and secretion and its induction by cell activation, mechanism, overview, APC affects signal transduction by increasing ERK phosphorylation, overview
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APC inhibits a pro-hemorrhagic tissue plasminogen activator-induced, NF-kappaB-dependent matrix metalloproteinase-9 pathway in ischemic brain endothelium in vivo and in vitro by acting through protease-activated receptor 1
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recombinant activated protein C upregulates the release of soluble fractalkine, a unique endothelial cell-derived chemokine that functions both as a chemoattractant and as an adhesion molecule, from human umbilical vein endothelial cells about 2.5fold, PAR-1- and PAR-2-agonist peptides stimulate the fractalkine release, the protein C zymogen is inactive, overview
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the enzyme is a vitamin K-dependent serine protease
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the recombinant enzyme shows in vitro anticoagulant activity alone and in combination with melagatran, a thrombin inhibitor, and with unfractionated or low molecular weight heparins, overview
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activated protein C treatment of human neutrophils results in a decreased interleukin-6 expression in a concentration-dependent manner and a decreased chemotaxis, without affecting other cytokines, apoptosis, or respiratory burst activity
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directly binds to beta1 and beta3 integrins and inhibits neutrophil migration, both in vitro and in vivo. Activated protein C possesses an Arg-Gly-Asp sequence, which is critical for the inhibition. The enzyme does not functionally alter the signaling pathway associated with chemotaxis receptors on neutrophil
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patients with frequent arteriovenous fistula/graft failures have a significantly lower level of APC-protein C inhibitor complex in plasma than those with less frequent arteriovenous fistula/graft failures
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pretreatment of endothelial monolayers with recombinant activated protein C concentrations (10-25 nmol) leads to significantly decreased adhesion of B16-F10 melanoma cells. A 44% reduction in lung metastases in recombinant activated protein C-treated compared with control mice. Recombinant activated protein C markedly decreases tumor cell entrapment within the liver of mice
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treatment of lipopolysaccharide-stimulated blood monocytes with recombinant activated protein C results in an upregulation of interleukin-10 protein production and mRNA synthesis and a downregulation of tissue factor Ag and activity levels. Serine protease activity is required for the upregulation of interleukin-10 by recombinant activated protein C
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APC activates Tie2, a tyrosine kinase receptor, not through its major ligand, angiopoietin-1, but instead by binding to endothelial protein C receptor, cleaving protease-activated receptor-1 and transactivating EGF receptor
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APC upregulates TNF receptor-associated factor 2, TRAF2, and phosphorylates NF-kappaB p65 at Ser276 and Ser536 independently of IkappaB degradation, real-time quantitative PCR analysis, overview
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lower concentrations of APC, 300-30000 ng/ml, show a cell-protective effect against hypoxia in vitro, whereas higher concentrations of about 0.120 mg/ml demonstrate cytotoxicity in both RPE and photoreceptor cells
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APC activity is measured using the commercial chromogenic substrate Spectrozyme PCa
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CRVO-induced retinal cell apoptosis is reduced dramatically by intravitreal injection of APC
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P4-P3' residues flanking cleavage sites in factors VIIIa and Va, overview
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cleavage of protease activated receptor 3 zymogen by thrombin at Lys38 fails to induce PAR3-dependent intracellular signaling pathways but rather activates PAR1 and PAR2
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both acyl and desacyl ghrelin are hydrolyzed at the peptide bond between Arg15 and Lys16, generating an N-terminal peptide consisting of the first 15 residues
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the enzyme has anticoagulant, antiapoptotic, and cytoprotective activities, murine injury models, mechanisms, overview
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both acyl and desacyl ghrelin are hydrolyzed at the peptide bond between Arg15 and Lys16, generating an N-terminal peptide consisting of the first 15 residues
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both acyl and desacyl ghrelin are hydrolyzed at the peptide bond between Arg15 and Lys16, generating an N-terminal peptide consisting of the first 15 residues
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the protein C pathway plays an important role in vascular function, and acquired deficiency during sepsis is associated with increased organ damage and dysfunction, and mortality, cecal ligation and puncture model, overview, activated protein C acts as feedback inhibitor of thrombin production and has receptor-mediated anti-inflammatory and cytoprotective effects, treatment with activated protein C results in suppression of cytokine response and improved organ function
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the activated protein C reduces endotoxin-induced white matter injury in the developing rat brain, the activated enzyme attenuates the lipopolysaccharide-induced protein expression of inflammatory cytokines, tumor necrosis factor-alpha, nd interleukin-6 in treated brains, overview
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activated protein C downregulates p38 mitogen-activated protein kinase p53 and improves clinical parameters in an in-vivo model of septic shock, overview
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