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
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3.4.21.69
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thrombosis
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venous
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leiden
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sepsis
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endothelial
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antithrombin
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thromboembolism
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thrombophilia
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clot
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thrombomodulin
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platelet
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procoagulant
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heparin
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arterial
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vein
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bleeding
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plasminogen
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hypercoagulable
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thromboplastin
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lupus
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fibrinogen
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fibrinolysis
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hemostatic
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viiia
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epcr
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intravascular
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contraceptive
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antiphospholipid
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antithrombotic
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prothrombotic
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fibrin
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k-dependent
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anticardiolipin
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d-dimers
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coagulopathy
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embolism
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prothrombinase
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amidolytic
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thrombin-antithrombin
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haemostasis
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par1
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profibrinolytic
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pharmacology
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goal-directed
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diagnostics
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drug development
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gamma-carboxyglutamic
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deep-vein
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time-based
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tafi
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hypofibrinolysis
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thromboprophylaxis
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medicine
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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
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results (Natural Substrates Products
Natural Substrates Products on EC 3.4.21.69 - Protein C (activated)
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NATURAL SUBSTRATE 
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
active factor Va + H2O
inactive factor V heavy chain + peptide fragment 307-709
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proteolytic inactivation
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-
?
active factor VIII + H2O
inactive factor VIII + domain B
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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
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-
?
protease activated receptor 3 zymogen H2O
active protease activated receptor 3 + ?
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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
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-
?
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
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-
?
active factor Va + H2O
inactive factor V + ?
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proteolytic inactivation
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-
?
active factor Va + H2O
inactive factor V + ?
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proteolytic inactivation of the cofactor in the prothrombinase complex
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-
?
active factor Va + H2O
inactive factor V + domain B
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proteolytic inactivation
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-
?
active factor Va + H2O
inactive factor V + domain B
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activated protein C inhibits the procoagulant function of activated factor V through proteolytic cleavage
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-
?
active factor Va + H2O
inactive factor V + domain B
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proteolytic inactivation requires interactions with both EPCR and PAR-1
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-
?
active factor VIIIa + H2O
inactive factor VIII + domain B
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proteolytic inactivation
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-
?
active factor VIIIa + H2O
inactive factor VIII + domain B
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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
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-
?
Factor Va + H2O
?
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natural anticoagulant, inhibits thrombin generation by degrading factors Va and VIIIa
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?
Factor Va + H2O
?
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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
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?
Factor Va + H2O
?
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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
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-
?
Factor Va + H2O
?
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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
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-
?
Factor Va + H2O
?
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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
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-
?
Factor Va + H2O
?
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cleavage at Arg306, Arg506, and Arg679 of the heavy chain
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-
?
Factor Va + H2O
?
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inactivation through cleavage at Arg306, Arg506, and Arg679
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-
?
Factor VIIIa + H2O
?
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natural anticoagulant, inhibits thrombin generation by degrading factors Va and VIIIa
-
?
Factor VIIIa + H2O
?
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natural anticoagulant, inhibits thrombin generation by degrading factors Va and VIIIa
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?
Factor VIIIa + H2O
?
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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
?
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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
?
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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
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-
?
Factor VIIIa + H2O
?
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APC cleaves factor VIIIa at two peptide bonds, Arg336 and Arg562
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-
?
Factor VIIIa + H2O
?
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inactivation through cleavages at Arg336 in the A1 subunit and Arg562 in the A2 subunit
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-
?
ghrelin + H2O
?
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ghrelin is converted into smaller fragments in blood plasma in circulation under thrombotic and inflammatory conditions
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-
?
ghrelin + H2O
?
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ghrelin is converted into smaller fragments in blood plasma in circulation under thrombotic and inflammatory conditions
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-
?
ghrelin + H2O
?
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ghrelin is converted into smaller fragments in blood plasma in circulation under thrombotic and inflammatory conditions
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-
?
ghrelin + H2O
?
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ghrelin is converted into smaller fragments in blood plasma in circulation under thrombotic and inflammatory conditions
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-
?
protease activated receptor 1 + H2O
?
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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
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-
?
protease activated receptor 1 + H2O
?
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APC exhibits cytoprotective and antiinflammatory activity through the endothelial protein C receptor-dependent cleavage of protease activated receptor 1, PAR-1, on endothelial cells
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-
?
additional information
?
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role of protein C in the regulation of blood coagulation
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-
?
additional information
?
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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
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-
?
additional information
?
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potential role of the enzyme in blood coagulation and hemostasis
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-
?
additional information
?
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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
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-
?
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
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-
?
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
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-
?
additional information
?
-
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does not seem to be necessary for blood coagulation
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-
?
additional information
?
-
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role of protein C in the regulation of blood coagulation
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-
?
additional information
?
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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
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-
?
additional information
?
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physiological relevance of the protein C anticoagulant pathway
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-
?
additional information
?
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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
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-
?
additional information
?
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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
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?
additional information
?
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activated protein C acts as feedback inhibitor of thrombin production
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?
additional information
?
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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, the activated enzyme prevents acidosis and tends to improve heart rate responses to endotoxia
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?
additional information
?
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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
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-
?
additional information
?
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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
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?
additional information
?
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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
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?
additional information
?
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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
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?
additional information
?
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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
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?
additional information
?
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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
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?
additional information
?
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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
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-
?
additional information
?
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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
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?
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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?
additional information
?
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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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?
additional information
?
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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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?
additional information
?
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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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?
additional information
?
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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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?
additional information
?
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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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?
additional information
?
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the recombinant enzyme shows antithrombotic and anticoagulant effects in a rat model of arterial thrombosis, overview
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?
additional information
?
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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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?
additional information
?
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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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?
additional information
?
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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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?
additional information
?
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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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?
additional information
?
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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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?
additional information
?
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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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?
additional information
?
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the enzyme has anticoagulant, antiapoptotic, and cytoprotective activities, murine injury models, mechanisms, overview
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?
additional information
?
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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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?
additional information
?
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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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?
