3.4.21.5: thrombin
This is an abbreviated version!
For detailed information about thrombin, go to the full flat file.
Word Map on EC 3.4.21.5
-
3.4.21.5
-
platelet
-
anticoagulant
-
heparin
-
thrombosis
-
bleeding
-
endothelial
-
artery
-
thromboplastin
-
collagen
-
agonist
-
thromboembolism
-
coronary
-
procoagulant
-
adp
-
antithrombotic
-
venous
-
fibrinolysis
-
thrombus
-
hemorrhage
-
hemostatic
-
hirudin
-
plasminogen
-
antiplatelet
-
thrombomodulin
-
protease-activated
-
arachidonic
-
plasmin
-
thromboxane
-
intravascular
-
viii
-
d-dimers
-
atrial
-
thrombocytopenia
-
aspirin
-
aptamer
-
hypercoagulability
-
willebrand
-
warfarin
-
percutaneous
-
p-selectin
-
rivaroxaban
-
platelet-rich
-
unfractionated
-
coagulopathy
-
prothrombotic
-
embolism
-
haemostasis
-
diagnostics
-
analysis
-
hemophilia
-
biotechnology
-
thrombolytic
-
nutrition
-
synthesis
-
clopidogrel
-
medicine
- 3.4.21.5
- platelet
-
anticoagulant
- heparin
- thrombosis
- bleeding
- endothelial
- artery
- thromboplastin
- collagen
- agonist
- thromboembolism
- coronary
-
procoagulant
- adp
-
antithrombotic
- venous
-
fibrinolysis
- thrombus
- hemorrhage
-
hemostatic
- hirudin
- plasminogen
-
antiplatelet
- thrombomodulin
-
protease-activated
-
arachidonic
- plasmin
-
thromboxane
-
intravascular
- viii
-
d-dimers
- atrial
- thrombocytopenia
- aspirin
- aptamer
- hypercoagulability
- willebrand
- warfarin
-
percutaneous
-
p-selectin
- rivaroxaban
-
platelet-rich
-
unfractionated
- coagulopathy
-
prothrombotic
- embolism
-
haemostasis
- diagnostics
- analysis
- hemophilia
- biotechnology
-
thrombolytic
- nutrition
- synthesis
- clopidogrel
- medicine
Reaction
selective cleavage of Arg-/-Gly bonds in fibrinogen to form fibrin and release fibrinopeptides A and B =
Synonyms
activated factor II, alpha-thrombin, alphaTh, beta-thrombin, blood-coagulation factor II, activated, blood-coagulation factor IIa, clotting factor IIa, EC 3.4.4.13, factor IIa, fibrinogenase, thrombase, thrombin, E, thrombin-C, thrombofort, TLE2, topical, tropostasin
ECTree
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Substrates Products
Substrates Products on EC 3.4.21.5 - thrombin
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REACTION DIAGRAM
Ac-Gly-Gly-Val-Arg-7-amido-4-methylcoumarin + H2O
Ac-Gly-Gly-Val-Arg + 7-amino-4-methylcoumarin
-
-
-
?
Ac-Leu-Gly-Val-Arg-7-amido-4-methylcoumarin + H2O
Ac-Leu-Gly-Val-Arg + 7-amino-4-methylcoumarin
-
-
-
?
Ac-Nle-Thr-Leu-Arg-7-amido-4-methylcoumarin + H2O
Ac-Nle-Thr-Leu-Arg + 7-amino-4-methylcoumarin
-
-
-
?
Ac-Nle-Thr-Pro-Arg-7-amido-4-methylcoumarin + H2O
Ac-Nle-Thr-Pro-Arg + 7-amino-4-methylcoumarin
-
-
-
?
Ac-Val-Thr-Pro-Arg-7-amido-4-methylcoumarin + H2O
Ac-Val-Thr-Pro-Arg + 7-amino-4-methylcoumarin
-
-
-
?
Ala-Ala-Pro-Phe-4-nitroanilide + H2O
Ala-Ala-Pro-Phe + 4-nitroaniline
-
synthetic chromogenic substrate
-
?
beta-Ala-Gly-Arg-4-nitroanilide + H2O
beta-Ala-Gly-Arg + 4-nitroaniline
-
-
-
-
?
D-Phe-L-pipecolyl-L-Arg-4-nitroanilide + H2O
D-Phe-L-pipecolyl-L-Arg + 4-nitroaniline
-
-
-
-
?
D-Phe-Pip-Arg-4-nitroanilide + H2O
D-Phe-Pip-Arg + 4-nitroaniline
-
i.e. S-2238
-
-
?
D-phenylalanyl-pipecolyl-L-arginine-4-nitroanilide + H2O
D-phenylalanyl-pipecolyl-L-arginine + 4-nitroaniline
di-L-Glu-L-Pro-L-Arg-4-nitroanilide + H2O
di-L-Glu-L-Pro-L-Arg + 4-nitroaniline
-
-
-
-
?
factor VIII mutant D392A/D394A + H2O
?
-
reduction in specific activity similar to a severe hemophilia phenotype. No cleavage at R740, while cleavage at R372 is not affected
-
-
?
factor VIII mutant Q370E/I371P/V374F/A375S + H2O
?
-
-
mutation to P3-P3' residues flanking Arg740, 98% of the activtiy with wild-type
-
?
factor VIII mutant Q370S/I371P/V374F/A375Q + H2O
?
-
-
mutation to P3-P3' residues flanking Arg1689, 14% of the activtiy with wild-type
-
?
factor VIII mutant R372H + H2O
?
-
naturally occuring mutation in hemophilia A patients. About 80fold decrease in cleavage rate compared to wild-type substrate, cleavage at H372-S373 bond
-
-
?
factor VIII(341-376) peptide + H2O
?
-
cleavage of Arg372 involving exosite II, the heparin binding site
-
?
factor XIII V34L mutant + H2O
activated factor XIII V34L mutant + ?
-
binding structure and interaction analysis, mutant substrate, a polymorphism exists within the activation peptide segment at the P4 position of FXIII resulting in substitution V34L, FXIII V34L occurs in approximately 30% of the human population worldwide, overview
-
-
?
Fc-[GRPS]-PEG + H2O
?
-
ferrocene-labelled tetrapeptide with a polyethylene glycol linker
-
-
?
Fc-[RFSRPQL]-PEG + H2O
?
-
ferrocene-labelled heptapeptide with a polyethylene glycol linker
-
-
?
fibrin I-plasma factor XIII complex + H2O
activation peptide + fibrinopeptide B
-
-
-
?
GLVPRGVNL + H2O
GLVPR + GVNL
-
residues 33-41 of factor XIII with mutation V34L
-
-
?
HD-cyclohexylglycyl-Ala-Arg-4-nitroanilide + H2O
HD-cyclohexylglycyl-Ala-Arg + 4-nitroaniline
-
assay method optimization with synthetic substrate HD-cyclohexylglycyl-Ala-Arg-4-nitroanilide, overview
-
-
?
N-(4-tosyl)-Gly-L-Pro-L-Arg-4-nitroanilide + H2O
N-(4-tosyl)-Gly-L-Pro-L-Arg + 4-nitroaniline
-
-
-
-
?
N-p-tosyl-Gly-Pro-Arg-4-nitroanilide + H2O
N-p-tosyl-Gly-Pro-Arg + 4-nitroaniline
-
-
-
-
?
Nalpha-benzyloxycarbonyl-L-Arg 4-nitrophenyl ester + H2O
Nalpha-benzyloxycarbonyl-L-Arg + 4-nitrophenol
-
-
-
-
?
Nalpha-benzyloxycarbonyl-L-Lys 4-nitrophenyl ester + H2O
Nalpha-benzyloxycarbonyl-L-Lys + 4-nitrophenol
-
-
-
-
?
PAR1 peptide + H2O
?
protease-activated receptor I peptide fragment, amino acid sequence
-
?
pro-factor XIII + H2O
factor XIII
-
activation by cleavage at Arg37 leading to blood coagulation
-
?
protease-activated receptor + H2O
activated protease-activated receptor + ?
-
activation
-
-
?
protease-activated receptor 1 + H2O
activated protease-activated receptor 1 + ?
-
activation
-
-
?
protease-activated receptor 4 + H2O
activated PAR-4 + ?
-
the cleaved form of protease-activated receptor 3, PAR-3, acts as a cofactor for thrombin cleavage and activation of PAR-4 on murine platelets, interaction analysis of thrombin with the extracellular part of PAR-4, overview
-
-
?
protease-activated receptor-1 + H2O
activated PAR-1
-
i.e. PAR-1, activation, major thrombin receptor
product induces connective tissue growth factor production, a fibroblast mitogen, which promotes extracellular matrix protein production
?
protein G + H2O
?
thrombin is able to cleave protein G, within its alpha-helix when a suitable cleavage sequence for the enzyme is introduced into this region. Thrombin is only cleaving within the alpha-helix when it is in an unfolded state. The introduction of destabilizing mutations within the protein increases the efficiency of cleavage by the enzyme
-
-
?
proteinase-activated receptor 1 + H2O
?
-
alpha-thrombin may not effectively catalyze proteinase-activated receptor 1-(1-41) generation
-
-
?
proteinase-activated receptor 4 + H2O
?
-
alpha-thrombin may not effectively catalyze proteinase-activated receptor 4-(1-47) generation
-
-
?
tosyl-Gly-L-Pro-L-Arg-4-nitroanilide + H2O
tosyl-Gly-L-Pro-L-Arg + 4-nitroaniline
-
-
-
-
?
TVELQGLVPRGVNL + H2O
TVELQGLVPR + GVNL
-
residues 28-41 of factor XIII with mutation V34L
-
-
?
?
-
proteolysis of ADAMTS-13 by thrombin causes an 8fold reduction in its affinity for von Willebrand factor VWF that contributes to its loss of VWF-cleaving function, physiologic function, overview
-
-
?
ADAMTS-13 + H2O
?
-
inactivation by cleavage at R257 and R1176, substrate is the plasma metalloprotease, a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13, no activity with R257A and R1176H ADAMTS-13 mutants
-
-
?
D-Phe-L-Pro-L-Arg + 4-nitroaniline
-
-
-
-
?
D-Phe-L-Pro-L-Arg-4-nitroanilide + H2O
D-Phe-L-Pro-L-Arg + 4-nitroaniline
-
-
-
-
?
D-Phe-L-Pro-L-Phe + 4-nitroaniline
-
-
-
-
?
D-Phe-L-Pro-L-Phe-4-nitroanilide + H2O
D-Phe-L-Pro-L-Phe + 4-nitroaniline
-
-
-
-
?
D-Phe-Pro-Arg + 4-nitroaniline
-
-
-
-
?
D-Phe-Pro-Arg-4-nitroanilide + H2O
D-Phe-Pro-Arg + 4-nitroaniline
-
synthetic chromogenic substrate
-
?
D-Phe-Pro-Lys-4-nitroanilide + H2O
D-Phe-Pro-Lys + 4-nitroaniline
-
synthetic chromogenic substrate
-
?
D-phenylalanyl-pipecolyl-L-arginine + 4-nitroaniline
-
i.e. S2238, synthetic chromogenic substrate
-
?
D-phenylalanyl-pipecolyl-L-arginine-4-nitroanilide + H2O
D-phenylalanyl-pipecolyl-L-arginine + 4-nitroaniline
-
-
-
-
?
D-phenylalanyl-pipecolyl-L-arginine-4-nitroanilide + H2O
D-phenylalanyl-pipecolyl-L-arginine + 4-nitroaniline
-
-
-
?
D-phenylalanyl-pipecolyl-L-arginine-4-nitroanilide + H2O
D-phenylalanyl-pipecolyl-L-arginine + 4-nitroaniline
-
i.e. S2238, synthetic chromogenic substrate
-
?
D-phenylalanyl-pipecolyl-L-arginine-4-nitroanilide + H2O
D-phenylalanyl-pipecolyl-L-arginine + 4-nitroaniline
-
i.e. S2238, synthetic chromogenic substrate
-
?
D-phenylalanyl-pipecolyl-L-arginine-4-nitroanilide + H2O
D-phenylalanyl-pipecolyl-L-arginine + 4-nitroaniline
-
i.e. S2238, synthetic chromogenic substrate
-
?
D-phenylalanyl-pipecolyl-L-arginine-4-nitroanilide + H2O
D-phenylalanyl-pipecolyl-L-arginine + 4-nitroaniline
-
i.e. S2238, synthetic chromogenic substrate
-
?
D-phenylalanyl-pipecolyl-L-arginine-4-nitroanilide + H2O
D-phenylalanyl-pipecolyl-L-arginine + 4-nitroaniline
-
i.e. S2238, synthetic chromogenic substrate
-
?
D-phenylalanyl-pipecolyl-L-arginine-4-nitroanilide + H2O
D-phenylalanyl-pipecolyl-L-arginine + 4-nitroaniline
-
i.e. S2238, synthetic chromogenic substrate
-
?
D-phenylalanyl-pipecolyl-L-arginine-4-nitroanilide + H2O
D-phenylalanyl-pipecolyl-L-arginine + 4-nitroaniline
-
i.e. S2238, synthetic chromogenic substrate
-
?
D-phenylalanyl-pipecolyl-L-arginine-4-nitroanilide + H2O
D-phenylalanyl-pipecolyl-L-arginine + 4-nitroaniline
i.e. S2238, synthetic chromogenic substrate
-
?
D-phenylalanyl-pipecolyl-L-arginine-4-nitroanilide + H2O
D-phenylalanyl-pipecolyl-L-arginine + 4-nitroaniline
-
D-phenylalanyl-pipecolyl-L-arginine-4-nitroanilide is S2238
-
-
?
factor VIII + H2O
?
-
-
proteolysis occurs at residues Arg372 and Arg740 in the facto VIII heavy chain and Arg1689 in the factor VIII light chain. The sequences at Arg740 and Arg1689 are more optimal for thrombin cleavage than at Arg372. Rates of thrombin cleavage at Arg372 are increased about 10fold and about 3fold compared with wild-type factor VIII when replaced with P3-P3' residues flanking Arg740 or Arg1689, respectively, and these values parallel increased rates of A2 subunit generation and procofactor activation. Positioning of more optimal residues flanking Arg372 abrogates the need for initial cleavage at Arg740 to facilitate this step
-
?
factor VIII + H2O
?
-
activation by cleavage of Arg372, Arg74, and Arg1689 involving exosite II, the heparin binding site
-
?
factor VIII + H2O
?
-
activation by cleavage of Arg372, Arg74, and Arg1689, plays a fundamental role in the amplification of the coagulation cascade
-
?
factor VIII + H2O
factor VIIIa + propeptide
-
high affinity site in A1 subunit of substrate, dependent on Na+-bound form of enzyme. Moderate affinity site in A2 subunit, independent of Na+-state of enzyme
-
-
?
factor XII + H2O
activated factor XII + ?
-
activated factor XII cross-links fibrin molecules and stabilizes the fibrin clot
-
-
?
activated factor XIII + ?
-
the enzyme is involved in the coagulation cascade, overview
-
-
?
factor XIII + H2O
activated factor XIII + ?
-
binding structure and interaction analysis, wild-type substrate, overview
-
-
?
Fibrinogen + H2O
?
-
cleavage of four Arg-Gly peptide bonds, the enzyme is involved in the final step in the coagulation of mammalian blood
-
-
?
Fibrinogen + H2O
?
-
the fully reversible interaction of alpha-thrombin with glycoprotein Ibalpha supports the association with platelets of a proteolytically active enzyme that may contribute to activation
-
-
?
Fibrinogen + H2O
?
-
in intact human erythrocyte leucemia cells thrombin activates adenylate cyclase
-
-
?
fibrinogen + H2O
fibrin + ?
-
the enzyme mediates the conversion of fibrinogen to fibrin
-
-
?
fibrin + fibrinopeptide A + fibrinopeptide B
-
-
-
-
?
fibrinogen + H2O
fibrin + fibrinopeptide A + fibrinopeptide B
-
-
669516, 704797, 707320, 707506, 707511, 707652, 707672, 707944, 707960, 708032, 708154, 708178, 708248, 708363, 708811, 708816, 709043, 709050, 709074, 709109, 709161, 709242, 709437, 709468, 709588, 710103, 710224, 710402, 710594, 710604, 710610, 710634, 717085, 717199, 717789, 732938
-
-
?
fibrinogen + H2O
fibrin + fibrinopeptide A + fibrinopeptide B
-
proteolytic activation
-
?
fibrinogen + H2O
fibrin + fibrinopeptide A + fibrinopeptide B
-
proteolytic activation
-
?
fibrinogen + H2O
fibrin + fibrinopeptide A + fibrinopeptide B
proteolytic activation
-
?
fibrinogen + H2O
fibrin + fibrinopeptide A + fibrinopeptide B
-
proteolytic activation
fibrinopeptide A D49 binds to thrombin R67
?
fibrinogen + H2O
fibrin + fibrinopeptide A + fibrinopeptide B
-
strongly inverse solvent isotope effects on reaction
-
-
?
fibrinogen + H2O
fibrin + fibrinopeptide A + fibrinopeptide B
-
oxidation impairs the capacity of isolated fibrinogen to form a fibrin clot under the effect of thrombin
-
-
?
fibrinogen + H2O
fibrin + fibrinopeptide A + fibrinopeptide B
-
from human and salmon
-
?
fibrin 1 + fibrinopeptide A + fibrinopeptide B
-
-
-
?
fibrinogen 1 + H2O
fibrin 1 + fibrinopeptide A + fibrinopeptide B
-
-
-
?
fibrinogen 1 + H2O
fibrin 1 + fibrinopeptide A + fibrinopeptide B
-
human, composed of 2 gamma-chains, gamma A and gamma'
fibrin 1 contains a low affinity binding site in the E doamin, and a high affinity binding site at residues 408-427 of the gamma'-chain, sequence VRPEHPAETEYDSLYPEDDL, for thrombin exosites, binding study, overview
?
fibrin 2 + fibrinopeptide A + fibrinopeptide B
-
-
-
?
fibrinogen 2 + H2O
fibrin 2 + fibrinopeptide A + fibrinopeptide B
-
-
-
?
fibrinogen 2 + H2O
fibrin 2 + fibrinopeptide A + fibrinopeptide B
-
human, composed of 2 gamma-chains, gamma A and gamma'
fibrin 2 contains a low affinity binding site in the E doamin, and a high affinity binding site at residues 408-427 of the gamma'-chain, sequence VRPEHPAETEYDSLYPEDDL, for thrombin exosites, binding study, overview
?
?
-
although intact isoform G8L stimulates neutrophil adhesion to substrate more efficiently than isoform G8M, the activity of isoform G8L but not that of isoform G8M decreases on thrombin digestion, overview
-
-
?
galectin-8 + H2O
?
-
cleavage site is -IAPRT- residing within the linker peptide, isoforms with the longest linker peptide, galectin-8L and galectin-9L, are highly susceptible to thrombin cleavage, whereas the predominant isoforms, galectin-8M and galectin-9M, and other members of human galectin family so far examined are resistant to thrombin, overview, human and murine substrates, and recombinant GST-tagged wild-type and mutant substrate, sbstrate specificity, overview
-
-
?
?
-
thrombin treatment almost completely abolishes eosinophil chemoattractant activity of isoform G9L, overview
-
-
?
galectin-9 + H2O
?
-
cleavage site is -PRPRG- residing within the linker peptide, isoforms with the longest linker peptide, galectin-8L and galectin-9L, are highly susceptible to thrombin cleavage, whereas the predominant isoforms, galectin-8M and galectin-9M, and other members of human galectin family so far examined are resistant to thrombin, overview, human and murine substrates, and recombinant GST-tagged wild-type and mutant substrate, sbstrate specificity, overview
-
-
?
protease-activated receptor 1 + H2O
?
-
endothelial protein C receptor-dependent cleavage of PAR-1 on vascular endothelial cells, the enzyme exhibts anti-inflammatory activity
-
-
?
protease-activated receptor 1 + H2O
?
-
endothelial protein C receptor-dependent cleavage of PAR-1
-
-
?
protease-activated receptor 1 + H2O
?
-
thrombin inhibits the tumor necrosis factor-alpha-mediated expression of secretory group IIA phospholipase A2-IIA through the cleavage of protease-activated receptor 1, the EPCR-dependent cleavage of protease-activated receptor 1by thrombin increases the phosphorylation of extracellular signalregulated kinase 1/2
-
-
?
protease-activated receptor-1 + H2O
?
-
PAR-1 is the major mediator of thrombin signalling and is involved in platelet activation, smooth muscle cells migration and proliferation, PAR-1 activation also regulates many aspects of endothelial cell biology and has been involved in vascular development
-
-
?
protease-activated receptor-1 + H2O
?
-
fibrin-bound thrombin, specific cleavage by thrombin at the extracellular N-terminus
-
-
?
protein C + H2O
?
-
the mutation E229K shifts the substrate specificity of thrombin by 130fold to favor the activation of the anticoagulant substrate protein C over the procoagulant substrate fibrinogen
-
-
?
protein C + H2O
?
-
mutation E229A substantially shifts thrombin's specificity in favour of the anticoagulant substrate, protein C
-
-
?
protein C zymogen + H2O
activated protein C + propeptide
-
activated protein C has a regulatory function in inhibiting thrombin activation, overview
-
-
?
protein C zymogen + H2O
activated protein C + propeptide
-
on vascular endothelial cells
-
-
?
S2238 + H2O
?
-
fibrin-bound thrombin activity, measured by selective chromogenic substrate S2238
-
-
?
thrombin-activatable fibrinolysis inhibitor + H2O
?
-
mutant variants with variants in the amino acids surrounding the scissile R92-A93 bond such as P91S, R92K, and S90P exhibit specific impairment of activation by thrombin or thrombin/thrombomodulin
-
-
?
tosyl-Gly-Pro-Arg + 4-nitroaniline
-
-
-
?
tosyl-Gly-Pro-Arg-4-nitroanilide + H2O
tosyl-Gly-Pro-Arg + 4-nitroaniline
-
-
-
-
?
tosyl-Gly-Pro-Arg-4-nitroanilide + H2O
tosyl-Gly-Pro-Arg + 4-nitroaniline
-
-
-
?
additional information
?
-
determination of enzyme activity by active site titration with 4-nitrophenyl guanidino-benzoate
-
?
additional information
?
-
-
enzyme stimulates a marked increase in inositol phosphate accumulation, which is fully mimicked by a selective PAR1 activating peptide. Mitogenic effect of enzyme involves activation of PDGF or EGF receptors and a Gi/o-dependent activation of phosphoinositide 3-kinase. Enzyme stimulates phosphatidylinositol-3,4,5-triphosphate mass accumulation
-
-
?
additional information
?
-
-
thrombin is a multifunctional trypsin-like protease that plays a role in the blood coagulation system, stimulates platelet aggregation, and promotes its own generation through the activation of factor XI and cofactors V and VII
-
-
?
additional information
?
-
-
when binding to thrombomodulin, thrombin can activate the protein C to regulate coagulation by inhibiting thrombin generation
-
-
?
additional information
?
-
the enzyme shows no factor XIII activation activity
-
-
?
additional information
?
-
-
determination of residues involved in ligand binding, overview, interaction with receptors glycoprotein Ibalpha GpIb and protease-activated receptor I PARI in platelet membrane, thrombin recognition domains and insertion loops are responsible for substrate specificity determination and interaction with inhibitors, unique within serine proteases, thrombin can be at the same time very efficient and specific for different substrates and inhibitors, overview
-
?
additional information
?
-
interaction with receptors glycoprotein Ibalpha GpIb and protease-activated receptor 1, i.e. PAR1, in platelet membrane
-
?
additional information
?
-
-
interaction with receptors glycoprotein Ibalpha GpIb and protease-activated receptor 1, i.e. PAR1, in platelet membrane
-
?
additional information
?
-
-
structural requirements for enzyme activity
-
?
additional information
?
-
-
substrate specificity, peptide substrate library scanning
-
?
additional information
?
-
-
enzyme deficienxy leads to umbilical cord bleeding at birth, development of hematoma, diminished vitamin K-dependent clotting factor, thrombocytopenia, and at least to lethal retroperitoneal bleeding
-
?
additional information
?
-
-
enzyme exerts pro-inflammatory and profibrotic effects via proteolytic activation of the major thrombin receptor
-
?
additional information
?
-
-
enzyme is important in blood coagulation
-
?
additional information
?
-
-
enzyme plays a pivotal role in hemostasis, thrombosis, cell differentiation, and is involved in the activation of many cell types and platelets
-
?
additional information
?
-
-
enzyme stimulates platelets and exposure of phosphatidylserine on the external surface
-
?
additional information
?
-
-
a hirudin-like pentapeptide from the COOH terminus of factor Va heavy chain regulates the rate and pathway for prothrombin activation, prothrombinase complex regultion, overview
-
-
?
additional information
?
-
-
Na+ binding to thrombin is an interaction at the basis of the procoagulant and prothrombotic roles of the enzyme in the blood
-
-
?
additional information
?
-
-
the ligand occupancy of endothelial protein C receptor by caveolin-1 switches the protease-activated receptor 1-dependent signaling specificity of thrombin from a permeability-enhancing to a barrier-protective response in endothelial cells, overview
-
-
?
additional information
?
-
-
thrombin is initially implicated in hemostasis and fibrin clot formation, and is also involved in cell biology since the discovery of its major receptor, the protease-activated receptor-1, PAR-1, fibrin-adsorbed thrombin interacts with endothelial progenitor cells via the thrombin receptor PAR-1, overview
-
-
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additional information
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extensive interactions between thrombin and the gamma' peptide mediated by electrostatic contacts with residues of exosite II and hydrophobic interactions with a pocket in close proximity to the Na+ binding site, complex structure and binding mode, the gamma' peptide completely overlaps with heparin bound to exosite II, overview
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both thrombin and thrombin receptor agonist peptide enhance the permeability barrier of HPAEC cells, both exhibit a potent barrier protective effect when cells are treated with inactive mutant S195A of protein C prior to stimulation. Thrombin exhibits a potent cytoprotective activity in the lipopolysaccharide-induced permeability and tumor necrosis factor alpha-induced apoptosis and adhesion assays in the protein C mutant S195A treated cells. Treatment with the cholesterol depleting molecule methyl-beta-cyclodextrin eliminates the protective effect
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both thrombin and thrombin receptor agonist peptides initiate proinflammatory responses in cells. The occupancy of endothelial protein C receptor by the inactive protein C mutant S195A switches the receptor PAR-1-dependent signaling specificity of thrombin leading to thrombin inhibition of the expression of cell surface adhesion molecules CCAM-I, ICAM-I and E-selectin as well as the binding of neutrophils to tumor necrosis factor alpha-activated endothelial cells. Both thrombin and thrombin receptor agonist peptides activate Rac I and inhibit the activation of RhoA and nuclear factor kappaB pathways in response to tumor necrosis factor alpha in cells pretreated with protein C mutant S195A
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in cell cultures of HUVEC and HPAEC cells, low concentrations of thrombin or of receptor PAR-1 agonist peptide induce significant anti-inflammatory activities. Relatively high concentration of thrombin or of PAR-1 agonist peptide show pro-inflammatory activities. The direct anti-inflammatory effects of low concentrations of thrombin are dependent on the activation of PAR-1 and PI3 kinase
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treatment of platelets with thrombin or ADP induces activation and mitochondrial association of active proapoptotic proteins Bid, Bax, and Bak. Thrombin evokes mitochondrial membrane depolarization, which is attenuated by catalase
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citrullinated fibrinogen is no substrate. Thrombin does not catalyze the conversion of citrullinated fibrinogen to fibrin or relase fibrinopeptide A or fibrinopeptide B
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protein context, as well as the identity of amino acids at protease cleavage sites, dictate protease specificity
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thrombin is generated by proteolysis of its precursor prothrombin at sites of injury
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determination of the extended substrate recognition profile. The consensus recognition sequence is, P2-Pro, P1-Arg, P19-Ser/Ala/Gly/Thr, P29-not acidic and P39-Arg. Residue P39-arginine in thrombin substrates lacking a P2-proline plays an important role. Upon insertion of the consensus sequence obtained in a linker region between two Escherichia coli thioredoxin molecules, mutations of P2-Pro and P39-Arg lead to an approximate 20fold and 14fold reduction, respectively in the rate of cleavage. Mutating both Pro and Arg results in a drop in cleavage of 200-400 times. No natural substrates display the obtained consensus sequence but represent sequences that show only 1-30% of the optimal cleavage rate for thrombin. Major effects on cleavage efficiency are also observed for residues as far away as 4 amino acids from the cleavage site. Insertion of an aspartic acid in position P4 results in a drop in cleavage by a factor of almost 20 times
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although differences between the two thrombin (FIIa) preparations using ecarin cleavage are observed, FIIa derived from recombinant human FII administered to human would likely be very similar in activity and function as FIIa formed from endogenous FII
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although differences between the two thrombin (FIIa) preparations using ecarin cleavage are observed, FIIa derived from recombinant human FII administered to human would likely be very similar in activity and function as FIIa formed from endogenous FII
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electropositive regions at a distance from the active site, so called exosites, are of major importance for the cleavage by human thrombin. Addition of these regions enhance the cleavage rate by more than fifty fold. The enhancement is highly dependent on the sequence of the actual cleavage site. A minimal site that shows poor activity by itself can be cleaved as efficiently as an optimal cleavage site when presented together with these negatively charged regions. Sites conforming closely to the optimal site are only minimally enhanced by the addition of these regions
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electropositive regions at a distance from the active site, so called exosites, are of major importance for the cleavage by human thrombin. Addition of these regions enhance the cleavage rate by more than fifty fold. The enhancement is highly dependent on the sequence of the actual cleavage site. A minimal site that shows poor activity by itself can be cleaved as efficiently as an optimal cleavage site when presented together with these negatively charged regions. Sites conforming closely to the optimal site are only minimally enhanced by the addition of these regions
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nestin gene expression is regulated by the thrombin-mediated transactivation of EGFR in serum-deprived primary cultures of vascular smooth muscle cells. Upon binding of thrombin, regulator PAR-1 induces c-Src resulting in direct intracellular phosphorylation of EGFR and in the extracellular activation of the matrix metalloprotease MMP-2-mediated shedding of HB-epidermal growth factor
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the presence of thrombin induces a significant increase in matrix metalloprotease-9 activity and also increases its mRNA expression in primary astrocytes. Thrombin-induced matrix metalloprotease-9 production is inhibited by the selective inhibitor of protease-activated receptor PAR-1, SCH 79797 and by PDS98059
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enzyme stimulates platelets and exposure of phosphatidylserine on the external surface
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following activation of platelets by thrombin, 26 proteins exhibit statistically significant differences. Deregulated proteins include proteins of the coagulation system and integrin signalling
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