| + |
F2 | up-regulates activity 
cleavage,
|
F5 |
0.882 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-263631 |
Arg1046 |
HHAPLSPrTFHPLRS |
in vitro |
|
| pmid |
sentence |
| 10026263 |
Thrombin is considered the physiological activator of factor V and is the most potent activator, catalyzing the cleavage of three peptide bonds at Arg709, Arg1018, and Arg1545 |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-263632 |
Arg737 |
LAAALGIrSFRNSSL |
in vitro |
|
| pmid |
sentence |
| 10026263 |
Thrombin is considered the physiological activator of factor V and is the most potent activator, catalyzing the cleavage of three peptide bonds at Arg709, Arg1018, and Arg1545 |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-263530 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 29880919 |
Thrombin also activates the cofactors FVIII (to FVIIIa) and FV (to FVa) and activates platelets such that they provide a procoagulant membrane surface to which these proteins then bind |
|
| Publications: |
3 |
Organism: |
In Vitro, Homo Sapiens |
| Tissue: |
Blood Plasma |
| + |
F2 | up-regulates activity
cleavage
|
F8 |
0.753 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-263639 |
Arg1708 |
EDENQSPrSFQKKTR |
in vitro |
|
| pmid |
sentence |
| 10350471 |
Activation of factor VIII by thrombin occurs via limited proteolysis at R372, R740, and R1689. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-263640 |
Arg391 |
SPSFIQIrSVAKKHP |
in vitro |
|
| pmid |
sentence |
| 10350471 |
Activation of factor VIII by thrombin occurs via limited proteolysis at R372, R740, and R1689. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-263641 |
Arg759 |
KNNAIEPrSFSQNSR |
in vitro |
|
| pmid |
sentence |
| 10350471 |
Activation of factor VIII by thrombin occurs via limited proteolysis at R372, R740, and R1689. |
|
| Publications: |
3 |
Organism: |
In Vitro |
| + |
F2 | up-regulates activity
cleavage
|
F2R |
0.887 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-263568 |
Arg25 |
PLLSARTrARRPESK |
in vitro |
|
| pmid |
sentence |
| 10978167 |
PAR1E and PAR2E (10 microM) were incubated in the presence of the different proteases | The enzymes were used at the following concentrations: 0.5 unit/mL thrombin, 2.5 nM trypsin, 20 nM plasmin, 20 nM cathepsin G, 20 nM elastase, 20 nM proteinase 3, and 2 units/mL calpain I and II|Protease-activated receptors (PARs) mediate cell activation after proteolytic cleavage of their extracellular amino terminus.|Protease-activated receptors (PARs) mediate cell activation after proteolytic cleavage of their extracellular amino terminus.|Protease-activated receptors (PARs) mediate cell activation after proteolytic cleavage of their extracellular amino terminus |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-263569 |
Arg41 |
TNATLDPrSFLLRNP |
in vitro |
|
| pmid |
sentence |
| 10978167 |
Thrombin cleaved PAR1E at the Arg41-Ser42 activation site at concentrations known to induce cellular activation, supporting a native conformation of the recombinant polypeptide. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-263608 |
|
|
in vitro |
|
| pmid |
sentence |
| 10978167 |
Thrombin selectively cleaves PAR1, PAR3, and PAR4 to induce activation of platelets and vascular cells, |
|
| Publications: |
3 |
Organism: |
In Vitro |
| + |
GGCX | up-regulates activity
carboxylation
|
F2 |
0.667 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-263675 |
Glu49 |
RRANTFLeEVRKGNL |
in vitro |
|
| pmid |
sentence |
| 10556651 |
We analyzed the number of glutamic acid (Glu) residues and their positions in the Gla domain (GD) of DCP to investigate the gamma-carboxylation mechanism of VK-dependent carboxylase. Several DCPs were found in each subject studied. The 10 Gla residues of human prothrombin were carboxylated in order from the N-terminal (residues 26, 25, 16, 29, 20, 19, 14, 32, 7 and 6)|In the absence of VK or in the presence of VK antagonists, hepatic VKdependent carboxylase activity is inhibited and des-g-carboxyprothrombin (abnormal prothrombin or PIVKA; protein induced by vitamin K antagonist, prothrombin) is released into the blood. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-263676 |
Glu50 |
RANTFLEeVRKGNLE |
in vitro |
|
| pmid |
sentence |
| 10556651 |
We analyzed the number of glutamic acid (Glu) residues and their positions in the Gla domain (GD) of DCP to investigate the gamma-carboxylation mechanism of VK-dependent carboxylase. Several DCPs were found in each subject studied. The 10 Gla residues of human prothrombin were carboxylated in order from the N-terminal (residues 26, 25, 16, 29, 20, 19, 14, 32, 7 and 6)|In the absence of VK or in the presence of VK antagonists, hepatic VKdependent carboxylase activity is inhibited and des-g-carboxyprothrombin (abnormal prothrombin or PIVKA; protein induced by vitamin K antagonist, prothrombin) is released into the blood. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-263677 |
Glu57 |
EVRKGNLeRECVEET |
in vitro |
|
| pmid |
sentence |
| 10556651 |
We analyzed the number of glutamic acid (Glu) residues and their positions in the Gla domain (GD) of DCP to investigate the gamma-carboxylation mechanism of VK-dependent carboxylase. Several DCPs were found in each subject studied. The 10 Gla residues of human prothrombin were carboxylated in order from the N-terminal (residues 26, 25, 16, 29, 20, 19, 14, 32, 7 and 6)|In the absence of VK or in the presence of VK antagonists, hepatic VKdependent carboxylase activity is inhibited and des-g-carboxyprothrombin (abnormal prothrombin or PIVKA; protein induced by vitamin K antagonist, prothrombin) is released into the blood. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-263678 |
Glu59 |
RKGNLEReCVEETCS |
in vitro |
|
| pmid |
sentence |
| 10556651 |
We analyzed the number of glutamic acid (Glu) residues and their positions in the Gla domain (GD) of DCP to investigate the gamma-carboxylation mechanism of VK-dependent carboxylase. Several DCPs were found in each subject studied. The 10 Gla residues of human prothrombin were carboxylated in order from the N-terminal (residues 26, 25, 16, 29, 20, 19, 14, 32, 7 and 6)|In the absence of VK or in the presence of VK antagonists, hepatic VKdependent carboxylase activity is inhibited and des-g-carboxyprothrombin (abnormal prothrombin or PIVKA; protein induced by vitamin K antagonist, prothrombin) is released into the blood. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-263679 |
Glu62 |
NLERECVeETCSYEE |
in vitro |
|
| pmid |
sentence |
| 10556651 |
We analyzed the number of glutamic acid (Glu) residues and their positions in the Gla domain (GD) of DCP to investigate the gamma-carboxylation mechanism of VK-dependent carboxylase. Several DCPs were found in each subject studied. The 10 Gla residues of human prothrombin were carboxylated in order from the N-terminal (residues 26, 25, 16, 29, 20, 19, 14, 32, 7 and 6)|In the absence of VK or in the presence of VK antagonists, hepatic VKdependent carboxylase activity is inhibited and des-g-carboxyprothrombin (abnormal prothrombin or PIVKA; protein induced by vitamin K antagonist, prothrombin) is released into the blood. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-263680 |
Glu63 |
LERECVEeTCSYEEA |
in vitro |
|
| pmid |
sentence |
| 10556651 |
We analyzed the number of glutamic acid (Glu) residues and their positions in the Gla domain (GD) of DCP to investigate the gamma-carboxylation mechanism of VK-dependent carboxylase. Several DCPs were found in each subject studied. The 10 Gla residues of human prothrombin were carboxylated in order from the N-terminal (residues 26, 25, 16, 29, 20, 19, 14, 32, 7 and 6)|In the absence of VK or in the presence of VK antagonists, hepatic VKdependent carboxylase activity is inhibited and des-g-carboxyprothrombin (abnormal prothrombin or PIVKA; protein induced by vitamin K antagonist, prothrombin) is released into the blood. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-263681 |
Glu68 |
VEETCSYeEAFEALE |
in vitro |
|
| pmid |
sentence |
| 10556651 |
We analyzed the number of glutamic acid (Glu) residues and their positions in the Gla domain (GD) of DCP to investigate the gamma-carboxylation mechanism of VK-dependent carboxylase. Several DCPs were found in each subject studied. The 10 Gla residues of human prothrombin were carboxylated in order from the N-terminal (residues 26, 25, 16, 29, 20, 19, 14, 32, 7 and 6)|In the absence of VK or in the presence of VK antagonists, hepatic VKdependent carboxylase activity is inhibited and des-g-carboxyprothrombin (abnormal prothrombin or PIVKA; protein induced by vitamin K antagonist, prothrombin) is released into the blood. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-263682 |
Glu69 |
EETCSYEeAFEALES |
in vitro |
|
| pmid |
sentence |
| 10556651 |
We analyzed the number of glutamic acid (Glu) residues and their positions in the Gla domain (GD) of DCP to investigate the gamma-carboxylation mechanism of VK-dependent carboxylase. Several DCPs were found in each subject studied. The 10 Gla residues of human prothrombin were carboxylated in order from the N-terminal (residues 26, 25, 16, 29, 20, 19, 14, 32, 7 and 6)|In the absence of VK or in the presence of VK antagonists, hepatic VKdependent carboxylase activity is inhibited and des-g-carboxyprothrombin (abnormal prothrombin or PIVKA; protein induced by vitamin K antagonist, prothrombin) is released into the blood. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-263683 |
Glu72 |
CSYEEAFeALESSTA |
in vitro |
|
| pmid |
sentence |
| 10556651 |
We analyzed the number of glutamic acid (Glu) residues and their positions in the Gla domain (GD) of DCP to investigate the gamma-carboxylation mechanism of VK-dependent carboxylase. Several DCPs were found in each subject studied. The 10 Gla residues of human prothrombin were carboxylated in order from the N-terminal (residues 26, 25, 16, 29, 20, 19, 14, 32, 7 and 6)|In the absence of VK or in the presence of VK antagonists, hepatic VKdependent carboxylase activity is inhibited and des-g-carboxyprothrombin (abnormal prothrombin or PIVKA; protein induced by vitamin K antagonist, prothrombin) is released into the blood. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-263684 |
Glu75 |
EEAFEALeSSTATDV |
in vitro |
|
| pmid |
sentence |
| 10556651 |
We analyzed the number of glutamic acid (Glu) residues and their positions in the Gla domain (GD) of DCP to investigate the gamma-carboxylation mechanism of VK-dependent carboxylase. Several DCPs were found in each subject studied. The 10 Gla residues of human prothrombin were carboxylated in order from the N-terminal (residues 26, 25, 16, 29, 20, 19, 14, 32, 7 and 6)|In the absence of VK or in the presence of VK antagonists, hepatic VKdependent carboxylase activity is inhibited and des-g-carboxyprothrombin (abnormal prothrombin or PIVKA; protein induced by vitamin K antagonist, prothrombin) is released into the blood. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-265918 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 31226734 |
Thus, vitamin K acts as a cofactor for GGCX via the vitamin K cycle and exerts physiological effects through its regulation of VKDPs [29]. More than 20 VKDPs have been found. Osteocalcin promotes bone formation, and blood coagulation factors II, VII, IX, and X activate blood coagulation. Matrix Gla protein suppresses cardiovascular calcification, and brain-expressed Gas 6 promotes neural differentiation [29]. GGCX is an enzyme that converts glutamic acid (Glu) residues to Gla residues, so that the Gla-containing proteins can exert various physiological actions such as blood coagulation and bone formation. |
|
| Publications: |
11 |
Organism: |
In Vitro, Homo Sapiens |
| Pathways: | Vitamin-K cycle |
| + |
F2 | down-regulates activity 
cleavage
|
F2R |
0.887 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-263570 |
Phe43 |
ATLDPRSfLLRNPND |
in vitro |
|
| pmid |
sentence |
| 10978167 |
PAR1E and PAR2E (10 microM) were incubated in the presence of the different proteases | The enzymes were used at the following concentrations: 0.5 unit/mL thrombin, 2.5 nM trypsin, 20 nM plasmin, 20 nM cathepsin G, 20 nM elastase, 20 nM proteinase 3, and 2 units/mL calpain I and II|Protease-activated receptors (PARs) mediate cell activation after proteolytic cleavage of their extracellular amino terminus.|Protease-activated receptors (PARs) mediate cell activation after proteolytic cleavage of their extracellular amino terminus.|Plasmin, calpain and leukocyte elastase, cathepsin G, and proteinase 3 cleaved at multiple sites and would be expected to disable PAR1 by cleaving COOH-terminal to the activation site. |
|
| Publications: |
1 |
Organism: |
In Vitro |
| + |
F2 | up-regulates
binding, cleavage
|
F2R |
0.887 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-199788 |
|
|
Homo sapiens |
Breast Cancer Cell, Prostate Gland Cancer Cell, Melanoma Cell |
| pmid |
sentence |
| 23450633 |
Thrombin, actin through par1 promotes tumor cell proliferation, migration and contributes to the metastatic potenital of breast, prostate, gastrointestinal cancers and melanoma. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-199007 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 22972936 |
The par1 receptor subtype is activated when the n terminus is proteolytically cleaved by the serine protease thrombin, resulting in an irreversible activation of the receptor. Thrombin activates platelets by binding and cleaving protease-activated receptors 1 and 4 (par1 and par4). |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| + |
F2 | up-regulates activity
|
F7 |
0.301 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-263529 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 29880919 |
Thrombin also activates the cofactors FVIII (to FVIIIa) and FV (to FVa) and activates platelets such that they provide a procoagulant membrane surface to which these proteins then bind |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Tissue: |
Blood Plasma |
| Pathways: | Vitamin-K cycle |
| + |
F10 | up-regulates activity
cleavage
|
F2 |
0.457 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-263539 |
|
|
Mus musculus |
|
| pmid |
sentence |
| 25769543 |
The present data point to key roles of FVIII and FIX in FX activation at the site of a platelet thrombus by supporting: (i) thrombin generation, (ii) thrombus growth and platelet phosphatidylserine exposure, and (iii) fibrin formation at the platelet surface. The likely mechanism is that tenase activity via FVIIIa and FIXa, which is confined to the sites of platelet thrombi, generates FXa that directly catalyzes the conversion of prothrombin into thrombin. |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| Tissue: |
Blood Plasma |
| Pathways: | Vitamin-K cycle |
| + |
F2 | form complex 
binding
|
Thrombin-Thrombomodulin |
0.905 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-263550 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 29880919 |
Thrombin also activates the negative regulators of the cascade, after complexing with thrombomodulin (TM) and endothelial protein C receptor (EPCR), to activate protein C (PC) to activated PC (APC). |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-263549 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 29880919 |
Thrombin also activates the negative regulators of the cascade, after complexing with thrombomodulin (TM) and endothelial protein C receptor (EPCR), to activate protein C (PC) to activated PC (APC). |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| Tissue: |
Blood Plasma |
| + |
F2 | up-regulates
binding
|
LRP1 |
0.282 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-41090 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 8626456 |
In vitro binding studies revealed that antithrombin iii (atiii)thrombin, heparin cofactor ii (hcii)thrombin, and ?1-antitrypsin (?1AT)trypsin bound to purified lrp |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
F2 | up-regulates activity
cleavage
|
Fibrinogen |
0.855 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-263525 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 29880919 |
Thrombin is a key enzyme in the pathway and cleaves fibrinogen to fibrin, which spontaneously forms the insoluble polymer that is the basis for the haemostatic plug. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Tissue: |
Blood Plasma |
| + |
SERPINA1 | down-regulates activity
binding
|
F2 |
0.423 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-263524 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 17635716 |
Alpha1PI, historically known as alpha1-antitrypsin, is a 51 kDa, 394 amino acid glycoprotein, synthesized in the liver, circulating at c. 1.3 mg mL-1 with a half-life of 4.5 days |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Tissue: |
Blood Plasma |
| + |
SERPINC1 | down-regulates activity
cleavage
|
F2 |
0.948 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-264136 |
|
|
|
|
| pmid |
sentence |
| 31030036 |
Antithrombin (AT), a member of the serine protease inhibitor (SERPIN) superfamily, is a major circulating inhibitor of blood coagulation proteases such as factor (F) IIa (known as thrombin), FXa and, to a lesser extent, FIXa, FXIa and FXIIa. SERPINC1, which encodes AT in humans, is located on chromosome 1q25.1 |
|
| Publications: |
1 |
| + |
F2 | up-regulates activity
binding
|
GPIb-IX-V complex |
0.578 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-261859 |
|
|
Homo sapiens |
Blood Platelet |
| pmid |
sentence |
| 25297919 |
Besides VWF as a main ligand, GPIbα also binds multiple ligands such as thrombospondin, Factor XII, Factor XI, thrombin, High Molecular Weight kininogen, P-selectin and Mac-1. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
F2 | up-regulates
binding
|
F2RL1 |
0.609 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-108183 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 11356985 |
Other major aspects of par-2 are highlighted, in particular the ability of several serine protease enzymes, in addition to trypsin, to function as activators of par-2. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Tissue: |
Skin |
| + |
F2 | up-regulates
binding
|
F2RL3 |
0.697 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-196003 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 22318735 |
Thrombin activates platelets by binding and cleaving protease-activated receptors 1 and 4 (par1 and par4). |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
dabigatran | down-regulates
chemical inhibition
|
F2 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-190314 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| Other |
|
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
F2 | up-regulates
binding
|
F2RL2 |
0.652 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-108225 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 11356985 |
as noted previously, the human form of par-3 activated phosphoinositide signaling in response to thrombin when overexpressed in cos-7 cells |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
Factor Va-Xa | up-regulates activity
cleavage
|
F2 |
0.669 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-263546 |
|
|
|
|
| pmid |
sentence |
| 11983337 |
This activation is accomplished at a physiologically relevant rate by the prothrombinase complex, a macromolecular association of the serine protease factor Xa (fXa) with its cognate cofactor, factor Va (fVa), and substrate, prothrombin|Factor Va Increases the Affinity of Factor Xa for Prothrombin |
|
| Publications: |
1 |
| + |
bivalirudin | down-regulates activity
chemical inhibition
|
F2 |
0.8 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-258346 |
|
|
in vitro |
|
| pmid |
sentence |
| 1290488 |
These data demonstrate that hirulog-1 is a specific inhibitor of thrombin forms with high fibrinogen-procoagulant activities and that its Arg-3-Pro-4 bond is slowly cleaved by these thrombin forms. |
|
| Publications: |
1 |
Organism: |
In Vitro |
4.0
F2
- 
- 