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
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3.4.21.5
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platelet
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anticoagulant
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heparin
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thrombosis
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bleeding
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endothelial
-
artery
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thromboplastin
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collagen
-
agonist
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thromboembolism
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coronary
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procoagulant
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adp
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antithrombotic
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venous
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fibrinolysis
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thrombus
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hemorrhage
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hemostatic
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hirudin
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plasminogen
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antiplatelet
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thrombomodulin
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protease-activated
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arachidonic
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plasmin
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thromboxane
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intravascular
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viii
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d-dimers
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atrial
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thrombocytopenia
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aspirin
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aptamer
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hypercoagulability
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willebrand
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warfarin
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percutaneous
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p-selectin
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rivaroxaban
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platelet-rich
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unfractionated
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coagulopathy
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prothrombotic
-
embolism
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haemostasis
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diagnostics
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analysis
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hemophilia
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biotechnology
-
thrombolytic
-
nutrition
-
synthesis
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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
3.4.21.5 thrombinAdvanced search results
results (
results (Engineering
Engineering on EC 3.4.21.5 - thrombin
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PROTEIN VARIANTS 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
C191A
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme
C220A
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme
D100A
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme
D120N
-
site-directed mutagenesis, the mutant shows conformational changes compared to the wild-type enzyme
D14A
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme
D14lA
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme
D178A
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme
D186aA
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme
D189A
D189E
-
site-directed mutagenesis, reduced substrate and monovalent cation specificity and enzyme activity
D189N
-
site-directed mutagenesis, reduced substrate and monovalent cation specificity and enzyme activity
D189S
-
site-directed mutagenesis, reduced substrate and monovalent cation specificity and proteolytic activity, amidolytic activity is slightly reduced
D1aA
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme
D221A
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme
D222A
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme
D60eA
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme
E14cA
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme
E14eA
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme
E14hA
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme
E186bA
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme
E192A
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme
E1cA
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme
E217A
E217C/K224C
-
mutant in which the 225-loop of the Na+-binding site is stabilized by an engineered disulfide bond, the activity of the mutant is dramatically impaired, though thrombomodulin interacts with this mutant with more than 20fold elevated KD to partially restore its activity, the mutant exhibits about 2-3fold higher KD for interaction with Na+ and does not clot fibrinogen or activated protein C in the presence of thrombomodulin
E217K
retains ability to activate the anticoagulant protein C pathway, inable to convert fibrinogen to a fibrin clot. Allosteric inactivation by destabilization of Na+ binding site, thus representing the Na+-free, catalytically slow form
E229A
-
mutation substantially shifts thrombin's specificity in favour of the anticoagulant substrate, protein C
E229K
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the mutation shifts the substrate specificity of thrombin by 130fold to favor the activation of the anticoagulant substrate protein C over the procoagulant substrate fibrinogen. The mutant enzyme is also less effective in activating platelets, is resistant to inhibition by antithrombin III and displays a prolonged half-life in plasma
E39A
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme
E77A
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme
E80A
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme
E8A
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme
E97aA
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme
F227A
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme
F245A
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme
F34A
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme
F60hA
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme
G193A
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme
G223a
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme
G226A
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme
G548A
-
naturally occuring mutant, substrate binding pocket mutation, loss of proteolytic activity against native substrates fibrinogen, protein C, and synthetic substrates, reduced ability to bind antithrombin III, causes dysprothrombinemia
H71A
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme
I174A
I24A
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme
I82A
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme
K109A
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme
K10A
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme
K110A
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme
K169A
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme
K186dA
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme
K224A
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme
K235A
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme
K236A
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme
K240A
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme
K36A
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme
K60fA
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme
K70A
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme
K81A
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme
K9A
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme
L60A
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site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme
L65A
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme
L99A
M84A
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme
N143P t
-
the mutant features no Na+-dependent enhancement of kcat yet binds Na+ with an affinity comparable to that of wild type
N60gA
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme
P186A
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme
P198A
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme
P37A
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme
P60bA
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme
P60cA
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme
Q38A
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme
R101A
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme
R126A
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme
R14dA
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme
R155A/R271A/R286A
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site-directed mutagenesis, the mutation of enzyme's proteolytic cleavage sites hinder the activation of the enzyme
R155A/R284A/R271A
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site-directed mutagenesis, the mutant enzyme can be cleaved only at Arg320, cleavage is completely inhibited by Asp-Tyr-Asp-Tyr-Gln
R155A/R284A/R320A
-
site-directed mutagenesis, the mutant enzyme can be cleaved only at Arg271, no inhibition of cleavage by Asp-Tyr-Asp-Tyr-Gln
R165A
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme
R173A
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme
R175A
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme
R187A
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme
R221aA
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme
R233A
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme
R35A
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme
R4A
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme
R67A
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme
R67C/I82C
-
mutant in which the 70-80 loop of exosite-1 is stabilized by an engineered disulfide bond, mutant does not bind thrombomodulin and exhibits a normal amidolytic activity. The mutant exhibits about 2-3fold higher KD for interaction with Na+ and does not clot fibrinogen or activated protein C in the presence of thrombomodulin
R73A
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme
R75A
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme
R77aA
R93A
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme
R97A
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme
S171A
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme
S195A
S214A
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme
S36aA
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme
T172A
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme
T60iA
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme
T74A
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme
V163A
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme
V200A
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme
W215A
W215A/E217A
W215A/E217K
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme, the mutant features a less pronounced anticoagulant/antithrombotic profile compared with the wild-type
W215D
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme
W215E
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme, mutant W215E is 10fold more specific for protein C than fibrinogen and PAR1
W215F
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme
W215H
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme
W215I
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme, mutant W215I features a kcat/Km value for cleavage of fibrinogen that is about 100000fold lower than that of wild-type. The kcat/Km value for PAR1 activation is 10,000fold lower compared with wild-type, but the kcat/Km value for activation of protein C in the presence of thrombomodulin is perturbed
W215L
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme
W215M
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme
W215P
W215R
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme
W215T
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme
W215V
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme
W215Y
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme
W237A
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme
W29A
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme
W60dA
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme
W96A
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme
Y117A
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme
Y184aA
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme
Y225A
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme
Y228A
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme
Y60aA
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme
Y76A
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme
Y89A
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme
K222D
-
introduction of activation by Na+ similar to human enzyme, wild-type is not activated by Na+
W215A/E217A
additional information
D189A
-
site-directed mutagenesis, reduced substrate and monovalent cation specificity and enzyme activity
D189A
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme
E217A
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme
E217A
-
site-directed mutagenesis, mutation of a residue involved in interaction with substrate factore XIII, the mutant shows reduced activity compared to the wild-type enzyme, the mutation affects hydrolysis of substrates due to interruption of key structural contacts involving the thrombin 220 loop and the S1 specificity pocket
I174A
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme
I174A
-
site-directed mutagenesis, mutation of a residue involved in interaction with substrate factore XIII, the mutant shows reduced activity compared to the wild-type enzyme
L99A
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme
L99A
-
site-directed mutagenesis, mutation of a residue involved in interaction with substrate factore XIII, the mutant shows eliminated activity compared to the wild-type enzyme
R77aA
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme
R77aA
-
the mutant of thrombin prevents the autolytic cleavage at R77a in exosite I and enables crystallization of thrombin free of inhibitors
W215A
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme
W215A
-
site-directed mutagenesis, mutation of a residue involved in interaction with substrate factore XIII, the mutant shows highly reduced activity compared to the wild-type enzyme
W215A
-
site-directed mutagenesis, the mutation significantly compromises cleavage of the anticoagulant protein C but has no effect on the hydrolysis of fibrinogen and PAR1
W215A/E217A
drastically impaired catalytic activity, but able to efficiently activate protein C in presence of thrombomodulin
W215A/E217A
-
strikingly compromised fibrinogen cleavage, severe reduction in cleavage of PAR1, PAR4
W215A/E217A
-
site-directed mutagenesis, mutation of a residue involved in interaction with substrate factore XIII, the mutant shows highly reduced activity compared to the wild-type enzyme
W215A/E217A
-
the thrombin mutant is a potent anticoagulant both in vitro and in vivo
W215A/E217A
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme, the mutant shows significant perturbation of fibrinogen and PAR1 cleavage over protein C activation
W215P
-
site-directed mutagenesis, altered substrate specificity compared to the wild-type enzyme
W215P
-
site-directed mutagenesis, the mutation significantly compromises cleavage of the anticoagulant protein C but has no effect on the hydrolysis of fibrinogen and PAR1
W215A/E217A
-
largely compromised fibrinogen cleavage, severe reduction in cleavage of PAR1, PAR4
W215A/E217A
-
the thrombin mutant is a potent anticoagulant both in vitro and in vivo
additional information
-
immobilization of thrombin, determination of optimal conditions, overview. Application of immobilized thrombin for production of S-thanatin, small antimicrobial peptide with 21 amino acid residue, expressed in Escherichia coli strain BL21(DE3) as a fusion protein containing thrombin cleavage site. The immobilizes thrombin in polyacrylamide gel shows excellent cleavage performance within wider ranges of pH value and temperature for reaction than free enzyme, and the residual activity remain above 75% after ten times of usage
additional information
a natural deletion mutant DELTAK9 of prothrombin from 2 homozygous humans lacks Lys9 and Lys10 residues of the A-chain shows 18fold reduced activity with substrate D-phenylalanyl-pipecolyl-L-arginine-4-nitroanilide and 60fold reduced activity with fibrinopeptide A compared to the wild-type enzyme, mutant shows reduced sensitivity to antithrombin, and Na+, and a defective PARI receptor recognition, thus reduced platelet activation, alteration of A-and B-chain conformation, especially insertion loop 60, and the catalytic triad residues
additional information
-
a natural deletion mutant DELTAK9 of prothrombin from 2 homozygous humans lacks Lys9 and Lys10 residues of the A-chain shows 18fold reduced activity with substrate D-phenylalanyl-pipecolyl-L-arginine-4-nitroanilide and 60fold reduced activity with fibrinopeptide A compared to the wild-type enzyme, mutant shows reduced sensitivity to antithrombin, and Na+, and a defective PARI receptor recognition, thus reduced platelet activation, alteration of A-and B-chain conformation, especially insertion loop 60, and the catalytic triad residues
additional information
-
construction of diverse mutants by site-directed mutagenesis, reduced activity or no remaining activity in activation of factor V and factor VIII, overview
additional information
-
defective mutant enzymes of 2 humans with congenital afibrinogenemia, termed MC and KU, show impaired binding of thrombin to the thrombin binding sites of fibrin and fibrin gamma' peptides, respectively
additional information
-
chemical modification of carboxyl groups by glycine ethyl ester. Modified enzyme induces platelet aggregation through the activation of PAR1, and modified anhydrothrombin inhibits this process completely. Neither modified anhydrothrombin nor modified thrombin inhibit thrombin-induced platelet aggregation
additional information
-
fusion of the N-terminal acidic extension, residues 1-75, of heparin cofactor II to alpha1-proteinase inhibitor M358R to the enzyme specifically increases the rate of thrombin inhibition by 6fold, the mutant is termed HAPI M358R, maximal enhancement of alpha1-PI M358R activity requires the acidic residues between HCII residues 55 and 75, because no enhancement is observed either by fusion of residues 1-54 alone or by fusion of a mutated HCII acidic extension in which all Glu and Asp residues between positions 55 and 75 are neutralized by mutation, overview
additional information
-
lack of thrombin generation in factor II-deficient plasma
additional information
-
engineering thrombin for selective specificity toward protein C and PAR1 by site-directed mutagenesis, overview
additional information
-
when the W215E mutation is combined with deletion of nine residues in the autolysis loop, which by itself shifts the specificity of the enzyme from fibrinogen and PAR1 to protein C, the resulting construct features significant activity only toward PAR1
additional information
-
in mice homozygously lacking the thrombin inhibitor protease nexin, the PI3K-Akt pathway is constitutively activated and expression of myofibroblastic marker smooth-muscle actin is enhanced in vivo in hair follicle dermal cells
