Information on EC 3.4.17.20 - Carboxypeptidase U

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The expected taxonomic range for this enzyme is: Eutheria

EC NUMBER
COMMENTARY
3.4.17.20
-
RECOMMENDED NAME
GeneOntology No.
Carboxypeptidase U
-
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
release of C-terminal Arg and Lys from a polypeptide
show the reaction diagram
reaction mechanism
-
release of C-terminal Arg and Lys from a polypeptide
show the reaction diagram
peptidyl-L-lysine (or L-arginine) + H2O = peptide + L-lysine (or L-arginine)
-
-
-
release of C-terminal Arg and Lys from a polypeptide
show the reaction diagram
catalytic mechanism and substrate specificity
-
release of C-terminal Arg and Lys from a polypeptide
show the reaction diagram
catalytically important residues are G207, I243, I247, S254, and I255, catalytic mechanism and substrate binding
-
release of C-terminal Arg and Lys from a polypeptide
show the reaction diagram
substrate binding involves residues ARg235, Tyr341, and Asn234, while catalysis involves residues Glu363 and ARg217, mechanism of action of TAFI, overview
-
release of C-terminal Arg and Lys from a polypeptide
show the reaction diagram
substrate binding involves residues ARg235, Tyr341, and Asn234, while catalysis involves residues Glu363 and ARg217, mechanism of action of TAFI, overview, Zn2+ is important in the catalytic mechanism
-
release of C-terminal Arg and Lys from a polypeptide
show the reaction diagram
the enzyme prefers C-terminal arginine over lysine
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of peptide bond
-
-
-
-
SYNONYMS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
aCAP
-
-
activated thrombin activable fibrinolysis inhibitor
-
-
activated thrombin-activable fibrinolysis inhibitor
-
-
activated thrombin-activatable fibrinolysis inhibitor
-
-
active acarboxypeptidase B
-
-
active thrombin-activatable fibrinolysis inhibitor
-
-
Arginine carboxypeptidase
-
-
-
-
Carboxypeptidase B, pro-
-
-
-
-
Carboxypeptidase R
-
-
-
-
Carboxypeptidase R
-
-
Carboxypeptidase R
-
-
Carboxypeptidase R
Q9JHH6
-
Carboxypeptidase R
-
-
carboxypeptidase U
-
-
Carboxypeptidase-U
-
-
-
-
CPR
Q9JHH6
-
CPU
-
-
-
-
Plasma carboxypeptidase B
-
-
-
-
Plasma carboxypeptidase B
-
-
Plasma carboxypeptidase B
-
-
Plasma carboxypeptidase B
-
-
plasma carboxypeptidase U
-
-
plasma procarboxypeptidase B
-
-
plasma procarboxypeptidase B-like proenzyme
-
-
plasma procarboxypeptidase U
-
-
pro-pCPB
-
-
-
-
Procarboxypeptidase B
-
-
-
-
Procarboxypeptidase B
-
-
Procarboxypeptidase B
-
-
procarboxypeptidase R
-
-
procarboxypeptidase R
-
-
procarboxypeptidase U
-
-
pTAFI
-
-
-
-
rTAFI
-
-
-
-
TAFI
-
-
-
-
TAFI
-
zymogen
TAFI
Q8IWV7
-
TAFI
-
zymogen
TAFI
Q9JHH6
-
TAFI
-
zymogen
TAFI
Q9EQV9
-
TAFI
-
zymogen
TAFIa
-
-
-
-
TAFIa
Q2KIG3
-
TAFIa
-
active enzyme
TAFIa
-
active form of TAFI
TFAI
-
-
thrombin activable fibrinolysis inhibitor
-
-
thrombin activatable fibrinolysis inhibitor
-
-
thrombin activatable fibrinolysis inhibitor
-
-
Thrombin-activable fibrinolysis inhibitor
-
-
-
-
thrombin-activatable fibrinolysis inhibitor
Q2KIG3
-
thrombin-activatable fibrinolysis inhibitor
Q8IWV7
-
thrombin-activatable fibrinolysis inhibitor
-
-
thrombin-activatable fibrinolysis inhibitor
Q9JHH6
-
thrombin-activatable fibrinolysis inhibitor
-
-
thrombin-activatable fibrinolysis inhibitor
Q9EQV9
-
CAS REGISTRY NUMBER
COMMENTARY
156621-18-0
-
37329-68-3
-
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
; variant A147/I325; variant A147/T325; variant T147/I325; variant T147/T325
-
-
Manually annotated by BRENDA team
genotypes 1040CC and 1040TT
-
-
Manually annotated by BRENDA team
isozyme T147/T325
-
-
Manually annotated by BRENDA team
polymorphism: A/T147, A/G152, A/G438, C/T530, C/T1053, T/G1102, A/G690, T/C1925
-
-
Manually annotated by BRENDA team
two isozymes T325 and I325
-
-
Manually annotated by BRENDA team
wild-type isozymes A147/T325 and A147/I325
-
-
Manually annotated by BRENDA team
women with normal and complicated pregnancies
-
-
Manually annotated by BRENDA team
male Wistar rats
-
-
Manually annotated by BRENDA team
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
Ala-Ser-His-Leu-Gly-Leu-Ala-Arg + H2O
Ala-Ser-His-Leu-Gly-Leu-Ala + Arg
show the reaction diagram
-
reaction is much more efficient than reaction with EC 3.4.17.3
-
?
anaphylatoxin C3a + H2O
?
show the reaction diagram
-
inactivation of the inflammatory mediator
-
-
?
anaphylatoxin C5a + H2O
?
show the reaction diagram
-
inactivation of the inflammatory mediator
-
-
?
anisylazoformyl-Lys + H2O
anisylazoformic acid + Lys
show the reaction diagram
-
-
-
?
Arg6-Leu5-enkephalin + H2O
Tyr-Gly-Gly-Phe-Leu + Arg
show the reaction diagram
-
i.e. Tyr-Gly-Gly-Phe-Leu-Arg
-
-
-
Arg6-Met5-enkephalin + H2O
Tyr-Gly-Gly-Phe-Met + Arg
show the reaction diagram
-
i.e. Tyr-Gly-Gly-Phe-Met-Arg
-
-
-
biotinyl-(epsilon-aminocaproic acid)-(epsilon-aminocaproic acid)-Gly-Leu-Met-Val-Gly-Gly-Val-Val-Arg-OH + H2O
biotinyl-(epsilon-aminocaproic acid)-(epsilon-aminocaproic acid)-Gly-Leu-Met-Val-Gly-Gly-Val-Val-OH + Arg
show the reaction diagram
-
-
-
?
Bradykinin + H2O
Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe + Arg
show the reaction diagram
-
i.e. Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg
-
-
-
complement component C3a octapeptide + H2O
?
show the reaction diagram
-
removal of terminal arginine, low activity
-
-
?
complement component C5a octapeptide + H2O
?
show the reaction diagram
-
removal of terminal arginine
-
-
?
Fibrin + H2O
?
show the reaction diagram
-
-
-
?
fibrin + H2O
Lys + ?
show the reaction diagram
-
-
-
?
fibrin + H2O
Lys + ?
show the reaction diagram
-
attenuates clot lysis by removing lysine residues from a fibrin clot
-
?
fibrin + H2O
fibrin + Lys
show the reaction diagram
-
anti-fibrinolytic activity
-
-
?
fibrin + H2O
fibrin + Lys
show the reaction diagram
-
cleavage of C-terminal Lys, regulation, overview
the cleaved fibrin cannot be bound by plasminogen and the plasminogen activator in contrast to the uncleaved fibrin, fibrinolysis and plasmin regulation cycle involving the enzyme, overview
-
?
fibrin + H2O
fibrin + Lys
show the reaction diagram
-
partially degraded fibrin in fibrin clots, cleavage of C-terminal Lys
-
-
?
fibrin + H2O
fibrin + Lys
show the reaction diagram
-
cleavage of C-terminal Lys
-
-
?
fibrin + H2O
fibrin + L-Lys
show the reaction diagram
-
-
-
-
?
Fibrin, partially degraded + H2O
Fibrin, partially degraded + L-Lys + L-Arg
show the reaction diagram
-
-
-
-
Fibrin, partially degraded + H2O
Fibrin, partially degraded + L-Lys + L-Arg
show the reaction diagram
-
-
-
-
Fibrin, partially degraded + H2O
Fibrin, partially degraded + L-Lys + L-Arg
show the reaction diagram
-
-
-
-
Fibrin, partially degraded + H2O
Fibrin, partially degraded + L-Lys + L-Arg
show the reaction diagram
-
-
-
-
-
Fibrin, partially degraded + H2O
?
show the reaction diagram
-
-
-
-
-
Fibrin, partially degraded + H2O
?
show the reaction diagram
-
the enzyme suppresses the ability of fibrin to catalyze plasminogen activation and thus delays clot lysis
-
-
-
Fibrin, partially degraded + H2O
?
show the reaction diagram
-
inhibition of fibrinolysis
-
-
-
Fibrin, partially degraded + H2O
?
show the reaction diagram
-
molecular connection between coagulation and fibrinolysis
-
-
-
Glu-plasminogen + H2O
Glu + plasmin
show the reaction diagram
-
-
-
-
?
hippuryl-Arg + H2O
hippuric acid + Arg
show the reaction diagram
-
-
-
?
hippuryl-Arg + H2O
hippuric acid + Arg
show the reaction diagram
-
-
-
?
hippuryl-Arg + H2O
hippuric acid + Arg
show the reaction diagram
-
-
-
?
hippuryl-Arg + H2O
hippuric acid + Arg
show the reaction diagram
-
-
-
?
hippuryl-Arg + H2O
hippuric acid + Arg
show the reaction diagram
-
-
-
?
hippuryl-Arg + H2O
hippuric acid + Arg
show the reaction diagram
-
-
-
?
hippuryl-Arg + H2O
hippuric acid + Arg
show the reaction diagram
-
-
-
-
?
hippuryl-Arg + H2O
hippuric acid + Arg
show the reaction diagram
-
-
-
?
hippuryl-Arg + H2O
hippuric acid + Arg
show the reaction diagram
Q9JHH6
-
-
?
hippuryl-Arg + H2O
hippuric acid + Arg
show the reaction diagram
Q2KIG3
-
-
-
?
hippuryl-arginine + H2O
hippuric acid + L-arginine
show the reaction diagram
-
substrate is used to measure the TAFI activation by plasmin
-
-
?
Hippuryl-L-Arg + H2O
Hippuric acid + L-Arg
show the reaction diagram
-
-
-
-
Hippuryl-L-Arg + H2O
Hippuric acid + L-Arg
show the reaction diagram
-
-
-
-
-
Hippuryl-L-Arg + H2O
Hippuric acid + L-Arg
show the reaction diagram
-
-
-
-
?
hippuryl-L-arginine + H2O
hippuric acid + L-arginine
show the reaction diagram
-
-
-
-
?
Hippuryl-L-argininic acid + H2O
Hippuric acid + argininic acid
show the reaction diagram
-
-
-
-
-
Hippuryl-L-Lys + H2O
Hippuric acid + L-Lys
show the reaction diagram
-
-
-
-
Hippuryl-L-Lys + H2O
Hippuric acid + L-Lys
show the reaction diagram
-
-
-
-
-
hippuryl-L-lysine + H2O
hippuric acid + L-lysine
show the reaction diagram
-
-
-
-
?
His-Lys-Asp-Met-Gln-Leu-Gly-Arg + H2O
His-Lys-Asp-Met-Gln-Leu-Gly + Arg
show the reaction diagram
-
i.e. C5a, reaction is much more efficient than reaction with EC 3.4.17.3, i.e. C5a, the enzyme significantly contributes to the inactivation of C5a, the most potent of the complement derived anaphylatoxins
-
?
Lys-plasminogen + H2O
Lys + plasmin
show the reaction diagram
-
preferred substrate
-
-
?
Lys6-Leu5-enkephalin + H2O
Tyr-Gly-Gly-Phe-Leu + Lys
show the reaction diagram
-
i.e. Tyr-Gly-Gly-Phe-Leu-Lys
-
-
-
N-benzoyl-2'-cyano-L-Phe-L-Arg + H2O
N-benzoyl-2'-cyano-L-Phe + L-Arg
show the reaction diagram
-
selective CPU substrate
-
-
?
N-benzoyl-Gly-L-Arg + H2O
N-benzoyl-Gly + L-Arg
show the reaction diagram
-
-
-
-
?
N-[3-(2-Furylacryloyl)]-L-Ala-L-Arg + H2O
N-[3-(2-Furylacryloyl)]-L-Ala + L-Arg
show the reaction diagram
-
-
-
-
-
N-[3-(2-Furylacryloyl)]-L-Ala-L-Lys + H2O
N-[3-(2-Furylacryloyl)]-L-Ala + L-Lys
show the reaction diagram
-
-
-
-
N-[3-(2-Furylacryloyl)]-L-Ala-L-Lys + H2O
N-[3-(2-Furylacryloyl)]-L-Ala + L-Lys
show the reaction diagram
-
-
-
-
-
osteopontin + H2O
?
show the reaction diagram
-
thrombin-cleaved substrate
-
-
?
p-anisylazoformyl-L-arginine + H2O
p-anisylazoformic acid + L-arginine
show the reaction diagram
-
substrate is used to measure the TAFI activation by thrombin and thrombin-thrombomodulin
-
-
?
[3-(2-furylacryloyl)]-L-alanyl-L-arginine + H2O
[3-(2-furylacryloyl)]-L-alanine + L-arginine
show the reaction diagram
-
-
-
-
?
[3-(2-furylacryloyl)]-L-phenylalanyl-L-phenylalanine + H2O
[3-(2-furylacryloyl)]-L-phenylalanine + L-phenylalanine
show the reaction diagram
-
-
-
-
?
Lys6-Met5-enkephalin + H2O
Tyr-Gly-Gly-Phe-Met + Lys
show the reaction diagram
-
i.e. Tyr-Gly-Gly-Phe-Met-Lys
-
-
-
additional information
?
-
-
no substrates are hippuryl-L-Phe, hippurylphenyllactic acid, hippuryl-Gly-Phe
-
-
-
additional information
?
-
-
removal of Lys or Arg from carboxy-terminus of peptides, specific for basic amino acids at carboxy-terminus
-
-
-
additional information
?
-
Q9JHH6
pro-carboxypeptidase R is an acute phase protein under inflammatory conditions
-
?
additional information
?
-
-
pro-carboxypeptidase R production is increased under inflammatory conditions
-
?
additional information
?
-
-
inhibition of the enzyme leads to facilitated induction of coronary artery thrombolysis involving the plasminogen activator
-
-
-
additional information
?
-
-
the activated enzyme shows anti-fibrinolytic and fibrin clot lysis activity
-
-
-
additional information
?
-
-
the enzyme circulates as inactive zymogen in the blood stream becoming activated upon blood clotting, the enzyme inhibits fibrinolysis by cleaving C-terminal lysine from the surface of partially degraded fibrin, which stimulates the tissue-type plasminogen activator-mediated conversion of plasminogen to plasmin, the enzyme might also be involved in regulation of inflammation and tissue repair, enzyme regulation overview
-
-
-
additional information
?
-
-
the enzyme down-regulates fibrinolysis by removing carboxy-terminal lysine residues, which are ligands for plasminogen and tissue-type plasminogen activator, from partially degraded fibrin, pharmacological profile and pathphysiological role of the enzyme in rat thrombolysis
-
-
-
additional information
?
-
-
the enzyme inhibits fibrinolysis
-
-
-
additional information
?
-
-
the enzyme inhibits fibrinolysis and has a distinct role in haemostasis and a possible risk factor for thrombotic disease involving the polymorphism at position 325, overview, the plasminogen activation system plays a role in enzyme regulation
-
-
-
additional information
?
-
-
the enzyme is involved and important in control of clot stability determined by clot formation and fibrinolysis, overview
-
-
-
additional information
?
-
-
the enzyme is involved in blood clot lysis
-
-
-
additional information
?
-
-
the enzyme is involved in the regulation of the coagulation and fibrinolytic systems preventing blood loss at sites of vessel wall damage and maintainthe fluidity of the blood in the body
-
-
-
additional information
?
-
-
the enzyme is partially accountable for the antifibrinolytic activity in amniotic fluid
-
-
-
additional information
?
-
-
the enzyme might be the primary in vivo regulator of complement component C5a-mediated inflammation in the circulation, the enzyme cleaves terminal lysine from the surface of fibrin clots preventing the binding and activation of plasminogen and inhibiting whole blood clot lysis
-
-
-
additional information
?
-
-
the enzyme, activated by thrombin, protects the fibrin clot against lysis, altered enzyme activity is involved in bleeding and thrombotic disorders, the enzyme is involved in wound healing and inflammation, overview
-
-
-
additional information
?
-
-
thrombin activatable fibrinolysis inhibitor and its fibrinolytic effect in normal pregnancy
-
-
-
additional information
?
-
-
thrombin activatable fibrinolysis inhibitor, TAFI, plays a role in the delicate balance between coagulation and fibrinolysis, the stability of the fibrin clot, inflammation, thrombosis, and in Behcets disease, vascular involvement pattern in patients, overview
-
-
-
additional information
?
-
-
enzyme assay using a specific chromogenic dipeptide substrate
-
-
-
additional information
?
-
-
the enzyme binds alpha2-macroglobulin and pregnancy zone protein, which does not inhibit the enzyme
-
-
-
additional information
?
-
-
the enzyme binds to plasminogen and fibrinogen
-
-
-
additional information
?
-
-
TFAI binds heparin
-
-
-
additional information
?
-
Q2KIG3
TFAI binds heparin
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
anaphylatoxin C3a + H2O
?
show the reaction diagram
-
inactivation of the inflammatory mediator
-
-
?
anaphylatoxin C5a + H2O
?
show the reaction diagram
-
inactivation of the inflammatory mediator
-
-
?
Fibrin + H2O
?
show the reaction diagram
-
-
-
?
fibrin + H2O
Lys + ?
show the reaction diagram
-
-
-
?
fibrin + H2O
Lys + ?
show the reaction diagram
-
attenuates clot lysis by removing lysine residues from a fibrin clot
-
?
fibrin + H2O
fibrin + Lys
show the reaction diagram
-
anti-fibrinolytic activity
-
-
?
fibrin + H2O
fibrin + Lys
show the reaction diagram
-
cleavage of C-terminal Lys, regulation, overview
the cleaved fibrin cannot be bound by plasminogen and the plasminogen activator in contrast to the uncleaved fibrin, fibrinolysis and plasmin regulation cycle involving the enzyme, overview
-
?
fibrin + H2O
fibrin + Lys
show the reaction diagram
-
partially degraded fibrin in fibrin clots, cleavage of C-terminal Lys
-
-
?
fibrin + H2O
fibrin + L-Lys
show the reaction diagram
-
-
-
-
?
Fibrin, partially degraded + H2O
?
show the reaction diagram
-
-
-
-
-
Fibrin, partially degraded + H2O
?
show the reaction diagram
-
the enzyme suppresses the ability of fibrin to catalyze plasminogen activation and thus delays clot lysis
-
-
-
Fibrin, partially degraded + H2O
?
show the reaction diagram
-
inhibition of fibrinolysis
-
-
-
Fibrin, partially degraded + H2O
?
show the reaction diagram
-
molecular connection between coagulation and fibrinolysis
-
-
-
Glu-plasminogen + H2O
Glu + plasmin
show the reaction diagram
-
-
-
-
?
His-Lys-Asp-Met-Gln-Leu-Gly-Arg + H2O
His-Lys-Asp-Met-Gln-Leu-Gly + Arg
show the reaction diagram
-
i.e. C5a, the enzyme significantly contributes to the inactivation of C5a, the most potent of the complement derived anaphylatoxins
-
?
osteopontin + H2O
?
show the reaction diagram
-
-
-
-
?
Lys-plasminogen + H2O
Lys + plasmin
show the reaction diagram
-
-
-
-
?
additional information
?
-
Q9JHH6
pro-carboxypeptidase R is an acute phase protein under inflammatory conditions
-
?
additional information
?
-
-
pro-carboxypeptidase R production is increased under inflammatory conditions
-
?
additional information
?
-
-
inhibition of the enzyme leads to facilitated induction of coronary artery thrombolysis involving the plasminogen activator
-
-
-
additional information
?
-
-
the activated enzyme shows anti-fibrinolytic and fibrin clot lysis activity
-
-
-
additional information
?
-
-
the enzyme circulates as inactive zymogen in the blood stream becoming activated upon blood clotting, the enzyme inhibits fibrinolysis by cleaving C-terminal lysine from the surface of partially degraded fibrin, which stimulates the tissue-type plasminogen activator-mediated conversion of plasminogen to plasmin, the enzyme might also be involved in regulation of inflammation and tissue repair, enzyme regulation overview
-
-
-
additional information
?
-
-
the enzyme down-regulates fibrinolysis by removing carboxy-terminal lysine residues, which are ligands for plasminogen and tissue-type plasminogen activator, from partially degraded fibrin, pharmacological profile and pathphysiological role of the enzyme in rat thrombolysis
-
-
-
additional information
?
-
-
the enzyme inhibits fibrinolysis
-
-
-
additional information
?
-
-
the enzyme inhibits fibrinolysis and has a distinct role in haemostasis and a possible risk factor for thrombotic disease involving the polymorphism at position 325, overview, the plasminogen activation system plays a role in enzyme regulation
-
-
-
additional information
?
-
-
the enzyme is involved and important in control of clot stability determined by clot formation and fibrinolysis, overview
-
-
-
additional information
?
-
-
the enzyme is involved in blood clot lysis
-
-
-
additional information
?
-
-
the enzyme is involved in the regulation of the coagulation and fibrinolytic systems preventing blood loss at sites of vessel wall damage and maintainthe fluidity of the blood in the body
-
-
-
additional information
?
-
-
the enzyme is partially accountable for the antifibrinolytic activity in amniotic fluid
-
-
-
additional information
?
-
-
the enzyme might be the primary in vivo regulator of complement component C5a-mediated inflammation in the circulation, the enzyme cleaves terminal lysine from the surface of fibrin clots preventing the binding and activation of plasminogen and inhibiting whole blood clot lysis
-
-
-
additional information
?
-
-
the enzyme, activated by thrombin, protects the fibrin clot against lysis, altered enzyme activity is involved in bleeding and thrombotic disorders, the enzyme is involved in wound healing and inflammation, overview
-
-
-
additional information
?
-
-
thrombin activatable fibrinolysis inhibitor and its fibrinolytic effect in normal pregnancy
-
-
-
additional information
?
-
-
thrombin activatable fibrinolysis inhibitor, TAFI, plays a role in the delicate balance between coagulation and fibrinolysis, the stability of the fibrin clot, inflammation, thrombosis, and in Behcets disease, vascular involvement pattern in patients, overview
-
-
-
additional information
?
-
-
TFAI binds heparin
-
-
-
additional information
?
-
Q2KIG3
TFAI binds heparin
-
-
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Ca2+
-
required for enzyme activation
Ca2+
-
required for activation of the enzyme
Zinc
-
zinc metalloenzyme
Zn2+
-
metalloproteinase
Zn2+
-
bound by residues His159, Glu162, and His288, Zn2+ is important in the catalytic mechanism
Zn2+
-
bound by residues His159, Glu162, and His288
Zn2+
-
the enzyme is a metallopeptidase
Zn2+
-
a metallocarboxypeptidase with a penta-coordinated zinc ion
Zn2+
-
-
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(R)-2-(3-guanidinophenyl)-3-mercaptopropanoic acid
-
-
(R)-2-guanidino-3-mercaptopropanoic acid
-
-
(R)-3-(2-aminoethylthio)-2-(3-((R)-3-cyclohexyl-1-oxo-1-((1R,2R,4R)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-ylamino)propan-2-yl)ureido)propanoic acid
-
-
(S)-2,5-dihydroxy-N-(1-hydroxy-3-phenylpropan-2-yl)benzamide
-
-
1,10-phenanthroline
-
-
2-(2-amino-pyridin-4-ylmethyl)-3-mercapto-propionic acid
-
reversible inhibition, IC50: 0.0032 mM
2-(2-guanidinoethylthio)succinic acid
-
-
2-(3-carbamimidamidophenyl)-3-sulfanylpropanoic acid
-
-
2-(6-amino-pyridin-3-ylmethyl)-2-mercaptomethyl-butyric acid
-
reversible inhibition, IC50: 0.25 mM
2-Bromo-4-methylbutan-1,4-olide
-
-
2-Guanidinoethylmercaptosuccinic acid
-
i.e. GEMSA
2-Guanidinoethylmercaptosuccinic acid
-
-
2-mercaptoethanol
-
-
2-mercaptomethyl-3-(6-amino-pyridin-3-yl)-2-fluoro-propionic acid
-
reversible inhibition, IC50: 0.0005 mM
2-mercaptomethyl-3-(6-amino-pyridin-3-yl)-2-hydroxy-propionic acid
-
reversible inhibition, IC50: 0.0009 mM
2-mercaptomethyl-3-piperidin-4-yl-propionic acid
-
reversible inhibition, IC50: 0.0032 mM
2-mercaptomethyl-3-pyrrolidin-3-yl-propionic acid
-
reversible inhibition, IC50: 0.0016 mM
2-[[(2-carbamimidamidoethyl)sulfanyl]methyl]butanedioic acid
-
reversible inhibition, IC50: 0.27 mM
3-(2-amino-thiazol-5-yl)-2-mercaptomethyl-propionic acid
-
reversible inhibition, IC50: 0.0013 mM
3-(2-guanidinoethylthio)-2-(mercaptomethyl)propanoic acid
-
-
3-(6-amino-2-methyl-pyridin-3-yl)-2-mercaptomethyl-propionic acid
-
reversible inhibition, IC50: 0.0063 mM
3-(6-amino-4-methyl-pyridin-3-yl)-2-mercaptomethyl-propionic acid
-
reversible inhibition, IC50: 0.0079 mM
3-(6-amino-5-chloro-pyridin-3-yl)-2-mercaptomethyl-propionic acid
-
reversible inhibition, IC50: 0.010 mM
3-(6-amino-5-hydroxymethyl-pyridin-3-yl)-2-mercaptomethyl-propionic acid
-
reversible inhibition, IC50: 0.013 mM
3-(6-amino-5-methyl-pyridin-3-yl)-2-(hydroxymethyl)-2-mercaptomethyl-propionic acid
-
reversible inhibition, IC50: 0.083 mM
3-(6-amino-5-methyl-pyridin-3-yl)-2-mercaptomethyl-2-methyl-propionic acid
-
reversible inhibition, IC50: 0.0016 mM; reversible inhibition, IC50: 0.001 mM
3-(6-amino-pyridin-3-yl)-2-mercaptomethyl-2-methyl-propionic acid
-
reversible inhibition, IC50: 0.0006 mM
3-(6-amino-pyridin-3-yl)-2-mercaptomethyl-propionic acid
-
reversible inhibition, IC50: 0.0002 mM
3-(6-aminopyridin-3-yl)-2-(1-((5-(5-chlorothiophen-2-yl)isoxazol-3-yl)methyl)-1H-imidazol-4-yl)propanoic acid
-
-
3-(6-aminopyridin-3-yl)-2-(1-isopentyl-1H-imidazol-4-yl)propanoic acid
-
-
3-(6-aminopyridin-3-yl)-2-(1H-imidazol-4-yl)propanoic acid
-
IC50: 0.000001 mM
3-(6-aminopyridin-3-yl)-2-(mercaptomethyl)propanoic acid
-
-
3-(6-aminopyridin-3-yl)-2-(sulfanylmethyl)propanoic acid
-
-
3-(6-aminopyridin-3-yl)-2-[1-(3-methylbutyl)-1H-imidazol-4-yl]propanoic acid
-
-
3-(cis-4-amino-cyclopent-2-yl)-2-mercaptomethyl-propionic acid
-
reversible inhibition, IC50: 0.001 mM
3-[(2-carbamimidamidoethyl)sulfanyl]-2-(sulfanylmethyl)propanoic acid
-
reversible inhibition, IC50: 0.02 mM
4-chloromercuribenzoate
-
-
5-amino-2-[(1-propyl-1H-imidazol-4-yl)methyl]pentanoic acid
-
-
6-Aminohexanoic acid
-
-
anabaenopeptin-type cyclic peptide
-
-
-
AZD-9684
-
-
BX 528
-
-
BX-528
-
i.e. (S)-2-[3-(aminomethyl)phenyl]-3-hydroxy[(R)-2-methyl-1-[(3-phenylpropyl)sulfonyl]aminopropyl]phosphoryl propanoic acid
CKPAKNARC
-
i.e. CPI-2KR
dithiothreitol
-
-
DL-2-mercapto methyl-3-guanidinoethyl-thiopropanoic acid
-
-
DL-2-mercaptomethyl-3-guanidinoethylthiopropanoic acid
-
-
DL-mercaptomethyl-3-guanidinoethylthiopropanoic acid
-
i.e. Plummer's inhibitor, IC50: 0.029 mM
EDTA
-
-
EF-6265
-
i.e. (2S)-7-amino-2-((hydroxyl((R)-2-methyl-1-(3-phenylpropanamido)propyl)phosphoryl)methyl)heptanoic acid
EF6265
-
i.e. (S)-7-amino-2-[([(R)-2-methyl-1-(3-phenylpropanoylamino)propyl]hydroxyphosphinoyl)methyl]heptanoic acid, IC50: 0.00000826 mM, inhibitory effect in vivo, overview
EF6265
-
i.e. (S)-7-amino-2-[([(R)-2-methyl-1-(3-phenylpropanoylamino)propyl]hydroxyphosphinoyl)methyl]heptanoic acid, IC50: 0.00000389 mM, inhibitory effect in vivo, overview
EF6265
-
i.e. (S)-7-amino-2-[([(R)-2-methyl-1-(3-phenylpropanoylamino)propyl]hydroxyphosphinoyl)methyl]heptanoic acid, IC50: 0.000001 mM
EF6265
-
specific inhibitor of activated form of TAFIa. A pharmacologic study to assess the effect of EF6265 on rat sepsis-induced organ dysfunction models is performed. In the endotoxemia model, posttreatment with EF6265 reduces fibrin deposits in the kidney and liver accompanied by no significant changes in platelet count and fibrinogen concentration in plasma. EF6265 also significantly decreases levels of plasma lactate dehydrogenase and aspartate aminotransferase, markers of organ dysfunction. In the sepsis model, EF6265, simultaneously administered with ceftazidime (CAZ) 2 h after Pseudomonas aeruginosa injection dramatically potentiates the interleukin-6-reducing effect of CAZ in plasma. This combined treatment also lowers plasma lactate dehydrogenase and blood urea nitrogen more potently than single treatment with CAZ
EF6265
-
-
epsilon-amino caproic acid
-
-
Epsilon-aminocaproic acid
-
-
GEMSA
-
reversible, mechanism, reduces enzyme activity 10fold
GEMSA
-
i.e. guanidinoethyl-thiopropanoic acid
glycyl-glycyl-L-cysteine
-
-
glycyl-L-cysteine
-
-
guanidinoethyl-mercaptosuccinic acid
-
-
Guanidinoethylmercaptosuccinic acid
-
-
guanidinyl-L-cysteine
-
IC50: 0.0094 mM in inhibition of plasma fibrin clot lysis
Hirudo medicinalis peptide inhibitor
-
-
-
LCI
-
leech carboxypeptidase inhibitor
leech carboxypeptidase inhibitor
-
-
-
MERGEPTA
-
-
MERGETPA
-
D,L-2-mercaptomethyl-3-guanidinoethyl-thipropanoic acid
o-phenanthroline
-
-
p-chloromercuribenzoate
-
-
PCI-2KR
-
i.e. peptide CKPAKNRC
peptide inhibitor from Hirudo medicinalis
-
-
-
Potato carboxypeptidase inhibitor
-
-
-
Potato carboxypeptidase inhibitor
-
-
-
Potato carboxypeptidase inhibitor
-
inhibition mechanism
-
Potato carboxypeptidase inhibitor
-
fibrinolytic vulnerability and the contribution of thrombin activatable fibrinolysis inhibitor to fibrinolytic defenses in normal subjects are analysed: Plasma from 30 normal subjects is exposed to tissue factor/kaolin and tissue-type plasminogen activator. Prior to activation of coagulation, samples are either not exposed or exposed to potato carboxypeptidase inhibitor (25 microg/ml, a thrombin activatable fibrinolysis inhibitor). Thrombin activatable fibrinolysis inhibitor's inhibition decreases the time to onset of maximum fibrinolysis by 45%, increases the rate of maximum lysis by 50%, and decreases clot lysis time by 45%
-
potato tuber carboxypeptidase inhibitor
-
competitive inhibition in the nanomolar range
-
PTCI
-
potato carboxypeptidase inhibitor
SAR-104772
-
-
-
tick carboxypeptidase inhibitor
Q2KIG3
proteinaceous inhibitor TCI which is found in in the hematophagous ixodid tick Rhipicephalus bursa consists of tandem structurally similar small modules, an N-terminal and a C-terminal domain. TCI inhibits TFAIa mainly through its C-terminal domain. The C-terminal residue His75 is cleaved and the new C-terminus Leu74 approaches and contacts the TAFIa catalytic zinc ion through its carboxylate atoms. In addition to this contact, the C-terminal domain of TCI itneracts with TFAIa through 15 hydrogen bonds and 5 hydrophobic contacts
-
tick carboxypeptidase inhibitor
-
-
-
UK-396082
-
i.e. (S)-5-amino-2-((1-propyl-1H-imidazol-4-yl)methyl)pentanoic acid
UK-396082
-
-
[(S)-7-amino-2-[[[(R)-2-methyl-1-(3-phenylpropanoylamino)propyl]hydroxyphosphinoyl]methyl]heptanoic acid]
-
IC50: 8.3 nM, potent and highly selective inhibitor. Systemically administered inhibitor enhances fibrinolysis in a dose- and time-dependent manner
MERGETPA
-
D,L-2-mercaptomethyl-3-guanidinoethyl-thipropanoic acid, a carboxypeptidase inhibitor
additional information
-
inhibitor synthesis, overview
-
additional information
-
the enzyme is spontaneously inactivated by conformational changes
-
additional information
-
argatroban enhances fibrinolysis via a differential inhibition of thrombin-mediated activation of TAFI and factor XIII: Plasma is exposed to argatroban or heparin, with coagulation initiated with kaolin/tissue factor and fibrinolysis initiated with tissue plasminogen activator. Argatroban significantly decreases clot lysis time and increases the maximum rate of lysis compared with unexposed plasma, whereas heparin exposure only diminishs clot lysis time. Experiments with TAFI-deficient and factor XIII-deficient plasma demonstrate a sparing of thrombin-mediated factor XIII activation with concurrent inhibition of TAFI activation
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
activation peptide
-
the activated TAFIa acts in complex with the activation peptide, enzyme regulation overview
-
plasmin
-
can activate purified enzyme, proteolytic cleavage at Arg92 produces active enzyme, cleavage at Arg330 yields inactive fragments
-
plasmin
-
overall catalytic efficiency for activation by plasmin is 1/5 of that for activation by thrombin in the presence of thrombomodulin
-
plasmin
-
-
-
Recombinant human prothrombin
-
activation
-
Thrombin
-
activation
-
Thrombin
-
poor activator of TAFI
-
Thrombin
-
-
-
thrombin-thrombomodulin
-
activation in the presence of thrombomodulin is considerably enhanced
-
thrombin-thrombomodulin
-
-
-
Thrombomodulin
-
activation
-
Thrombomodulin
-
the epidermal growth factor-like domain 3 of thrombomodulin is required for activation
-
Thrombomodulin
-
proteolytic cleavage at Arg92 produces active enzyme, cleavage at Arg330 yields inactive fragments, activates 1000fold
-
Thrombomodulin
-
-
-
Trypsin
-
can activate purified enzyme, proteolytic cleavage at Arg92 produces active enzyme, cleavage at Arg330 yields inactive fragments
-
factor VIII
-
TAFI activation increases in plasma as the concentration of factor VIII increases
-
additional information
-
activation of TAFI by thrombin is an inefficient process, thrombomodulin stimulates the activation 1250fold. Activation by plasmin is stimulated by glycosaminoglycan
-
additional information
-
dexamethasone induces expression of the enzyme 2fold
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.979
anisylazoformyl-Lys
-
24C
1.089
anisylazoformyl-Lys
-
24C
1.11
anisylazoformyl-Lys
-
24C
1.26
anisylazoformyl-Lys
-
24C
63
Arg6-Leu5-enkephalin
-
-
140
Arg6-Met5-enkephalin
-
-
0.012
biotinyl-(epsilon-aminocaproic acid)-(epsilon-aminocaproic acid)-Gly-Leu-Met-Val-Gly-Gly-Val-Val-Arg-OH
-
room temperature
10
bradykinin
-
-
2.38
hippuryl-Arg
-
Vmax: 44.86 micromol/l/min
3.44
hippuryl-Arg
Q2KIG3
Vmax: 46.05 micromol/l/min
0.000005
hippuryl-arginine
-
mutant S90D/S94V/S90D, activation of TAFI by plasmin; wild-type, activation of TAFI by plasmin
0.000006
hippuryl-arginine
-
mutant R92K, activation of TAFI by plasmin; mutant S94V, activation of TAFI by plasmin
0.000007
hippuryl-arginine
-
mutant P91S, activation of TAFI by plasmin
0.000009
hippuryl-arginine
-
mutant S90P, activation of TAFI by plasmin
0.00001
hippuryl-arginine
-
mutant A93V, activation of TAFI by plasmin
1.12
hippuryl-L-Arg
-
-
180
hippuryl-L-Arg
-
-
783
hippuryl-L-Arg
-
recombinant enzyme
817
hippuryl-L-Arg
-
plasma-derived enzyme
240
Hippuryl-L-argininic acid
-
-
1.45
Hippuryl-L-Lys
-
-
270
Hippuryl-L-Lys
-
-
766
Hippuryl-L-Lys
-
plasma-derived enzyme
933
Hippuryl-L-Lys
-
recombinant enzyme
110
Lys6-Leu5-enkephalin
-
-
220
Lys6-Met5-enkephalin
-
-
0.02
N-benzoyl-2'-cyano-L-Phe-L-Arg
-
in 50 mM HEPES (pH 8.0) at 25C
0.84
N-benzoyl-Gly-L-Arg
-
in 50 mM HEPES (pH 8.0) at 25C
210
N-[3-(2-Furylacryloyl)]-L-Ala-L-Arg
-
-
3.41
N-[3-(2-Furylacryloyl)]-L-Ala-L-Lys
-
recombinant enzyme
4.71
N-[3-(2-Furylacryloyl)]-L-Ala-L-Lys
-
plasma-derived enzyme
280
N-[3-(2-Furylacryloyl)]-L-Ala-L-Lys
-
-
0.000162
p-anisylazoformyl-L-arginine
-
mutant S90P, activation of TAFI by thrombin in the presence of thrombomodulin
0.000169
p-anisylazoformyl-L-arginine
-
mutant A93V, activation of TAFI by thrombin in the presence of thrombomodulin
0.000178
p-anisylazoformyl-L-arginine
-
wild-type, activation of TAFI by thrombin in the presence of thrombomodulin
0.000229
p-anisylazoformyl-L-arginine
-
mutant R92K, activation of TAFI by thrombin in the presence of thrombomodulin
0.000232
p-anisylazoformyl-L-arginine
-
mutant S94V, activation of TAFI by thrombin in the presence of thrombomodulin
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
15.9
anisylazoformyl-Lys
-
24C
26.8
anisylazoformyl-Lys
-
24C
27
anisylazoformyl-Lys
-
24C
27.4
anisylazoformyl-Lys
-
24C
29.5
anisylazoformyl-Lys
-
24C
748
Arg6-Leu5-enkephalin
-
-
647
Arg6-Met5-enkephalin
-
-
2.3
biotinyl-(epsilon-aminocaproic acid)-(epsilon-aminocaproic acid)-Gly-Leu-Met-Val-Gly-Gly-Val-Val-Arg-OH
-
room temperature
121
bradykinin
-
-
2.67
hippuryl-Arg
-
-
2.74
hippuryl-Arg
Q2KIG3
-
0.00004
hippuryl-arginine
-
mutant S90D/S94V/S90D, activation of TAFI by plasmin
0.00008
hippuryl-arginine
-
mutant S90P, activation of TAFI by plasmin
0.0002
hippuryl-arginine
-
mutant P91S, activation of TAFI by plasmin
0.0003
hippuryl-arginine
-
mutant S94V, activation of TAFI by plasmin
0.00039
hippuryl-arginine
-
mutant R92K, activation of TAFI by plasmin
0.00042
hippuryl-arginine
-
wild-type, activation of TAFI by plasmin
0.00043
hippuryl-arginine
-
mutant A93V, activation of TAFI by plasmin
26
hippuryl-L-Arg
-
-
52.4
hippuryl-L-Arg
-
plasma-derived enzyme
56.7
hippuryl-L-Arg
-
recombinant enzyme
169
Hippuryl-L-argininic acid
-
-
15
Hippuryl-L-Lys
-
-
40.7
Hippuryl-L-Lys
-
plasma-derived enzyme
45.6
Hippuryl-L-Lys
-
recombinant enzyme
282
Lys6-Leu5-enkephalin
-
-
290
Lys6-Met5-enkephalin
-
-
59
N-benzoyl-2'-cyano-L-Phe-L-Arg
-
in 50 mM HEPES (pH 8.0) at 25C
64
N-benzoyl-Gly-L-Arg
-
in 50 mM HEPES (pH 8.0) at 25C
36
N-[3-(2-Furylacryloyl)]-L-Ala-L-Arg
-
-
29
N-[3-(2-Furylacryloyl)]-L-Ala-L-Lys
-
-
248
N-[3-(2-Furylacryloyl)]-L-Ala-L-Lys
-
recombinant enzyme
293
N-[3-(2-Furylacryloyl)]-L-Ala-L-Lys
-
plasma-derived enzyme
0.205
p-anisylazoformyl-L-arginine
-
mutant A93V, activation of TAFI by thrombin in the presence of thrombomodulin
0.215
p-anisylazoformyl-L-arginine
-
mutant R92K, activation of TAFI by thrombin in the presence of thrombomodulin
0.315
p-anisylazoformyl-L-arginine
-
wild-type, activation of TAFI by thrombin in the presence of thrombomodulin
0.328
p-anisylazoformyl-L-arginine
-
mutant S94V, activation of TAFI by thrombin in the presence of thrombomodulin
0.377
p-anisylazoformyl-L-arginine
-
mutant S90P, activation of TAFI by thrombin in the presence of thrombomodulin
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
2950
N-benzoyl-2'-cyano-L-Phe-L-Arg
-
in 50 mM HEPES (pH 8.0) at 25C
40532
76
N-benzoyl-Gly-L-Arg
-
in 50 mM HEPES (pH 8.0) at 25C
31564
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00008
(R)-2-guanidino-3-mercaptopropanoic acid
-
-
0.0044
2-Guanidinoethylmercaptosuccinic acid
-
-
0.000001
3-(6-aminopyridin-3-yl)-2-(sulfanylmethyl)propanoic acid
-
-
0.0001
5-amino-2-[(1-propyl-1H-imidazol-4-yl)methyl]pentanoic acid
-
-
0.0004071
CKPAKNARC
-
pH 7.5
0.0002
DL-2-mercaptomethyl-3-guanidinoethylthiopropanoic acid
-
-
0.0001
DL-mercaptomethyl-3-guanidinoethylthiopropanoic acid
-
22C
0.8
epsilon-amino caproic acid
-
-
0.8
Epsilon-aminocaproic acid
-
-
1
Epsilon-aminocaproic acid
-
-
110
Epsilon-aminocaproic acid
-
-
0.001 - 0.1
GEMSA
-
-
0.00099
glycyl-glycyl-L-cysteine
-
22C
0.00014
glycyl-L-cysteine
-
22C
0.018
Guanidinoethylmercaptosuccinic acid
-
-
0.00008
guanidinyl-L-cysteine
-
22C
0.000001
LCI
-
-
0.00001
PCI-2KR
-
-
0.0000004
Potato carboxypeptidase inhibitor
-
-
-
0.0000014
Potato carboxypeptidase inhibitor
-
pH 7.5
-
0.0000021
Potato carboxypeptidase inhibitor
-
-
-
0.000004
Potato carboxypeptidase inhibitor
-
-
-
0.00001
UK-396082
-
-
0.0001 - 0.001
MERGETPA
-
-
additional information
additional information
-
the Ki-value for protamine is above 50 mM
-
additional information
additional information
-
inhibition kinetics
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.000003
(R)-2-(3-guanidinophenyl)-3-mercaptopropanoic acid
-
-
0.0000007
(R)-3-(2-aminoethylthio)-2-(3-((R)-3-cyclohexyl-1-oxo-1-((1R,2R,4R)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-ylamino)propan-2-yl)ureido)propanoic acid
-
-
0.044
(S)-2,5-dihydroxy-N-(1-hydroxy-3-phenylpropan-2-yl)benzamide
-
-
0.0032
2-(2-amino-pyridin-4-ylmethyl)-3-mercapto-propionic acid
-
reversible inhibition, IC50: 0.0032 mM
0.0044
2-(2-guanidinoethylthio)succinic acid
-
-
0.000003
2-(3-carbamimidamidophenyl)-3-sulfanylpropanoic acid
-
-
0.25
2-(6-amino-pyridin-3-ylmethyl)-2-mercaptomethyl-butyric acid
-
reversible inhibition, IC50: 0.25 mM
0.0005
2-mercaptomethyl-3-(6-amino-pyridin-3-yl)-2-fluoro-propionic acid
-
reversible inhibition, IC50: 0.0005 mM
0.0009
2-mercaptomethyl-3-(6-amino-pyridin-3-yl)-2-hydroxy-propionic acid
-
reversible inhibition, IC50: 0.0009 mM
0.0032
2-mercaptomethyl-3-piperidin-4-yl-propionic acid
-
reversible inhibition, IC50: 0.0032 mM
0.0016
2-mercaptomethyl-3-pyrrolidin-3-yl-propionic acid
-
reversible inhibition, IC50: 0.0016 mM
0.0013
3-(2-amino-thiazol-5-yl)-2-mercaptomethyl-propionic acid
-
reversible inhibition, IC50: 0.0013 mM
0.0002
3-(2-guanidinoethylthio)-2-(mercaptomethyl)propanoic acid
-
-
0.0063
3-(6-amino-2-methyl-pyridin-3-yl)-2-mercaptomethyl-propionic acid
-
reversible inhibition, IC50: 0.0063 mM
0.0079
3-(6-amino-4-methyl-pyridin-3-yl)-2-mercaptomethyl-propionic acid
-
reversible inhibition, IC50: 0.0079 mM
0.01
3-(6-amino-5-chloro-pyridin-3-yl)-2-mercaptomethyl-propionic acid
-
reversible inhibition, IC50: 0.010 mM
0.013
3-(6-amino-5-hydroxymethyl-pyridin-3-yl)-2-mercaptomethyl-propionic acid
-
reversible inhibition, IC50: 0.013 mM
0.083
3-(6-amino-5-methyl-pyridin-3-yl)-2-(hydroxymethyl)-2-mercaptomethyl-propionic acid
-
reversible inhibition, IC50: 0.083 mM
0.001
3-(6-amino-5-methyl-pyridin-3-yl)-2-mercaptomethyl-2-methyl-propionic acid
-
reversible inhibition, IC50: 0.001 mM
0.0016
3-(6-amino-5-methyl-pyridin-3-yl)-2-mercaptomethyl-2-methyl-propionic acid
-
reversible inhibition, IC50: 0.0016 mM
0.0006
3-(6-amino-pyridin-3-yl)-2-mercaptomethyl-2-methyl-propionic acid
-
reversible inhibition, IC50: 0.0006 mM
0.0002
3-(6-amino-pyridin-3-yl)-2-mercaptomethyl-propionic acid
-
reversible inhibition, IC50: 0.0002 mM
0.000004
3-(6-aminopyridin-3-yl)-2-(1-((5-(5-chlorothiophen-2-yl)isoxazol-3-yl)methyl)-1H-imidazol-4-yl)propanoic acid
-
-
0.000002
3-(6-aminopyridin-3-yl)-2-(1-isopentyl-1H-imidazol-4-yl)propanoic acid
-
-
0.000001
3-(6-aminopyridin-3-yl)-2-(1H-imidazol-4-yl)propanoic acid
-
IC50: 0.000001 mM
0.0002
3-(6-aminopyridin-3-yl)-2-(mercaptomethyl)propanoic acid
-
-
0.000002
3-(6-aminopyridin-3-yl)-2-[1-(3-methylbutyl)-1H-imidazol-4-yl]propanoic acid
-
-
0.001
3-(cis-4-amino-cyclopent-2-yl)-2-mercaptomethyl-propionic acid
-
reversible inhibition, IC50: 0.001 mM
0.02
3-[(2-carbamimidamidoethyl)sulfanyl]-2-(sulfanylmethyl)propanoic acid
-
reversible inhibition, IC50: 0.02 mM
0.0002
anabaenopeptin-type cyclic peptide
-
-
-
0.000002
BX-528
-
-
0.029
DL-mercaptomethyl-3-guanidinoethylthiopropanoic acid
-
i.e. Plummer's inhibitor, IC50: 0.029 mM
0.0000083
EF-6265
-
-
0.000001
EF6265
-
i.e. (S)-7-amino-2-[([(R)-2-methyl-1-(3-phenylpropanoylamino)propyl]hydroxyphosphinoyl)methyl]heptanoic acid, IC50: 0.000001 mM
0.00000389
EF6265
-
i.e. (S)-7-amino-2-[([(R)-2-methyl-1-(3-phenylpropanoylamino)propyl]hydroxyphosphinoyl)methyl]heptanoic acid, IC50: 0.00000389 mM, inhibitory effect in vivo, overview
0.00000826
EF6265
-
i.e. (S)-7-amino-2-[([(R)-2-methyl-1-(3-phenylpropanoylamino)propyl]hydroxyphosphinoyl)methyl]heptanoic acid, IC50: 0.00000826 mM, inhibitory effect in vivo, overview
0.0094
guanidinyl-L-cysteine
-
IC50: 0.0094 mM in inhibition of plasma fibrin clot lysis
0.0000083
[(S)-7-amino-2-[[[(R)-2-methyl-1-(3-phenylpropanoylamino)propyl]hydroxyphosphinoyl]methyl]heptanoic acid]
-
IC50: 8.3 nM, potent and highly selective inhibitor. Systemically administered inhibitor enhances fibrinolysis in a dose- and time-dependent manner
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.017
-
substrate hippuryl-L-Arg
8
-
substrate hippuryl-L-Lys
11.4
-
substrate hippuryl-L-Arg
2000
-
-
additional information
-
-
additional information
-
electroluminescence assay. The high sensitivity of the assay allows the determination of the activatable levels of TAFI in human and other animal plasma in presence of epsilon-aminocaproic acid, an active-site inhibitor that stabilizes TAFIa
additional information
-
binding capacity of recombinant wild-type and chimeric mutant isozymes to fibrinogen and plasminogen, overview
additional information
-
-
additional information
-
in vivo arteriovenous shunt thrombosis model, ex vivo clot lysis assay
additional information
-
coupled assay methods, overview
additional information
-
assay development and optimization, overview
additional information
-
plasminogen and fibrinogen binding activity of the enzyme
additional information
-
develpoment of a fast kinetic assay for plasma enzyme quantification, coupled assay with pyruvate kinase/lactate dehydrogenase in microtiter plates, reaction scheme overview
additional information
-
TAFI activity changes during gestation
additional information
-
enzyme plasma concentration of healthy male persons, correlation of enzyme plasma concentration to cardiovascular diseases, overview
additional information
-
hemodynamics in untreated hearts of dogs and hearts treated with enzyme inhibitor MERGETPA and/or plasminogen activator, overview
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.3 - 7.6
-
assay at
7.4 - 8
-
assay at
7.4
Q2KIG3
assay at
7.5 - 8
-
peptide substrates
7.5 - 9
-
ester substrates
8
-
assay at
8.5
-
assay at
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
22 - 25
-
assay at
22
-
assay at room temperatur
37
Q2KIG3
assay at
37
-
assay at
pI VALUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
5
-
the attachment of carbohydrates to the protein constitutes approximately 20% of the total mass
5
-
about, inactive TAFI, isoelectric focusing
8
-
about, active TAFIa, isoelectric focusing
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
TAFI amount in amniotic fluids of women with normal and complicated pregnancies, overview
Manually annotated by BRENDA team
-
the enzyme circulates as inactive zymogen in the blood stream becoming activated upon blood clotting
Manually annotated by BRENDA team
-
TAFI circulates at a concentration of 0.004-0.015 mg/ml
Manually annotated by BRENDA team
-
maternal and fetal
Manually annotated by BRENDA team
-
CPU circulates in plasma as an inactive precursor, designated procarboxypeptidase U (proCPU or TAFI) from which it is released after activation by thrombin, plasmin, or the thrombin-thrombomodulin complex
Manually annotated by BRENDA team
-
TAFI is detected in gastric mucosal epithelial cells. The concentration of TAFI is correlated with the degree of gastric mucosal atrophy, inflammation, and disease activity
Manually annotated by BRENDA team
-
strong expression
Manually annotated by BRENDA team
-
hepatocytic expression, pro-carboxypeptidase R mRNA is detected only in liver
Manually annotated by BRENDA team
-
synthesized in
Manually annotated by BRENDA team
-
CPU is secreted by the liver
Manually annotated by BRENDA team
-
alveolar epithelium and macrophages, broncheal epithelium
Manually annotated by BRENDA team
-
synthesized by the liver, released to the plasma, concentration in the latter: 2.5 microgram/ml
Manually annotated by BRENDA team
-
concentration in plasma: 75 nM
Manually annotated by BRENDA team
-
TAFI content changes during gestation, correlation to protein C and plasma thrombomodulin, overview
Manually annotated by BRENDA team
-
strong expression
Manually annotated by BRENDA team
additional information
-
analysis of expression and distribution, overview, no expression in brain, kidney, placenta, and skeletal muscle
Manually annotated by BRENDA team
additional information
-
no enzyme expression in kidney and testis
Manually annotated by BRENDA team
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
35000
-
Western blot
696559
435000
-
gel permeation chromatography
28944
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
?
-
x * 60000, SDS-PAGE
?
-
x * 60000-62000, zymogen, SDS-PAGE
?
-
x * 53000, SDS-PAGE, gel filtration after treatment with guanidine-HCL
?
-
derived from zymogen by cleavage at Arg92, SDS-PAGE
?
-
x * 25000 + x * 12000, derived by cleavage at Arg330, inactive form, SDS-PAGE
?
-
x * 46000, enzymes rTAFI and pTAFI, deglycosylated enzymes, slight differences in MW might be due to differences in glycosylation, SDS-PAGE
?
-
x * 35000, active enzyme
?
-
x * 35000, processed mature glycosylated enzyme, SDS-PAGE
?
-
x * 60000
additional information
-
active site ligand complex model building using D-Cys, guanidinyl-L-cysteine, glycyl-glycyl-L-cysteine, and glycyl-L-cysteine
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
proteolytic modification
-
carboxypeptidase R is generated from pro-carboxypeptidase R by trypsin-like enzymes such as thrombin. Carboxypeptidase R regulates not only inflammatory peptides but also restricts fibrinolysis
glycoprotein
-
-
glycoprotein
-
the activation peptide contains four potential N-linked glycosylation sites at Asn22, Asn51, Asn63 and Asn96. The 36000 catalytic unit of 309 amino acids is not glycosylated. The glycosylation of the activation peptide may act to stabilize and increase the half-life of circulating TAFI
glycoprotein
-
5 N-glycosylation sites at Asn22, Asn51, Asn63, Asn86, and Asn219, detailed carbohydrate analysis, overview, no O-glycosylation
glycoprotein
-
different glycosylation patterns dependent on the enzyme source
glycoprotein
-
the enzyme contains 4 potential N-glycosylation sites at Asn22, Asn51, Asn63, and Asn96, carbohydrates account for 20% of total mass of TAFI and are responsable for stabilization
proteolytic modification
-
carboxypeptidase R is generated from pro-carboxypeptidase R by trypsin-like enzymes such as thrombin. Carboxypeptidase R regulates not only inflammatory peptides but also restricts fibrinolysis
proteolytic modification
-
elastase can activate pro-carboxypeptidase R directly or indirectly through activation of some proteases
proteolytic modification
-
the proenzyme has a MW of 55000 Da (401 aa), the enzyme has a MW of 35999 Da (309 aa), activated at proteolytis at Arg92
proteolytic modification
-
the TAFI zymogen is activated to TAFIa by plasmin, thrombin, or the thrombin-thrombomodulin complex. Turnover-number for TAFI activation by solunin in presence of throbin is 0.74 per s, the Km-value is 0.00067 mM, the TAFI zymogen is activated to TAFIa by plasmin, thrombin, or the thrombin-thrombomodulin complex. Turnover-number for TAFI activation by solunin in presence of throbin is 1.06 per s, the Km-value is 0.00084 mM, the TAFI zymogen is activated to TAFIa by plasmin, thrombin, or the thrombin-thrombomodulin complex. Turnover-number for TAFI activation by solunin in presence of thrombin is 0.74 per s, the Km-value is 0.00082 mM, the TAFI zymogen is activated to TAFIa by plasmin, thrombin, or the thrombin-thrombomodulin complex. Turnover-number for TAFI activation by solunin in presence of thrombin is 0.85 per s, the Km-value is 0.00083 mM
proteolytic modification
-
activation of TAFI to TAFIa by cleavage through thrombin, activation reaction kinetics with wild-type isozymes and mutant enzymes at 37C and pH 7.4
proteolytic modification
-
activation pathways overview, cleavage of the activation peptide from proCPU, in vitro catalyzed through thrombin, meizothrombin, plasmin, trypsin, or neutrophil elastase, only the thrombin cleaved enzyme is active, in vivo by the thrombin/thrombomodulin complex in a Ca2+-dependent manner, kinetics, overview, the plasminogen activation system, overview
proteolytic modification
-
Ca2+-dependent activation by thrombin at room temperature
proteolytic modification
-
Ca2+-dependent activation by thrombin/thrombumodulin or plasmin by cleavage of the activation peptide
proteolytic modification
-
Ca2+-dependent activation by thrombin/thrombumodulin or plasmin by cleavage of the activation peptide, in vitro activation by trypsin at 37C and pH 7.5
proteolytic modification
-
ProCPU is activated by thrombin
proteolytic modification
-
ProCPU is activated by thrombin or plasmin, the reaction is highly enhanced by thrombomodulin and glycosaminoglycans
proteolytic modification
-
the enzyme is activated by thrombin
proteolytic modification
-
the enzyme is synthesized as procarboxypeptidase B, activation through cleavage results in the active carboxypeptidase B and in the activation peptide of procarboxypeptidase B, enzyme activation is icreased in patients with acute pancreatitis, quantitative analysis of healthy persons' and patients' serum content of activation peptide, overview
proteolytic modification
-
the enzyme is synthesized as zymogen TAFI, activation by the thrombin/thrombomodulin or by plasmin to the active form TAFIa, cleavage patterns, overview
proteolytic modification
-
the enzyme is synthesized as zymogen, activation by the thrombin/thrombomodulin complex
proteolytic modification
-
the enzyme is synthesized as zymogen, activation by the thrombin/thrombomodulin complex or by plasmin
proteolytic modification
-
the enzyme is synthesized as zymogen, activation by thrombin and thrombomodulin at pH 8.5
proteolytic modification
-
the enzyme is synthesized as zymogen, activation of TAFI by thrombin to TAFIa, inactivation of TAFIa by cleavage through thrombin at Arg302
proteolytic modification
-
the inactive zymogen proCPU is Ca2+-dependently activated by thrombin/thrombumodulin or plasmin
proteolytic modification
-
the proenzyme is activated by many factors including thrombin, thrombomodulin, plasmmin, and trypsin
proteolytic modification
-
the recombinant pre-enzyme and pre-enzyme chimera are activated by thrombin/thrombomodulin in presence of Ca2+ through cleavage at Arg92 releasing the activation peptide, cleavage of Arg302 leads to inactivation by disruption of the active site, cleavage pattern with wild-type and chimeric muatnt enzymes, overview, plasmin activates inactive TAFI and inactivates active TAFI, overview
proteolytic modification
-
proteolytic enzymes activate TAFI into TAFIa, by cleaving off the N-terminal activation peptide (amino acids 1-92), from the enzyme moiety. TAFIa is active both before and after removal of the activation peptide, and the half-life of TAFIa is identical in the two preparations
proteolytic modification
-
the plasma zymogen pro-carboxypeptidase R is a plasma zymogen activated during coagulation
proteolytic modification
-
the enzyme is synthesized as zymogen TAFI, activation by the thrombin to the active form TAFIa
proteolytic modification
-
the enzyme is synthesized as zymogen, activation of TAFI by thrombin to TAFIa, inactivation of TAFIa by cleavage through thrombin at Arg302
proteolytic modification
-
carboxypeptidase R is generated from pro-carboxypeptidase R by trypsin-like enzymes such as thrombin. Carboxypeptidase R regulates not only inflammatory peptides but also restricts fibrinolysis
proteolytic modification
-
procarboxypeptidase R is generated from pro-carboxypeptidase R, a plasma zymogen, by proteolytic enzymes such as thrombin, thrombin-thrombomodulin complex and plasmin
proteolytic modification
-
the enzyme is activated by thrombin
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
using the sitting-drop vapor diffusion method. TAFIa conforms to the alpha/beta-hydrolase fold of metallocarboxypeptidases and displays two unique flexible loops on the molecular surface, accounting for structural instability and susceptibility to proteolysis
Q2KIG3
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0
-
enzyme pTAFI and rTAFI stable
28933
0
-
stable for several days
670940
4
-
at 4C higher stability than at 30C, but nevertheless unstable
28944
22
-
half-life 120-150 min
28933
22
-
half-life: several hours
653977
22
-
TAFIa half-life: 10 min; TAFIa half-life: several hours
670474
25
-
half-life: 147 min; half-life: 162 min; half-life: 73.8 min; half-life: 77.2 min
652361
25
-
half-life of carboxypeptidase R: 53 min, half-life of thrombin/thrombomodulin complex activated carboxypeptidase R: 29 min
653145
25
-
no decay of carboxypeptidase R after 60 min, half-life of thrombin/thrombomodulin complex activated carboxypeptidase R: 139 min
653145
25
-
half-life of thrombin/thrombomodulin complex activated carboxypeptidase R: 47 min
653145
25
-
half-life of carboxypeptidase R: 36 min, half-life of thrombin/thrombomodulin complex activated carboxypeptidase R: 27 min
653145
30
-
half-life 40-50 min
28933
30
-
half-life 60 min
28944
30
-
half-life: 28.3 min; half-life: 28.6 min; half-life: 54 min
652361
30
-
half-life: 45 min
653977
33
-
half-life: 14.5 min; half-life: 15.4 min; half-life: 27.2 min; half-life: 27.4 min
652361
37
-
half-life 8-9 min, stable in presence of inhibitors 2-guanidinoethylmercaptosuccinic acid or 6-aminohexanoic acid
28933
37
-
30 min, 80% loss of activity
28944
37
-
half-life: 14.7 min; half-life: 15 min; half-life: 7.8 min; half-life: 7.8 min for wild-type enzyme, 7.6 min for mutant enzyme S90A and 7.5 min for mutant enzyme D87A; half-life: 8.0 min
652361
37
-
half-life of carboxypeptidase R: 11 min, half-life of thrombin/thrombomodulin complex activated carboxypeptidase R: 8.3 min
653145
37
-
half-life of carboxypeptidase R: 6.3 min, half-life of thrombin/thrombomodulin complex activated carboxypeptidase R: 9.1 min
653145
37
-
half-life of carboxypeptidase R: 18 min, half-life of thrombin/thrombomodulin complex activated carboxypeptidase R: 10 min
653145
37
-
half-life of carboxypeptidase R: 16 min, half-life of thrombin/thrombomodulin complex activated carboxypeptidase R: 13 min
653145
37
-
half-life: 10 min
653977
37
-
half-life of wild-type TAFIa is 9.4 min, half-life of TAFIa mutant S305C/T329I is 70 min
669459
37
-
body temperature, spontaneous decay, half-life 10 min
670940
additional information
-
the activated enzyme is thermolabile and inactivated through a conformational change
669459
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
activateds TAFI, TAFI, is unstable and highly sensitive to temperature
-
analysis of stability of recombinant wild-type and chimeric mutant isozymes, the chimeric mutants show increase stability and half-life compared to the wild-type TAFI, overview
-
epsilon-aminocaproic acid, heparin or guanidinoethyl-mercaptosuccinic acid stabilize
-
inactivation of TAFIa is the result of the conformational instability of TAFIa and not a direct result of proteolysis of TAFIa. It is possible that the conformational changes that take place as a result of the conformational instability make the inactivated 35800 Da enzyme form more susceptible to proteolysis. epsilon-Aminocaproic acid stabilizes
-
intrinsic stability of activated TAFI (half-life): 6.8 min (wild-type)
-
proteolytic cleavage at Arg330 and subsequent inactivation can be diminished by the addition of 6-aminohexanoic acid, 5-aminopentanoic acid, 7-aminoheptanoic acid, hippuryl-L-Lys, hippuryl-L-Arg, L-Arg, or L-Lys
-
the activated enzyme TAFIa is highly unstable and less soluble compared to inactive TAFI, which is not due to posttranslational modifications, but to a loss of 80% of the attached glycans and a shift in pI of TAFIa, overview
-
the enzyme is spontaneously inactivated by conformational changes
-
very unstable in gel filtration procedures
-
activateds TAFI, TAFI, is unstable and highly sensitive to temperature
-
the enzyme is spontaneously inactivated by conformational changes
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
purified from plasma using a ECH-lysine sepharose column and anion-exchange chromatography
Q2KIG3
development of a method to isolate in situ activated TAFIa from serum in presence of epsilon-aminocaproic acid
-
development of a method to isolate in situ activated TAFIa from human serum in presence of epsilon-aminocaproic acid
-
from plasma
-
from plasma by a plasminogen affinity based method
-
native pro-CPU from human plasma by two steps of ion exchange chromatography, plasminogen affinity chromatography, gel filtration, and anion exchange chromatography, recombinant pro-CPU from Sf21 and H5 insect cells using the same method as for the native enzyme, to homogeneity
-
of cloned enzyme from BHK-cells
-
purified by chromatography on Q-Sepharose Fast Flow, Heparin-Sepharose CL-6B, Sephacryl S-300, and plasminogen-Sepharose columns
-
recombinant enzyme and mutant enzyme R302Q
-
recombinant TAFI and TAFI/CPB(carboxypeptidase B) chimeras; recombinant wild-type TAFI isozymes Thr147 and Thr325 and TAFI-carboxypeptidase B chimeric proteins from baby hamster kidney cells by immunoaffinity and ion exchange chromatography
-
using a Nik-9H10-Sepharose column, coupled with the antibody Nig9H10 whose epitope is located on the activation peptide of TAFI
-
using immunoaffinity chromatography in which monoclonal antibody MA-T4E3 is coupled to CNBr-activated Sepharose 4B
-
wild-type and mutant enzymes
-
development of a method to isolate in situ activated TAFIa from serum in presence of epsilon-aminocaproic acid
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
; recombinant TAFI is expressed in BHK cells
-
expression in BHK cells
-
expression in BHK-cells
-
expression of pro-CPU in Spodoptera frugiperda Sf21 and Trichoplusia ni H5 insect cells, the recombinant enzymes show different glycosylation patterns, expression rates, overview
-
expression of wild-type TAFI isozymes Thr147 and Thr325 and of two TAFI-carboxypeptidase B chimeric proteins, the CPB fragments fused to TAFI comprise residues 288-395 and 288-327, respectively, in baby hamster kidney cells; recombinant TAFI and TAFI/CPB(carboxypeptidase B) chimeras
-
gene CPB2, gene mapping, genetic organization, DNA and amino acid sequence determination and analysis, regulation of enzyme expression involves the glucocorticoid receptor and the CCAAT/enhancer binding protein sites, polymorphisms at positions 325, 147, and 505
-
TAFI gene genotyping, polymorphisms lead to 25% of TAFI level variety, especially due to polymorphisms at 5'-G1102T and 3'-T1583A, isozyme variations at residue 325 being Thr or Ile, overview
-
procarboxypeptidase R, expression in COS-7 cells
-
expression in CHO cells
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
proCPU concentration decreases significantly in the first 72 h after stroke onset and thereafter returns to baseline
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
A505G
-
naturally occurring polymorphism
A93V
-
mutant is comparably to wild-type activated by thrombin, mutant is slightly less activated by thrombin in the presence of thrombomodulin, kcat (1/sec) (p-anisylazoformyl-L-arginine, activated by thrombin in the presence of thrombomodulin): 0.205, Km (mM) (p-anisylazoformyl-L-arginine, activated by thrombin in the presence of thrombomodulin): 0.000169, mutation shows no effect on the activation by plasmin, kcat (1/sec) (hippuryl-arginine, activated by plasmin): 0.00043, Km (mM) (hippuryl-arginine, activated by plasmin): 0.00001, intrinsic stability of activated TAFI (half-life): 6.3 min
D87A
-
activated with similar kinetics as wild-type enzyme by thrombin-thrombomodulin. Increase in activation by plasmin. Thermal inactivation at 37C is similar to that of the wild-type enzyme
I182R
-
site-directed mutagenesis, the mutant shows reduced activition by thrombin but similar fibrinogen and plasminogen binding capacitiy compared to the wild-type enzyme
I183E
-
site-directed mutagenesis, the mutant shows reduced activition by thrombin but similar fibrinogen and plasminogen binding capacitiy compared to the wild-type enzyme
P91S
-
mutant exhibits specific impairment of activation by thrombin or thrombin-TM, thrombin alone, and thrombin alone or plasmin, respectively, mutant is not activated by thrombin or by thrombin in the presence of thrombomodulin, mutant is weakly activated by plasmin, kcat (1/sec) (hippuryl-arginine, activated by plasmin): 0.00020, Km (mM) (hippuryl-arginine, activated by plasmin): 0.000007, intrinsic stability of activated TAFI (half-life): 6.3 min
R302Q
-
specific activity with hippuryl-Arg is approximately half that of either recombinant wild-type enzyme or plasma derived enzymeR302Q-TAFIa is not proteolyzed by thrombin, even when 10times higher concentrations of thrombin/thrombomodulin are used
R302Q
-
mutant aggregates similarly to wild-type protein
R92K
-
mutant exhibits specific impairment of activation by thrombin or thrombin-TM, thrombin alone, and thrombin alone or plasmin, respectively, mutant is not activated by thrombin, mutant is very efficiently activated by thrombin in the presence of thrombomodulin, kcat (1/sec) (p-anisylazoformyl-L-arginine, activated by thrombin in the presence of thrombomodulin): 0.215, Km (mM) (p-anisylazoformyl-L-arginine, activated by thrombin in the presence of thrombomodulin): 0.000229, mutant is activated by plasmin with similar kinetics as wild-type, kcat (1/sec) (hippuryl-arginine, activated by plasmin): 0.00039, Km (mM) (hippuryl-arginine, activated by plasmin): 0.000006, intrinsic stability of activated TAFI (half-life): 7.1 min
S305C/T329I
-
generation of a stable activated thrombin activable fibrinolysis inhibitor variant by site-directed mutagenesis, the mutant's half-life is 11fold increased compared to the wild-type enzyme, the mutant also shows about 3fold higher fibrin clot lysis activityoverview
S90A
-
activated with similar kinetics as wild-type enzyme by thrombin-thrombomodulin. Increase in activation by plasmin. Thermal inactivation at 37C is similar to that of the wild-type enzyme
S90D/S94V/S90D
-
mutant is not activated by thrombin or by thrombin in the presence of thrombomodulin, mutant is weakly activated by plasmin, kcat (1/sec) (hippuryl-arginine, activated by plasmin): 0.00004, Km (mM) (hippuryl-arginine, activated by plasmin): 0.000005, intrinsic stability of activated TAFI (half-life): 5.9 min
S90P
-
mutant exhibits specific impairment of activation by thrombin or thrombin-TM, thrombin alone, and thrombin alone or plasmin, respectively, mutant is not activated by thrombin, mutant is very efficiently activated by thrombin in the presence of thrombomodulin, kcat (1/sec) (p-anisylazoformyl-L-arginine, activated by thrombin in the presence of thrombomodulin): 0.377, Km (mM) (p-anisylazoformyl-L-arginine, activated by thrombin in the presence of thrombomodulin): 0.000162, mutant is weakly activated by plasmin, kcat (1/sec) (hippuryl-arginine, activated by plasmin): 0.00008, Km (mM) (hippuryl-arginine, activated by plasmin): 0.000009, intrinsic stability of activated TAFI (half-life): 5.5 min
S94V
-
mutant is considerably more effectively activated by thrombin, mutant is also activated by thrombin in the presence of thrombomodulin, kcat (1/sec) (p-anisylazoformyl-L-arginine, activated by thrombin in the presence of thrombomodulin): 0.328, Km (mM) (p-anisylazoformyl-L-arginine, activated by thrombin in the presence of thrombomodulin): 0.000232, mutation shows no effect on the activation by plasmin, kcat (1/sec) (hippuryl-arginine, activated by plasmin): 0.0003, Km (mM) (hippuryl-arginine, activated by plasmin): 0.000006, intrinsic stability of activated TAFI (half-life): 6.1 min
T147A
-
naturally occurring polymorphism
T325I
-
naturally occurring mutant showing a twofold increased stability compared to the wild-type enzyme
T325I
-
naturally occurring polymorphism
T325I
-
distribution of the Thr325Ile proCPU polymorphism in 193 patients with mucocutaneous bleeding of whom 116 are bleeders of unknown cause , and in 143 healthy, age and sex-matched controls is analyzed. ProCPU concentration is higher in women than in men, increases with age, and is significantly correlated with clot lysis time, platelet count, APTT, and PT. proCPU levels are unexpectedly higher in patients than in controls. The allele distribution of the Thr325Ile proCPU polymorphism is similar in both groups, with a low percentage of homozygous Ile/Ile
T325I/T329I/H333Y/H335Q
-
inactive mutant has a 70fold increased half-life and a 3fold to 5fold increased antifibrinolytic function as compared to wild-type, mutant aggregates into large, insoluble complexes that can be removed by centrifugation
I325I
-
a higher frequency of the most stable Ile325Ile proCPU is seen among carriers of FII G20210A mutation compared to the control group in comparison to Thr325Thr and Thr325Ile proCPU. In addition, proCPU as a risk factor for thrombosis is evaluated. In heterozygous carriers of FV Leiden or FII G20210A high levels of proCPU confers to an almost 4fold increased risk for spontaneous onset thrombosis. The more stable Ile325Ile proCPU seems to impose a higher risk for clinical manifestation of the thrombophilic condition
additional information
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generation of a TAFI a form with a highly stable activity by replacing a region in TAFI with the corresponding region in pancreatic CPB (carboxypeptidase B). TAFI-CPB(293-333) can be activated by thrombin-thrombomodulin, but not as efficient as wild-type TAFI. After activation, this chimeric enzyme is unstable and hardly able to prolong clot lysis of TAFI-deficient plasma. Binding of the mutant enzyme to both plasminogen and fibrinogen is normal compared to wild-type TAFI. TAFI-CPB(293-401) can be activated by thrombin-thrombomodulin, although at a lower rate compared with wild-type TAFI. The activated mutant displays a markedly prolonged half-life of 1.5 h. The chimeric enzyme does not bind plasminogen and fibrinogen and can prolong the clot lysis time in TAFI-deficient plasma, although not as efficiently as wild-type TAFI
additional information
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mutant with the fibrinogen Bbeta thrombin cleavage site Ala-Arg-Gly-His-Arg substituted into positions 91-95: activated with similar kinetics as wild-type enzyme by thrombin-thrombomodulin, activated by plasmin with the same kinetics as wild-type enzyme. Mutant enzyme with the protein C thrombin cleavage site Asp-Pro-Arg-Leu-Ile-Asp substituted into positions 90-95: no measurable activation by plasmin
additional information
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construction of chimeric proteins composed by wild-type TAFI isozymes Thr147 and Thr325, and carboxypeptidase B, CPB, fragments comprising residues 288-395 and 288-327, the chimeric mutants show increase stability and 32-34fold increased half-lives compared to the wild-type TAFI
additional information
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enzyme disorder phenotype, overview
additional information
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immobilization of purified recombinnat Pro-CPU on Sepharose for specific antibody purification
additional information
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the enzyme shows polymorphisms, e.g. at residue 325, genotypes, correlated diseases, overview
additional information
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circulating TAFI levels and carotid intima-media thickness (CIMT) in polycystic ovary syndrome (PCOS) patients and control subjects are analysed. Plasma TAFI levels are similarly in polycystic ovary syndrome patients compared with healthy controls. No difference is observed in the combined IMT among the studied groups
additional information
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coagulation and fibrinolytic parameters including TAFI and TFPI are assessed in patients with hypothyroidism: Factors V, VII, VIII activities, von Willebrand factor, protein C, protein S, thrombomodulin, TFPI, and TAFI are measured. Compared with the control subjects, factor VII activity, and thrombomodulin Ag and TAFI Ag levels are significantly increased in patients with hypothyroidism, whereas FV, FVIII, vWF, protein C and protein S activities, and TFPI Ag levels are significantly decreased
additional information
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HT1080 cells mediate activation of TAFI in plasma in the presence of soluble-type thrombomodulin through cell-dependent prothrombin activation. HT1080 cells stably expressing thrombomodulin (TM-HT1080) mediate plasma TAFI activation without added soluble-type thrombomodulin, wild-type cells and Mock-transfected HT1080 cells (Mock) do not. Production of TAFIa suppresses cell-mediated plasminogen activation. Cell invasion by TMHT1080 is partially enhanced by addition of a TAFIa/CPB inhibitor
additional information
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plasma TAFI and PAI-1 antigen levels are measured in pregnant women with gestational diabetes, pregnant women with normal glucose tolerance, and age-matched non-pregnant women with no history of gestational diabetes. Increased plasma TAFI antigen levels are found in pregnant women compared to non-pregnant controls. No statistically significant difference in TAFI antigen levels is observed between women with gestational diabetes and pregnant controls. Plasma PAI-1 antigen levels are higher in gestational diabetes than pregnant and non-pregnant controls
additional information
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proCPU levels in thrombophilia carriers and healthy subjects are assessed: Results show that patients with inherited thrombophilia have a tendency toward lower mean proCPU plasma levels compared to healthy controls. This difference is only significant in carriers of factor II G20210A
additional information
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TAFI activity status and the effect of L-thyroxin hormone replacement treatment on fibrinolytic system in patients with Hashimotos thyroiditis is analysed: In the control group, TAFI activity levels are 9.6 microgram/ml. In patients with L-thyroxin before and after treatment there are high levels of TAFI activity value of 14.2 and 12.9 microgram/ml, respectively. In the patient group, after L-thyroxin treatment TAFI activity levels are decreased but they are not statistically significant. When compared to the control group, high levels of TAFI activity are observed in the patient group
additional information
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the gastric intramucosal concentrations of TAFI are measured by enzyme immunoassay. This study comprises 65 patients with gastroduodenal disorders. The gastric levels of TAFI and plasminogen activator inhibitor-1 are significantly increased in patients with Helicobacter pylori compared to those without infection or cured Helicobacter pylori
additional information
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the levels of TAFI antigen and also its relationship with other hemostasis markers in a group of patients affected with polycystic ovary syndrome (PCOS)-under Diane-35 (ethinyl estradiol/cyproterone acetate) treatment or not compared with a group of healthy controls is analysed. TAFI antigen levels of groups A and B are significantly higher than in controls, but no difference is observed between them. All of the other coagulation and fibrinolysis parameters are comparable between the three groups
additional information
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variant mutants are constructed and expressed mutant variants that have key substitutions in the amino acids surrounding the scissile Arg92-Ala93 bond. Variants are identified that show patterns of resistance to specific activators. The variants that are tested also showed antifibrinolytic potentials that can be rationalized in terms of which enzymes are capable of activating them
moe
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construction of enzyme-deficient mice by gene disruption, which is not lethal and does not cause a pathogenic phenotype, the mice show delayed wound healing, overview
additional information
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enzyme-deficient mice phenotype, overview
additional information
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the development of immune complex-mediated glomerulonephritis in wild-type and TAFI-deficient mice is compared. After six weeks of treatment with horse spleen apoferritin and lipoplysaccharide to induce glomerulonephritis, mice deficient in TAFI have significantly better renal function as shown by lower concentrations of albumin in urine and blood urea nitrogen compared to wild-type mice. The activity of plasmin and matrix metalloproteinases is significantly increased, and mesangial matrix expansion and the deposition of collagen and fibrin in kidney tissues are significantly decreased in TAFI-knockout mice as compared to their wild-type counterparts
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
diagnostics
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the activation peptide of procarboxypeptidase B, set free during activation of procarboxypeptidase B, is a marker for acute pancreatitis
medicine
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agents that improve the efficiency of TAFI to downregulate fibrinolysis might become available for the treatment of bleeding disorders such as hemophilias A and B
medicine
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a range of fibrinolytic kinetic values and the contribution of thrombin activatable fibrinolysis inhibitor in normal subjects are established. Study of disease states involving potential hypofibrinolysis can be conducted using this system to link fibrinolytic vulnerability and thrombophilia
medicine
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argatroban enhances fibrinolysis via a differential inhibition of thrombin-mediated activation of TAFI and factor XIII
medicine
Q8IWV7
coagulation pathway in patients with non-small-cell lung cancer (NSCLC) is investigated: The TAFI activity, prothrombin fragment 1 + 2 levels, and tissue factor pathway inhibitor activity are significantly higher in patients with lung cancer than in subjects in the control group. There is no statistically significant associations between TAFI activity levels and patient age, sex, body mass index, histopathology, or stage of disease
medicine
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important differences in the hemostatic parameters between the patients with hypothyroidism and healthy controls are found. Increased FVII, TM, and TAFI and decreased FV, FVIII, vWF, protein C, protein S, and TFPI in these patients represent a potential hypercoagulable and hypofibrinolytic state, possible endothelial dysfunction, which might augment the risk for atherosclerotic and atherothrombotic complications in patients with hypothyroidism
medicine
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in Hashimoto thyroiditis, patients have high levels of TAFI activity compared to controls. A high level of TAFI activity suggests fibrinolytic deficit or thrombotic tendency in hypothyroid patients and this deficit is persistent after L-thyroxine replacement
medicine
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it is investigated whether it is possible to detect the activation of the proCPU/CPU system during therapeutic thrombolysis of patients with acute ischemic stroke: activation of the proCPU system during intravenous recombinant tissue plasminogen activator and intra-arterial administration of urokinase in patients with acute ischemic stroke is shown
medicine
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no significant difference in lipid parameters is determined between patients with polycystic ovary syndrome and healthy controls. In addition, no difference in CIMT measurements and TAFI levels between patients with polycystic ovary syndrome and healthy controls is shown
medicine
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pregnancy is associated with elevated plasma TAFI antigen levels but no additional effect of gestational diabetes is found on plasma TAFI antigen levels beyond pregnancy
medicine
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proCPU activation and its relatedness to efficacy and safety of thrombolytic therapy in ischemic stroke patients is investigated. In 12 patients with ischemic stroke who are treated with intravenous or intraarterial thrombolysis, venous blood samples are taken at different time points before, during and after thrombolytic therapy. No correlations between maximal CPU activity or proCPU consumption and patient or stroke characteristics are found. Maximal CPU activity is associated with evolution of the clinical deficit and achieved recanalisation. ProCPU consumption is related to the risk of intracranial hemorrhage, mortality and final infarct volume
medicine
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results suggest that women with polycystic ovary syndrome have impaired fibrinolysis, as reflected by increased TAFI. This impairment can contribute to the risk of cardiovascular disease in polycystic ovary syndrome
medicine
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TAFI as well as plasminogen activator inhibitor-1 plasma levels in inflammatory bowel disease patients are compared with healthy controls. Mean plasma plasminogen activator inhibitor-1 levels are significantly higher in both ulcerative colitis patients and Crohns disease patients compared with healthy controls. Mean plasma TAFI levels are significantly lower in both ulcerative colitis patients and Crohns disease patients compared with healthy controls. These results suggest an imbalance of fibrinolysis in inflammatory bowel disease patients
medicine
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TAFI is present in the gastric mucosa and it may play a role in the pathogenesis of Helicobacter pylori infection-associated gastroduodenal disorders
medicine
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the absolute risk of venous and arterial thromboembolism in subjects with high TAFI levels versus subjects with normal levels, and the contribution of other concomitant thrombophilic defects is assessed. Relatives from four identical cohort studies in families with either deficiencies of antithrombin, protein C or protein S, prothrombin 20210A, high factor VIII levels, or hyperhomocysteinemia are pooled. Only high factor VIII levels are associated with an increased risk of venous and arterial thrombosis, independently of TAFI levels. None of these concomitant defects shows interaction with high TAFI levels. High TAFI levels are not associated with an increased risk of venous and arterial thromboembolism in thrombophilic families
medicine
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the extent of TAFI activation over time in normal plasma and factor VIII deficient plasma (FVIII-DP) is analysed and it is determined whether soluble thrombomodulin can correct the lysis defect in factor VIII deficient plasma. TAFI activation increases as the concentration of factor VIII increases. Factor VIII at a level of 10% fully corrects the lysis defect in spite of the extent of TAFI activation being only one half that obtained with 100% factor VIII. In addition, thrombomodulin increases TAFI activation sufficiently to correct the premature lysis defect in factor VIII-deficient plasma
medicine
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the increased risk of thrombosis in thrombophilia patients is not only ascribable to an increased thrombin generation, but also high levels of proCPU and the presence of the 325Ile genotype tip the balance towards thrombotic tendency even further
medicine
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the proCPU system is not of major importance in the bleeding pathogenesis of these patients. The higher proCPU levels in the patients may even modestly counteract the bleeding tendency
medicine
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this study aims to assess concomitantly the effects of fenofibrate therapy on thrombin-activatable fibrinolysis inhibitor concentrations and endothelial functions in patients with metabolic syndrome. Twenty-five patients are enrolled in the study. Fenofibrate decreases thrombin-activatable fibrinolysis inhibitor levels and improves endothelial function in metabolic syndrome and, thus, suggests a potential for protection against cardiovascular effects
medicine
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the decrease in proCPU concentration in the first 72 h after stroke onset correlates with more severe stroke, unfavourable stroke evolution, and poor longterm stroke outcome
molecular biology
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results demonstrate that the activation peptide is not required for TAFIa activity or for stabilization of the enzyme, but solely for stabilization of the zymogen
molecular biology
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thrombomodulin suppresses pericellular fibrinolysis and plasma-induced tumor cell invasion which is mediated by plasma TAFI activation
pharmacology
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enzyme inhibitors are valid as enhancer of physiological fibrinolysis in microcirculation and as adjunctive agent to tissue-type plasminogen activator for thromboembolic diseases in humans while maintaining a small effect on primary hemostasis
medicine
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TAFI-mediated inhibition of plasmin generation plays a role in the pathogenesis of glomerulonephritis, and it might constitute a novel molecular target for therapy
medicine
Q9EQV9
results provide evidence for a role of TAFI in arterial thrombosis in rats and suggest that TAFI inhibition could be explored as an attractive target for the development of new antithrombotic drugs
medicine
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TAFI plays an important role in the deterioration of organ dysfunction in sepsis and the inhibitor of TAFIa protects against sepsis-induced tissue damage through regulation of fibrinolysis and inflammation