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Information on EC 3.4.17.20 - Carboxypeptidase U and Organism(s) Homo sapiens and UniProt Accession Q8IWV7
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3.4.17.20 Carboxypeptidase USpecify your search results
Word Map
- 3.4.17.20
- plasminogen
- coagulation
- clot
-
fibrinolytic
- thrombosis
- thrombomodulin
- plasmin
- fibrinogen
- pai-1
-
bleeding
- inhibitor-1
-
antifibrinolytic
-
hemostatic
- prothrombin
- zymogen
- venous
-
anticoagulant
- thromboembolism
-
tissue-type
-
d-dimers
-
hypofibrinolysis
-
profibrinolytic
-
thrombolytic
- thrombin-thrombomodulin
-
hypercoagulable
-
procoagulant
- c5a
- antithrombin
- thrombus
-
prothrombotic
-
thrombin-antithrombin
-
thrombin-mediated
- coagulopathy
-
plasmin-antiplasmin
-
haemostasis
- thromboplastin
- medicine
- antiplasmin
- alpha2-antiplasmin
-
fxiii
- metallocarboxypeptidase
- anaphylatoxins
- molecular biology
- pharmacology
-
plasmin-mediated
- thrombophilia
-
thrombelastography
-
activator-induced
-
thrombin-dependent
- rfviia
-
t-pa-induced
-
thrombin-cleaved
-
euglobulin
- diagnostics
The taxonomic range for the selected organisms is: Homo sapiens
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Synonyms
tafia, thrombin-activatable fibrinolysis inhibitor, thrombin activatable fibrinolysis inhibitor, procpu, procarboxypeptidase b, carboxypeptidase u, thrombin-activable fibrinolysis inhibitor, procarboxypeptidase u, carboxypeptidase b2, plasma carboxypeptidase b, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
Arginine carboxypeptidase
-
-
-
-
Carboxypeptidase B, pro-
-
-
-
-
Carboxypeptidase R
Carboxypeptidase-U
-
-
-
-
CPU
Plasma carboxypeptidase B
plasma procarboxypeptidase U
pro-pCPB
-
-
-
-
Procarboxypeptidase B
proCPU
pTAFI
-
-
-
-
rTAFI
-
-
-
-
TAFI
TAFIa
thrombin activatable fibrinolysis inhibitor
-
-
Thrombin-activable fibrinolysis inhibitor
-
-
-
-
thrombin-activatable fibrinolysis inhibitor
Carboxypeptidase R
-
-
-
-
CPU
-
-
-
-
Plasma carboxypeptidase B
-
-
-
-
Procarboxypeptidase B
-
-
-
-
TAFI
-
-
-
-
TAFI
-
-
TAFIa
-
-
-
-
TAFIa
-
-
thrombin-activatable fibrinolysis inhibitor
-
-
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
release of C-terminal Arg and Lys from a polypeptide
catalytic mechanism and substrate specificity
-
release of C-terminal Arg and Lys from a polypeptide
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
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
the enzyme prefers C-terminal arginine over lysine
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of peptide bond
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
156621-18-0
-
37329-68-3
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
Ala-Ser-His-Leu-Gly-Leu-Ala-Arg + H2O
Ala-Ser-His-Leu-Gly-Leu-Ala + Arg
-
reaction is much more efficient than reaction with EC 3.4.17.3
-
?
Arg6-Leu5-enkephalin + H2O
Tyr-Gly-Gly-Phe-Leu + Arg
-
i.e. Tyr-Gly-Gly-Phe-Leu-Arg
-
-
?
Arg6-Met5-enkephalin + H2O
Tyr-Gly-Gly-Phe-Met + Arg
-
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
-
-
-
?
bradykinin + H2O
Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe + Arg
-
i.e. Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg
-
-
?
complement component C3a octapeptide + H2O
?
-
removal of terminal arginine, low activity
-
-
?
complement component C5a octapeptide + H2O
?
-
removal of terminal arginine
-
-
?
hippuryl-arginine + H2O
hippuric acid + L-arginine
-
substrate is used to measure the TAFI activation by plasmin
-
-
?
hippuryl-L-arginine + H2O
hippuric acid + L-arginine
-
-
-
-
?
Lys6-Leu5-enkephalin + H2O
Tyr-Gly-Gly-Phe-Leu + Lys
-
i.e. Tyr-Gly-Gly-Phe-Leu-Lys
-
-
?
Lys6-Met5-enkephalin + H2O
Tyr-Gly-Gly-Phe-Met + Lys
-
i.e. Tyr-Gly-Gly-Phe-Met-Lys
-
-
?
N-benzoyl-2'-cyano-L-Phe-L-Arg + H2O
N-benzoyl-2'-cyano-L-Phe + L-Arg
-
selective CPU substrate
-
-
?
N-[3-(2-Furylacryloyl)]-L-Ala-L-Arg + H2O
N-[3-(2-Furylacryloyl)]-L-Ala + L-Arg
-
-
-
-
?
p-anisylazoformyl-L-arginine + H2O
p-anisylazoformic acid + L-arginine
-
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
-
-
-
-
?
[3-(2-furylacryloyl)]-L-phenylalanyl-L-phenylalanine + H2O
[3-(2-furylacryloyl)]-L-phenylalanine + L-phenylalanine
-
-
-
-
?
fibrin + H2O
fibrin + Lys
-
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
-
partially degraded fibrin in fibrin clots, cleavage of C-terminal Lys
-
-
?
fibrin + H2O
Lys + ?
-
attenuates clot lysis by removing lysine residues from a fibrin clot
-
?
Fibrin, partially degraded + H2O
?
-
the enzyme suppresses the ability of fibrin to catalyze plasminogen activation and thus delays clot lysis
-
-
?
Fibrin, partially degraded + H2O
?
-
molecular connection between coagulation and fibrinolysis
-
-
?
Fibrin, partially degraded + H2O
Fibrin, partially degraded + L-Lys + L-Arg
-
-
-
?
Fibrin, partially degraded + H2O
Fibrin, partially degraded + L-Lys + L-Arg
-
-
-
?
Fibrin, partially degraded + H2O
Fibrin, partially degraded + L-Lys + L-Arg
-
-
-
?
Fibrin, partially degraded + H2O
Fibrin, partially degraded + L-Lys + L-Arg
-
-
-
-
?
His-Lys-Asp-Met-Gln-Leu-Gly-Arg + H2O
His-Lys-Asp-Met-Gln-Leu-Gly + Arg
-
i.e. C5a, reaction is much more efficient than reaction with EC 3.4.17.3
-
?
His-Lys-Asp-Met-Gln-Leu-Gly-Arg + H2O
His-Lys-Asp-Met-Gln-Leu-Gly + Arg
-
i.e. C5a, the enzyme significantly contributes to the inactivation of C5a, the most potent of the complement derived anaphylatoxins
-
?
N-[3-(2-Furylacryloyl)]-L-Ala-L-Lys + H2O
N-[3-(2-Furylacryloyl)]-L-Ala + L-Lys
-
-
-
?
N-[3-(2-Furylacryloyl)]-L-Ala-L-Lys + H2O
N-[3-(2-Furylacryloyl)]-L-Ala + L-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
?
-
-
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 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 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
?
-
the effects of the carboxypeptidase U system on the regulation of fibrinolysis is investigated and compared in four different in vitro models of fibrinolysis
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
His-Lys-Asp-Met-Gln-Leu-Gly-Arg + H2O
His-Lys-Asp-Met-Gln-Leu-Gly + Arg
-
i.e. C5a, the enzyme significantly contributes to the inactivation of C5a, the most potent of the complement derived anaphylatoxins
-
?
fibrin + H2O
fibrin + Lys
-
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
-
partially degraded fibrin in fibrin clots, cleavage of C-terminal Lys
-
-
?
fibrin + H2O
Lys + ?
-
attenuates clot lysis by removing lysine residues from a fibrin clot
-
?
Fibrin, partially degraded + H2O
?
-
the enzyme suppresses the ability of fibrin to catalyze plasminogen activation and thus delays clot lysis
-
-
?
Fibrin, partially degraded + H2O
?
-
molecular connection between coagulation and fibrinolysis
-
-
?
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 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 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
?
-
the effects of the carboxypeptidase U system on the regulation of fibrinolysis is investigated and compared in four different in vitro models of fibrinolysis
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Ca2+
Zn2+
Zn2+
-
bound by residues His159, Glu162, and His288, Zn2+ is important in the catalytic mechanism
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(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
-
-
2-(2-amino-pyridin-4-ylmethyl)-3-mercapto-propionic acid
-
reversible inhibition, IC50: 0.0032 mM
2-(6-amino-pyridin-3-ylmethyl)-2-mercaptomethyl-butyric acid
-
reversible inhibition, IC50: 0.25 mM
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-(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-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-(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
BX-528
-
i.e. (S)-2-[3-(aminomethyl)phenyl]-3-hydroxy[(R)-2-methyl-1-[(3-phenylpropyl)sulfonyl]aminopropyl]phosphoryl propanoic acid
DL-mercaptomethyl-3-guanidinoethylthiopropanoic acid
-
i.e. Plummer's inhibitor, IC50: 0.029 mM
EF-6265
-
i.e. (2S)-7-amino-2-((hydroxyl((R)-2-methyl-1-(3-phenylpropanamido)propyl)phosphoryl)methyl)heptanoic acid
guanidinyl-L-cysteine
-
IC50: 0.0094 mM in inhibition of plasma fibrin clot lysis
potato tuber carboxypeptidase inhibitor
-
competitive inhibition in the nanomolar range
-
[(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
3-(6-amino-5-methyl-pyridin-3-yl)-2-mercaptomethyl-2-methyl-propionic acid
-
reversible inhibition, IC50: 0.001 mM
3-(6-amino-5-methyl-pyridin-3-yl)-2-mercaptomethyl-2-methyl-propionic acid
-
reversible inhibition, IC50: 0.0016 mM
EF6265
-
i.e. (S)-7-amino-2-[([(R)-2-methyl-1-(3-phenylpropanoylamino)propyl]hydroxyphosphinoyl)methyl]heptanoic acid, IC50: 0.000001 mM
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
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%
-
UK-396082
-
i.e. (S)-5-amino-2-((1-propyl-1H-imidazol-4-yl)methyl)pentanoic acid
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
-
additional information
inhibition of the carboxypeptidase U system because of hemolysis results in an increase of lysis in functional fibrinolysis assays
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
activation peptide
-
the activated TAFIa acts in complex with the activation peptide, enzyme regulation overview
-
factor VIII
-
TAFI activation increases in plasma as the concentration of factor VIII increases
-
Trypsin
-
can activate purified enzyme, proteolytic cleavage at Arg92 produces active enzyme, cleavage at Arg330 yields inactive fragments
-
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
-
thrombin-thrombomodulin
-
activation in the presence of thrombomodulin is considerably enhanced
-
Thrombomodulin
-
proteolytic cleavage at Arg92 produces active enzyme, cleavage at Arg330 yields inactive fragments, activates 1000fold
-
Thrombomodulin
-
the epidermal growth factor-like domain 3 of thrombomodulin is required for activation
-
additional information
-
activation of TAFI by thrombin is an inefficient process, thrombomodulin stimulates the activation 1250fold. Activation by plasmin is stimulated by glycosaminoglycan
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.012
biotinyl-(epsilon-aminocaproic acid)-(epsilon-aminocaproic acid)-Gly-Leu-Met-Val-Gly-Gly-Val-Val-Arg-OH
-
room temperature
additional information
additional information
-
binding kinetics of recombinant wild-type and chimeric mutant isozymes to fibrinogen and plasminogen, overview
-
0.000005
hippuryl-arginine
-
mutant S90D/S94V/S90D, activation of TAFI by plasmin
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
2.3
biotinyl-(epsilon-aminocaproic acid)-(epsilon-aminocaproic acid)-Gly-Leu-Met-Val-Gly-Gly-Val-Val-Arg-OH
-
room temperature
0.00004
hippuryl-arginine
-
mutant S90D/S94V/S90D, activation of TAFI by plasmin
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
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
-
the Ki-value for protamine is above 50 mM
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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
Homo sapiens
-
-
0.0032
2-(2-amino-pyridin-4-ylmethyl)-3-mercapto-propionic acid
Homo sapiens
-
reversible inhibition, IC50: 0.0032 mM
0.25
2-(6-amino-pyridin-3-ylmethyl)-2-mercaptomethyl-butyric acid
Homo sapiens
-
reversible inhibition, IC50: 0.25 mM
0.0005
2-mercaptomethyl-3-(6-amino-pyridin-3-yl)-2-fluoro-propionic acid
Homo sapiens
-
reversible inhibition, IC50: 0.0005 mM
0.0009
2-mercaptomethyl-3-(6-amino-pyridin-3-yl)-2-hydroxy-propionic acid
Homo sapiens
-
reversible inhibition, IC50: 0.0009 mM
0.0032
2-mercaptomethyl-3-piperidin-4-yl-propionic acid
Homo sapiens
-
reversible inhibition, IC50: 0.0032 mM
0.0016
2-mercaptomethyl-3-pyrrolidin-3-yl-propionic acid
Homo sapiens
-
reversible inhibition, IC50: 0.0016 mM
0.0013
3-(2-amino-thiazol-5-yl)-2-mercaptomethyl-propionic acid
Homo sapiens
-
reversible inhibition, IC50: 0.0013 mM
0.0063
3-(6-amino-2-methyl-pyridin-3-yl)-2-mercaptomethyl-propionic acid
Homo sapiens
-
reversible inhibition, IC50: 0.0063 mM
0.0079
3-(6-amino-4-methyl-pyridin-3-yl)-2-mercaptomethyl-propionic acid
Homo sapiens
-
reversible inhibition, IC50: 0.0079 mM
0.01
3-(6-amino-5-chloro-pyridin-3-yl)-2-mercaptomethyl-propionic acid
Homo sapiens
-
reversible inhibition, IC50: 0.010 mM
0.013
3-(6-amino-5-hydroxymethyl-pyridin-3-yl)-2-mercaptomethyl-propionic acid
Homo sapiens
-
reversible inhibition, IC50: 0.013 mM
0.083
3-(6-amino-5-methyl-pyridin-3-yl)-2-(hydroxymethyl)-2-mercaptomethyl-propionic acid
Homo sapiens
-
reversible inhibition, IC50: 0.083 mM
0.0006
3-(6-amino-pyridin-3-yl)-2-mercaptomethyl-2-methyl-propionic acid
Homo sapiens
-
reversible inhibition, IC50: 0.0006 mM
0.0002
3-(6-amino-pyridin-3-yl)-2-mercaptomethyl-propionic acid
Homo sapiens
-
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
Homo sapiens
-
-
0.000002
3-(6-aminopyridin-3-yl)-2-(1-isopentyl-1H-imidazol-4-yl)propanoic acid
Homo sapiens
-
-
0.000001
3-(6-aminopyridin-3-yl)-2-(1H-imidazol-4-yl)propanoic acid
Homo sapiens
-
IC50: 0.000001 mM
0.000002
3-(6-aminopyridin-3-yl)-2-[1-(3-methylbutyl)-1H-imidazol-4-yl]propanoic acid
Homo sapiens
-
-
0.001
3-(cis-4-amino-cyclopent-2-yl)-2-mercaptomethyl-propionic acid
Homo sapiens
-
reversible inhibition, IC50: 0.001 mM
0.02
3-[(2-carbamimidamidoethyl)sulfanyl]-2-(sulfanylmethyl)propanoic acid
Homo sapiens
-
reversible inhibition, IC50: 0.02 mM
0.27
5-bromo-4-chloro-indolyl beta-D-galactopyranosyl-alpha-2,6-N-acetyl-neuraminic acid
Homo sapiens
-
reversible inhibition, IC50: 0.27 mM
0.029
DL-mercaptomethyl-3-guanidinoethylthiopropanoic acid
Homo sapiens
-
i.e. Plummer's inhibitor, IC50: 0.029 mM
0.0094
guanidinyl-L-cysteine
Homo sapiens
-
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]
Homo sapiens
-
IC50: 8.3 nM, potent and highly selective inhibitor. Systemically administered inhibitor enhances fibrinolysis in a dose- and time-dependent manner
0.001
3-(6-amino-5-methyl-pyridin-3-yl)-2-mercaptomethyl-2-methyl-propionic acid
Homo sapiens
-
reversible inhibition, IC50: 0.001 mM
0.0016
3-(6-amino-5-methyl-pyridin-3-yl)-2-mercaptomethyl-2-methyl-propionic acid
Homo sapiens
-
reversible inhibition, IC50: 0.0016 mM
0.000001
EF6265
Homo sapiens
-
i.e. (S)-7-amino-2-[([(R)-2-methyl-1-(3-phenylpropanoylamino)propyl]hydroxyphosphinoyl)methyl]heptanoic acid, IC50: 0.000001 mM
0.00000826
EF6265
Homo sapiens
-
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
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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
-
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
-
enzyme plasma concentration of healthy male persons, correlation of enzyme plasma concentration to cardiovascular diseases, overview
additional information
-
plasminogen and fibrinogen binding activity of the enzyme
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
pI VALUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
5
-
the attachment of carbohydrates to the protein constitutes approximately 20% of the total mass
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
TAFI amount in amniotic fluids of women with normal and complicated pregnancies, overview
-
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
additional information
-
analysis of expression and distribution, overview, no expression in brain, kidney, placenta, and skeletal muscle
-
the enzyme circulates as inactive zymogen in the blood stream becoming activated upon blood clotting
-
-
647563, 651987, 653008, 667916, 668287, 670058, 670060, 670291, 670474, 670939, 670940, 670944, 696559, 696925, 696926, 697399, 697427, 697552, 697622, 697721, 697791, 698144, 698377, 699864, 699870, 700206, 701278, 701295, 707122, 707597, 709725, 709727
-
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
activity levels are higher in patients with acute myocardial infarction than in controls
in all individuals, carboxypeptidase U generation is biphasic. Marked inter-individual differences are present and a reference range is determined. The endogenous Carboxypeptidase U generation potential is the composite effect of multiple factors. With respect to the first carboxypeptidase U activity peak characteristics, a correlations with baseline proCPU concentration, proCPU Thr325Ile polymorphism, time to clot initiation and the clot lysis time is detected. The second CPU peak is related with baseline proCPU levels and with the maximum turbidity of the clot lysis profile
-
-
28932, 28933, 28934, 28935, 28936, 28938, 28940, 28941, 28942, 28943, 28944, 28945, 652560, 669459, 696929
-
synthesized by the liver, released to the plasma, concentration in the latter: 2.5 microgram/ml
-
TAFI content changes during gestation, correlation to protein C and plasma thrombomodulin, overview
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
-
-
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
12000
-
x * 25000 + x * 12000, derived by cleavage at Arg330, inactive form, SDS-PAGE
25000
-
x * 25000 + x * 12000, derived by cleavage at Arg330, inactive form, SDS-PAGE
35000
46000
-
x * 46000, enzymes rTAFI and pTAFI, deglycosylated enzymes, slight differences in MW might be due to differences in glycosylation, SDS-PAGE
60000
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
-
active site ligand complex model building using D-Cys, guanidinyl-L-cysteine, glycyl-glycyl-L-cysteine, and glycyl-L-cysteine
?
-
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
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
glycoprotein
proteolytic modification
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
-
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
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 1.06 per s, the Km-value is 0.00084 mM
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 thrombin is 0.74 per s, the Km-value is 0.00082 mM
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 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 37°C 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 37°C and pH 7.5
proteolytic modification
-
ProCPU is activated by thrombin or plasmin, the reaction is highly enhanced by thrombomodulin and glycosaminoglycans
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 inactive precursor procarboxypeptidase U is converted to its active form by thrombin, the thrombin-thrombomodulin complex or plasmin
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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 37°C 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
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
P91S
R302Q
R92K
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 37°C 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
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
T325I
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
additional information
P91S
-
mutant exhibits specific impairment of activation by thrombin or thrombin-TM, thrombin alone, and thrombin alone or plasmin, respectively
P91S
-
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
R92K
-
mutant exhibits specific impairment of activation by thrombin or thrombin-TM, thrombin alone, and thrombin alone or plasmin, respectively
R92K
-
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
S90P
-
mutant exhibits specific impairment of activation by thrombin or thrombin-TM, thrombin alone, and thrombin alone or plasmin, respectively
S90P
-
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
T325I
-
naturally occurring mutant showing a twofold increased stability compared to the wild-type enzyme
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
additional information
-
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
-
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
-
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
immobilization of purified recombinnat Pro-CPU on Sepharose for specific antibody purification
additional information
-
immobilization of purified recombinnat Pro-CPU on Sepharose for specific antibody purification
additional information
-
the enzyme shows polymorphisms, e.g. at residue 325, genotypes, correlated diseases, overview
additional information
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
22
25
30
33
37
additional information
-
the activated enzyme is thermolabile and inactivated through a conformational change
25
-
no decay of carboxypeptidase R after 60 min, half-life of thrombin/thrombomodulin complex activated carboxypeptidase R: 139 min
37
-
half-life 8-9 min, stable in presence of inhibitors 2-guanidinoethylmercaptosuccinic acid or 6-aminohexanoic acid
37
-
half-life of carboxypeptidase R: 6.3 min, half-life of thrombin/thrombomodulin complex activated carboxypeptidase R: 9.1 min
37
-
half-life: 7.8 min for wild-type enzyme, 7.6 min for mutant enzyme S90A and 7.5 min for mutant enzyme D87A
37
-
half-life of wild-type TAFIa is 9.4 min, half-life of TAFIa mutant S305C/T329I is 70 min
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
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
-
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
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
development of a method to isolate in situ activated TAFIa from human serum in presence of epsilon-aminocaproic acid
-
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
purified by chromatography on Q-Sepharose Fast Flow, Heparin-Sepharose CL-6B, Sephacryl S-300, and plasminogen-Sepharose columns
-
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
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
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
-
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
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
proCPU concentration decreases significantly in the first 72 h after stroke onset and thereafter returns to baseline
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
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
diagnostics
-
the activation peptide of procarboxypeptidase B, set free during activation of procarboxypeptidase B, is a marker for acute pancreatitis
medicine
molecular biology
pharmacology
-
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
-
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
-
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
-
argatroban enhances fibrinolysis via a differential inhibition of thrombin-mediated activation of TAFI and factor XIII
medicine
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
TAFI is present in the gastric mucosa and it may play a role in the pathogenesis of Helicobacter pylori infection-associated gastroduodenal disorders
medicine
-
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
-
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
-
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
-
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
-
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
-
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
-
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
-
thrombomodulin suppresses pericellular fibrinolysis and plasma-induced tumor cell invasion which is mediated by plasma TAFI activation
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Bajazar, L.; Nesheim, M.; Morser, J.; Tracy, P.B.
Both cellular and soluble forms of thrombomodulin inhibit fibrinolysis by potentiating the activation of thrombin-activable fibrinolysis inhibitor
J. Biol. Chem.
273
2792-2798
1998
Homo sapiens
Boffa, M.B.; Wang, W.; Bajzar, l.; Nesheim, M.E.
Plasma and recombinant thrombin-activable fibrinolysis inhibitor (TAFI) and activated TAFI compared with respsct to glycosylation, thrombin/thrombomodulin-dependent activation, thermal stability, and enzymatic properties
J. Biol. Chem.
273
2127-2135
1998
Homo sapiens
Kokame, K.; Zheng, X.; Sadler, J.E.
Activation of thrombin-activable fibrinolysis inhibitor requires epidermal growth factor-like domain 3 of thrombomodulin and is inhibited competitively by protein C
J. Biol. Chem.
273
12135-12139
1998
Homo sapiens
Cote, H.; Bajzar, L.; Stevens, W.K.; Samis, J.A.; Morser, J.; MacGillivray, R.T.A.; Nesheim, M.E.
Functional characterization of recombinant human meizothrombin and meizothrombin (desF1)
J. Biol. Chem.
272
6194-6200
1997
Homo sapiens
Sakharov, D.V.; Plow, E.F.; Rijken, D.C.
On the mechanism of the antifibrinolytic activity of plasma carboxypeptidase B
J. Biol. Chem.
272
14477-14482
1997
Homo sapiens
Nesheim, M.; Wang, W.; Boffa, M.; Nagashima, M.; Morser, J.; Bajzar, L.
Thrombin, thrombomodulin and TAFI in the molecular link between coagulation and fibrinolysis
Thromb. Haemost.
78
386-391
1997
Homo sapiens
Von dem Borne, P.A.K.; Bajzar, L.; Meijers, J.C.M.; Nesheim, M.E.; Bouma, B.N.
Thrombin-mediated activation of factor XI results in a thrombin-activable fibrinolysis inhibitor-dependent inhibition of fibrinolysis
J. Clin. Invest.
99
2323-2327
1997
Homo sapiens
Broze, G.J.
Thrombin-dependent inhibition of fibrinolysis
Curr. Opin. Hematol.
3
390-394
1996
Homo sapiens
Bajzar, L.; Morser, J.; Nesheim, M.
TAFI, or plasma procarboxypeptidase B couples the coagulation and fibrinolytic cascades through the thrombin-thrombomodulin complex
J. Biol. Chem.
271
16603-16608
1996
Homo sapiens
Broze, G.J.; Higuchi, D.A.
Coagulation-dependent inhibition of fibrinolysis: role of carboxypeptidase-U and the premature lysis of clots from hepatitis plasma
Blood
88
3815-3823
1996
Homo sapiens
Tan, A.K.; Eaton, D.L.
Activation and characterization of procarboxypeptidase B from human plasma
Biochemistry
34
5811-5816
1995
Homo sapiens
Bajzar, L.; Manuel, R.; Nesheim, M.E.
Purification and characterization of TAFI, a thrombin-activable fibrinolysis inhibitor
J. Biol. Chem.
270
14477-14484
1995
Homo sapiens
Wang, W.; Hendricks, D.F.; Scharpe, S.S.
Carboxypeptidase U, a plasma carboxypeptidase with high affinity for plasminogen
J. Biol. Chem.
269
15937-15944
1994
Homo sapiens
Eaton, D.L.; Malloy, B.E.; Tsai, S.P.; Henzel, W.; Drayna, D.
Isolation, molecular cloning, and partial characterization of a novel carboxypeptidase B from human plasma
J. Biol. Chem.
266
21833-21838
1991
Homo sapiens
Kawamura, T.; Okada, N.; Okada, H.
Elastase from activated human neutrophils activates procarboxypeptidase R
Microbiol. Immunol.
46
225-230
2002
Homo sapiens
Mao, S.S.; Colussi, D.; Bailey, C.M.; Bosserman, M.; Burlein, C.; Gardell, S.J.; Carroll, S.S.
Electrochemiluminescence assay for basic carboxypeptidases: inhibition of basic carboxypeptidases and activation of thrombin-activatable fibrinolysis inhibitor
Anal. Biochem.
319
159-170
2003
Chlorocebus aethiops, Canis lupus familiaris, Homo sapiens, Macaca mulatta, Rattus norvegicus
Lazoura, E.; Campbell, W.; Yamaguchi, Y.; Kato, K.; Okada, N.; Okada, H.
Rational structure-based design of a novel carboxypeptidase R inhibitor
Chem. Biol.
9
1129-1139
2002
Homo sapiens
Marx, P.F.; Hackeng, T.M.; Dawson, P.E.; Griffin, J.H.; Meijers, J.C.; Bouma, B.N.
Inactivation of active thrombin-activable fibrinolysis inhibitor takes place by a process that involves conformational instability rather than proteolytic cleavage
J. Biol. Chem.
275
12410-12415
2000
Homo sapiens
Schneider, M.; Nagashima, M.; Knappe, S.; Zhao, L.; Morser, J.; Nesheim, M.
Amino acid residues in the P6-P'3 region of thrombin-activable fibrinolysis inhibitor (TAFI) do not determine the thrombomodulin dependence of TAFI activation
J. Biol. Chem.
277
9944-9951
2002
Homo sapiens
Marx, P.F.; Havik, S.R.; Marquart, J.A.; Bouma, B.N.; Meijers, J.C.
Generation and characterization of a highly stable form of activated thrombin-activable fibrinolysis inhibitor
J. Biol. Chem.
279
6620-6628
2004
Homo sapiens
Suzuki, K.; Muto, Y.; Fushihara, K.; Kanemoto, K.; Iida, H.; Sato, E.; Kikuchi, C.; Matsushima, T.; Kato, E.; Nomoto, M.; Yoshioka, S.; Ishii, H.
Enhancement of fibrinolysis by EF6265 [(S)-7-amino-2-[[[(R)-2-methyl-1-(3-phenylpropanoylamino)propyl]hydroxypho sphinoyl] methyl]heptanoic acid], a specific inhibitor of plasma carboxypeptidase B
J. Pharmacol. Exp. Ther.
309
607-615
2004
Homo sapiens, Rattus norvegicus
Campbell, W.D.; Lazoura, E.; Okada, N.; Okada, H.
Inactivation of C3a and C5a octapeptides by carboxypeptidase R and carboxypeptidase N
Microbiol. Immunol.
46
131-134
2002
Homo sapiens
Komura, H.; Shimomura, Y.; Yumoto, M.; Katsuya, H.; Okada, N.; Okada, H.
Heat stability of carboxypeptidase R of experimental animals
Microbiol. Immunol.
46
217-223
2002
Cavia porcellus, Homo sapiens, Oryctolagus cuniculus, Rattus norvegicus
Bouma, B.N.; Marx, P.F.; Mosnier, L.O.; Meijers, J.C.
Thrombin-activatable fibrinolysis inhibitor (TAFI, plasma procarboxypeptidase B, procarboxypeptidase R, procarboxypeptidase U)
Thromb. Res.
101
329-354
2001
Papio sp., Canis lupus familiaris, Cavia porcellus, Oryctolagus cuniculus, Homo sapiens, Mus musculus, Rattus norvegicus, Sus scrofa
Valnickova, Z.; Christensen, T.; Skottrup, P.; Th?gersen, I.B.; H?jrup, P.; Enghild, J.J.
Post-translational modifications of human thrombin-activatable fibrinolysis inhibitor (TAFI): evidence for a large shift in the isoelectric point and reduced solubility upon activation
Biochemistry
45
1525-1535
2006
Homo sapiens (Q96IY4), Homo sapiens
Polla, M.O.; Tottie, L.; Norden, C.; Linschoten, M.; Muesil, D.; Trumpp-Kallmeyer, S.; Aukrust, I.R.; Ringom, R.; Holm, K.H.; Neset, S.M.; Sandberg, M.; Thurmond, J.; Yu, P.; Hategan, G.; Anderson, H.
Design and synthesis of potent, orally active, inhibitors of carboxypeptidase U (TAFIa)
Bioorg. Med. Chem.
12
1151-1175
2004
Homo sapiens
Willemse, J.L.; Hendriks, D.F.
Measurement of procarboxypeptidase U (TAFI) in human plasma: a laboratory challenge
Clin. Chem.
52
30-36
2006
Homo sapiens
Stroemqvist, M.; Hansson, L.; Andersson, J.O.; Johansson, T.; Edlund, M.; Enoksson, M.; Goossens, F.; Scharpe, S.; Hendriks, D.
Properties of recombinant human plasma procarboxypeptidase U produced in mammalian and insect cells
Clin. Chim. Acta
347
49-59
2004
Homo sapiens (Q96IY4), Homo sapiens
Marx, P.F.
Thrombin-activatable fibrinolysis inhibitor
Curr. Med. Chem.
11
2335-2348
2004
Homo sapiens, Mus musculus
Ceresa, E.; Van de Borne, K.; Peeters, M.; Lijnen, H.R.; Declerck, P.J.; Gils, A.
Generation of a stable activated thrombin activable fibrinolysis inhibitor variant
J. Biol. Chem.
281
15878-15883
2006
Homo sapiens
Marx P. , M.P.; Meijers J. C. , M.J.
Mechanism of action of carboxypeptidase U: staying above the threshold
J. Thromb. Haemost.
2
414-415
2004
Homo sapiens
Guimaraes, A.H.; Bertina, R.M.; Rijken, D.C.
A new functional assay of thrombin activatable fibrinolysis inhibitor
J. Thromb. Haemost.
3
1284-1292
2005
Homo sapiens
Marx, P.F.; Havik, S.R.; Bouma, B.N.; Meijers, J.C.
Role of isoleucine residues 182 and 183 in thrombin-activatable fibrinolysis inhibitor
J. Thromb. Haemost.
3
1293-1300
2005
Homo sapiens
Willemse, J.L.; Leurs, J.R.; Hendriks, D.F.
Fast kinetic assay for the determination of procarboxypeptidase U in human plasma
J. Thromb. Haemost.
3
2353-2355
2005
Homo sapiens
Matthews, K.W.; Mueller-Ortiz, S.L.; Wetsel, R.A.
Carboxypeptidase N: a pleiotropic regulator of inflammation
Mol. Immunol.
40
785-793
2004
Homo sapiens
Borgstroem, A.; Regner, S.
Active carboxypeptidase B is present in free form in serum from patients with acute pancreatitis
Pancreatology
5
530-536
2005
Homo sapiens
Bouma, B.N.; Mosnier, L.O.
Thrombin activatable fibrinolysis inhibitor (TAFI) at the interface between coagulation and fibrinolysis
Pathophysiol. Haemost. Thromb.
33
375-381
2005
Homo sapiens, Mus musculus
Bouma, B.N.; Meijers, J.C.
New insights into factors affecting clot stability: A role for thrombin activatable fibrinolysis inhibitor (TAFI; plasma procarboxypeptidase B, plasma procarboxypeptidase U, procarboxypeptidase R)
Semin. Hematol.
41 Suppl 1
13-19
2004
Homo sapiens
Mousa, H.A.; Downey, C.; Alfirevic, Z.; Toh, C.H.
Thrombin activatable fibrinolysis inhibitor and its fibrinolytic effect in normal pregnancy
Thromb. Haemost.
92
1025-1031
2004
Homo sapiens
Frere, C.; Morange, P.E.; Saut, N.; Tregouet, D.A.; Grosley, M.; Beltran, J.; Juhan-Vague, I.; Alessi, M.C.
Quantification of thrombin activatable fibrinolysis inhibitor (TAFI) gene polymorphism effects on plasma levels of TAFI measured with assays insensitive to isoform-dependent artefact
Thromb. Haemost.
94
373-379
2005
Homo sapiens
Leurs, J.; Hendriks, D.
Carboxypeptidase U (TAFIa): a metallocarboxypeptidase with a distinct role in haemostasis and a possible risk factor for thrombotic disease
Thromb. Haemost.
94
471-487
2005
Homo sapiens
Donmez, A.; Aksu, K.; Celik, H.A.; Keser, G.; Cagirgan, S.; Omay, S.B.; Inal, V.; Aydin, H.H.; Tombuloglu, M.; Doganavsargil, E.
Thrombin activatable fibrinolysis inhibitor in Behcets disease
Thromb. Res.
115
287-292
2005
Homo sapiens
Do, Y.H.; Gifford-Moore, D.S.; Beight, D.W.; Rathnachalam, R.; Klimkowski, V.J.; Warshawsky, A.M.; Lu, D.
Inhibition of thrombin activatable fibrinolysis inhibitor by cysteine derivatives
Thromb. Res.
116
265-271
2005
Homo sapiens
Uszynski, W.; Uszynski, M.; Zekanowska, E.
Thrombin activatable fibrinolysis inhibitor (TAFI) in human amniotic fluid. A preliminary study
Thromb. Res.
119
241-245
2006
Homo sapiens
Higuchi, T.; Nakamura, T.; Kakutani, H.; Ishii, H.
Thrombomodulin suppresses invasiveness of HT1080 tumor cells by reducing plasminogen activation on the cell surface through activation of thrombin-activatable fibrinolysis inhibitor
Biol. Pharm. Bull.
32
179-185
2009
Homo sapiens
Nielsen, V.G.
Clot life span model analysis of clot growth and fibrinolysis in normal subjects: role of thrombin activatable fibrinolysis inhibitor
Blood Coagul. Fibrinolysis
19
283-287
2008
Homo sapiens
Kilicarslan, A.; Yavuz, B.; Guven, G.S.; Atalar, E.; Sahiner, L.; Beyazit, Y.; Kekilli, M.; Ozer, N.; Oz, G.; Haznedaroglu, I.C.; Sozen, T.
Fenofibrate improves endothelial function and decreases thrombin-activatable fibrinolysis inhibitor concentration in metabolic syndrome
Blood Coagul. Fibrinolysis
19
310-314
2008
Homo sapiens
Nielsen, V.G.; Kirklin, J.K.
Argatroban enhances fibrinolysis by differential inhibition of thrombin-mediated activation of thrombin activatable fibrinolysis inhibitor and factor XIII
Blood Coagul. Fibrinolysis
19
793-800
2008
Homo sapiens
Matus, V.; Willemse, J.; Quiroga, T.; Goycoolea, M.; Aranda, E.; Panes, O.; Pereira, J.; Hendriks, D.; Mezzano, D.
Procarboxypeptidase U (TAFI) and the Thr325Ile proCPU polymorphism in patients with hereditary mucocutaneous hemorrhages
Clin. Chim. Acta
401
158-161
2009
Homo sapiens
Koldas, M.; Gummus, M.; Seker, M.; Seval, H.; Hulya, K.; Dane, F.; Kural, A.; Gumus, A.; Salepci, T.; Turhal, N.S.
Thrombin-activatable fibrinolysis inhibitor levels in patients with non-small-cell lung cancer
Clin. Lung Cancer
9
112-115
2008
Homo sapiens (Q8IWV7), Homo sapiens
Brouns, R.; Heylen, E.; Sheorajpanday, R.; Willemse, J.L.; Kunnen, J.; De Surgeloose, D.; Hendriks, D.F.; De Deyn, P.P.
Carboxypeptidase U (TAFIa) decreases the efficacy of thrombolytic therapy in ischemic stroke patients
Clin. Neurol. Neurosurg.
111
165-170
2009
Homo sapiens
Akinci, B.; Demir, T.; Saygili, S.; Yener, S.; Alacacioglu, I.; Saygili, F.; Bayraktar, F.; Yesil, S.
Gestational diabetes has no additional effect on plasma thrombin-activatable fibrinolysis inhibitor antigen levels beyond pregnancy
Diabetes Res. Clin. Pract.
81
93-96
2008
Homo sapiens
Erem, C.; Ucuncu, O.; Yilmaz, M.; Kocak, M.; Nuhoglu, I.; Ersoz, H.O.
Increased thrombin-activatable fibrinolysis inhibitor and decreased tissue factor pathway inhibitor in patients with hypothyroidism
Endocrine
35
75-80
2009
Homo sapiens
Koutroubakis, I.E.; Sfiridaki, A.; Tsiolakidou, G.; Coucoutsi, C.; Theodoropoulou, A.; Kouroumalis, E.A.
Plasma thrombin-activatable fibrinolysis inhibitor and plasminogen activator inhibitor-1 levels in inflammatory bowel disease
Eur. J. Gastroenterol. Hepatol.
20
912-916
2008
Homo sapiens
Erdogan, M.; Karadeniz, M.; Alper, G.E.; Tamsel, S.; Uluer, H.; Caglayan, O.; Saygili, F.; Yilmaz, C.
Thrombin-activatable fibrinolysis inhibitor and cardiovascular risk factors in polycystic ovary syndrome
Exp. Clin. Endocrinol. Diabetes
116
143-147
2008
Homo sapiens
Karakurt, F.; Gumus, I.I.; Bavbek, N.; Kargili, A.; Koca, C.; Selcoki, Y.; Ozbek, M.; Kosar, A.; Akcay, A.
Increased thrombin-activatable fibrinolysis inhibitor antigen levels as a clue for prothrombotic state in polycystic ovary syndrome
Gynecol. Endocrinol.
24
491-497
2008
Homo sapiens
Ikeda, A.; Gabazza, E.C.; Morser, J.; Imoto, I.; Kuroda, M.; DAlessandro-Gabazza, C.N.; Hara, K.; Ruiz, D.B.; Bernabe, P.G.; Katsurahara, M.; Toda, M.; Kobayashi, Y.; Yano, Y.; Sumida, Y.; Suzuki, K.; Taguchi, O.; Takei, Y.
Presence of thrombin-activatable fibrinolysis inhibitor in Helicobacter pylori-associated gastroduodenal disease
Helicobacter
14
147-155
2009
Homo sapiens
Cetinkalp, S.; Tobu, M.; Karadeniz, M.; Buyukkececi, F.; Yilmaz, C.
The effect of hormone replacement treatment on thrombin-activatable fibrinolysis inhibitor activity levels in patients with Hashimoto thyroiditis
Intern. Med.
48
281-285
2009
Homo sapiens
Willemse, J.L.; Brouns, R.; Heylen, E.; De Deyn, P.P.; Hendriks, D.F.
Carboxypeptidase U (TAFIa) activity is induced in vivo in ischemic stroke patients receiving thrombolytic therapy
J. Thromb. Haemost.
6
200-202
2008
Homo sapiens
Marx, P.F.; Plug, T.; Havik, S.R.; Moergelin, M.; Meijers, J.C.
The activation peptide of thrombin-activatable fibrinolysis inhibitor: a role in activity and stability of the enzyme?
J. Thromb. Haemost.
7
445-452
2009
Homo sapiens
Foley, J.H.; Nesheim, M.E.
Soluble thrombomodulin partially corrects the premature lysis defect in FVIII-deficient plasma by stimulating the activation of thrombin activatable fibrinolysis inhibitor
J. Thromb. Haemost.
7
453-459
2009
Homo sapiens
Miah, M.F.; Boffa, M.B.
Functional analysis of mutant variants of thrombin-activatable fibrinolysis inhibitor resistant to activation by thrombin or plasmin
J. Thromb. Haemost.
7
665-672
2009
Homo sapiens
Sanglas, L.; Valnickova, Z.; Arolas, J.L.; Pallares, I.; Guevara, T.; Sola, M.; Kristensen, T.; Enghild, J.J.; Aviles, F.X.; Gomis-Rueth, F.X.
Structure of activated thrombin-activatable fibrinolysis inhibitor, a molecular link between coagulation and fibrinolysis
Mol. Cell
31
598-606
2008
Homo sapiens, Bos taurus (Q2KIG3), Bos taurus
Folkeringa, N.; Coppens, M.; Veeger, N.J.; Bom, V.J.; Middeldorp, S.; Hamulyak, K.; Prins, M.H.; Bueller, H.R.; van der Meer, J.
Absolute risk of venous and arterial thromboembolism in thrombophilic families is not increased by high thrombin-activatable fibrinolysis inhibitor (TAFI) levels
Thromb. Haemost.
100
38-44
2008
Homo sapiens
Heylen, E.; Miljic, P.; Willemse, J.; Djordjevic, V.; Radojkovic, D.; Colovic, M.; Elezovic, I.; Hendriks, D.
Procarboxypeptidase U (TAFI) contributes to the risk of thrombosis in patients with hereditary thrombophilia
Thromb. Res.
124
427-432
2009
Homo sapiens
Heylen, E.; Van Goethem, S.; Willemse, J.; Olsson, T.; Augustyns, K.; Hendriks, D.
Development of a sensitive and selective assay for the determination of procarboxypeptidase U (thrombin-activatable fibrinolysis inhibitor) in plasma
Anal. Biochem.
396
152-154
2010
Homo sapiens
Heylen, E.; Van Goethem, S.; Augustyns, K.; Hendriks, D.
Measurement of carboxypeptidase U (active thrombin-activatable fibrinolysis inhibitor) in plasma: Challenges overcome by a novel selective assay
Anal. Biochem.
403
114-116
2010
Homo sapiens
Fernandez, D.; Pallares, I.; Vendrell, J.; Aviles, F.X.
Progress in metallocarboxypeptidases and their small molecular weight inhibitors
Biochimie
93
1484-1500
2010
Homo sapiens
Willemse, J.L.; Heylen, E.; Nesheim, M.E.; Hendriks, D.F.
Carboxypeptidase U (TAFIa): a new drug target for fibrinolytic therapy?
J. Thromb. Haemost.
7
1962-1971
2009
Homo sapiens
Brouns, R.; Heylen, E.; Willemse, J.L.; Sheorajpanday, R.; De Surgeloose, D.; Verkerk, R.; De Deyn, P.P.; Hendriks, D.F.
The decrease in procarboxypeptidase U (TAFI) concentration in acute ischemic stroke correlates with stroke severity, evolution and outcome
J. Thromb. Haemost.
8
75-80
2010
Homo sapiens
Leenaerts, D.; Bosmans, J.M.; van der Veken, P.; Sim, Y.; Lambeir, A.M.; Hendriks, D.
Plasma levels of carboxypeptidase U (CPU, CPB2 or TAFIa) are elevated in patients with acute myocardial infarction
J. Thromb. Haemost.
13
2227-2232
2015
Homo sapiens (Q96IY4), Homo sapiens
Leenaerts, D.; Loyau, S.; Mertens, J.C.; Boisseau, W.; Michel, J.B.; Lambeir, A.M.; Jandrot-Perrus, M.; Hendriks, D.
Carboxypeptidase U (CPU, carboxypeptidase B2, activated thrombin-activatable fibrinolysis inhibitor) inhibition stimulates the fibrinolytic rate in different invitro models
J. Thromb. Haemost.
16
2057-2069
2018
Homo sapiens (Q96IY4)
Mertens, J.; Claesen, K.; Leenaerts, D.; Sim, Y.; Lambeir, A.; Hendriks, D.
Inhibition of the procarboxypeptidase U (proCPU, TAFI, proCPB2) system due to hemolysis
J. Thromb. Haemost.
17
878-884
2019
Homo sapiens (Q96IY4)
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