Information on EC 3.4.17.20 - Carboxypeptidase U

New: Word Map on EC 3.4.17.20
Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
Specify your search results
Mark a special word or phrase in this record:
Search Reference ID:
Select one or more organisms in this record:
Show additional data
Do not include text mining results
Include (text mining) results (more...)
Include results (AMENDA + additional results, but less precise; more...)


The expected taxonomic range for this enzyme is: Eutheria

EC NUMBER
COMMENTARY hide
3.4.17.20
-
RECOMMENDED NAME
GeneOntology No.
Carboxypeptidase U
-
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
release of C-terminal Arg and Lys from a polypeptide
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
hydrolysis of peptide bond
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY hide
156621-18-0
-
37329-68-3
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
UniProt
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
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
anaphylatoxin C5a + H2O
?
show the reaction diagram
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
fibrin + L-Lys
show the reaction diagram
-
-
-
-
?
fibrin + H2O
fibrin + Lys
show the reaction diagram
fibrin + H2O
Lys + ?
show the reaction diagram
Fibrin, partially degraded + H2O
?
show the reaction diagram
Fibrin, partially degraded + H2O
Fibrin, partially degraded + L-Lys + L-Arg
show the reaction diagram
Glu-plasminogen + H2O
Glu + plasmin
show the reaction diagram
-
-
-
-
?
hippuryl-Arg + H2O
hippuric acid + Arg
show the reaction diagram
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-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-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
Lys-plasminogen + H2O
Lys + plasmin
show the reaction diagram
Lys6-Leu5-enkephalin + H2O
Tyr-Gly-Gly-Phe-Leu + Lys
show the reaction diagram
-
i.e. Tyr-Gly-Gly-Phe-Leu-Lys
-
-
-
Lys6-Met5-enkephalin + H2O
Tyr-Gly-Gly-Phe-Met + Lys
show the reaction diagram
-
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
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
osteopontin + H2O
?
show the reaction diagram
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
-
-
-
-
?
additional information
?
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
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
fibrin + L-Lys
show the reaction diagram
-
-
-
-
?
fibrin + H2O
fibrin + Lys
show the reaction diagram
fibrin + H2O
Lys + ?
show the reaction diagram
Fibrin, partially degraded + H2O
?
show the reaction diagram
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
-
?
Lys-plasminogen + H2O
Lys + plasmin
show the reaction diagram
-
-
-
-
?
osteopontin + H2O
?
show the reaction diagram
-
-
-
-
?
additional information
?
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Zinc
-
zinc metalloenzyme
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
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
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
epsilon-amino caproic acid
-
-
Epsilon-aminocaproic 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
o-phenanthroline
-
-
p-chloromercuribenzoate
-
-
PCI-2KR
-
i.e. peptide CKPAKNRC
peptide inhibitor from Hirudo medicinalis
-
-
-
Potato carboxypeptidase inhibitor
potato tuber carboxypeptidase inhibitor
-
competitive inhibition in the nanomolar range
-
PTCI
-
potato carboxypeptidase inhibitor
SAR-104772
-
-
-
tick carboxypeptidase inhibitor
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
additional information
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
activation peptide
factor VIII
-
TAFI activation increases in plasma as the concentration of factor VIII increases
-
plasmin
Recombinant human prothrombin
-
activation
-
thrombin
thrombin-thrombomodulin
Thrombomodulin
Trypsin
-
can activate purified enzyme, proteolytic cleavage at Arg92 produces active enzyme, cleavage at Arg330 yields inactive fragments
-
additional information
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.979 - 1.26
anisylazoformyl-Lys
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 - 3.44
hippuryl-Arg
0.000005 - 0.00001
hippuryl-arginine
1.12 - 817
hippuryl-L-Arg
240
Hippuryl-L-argininic acid
-
-
1.45 - 933
Hippuryl-L-Lys
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 - 280
N-[3-(2-Furylacryloyl)]-L-Ala-L-Lys
0.000162 - 0.000232
p-anisylazoformyl-L-arginine
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
15.9 - 29.5
anisylazoformyl-Lys
748
Arg6-Leu5-enkephalin
Homo sapiens
-
-
647
Arg6-Met5-enkephalin
Homo sapiens
-
-
2.3
biotinyl-(epsilon-aminocaproic acid)-(epsilon-aminocaproic acid)-Gly-Leu-Met-Val-Gly-Gly-Val-Val-Arg-OH
Homo sapiens
-
room temperature
121
bradykinin
Homo sapiens
-
-
2.67 - 2.74
hippuryl-Arg
0.00004 - 0.00043
hippuryl-arginine
26 - 56.7
hippuryl-L-Arg
169
Hippuryl-L-argininic acid
Homo sapiens
-
-
15 - 45.6
Hippuryl-L-Lys
282
Lys6-Leu5-enkephalin
Homo sapiens
-
-
290
Lys6-Met5-enkephalin
Homo sapiens
-
-
59
N-benzoyl-2'-cyano-L-Phe-L-Arg
Homo sapiens
-
in 50 mM HEPES (pH 8.0) at 25C
64
N-benzoyl-Gly-L-Arg
Homo sapiens
-
in 50 mM HEPES (pH 8.0) at 25C
36
N-[3-(2-Furylacryloyl)]-L-Ala-L-Arg
Homo sapiens
-
-
29 - 293
N-[3-(2-Furylacryloyl)]-L-Ala-L-Lys
0.205 - 0.377
p-anisylazoformyl-L-arginine
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
2950
N-benzoyl-2'-cyano-L-Phe-L-Arg
Homo sapiens
-
in 50 mM HEPES (pH 8.0) at 25C
40532
76
N-benzoyl-Gly-L-Arg
Homo sapiens
-
in 50 mM HEPES (pH 8.0) at 25C
31564
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
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
1 - 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
-
-
0.0001 - 0.001
MERGETPA
-
-
0.00001
PCI-2KR
-
-
0.0000004 - 0.000004
Potato carboxypeptidase inhibitor
0.00001
UK-396082
-
-
additional information
additional information
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.000003
(R)-2-(3-guanidinophenyl)-3-mercaptopropanoic acid
Homo sapiens
-
-
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
-
-
0.044
(S)-2,5-dihydroxy-N-(1-hydroxy-3-phenylpropan-2-yl)benzamide
Homo sapiens
-
-
0.0032
2-(2-amino-pyridin-4-ylmethyl)-3-mercapto-propionic acid
Homo sapiens
-
reversible inhibition, IC50: 0.0032 mM
0.0044
2-(2-guanidinoethylthio)succinic acid
Homo sapiens
-
-
0.000003
2-(3-carbamimidamidophenyl)-3-sulfanylpropanoic acid
Homo sapiens
-
-
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
0.0002
3-(2-guanidinoethylthio)-2-(mercaptomethyl)propanoic acid
Homo sapiens
-
-
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
0.001 - 0.0016
3-(6-amino-5-methyl-pyridin-3-yl)-2-mercaptomethyl-2-methyl-propionic acid
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
0.0002
3-(6-aminopyridin-3-yl)-2-(mercaptomethyl)propanoic acid
Homo sapiens
-
-
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
0.0002
anabaenopeptin-type cyclic peptide
Homo sapiens
-
-
-
0.000002
BX-528
Homo sapiens
-
-
0.029
DL-mercaptomethyl-3-guanidinoethylthiopropanoic acid
Homo sapiens
-
i.e. Plummer's inhibitor, IC50: 0.029 mM
0.0000083
EF-6265
Homo sapiens
-
-
0.000001 - 0.00000826
EF6265
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
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.017
-
substrate hippuryl-L-Arg
8
-
substrate hippuryl-L-Lys
11.4
-
substrate hippuryl-L-Arg
2000
-
-
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.3 - 7.6
-
assay at
7.4
assay at
7.4 - 8
-
assay at
7.5 - 8
-
peptide substrates
7.5 - 9
-
ester substrates
8
-
assay at
8.5
-
assay at
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
22 - 25
-
assay at
22
-
assay at room temperatur
pI VALUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
8
-
about, active TAFIa, isoelectric focusing
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
TAFI amount in amniotic fluids of women with normal and complicated pregnancies, overview
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
-
alveolar epithelium and macrophages, broncheal epithelium
Manually annotated by BRENDA team
-
strong expression
Manually annotated by BRENDA team
additional information
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
35000
-
Western blot
435000
-
gel permeation chromatography
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
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 hide
LITERATURE
glycoprotein
proteolytic modification
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
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
4
-
at 4C higher stability than at 30C, but nevertheless unstable
33
-
half-life: 14.5 min; half-life: 15.4 min; half-life: 27.2 min; half-life: 27.4 min
additional information
-
the activated enzyme is thermolabile and inactivated through a conformational change
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
-
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
-
development of a method to isolate in situ activated TAFIa from 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
-
purified from plasma using a ECH-lysine sepharose column and anion-exchange chromatography
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
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
; recombinant TAFI is expressed in BHK cells
-
expression in BHK cells
-
expression in BHK-cells
-
expression in CHO 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
-
procarboxypeptidase R, expression in COS-7 cells
-
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
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
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
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
-
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
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/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
moe
-
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
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
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