3.4.21.73: u-Plasminogen activator
This is an abbreviated version!
For detailed information about u-Plasminogen activator, go to the full flat file.
Word Map on EC 3.4.21.73
-
3.4.21.73
-
fibrinolytic
-
pai-1
-
artery
-
metastasis
-
thrombolysis
-
tissue-type
-
fibrin
-
endothelial
-
clot
-
vein
-
inhibitor-1
-
infarct
-
heparin
-
streptokinase
-
thrombus
-
catheter
-
venous
-
myocardial
-
fibrinogen
-
embolism
-
coronary
-
bleeding
-
angiogenesis
-
hemorrhage
-
coagulation
-
anticoagulation
-
single-chain
-
zymography
-
mmp-9
-
metalloproteinases
-
angioplasty
-
patency
-
angiography
-
recanalization
-
percutaneous
-
thrombotic
-
thromboembolism
-
vitronectin
-
occlusions
-
kringle
-
intraarterial
-
pericellular
-
transluminal
-
intracoronary
-
thrombectomy
-
amidolytic
-
2-antiplasmin
-
euglobulin
-
alteplase
-
reocclusion
-
drug development
-
pharmacology
-
analysis
-
agriculture
-
diagnostics
-
medicine
- 3.4.21.73
-
fibrinolytic
- pai-1
- artery
- metastasis
-
thrombolysis
-
tissue-type
- fibrin
- endothelial
- clot
- vein
- inhibitor-1
- infarct
- heparin
- streptokinase
- thrombus
-
catheter
- venous
- myocardial
- fibrinogen
- embolism
- coronary
- bleeding
- angiogenesis
- hemorrhage
- coagulation
-
anticoagulation
-
single-chain
-
zymography
- mmp-9
- metalloproteinases
-
angioplasty
-
patency
-
angiography
-
recanalization
-
percutaneous
-
thrombotic
- thromboembolism
- vitronectin
- occlusions
-
kringle
-
intraarterial
-
pericellular
-
transluminal
-
intracoronary
-
thrombectomy
-
amidolytic
-
2-antiplasmin
-
euglobulin
- alteplase
-
reocclusion
- drug development
- pharmacology
- analysis
- agriculture
- diagnostics
- medicine
Reaction
Specific cleavage of Arg-/-Val bond in plasminogen to form plasmin =
Synonyms
Abbokinase, Cellular plasminogen activator, Double-chain urokinase-type plasminogen activator, EC 3.4.21.31, EC 3.4.99.26, Plasminogen activator, urokinase-type, PLAU, Two-chain urokinase-type plasminogen activator, u-PA, U-plasminogen activator, UK, uPA, uPA-type Plg activator, Urinary esterase A, Urinary plasminogen activator, Urokinase, Urokinase plasminogen activator, urokinase type plasminogen activator, urokinase-plasminogen activator, urokinase-type PA, urokinase-type plasmin activator, urokinase-type plasminogen, Urokinase-type plasminogen activator, urokinase-type Plg activator, urokine-type plasminogen activator
ECTree
3.4.21.73 u-Plasminogen activatorAdvanced search results
results (
results (Engineering
Engineering on EC 3.4.21.73 - u-Plasminogen activator
Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
top
PROTEIN VARIANTS 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
H99Y
H99Y/Q192K
-
site-directed mutagenesis, the mutations exchanges the human residues for the murine equivalents, rendering the mutant enzyme susceptible for inhibition by the murine peptide sequence mupain-1, overview
L97bG/H99Y/S195A/R217E
site-directed mutagenesis, the mutant shows altered interaction with human plasminogen activator inhibitor-1 compare to wild-type
L97bG/S195A
site-directed mutagenesis, the mutant shows altered interaction with human plasminogen activator inhibitor-1 compare to wild-type
L97bG/S195A/R217E
site-directed mutagenesis, the mutant shows altered interaction with human plasminogen activator inhibitor-1 compare to wild-type
P309D
-
200% increase in KM-value for L-pyroGlu-Gly-L-Arg-4-nitroanilide, about 15% decrease in activation by Lys-plasmin
P309F
-
500% increase in KM-value for L-pyroGlu-Gly-L-Arg-4-nitroanilide, about 15% decrease in activation by Lys-plasmin
P309H
-
400% increase in KM-value for L-pyroGlu-Gly-L-Arg-4-nitroanilide, about 15% decrease in activation by Lys-plasmin
P309R
-
350% increase in KM-value for L-pyroGlu-Gly-L-Arg-4-nitroanilide, about 15% decrease in activation by Lys-plasmin
P309T
-
60% increase in KM-value for L-pyroGlu-Gly-L-Arg-4-nitroanilide, about 15% decrease in activation by Lys-plasmin
R178A/R179A/R181A
-
site-directed mutagenesis, the mutant shows reduced receptor binding
R340A
-
site-directed mutagenesis, the binding of the mutant enzyme to maspin is not affected
S195A
S195A/R217E
site-directed mutagenesis, the mutant shows altered interaction with human plasminogen activator inhibitor-1 compare to wild-type
V41K/H99Y
-
site-directed mutagenesis, the mutations exchanges the human residues for the murine equivalents, rendering the mutant enzyme susceptible for inhibition by the murine peptide sequence mupain-1, overview
V41K/H99Y/Q192K
-
site-directed mutagenesis, the mutations exchanges the human residues for the murine equivalents, rendering the mutant enzyme susceptible for inhibition by the murine peptide sequence mupain-1, overview
E137A
-
site-directed mutagenesis, introduction of the mutations F40Y or E137A into muPA(16-243) increased exposure of the N-terminus (Ile16) and resulted in large changes in the thermodynamic parameters for mupain-1-16 binding
F40Y
-
site-directed mutagenesis, introduction of the mutations F40Y or E137A into muPA(16-243) increased exposure of the N-terminus (Ile16) and resulted in large changes in the thermodynamic parameters for mupain-1-16 binding
additional information
H99Y
-
site-directed mutagenesis, the mutation exchanges the human residue H99 for the murine equivalent Y99, rendering the mutant enzyme susceptible for inhibition by the murine peptide sequence mupain-1, overview
S195A
site-directed mutagenesis, the mutant contains the catalytically inactive form of the human uPA protease domain
S195A
-
site-directed mutagenesis, the active site mutant is not able to activate the epithelial sodium channel in contrast to the wild-type enzyme
S195A
site-directed mutagenesis, the mutant shows altered interaction with human plasminogen activator inhibitor-1 compare to wild-type
additional information
-
reduction of enzyme expression by 53% by stable transfection with antisense/vector construct and by 65% by siRNa transfection results in strong decrease of cellular proliferation activity. Exogenous addition of high-molecular-weight enzyme or enzyme N-terminal fragment lead to increased cell proliferation
additional information
-
deletion of the N-terminal growth factor domain of uPA reduced the affinity for enzyme receptors 2-4fold, depending on the receptor, e.g. VLDLR-I, SorLA, or LRP-1A, and deletion of both the growth factor domain and the kringle reduced the receptor affinity 7fold, overview
additional information
-
functional overexpression of the enzyme in hepatic stellate cells, using an adenoviral vector system, produces downregulation of pro-fibrogenic genes involved in liver fibrosis, and results in a highly specific decrease of TGF-beta expression, and at the same time of genes such as PAI-1, TIMP-1, and collagen type I, which respond to intracellular signals generated by TGF-beta and are involved in perpetuation of fibrogenesis, it also results in upregulation of MMP-3, MMP-2 and MMP-9 activities, overview
additional information
-
the isolated recombinant kringle domain UK1 of uPA shows in vivo antitumor effects in a brain tumor model, systemic administration of purified recombinant UK1 leads to suppression of the growth of a U87 human glioma xenograft, implanted into the brains of male BALB/cSlc nude mice, overview
additional information
-
use of uPA/SCID transgenic mice. Homozygous uPA/SCID mice have a small offspring. Female uPA/SCID mice display a deregulation of ovarian function with an absence of corpus luteum. In male uPA/SCID mice, a decrease of the weight of the testes, epididymis, seminal vesicle, and prostate is measured, associated with an absence of seminal and prostatic secretions and a reduction in testicular sperm production. Transplantation of hepatocytes from mice lacking the uPA transgene results in total repopulation of the livers of uPA/SCID mice and restoration of normal body weight, life span, and reproductive organ function
additional information
-
overexpression of the urokinase-type plasminogen activator N-terminal fragment, uPA ATF, inhibits the combination of uPA receptor and uPA competitively, and the cell invasive migration
additional information
-
transduction of blood monocyte-derived macrophages with uPA-containing adenovirus leads to uPA overexpression. Uptake of the cells into an induced thrombus in mouse leads to increased migration rate of the macrophages and MM6 cells in the thombus, overview. Systemic administration of uPA up-regulated human blood monocyte-derived macrophages reduces thrombus size in an experimental model of venous thrombosis. Adenovirus-uPA transduction increases blood monocyte-derived macrophages fibrinolytic activity by 150fold, and uPAR and PAI-1 production by 1.6fold, it also induces cytokine expression, overview
additional information
-
treatment with uPAR siRNA significantly increases the G0-G1 population by 27% in the CFPAC-1 cells and 20.4% in the PANC-1 cells, compared to control, PAI-2 or uPA siRNA, overview. uPA siRNA treatment reduces cell migration by approximately 25% for CFPAC-1 and 18% for PANC-1 cells. Transfection with PAI-2 siRNA has no effect on cell migration compared to non-silencing siRNA controls
additional information
-
expression of recombinant human uPA in enzyme-ablated mouse livers using adenoviral transfection
additional information
generation of strain AlbPLG1/uPA-/- enzyme-deficient mice
additional information
-
generation of strain AlbPLG1/uPA-/- enzyme-deficient mice
additional information
-
three truncation mutants of the N-terminal fragment of the enzyme still activate the epithelial sodium channel
additional information
analysis of interaction kinetics of the wild-type and mutant human enzymes with human and zebrafish plasminogen activator inhibitor-1 and of the zebrafish wild-type and mutant enzyme with both inhibitors, overview
additional information
-
analysis of interaction kinetics of the wild-type and mutant human enzymes with human and zebrafish plasminogen activator inhibitor-1 and of the zebrafish wild-type and mutant enzyme with both inhibitors, overview
additional information
-
compensatory skeletal muscle hypertrophy is abrogated in enzyme null mice, overview
additional information
-
enzyme-deficient mice show decreased accumulation of macrophages following muscle injury and severely impaired muscle regeneration, overview
additional information
-
mice deficient for uPA activity fail to induce uPA receptor expression after lipopolysaccharide treatment. In these mice, lipopolysaccharide treatment fails to alter the binding of phosphoglycerate kinase and heterogenous nuclear ribonucleoprotein C with uPA receptor mRNA due to lack of tyrosine phophorylation
additional information
-
mice deficient in uPA show markedly reduced hepatocyte growth factor levels and c-met activation after muscle damage, associated with decreased cell proliferation, myoblast accumulation, and new muscle fiber formation, phenotype, overview. On the other hand, hepatocyte growth factor activity is enhanced at early time points in enzyme inhibitor-deficient PAI-1-/- mice compared with wild-type mice, and the PAI-1-/- animals exhibit accelerated muscle fiber regeneration. Administration of exogenous uPA rescues hepatocyte growth factor levels and muscle regeneration in uPA-/- mice
additional information
-
the distorted state of truncated mutant muPA(16-243) is conformationally ordered upon binding of ligands to the active site and upon binding of mU3 to the 37- and 70-loop
additional information
-
compensatory skeletal muscle hypertrophy is abrogated in enzyme null mice, overview
-
additional information
-
enzyme-deficient mice show decreased accumulation of macrophages following muscle injury and severely impaired muscle regeneration, overview
-
additional information
-
mice deficient in uPA show markedly reduced hepatocyte growth factor levels and c-met activation after muscle damage, associated with decreased cell proliferation, myoblast accumulation, and new muscle fiber formation, phenotype, overview. On the other hand, hepatocyte growth factor activity is enhanced at early time points in enzyme inhibitor-deficient PAI-1-/- mice compared with wild-type mice, and the PAI-1-/- animals exhibit accelerated muscle fiber regeneration. Administration of exogenous uPA rescues hepatocyte growth factor levels and muscle regeneration in uPA-/- mice
-
