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
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3.4.21.73
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fibrinolytic
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pai-1
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artery
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metastasis
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thrombolysis
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tissue-type
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fibrin
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endothelial
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clot
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vein
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inhibitor-1
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infarct
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heparin
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streptokinase
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thrombus
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catheter
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venous
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myocardial
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fibrinogen
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embolism
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coronary
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bleeding
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angiogenesis
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hemorrhage
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coagulation
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anticoagulation
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single-chain
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zymography
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mmp-9
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metalloproteinases
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angioplasty
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patency
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angiography
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recanalization
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percutaneous
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thrombotic
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thromboembolism
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vitronectin
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occlusions
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kringle
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intraarterial
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pericellular
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transluminal
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intracoronary
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thrombectomy
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amidolytic
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2-antiplasmin
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euglobulin
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alteplase
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reocclusion
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drug development
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pharmacology
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analysis
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agriculture
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diagnostics
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medicine
- 3.4.21.73
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fibrinolytic
- pai-1
- artery
- metastasis
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thrombolysis
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tissue-type
- fibrin
- endothelial
- clot
- vein
- inhibitor-1
- infarct
- heparin
- streptokinase
- thrombus
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catheter
- venous
- myocardial
- fibrinogen
- embolism
- coronary
- bleeding
- angiogenesis
- hemorrhage
- coagulation
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anticoagulation
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single-chain
-
zymography
- mmp-9
- metalloproteinases
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angioplasty
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patency
-
angiography
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recanalization
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percutaneous
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thrombotic
- thromboembolism
- vitronectin
- occlusions
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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
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Natural Substrates Products on EC 3.4.21.73 - u-Plasminogen activator
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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
alpha6 integrin + H2O
?
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alpha6 integrin is present on prostate carcinoma escaping the gland via nerves. Urokinase-dependent cleavage of the laminin binding domain from the prostate tumor cell surface
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?
urokinase plasminogen activator receptor + H2O
?
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receptor cleavage by u-PA, u-PAR is susceptible to proteolysis by its cognate ligand and several other proteases, biological significance, overview
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?
plasminogen + H2O
?
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the enzyme mediates pericellular proteolysis during cell migration and tissue remodelling under physiological and pathophysiological conditions
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-
?
plasminogen + H2O
?
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potential role for uPA is a direct regulation of metalloproteinases-mediated extracellular proteolysis via the cleavage of the 72000 MW gelatinase/type IV collagenase to an 62000 MW form
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-
?
plasminogen + H2O
?
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key enzyme in the thrombolytic cascade converting plasminogen into plasmin, which in turn degrades thrombus fibrin
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-
?
plasminogen + H2O
?
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the enzyme promotes fibrinolysis by catalyzing the conversion of plasminogen to plasmin
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?
plasminogen + H2O
?
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when localized to the external cell surface it contributes to tissue remodelling and cellular migration
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-
?
plasminogen + H2O
?
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the enzyme is responsible for plasminogen activation, it is also involved in cell adhesion, chemotaxis, and proliferation, the signaling events are not mediated by uPA receptor uPAR/CD87, but require the kringle domain of the enzyme, which binds integrin alphanybeta3 for induction of cell migration, e.g. of CHO cells, overview
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?
plasminogen + H2O
plasmin + ?
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669677, 683130, 683220, 683299, 683456, 683550, 707518, 707866, 707901, 708639, 710248, 717213, 717386, 717916, 718142
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?
plasminogen + H2O
plasmin + ?
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principal function is fibrinolysis, u-PA also been implicated in other physiological functions such as embryogenesis, cell migration, tissue remodeling, ovulation, and wound healing
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?
plasminogen + H2O
plasmin + ?
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hearts with end-stage failure and fibrosis have macrophage accumulation and elevated plasminogen activator activity, mechanisms that link macrophage accumulation and plasminogen activator activity with cardiac fibrosis, dependent on localization of uPA by the uPA receptor uPAR, on activation of plasminogen by uPA and subsequent activation of transforming growth factor-beta1 and matrix metalloproteinase MMP-2 and MMP-9 by plasmin, overview, uPA-induced cardiac fibrosis can be attenuated by treatment with verapamil, plasminogen is necessary for uPA-induced cardiac fibrosis and macrophage accumulation, but uPAR is not
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?
plasminogen + H2O
plasmin + ?
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the uPA proteolytic domain specifically cleaves plasminogen and converts it into the serine protease plasmin with wide substrate specificity. Plasmin directly degrades fibrin, leading to thrombus dissolution and activating a number of matrix metalloproteinases
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-
?
plasminogen + H2O
plasmin + ?
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u-PA forms a complex with its receptor u-PAR in plasminogen ativation
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?
plasminogen + H2O
plasmin + ?
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the urokinase-type and tissue-type plasminogen activators regulate liver matrix remodelling through the conversion of plasminogen to the active protease plasmin, uPA is bound to its receptor uPAR, overview
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?
plasminogen + H2O
plasmin + ?
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the uPA proteolytic domain specifically cleaves plasminogen and converts it into the serine protease plasmin with wide substrate specificity. Plasmin directly degrades fibrin, leading to thrombus dissolution and activating a number of matrix metalloproteinases
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?
plasminogen + H2O
plasmin + ?
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the uPA proteolytic domain specifically cleaves plasminogen and converts it into the serine protease plasmin with wide substrate specificity. Plasmin directly degrades fibrin, leading to thrombus dissolution and activating a number of matrix metalloproteinases
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?
pro-hepatic growth factor + H2O
mature hepatic growth factor + ?
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uPA activates the hepatic growth factor from its inactive single-chain form to the active alpha-chain form
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?
pro-hepatic growth factor + H2O
mature hepatic growth factor + ?
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uPA activates the hepatic growth factor from its inactive single-chain form to the active alpha-chain form
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?
additional information
?
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active enzyme promotes tumor progression, activation of enzyme appears as a key step in tumor progression
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?
additional information
?
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enzyme released by alveolar epithelial cells alters alveolar epithelial repair in vitro by modulating the underlying fibrin matrix
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?
additional information
?
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structure and interdomain contacts of the N-terminal domain of the enzyme with the uPA receptor, binding structure, mechanisms responsible for the cellular responses induced by uPA binding, overview
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?
additional information
?
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the enzyme is a serine protease involved in tissue remodeling and cell migration, the active form of uPA is bound to its high affinity receptor on the cell surface, where specific inhibitors modulate its enzymatic activity, such inhibitors also regulate the cell surface levels of uPA by triggering the internalization of the uPA-receptor-inhibitor complex via endocytosis, overview, the C-terminus of the N-terminal region contains a sequence that interacts with alphaVbeta3 integrin and is relevant for cell migration, overview
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?
additional information
?
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the enzyme is involved in colorectal cancer invasion and metastasis
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?
additional information
?
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the enzyme plays a major role in extracellular proteolytic events associated with tumor cell growth, migration and angiogenesis
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?
additional information
?
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the enzyme-plasminogen activator inhibitor-1 complex in intenalized by endocytosis via binding of membrane-bound receptors, overview
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?
additional information
?
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trans-3,4-dimethyl-3-hydroxyflavanone, a hair growth enhancing active component, decreases active transforming growth factor beta2 and the TGF-b 2 activation cascade through control of uPA on the surface of keratinocytes, mechanism, overview
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?
additional information
?
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uPA interacts with the uPA receptor, which is important for many of the enzyme's biological functions
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?
additional information
?
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incubation of THP-1 macrophage-like cells with uPA results in increased expression of paraoxonase 2. The effect requires uPA/uPA receptor interaction and is abolished by cell treatment with antioxidants. Presence of uPA increases macrophage oxidative stress, reactive oxygen formation, superoxide anion release, and cell-mediated low-density lipoprotein oxidation. Effects are related to uPA-mediated activation of NADPH oxidase
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?
additional information
?
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uterine natural killer cells may regulate extravillous trophoblast invasion and spiral artery remodeling via the uPA system
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?
additional information
?
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uPA forms a complex with its cogante receptor uPAR, specific interctions, analysis, overview
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?
additional information
?
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uPA, uPA receptor, and plasminogen activator inhibitor form the urokinase-type plasminogen activator system
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?
additional information
?
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uPA-uPAR complexes concentrate the plasmin production that provides extracellular matrix proteolysis, weakened cell-cell contact, and increased cell motility. The proteolytic mechanisms include uPA-induced plasmin generation at focal adhesion sites, which results in extracellular matrix degradation and thus facilitates the detachment of the cell's trailing edge. Plasmin inhibitors can suppress cell migration both in vitro, mechanisms by which uPA can regulate arterial remodeling, angiogenesis, and cell migration and proliferation after arterial injury, overview. Urokinase signaling, overview
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?
additional information
?
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urokinase-type plasmin activator, uPA, binding to uPA receptor, uPAR, induces migration/invasion through multiple interactors including integrins, overview. ECRG2 binds specifically to the kringle domain of uPA, and forms a complex with uPA-uPAR, the trinary complex modifies the dynamical association of uPAR with beta1 integrins. Identification of ECRG2-binding sequence in uPA, overview. Complex disruption inhibits the Src/mitogen-activated protein kinase pathway, resulting in suppression of cell migration/invasion
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?
additional information
?
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uPA-induced phosphorylation of endothelial nitric oxide synthase, eNOS, which is inhibited by myristoylated PKI, a protein kinase A inhibitor
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?
additional information
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enzyme protein is consistently elevated in the hyperproliferative hair follicle keratinocyte, and inhibiton of enzyme decreases hair follicle keratinocyte proliferation
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?
additional information
?
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the enzyme supports liver repair independent of its cellular receptor uPAR, overview
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?
additional information
?
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urokinase-type plasminogen activator and macrophages are required for skeletal muscle hypertrophy in mice, depletion of macrophages leads to reduced hypertrophy of muscles, overview
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?
additional information
?
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urokinase-type plasminogen activator plays essential roles in skeletal muscle regeneration and healing, macrophage depletion leads to impaired muscle regeneration, molecular mechanism, overview, the macrophage enzyme is essentially required for chemotaxis, mechanism independent of receptor binding, overview
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?
additional information
?
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addition of uPA to natural killer cell receptor Ly49E positive adult and fetal natural killer cells inhibits interferon-gamma secretion and reduces their cytotoxic potential, respectively. Effects are dependent on receptor Ly49E
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?
additional information
?
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incubation of macrophages with uPA results in increased expression of paraoxonase 2. The resulting effects such as increase in macrophage oxidative stress, reactive oxygen formation, superoxide anion release, and cell-mediated low-density lipoprotein oxidation cannot be reproduced in macrophages harvested from p47phox-/- mice
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?
additional information
?
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induction of endotoxin lipopolysaccharide-mediated uPA receptor expression is mediated through tyrosine phosphorylation of phophoglycerate kinase and heterogenous nuclear ribonucleoprotein C. This involves expression of uPA as an obligate intermediary
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?
additional information
?
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inhalation of urokinase-type plasminogen activator reduces airway remodeling in a murine asthma model, overview. The uPA/plasmin system participates in pericellular proteolysis and is capable of directly degrading matrix components, activating latent proteinases, and activating growth factors
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?
additional information
?
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uPA-uPAR complexes concentrate the plasmin production that provides extracellular matrix proteolysis, weakened cell-cell contact, and increased cell motility. The proteolytic mechanisms include uPA-induced plasmin generation at focal adhesion sites, which results in extracellular matrix degradation and thus facilitates the detachment of the cell's trailing edge. Plasmin inhibitors can suppress cell migration both in vitro, mechanisms by which uPA can regulate arterial remodeling, angiogenesis, and cell migration and proliferation after arterial injury, overview. Urokinase signaling, overview
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-
?
additional information
?
-
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inhalation of urokinase-type plasminogen activator reduces airway remodeling in a murine asthma model, overview. The uPA/plasmin system participates in pericellular proteolysis and is capable of directly degrading matrix components, activating latent proteinases, and activating growth factors
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?
additional information
?
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urokinase-type plasminogen activator and macrophages are required for skeletal muscle hypertrophy in mice, depletion of macrophages leads to reduced hypertrophy of muscles, overview
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?
additional information
?
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urokinase-type plasminogen activator plays essential roles in skeletal muscle regeneration and healing, macrophage depletion leads to impaired muscle regeneration, molecular mechanism, overview, the macrophage enzyme is essentially required for chemotaxis, mechanism independent of receptor binding, overview
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?
additional information
?
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uPA-uPAR complexes concentrate the plasmin production that provides extracellular matrix proteolysis, weakened cell-cell contact, and increased cell motility. The proteolytic mechanisms include uPA-induced plasmin generation at focal adhesion sites, which results in extracellular matrix degradation and thus facilitates the detachment of the cell's trailing edge. Plasmin inhibitors can suppress cell migration both in vitro, mechanisms by which uPA can regulate arterial remodeling, angiogenesis, and cell migration and proliferation after arterial injury, overview. Urokinase signaling, overview
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