3.4.21.68: t-Plasminogen activator
This is an abbreviated version!
For detailed information about t-Plasminogen activator, go to the full flat file.
Word Map on EC 3.4.21.68
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3.4.21.68
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pai-1
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stroke
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inhibitor-1
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artery
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thrombolysis
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fibrinolysis
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endothelial
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infarct
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phorbol
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hemorrhage
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urokinase
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fibrin
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coronary
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clot
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myocardial
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coagulation
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cerebral
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12-o-tetradecanoylphorbol-13-acetate
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fibrinogen
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occlusion
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bleeding
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platelet
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reperfusion
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heparin
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venous
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pkc
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urokinase-type
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upa
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13-acetate
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anticoagulant
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embolism
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thrombus
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intracranial
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willebrand
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angiography
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thrombotic
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recanalization
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streptokinase
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hemostatic
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prothrombin
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d-dimers
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thromboembolic
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patency
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endovascular
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intra-arterial
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antithrombin
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angioplasty
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thrombomodulin
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prothrombotic
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hypercoagulable
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drug development
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diagnostics
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medicine
- 3.4.21.68
- pai-1
- stroke
- inhibitor-1
- artery
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thrombolysis
-
fibrinolysis
- endothelial
- infarct
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phorbol
- hemorrhage
- urokinase
- fibrin
- coronary
- clot
- myocardial
- coagulation
- cerebral
- 12-o-tetradecanoylphorbol-13-acetate
- fibrinogen
- occlusion
- bleeding
- platelet
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reperfusion
- heparin
- venous
- pkc
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urokinase-type
- upa
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13-acetate
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anticoagulant
- embolism
- thrombus
- intracranial
- willebrand
-
angiography
-
thrombotic
-
recanalization
- streptokinase
-
hemostatic
- prothrombin
-
d-dimers
-
thromboembolic
-
patency
-
endovascular
-
intra-arterial
- antithrombin
-
angioplasty
- thrombomodulin
-
prothrombotic
-
hypercoagulable
- drug development
- diagnostics
- medicine
Reaction
Specific cleavage of Arg-/-Val bond in plasminogen to form plasmin =
Synonyms
Alteplase, BAT-PA, desmoteplase, DSPA beta, DSPA gamma, EC 3.4.21.31, EC 3.4.99.26, human tissue-type plasminogen activator, IV t-PA, IV tissue plasminogen activator, More, plasminogen activator, Plasminogen activator, tissue-type, PLAT, r-tPA, recombinant tissue plasminogen activator, Reteplase, rt-PA, rtPA, sc-tPA, sctPA, single chain enzyme tPA, t-PA, t-PA protein, t-plasminogen activator, tc-tPA, tctPA, Tissue plasminogen activator, tissue type plasminogen activator, tissue-plasminogen activator, Tissue-type plasminogen activator, tissue-type plasmiongen activator, tPA, two chain tPA
ECTree
3.4.21.68 t-Plasminogen activatorAdvanced search results
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General Information on EC 3.4.21.68 - t-Plasminogen activator
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GENERAL INFORMATION 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
evolution
human tissue plasminogen activator belongs to the serine protease family
malfunction
metabolism
physiological function
additional information
malfunction
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decreased serotonin levels associated with behavioral disinhibition in tissue plasminogen activator deficient -/- mice, the tPA-/- mice demonstrate an enhanced tendency to actively explore and engage in behaviors involving more exposure in the open field, O-maze and elevated plus maze
malfunction
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the concentrations of t-PA and PAI-1 in the plasma have been identified as variables contributing to the risk of arterial thrombosis
malfunction
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altered tPA activity levels in mouse models of Alzheimer's disease and spinocerebellar ataxia type-1, SCA1. Decreased tPA activity is detected in the cortex and subcortex of Alzheimer's disease mice, whereas increased tPA activity is found in the cerebellum of SCA1 mice
malfunction
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tissue-plasminogen activator and plasminogen activator inhibitor, PAI-1, polymorphisms play a role in myocardial infarction within the Pakistanian population. The PAI-1 gene polymorphism has a gender specific role in the female myocardial infarction patients
malfunction
tPA-deficient ALBPLG1 mice show no difference in survival, bacterial dissemination or the pathology of GAS infection in the absence of tPA in AlbPLG1/tPA-/- mice compared to wild-type AlbPLG1 mice
malfunction
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altered tPA activity levels in mouse models of Alzheimer's disease and spinocerebellar ataxia type-1, SCA1. Decreased tPA activity is detected in the cortex and subcortex of Alzheimer's disease mice, whereas increased tPA activity is found in the cerebellum of SCA1 mice
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metabolism
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tissue-type plasminogen activator functions as the main activator of the fibrinolytic process in the intravascular compartment
metabolism
the plasminogen-plasmin (PLG-PLA) system plays a role in thrombolysis, being capable of degrading blood clots. THe system consists of plasminogen, the inactive zymogen produced principally in the liver, its activators (tissue plasminogen activator, tPA and uroquinase plasminogen activator, uPA (EC 3.4.21.73)), their inhibitors (belonging to the serpin gene superfamily, named PAI-1, PAI-2, PAI-3 and protease nexin I), the uPA receptor and, finally, the active enzyme plasmin and its inhibitor, alpha-antiplasmin (alpha-PL). Apart from its fibrinolytic function, the PLG-PLA system is important in degrading the extracellular matrix in multiple tissues contributing to cell migration, angiogenesis, tissue repair and remodelling or tumour invasion
metabolism
urokinase-type plasminogen activator (uPA) and tissue-type plasminogen activator (tPA) are two serine proteases that contribute to initiating fibrinolysis by activating plasminogen. uPA is also an important tumour-associated protease due to its role in extracellular matrix remodelling
metabolism
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the plasminogen-plasmin (PLG-PLA) system plays a role in thrombolysis, being capable of degrading blood clots. THe system consists of plasminogen, the inactive zymogen produced principally in the liver, its activators (tissue plasminogen activator, tPA and uroquinase plasminogen activator, uPA (EC 3.4.21.73)), their inhibitors (belonging to the serpin gene superfamily, named PAI-1, PAI-2, PAI-3 and protease nexin I), the uPA receptor and, finally, the active enzyme plasmin and its inhibitor, alpha-antiplasmin (alpha-PL). Apart from its fibrinolytic function, the PLG-PLA system is important in degrading the extracellular matrix in multiple tissues contributing to cell migration, angiogenesis, tissue repair and remodelling or tumour invasion
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physiological function
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serine protease, which converts plasminogen into plasmin, which in turn degrades fibrin and other extracellular matrix components, tPA plays an important role in the processes of learning and memory, demonstrated at the level of behavior and synaptic plasticity, role in neurodegeneration
physiological function
tissue plasminogen activator and plasminogen activator inhibitor type 1 are the major regulators of plasmin generation, tissue plasminogen activator plays a pivotal role in the fibrinolytic system by converting the proenzyme plasminogen into the active enzyme plasmin
physiological function
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tissue-type plasminogen activator is a serine protease that converts plasminogen into the active enzyme plasmin, which in turn degrades the fibrin of the forming thrombus
physiological function
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antiangiogenic activity can be elicited by the kringle domains 1 and 2 of tissue-type plasminogen activator, TK12, or the kringle 2 domain alone, overview. The anti-migratory effect of TK12 is mediated in part by its interference with integrin alpha2beta1, which is blocked by the Asp-Gly-Glu-Ala, DGDA, amino acid sequence, the DGDA peptide alone shows antiangiogenic activity and effectively inhibites VEGF-induced migration of HUVECs
physiological function
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despite its pro-fibrinolytic activity, tPA is a serine protease known to influence a number of physiological and pathological functions in the central nervous system. Accordingly, tPA mediates some of its functions in the central nervous system through N-methyl-D-aspartate receptors, low-density lipoprotein receptor-related protein, or annexin II. tPA can mediate proteolysis and subsequent delocalization of neuronal nitric oxide synthase, nNOS, thereby reducing endogenous neuronal nitric oxide release, independent of NMDA receptors, calpains, and low-density lipoprotein receptor-related proteins. tPA promotes proteolysis of nNOS through a plasmin-dependent mechanism, which is prevented in the presence of aprotinin and alpha2-antiplasmin, two blockers of the proteolytic activity of plasmin, overview
physiological function
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ethanol exposure during developmental synaptogenesis can lead to brain defects referred to as fetal alcohol syndrome, which can include mental health problems such as cognitive deficits and mental retardation. Tissue plasminogen activator is implicated in neurodegeneration and is a critical signaling component in FAS. In wild-type mice, ethanol elicits caspase-3 activation, significant forebrain neurodegeneration, and decreases contextual fear conditioning in adults. However, tPA-deficient mice are protected from these neurotoxicities, and this protection can be abrogated by exogenous tPA. The effects of tPA are mediated by the NR2B subunit of the NMDA receptor, but tPA catalytic activity Is not required to promote ethanol-induced neurodegenration
physiological function
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human tissue-plasminogen activator is a thrombolytic protein that plays an active role in dissolving fibrin clots by fibrinolysis and in activating plasminogen to plasmin in blood vessels
physiological function
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mechanism of action of tPA on oligodendrocyte survival and on the extent of white matter lesions in stroke, overview. tPA protects oligodendrocytes from apoptosis through an unexpected cytokine-like effect by the virtue of its epidermal growth factor-like domain, and tPA protects white matter from stroke-induced lesions. Aging differentially influences gray and white matter susceptibility to stroke. tPA, via extracellular regulated kinase 1/2 and Akt intracellular pathways, regulates the balance between proand antiapoptotic factors and reduces the activity of caspase 3
physiological function
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mechanism of action of tPA on oligodendrocyte survival and on the extent of white matter lesions in stroke, overview. tPA protects oligodendrocytes from apoptosis through an unexpected cytokine-like effect by the virtue of its epidermal growth factor-like domain, and tPA protects white matter from stroke-induced lesions. Aging differentially influences gray and white matter susceptibility to stroke. tPA, via extracellular regulated kinase 1/2 and Akt intracellular pathways, regulates the balance between proand antiapoptotic factors and reduces the activity of caspase 3
physiological function
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regulatory mechanism of the plasminogen activator system in astrocytes, overview
physiological function
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the interplay between tissue plasminogen activator domains and fibrin structures plays a role in the regulation of fibrinolysis, kinetics, overview. The regulation of fibrinolysis depends on the starting nature of fibrin fibers and complex dynamic interaction between tPA and fibrin structures that vary over time. Fine fibrin is a better surface for plasminogen activation but more resistant to lysis
physiological function
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the Kringle-2 domain, residues 176-262 of TPA, is the essential structure required for the brain-protective activity of TPA, employing the rat middle cerebral artery occlusion, MCAO, model. The Kringle-2 domain of tissue plasminogen activator significantly reduces mortality and brain infarction in middle cerebral artery occlusion rats. Tissue plasminogen activator shows brainprotective activity within the first 15 min after cerebral ischemia in rats
physiological function
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tissue plasminogen activator is a secreted serine protease and is also proepileptic and excitotoxic. Wild-type tPA and S481A catalytically inactive tPA mutant mediate zinc uptake via the zinc influx transporter, ZIP4, overview. ZIP4 is upregulated after excitotoxin stimulation of the mouse, male and female, hippocampus. ZIP4 physically interacts with tPA, correlating with an increased intracellular zinc influx and lysosomal sequestration. This sequestration might result in neuroprotection. tPA mutants with deletion of the second kringle domain, DELTAK2, or deletion of the growth factor domain, DELTAGF, are less effective
physiological function
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tissue plasminogen activator is a thrombolytic protein that plays a key role in fibrinolysis by converting the plasminogen into plasmin which degrades fibrin clots in blood vessels
physiological function
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tissue plasminogen activator, t-PA, plays a pivotal role in the treatment of acute myocardial infarction, ischemic stroke, and deep vein thrombosis
physiological function
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tissue plasminogen activator, tPA, and its inhibitors contribute to neurite outgrowth in the central nervous system after treatment of stroke with multipotent mesenchymal stromal cells. Critical role of tPA in facilitating neurite outgrowth. Bone marrow stromal cells modulate endogenous tPA level and activity in the ischemic boundary zone, IBZ
physiological function
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tissue plasminogen activator, tPA, is the primary source of plasminogen activator in the brain, and is a member of the fibrinolytic system and a serine protease that converts the zymogen plasminogen into the active protease plasmin, and thus cleaves fibrin and dissolves newly formed clots. Bone marrow stromal cells significantly improve functional recovery from stroke dependent on tPA function, overview. In tPA knockout mice, no bone marrow stromal cell effect is observed on functional recovery
physiological function
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tissue type plasminogen activator regulates myeloid-cell dependent neoangiogenesis during tissue regeneration. Serpin-resistant form of tPA expands the myeloid cell pool and mobilizes CD45+ CD11b+ proangiogenic, myeloid cells, by activating the extracellular proteases matrix metalloproteinase-9 and plasmin, a process dependent on vascular endothelial growth factor-A and Kit ligand signaling. tPA improves the incorporation of CD11b+ cells into ischemic tissues and increases expression of neoangiogenesis-related genes, including VEGF-A, kinetics and mechanism, overview. tPA can induce cell migration by binding to CD11b and degrading fibrin. Batroxobin, a drug that reduces circulating fibrinogen, prevents the tPA-mediated WBC and CD11b+ cell increase. Inhibition of VEGF signaling suppresses tPA-induced neovascularization in a model of hind limb ischemia
physiological function
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tPA is a pivotal player in slowly progressing activity deprivation-induced neurodegeneration, e.g. induced by blockade of neuronal activity using tetrodotoxin, TTX. Neurons degenerate slowly and die in a manner resembling neurodegenerative diseases-induced neuronal cell death. Transfection of an endogenous tPA inhibitor, plasminogen activator inhibitor-1, protected the TTX-exposed neurons from dying
physiological function
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tPA is an initiator of intravascular fibrinolysis and is a complex mediator of brain function and dysfunction. tPA participates in various forms of chronic neurodegeneration, and plays a functional role following morphine administration, epileptic seizures, traumatic brain injury and ischaemic stroke-neurological settings
physiological function
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tPA potentiates excitotoxicity by interacting with and cleaving the N-terminal end of the NR1 subunit of N-methyl-D-aspartate receptors, leading to an increased calcium influx, Erk1/2 activation, and neurotoxicity, mechanism, overview
physiological function
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tPA shows fibrinolytic activity and is used for fibrin clot-lysis
physiological function
the enzyme may directly interact with NR2B subunits of N-methyl-D-aspartate receptors leading to a change in pharmacological properties of NR2B-containing NMDA receptors
physiological function
the human tissue plasminogen activator is a serine protease known as the key component of the fibrinolytic system. t-PA converts the proenzyme plasminogen to plasmin, which in turn mediates the degradation of fibrin
physiological function
plasmin(ogen) acquisition is critical for invasive disease initiation by Streptococcus pyogenes (GAS), limited role of tissue-type plasminogen activator in a mouse model of Group A streptococcal infection
physiological function
tissue plasminogen activator (tPA) of paternal origin is necessary for the success of in vitro but not of in vivo fertilisation in the mouse. The presence of exogenous plasminogen drastically reduces the fertilisation rate under in vitro conditions. When plasminogen is present in combination with inhibitors (e.g. alpha-PL or EACA), the fertilisation rate is partially restored
physiological function
tissue-type plasminogen activator (tPA) is a serine protease that plays a crucial role in the fibrinolytic system
physiological function
-
the Kringle-2 domain, residues 176-262 of TPA, is the essential structure required for the brain-protective activity of TPA, employing the rat middle cerebral artery occlusion, MCAO, model. The Kringle-2 domain of tissue plasminogen activator significantly reduces mortality and brain infarction in middle cerebral artery occlusion rats. Tissue plasminogen activator shows brainprotective activity within the first 15 min after cerebral ischemia in rats
-
physiological function
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regulatory mechanism of the plasminogen activator system in astrocytes, overview
-
physiological function
-
tPA potentiates excitotoxicity by interacting with and cleaving the N-terminal end of the NR1 subunit of N-methyl-D-aspartate receptors, leading to an increased calcium influx, Erk1/2 activation, and neurotoxicity, mechanism, overview
-
physiological function
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tissue plasminogen activator (tPA) of paternal origin is necessary for the success of in vitro but not of in vivo fertilisation in the mouse. The presence of exogenous plasminogen drastically reduces the fertilisation rate under in vitro conditions. When plasminogen is present in combination with inhibitors (e.g. alpha-PL or EACA), the fertilisation rate is partially restored
-
physiological function
-
mechanism of action of tPA on oligodendrocyte survival and on the extent of white matter lesions in stroke, overview. tPA protects oligodendrocytes from apoptosis through an unexpected cytokine-like effect by the virtue of its epidermal growth factor-like domain, and tPA protects white matter from stroke-induced lesions. Aging differentially influences gray and white matter susceptibility to stroke. tPA, via extracellular regulated kinase 1/2 and Akt intracellular pathways, regulates the balance between proand antiapoptotic factors and reduces the activity of caspase 3
-
physiological function
-
tPA is an initiator of intravascular fibrinolysis and is a complex mediator of brain function and dysfunction. tPA participates in various forms of chronic neurodegeneration, and plays a functional role following morphine administration, epileptic seizures, traumatic brain injury and ischaemic stroke-neurological settings
-
physiological function
-
tissue type plasminogen activator regulates myeloid-cell dependent neoangiogenesis during tissue regeneration. Serpin-resistant form of tPA expands the myeloid cell pool and mobilizes CD45+ CD11b+ proangiogenic, myeloid cells, by activating the extracellular proteases matrix metalloproteinase-9 and plasmin, a process dependent on vascular endothelial growth factor-A and Kit ligand signaling. tPA improves the incorporation of CD11b+ cells into ischemic tissues and increases expression of neoangiogenesis-related genes, including VEGF-A, kinetics and mechanism, overview. tPA can induce cell migration by binding to CD11b and degrading fibrin. Batroxobin, a drug that reduces circulating fibrinogen, prevents the tPA-mediated WBC and CD11b+ cell increase. Inhibition of VEGF signaling suppresses tPA-induced neovascularization in a model of hind limb ischemia
-
physiological function
-
tissue plasminogen activator is a secreted serine protease and is also proepileptic and excitotoxic. Wild-type tPA and S481A catalytically inactive tPA mutant mediate zinc uptake via the zinc influx transporter, ZIP4, overview. ZIP4 is upregulated after excitotoxin stimulation of the mouse, male and female, hippocampus. ZIP4 physically interacts with tPA, correlating with an increased intracellular zinc influx and lysosomal sequestration. This sequestration might result in neuroprotection. tPA mutants with deletion of the second kringle domain, DELTAK2, or deletion of the growth factor domain, DELTAGF, are less effective
-
physiological function
-
tissue plasminogen activator, tPA, is the primary source of plasminogen activator in the brain, and is a member of the fibrinolytic system and a serine protease that converts the zymogen plasminogen into the active protease plasmin, and thus cleaves fibrin and dissolves newly formed clots. Bone marrow stromal cells significantly improve functional recovery from stroke dependent on tPA function, overview. In tPA knockout mice, no bone marrow stromal cell effect is observed on functional recovery
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additional information
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alteplase is the full-length recombinant human TPA, while reteplase, K2P, is the domain deletion mutant comprising only the Kringle-2 domain and protease domain of TPA. Reteplase shows a better protective effect than alteplase, suggesting that F, P, or K1 domain in TPA diminishes the brain-protective effect
additional information
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production of active K2S in Escherichia coli without the requirements of in vitro refolding process, method optimization, overview
additional information
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t-PA is a serine-protease enzyme containing 527 amino acid residues in five structural domains
additional information
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the DGDA sequence presents a functional epitope of TK12 and can be used as a potential novel antiangiogenic peptide
additional information
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the synthetic deca-peptide corresponding to the amino acid sequence Arg54-Trp63 of human tissue-type plasminogen activator kringle 2 domain, i.e. TKII-10, effectively inhibits VEGF-stimulated HUVECs migration and tube formation, but it demonstrats no inhibitory effect on VEGF-stimulated HUVECs proliferation, overview. TKII-10 effectively inhibits angiogenesis in vivo
additional information
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alteplase is the full-length recombinant human TPA, while reteplase, K2P, is the domain deletion mutant comprising only the Kringle-2 domain and protease domain of TPA. Reteplase shows a better protective effect than alteplase, suggesting that F, P, or K1 domain in TPA diminishes the brain-protective effect
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