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Information on EC 3.4.21.68 - t-Plasminogen activator and Organism(s) Rattus norvegicus and UniProt Accession P19637

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EC Tree
     3 Hydrolases
         3.4 Acting on peptide bonds (peptidases)
             3.4.21 Serine endopeptidases
                3.4.21.68 t-Plasminogen activator
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This record set is specific for:
Rattus norvegicus
UNIPROT: P19637 not found.
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Word Map
The taxonomic range for the selected organisms is: Rattus norvegicus
The enzyme appears in selected viruses and cellular organisms
Synonyms
tpa, plasminogen activator, tissue plasminogen activator, rt-pa, tissue-type plasminogen activator, alteplase, recombinant tissue plasminogen activator, reteplase, r-tpa, tissue-plasminogen activator, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Tissue plasminogen activator
-
Tissue-type plasminogen activator
-
Alteplase
BAT-PA
-
-
-
-
DSPA beta
-
-
-
-
DSPA gamma
-
-
-
-
Plasminogen activator, tissue-type
-
-
-
-
Reteplase
-
-
-
-
t-plasminogen activator
-
-
-
-
Tissue plasminogen activator
Tissue-type plasminogen activator
additional information
-
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
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
hydrolysis of peptide bond
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY hide
139639-23-9
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
plasminogen + H2O
plasmin + ?
show the reaction diagram
-
-
-
?
casein + H2O
?
show the reaction diagram
methylsulfonyl-D-cyclohexylglycyl-Arg-7-amido-4-methylcoumarin + H2O
methylsulfonyl-D-cyclohexylglycyl-Arg + 7-amino-4-methylcoumarin
show the reaction diagram
-
chromogenic substrate
-
-
?
plasminogen + H2O
plasmin + ?
show the reaction diagram
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
plasminogen + H2O
plasmin + ?
show the reaction diagram
-
-
-
?
plasminogen + H2O
plasmin + ?
show the reaction diagram
-
-
-
-
?
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
2,7-bis-(4-amidinobenzylidene)-cycloheptanone-(1)dihydrochloride
-
H89
-
inhibits dibutyryl-cAMP-mediated changes in tPA activity without affecting metalloproteinase-9 activity
lipopolysaccharide
-
decreases tPA activity. Co-treatment with dibutyryl-cAMP and lipopolysaccharide dose-dependently prevents lipopolysaccharide-induced downregulation of tPA activity
plasminogen activator inhibitor type-1
-
major inhibitor of tissue-type plasminogen activator in the blood
-
plasminogen activator inhibitor-1
Rp-cAMP
-
inhibits dibutyryl-cAMP-mediated changes in tPA activity without affecting metalloproteinase-9 activity
xenon
-
intraischemic xenon dose-dependently inhibits tissue-type plasminogen activator-induced thrombolysis and subsequent reduction of ischemic brain damage, postischemic xenon virtually suppresses ischemic brain damage and tissue-type plasminogen activator-induced brain hemorrhages and disruption of the blood-brain barrier, therefore xenon should not be administered before or together with a tissue-type plasminogen activator therapy
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
dibutyryl-cAMP
-
slightly increases level of tPA mRNA expression. Concentration-dependently increases tPA activity in both basal and lipopolysaccharide-stimulated rat primary astrocytes. Treatment with 100 micromol increases tPA activity by 757.9% compared with lipopolysaccharide treatment. Differentially modulates MMP-9 and tPA activity through a mechanism related to PKA activation. Co-treatment with lipopolysaccharide and dibutyryl-cAMP does not have an additive effect on tPA mRNA induction
IBMX
-
increases tPA activity in lipopolysaccharide-stimulated rat primary astrocytes
lipopolysaccharide
-
slightly increases level of tPA mRNA expression. Co-treatment with lipopolysaccharide and dibutyryl-cAMP does not have an additive effect on tPA mRNA induction
rolipram
-
increases tPA activity in lipopolysaccharide-stimulated rat primary astrocytes
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.000035
2,7-bis-(4-amidinobenzylidene)-cycloheptanone-(1)dihydrochloride
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
additional information
xenon
Rattus norvegicus
-
although xenon at 25% (v/v) has no effect, xenon at higher concentrations of 37.5, 50 and 75% inhibit the catalytic efficiencies of murine enzyme, IC50 is 37.39% (v/v)
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
additional information
-
tPA and PAI-1 activities in neural cells, overview
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
8
-
assay at
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
SwissProt
Manually annotated by BRENDA team
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
primary hippocampal neuron
Manually annotated by BRENDA team
-
primary astroglial cultures prepared from newborn rat cerebral cortices
Manually annotated by BRENDA team
-
in vitro model of the blood-brain barrier, primary rat astrocyte-enriched cultures are co-cultured with primary adult rat brain microvascular endothelial cells on opposite sides of a transwell membrane
Manually annotated by BRENDA team
-
primary culture
Manually annotated by BRENDA team
-
primary culture
Manually annotated by BRENDA team
-
1- to 2-day-old pups
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
-
tPA activity in both the cellular extract and the supernatant of cultured astrocytes
-
Manually annotated by BRENDA team
-
tPA activity in both the cellular extract and the supernatant of cultured astrocytes
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
metabolism
-
tissue-type plasminogen activator functions as the main activator of the fibrinolytic process in the intravascular compartment
physiological function
additional information
-
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
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
TPA_RAT
559
0
62903
Swiss-Prot
Secretory Pathway (Reliability: 2)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
68000
-
casein zymography or gel filtration
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
S478A
-
non-proteolytic TPA full-length mutant
additional information
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
astrocytes co-transfected with metalloproteinase-9 or tPA luciferase reporter plasmid and pCMV-beta-galactosidase reporter plasmid
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
influence of endothelial cells on astrocytic gene expression of t-PA using an in vitro model of the blood-brain barrier, primary rat astrocyte-enriched cultures are cocultured with primary adult rat brain microvascular endothelial cells on opposite sides of a transwell membrane, after co-culturing for 9-11 days, the cultures are treated with lipopolysaccharide for 8 h or 24 h, t-PA mRNA expression in astrocytes are unaffected by co-cultivation and/or lipopolysaccharide treatment, analysis of endothelial t-PA gene expression reveals increased unaltered t-PA mRNA levels
-
the effects of lipopolysaccharide treatment on the astrocyte levels t-PA transcripts are investigated, lipopolysaccharide does not induce any significant alterations in t-PA gene expression in either monocultured or co-cultured astrocytes
-
the influence of astrocytes on endothelial t-PA mRNA expression is studied, for co-cultured endothelial cells, no altered t-PA mRNA levels are observed between the co-cultured cells and the monocultured endothelial cells after treatment with lipopolysaccharide
-
when astrocytes are co-cultured with endothelial cells, no significant alterations in the mRNA levels of t-PA mRNA expression are observed in cocultured astrocytes
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
-
therapy for acute ischemic stroke
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Lijnen, H.R.; Webb, P.D.; van Hoef, B.; De Cock, F.; Stassen, J.M.; Prior, S.D.; Collen, D.
Biochemical and biological properties of a recombinant tissue-type plasminogen activator derived from the rat JMI-229 cell line
Thromb. Haemost.
67
239-247
1992
Rattus norvegicus
Manually annotated by BRENDA team
Medina, M.G.; Ledesma, M.D.; Dominguez, J.E.; Medina, M.; Zafra, D.; Alameda, F.; Dotti, C.G.; Navarro, P.
Tissue plasminogen activator mediates amyloid-induced neurotoxicity via Erk1/2 activation
EMBO J.
24
1706-1716
2005
Mus musculus (P11214), Rattus norvegicus (P19637)
Manually annotated by BRENDA team
Hu, K.; Yang, J.; Tanaka, S.; Gonias, S.L.; Mars, W.M.; Liu, Y.
Tissue-type plasminogen activator acts as a cytokine that triggers intracellular signal transduction and induces matrix metalloproteinase-9 gene expression
J. Biol. Chem.
281
2120-2127
2006
Mus musculus (P11214), Mus musculus, Rattus norvegicus (P19637)
Manually annotated by BRENDA team
Komoriya, K.; Kato, Y.; Hayashi, Y.; Ohsuye, K.; Nishigaki, R.; Sugiyama, Y.
Characterization of the hepatic disposition of lanoteplase, a rationally designed variant of tissue plasminogen activator in rodents
Drug Metab. Dispos.
35
469-475
2007
Rattus norvegicus
Manually annotated by BRENDA team
Adibhatla, R.M.; Hatcher, J.F.
Tissue plasminogen activator (tPA) and matrix metalloproteinases in the pathogenesis of stroke: therapeutic strategies
CNS Neurol. Disord. Drug Targets
7
243-253
2008
Homo sapiens, Mus musculus, Rattus norvegicus, Desmodus rotundus
Manually annotated by BRENDA team
Lee, S.Y.; Kim, H.J.; Lee, W.J.; Joo, S.H.; Jeon, S.J.; Kim, J.W.; Kim, H.S.; Han, S.H.; Lee, J.; Park, S.H.; Cheong, J.H.; Kim, W.K.; Ko, K.H.; Shin, C.Y.
Differential regulation of matrix metalloproteinase-9 and tissue plasminogen activator activity by the cyclic-AMP system in lipopolysaccharide-stimulated rat primary astrocytes
Neurochem. Res.
33
2324-2334
2008
Rattus norvegicus
Manually annotated by BRENDA team
David, H.N.; Haelewyn, B.; Risso, J.J.; Colloch, N.; Abraini, J.H.
Xenon is an inhibitor of tissue-plasminogen activator: adverse and beneficial effects in a rat model of thromboembolic stroke
J. Cereb. Blood Flow Metab.
30
718-728
2010
Rattus norvegicus, Homo sapiens (P00750), Homo sapiens
Manually annotated by BRENDA team
Hultman, K.; Bjoerklund, U.; Hansson, E.; Jern, C.
Potentiating effect of endothelial cells on astrocytic plasminogen activator inhibitor type-1 gene expression in an in vitro model of the blood-brain barrier
Neuroscience
166
408-415
2010
Rattus norvegicus
Manually annotated by BRENDA team
Zhang, H.; Bi, F.; Xiao, C.; Liu, J.; Wang, Z.; Liu, J.N.; Zhang, J.
The Kringle-2 domain of tissue plasminogen activator significantly reduces mortality and brain infarction in middle cerebral artery occlusion rats
Int. J. Mol. Med.
26
225-230
2010
Rattus norvegicus, Rattus norvegicus Sprague-Dawley
Manually annotated by BRENDA team
Kim, J.W.; Lee, S.H.; Ko, H.M.; Kwon, K.J.; Cho, K.S.; Choi, C.S.; Park, J.H.; Kim, H.Y.; Lee, J.; Han, S.H.; Ignarro, L.J.; Cheong, J.H.; Kim, W.K.; Shin, C.Y.
Biphasic regulation of tissue plasminogen activator activity in ischemic rat brain and in cultured neural cells: Essential role of astrocyte-derived plasminogen activator inhibitor-1
Neurochem. Int.
58
423-433
2011
Rattus norvegicus, Rattus norvegicus Sprague-Dawley
Manually annotated by BRENDA team
Schonfeld-Dado, E.; Segal, M.
Activity deprivation induces neuronal cell death: mediation by tissue-type plasminogen activator
PLoS ONE
6
e25919
2011
Rattus norvegicus
Manually annotated by BRENDA team