Information on EC 3.4.21.7 - plasmin

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The expected taxonomic range for this enzyme is: Eutheria

EC NUMBER
COMMENTARY
3.4.21.7
-
RECOMMENDED NAME
GeneOntology No.
plasmin
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
Preferential cleavage: Lys-/- > Arg-/-; higher selectivity than trypsin. Converts fibrin into soluble products
show the reaction diagram
-
-
-
-
SYNONYMS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
actase
-
-
-
-
fibrinase
-
-
-
-
fibrinolysin
-
-
-
-
serum tryptase
-
-
-
-
thrombolysin
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
9001-90-5
-
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
commercial product
-
-
Manually annotated by BRENDA team
human plasmin binds to the extracellular alpha-enolase Eno of Streptococcus pneumoniae
-
-
Manually annotated by BRENDA team
patients with a history of systemic reaction to Hymenoptera and Diptera venom
-
-
Manually annotated by BRENDA team
patients with systemic reactions to Hymenoptera stings
-
-
Manually annotated by BRENDA team
plasminogen; gene PLG
UniProt
Manually annotated by BRENDA team
various forms of enzyme: Glu1-plasmin, Lys77-plasmin, Val442-plasmin, Val561-plasmin
-
-
Manually annotated by BRENDA team
C57BL/6J mice, SCID mice, and BALB/c mice
-
-
Manually annotated by BRENDA team
Mus musculus C57BL/6
-
-
-
Manually annotated by BRENDA team
ovalbumin-induced rat model of asthma
-
-
Manually annotated by BRENDA team
synthetic construct
-
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
-
in plasminogen activator inhibotr-1 knock-out mouse embryonic fibroblasts plasmin activity. Unregulated plasmin activity is only partially responsible for TGF-beta activation as evidenced by a mere 25% reduction in TGF-beta activity when plasmin is inhibited
malfunction
P00747
Defects or mutations in the PLG gene are the cause of thrombophilia, a form of recurrent thrombosis, and type I plasminogen deficiency. Ligneous conjunctivitis is usually the most common and initial form of type I plasminogen deficiency and is a rare form of chronic conjunctivitis characterized by chronic tearing and redness of the conjunctivae
malfunction
-
in plasminogen-deficient mice, periodontitis progresses rapidly, within 20 weeks. The plasminogen-deficient mice show detachment of gingival tissue, resorption of the cementum layer, formation of necrotic tissue, and severe alveolar bone degradation, phenotype, overview. Supplementation by injection of plasminogen-deficient mice with human plasminogen for 10 days leads to necrotic tissue absorption, inflammation subsidence, and full regeneration of gum tissues
malfunction
-
plasmin inhibition by tranexamic acid upregulates the profibrogenic genes, which respond to TGF-beta-intracellular signalling
malfunction
-
the plasminogen activation system is impaired in idiopathic pulmonary fibrosis
malfunction
Mus musculus C57BL/6
-
the plasminogen activation system is impaired in idiopathic pulmonary fibrosis
-
physiological function
-
application of plasmin to primary neurons blocks isoflurane-mediated reduction in dendritic filopodial spines and neuronal apoptosis in vitro
physiological function
-
microglia-derived plasminogen/plasmin facilitate the production/secretion of TGFbeta3 in astrocytes through both proteinase-activated receptor-1 and the downstream phosphatidylinositol 3-kinase-Akt/protein kinase B signaling cascade
physiological function
-
Western blot analysis of the endometrial stromal cell culture media reveals that cholesterol sulfate inhibits the conversion by plasmin of matrix metalloproteinase-3 from the precursor form to the active form
physiological function
-
contribution of plasmin to amplification of inflammation in patients with psoriasis. Annexin II, a receptor for plasmin is dramatically increased in both dermis and epidermis in psoriasis. Plasmin at sites of inflammation is pro-inflammatory, eliciting production of inflammatory factors, including CC chemokine ligand 20 and interleukin-23, that is mediated by the nuclear factor-kappaB (NF-kB) signaling pathway and that has an essential role in the recruitment and activation of pathogenic C-C chemokine receptor type 6+ T cells
physiological function
-
inactivation of ADAMTS13 by plasmin as a potential cause of thrombotic thrombocytopenic purpura, propagation by deficiency of alpha2-antiplasmin function in acute-phase, but not remission-phase plasma, overview. ADAMTS13 is truncated at the C-terminus during the acute phase
physiological function
-
plasmin and urokinase-type plasminogen activator are ubiquitous proteases that regulate the extracellular environment. Although neither plasmin nor urokinase-type plasminogen activator exhibits allosteric cooperativity, modeling shows that cooperativity occurs at the system level because of substrate competition
physiological function
-
plasmin is essential in preventing periodontitis in mice
physiological function
-
plasmin is the principal protease in milk. Plasmin, but not cathepsin D, cleavage of osteopontin increases cell adhesion mediated by the alphaVbeta3- or alpha5beta1-integrins. Similar cellular adhesion is mediated by plasmin and thrombin-cleaved osteopontin, plasmin can be a potent regulator of osteopontin activity
physiological function
-
plasmin plays a key role in the regulation of profibrogenic molecules in hepatic stellate cells, role of plasmin in profibrogenic molecule expression, SnoN transcriptional kinetics and gelatinase activation
physiological function
-
plasmin stimulates phosphorylation of ERK1/2 and p38 MAPK. Plasminogen/plasmin modulates bone metabolism by regulating the osteoblast and osteoclast function. Exogenous plasmin clearly induces the osteoprotegerin expression in plasminogen-deficient osteoblasts. Plasmin activates JNK, but the inhibition of JNK does not attenuate plasmin-induced osteoprotegerin expression
physiological function
-
plasmin triggers chemotaxis of monocyte-derived dendritic cells through an Akt2-dependent pathway and promotes a T-helper type-1 response. Plasmin requires the annexin A2 heterotetramer for chemotactic signaling. Activation of Akt2 leads to extracellular signal-regulated kinase 1/2 activation and the chemotactic response. Plasmin elicits a time-dependent actin polymerization and triggers rapid activation of Akt and mitogen-activated protein kinases, followed by phosphorylation of the regulatory myosin light chain and chemotaxis. In dendritic cells, plasmin activates exclusively Akt2 via a p38 mitogen-activated protein kinase-dependent pathway, not Akt1 and Akt3. Plasmin-stimulated dendritic cells induce polarization of CD4+ T cells toward the interferon-gamma--producing, proinflammatory Th1 phenotype
physiological function
-
plasmin, converted from plasminogen by plasminogen activators, plays an essential role in amplification of psoriasiform skin inflammation in mice. Intradermal injection of plasmin or plasmin together with recombinant monocyte/macrophage chemotactic protein-1 results in induction of psoriasiform skin inflammation around the injection sites in mice. Histological analysis of skin sections from mice treated with plasmin and rMCP-1 reveal acanthosis, hyperorthokeratosis, subcorneal microabscesses, dilated lymphatic vessels and a diffuse inflammatory infiltrates in the dermis compared to normal epidermis and dermis in the ears of control mice. Plasmin triggers NF-kB-dependent IL-23 and CCL20 expression in macrophages
physiological function
-
plasminogen incubated with adherent cells is converted into plasmin for activation by constitutively expressed tPA, i.e. tissue-type plasminogen activator, or uPA, i.e. urokinase-type plasminogen activator. Plasmin formed on the cell membrane then induces a unique response characterized by membrane blebbing and vesiculation. If plasmin formation persists, matrix proteins are then degraded, cells lose their attachments and enter the apoptotic process, characterized by DNA fragmentation and specific ultrastructural features. In plasminogen-treated cells, the nucleus shows chromatin condensation, the cytoplasm is disorganized, contains lysis vesicles and mitochondria become electron-dense
physiological function
P00747
primary function of plasmin is the cleavage of insoluble fibrin polymers at specific sites resulting in soluble fragments. In addition, plasmin acts as a proteolytic factor in many other physiological processes such as mediation of cell migration by degrading the extracellular matrix, wound healing, tissue remodelling, angiogenesis, embryogenesis, and pathogen and tumour cell invasion. The plasmin-antiplasmin system plays a key role in blood coagulation and fibrinolysis. Plasmin and alpha2-antiplasmin are primarily responsible for a controlled and regulated dissolution of the fibrin polymers into soluble fragments
physiological function
-
the plasminogen activation system, in which plasminogen is cleaved to plasmin, comprises an anti-fibrotic pathway that both suppresses the development of pulmonary fibrosis in vivo
physiological function
Mus musculus C57BL/6
-
the plasminogen activation system, in which plasminogen is cleaved to plasmin, comprises an anti-fibrotic pathway that both suppresses the development of pulmonary fibrosis in vivo
-
metabolism
P00747
besides the main physiological inhibitor alpha2-antiplasmin, the plasmin-antiplasmin system is also regulated by the general protease inhibitor alpha2-macroglobulin, a member of the protease inhibitor I39 family. The activity of the plasminogen activators is primarily regulated by the plasminogen activator inhibitors 1 and 2, members of the serine protease inhibitor superfamily
additional information
-
overexpression of human urokinase plasminogen activator in HSC 180 cells leads to increased plasmin activity, which is blocked by tranexamic acid in the transduced. Plasmin overexpression in the transduced cells significantly decreases gene expression of profibrogenic molecules, i.e. a1(I)collagen by 66%, TIMP-1 by 59%, alpha-smooth muscle actin by 90%, and TGF-beta by 55%. Both SnoN gene and protein expression increased prominently
additional information
-
pasteurization of whey protein-free retentate of micro- and difiltrated milk at 95C for 15 s does not significantly affect plasmin or plasminogen-derived activities. The retentate contains increased plasmin activity, proportional to the concentration of beta-lactoglobulin
additional information
-
plasminogen activation to plasmin restores lipid mediator prostaglandin E2 sensitivity in fibrotic lung fibroblasts involving amplified protein kinase A signaling resulting from the promotion of new interactions between AKAP9 and protein kinase A regulatory subunit II in the perinuclear region as well as from the inhibition of protein phosphatase 2A
additional information
-
plasminogen is a major surface-bound protein interacting with pathogen Bacillus anthracis, it efficiently binds to spores of Bacillus anthracis in a lysine- and exosporium-dependent manner with alpha-enolase and elongation factor as specific receptors. Plasminogen-bound spores are capable of exhibiting anti-opsonic properties by cleaving C3b molecules in vitro and in rabbit bronchoalveolar lavage fluid, resulting in a decrease in macrophage phagocytosis. Mechanisms involved in the evasion of innate immunity by Bacillus anthracis through recruitment of plasminogen resulting in the enhancement of anti-complement and anti-opsonization properties of the pathogen, overview
additional information
-
released from CORM-2 and nitric oxide via a NO donor to induce carboxyheme and metheme states, respectively. CO elicits hypofibrinolysis by enhancing alpha2-antiplasmin activity and decreasing plasmin activity
additional information
P00747
the catalytic triad is formed by His603, Asp646, and Ser741
additional information
Mus musculus C57BL/6
-
plasminogen activation to plasmin restores lipid mediator prostaglandin E2 sensitivity in fibrotic lung fibroblasts involving amplified protein kinase A signaling resulting from the promotion of new interactions between AKAP9 and protein kinase A regulatory subunit II in the perinuclear region as well as from the inhibition of protein phosphatase 2A
-
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
Ac-FM(O2)YK-4-nitroanilide + H2O
Ac-FM(O2)YK + 4-nitroaniline
show the reaction diagram
-
peptide substrate, M(O2) i.e. L-methionine sulfone
M(O2) i.e. L-methionine sulfone
-
?
Ac-KM(O2)FR-4-nitroanilide + H2O
Ac-KM(O2)FR + 4-nitroaniline
show the reaction diagram
-
peptide substrate, M(O2) i.e. L-methionine sulfone
M(O2) i.e. L-methionine sulfone
-
?
Ac-KM(O2)YR-4-nitroanilide + H2O
Ac-KM(O2)YR + 4-nitroaniline
show the reaction diagram
-
peptide substrate, M(O2) i.e. L-methionine sulfone
M(O2) i.e. L-methionine sulfone
-
?
Ac-RM(O2)WR-4-nitroanilide + H2O
Ac-RM(O2)WR + 4-nitroaniline
show the reaction diagram
-
peptide substrate, M(O2) i.e. L-methionine sulfone
M(O2) i.e. L-methionine sulfone
-
?
Ac-RM(O2)YR-4-nitroanilide + H2O
Ac-RM(O2)YR + 4-nitroaniline
show the reaction diagram
-
peptide substrate, M(O2) i.e. L-methionine sulfone
M(O2) i.e. L-methionine sulfone
-
?
ADAMTS13 + H2O
?
show the reaction diagram
-
-
-
-
?
ADAMTS13 + H2O
?
show the reaction diagram
-
inactivation
-
-
?
AIYRSR + H2O
AIYR + Ser-Arg
show the reaction diagram
-
-
-
?
alpha-lactalbumin + H2O
?
show the reaction diagram
-
hydrolysis is highly dependent on photooxidation state of substrate
-
-
?
alphaS-casein + H2O
?
show the reaction diagram
-
hydrolysis is highly dependent on photooxidation state of substrate
-
-
?
alphas1-casein + H2O
?
show the reaction diagram
-
-
-
-
?
amyloid beta peptide Abeta42 + H2O
?
show the reaction diagram
-
cleavage prevents the aggregation of Abeta42 and its cleavage products into beta-pleated sheet structure
-
?
amyloid-beta + H2O
?
show the reaction diagram
-
plasmin cleaves at multiple sites, the plasmin pathway is induced by aggregated amyloid-beta, which can lead to amyloid-beta degradation and inhibition of amyloid-beta actions
-
?
annexin A2 + H2O
?
show the reaction diagram
-
interaction of plasmin with annexin A2 results in the stimulation of ERK1/2 and p38 MAPK, cyclooxygenase-2, and PGE(2), leading to increased matrix metalloproteinase-1 production
-
-
?
annexin A2 + H2O
?
show the reaction diagram
-
stimulation of macrophages with plasmin leads to cleavage of ca. 6% of annexin A2 yielding a proteolytic fragment of ca. 33 kDa
-
-
?
benzyloxycarbonyl-Lys-p-nitrophenyl ester + H2O
?
show the reaction diagram
-
-
-
-
?
beta-casein + H2O
?
show the reaction diagram
-
-
-
-
?
beta-casein + H2O
?
show the reaction diagram
-
-
-
-
?
beta-casein + H2O
?
show the reaction diagram
-
hydrolysis is highly dependent on photooxidation state of substrate
-
-
?
beta-lactoglobulin + H2O
?
show the reaction diagram
-
hydrolysis is highly dependent on photooxidation state of substrate
-
-
?
beta2-glycoprotein I + H2O
?
show the reaction diagram
-
in human plasma beta2-glycoprotein I is proteolytically cleaved by plasmin in its domain V (nicked beta2GPI), resulting in binding to plasminogen
-
-
?
Boc-Glu-Lys-Lys-4-methylcoumaryl-7-amide + H2O
Boc-Glu-Lys-Lys + 7-amino-4-methylcoumarin
show the reaction diagram
-
-
-
-
?
Boc-Val-Leu-Lys-4-methylcoumaryl-7-amide + H2O
Boc-Val-Leu-Lys + 7-amino-4-methylcoumarin
show the reaction diagram
-
-
-
?
Boc-Val-Leu-Lys-4-methylcoumaryl-7-amide + H2O
Boc-Val-Leu-Lys + 7-amino-4-methylcoumarin
show the reaction diagram
-
-
-
-
?
Boc-Val-Leu-Lys-4-methylcoumaryl-7-amide + H2O
Boc-Val-Leu-Lys + 7-amino-4-methylcoumarin
show the reaction diagram
-
-
-
?
C1 inhibitor + H2O
?
show the reaction diagram
-
the C1-inhibitor in its native state inhibits plasmin without significant degradation. If the C1-inhibtor is in a denatured polymeric state as can easily occur during storage, or as produced by heating of the native protein, it will be extensively degraded by plasmin
-
?
cadherin + H2O
?
show the reaction diagram
-
plasmin bound to pneumococci is able to cleave recombinant vascular endothelial cadherin
-
-
?
carboxypeptidase N + H2O
?
show the reaction diagram
-
plasmin cleaves the 83 kDa subunit of carboxypeptidase N between Arg457 and Ser458 and after prolonged incubation between Arg218 and Arg219. The small 55 kDa is cleaved to a 48 kDa product. The cleavage enhances the activity of carboxypeptidase N to 150% of the uncleaved enzyme
-
-
?
casein + H2O
?
show the reaction diagram
-
-
-
-
?
casein + H2O
?
show the reaction diagram
-
-
-
-
?
casein + H2O
?
show the reaction diagram
-
acid casein
-
-
?
chromogenic substrate S-2551 + H2O
?
show the reaction diagram
-
-
-
?
chromogranin A + H2O
hCgA-(360-373) + ?
show the reaction diagram
-
the product hCgA-(360-373) is a bioactive fragment that inhibits nicotinic-mediated catecholamine release. The plasminogen/plasmin system through its interaction with chromogranin A may play a major role in catecholaminergic function
-
?
chromogranin A + H2O
catestatin + ?
show the reaction diagram
-
chromogranin A-wild-type, chromogranin A-Gly364Ser and chromogranin A-Arg374Gln completely digested with plasmin at 0.0004 mM
-
-
?
chromozyme PL + H2O
?
show the reaction diagram
-
-
-
-
?
CIYRSR + H2O
CIYR + Ser-Arg
show the reaction diagram
-
-
-
?
D-Ile-Phe-Lys + H2O
?
show the reaction diagram
-
-
-
-
?
D-Nle-hexa-hydrotyrosyl-Lys-4-nitroanilide + H2O
D-Nle-hexa-hydrotyrosyl-Lys + 4-nitroaniline
show the reaction diagram
-
-
-
?
D-Nle-hexahydrotyrosyl-Lys-4-nitroanilide + H2O
D-Nle-hexahydrotyrosyl-Lys + 4-nitroanilide
show the reaction diagram
-
-
-
?
D-norleucyl-hexahydrotyrosyl-lysine-p-nitroanilide + H2O
?
show the reaction diagram
synthetic construct
-
-
-
-
?
D-Val-L-Leu-L-Lys-4-nitroanilide + H2O
D-Val-L-Leu-L-Lys + 4-nitroaniline
show the reaction diagram
-
-
-
-
?
D-Val-L-Leu-L-Lys-4-nitroanilide + H2O
D-Val-L-Leu-L-Lys + 4-nitroaniline
show the reaction diagram
-
i.e. S2251
-
-
?
D-Val-Leu-Lys-4-nitroanilide + H2O
D-Val-Leu-Lys + 4-nitroaniline
show the reaction diagram
-
-
-
?
D-Val-Leu-Lys-4-nitroanilide + H2O
D-Val-Leu-Lys + 4-nitroaniline
show the reaction diagram
-
-
-
?
D-Val-Leu-Lys-4-nitroanilide + H2O
D-Val-Leu-Lys + 4-nitroaniline
show the reaction diagram
-
-
-
-
?
D-Val-Leu-Lys-4-nitroanilide + H2O
D-Val-Leu-Lys + 4-nitroanilide
show the reaction diagram
-
-
-
?
D-Val-Leu-Lys-p-nitroanilide + H2O
D-Val-Leu-Lys + p-nitroaniline
show the reaction diagram
-
-
-
-
?
D-Val-Leu-Lys-p-nitroanilide + H2O
D-Val-Leu-Lys + p-nitroaniline
show the reaction diagram
-
-
-
-
?
D-Val-Leu-Lys-p-nitroanilide + H2O
D-Val-Leu-Lys + p-nitroaniline
show the reaction diagram
synthetic construct
-
-
-
-
?
D-Val-Leu-Lys-p-nitroanilide + H2O
D-Val-Leu-Lys + p-nitroaniline
show the reaction diagram
-
hydrolysis by the plasmin-staphylokinase complex is twofold lower than in the case of the plasmin(ogen)-streptokinase complex
-
-
?
D-Val-Leu-Lys-p-nitroanilide + H2O
?
show the reaction diagram
-
-
-
-
?
D-valyl-L-leucyl-L-lysine-4-nitroanilide + H2O
?
show the reaction diagram
-
-
-
-
?
epithelial sodium channel gamma subunit + H2O
?
show the reaction diagram
-
plasmin activates epithelial sodium channels in association with inducing cleavage of the gamma subunit at gammaLys194, a site distal to the furin site. A gammaK194A mutant epithelial sodium channel subunit prevents both plasmin-dependent activation of epithelial sodium channel and plasmin-dependent production of a unique 70-kDa carboxyl-terminal gamma subunit cleavage fragment
-
-
?
ERK1/2
?
show the reaction diagram
-
triggers activation
-
-
?
factor VIII + H2O
?
show the reaction diagram
-
cleaves the heavy chain of factor VIII into two terminal products, A137336 and A2 subunits, by limited proteolysis at Lys36, Arg336, Arg372, and Arg740. The 80-kDa light chain is converted into a 67-kDa subunit by cleavage at Arg1689 and Arg1721
-
-
?
factor VIII + H2O
?
show the reaction diagram
-
plasmin catalyzes activation or inactivation of factor VIII. The A2 domain of factor VIII, in particular residue Arg484, contributes to a unique plasmin-interactive site within the heavy chain that promotes plasmin docking during cofactor inactivation cleavage of the heavy chain
-
-
?
Fibrin + H2O
?
show the reaction diagram
-
-
-
-
?
Fibrin + H2O
?
show the reaction diagram
-
-
-
?
Fibrin + H2O
?
show the reaction diagram
-
-
-
?
Fibrin + H2O
?
show the reaction diagram
-
-
-
-
?
Fibrin + H2O
?
show the reaction diagram
-
-
-
-
?
Fibrin + H2O
?
show the reaction diagram
-
the activation of plasminogen in blood plasma is the central event that results in the dissolution of the fibrin clot by proteolysis
-
-
-
Fibrin + H2O
?
show the reaction diagram
-
fibrin is broken down through the liberation of plasmin from plasminogen via cleavage by either tissue plasminogen activator and/or urokinase plasminogen activator
-
-
?
Fibrin + H2O
?
show the reaction diagram
-
fibrin is formed from fibrinogen by thrombin, EC 3.4.21.5
-
-
?
fibrin + H2O
soluble fibrin fragments
show the reaction diagram
P00747
cleavage of the Lys583-Met584 peptide bond in the Aalpha chain, followed by the cleavage of the peptide bonds Lys206-Met207 and Lys230-Ala231, also in the Aalpha chain, thus releasing a C-terminal 40-kDa fragment and generating fragment X possessing 260 kDa. Cleavage of fragment X in all three chains results in one fragment Y (160 kDa) and one fragment D (100 kDa), and further cleavage of fragment Y produces a second fragment D and fragment E (60 kDa)
-
-
?
Fibrinogen + H2O
?
show the reaction diagram
-
-
-
-
?
fibrinogen + H2O
fragment X
show the reaction diagram
-
fragment X generated by limited plasmin digestion of fibrinogen
-
-
?
Fibronectin + H2O
?
show the reaction diagram
-
-
-
-
?
GIVRSR + H2O
GIVR + Ser-Arg
show the reaction diagram
-
-
-
?
GIYRSR + H2O
GIYR + Ser-Arg
show the reaction diagram
-
-
-
?
Glu-plasminogen + H2O
angiostatin 4.5 (AS4.5)
show the reaction diagram
-
AS4.5 is prepared from Glu-plasminogen by plasmin digestion
-
-
?
GPGRVV + H2O
GPGR + Val-Val
show the reaction diagram
-
-
-
?
H-D-norleucyl-hexahydrotyrosol-lysine-para nitroanilide diacetate + H2O
?
show the reaction diagram
-
-
-
-
?
H-D-Val-Leu-Lys-p-nitroaniline dihydrochloride + H2O
?
show the reaction diagram
-
-
-
-
?
hemofiltrate CC chemokine 1 + H2O
[9-74] processed variant of hemofiltrate CC chemokine 1 + ?
show the reaction diagram
-
-
further degradation of the active product
?
hemofiltrate CC chemokine 1 + H2O
[9-74] processed variant of hemofiltrate CC chemokine 1 + ?
show the reaction diagram
-
urokinase plasminogen activator and plasmin efficiently convert hemofiltrate CC chemokine 1 into its active [9-74] processed variant
-
?
IkappaBalpha
?
show the reaction diagram
-
plasmin induces phosphorylation of IkappaBalpha, targeting the inhibitor to proteosomal degradation, consequently allowing nuclear translocation of NF-kappaB
-
-
?
insulin + H2O
?
show the reaction diagram
-
cleavage of the Arg25-Gly and Lys29-Ala peptide bonds of the beta-chain of oxidized bovine insulin
-
-
?
JAK1
?
show the reaction diagram
-
triggers tyrosine phosphorylation
-
-
?
kappa-casein + H2O
?
show the reaction diagram
-
hydrolysis is highly dependent on photooxidation state of substrate
-
-
?
KKSPGRVVGGSVAH + H2O
KKSPGR + VVGGSVAH
show the reaction diagram
-
-
-
?
KQWK-4-nitroanilide + H2O
KQWK + 4-nitroaniline
show the reaction diagram
-
peptide substrate
-
-
?
KTFK-4-nitroanilide + H2O
KTFK + 4-nitroaniline
show the reaction diagram
-
peptide substrate
-
-
?
L-Ile-Phe-Lys + H2O
?
show the reaction diagram
-
-
-
-
?
lactoferrin + H2O
?
show the reaction diagram
-
hydrolysis is highly dependent on photooxidation state of substrate
-
-
?
Laminin + H2O
?
show the reaction diagram
-
-
-
-
?
LGGSAMSRMSSLE + H2O
LGGSAMSR + MSSLE
show the reaction diagram
-
-
-
?
LGGSGANFRGKLE + H2O
LGGSGANFR + GKLE
show the reaction diagram
-
-
-
?
LGGSGAVYKAGLE + H2O
LGGSGAVYK + AGLE
show the reaction diagram
-
-
-
?
LGGSGIGRSRSLE + H2O
LGGSGIGR + SRSLE
show the reaction diagram
-
-
-
?
LGGSGIYRSRSLE + H2O
LGGSGIYR + SRSLE
show the reaction diagram
-
-
-
?
LGGSGIYRSVSLE + H2O
LGGSGIYR + SVSLE
show the reaction diagram
-
-
-
?
LGGSGIYRVRSLE + H2O
LGGSGIYR + VRSLE
show the reaction diagram
-
-
-
?
LGGSGPYRSRSLE + H2O
LGGSGPYR + SRSLE
show the reaction diagram
-
-
-
?
LGGSGTQRRLRLE + H2O
LGGSGTQR + RLRLE
show the reaction diagram
-
-
-
?
LGGSGYKIGGSLE + H2O
LGGSGYK + IGGSLE
show the reaction diagram
-
-
-
?
LGGSIRYKGKSLE + H2O
LGGSIRYK + GKSLE
show the reaction diagram
-
-
-
?
N-methyl-D-aspartate receptor NR2A subunit
?
show the reaction diagram
-
plasmin cleaves the native NR2A amino-terminal domain, removing the functional high affinity Zn2+ binding site. Plasmin also cleaves recombinant NR2A amino-terminal domain at lysine 317, thereby producing a 40 kDa fragment, consistent with plasmin-induced NR2A cleavage fragmentsobserved in rat brain preparations. Zn2+ inhibition of agonist-evoked N-methyl-D-aspartate receptor currents of NR1/NR2A-transfected HEK 293 cells and cultured cortical neurons is significantly reduced by plasmin treatment. Mutating the plasmin cleavage site Lys317 on NR2A to alanine blocks plasmins effect on Zn2+ inhibition
-
-
-
N-Suc-L-Ala-L-Phe-L-Lys-7-amido-4-methylcoumarin + H2O
?
show the reaction diagram
-
-
-
-
?
N-succinyl-L-alanyl-L-phenylalanyl-L-lysyl-7-amido-4-methylcoumarin + H2O
N-succinyl-L-alanyl-L-phenylalanyl-L-lysine + 7-amino-4-methylcoumarin
show the reaction diagram
-
-
-
-
?
osteopontin + H2O
?
show the reaction diagram
-
osteopontin is cleaved at multiple sites close to its integrin-binding motifs in milk and is a substrate for plasmin and cathepsin D, osteopontin, purified from human milk, is cleaved at multiple sites close to its integrin-binding motifs, e.g. cleavage at Arg152-Ser153, detailed overview
-
-
?
p-nitrophenyl-p'-(guanidinium)benzoate + H2O
?
show the reaction diagram
-
-
-
-
?
p-nitrophenyl-p'-(methylethylsulfoniummethyl)benzoate + H2O
?
show the reaction diagram
-
-
-
-
?
p-nitrophenyl-p'-(pyridiniummethyl)-benzoate + H2O
?
show the reaction diagram
-
-
-
-
?
p-nitrophenyl-p'-(thiouroniummethyl)benzoate + H2O
?
show the reaction diagram
-
-
-
-
?
p38 MAPK
?
show the reaction diagram
-
triggers phosphorylation
-
-
?
p65
?
show the reaction diagram
-
triggeres nuclear translocation
-
-
?
plasminogen + H2O
?
show the reaction diagram
-
-
-
-
?
platelet-derived growth factor-C + H2O
?
show the reaction diagram
-
plasmin is the major protease responsible for processing platelet-derived growth factor-C in patients undergoing retinal surgery. Plasmin is vastly more potent (192times faster) than tissue plasminogen activator in processing the substrate
-
-
?
platelet-derived growth factor-C + H2O
?
show the reaction diagram
-
plasmin is the major protease responsible for processing platelet-derived growth factor-C in rabbits with proliferative vitreoretinopathy
-
-
?
pro-brain-derived neurotrophic factor + H2O
?
show the reaction diagram
-
plasmin is a specific and efficient activator of pro-brain-derived neurotrophic factor. The pro-form is rapidly processed to an 18 kDa fragment at a low concentration of plasmin. This C-terminal fragment is equivalent in size to the furin-processed, mature form of wild-type brain-derived neurotrophic factor. The proteolytic cleavage site is Arg125-Val126, within the consensus furin-cleavage motif
-
-
?
pro-matrix metalloproteinase-1 + H2O
active matrix metalloproteinase-1
show the reaction diagram
-
matrix metalloproteinase-1 activation by the UP A/plasmin system
-
-
?
pro-matrix metalloproteinase-3 + H2O
matrix metalloproteinase-3 + ?
show the reaction diagram
-
-
-
-
?
probrain derived neurotrophic factor + H2O
mature brain derived neurotrophic factor
show the reaction diagram
-
-
-
-
?
protamin-heparin complex + H2O
?
show the reaction diagram
-
-
-
-
?
RQFR-4-nitroanilide + H2O
RQFR + 4-nitroaniline
show the reaction diagram
-
peptide substrate
-
-
?
RQWK-4-nitroanilide + H2O
RQWK + 4-nitroaniline
show the reaction diagram
-
peptide substrate
-
-
?
S-2251 + H2O
?
show the reaction diagram
-
-
-
?
S-sulfo-fibrinogen + H2O
?
show the reaction diagram
-
cleaves only Lys and Arg peptide bonds
-
-
?
SPGRVV + H2O
SPGR + Val-Val
show the reaction diagram
-
-
-
?
STAT3
?
show the reaction diagram
-
phosphorylates on Tyr705 and Ser727. Triggeres activation and nuclear translocation of STAT3
-
-
?
Suc-Ala-Phe-Lys-7-amido-4-methylcoumarin + H2O
?
show the reaction diagram
synthetic construct
-
-
-
-
?
thrombin-activatable fibrinolysis inhibitor + H2O
?
show the reaction diagram
-
mutant variants with variants in the amino acids surrounding the scissile R92-A93 bond such as P91S, R92K, and S90P exhibit specific impairment of activation by plasmin
-
-
?
tissue factor pathway inhibitor + H2O
?
show the reaction diagram
-
plasmin increases tissue factor activity by inactivating the cell-associated tissue factor pathway inhibitor by a limited proteolysis
-
-
?
Tosyl-Arg methyl ester + H2O
?
show the reaction diagram
-
-
-
-
?
Tosyl-Arg methyl ester + H2O
?
show the reaction diagram
-
p-tosyl-Arg methyl ester
-
-
?
tosyl-Gly-Pro-Lys-4-nitroanilide + H2O
tosyl-Gly-Pro-Lys + 4-nitroaniline
show the reaction diagram
-
-
-
?
tosyl-Gly-Pro-Lys-4-nitroanilide + H2O
tosyl-Gly-Pro-Lys + 4-nitroaniline
show the reaction diagram
-
-
-
-
?
transforming growth factor beta 2 + H2O
?
show the reaction diagram
-
-
-
-
?
TYK2
?
show the reaction diagram
-
triggers tyrosine phosphorylation
-
-
?
vascular endothelial growth factor + H2O
?
show the reaction diagram
-
cleavage site: Arg110-/-Ala111. The mutant vascular endothelial growth factors R110A, R110Q and A111P are resistant to cleavage, in non-healing wounds plasmin cleaves and inactivates vascular endothelial growth factor VEGF165
-
?
VQYK-4-nitroanilide + H2O
VQYK + 4-nitroaniline
show the reaction diagram
-
peptide substrate
-
-
?
VQYR-4-nitroanilide + H2O
VQYR + 4-nitroaniline
show the reaction diagram
-
peptide substrate
-
-
?
LGGSSIYRSRSLE + H2O
LGGSSIYR + SRSLE
show the reaction diagram
-
-
-
?
additional information
?
-
-
complexes of streptokinase with human plasminogen can hydrolytically activate other plasminogen molecules to plasmin, which then dissolve blood clots
-
-
-
additional information
?
-
-
the plasminogen activation system is mostly recognized for its fibrinolytic activity but is also upregulated in chronic inflammatory diseases, including atherosclerosis and arthritis. Plasmin is a potent activator of human monocytes and a number of other cells. In monocytes plasmin elicits full-blown proinflammatory activation encompassing lipid mediator release, chemotaxis and induction of cytokines and other proinflammatory genes. Cell activation is dependent on the binding of the plasmin molecule via its lysine binding sites as well as on the intact catalytic center of plasmin, indicating proteolytic activation. Cell activation occurs through a yet unidentified receptor which is specific for plasmin and that, at least in monocytes, is not activated by other proteases, such as factor Va and Xa, the serine proteases thrombin, alpha-chymotrypsin, human neutrophil elastase or cathepsin G
-
?
additional information
?
-
-
plasmin can activate collagenases
-
-
-
additional information
?
-
-
plasmin does not induce phosphorylation of JAK2 or JAK3. Does not activate SAP/JNK. Does not trigger activation and nuclear translocation ofSTAT1, STAT5A, or STAT5B
-
-
-
additional information
?
-
-
plasmin is 3-4fold less efficient in processing of the chromogranin A-Pro370Leu variant as compared to wild-type and the other varinats due to less efficient cleavage between Arg373-Arg374
-
-
-
additional information
?
-
-
plasmin triggeres phosphorylation of ERK1/2 in a concentration-dependent manner, but not of Akt
-
-
-
additional information
?
-
synthetic construct
-
potentiates TLR2 and TLR4 signalling in RAW264.7 macrophages. Enhances endogenous production of TNFalpha and activation of an NF-kappaB reporter plasmid
-
-
-
additional information
?
-
-
addition of plasmin to fibroblast-like cells from dental pulp induces an increase in the intracellular Ca2+ concentration, which may be inhibited by inhibition of receptor PAR-1. Plasmin stimulates the expression of interleukin-8 mRNA and prostaglandin E2 release
-
-
-
additional information
?
-
-
both plasmin and thrombin increase cell surface tissue factor activity in human pleural mesothelial cells by 3- to 4fold. Plasmin-induced tissue factor activity is not dependent on the de novo synthesis of tissue factor. In HUVEC, plasmin has a minimal effect on unperturbed HUVEC whereas it markedly increases tissue factor activity of activated HUVEC. Plasmin treatment neither affects anionic phospholipid levels at the cell surface nor releases protein disulfide isomerase
-
-
-
additional information
?
-
-
intravitreal plasmin injection increases the rate of vitreous removal in rabbits
-
-
-
additional information
?
-
-
plasmin can differentially modulate platelet aggregation in response to intrinsic heterogeneities within the insulin-like growth factor/insulin-like growth factor binding protein complexes
-
-
-
additional information
?
-
-
plasmin may serve as an endogenous PAR1 activator that can increase Ca2+ concentration, in astrocytes and potentiate N-methyl-D-aspartate receptor synaptic currents in CA1 pyramidal neurons
-
-
-
additional information
?
-
-
role for plasmin in augmenting hematopoietic progenitor cell mobilization in response to granulocyte colony-stimulating factor
-
-
-
additional information
?
-
-
adherence of plasmin-coated encapsulated or unencapsulated pneumococci induces sporadic disruption of EaHy or A549 monolayer cell junctions
-
-
-
additional information
?
-
-
protein context, as well as the identity of amino acids at protease cleavage sites, dictate protease specificity
-
-
-
additional information
?
-
-
steroid-treated ovariectomized mice deficient in tissue inhibitor of metalloprotease-1 and exposed to estrogen show a significant increase in plasmin activity. Increase is probably due to reduced expression of plasmin inhibitors serpinb7 and serpinb2
-
-
-
additional information
?
-
-
plasmin selectively cleaves arginyl-X and lysyl-X peptide bonds in many target proteins
-
-
-
additional information
?
-
P00747
rather broad specificity of plasmin in vivo catalyzing the inactivation and degradation of matrix proteins such as collagens, fibronectin, and laminins, and components of the blood coagulation cascade such as coagulation factor FVa, von Willebrand factor, and thrombospondin
-
-
-
additional information
?
-
-
subsite interactions of plasmin with substrates and inhibitors through computational docking analysis using the structure with PDB ID 1BML for plasmin in complex with streptokinase and no ligand molecules, molecular dynamic simulation of plasmin, overview. D/L-Ile-Phe-Lys substrate-binding modes
-
-
-
additional information
?
-
-
plasmin, possessing various substrate binding sites, shows substrate binding site cooperativity, molecular modeling of the plasmin-Ac-RM(O2)YR-H complex
-
-
-
additional information
?
-
-
staphylokinase forms a 1:1 stoichiometric complex with human plasmin and switches its substrate specificity to generate a plasminogen activator complex
-
-
-
additional information
?
-
-
substrate competition with urokinase-type plasminogen activator and bistability, overview
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
ADAMTS13 + H2O
?
show the reaction diagram
-
inactivation
-
-
?
amyloid-beta + H2O
?
show the reaction diagram
-
the plasmin pathway is induced by aggregated amyloid-beta, which can lead to amyloid-beta degradation and inhibition of amyloid-beta actions
-
?
beta2-glycoprotein I + H2O
?
show the reaction diagram
-
in human plasma beta2-glycoprotein I is proteolytically cleaved by plasmin in its domain V (nicked beta2GPI), resulting in binding to plasminogen
-
-
?
chromogranin A + H2O
hCgA-(360-373) + ?
show the reaction diagram
-
the product hCgA-(360-373) is a bioactive fragment that inhibits nicotinic-mediated catecholamine release. The plasminogen/plasmin system through its interaction with chromogranin A may play a major role in catecholaminergic function
-
?
epithelial sodium channel gamma subunit + H2O
?
show the reaction diagram
-
plasmin activates epithelial sodium channels in association with inducing cleavage of the gamma subunit at gammaLys194, a site distal to the furin site. A gammaK194A mutant epithelial sodium channel subunit prevents both plasmin-dependent activation of epithelial sodium channel and plasmin-dependent production of a unique 70-kDa carboxyl-terminal gamma subunit cleavage fragment
-
-
?
Fibrin + H2O
?
show the reaction diagram
-
the activation of plasminogen in blood plasma is the central event that results in the dissolution of the fibrin clot by proteolysis
-
-
-
fibrin + H2O
soluble fibrin fragments
show the reaction diagram
P00747
-
-
-
?
Glu-plasminogen + H2O
angiostatin 4.5 (AS4.5)
show the reaction diagram
-
AS4.5 is prepared from Glu-plasminogen by plasmin digestion
-
-
?
N-methyl-D-aspartate receptor NR2A subunit
?
show the reaction diagram
-
plasmin cleaves the native NR2A amino-terminal domain, removing the functional high affinity Zn2+ binding site. Plasmin also cleaves recombinant NR2A amino-terminal domain at lysine 317, thereby producing a 40 kDa fragment, consistent with plasmin-induced NR2A cleavage fragmentsobserved in rat brain preparations. Zn2+ inhibition of agonist-evoked N-methyl-D-aspartate receptor currents of NR1/NR2A-transfected HEK 293 cells and cultured cortical neurons is significantly reduced by plasmin treatment. Mutating the plasmin cleavage site Lys317 on NR2A to alanine blocks plasmins effect on Zn2+ inhibition
-
-
-
osteopontin + H2O
?
show the reaction diagram
-
osteopontin is cleaved at multiple sites close to its integrin-binding motifs in milk and is a substrate for plasmin and cathepsin D
-
-
?
probrain derived neurotrophic factor + H2O
mature brain derived neurotrophic factor
show the reaction diagram
-
-
-
-
?
tissue factor pathway inhibitor + H2O
?
show the reaction diagram
-
plasmin increases tissue factor activity by inactivating the cell-associated tissue factor pathway inhibitor by a limited proteolysis
-
-
?
vascular endothelial growth factor + H2O
?
show the reaction diagram
-
in non-healing wounds plasmin cleaves and inactivates vascular endothelial growth factor VEGF165
-
?
hemofiltrate CC chemokine 1 + H2O
[9-74] processed variant of hemofiltrate CC chemokine 1 + ?
show the reaction diagram
-
urokinase plasminogen activator and plasmin efficiently convert hemofiltrate CC chemokine 1 into its active [9-74] processed variant
-
?
additional information
?
-
-
addition of plasmin to fibroblast-like cells from dental pulp induces an increase in the intracellular Ca2+ concentration, which may be inhibited by inhibition of receptor PAR-1. Plasmin stimulates the expression of interleukin-8 mRNA and prostaglandin E2 release
-
-
-
additional information
?
-
-
both plasmin and thrombin increase cell surface tissue factor activity in human pleural mesothelial cells by 3- to 4fold. Plasmin-induced tissue factor activity is not dependent on the de novo synthesis of tissue factor. In HUVEC, plasmin has a minimal effect on unperturbed HUVEC whereas it markedly increases tissue factor activity of activated HUVEC. Plasmin treatment neither affects anionic phospholipid levels at the cell surface nor releases protein disulfide isomerase
-
-
-
additional information
?
-
-
intravitreal plasmin injection increases the rate of vitreous removal in rabbits
-
-
-
additional information
?
-
-
plasmin can differentially modulate platelet aggregation in response to intrinsic heterogeneities within the insulin-like growth factor/insulin-like growth factor binding protein complexes
-
-
-
additional information
?
-
-
plasmin may serve as an endogenous PAR1 activator that can increase Ca2+ concentration, in astrocytes and potentiate N-methyl-D-aspartate receptor synaptic currents in CA1 pyramidal neurons
-
-
-
additional information
?
-
-
role for plasmin in augmenting hematopoietic progenitor cell mobilization in response to granulocyte colony-stimulating factor
-
-
-
additional information
?
-
-
plasmin selectively cleaves arginyl-X and lysyl-X peptide bonds in many target proteins
-
-
-
additional information
?
-
P00747
rather broad specificity of plasmin in vivo catalyzing the inactivation and degradation of matrix proteins such as collagens, fibronectin, and laminins, and components of the blood coagulation cascade such as coagulation factor FVa, von Willebrand factor, and thrombospondin
-
-
-
additional information
?
-
-
subsite interactions of plasmin with substrates and inhibitors through computational docking analysis using the structure with PDB ID 1BML for plasmin in complex with streptokinase and no ligand molecules, molecular dynamic simulation of plasmin, overview. D/L-Ile-Phe-Lys substrate-binding modes
-
-
-
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(10S,13S)-10-(1H-indol-3-ylmethyl)-8,11-dioxo-N-(4-oxotetrahydrofuran-3-yl)-2-oxa-9,12-diazabicyclo[13.2.2]nonadeca-1(17),15,18-triene-13-carboxamide
synthetic construct
-
-
(12S,15S)-12-(1H-indol-3-ylmethyl)-10,13-dioxo-N-(4-oxotetrahydrofuran-3-yl)-2-oxa-11,14-diazabicyclo[15.2.2]henicosa-1(19),17,20-triene-15-carboxamide
synthetic construct
-
-
(4-[2-[(4-aminomethyl-cyclohexanecarbonyl)-amino]-3-phenyl-propionylamino]-phenyl)-acetic acid
-
IC50 in reaction with D-Val-Leu-Lys-4-nitroanilide is 0.63 mM
(9S,12S)-9-(1H-indol-3-ylmethyl)-7,10-dioxo-N-(4-oxotetrahydrofuran-3-yl)-2-oxa-8,11-diazabicyclo[12.2.2]octadeca-1(16),14,17-triene-12-carboxamide
synthetic construct
-
-
2-(3-[3-[(6-amino-hexyl)-(2-benzyloxycarbonylamino-3-phenyl-propionyl)-amino]-2-oxo-cyclohexyl]-propionylamino)-3-(1H-indol-3-yl)-propionic acid methyl ester
-
IC50: 0.024 mM
2-[(4-Aminomethyl-cyclohexanecarbonyl)-amino]-3-[4-(2-bromo-benzyloxycarbonyloxy)-phenyl]-propionic acid pyridin-2-ylmethyl ester
-
IC50 in reaction with D-Val-Leu-Lys-4-nitroanilide is 0.0042 mM
2-[3-(3-[(6-amino-hexyl)-[2-benzyloxycarbonylamino-3-(1H-indol-3-yl)-propionyl]-amino]-2-oxo-cyclohexyl)-propionylamino]-3-(1H-indol-3-yl)-propionic acid methyl ester
-
IC50: 0.02 mM
4-(2-aminoethyl)benzenesulfonyl fluoride
-
-
4-({2-(6-amino-hexanoylamino)-3-[4-(2-bromo-benzyloxycarbonyloxy)-phenyl]-propionylamino}-methyl)-cyclohexanecarboxylic acid heptyl ester
-
IC50 in reaction with D-Val-Leu-Lys-4-nitroanilide is 0.024 mM, IC50 in reaction with fibrin is 0.0039 mM
4-({2-(6-amino-hexanoylamino)-3-[4-(2-bromo-benzyloxycarbonyloxy)-phenyl]-propionylamino}-methyl)-cyclohexanecarboxylic acid hexyl ester
-
IC50 in reaction with D-Val-Leu-Lys-4-nitroanilide is 0.018 mM, IC50 in reaction with fibrin is 0.0043 mM
4-({2-(6-amino-hexanoylamino)-3-[4-(2-bromo-benzyloxycarbonyloxy)-phenyl]-propionylamino}-methyl)-cyclohexanecarboxylic acid methyl ester
-
IC50 in reaction with D-Val-Leu-Lys-4-nitroanilide is 0.0009 mM, IC50 in reaction with fibrin is 0.0061 mM
4-({2-(6-amino-hexanoylamino)-3-[4-(2-bromo-benzyloxycarbonyloxy)-phenyl]-propionylamino}-methyl)-cyclohexanecarboxylic acid octyl ester
-
IC50 in reaction with D-Val-Leu-Lys-4-nitroanilide is above 0.1 mM, IC50 in reaction with fibrin is 0.005 mM
4-({2-[(4-aminomethyl-cyclohexanecarbonyl)-amino]-3-[4-(2-bromo-benzyloxycarbonyloxy)-phenyl]-propionylamino}-methyl)-cyclohexanecarboxylic acid heptyl ester
-
IC50 in reaction with D-Val-Leu-Lys-4-nitroanilide is 0.0014 mM, IC50 in reaction with fibrin is 0.00042 mM
4-({2-[(4-aminomethyl-cyclohexanecarbonyl)-amino]-3-[4-(2-bromo-benzyloxycarbonyloxy)-phenyl]-propionylamino}-methyl)-cyclohexanecarboxylic acid hexyl ester
-
IC50 in reaction with D-Val-Leu-Lys-4-nitroanilide is 0.0015 mM, IC50 in reaction with fibrin is 0.0004 mM
4-({2-[(4-aminomethyl-cyclohexanecarbonyl)-amino]-3-[4-(2-bromo-benzyloxycarbonyloxy)-phenyl]-propionylamino}-methyl)-cyclohexanecarboxylic acid methyl ester
-
IC50 in reaction with D-Val-Leu-Lys-4-nitroanilide is 0.001 mM, IC50 in reaction with fibrin is 0.00078 mM
4-({2-[(4-aminomethyl-cyclohexanecarbonyl)-amino]-3-[4-(2-bromo-benzyloxycarbonyloxy)-phenyl]-propionylamino}-methyl)-cyclohexanecarboxylic acid octyl ester
-
IC50 in reaction with D-Val-Leu-Lys-4-nitroanilide is 0.0025 mM, IC50 in reaction with fibrin is 0.00056 mM
4-amidinophenyl methane-sulfonyl fluoride
-
abolishes plasmin-induced Ca2+ elevation by its pretreatment of plasmin
4-amidinophenyl methane-sulfonyl fluoride
-
substantially abrogates the relaxing effect of plasmin. Abolishes plasmin-induced Ca2+ elevation by its pretreatment of plasmin
479-504 peptide of factor VIII
-
blocks A2 subunit binding to Ah-plasmin by ca. 50% in a dose-dependent manner
-
484-509 peptide of factor VIII
-
blocks A2 subunit binding to Ah-plasmin by ca. 50% in a dose-dependent manner
-
489-514 peptide of factor VIII
-
weakly inhibits binding of the A2 subunit and plasmin with ca. 80% residual binding at the highest concentration (0.8 mM) of peptide
-
6-Aminohexanoic acid
-
blocks the interactions between light chain and plasmin in a dose-dependent manner by more than 90%. Blocks A2 subunit and plasmin interaction weakly by ca. 30%. Inhibitory effect of 6-aminohexanoic acid on the interaction between the heavy chain or factor VIII and Ah-plasmin is similar to that for the A2 interaction
6-Aminohexanoic acid
-
weak, competitive
6-Aminohexanoic acid
-
noncompetitive
6-Aminohexanoic acid
-
the heavy chain plays an important role in the inhibition of the enzyme by 6-aminohexanoate
A2 subunit of factor VIII
-
plasmin-catalyzed activation of factor VIII is significantly inhibited by the addition of isolated A2 subunit of factor VIII in a dose-dependent manner
-
AG490
-
JAK inhibitor, inhibits JAK1 but does not inhibit TYK2 phosporylation by plasmin. Impairs plasmin-mediated phosphorylation of ERK1/2, Akt1, and the subsequent phosphorylation of IkappaBalpha, but not that of p38 MAPK. Inhibits plasmin-induced TNF-alpha release by 63% and IL-6 release by 76%
Ah-plasmin
-
immobilized Ah-plasmin inhibits the A2 binding to Ah-plasmin by ca. 80% in a dose-dependent manner
-
AKbetaBA
-
inhibits plasmin-induced TNF-alpha release by 70%. Inhibits plasmin-induced activation of NF-kappaB by 66%
alpha(2)-plasmin inhibitor
-
blocks plasmin activity
-
alpha-antitrypsin
-
-
-
alpha-Lactalbumin
-
shows a strong correlation with plasmin activity and may have inhibitory activity against plasmin
-
alpha1 globulin
-
-
-
alpha1-protease inhibitor
-
plasmin bound to fibrin is completely protected
-
alpha2 globulin
-
-
-
alpha2-antiplasmin
-
kinetics of plasmin type 1 and 2 inhibition in absence of soluble fibrin or epsilon-caproic acid is a reversible slow binding inhibition with an initial loose complex and a following tight complex. Epsilon-amino-caproic acid slows down the first step of the reaction without effect on the second step. Fibrin slows down both reaction steps
-
alpha2-antiplasmin
-
inhibitory activity is neutralized by addition of the antibody against alpha2-antiplasmin
-
alpha2-antiplasmin
-
-
-
alpha2-antiplasmin
-
plasmin inhibitor, completely blocks ability of noninhibitory plasminogen activator inhibitor-type 1 to normalize ECM degradation
-
alpha2-antiplasmin
-
similar inhibition of native enzyme and deletion mutant lacking the middle portion of the molecule
-
alpha2-antiplasmin
P00747
the main physiological inhibitor and a serpin
-
alpha2-antiplasmin
-
-
-
alpha2-antiplasmin
-
inhibits proteolysis of rADAMTS13
-
alpha2-antiplasmin
-
contributes to the inactivation of plasmin activity
-
alpha2-antiplasmin
-
inactivation is reduced in plasmin that is bound to fibrin
-
alpha2-Macroglobulin
-
similar inhibition 0f native enzyme and deletion mutant lacking the middle portion of the molecule
-
alpha2-Macroglobulin
P00747
general protease inhibitor
-
alpha2-Macroglobulin
-
plasmin bound to fibrin is completely protected
-
alpha2-Plasmin inhibitor
-
kringle domains K2, K3, and K5 are involved in the modulation of Plm activity
-
Amino methyl cyclohexane carboxylic acid
-
-
-
annexin II tetramer
-
promotes plasmin inactivation by stimulating the autoproteolytic digestion of plasmin heavy and light chains, also stimulates formation of plasmin. annexin II tetramer may function to provide the cell surface with a transient pulse of plasmin activity
-
antiplasmin
-
the inhibition of plasmin by antiplasmin can be reduced by high molecular weight fibrin degradation products with carboxy-terminal lysine residues
-
Aprotinin
-
complete inhibition of pro-matrix metalloproteinase-3 activation at 0.05 mM
Aprotinin
-
inhibits plasmin-induced phosphorylation of ERK1/2
Aprotinin
-
plasmin inhibitor, completely blocks ability of noninhibitory plasminogen activator inhibitor-type 1 to normalize ECM degradation
Aprotinin
-
in a mouse tail-vein bleeding model, intravenous textilinin-1 and aprotinin cause similar decreases in blood loss while time to hemostasis in the textilinin-treated animals is significantly shorter
Aprotinin
-
-
Aprotinin
-
-
arachidonate
synthetic construct
-
-
arsenic acid
-
organometallic complexes composed of humic acid and arsenic acid show enhanced inhibition of plasmin activity as compared with either arsenic or humic acid alone
benzamidine
-
-
benzamidine
-
competitive
beta-Lactoglobulin
-
native and denatured beta-lactoglobulin inhibits activity with D-Val-L-Leu-L-Lys-p-nitroanilide and casein
-
Blood serum
-
bovine or ovine blood serum do not affect hydrolysis of caseins in milk by plasmin. Equine and particularly porcine serum strongly inhibit casein hydrolysis. Heated serum (70C for 5 min) from any of the species does not influence plasmin-induced hydrolysis of caseins. Bovine or ovine serum (2%) have no effect on plasmin activity when assayed on N-Suc-L-Ala-L-Phe-L-Lys-7-amido-4-methyl-coumarin in milk. 2.0% porcine serum reduces plasmin activity on this peptide by ca. 40%
-
C1 inhibitor
-
the C1-inhibitor in its native state inhibits plasmin without significant degradation. If the C1-inhibitor is in a denatured polymeric state as can easily occur during storage, or as produced by heating of the native protein, it will be extensively degraded by plasmin
-
Carbonic acid 4-[(S)-2-(6-amino-hexanoylamino)-2-(1,1-dimethyl-propylcarbamoyl)-ethyl]-phenyl ester 2-bromo-benzyl ester
-
IC50 in reaction with D-Val-Leu-Lys-4-nitroanilide is 0.0062 mM, IC50 in reaction with fibrin is 0.0012 mM
Carbonic acid 4-[(S)-2-(6-amino-hexanoylamino)-2-heptylcarbamoyl-ethyl]-phenyl ester 2-bromo-benzyl ester
-
IC50 in reaction with D-Val-Leu-Lys-4-nitroanilide is 0.011 mM, IC50 in reaction with fibrin is 0.0033 mM
Carbonic acid 4-[(S)-2-(6-amino-hexanoylamino)-2-hexylcarbamoyl-ethyl]-phenyl ester 2-bromo-benzyl ester
-
IC50 in reaction with D-Val-Leu-Lys-4-nitroanilide is 0.013 mM, IC50 in reaction with fibrin is 0.0027 mM
Carbonic acid 4-[(S)-2-(6-amino-hexanoylamino)-2-nonylcarbamoyl-ethyl]-phenyl ester 2-bromo-benzyl ester
-
IC50 in reaction with D-Val-Leu-Lys-4-nitroanilide is 0.0083 mM, IC50 in reaction with fibrin is 0.0013 mM
Carbonic acid 4-[(S)-2-(6-amino-hexanoylamino)-2-octylcarbamoyl-ethyl]-phenyl ester 2-bromo-benzyl ester
-
IC50 in reaction with D-Val-Leu-Lys-4-nitroanilide is 0.007 mM, IC50 in reaction with fibrin is 0.0018 mM
Carbonic acid 4-[(S)-2-(6-amino-hexanoylamino)-2-pentylcarbamoyl-ethyl]-phenyl ester 2-bromo-benzyl ester
-
IC50 in reaction with D-Val-Leu-Lys-4-nitroanilide is 0.01 mM, IC50 in reaction with fibrin is 0.0013 mM
carbonic acid 4-[2-(6-amino-hexanoylamino)-2-(1,1-dimethyl-propylcarbamoyl)-ethyl]-phenyl ester 2-bromo-benzyl ester
-
IC50 in reaction with D-Val-Leu-Lys-4-nitroanilide is 0.085 mM, IC50 in reaction with fibrin is 0.019 mM
carbonic acid 4-[2-(6-amino-hexanoylamino)-2-(4-butyl-phenylcarbamoyl)-ethyl]-phenyl ester 2-bromo-benzyl ester
-
IC50 in reaction with D-Val-Leu-Lys-4-nitroanilide is 0.009 mM, IC50 in reaction with fibrin is 0.0023 mM
carbonic acid 4-[2-(6-amino-hexanoylamino)-2-(4-hexyl-phenylcarbamoyl)-ethyl]-phenyl ester 2-bromo-benzyl ester
-
IC50 in reaction with D-Val-Leu-Lys-4-nitroanilide is 0.006 mM, IC50 in reaction with fibrin is 0.0035 mM
carbonic acid 4-[2-(6-amino-hexanoylamino)-2-(4-pentyl-phenylcarbamoyl)-ethyl]-phenyl ester 2-bromo-benzyl ester
-
IC50 in reaction with D-Val-Leu-Lys-4-nitroanilide is 0.009 mM, IC50 in reaction with fibrin is 0.0047 mM
carbonic acid 4-[2-(6-amino-hexanoylamino)-2-propylcarbamoyl-ethyl]-phenyl ester 2-bromo-benzyl ester
-
IC50 in reaction with D-Val-Leu-Lys-4-nitroanilide is 0.0092 mM, IC50 in reaction with fibrin is 0.002 mM
carbonic acid 4-[2-[(4-aminomethyl-cyclohexanecarbonyl)-amino]-2-(1,1-dimethyl-propylcarbamoyl)-ethyl]-phenyl ester 2-bromo-benzyl ester
-
IC50 in reaction with D-Val-Leu-Lys-4-nitroanilide is 0.013 mM, IC50 in reaction with fibrin is 0.0017 mM
carbonic acid 4-[2-[(4-aminomethyl-cyclohexanecarbonyl)-amino]-2-(3-methyl-butylcarbamoyl)-ethyl]-phenyl ester 2-bromo-benzyl ester
-
IC50 in reaction with D-Val-Leu-Lys-4-nitroanilide is 0.00046 mM, IC50 in reaction with fibrin is 0.000056 mM
carbonic acid 4-[2-[(4-aminomethyl-cyclohexanecarbonyl)-amino]-2-(4-butyl-phenylcarbamoyl)-ethyl]-phenyl ester 2-bromo-benzyl ester
-
IC50 in reaction with D-Val-Leu-Lys-4-nitroanilide is 0.00079 mM, IC50 in reaction with fibrin is 0.00009 mM
carbonic acid 4-[2-[(4-aminomethyl-cyclohexanecarbonyl)-amino]-2-(4-ethyl-phenylcarbamoyl)-ethyl]-phenyl ester 2-bromo-benzyl ester
-
IC50 in reaction with D-Val-Leu-Lys-4-nitroanilide is 0.00063 mM, IC50 in reaction with fibrin is 0.000098 mM
carbonic acid 4-[2-[(4-aminomethyl-cyclohexanecarbonyl)-amino]-2-(4-hexyl-phenylcarbamoyl)-ethyl]-phenyl ester 2-bromo-benzyl ester
-
IC50 in reaction with D-Val-Leu-Lys-4-nitroanilide is 0.00049 mM, IC50 in reaction with fibrin is 0.00024 mM
carbonic acid 4-[2-[(4-aminomethyl-cyclohexanecarbonyl)-amino]-2-(4-methoxymethyl-phenylcarbamoyl)-ethyl]-phenyl ester 2-bromo-benzyl ester
-
IC50 in reaction with D-Val-Leu-Lys-4-nitroanilide is 0.00023 mM, IC50 in reaction with fibrin is mM
carbonic acid 4-[2-[(4-aminomethyl-cyclohexanecarbonyl)-amino]-2-(4-pentyl-phenylcarbamoyl)-ethyl]-phenyl ester 2-bromo-benzyl ester
-
IC50 in reaction with D-Val-Leu-Lys-4-nitroanilide is 0.00057 mM, IC50 in reaction with fibrin is 0.00007 mM
carbonic acid 4-[2-[(4-aminomethyl-cyclohexanecarbonyl)-amino]-2-(pyridin-4-ylcarbamoyl)-ethyl]-phenyl ester 2-bromo-benzyl ester
-
IC50 in reaction with D-Val-Leu-Lys-4-nitroanilide is 0.00098 mM, IC50 in reaction with fibrin is 0.00017 mM
carbonic acid 4-{2-[(4-aminomethyl-cyclohexanecarbonyl)-amino]-2-heptylcarbamoyl-ethyl}-phenyl ester 2-bromo-benzyl ester
-
IC50 in reaction with D-Val-Leu-Lys-4-nitroanilide is 0.0011 mM, IC50 in reaction with fibrin is 0.00043 mM
carbonic acid 4-{2-[(4-aminomethyl-cyclohexanecarbonyl)-amino]-2-hexylcarbamoyl-ethyl}-phenyl ester 2-bromo-benzyl ester
-
IC50 in reaction with D-Val-Leu-Lys-4-nitroanilide is 0.0012 mM, IC50 in reaction with fibrin is 0.00038 mM
carbonic acid 4-{2-[(4-aminomethyl-cyclohexanecarbonyl)-amino]-2-nonylcarbamoyl-ethyl}-phenyl ester 2-bromo-benzyl ester
-
potent and selective inhibitor for plasmin, IC50 in reaction with D-Val-Leu-Lys-4-nitroanilide is 0.0005 mM, IC50 in reaction with fibrin is 0.0001 mM
carbonic acid 4-{2-[(4-aminomethyl-cyclohexanecarbonyl)-amino]-2-pentylcarbamoyl-ethyl}-phenyl ester 2-bromo-benzyl ester
-
IC50 in reaction with D-Val-Leu-Lys-4-nitroanilide is 0.011 mM, IC50 in reaction with fibrin is 0.0001 mM
carbonic acid 4-{2-[(4-aminomethyl-cyclohexanecarbonyl)-amino]-2-[(pyridin-2-ylmethyl)-carbamoyl]-ethyl}-phenyl ester 2-bromo-benzyl ester
-
IC50 in reaction with D-Val-Leu-Lys-4-nitroanilide is 0.0015 mM, IC50 in reaction with fibrin is 0.00052 mM
carbonic acid 4-{2-[(4-aminomethyl-cyclohexanecarbonyl)-amino]-2-[(pyridin-4-ylmethyl)-carbamoyl]-ethyl}-phenyl ester 2-bromo-benzyl ester
-
IC50 in reaction with D-Val-Leu-Lys-4-nitroanilide is0.0053 mM, IC50 in reaction with fibrin is 0.0014 mM
carbonic acid 4-{2-[(4-aminomethyl-cyclohexanecarbonyl)-amino]-2-[benzyl-carbamoyl]-ethyl}-phenyl ester 2-bromo-benzyl ester
-
IC50 in reaction with D-Val-Leu-Lys-4-nitroanilide is 0.0011 mM, IC50 in reaction with fibrin is 0.0003 mM
Cholesterol sulfate
-
reduces plasmin activity in a dose-dependent manner
cis-parinaric acid
-
more than 60% inhibition of pro-matrix metalloproteinase-3 activation at 0.05 mM
CO
-
CO elicits hypofibrinolysis by enhancing alpha2-antiplasmin activity and decreasing plasmin activity
D-Ile-Phe-Lys-CN
-
-
-
D-Ile-Phe-Lys-NH2
-
-
-
D-Leu-Lys-benzylamide
-
weak inhibitor of amidolytic activity
D-Phe-Lys-benzylamide
-
inhibition of fibrinolytic activity, no inhibition of amidolytic activity
D-Val-Phe-Lys-chloromethyl ketone
synthetic construct
-
inhibits the ability of plasmin to potentiate lipopolysaccharide signalling. Significantly inhibits the generation of TNFalpha from untransfected RAW cells after plasmin pretreatment and stimulated with LPS
diisopropyl fluorophosphate
-
does not block binding of hepatocytes from mice to immobilized plasmin, but blocks active site of plasmin and its ability to phosphorylate ERK1/2
discreplasminin
-
isolated from Tityus discrepans scorpion venom. Peptide with a relative molecular weight of less than 6000 Da and a pI value of 8.0. Discreplasminin strongly inhibits plasmin and moderately inhibits tissue plasminogen activator
-
elaidic acid
-
60% inhibition of pro-matrix metalloproteinase-3 activation at 0.05 mM
Epsilon-aminocaproic acid
-
inhibits plasmin-induced phosphorylation of ERK1/2; lysine binding sites inhibitor, partially blocks binding of hepatocytes from mice to immobilized plasmin at 10 mM, but not at 0.01 mM
Fibrin
-
inhibits hydrolysis of D-Val-Leu-Lys-p-nitroanilide
Fibrinogen
-
competitive inhibitor of plasmin chromogenic activity
-
Fibrinogen
-
inhibits hydrolysis of D-Val-Leu-Lys-p-nitroanilide. 6-aminohexanoic acid abolishes inhibition
-
fragment X
-
competitive inhibitor of plasmin chromogenic activity
-
histidine-rich glycoprotein
P00747
binds at sites of tissue injury and seems to act as a high-affinity receptor to immobilize plasminogen on cell surfaces
-
human aprotinin analogue
-
-
-
human plasma protein inhibitors
-
-
-
humic acid
-
0.02-0.48 mg/ml, up to 95% inhibition, natural and synthetic. Organometallic complexes composed of humic acid and arsenic acid show enhanced inhibition of plasmin activity as compared with either arsenic or humic acid alone
hydroxyethyl starch 130
-
plasma diluted with hydroxyethyl starch 130 has a significant more than 25% attenuation of plasmin-mediated decreases in the maximum rate of thrombus generation and total thrombus generation compared with 0.9% NaCl diluted and undiluted plasma. Enhances fibrinolysis by diminishing alpha2-antiplasmin-plasmin interactions
-
L-tryptophyl-N-(4-oxotetrahydrofuran-3-yl)-L-phenylalaninamide
synthetic construct
-
-
LEKTI
-
potent noncompetitive inhibitor, recombinant LEKTI is purified using a baculovirus/insect cell expression system
Leu-Lys-benzylamide
-
inhibition of fibrinolytic activity, no inhibition of amidolytic activity
Leupeptin
synthetic construct
-
inhibits the ability of plasmin to potentiate lipopolysaccharide signalling
Lima bean trypsin inhibitor
-
-
-
Lys-Met(sulfone)-Tyr-Arg
-
shows 25fold selectivity for plasmin over plasma kallikrein
-
mAb413
-
antibody of A2 subunit, that blocks plasmin-catalyzed factor VIII heavy chain cleavage at Arg336 and Arg372, but not at Arg740. This antibody does not affect plasmin-catalyzed cleavage of the light chain
-
MG-132
-
prevents facilitation of degradation of Bim(EL) by plasmin in hepatocytes from mice pretreated with cycloheximide
N-(trans-4-aminomethylcyclohexanecarbonyl)-Tyr(O-2-bromobenzyloxycarbonyl)-octylamide
-
potent and selective inhibitor for plasmin, IC50 in reaction with D-Val-Leu-Lys-4-nitroanilide is 0.00023 mM, IC50 in reaction with fibrin is 0.0008 mM
N-[(1S)-5-amino-1-cyanopentyl]-3-([3-[1-(4-fluorobenzyl)-1H-indol-3-yl]propanoyl]amino)-4-(pyridin-4-ylmethoxy)benzamide
-
molecular modeling
N-[(1S)-5-amino-1-cyanopentyl]-3-[(naphthalen-1-ylacetyl)amino]-4-(pyridin-4-ylmethoxy)benzamide
-
-
N-[(1S)-5-amino-1-cyanopentyl]-3-[(naphthalen-2-ylacetyl)amino]-4-(pyridin-4-ylmethoxy)benzamide
-
-
N-[(1S)-5-amino-1-cyanopentyl]-3-[[(4-fluorophenyl)acetyl]amino]-4-(pyridin-4-ylmethoxy)benzamide
-
-
N-[(1S)-5-amino-1-cyanopentyl]-3-[[3-(1H-indol-3-yl)propanoyl]amino]-4-(pyridin-4-ylmethoxy)benzamide
-
-
N-[(1S)-5-amino-1-cyanopentyl]-4-(pyridin-4-ylmethoxy)benzamide
-
-
N-[(benzyloxy)carbonyl]-L-tryptophyl-N-(1,1-dioxido-4-oxotetrahydrothiophen-3-yl)-L-phenylalaninamide
synthetic construct
-
-
N-[(benzyloxy)carbonyl]-L-tryptophyl-N-(1-glycyl-4-oxopyrrolidin-3-yl)-L-phenylalaninamide
synthetic construct
-
-
N-[(benzyloxy)carbonyl]-L-tryptophyl-N-(2-oxocyclohexyl)-L-phenylalaninamide
synthetic construct
-
-
N-[(benzyloxy)carbonyl]-L-tryptophyl-N-(2-oxocyclopentyl)-L-phenylalaninamide
synthetic construct
-
-
N-[(benzyloxy)carbonyl]-L-tryptophyl-N-(4-aminobenzyl)-N-(4-oxotetrahydrofuran-3-yl)-L-phenylalaninamide
synthetic construct
-
-
N-[(benzyloxy)carbonyl]-L-tryptophyl-N-(4-aminobutyl)-N-(4-oxotetrahydrofuran-3-yl)-L-phenylalaninamide
synthetic construct
-
-
N-[(benzyloxy)carbonyl]-L-tryptophyl-N-(4-oxotetrahydrofuran-3-yl)-L-phenylalaninamide
synthetic construct
-
-
N-[(benzyloxy)carbonyl]-L-tryptophyl-N-(4-oxotetrahydrofuran-3-yl)-L-tryptophanamide
synthetic construct
-
-
N-[(benzyloxy)carbonyl]-L-tryptophyl-N-(5-aminopentyl)-N-(4-oxotetrahydrofuran-3-yl)-L-phenylalaninamide
synthetic construct
-
-
N-[(benzyloxy)carbonyl]-L-tryptophyl-N-(6-aminohexyl)-N-(1,1-dioxido-4-oxotetrahydrothiophen-3-yl)-L-phenylalaninamide
synthetic construct
-
-
N-[(benzyloxy)carbonyl]-L-tryptophyl-N-(6-aminohexyl)-N-(4-oxotetrahydrofuran-3-yl)-L-phenylalaninamide
synthetic construct
-
-
N-[(benzyloxy)carbonyl]-L-tryptophyl-N-(7-aminoheptyl)-N-(4-oxotetrahydrofuran-3-yl)-L-phenylalaninamide
synthetic construct
-
-
N-[(benzyloxy)carbonyl]-L-tryptophyl-N-[(trans-4-aminocyclohexyl)methyl]-N-(4-oxotetrahydrofuran-3-yl)-L-phenylalaninamide
synthetic construct
-
-
Nalpha-[[trans-4-(aminomethyl)cyclohexyl]carbonyl]-N-hexyl-O-(pyridin-4-ylmethyl)-L-tyrosinamide
-
binding mode
natural aprotinin
-
-
-
neuroserpin
P00747
mainly expressed in the brain, a serpin and single-chain glycoprotein of 55 kDa containing three potential N-glycosylation sites at Asn141, Asn305, and Asn385
-
neuroserpin
-
an axonally secreted serine proteinase inhibitor
-
Nomega-nitro-L-arginine methyl ester
-
almost completely abolishes plasmin-induced relaxation
oleate
synthetic construct
-
-
oleic acid
-
59% inhibition of pro-matrix metalloproteinase-3 activation at 0.05 mM
Pancreatic trypsin inhibitor
-
-
-
Pancreatic trypsin inhibitor
-
-
-
PD98059
-
MEK inhibitor, completely abolishes plasmin-induced phosphorylation of ERK1/2 at 0.05 mM
pefabloc
-
-
peptide GHRPYam
-
delays appearance of plasmin activity
peroxynitrite
-
50% inhibition at 280 microM and an enzyme concentration of 10 microM
Phe-Lys-benzylamide
-
inhibition of fibrinolytic activity, no inhibition of amidolytic activity
plasminogen activator inhibitor I
-
inhibits plasminogen activation to plasmin by urokinase-type plasminogen activator
-
plasminogen activator inhibitor II
-
inhibits plasminogen activation to plasmin by urokinase-type plasminogen activator
-
plasminogen activator inhibitor-type 1
-
totally blocks plasmin activity and degradation of casein
-
plasminogen activator inhibitors 1
P00747
-
-
plasminogen activator inhibitors 2
P00747
-
-
Protein C inhibitor
-
from Bos taurus
-
R484A mutant of A2
-
subunit of factor VIII, possessing ca. 250fold reduced affinity for plasmin, weakly inhibits factor VIIIa inactivation by ca. 20%
-
recombinant aprotinin
-
-
-
RG1192
-
dextran containing carboxymethylsulfate as well as benzylamide groups. Lysine-binding site domain of plasmin is the RG1192 binding site. In addition RG1192 blocks the generation of plasmin from Glu-plasminogen and inhibits the plasmin-mediated proteolysis of fibronectin and laminin
-
RG1503
-
-
-
SB203580
-
inhibits plasmin-induced TNF-alpha release by 75% and IL-6 release by 79%
serpinb2
-
steroid-treated ovariectomized mice deficient in tissue inhibitor of metalloprotease-1 and exposed to estrogen show a significant increase in plasmin activity. Increase is probably due to reduced expression of plasmin inhibitors serpinb7 and serpinb2
-
serpinb7
-
steroid-treated ovariectomized mice deficient in tissue inhibitor of metalloprotease-1 and exposed to estrogen show a significant increase in plasmin activity. Increase is probably due to reduced expression of plasmin inhibitors serpinb7 and serpinb2. Serpinb7 is localized to luminal and glandular epithelial cells of the uterus. Expression of serpinb7 is decreased by estrogen and shows an inverse relationship with plasmin activity
-
Soybean trypsin inhibitor
-
-
-
Soybean trypsin inhibitor
-
-
-
stearate
synthetic construct
-
-
streptokinase
-
-
-
sulfated polyvinylalcohol-acrylate copolymers
-
both the amidolytic and fibrinolytic activities are inhibited
-
tert-butyl 3-(3-[[5-[[(1S)-5-amino-1-cyanopentyl]carbamoyl]-2-(pyridin-4-ylmethoxy)phenyl]amino]-3-oxopropyl)-1H-indole-1-carboxylate
-
-
textilinin-1
-
potent and reversible inhibition. At 5 microM almost complete inhibition of tissue plasminogen activator-induced fibrinolysis of whole blood clots without affecting the activated partial thromboplastin time for plasma. In a mouse tail-vein bleeding model, intravenous textilinin-1 and aprotinin cause similar decreases in blood loss while time to hemostasis in the textilinin-treated animals is significantly shorter
-
textilinin-1
-
textilinin-1 is a Kunitz-type serine protease inhibitor isolated from the venom of the Australian common brown snake, Pseudonaja textilis. This molecule binds to and blocks the activity plasmin
-
Tranexamic acid
-
substantially abrogates the relaxing effect of plasmin
Tranexamic acid
-
plasmin inhibitor, completely blocks ability of noninhibitory plasminogen activator inhibitor-type 1 to normalize ECM degradation
Tranexamic acid
-
a synthetic inhibitor efficiently decreasing plasmin activity, plasmin inhibition by tranexamic acid upregulates the profibrogenic genes, which respond to TGF-beta-intracellular signalling
trans-parinaric acid
-
60% inhibition of pro-matrix metalloproteinase-3 activation at 0.05 mM
VFK-CMK
-
-
[4-[(N-[[trans-4-(aminomethyl)cyclohexyl]carbonyl]-L-phenylalanyl)amino]phenyl]acetic acid
-
binding mode
MgCl2
-
0.01 M and above
additional information
-
no inhibition by protein C inhibitor from Bos taurus
-
additional information
-
inhibition of ERK1/2 by MEK inhibitor U0126 does not affect plasmin-mediated expression of TNF-alpha
-
additional information
-
pretreatment with plasmin, thrombin and trypsin significantly but, only partly, attenuates subsequent relaxation induced by plasmin. Major part of the plasmin-induced relaxation is resistant to these pretreatments
-
additional information
-
synthetic peptides GHRPam, GHRPLam, and GHRPYam mimicking the B knobs, render fibrin less vulnerable to attack by plasmin. None of the three synthetic peptides have a significant effect on the plasmin catalyzed hydrolysis of the chromogenic peptide D-Val-Leu-Lys-p-nitroanilide. Even in the absence of synthetic peptides there is a lag in plasmin generation accompanying fibrin formation
-
additional information
synthetic construct
-
peptide inhibitors that incorporate 3-oxotetrahydrofuran and 3-oxotetrahydrothiophene 1,1-dioxide groups have the highest activities. For cyclopentanone-based inhibitors, incorporation of electron-withdrawing groups such as O and SO2 into the ring improves their activities. Alkylamino substituents, with an optimal spacer length of 6 carbon atoms, can be added to the inhibitors to bind in the S1 subsite. Incorporating conformationally constrained peptide segments into the inhibitors do not improve their activities
-
additional information
-
dilution of normal plasma with 0.9% NaCl does not significantly affect plasmin-mediated decreases in the maximum rate of thrombus and total thrombus generation compared with undiluted plasma
-
additional information
-
inactive plasmin, in which the catalytic site has been irreversibly blocked with a peptide inhibitor
-
additional information
-
noninhibitory plasminogen activator inhibitor-type 1 has no effect on plasmin activity and degradation of casein
-
additional information
-
development and evaluation of alternative potent and selective serine lysine analogues to inhibit plasmin, usage of a noncombinatorial peptide library to define plasmin's extended substrate specificity and guide the design of potent transition state analogue inhibitors, molecular modeling, overview
-
additional information
-
preparation and analysis of lysine-nitrile derivatives having a trisubstituted benzene for inhibitory activities against plasmin and the highly homologous plasma kallikrein and urokinase. Development of specific and selective inhibitors based on 9, overview. No inhibition by N-[(1S)-5-amino-1-cyanopentyl]-3-([3-[1-(4-fluorobenzyl)-1H-indol-3-yl]propanoyl]amino)-4-methoxybenzamide
-
additional information
P00747
features and mode of action of plasmin inhibitors, detailed overview
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Aprotinin
-
augments binding of hepatocytes from mice to immobilized plasmin
arachidonate
synthetic construct
-
-
Blood serum
-
2.0% equine serum increases plasmin activity by ca.50% when assayed with N-Suc-L-Ala-L-Phe-L-Lys-7-amido-4-methyl-coumarin in milk
-
Factor IXa
-
regulates plasmin-catalyzed factor VIIIa inactivation
-
fragment X
-
profibrinolytic effect with plasmin. Rates of plasmin formation increase with increasing fragment X concentrations. Plasmin degrades clots containing fragment X more rapidly than fibrin clots
-
high molecular weight urokinase-type plasminogen activator
-
induces a significant increase in plasmin activity in unstimulated or lipopolysaccharide-stimulated monocytes
-
oleate
synthetic construct
-
-
stearate
synthetic construct
-
-
urokinase-type plasminogen activator
-
cleaves plasminogen to give active plasmin
-
low molecular weight urokinase-type plasminogen activator
-
induces a significant increase in plasmin activity in unstimulated or lipopolysaccharide-stimulated monocytes
-
additional information
-
activation of a low concentration of plasminogen by cell-associated plasminogen activators produces sufficient active plasmin to rapidly and efficiently process pro-brain-derived neurotrophic factor in the pericellular environment
-
additional information
-
ATF-urokinase-type plasminogen activator causes little, if any, increase in plasmin activity in unstimulated or lipopolysaccharide-stimulated monocytes
-
additional information
-
Glu-plasminogen incubated with adherent cells, i.e. CHO-K1, HEK-293 and HMEC-1 cells, is converted into plasmin for activation by constitutively expressed tPA, i.e. tissue-type plasminogen activator, or uPA, i.e. urokinase-type plasminogen activator
-
additional information
P00747
the main physiological activators of plasminogen are tissue-type plasminogen activator, which is mainly involved in the dissolution of the fibrin polymers by plasmin, and urokinase-type plasminogen activator, which is primarily responsible for the generation of plasmin activity in the intercellular space. Both activators are multidomain serine proteases
-
additional information
-
staphylokinase, SAK, forms a 1:1 stoichiometric complex with human plasmin and switches its substrate specificity to generate a plasminogen activator complex with a crucial requirement of a positively charged and an aromatic residue, respectively, at positions 43 and 44, i.e. SAKHis43 and SAKTyr44, for optimal functioning of SAK-Pm activator complex. Role of these residues in making cation-pi and pi-pi interactions with Trp215 of plasmin and thus establishing the crucial intermolecular contacts within the active site cleft of the activator complex for the cofactor activity of staphylokinase. Molecular modeling and structure analysis, overview
-
additional information
-
the increased activity of plasmin after diafiltration may be also due to elimination of small enzyme inhibitor proteins
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.003
AIYRSR
-
pH 8.0
0.0135
benzyloxycarbonyl-Lys-p-nitrophenyl ester
-
Glu1-plasminogen
0.015
benzyloxycarbonyl-Lys-p-nitrophenyl ester
-
Lys77-plasminogen
0.083
benzyloxycarbonyl-Lys-p-nitrophenyl ester
-
Val561-plasminogen
0.004
CIYRSR
-
pH 8.0
0.02
D-Ile-Phe-Lys
-
pH and temperature not specified in the publication
-
0.00589
D-norleucyl-hexahydrotyrosyl-lysine-p-nitroanilide
synthetic construct
-
in the absence of fatty acids
0.00817
D-norleucyl-hexahydrotyrosyl-lysine-p-nitroanilide
synthetic construct
-
in the presence of 0.065 mM stearate
0.01133
D-norleucyl-hexahydrotyrosyl-lysine-p-nitroanilide
synthetic construct
-
in the presence of 0.115 mM stearate
0.01258
D-norleucyl-hexahydrotyrosyl-lysine-p-nitroanilide
synthetic construct
-
in the presence of 0.01 mM oleate
0.02009
D-norleucyl-hexahydrotyrosyl-lysine-p-nitroanilide
synthetic construct
-
in the presence of 0.025 mM oleate
0.02337
D-norleucyl-hexahydrotyrosyl-lysine-p-nitroanilide
synthetic construct
-
in the presence of 0.175 mM stearate
0.02371
D-norleucyl-hexahydrotyrosyl-lysine-p-nitroanilide
synthetic construct
-
in the presence of 0.01 mM arachidonate
0.02749
D-norleucyl-hexahydrotyrosyl-lysine-p-nitroanilide
synthetic construct
-
in the presence of 0.045 mM oleate
0.04265
D-norleucyl-hexahydrotyrosyl-lysine-p-nitroanilide
synthetic construct
-
in the presence of 0.025 mM arachidonate
0.05751
D-norleucyl-hexahydrotyrosyl-lysine-p-nitroanilide
synthetic construct
-
in the presence of 0.045 mM arachidonate
0.05985
D-norleucyl-hexahydrotyrosyl-lysine-p-nitroanilide
synthetic construct
-
in the presence of 0.065 mM arachidonate
0.07296
D-norleucyl-hexahydrotyrosyl-lysine-p-nitroanilide
synthetic construct
-
in the presence of 0.23 mM stearate
0.1311
D-norleucyl-hexahydrotyrosyl-lysine-p-nitroanilide
synthetic construct
-
in the presence of 0.065 mM oleate
0.138
D-Val-L-Leu-L-Lys-4-nitroanilide
-
deletion mutant lacking the middle portion of the protein
0.193
D-Val-L-Leu-L-Lys-4-nitroanilide
-
native enzyme
0.21
D-Val-Leu-Lys-p-nitroanilide
-
Lys77-plasmin
0.23
D-Val-Leu-Lys-p-nitroanilide
-
plasmin adsorbed onto a carbon paste electrode
0.28
D-Val-Leu-Lys-p-nitroanilide
-
Val442-plasmin
1.26
D-Val-Leu-Lys-p-nitroanilide
-
Val561-plasmin
0.03
Fibrinogen
-
-
-
0.012
GIVRSR
-
pH 8.0
0.002
GIYRSR
-
pH 8.0
0.0058
GIYRSR
-
pH 8.0
0.0047
GPGRVV
-
pH 8.0
0.00076
hemofiltrate CC chemokine 1
-
-
-
5.1
KKSPGRVVGGSVAH
-
pH 8.0
0.33
L-Ile-Phe-Lys
-
pH and temperature not specified in the publication
-
1.6
LGGSAMSRMSSLE
-
pH 8.0
2.4
LGGSGANFRGKLE
-
pH 8.0
0.42
LGGSGAVYKAGLE
-
pH 8.0
1.85
LGGSGIGRSRSLE
-
pH 8.0
0.1
LGGSGIYRSRSLE
-
pH 8.0
3.7
LGGSGIYRSVSLE
-
pH 8.0
0.47
LGGSGIYRVRSLE
-
pH 8.0
1.7
LGGSGPYRSRSLE
-
pH 8.0
2.9
LGGSGTQRRLRLE
-
pH 8.0
0.21
LGGSGYKIGGSLE
-
pH 8.0
0.75
LGGSIRYKGKSLE
-
pH 8.0
0.0052
p-nitrophenyl-p'-(guanidinium)benzoate
-
plasmin 1
-
0.0113
p-nitrophenyl-p'-(guanidinium)benzoate
-
plasmin 2
-
0.214
p-nitrophenyl-p'-(methylethylsulfoniummethyl)benzoate
-
plasmin 1
-
0.258
p-nitrophenyl-p'-(methylethylsulfoniummethyl)benzoate
-
plasmin 2
-
0.21
p-nitrophenyl-p'-(pyridiniummethyl)-benzoate
-
plasmin 1
-
0.23
p-nitrophenyl-p'-(pyridiniummethyl)-benzoate
-
plasmin 2
-
0.027
p-nitrophenyl-p'-(thiouroniummethyl)benzoate
-
plasmin 1
-
0.043
p-nitrophenyl-p'-(thiouroniummethyl)benzoate
-
plasmin 1
-
0.021
p-tosyl-Arg methyl ester
-
-
0.036
SPGRVV
-
pH 8.0
0.005
thrombin-activatable fibrinolysis inhibitor
-
-
-
5.3
tosyl-Arg methyl ester
-
enzyme form F-1
5.3
tosyl-Arg methyl ester
-
-
7
tosyl-Arg methyl ester
-
enzyme form F-2
7
tosyl-Arg methyl ester
-
-
6.8
LGGSSIYRSRSLE
-
pH 8.0
additional information
additional information
-
ratio of kcat/Km values is 0.063 microM/s, pH 8.0, 37C
-
additional information
additional information
-
plasmin shows substrate binding site cooperativity,
-
additional information
additional information
-
although neither plasmin nor urokinase-type plasminogen activator exhibits allosteric cooperativity, modeling shows that cooperativity occurs at the system level because of substrate competition, molecular modeling and simulation, substrate competition and bistability, overview
-
additional information
additional information
-
the enzyme activity follows Michaelis-Menten kinetics
-
additional information
additional information
-
-
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.036
AIYRSR
-
pH 8.0
2.1
benzyloxycarbonyl-Lys-p-nitrophenyl ester
-
Val561-plasminogen
22.3
benzyloxycarbonyl-Lys-p-nitrophenyl ester
-
Glu1-plasminogen and Lys77-plasminogen
2.7
CIYRSR
-
pH 8.0
12.6
D-Val-L-Leu-L-Lys-4-nitroanilide
-
deletion mutant lacking the middle portion of the protein
12.7
D-Val-L-Leu-L-Lys-4-nitroanilide
-
native enzyme
14.5
D-Val-Leu-Lys-p-nitroanilide
-
Val561-plasmin
25.5
D-Val-Leu-Lys-p-nitroanilide
-
Val442-plasmin
25.7
D-Val-Leu-Lys-p-nitroanilide
-
Lys77-plasmin
0.039
GIVRSR
-
pH 8.0
0.6
GIYRSR
-
pH 8.0
1.5
GIYRSR
-
pH 8.0
0.0016
GPGRVV
-
pH 8.0
6
hemofiltrate CC chemokine 1
-
-
-
0.0086
KKSPGRVVGGSVAH
-
pH 8.0
3.2
LGGSAMSRMSSLE
-
pH 8.0
68
LGGSGANFRGKLE
-
pH 8.0
40
LGGSGAVYKAGLE
-
pH 8.0
53
LGGSGIGRSRSLE
-
pH 8.0
120
LGGSGIYRSRSLE
-
pH 8.0
39
LGGSGIYRSVSLE
-
pH 8.0
16
LGGSGIYRVRSLE
-
pH 8.0
92
LGGSGPYRSRSLE
-
pH 8.0
12
LGGSGTQRRLRLE
-
pH 8.0
12
LGGSGYKIGGSLE
-
pH 8.0
44
LGGSIRYKGKSLE
-
pH 8.0
35
LGGSSIYRSRSLE
-
pH 8.0
0.125
p-nitrophenyl-p'-(guanidinium)benzoate
-
plasmin 1 and plasmin 2
-
0.117
p-nitrophenyl-p'-(methylethylsulfoniummethyl)benzoate
-
plasmin 1
-
0.144
p-nitrophenyl-p'-(methylethylsulfoniummethyl)benzoate
-
plasmin 2
-
0.122
p-nitrophenyl-p'-(pyridiniummethyl)-benzoate
-
plasmin 1
-
0.127
p-nitrophenyl-p'-(pyridiniummethyl)-benzoate
-
plasmin 2
-
0.333
p-nitrophenyl-p'-(thiouroniummethyl)benzoate
-
plasmin 2
-
0.364
p-nitrophenyl-p'-(thiouroniummethyl)benzoate
-
plasmin 1
-
0.039
SPGRVV
-
pH 8.0
0.00042
thrombin-activatable fibrinolysis inhibitor
-
-
-
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0057
479-504 peptide of factor VIII
-
-
-
0.0103
484-509 peptide of factor VIII
-
-
-
0.0628
489-514 peptide of factor VIII
-
-
-
0.0068
6-Aminohexanoic acid
-
blocked interaction between light chain and plasmin
0.0113
6-Aminohexanoic acid
-
blocked interaction between A2 subunit and plasmin
0.0038
Fibrinogen
-
-
-
0.0095
fragment X
-
-
-
0.0000227
human aprotinin analogue
-
compared with recombinant-aprotinin, the Ki of the human aprotinin analogue is found to increase by about 2.6fold, suggesting that the substitution of Arg17-Ile18 with Lys17-Met18 in aprotinin somehow impair its interaction with plasmin
-
0.000027
LEKTI
-
-
0.0000031
Lys-Met(sulfone)-Tyr-Arg
-
pH 8.0, 22C
-
0.0000075
natural aprotinin
-
-
-
0.00015
Protein C inhibitor
-
37C
-
0.0000086
recombinant aprotinin
-
-
-
0.000028
RG1192
-
pH 7.4, 37C
-
0.00011
RG1503
-
pH 7.4, 37C
-
0.0002
stearate
synthetic construct
-
in the presence of 0.23 mM stearate
0.0007
stearate
synthetic construct
-
in the presence of 0.175 mM stearate
0.0012
stearate
synthetic construct
-
in the presence of 0.115 mM stearate
0.0025
stearate
synthetic construct
-
in the presence of 0.065 mM stearate
0.0000035
textilinin-1
-
-
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.062
(10S,13S)-10-(1H-indol-3-ylmethyl)-8,11-dioxo-N-(4-oxotetrahydrofuran-3-yl)-2-oxa-9,12-diazabicyclo[13.2.2]nonadeca-1(17),15,18-triene-13-carboxamide
synthetic construct
-
-
0.025
(12S,15S)-12-(1H-indol-3-ylmethyl)-10,13-dioxo-N-(4-oxotetrahydrofuran-3-yl)-2-oxa-11,14-diazabicyclo[15.2.2]henicosa-1(19),17,20-triene-15-carboxamide
synthetic construct
-
-
0.63
(4-[2-[(4-aminomethyl-cyclohexanecarbonyl)-amino]-3-phenyl-propionylamino]-phenyl)-acetic acid
-
IC50 in reaction with D-Val-Leu-Lys-4-nitroanilide is 0.63 mM
0.3
(9S,12S)-9-(1H-indol-3-ylmethyl)-7,10-dioxo-N-(4-oxotetrahydrofuran-3-yl)-2-oxa-8,11-diazabicyclo[12.2.2]octadeca-1(16),14,17-triene-12-carboxamide
synthetic construct
-
-
0.024
2-(3-[3-[(6-amino-hexyl)-(2-benzyloxycarbonylamino-3-phenyl-propionyl)-amino]-2-oxo-cyclohexyl]-propionylamino)-3-(1H-indol-3-yl)-propionic acid methyl ester
-
IC50: 0.024 mM
0.0042
2-[(4-Aminomethyl-cyclohexanecarbonyl)-amino]-3-[4-(2-bromo-benzyloxycarbonyloxy)-phenyl]-propionic acid pyridin-2-ylmethyl ester
-
IC50 in reaction with D-Val-Leu-Lys-4-nitroanilide is 0.0042 mM
0.02
2-[3-(3-[(6-amino-hexyl)-[2-benzyloxycarbonylamino-3-(1H-indol-3-yl)-propionyl]-amino]-2-oxo-cyclohexyl)-propionylamino]-3-(1H-indol-3-yl)-propionic acid methyl ester
-
IC50: 0.02 mM
0.0039
4-({2-(6-amino-hexanoylamino)-3-[4-(2-bromo-benzyloxycarbonyloxy)-phenyl]-propionylamino}-methyl)-cyclohexanecarboxylic acid heptyl ester
-
IC50 in reaction with D-Val-Leu-Lys-4-nitroanilide is 0.024 mM, IC50 in reaction with fibrin is 0.0039 mM
0.0043
4-({2-(6-amino-hexanoylamino)-3-[4-(2-bromo-benzyloxycarbonyloxy)-phenyl]-propionylamino}-methyl)-cyclohexanecarboxylic acid hexyl ester
-
IC50 in reaction with D-Val-Leu-Lys-4-nitroanilide is 0.018 mM, IC50 in reaction with fibrin is 0.0043 mM
0.0061
4-({2-(6-amino-hexanoylamino)-3-[4-(2-bromo-benzyloxycarbonyloxy)-phenyl]-propionylamino}-methyl)-cyclohexanecarboxylic acid methyl ester
-
IC50 in reaction with D-Val-Leu-Lys-4-nitroanilide is 0.0009 mM, IC50 in reaction with fibrin is 0.0061 mM
0.005
4-({2-(6-amino-hexanoylamino)-3-[4-(2-bromo-benzyloxycarbonyloxy)-phenyl]-propionylamino}-methyl)-cyclohexanecarboxylic acid octyl ester
-
IC50 in reaction with D-Val-Leu-Lys-4-nitroanilide is above 0.1 mM, IC50 in reaction with fibrin is 0.005 mM
0.00042
4-({2-[(4-aminomethyl-cyclohexanecarbonyl)-amino]-3-[4-(2-bromo-benzyloxycarbonyloxy)-phenyl]-propionylamino}-methyl)-cyclohexanecarboxylic acid heptyl ester
-
IC50 in reaction with D-Val-Leu-Lys-4-nitroanilide is 0.0014 mM, IC50 in reaction with fibrin is 0.00042 mM
0.0004
4-({2-[(4-aminomethyl-cyclohexanecarbonyl)-amino]-3-[4-(2-bromo-benzyloxycarbonyloxy)-phenyl]-propionylamino}-methyl)-cyclohexanecarboxylic acid hexyl ester
-
IC50 in reaction with D-Val-Leu-Lys-4-nitroanilide is 0.0015 mM, IC50 in reaction with fibrin is 0.0004 mM
0.00078
4-({2-[(4-aminomethyl-cyclohexanecarbonyl)-amino]-3-[4-(2-bromo-benzyloxycarbonyloxy)-phenyl]-propionylamino}-methyl)-cyclohexanecarboxylic acid methyl ester
-
IC50 in reaction with D-Val-Leu-Lys-4-nitroanilide is 0.001 mM, IC50 in reaction with fibrin is 0.00078 mM
0.00056
4-({2-[(4-aminomethyl-cyclohexanecarbonyl)-amino]-3-[4-(2-bromo-benzyloxycarbonyloxy)-phenyl]-propionylamino}-methyl)-cyclohexanecarboxylic acid octyl ester
-
IC50 in reaction with D-Val-Leu-Lys-4-nitroanilide is 0.0025 mM, IC50 in reaction with fibrin is 0.00056 mM
0.000151
Ah-plasmin
-
-
-
0.0012
Carbonic acid 4-[(S)-2-(6-amino-hexanoylamino)-2-(1,1-dimethyl-propylcarbamoyl)-ethyl]-phenyl ester 2-bromo-benzyl ester
-
IC50 in reaction with D-Val-Leu-Lys-4-nitroanilide is 0.0062 mM, IC50 in reaction with fibrin is 0.0012 mM
0.0033
Carbonic acid 4-[(S)-2-(6-amino-hexanoylamino)-2-heptylcarbamoyl-ethyl]-phenyl ester 2-bromo-benzyl ester
-
IC50 in reaction with D-Val-Leu-Lys-4-nitroanilide is 0.011 mM, IC50 in reaction with fibrin is 0.0033 mM
0.0027
Carbonic acid 4-[(S)-2-(6-amino-hexanoylamino)-2-hexylcarbamoyl-ethyl]-phenyl ester 2-bromo-benzyl ester
-
IC50 in reaction with D-Val-Leu-Lys-4-nitroanilide is 0.013 mM, IC50 in reaction with fibrin is 0.0027 mM
0.0013
Carbonic acid 4-[(S)-2-(6-amino-hexanoylamino)-2-nonylcarbamoyl-ethyl]-phenyl ester 2-bromo-benzyl ester
-
IC50 in reaction with D-Val-Leu-Lys-4-nitroanilide is 0.0083 mM, IC50 in reaction with fibrin is 0.0013 mM
0.0018
Carbonic acid 4-[(S)-2-(6-amino-hexanoylamino)-2-octylcarbamoyl-ethyl]-phenyl ester 2-bromo-benzyl ester
-
IC50 in reaction with D-Val-Leu-Lys-4-nitroanilide is 0.007 mM, IC50 in reaction with fibrin is 0.0018 mM
0.0013
Carbonic acid 4-[(S)-2-(6-amino-hexanoylamino)-2-pentylcarbamoyl-ethyl]-phenyl ester 2-bromo-benzyl ester
-
IC50 in reaction with D-Val-Leu-Lys-4-nitroanilide is 0.01 mM, IC50 in reaction with fibrin is 0.0013 mM
0.019
carbonic acid 4-[2-(6-amino-hexanoylamino)-2-(1,1-dimethyl-propylcarbamoyl)-ethyl]-phenyl ester 2-bromo-benzyl ester
-
IC50 in reaction with D-Val-Leu-Lys-4-nitroanilide is 0.085 mM, IC50 in reaction with fibrin is 0.019 mM
0.0023
carbonic acid 4-[2-(6-amino-hexanoylamino)-2-(4-butyl-phenylcarbamoyl)-ethyl]-phenyl ester 2-bromo-benzyl ester
-
IC50 in reaction with D-Val-Leu-Lys-4-nitroanilide is 0.009 mM, IC50 in reaction with fibrin is 0.0023 mM
0.0035
carbonic acid 4-[2-(6-amino-hexanoylamino)-2-(4-hexyl-phenylcarbamoyl)-ethyl]-phenyl ester 2-bromo-benzyl ester
-
IC50 in reaction with D-Val-Leu-Lys-4-nitroanilide is 0.006 mM, IC50 in reaction with fibrin is 0.0035 mM
0.0047
carbonic acid 4-[2-(6-amino-hexanoylamino)-2-(4-pentyl-phenylcarbamoyl)-ethyl]-phenyl ester 2-bromo-benzyl ester
-
IC50 in reaction with D-Val-Leu-Lys-4-nitroanilide is 0.009 mM, IC50 in reaction with fibrin is 0.0047 mM
0.002
carbonic acid 4-[2-(6-amino-hexanoylamino)-2-propylcarbamoyl-ethyl]-phenyl ester 2-bromo-benzyl ester
-
IC50 in reaction with D-Val-Leu-Lys-4-nitroanilide is 0.0092 mM, IC50 in reaction with fibrin is 0.002 mM
0.0017
carbonic acid 4-[2-[(4-aminomethyl-cyclohexanecarbonyl)-amino]-2-(1,1-dimethyl-propylcarbamoyl)-ethyl]-phenyl ester 2-bromo-benzyl ester
-
IC50 in reaction with D-Val-Leu-Lys-4-nitroanilide is 0.013 mM, IC50 in reaction with fibrin is 0.0017 mM
0.000056
carbonic acid 4-[2-[(4-aminomethyl-cyclohexanecarbonyl)-amino]-2-(3-methyl-butylcarbamoyl)-ethyl]-phenyl ester 2-bromo-benzyl ester
-
IC50 in reaction with D-Val-Leu-Lys-4-nitroanilide is 0.00046 mM, IC50 in reaction with fibrin is 0.000056 mM
0.00009
carbonic acid 4-[2-[(4-aminomethyl-cyclohexanecarbonyl)-amino]-2-(4-butyl-phenylcarbamoyl)-ethyl]-phenyl ester 2-bromo-benzyl ester
-
IC50 in reaction with D-Val-Leu-Lys-4-nitroanilide is 0.00079 mM, IC50 in reaction with fibrin is 0.00009 mM
0.000098
carbonic acid 4-[2-[(4-aminomethyl-cyclohexanecarbonyl)-amino]-2-(4-ethyl-phenylcarbamoyl)-ethyl]-phenyl ester 2-bromo-benzyl ester
-
IC50 in reaction with D-Val-Leu-Lys-4-nitroanilide is 0.00063 mM, IC50 in reaction with fibrin is 0.000098 mM
0.00024
carbonic acid 4-[2-[(4-aminomethyl-cyclohexanecarbonyl)-amino]-2-(4-hexyl-phenylcarbamoyl)-ethyl]-phenyl ester 2-bromo-benzyl ester
-
IC50 in reaction with D-Val-Leu-Lys-4-nitroanilide is 0.00049 mM, IC50 in reaction with fibrin is 0.00024 mM
0.00007
carbonic acid 4-[2-[(4-aminomethyl-cyclohexanecarbonyl)-amino]-2-(4-pentyl-phenylcarbamoyl)-ethyl]-phenyl ester 2-bromo-benzyl ester
-
IC50 in reaction with D-Val-Leu-Lys-4-nitroanilide is 0.00057 mM, IC50 in reaction with fibrin is 0.00007 mM
0.00017
carbonic acid 4-[2-[(4-aminomethyl-cyclohexanecarbonyl)-amino]-2-(pyridin-4-ylcarbamoyl)-ethyl]-phenyl ester 2-bromo-benzyl ester
-
IC50 in reaction with D-Val-Leu-Lys-4-nitroanilide is 0.00098 mM, IC50 in reaction with fibrin is 0.00017 mM
0.00043
carbonic acid 4-{2-[(4-aminomethyl-cyclohexanecarbonyl)-amino]-2-heptylcarbamoyl-ethyl}-phenyl ester 2-bromo-benzyl ester
-
IC50 in reaction with D-Val-Leu-Lys-4-nitroanilide is 0.0011 mM, IC50 in reaction with fibrin is 0.00043 mM
0.00038
carbonic acid 4-{2-[(4-aminomethyl-cyclohexanecarbonyl)-amino]-2-hexylcarbamoyl-ethyl}-phenyl ester 2-bromo-benzyl ester
-
IC50 in reaction with D-Val-Leu-Lys-4-nitroanilide is 0.0012 mM, IC50 in reaction with fibrin is 0.00038 mM
0.0001
carbonic acid 4-{2-[(4-aminomethyl-cyclohexanecarbonyl)-amino]-2-nonylcarbamoyl-ethyl}-phenyl ester 2-bromo-benzyl ester
-
potent and selective inhibitor for plasmin, IC50 in reaction with D-Val-Leu-Lys-4-nitroanilide is 0.0005 mM, IC50 in reaction with fibrin is 0.0001 mM
0.0001
carbonic acid 4-{2-[(4-aminomethyl-cyclohexanecarbonyl)-amino]-2-pentylcarbamoyl-ethyl}-phenyl ester 2-bromo-benzyl ester
-
IC50 in reaction with D-Val-Leu-Lys-4-nitroanilide is 0.011 mM, IC50 in reaction with fibrin is 0.0001 mM
0.00052
carbonic acid 4-{2-[(4-aminomethyl-cyclohexanecarbonyl)-amino]-2-[(pyridin-2-ylmethyl)-carbamoyl]-ethyl}-phenyl ester 2-bromo-benzyl ester
-
IC50 in reaction with D-Val-Leu-Lys-4-nitroanilide is 0.0015 mM, IC50 in reaction with fibrin is 0.00052 mM
0.0014
carbonic acid 4-{2-[(4-aminomethyl-cyclohexanecarbonyl)-amino]-2-[(pyridin-4-ylmethyl)-carbamoyl]-ethyl}-phenyl ester 2-bromo-benzyl ester
-
IC50 in reaction with D-Val-Leu-Lys-4-nitroanilide is0.0053 mM, IC50 in reaction with fibrin is 0.0014 mM
0.0003
carbonic acid 4-{2-[(4-aminomethyl-cyclohexanecarbonyl)-amino]-2-[benzyl-carbamoyl]-ethyl}-phenyl ester 2-bromo-benzyl ester
-
IC50 in reaction with D-Val-Leu-Lys-4-nitroanilide is 0.0011 mM, IC50 in reaction with fibrin is 0.0003 mM
0.078
D-Ile-Phe-Lys-CN
-
pH and temperature not specified in the publication
-
0.29
D-Ile-Phe-Lys-NH2
-
pH and temperature not specified in the publication
-
0.375
L-tryptophyl-N-(4-oxotetrahydrofuran-3-yl)-L-phenylalaninamide
synthetic construct
-
-
0.0008
N-(trans-4-aminomethylcyclohexanecarbonyl)-Tyr(O-2-bromobenzyloxycarbonyl)-octylamide
-
potent and selective inhibitor for plasmin, IC50 in reaction with D-Val-Leu-Lys-4-nitroanilide is 0.00023 mM, IC50 in reaction with fibrin is 0.0008 mM
0.14
N-[(1S)-5-amino-1-cyanopentyl]-3-([3-[1-(4-fluorobenzyl)-1H-indol-3-yl]propanoyl]amino)-4-(pyridin-4-ylmethoxy)benzamide
-
pH and temperature not specified in the publication
0.57
N-[(1S)-5-amino-1-cyanopentyl]-3-[(naphthalen-1-ylacetyl)amino]-4-(pyridin-4-ylmethoxy)benzamide
-
pH and temperature not specified in the publication
0.22
N-[(1S)-5-amino-1-cyanopentyl]-3-[(naphthalen-2-ylacetyl)amino]-4-(pyridin-4-ylmethoxy)benzamide
-
pH and temperature not specified in the publication
0.59
N-[(1S)-5-amino-1-cyanopentyl]-3-[[(4-fluorophenyl)acetyl]amino]-4-(pyridin-4-ylmethoxy)benzamide
-
pH and temperature not specified in the publication
0.37
N-[(1S)-5-amino-1-cyanopentyl]-3-[[3-(1H-indol-3-yl)propanoyl]amino]-4-(pyridin-4-ylmethoxy)benzamide
-
pH and temperature not specified in the publication
0.24
N-[(1S)-5-amino-1-cyanopentyl]-4-(pyridin-4-ylmethoxy)benzamide
-
pH and temperature not specified in the publication
0.013
N-[(benzyloxy)carbonyl]-L-tryptophyl-N-(1,1-dioxido-4-oxotetrahydrothiophen-3-yl)-L-phenylalaninamide
synthetic construct
-
-
0.35
N-[(benzyloxy)carbonyl]-L-tryptophyl-N-(1-glycyl-4-oxopyrrolidin-3-yl)-L-phenylalaninamide
synthetic construct
-
-
1
N-[(benzyloxy)carbonyl]-L-tryptophyl-N-(2-oxocyclohexyl)-L-phenylalaninamide
synthetic construct
-
-
1
N-[(benzyloxy)carbonyl]-L-tryptophyl-N-(2-oxocyclopentyl)-L-phenylalaninamide
synthetic construct
-
-
0.019
N-[(benzyloxy)carbonyl]-L-tryptophyl-N-(4-aminobenzyl)-N-(4-oxotetrahydrofuran-3-yl)-L-phenylalaninamide
synthetic construct
-
-
0.14
N-[(benzyloxy)carbonyl]-L-tryptophyl-N-(4-aminobutyl)-N-(4-oxotetrahydrofuran-3-yl)-L-phenylalaninamide
synthetic construct
-
-
0.022
N-[(benzyloxy)carbonyl]-L-tryptophyl-N-(4-oxotetrahydrofuran-3-yl)-L-phenylalaninamide
synthetic construct
-
-
0.03
N-[(benzyloxy)carbonyl]-L-tryptophyl-N-(4-oxotetrahydrofuran-3-yl)-L-tryptophanamide
synthetic construct
-
-
0.1
N-[(benzyloxy)carbonyl]-L-tryptophyl-N-(5-aminopentyl)-N-(4-oxotetrahydrofuran-3-yl)-L-phenylalaninamide
synthetic construct
-
-
0.0057
N-[(benzyloxy)carbonyl]-L-tryptophyl-N-(6-aminohexyl)-N-(1,1-dioxido-4-oxotetrahydrothiophen-3-yl)-L-phenylalaninamide
synthetic construct
-
one of the most effective inhibitors
0.009
N-[(benzyloxy)carbonyl]-L-tryptophyl-N-(6-aminohexyl)-N-(4-oxotetrahydrofuran-3-yl)-L-phenylalaninamide
synthetic construct
-
one of the most effective inhibitors
0.051
N-[(benzyloxy)carbonyl]-L-tryptophyl-N-(7-aminoheptyl)-N-(4-oxotetrahydrofuran-3-yl)-L-phenylalaninamide
synthetic construct
-
-
0.054
N-[(benzyloxy)carbonyl]-L-tryptophyl-N-[(trans-4-aminocyclohexyl)methyl]-N-(4-oxotetrahydrofuran-3-yl)-L-phenylalaninamide
synthetic construct
-
-
0.00053
Nalpha-[[trans-4-(aminomethyl)cyclohexyl]carbonyl]-N-hexyl-O-(pyridin-4-ylmethyl)-L-tyrosinamide
-
pH and temperature not specified in the publication
0.22
tert-butyl 3-(3-[[5-[[(1S)-5-amino-1-cyanopentyl]carbamoyl]-2-(pyridin-4-ylmethoxy)phenyl]amino]-3-oxopropyl)-1H-indole-1-carboxylate
-
pH and temperature not specified in the publication
0.65
[4-[(N-[[trans-4-(aminomethyl)cyclohexyl]carbonyl]-L-phenylalanyl)amino]phenyl]acetic acid
-
pH and temperature not specified in the publication
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
-
electrochemical assay and properties of plasmin adsorbed onto a carbon paste electrode
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.4 - 8
-
assay at
7.4
-
assay at
7.4
-
assay at
7.5
-
assay at
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
4.8 - 6.6
-
-
7.5 - 9.5
-
pH 7.5: about 40% of maximal activity, pH 9.5: about 50% of maximal activity
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
22 - 37
-
assay at 37C or at room temperature
37 - 45
-
-
37
-
assay at
37
-
assay at
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
plasmin is generated by the plasmin/u-PA system on surfaces of A-549 alveolar lining cells
Manually annotated by BRENDA team
-
vessel wall
Manually annotated by BRENDA team
-
plasmin evokes an increase in both phosphoinositide hydrolysis and Fura-2/AM fluorescence in cultured cortical astrocytes. Plasmin activiates extracellular signal-regulated kinase and induces a rise in intracellular Ca2+ concentration and phopho-ERK1/2 levels
Manually annotated by BRENDA team
-
plasma obtained from coronary artery disease patients contains 1.7fold more plasmin compared to controls
Manually annotated by BRENDA team
-
plasmin has no effect on ERK1/2 signaling or Ca2+ concentraion in primary cultured hippocampal neurons or hippocampal slices
Manually annotated by BRENDA team
-
originally isolated from a cirrhotic liver
Manually annotated by BRENDA team
-
plasmin induces scattering of HT-29-M6 cells in the presence of 12-myristate 13-acetate
Manually annotated by BRENDA team
-
plasmin induces a concentration-dependent transient elevation in the cytosolic Ca2+ concentrations
Manually annotated by BRENDA team
-
leukaemic cell line. In L5178Y cells with knock-out of the gene for annexin A2, the mRNA level of plasminogen is not substantially changed, but the protein level of plasmin is significantly lowered. mRNA and protein levels of S100A10 and fascin are lower in annexin A2 knock-out cells than in wild-type L5178Y cells
Manually annotated by BRENDA team
-
plasmin triggers expression and release of proinflammatory cytokines such as TNF-alpha and IL-6 in human monocyte-derived macrophages with a somewhat lower potency than the standard stimulus lipopolysaccharide. Plasmin-induced activation of JAK1, p38, ERK1/2, and NF-kappaB is indispensable for the cytokine expression
Manually annotated by BRENDA team
-
plasmin is the principal protease in milk
Manually annotated by BRENDA team
P00747
in blood as zymogen plasminogen
Manually annotated by BRENDA team
-
in CA1 pyramidal neuron, plasmin application potentiates the N-methyl-D-aspartate receptor-dependent component of miniature excitatory postsynaptic currents recorded from CA1 pyramidal neurons but has no effect on -amino-3-hydroxy-5-methyl-4-isoxazole propionate- or -aminobutyric acid receptor-mediated synaptic currents. Plasmin also increased N-methyl-D-aspartate-induced whole cell receptor currents recorded from CA1 pyramidal cells
Manually annotated by BRENDA team
-
plasmin activity and alpha1-antitrypsin activity increase with age with a direct correlation between body mass index and elastase and plasmin activity, and alpha1-antitrypsin concentration. Plasmin and elastase activity and cholesterol concentration inversely correlate with trypsin activity and matrix metalloproteinase-9 concentration
Manually annotated by BRENDA team
-
of the ears
Manually annotated by BRENDA team
-
steroid-treated ovariectomized mice deficient in tissue inhibitor of metalloprotease-1 and exposed to estrogen show a significant increase in plasmin activity. Increase is probably due to reduced expression of plasmin inhibitors serpinb7 and serpinb2
Manually annotated by BRENDA team
-
normal eyes have a low, albeit detectable, level of plasmin. Levels of plasmin are higher in eyes from rabbits with proliferative vitreoretinopathy. Amounts correlate with the stage of proliferative vitreoretinopathy
Manually annotated by BRENDA team
-
vitreous from patients with proliferative vitreoretinopathy have readily detectable levels of plasmin. Presence of plasmin is not unique to patients with proliferative vitreoretinopathy, but also present in a patient undergoing retinal surgery unrelated to proliferative vitreoretinopathy
Manually annotated by BRENDA team
additional information
-
tubular epithelial cell
Manually annotated by BRENDA team
additional information
-
ECM
Manually annotated by BRENDA team
additional information
-
high level of plasmin activity in high electrolyte ratio breast cysts, which have a low risk for cancer development
Manually annotated by BRENDA team
additional information
-
in PC-3 cells, processing of pro-brain-derived neurotrophic factor by plasmin occurs in the pericellular environment
Manually annotated by BRENDA team
additional information
-
in PCAEC cells, plasmin induces an endothelium-dependent relaxation and a concentration-dependent transient elevation in the cytosolic Ca2+ concentrations. Plasmin concentration-dependently induces NO production
Manually annotated by BRENDA team
additional information
-
plasmin is abundant in human atherosclerotic lesions, where it colocalizes with dendritic cells
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
plasminogen is a major surface-bound protein
Manually annotated by BRENDA team
PDB
SCOP
CATH
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
75400
-
equilibrium sedimentation
95552
82000 - 84000
-
enzyme inactivated with diisopropyl fluorophosphate, enzyme form F-2, high speed analytical ultracentrifugation
95550
83000 - 86000
-
enzyme inactivated with diisopropyl fluorophosphate, enzyme form F-1, high speed analytical ultracentrifugation
95550
85000
-
-
95549
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
?
P00747
x * 90000, plasminogen, SDS-PAGE, x * 88432, plasminogen, sequence determination
monomer
-
the enzyme consists of a 24000-26000 Da light chain and a 60000-63000 Da heavy chain, enzyme form F-1, high speed analytical ultracentrifugation in 6 M guanidine HCl
monomer
-
x * 48800, A-chain, + x * 25700, B-chain, equilibrium sedimentation after cleavage of a single disulfide bond in Lys-plasminogen
monomer
-
the enzyme consists of a 24000-26000 Da light chain and a 59000-62000 Da heavy chain, enzyme form F-2, high speed analytical ultracentrifugation in 6 M guanidine HCl
monomer
-
single chain protein consists of 2 disulfide-linked polypeptide chains of 60000 Da and 24000-26000 Da
additional information
-
the light chain of 50000 Da, determined by SDS-PAGE results in two bands of 30000 Da and 26000 Da
additional information
P00747
plasminogen is a single-chain, multidomain glycoprotein, and is composed of an N-terminal peptide, five triple-loop structures stabilized by three intrachain disulfide bridges called kringles, and the trypsin-like serine protease part carrying the catalytic triad His603, Asp646, and Ser741. Primary structure of human plasminogen, overview. The three-dimensional structural model of human plasminogen based on known and overlapping 3-D structures of plasminogen fragments exhibits a spiral shape
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
proteolytic modification
-
activation through cleavage by urokinase-type plasminogen activator is stimulated by the bacterial protease m3/6 from Pseudomonas fluorescens
glycoprotein
P00747
the human plasminogen is partially N-glycosylated at Asn289 and O-glycosylated at Ser249 and Thr346 giving rise to plasminogen variants I (Asn289, Thr346) and II (only Thr346)
phosphoprotein
P00747
plasminogen is partially phosphorylated at Ser578
proteolytic modification
-
activation of plasminogen by cleavage of a sensitive Arg-Val peptide bond in the COOH-terminal portion of Glu-plasminogen to give the two-chain plasmin molecule, followed by the cleavage of a Lys-Lys peptide bond in the NH2-terminal portion of the molecule. The latter event results in the release of a peptide, or peptides
proteolytic modification
-
mechanism of activation by urokinase, streptokinase, trypsin and pig heart activator is specific and proceeds primarily through the cleavage of a single Arg-Val bond
proteolytic modification
-
zymogen: plasminogen
proteolytic modification
-
during activation of plasminogen, a peptide of 8200 Da is released from the plasminogen amino terminus
proteolytic modification
-
cleavage of plasminogen to active plasmin by urokinase-type plasminogen activator, complex dynamics and mathematical modeling, overview
proteolytic modification
-
Glu-plasminogen is cleaved to plasmin for activation by thrombin, as well as by constitutively expressed tPA, i.e. tissue-type plasminogen activator, or uPA, i.e. urokinase-type plasminogen activator
proteolytic modification
P00747
the main physiological activators of plasminogen are tissue-type plasminogen activator, which is mainly involved in the dissolution of the fibrin polymers by plasmin, and urokinase-type plasminogen activator, which is primarily responsible for the generation of plasmin activity in the intercellular space. Both activators are multidomain serine proteases. Pgn is activated by the two main physiological plasminogen activators to the active, two-chain plasmin molecule held together by two interchain disulfide bridges, Cys548-Cys666, Cys558-Cys566, by cleavage of the Arg561-Val562 peptide bond and the release of the 77-residue N-terminal peptide. Two N-terminally different forms of plasminogen exist, Glu-Pgn and Lys-Pgn. Lys-Pgn is formed by cleavage of the Lys77-Lys78 peptide bond in Glu-Pgn, releasing the N-terminal peptide
proteolytic modification
-
urokinase-type plasminogen activator cleaves plasminogen to give active plasmin
side-chain modification
-
glycoprotein
side-chain modification
-
the enzyme contains less than 2% carbohydrate
proteolytic modification
-
urokinase-type plasminogen activator cleaves plasminogen to give active plasmin
proteolytic modification
Mus musculus C57BL/6
-
urokinase-type plasminogen activator cleaves plasminogen to give active plasmin
-
proteolytic modification
-
zymogen: plasminogen
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
crystal structure of plasmin complexed with streptokinase
-
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
4
-
very stable below
95552
7
-
unstable in absence of glycerol
95552
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
56
-
rapid destruction or inactivation
95553
65
-
denaturation above 65C, thermal stability of plasmin in milk is very much dependent upon its interaction with beta-lactoglobulin
669641
90
-
stable for 108 min in acid whey and 0.02 min in sweet whey
668955
95
-
pasteurization of whey protein-free retentate of micro- and difiltrated milk at 95C for 15 s does not significantly affect plasmin or plasminogen-derived activities. The retentate contains increased plasmin activity, proportional to the concentration of beta-lactoglobulin
717666
additional information
-
the increased activity of plasmin after heat treatment may be also due to inactivation of enzyme inhibitor proteins
717666
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
freezing and thawing results in loss of activity
-
plasmin-staphylokinase complex is more stable than plasmin(ogen)-streptokinase complex
-
reduction with 2-mercaptoethanol in 8 M urea at pH 9.0, complete loss of activity by cleavage of a single disulfide bond
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-20C to -30C, pH 9.0, Tris-Lys-NaCl-EDTA buffer containing 25% glycerol, stable
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
affinity chromatography
-
enzyme form F-1 and enzyme form F-2
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expression in Escherichia coli
-
mutant enzyme P611I expressed in recombinant baculovirus-infected Spodoptera frugiperda cells
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
-
active-site modified plasmin (Ah-plasmin) lacking enzymatic activity. Factor VIII binds with higher affinity than the A2 subunit to Ah-plasmin. The intact heavy chain also binds with ca. 10fold higher affinity than the light chain. Binding affinity of the R484A mutant of A2 subunit of factor VIII to Ah-plasmin is ca. 250fold lower than that of wild-type A2. A2 mutants (K377A, K466A, and R471A) also exhibit reduced binding affinity (by 10-20fold) compared with wild-type A2
additional information
-
construction of a deletion mutant of plasminogen lacking the middle portion of the molecule, resulting in kringle I attachment to the serine protease domain. After expression in Escherichia coli and purification, mutant plasminogen is effectively converted to mutant plasmin by tissue plasminogen activator. Mutant plasmin is rapidly inhibited by alpha2-antiplasmin an alpha2-macroglobulin. It demonstrates fibrinolytic potency comparable to human plasma-derived plasmin
P611I
-
mutant enzyme has no amidolytic activity with D-Val-Leu-Lys-p-nitroanilide
additional information
-
in L5178Y cells with knock-out of the gene for annexin A2, the mRNA level of plasminogen is not substantially changed, but the protein level of plasmin is significantly lowered. mRNA and protein levels of S100A10 and fascin are lower in annexin A2 knock-out cells than in wild-type L5178Y cells
additional information
-
mice homozygotically lacking the plasminogen inhibitor Pai-1 or the plasmin inhibitor alpha2-antiplasmin show an increase in hematopoietic progenitor cell mobilization in response to granulocyte colony-stimulating factor
additional information
synthetic construct
-
truncated plasmin variants. Miniplasmin (des-kringle 1-4 plasmin) contains the kringle 5 and the catalytic domain of plasmin, whereas microplasmin (des-kringle 1-5 plasmin) is composed of the catalytic domain only. Miniplasmin (des-kringle 1-4 plasmin) is as sensitive to fatty acids as plasmin, whereas the activity of microplasmin (des-kringle 1-5 plasmin) is not affected
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
agriculture
-
effect of plasmin on in vitro embryo production. Plasmin added to the 18 h in vitro maturation medium increases the maturation rate of embryos without affecting fertilization or embryo development rates
food industry
-
milk retentate with increased plasmin activity is an interesting starting material for cheese-making. Increased plasmin activity increases cheese flavour and decreases ripening time
nutrition
-
hydrolysis of milk proteins alphaS-casein, beta-casein, kappa-casein, alpha-lactalbumin, beta-lactoglobulin, and lactoferrin is highly dependent on photooxidation state of substrate. Changes in the formation of potential angiotensin I-converting enzyme-inhibitory peptides as well as peptides proposed to have anti-bactericidal activities are observed after oxidation of substrates before plasmin hydrolysis
analysis
-
electrochemical assay of plasmin activity based on a ferrocenyl peptide substrate having a plasmin-specific substrate sequence, Lys-thr-Phe-Lys, and immobilized on a gold electrode. Detection limit for plasmin is around 50 ng/ml or 0.15 mU/ml. Ratio of kcat/Km values is 0.063 microM/s
degradation
-
cleavage at Arg336 is a central mechanism of plasmin-catalyzed factor VIII inactivation. Cleavages at Arg336 and Lys36 are selectively regulated by the A2 and A3-C1-C2 domains, respectively, interacting with plasmin
medicine
-
a reversibly acylated plasmin-staphylokinase complex might be protected from rapid irreversible inhibition by alpha2-antiplasmin in plasma, exhibits a prolonged plasma half-life and has altered pharmacodynamic properties
medicine
-
binding of inactive plasmin to annexin A2 inhibits plasmin induction of matrix metalloproteinase-1. Inactive plasmin may be useful in suppressing inflammatory diseases that involve a series of proteases (e.g., matrix metalloproteinases)
medicine
-
blocking plasmin prevents the generation of active platelet-derived growth factor-C, which is the major platelet-derived growth factor isoform relevant for proliferative vitreoretinopathy. Thus, plasmin is a therapeutic target for patients with proliferative vitreoretinopathy
medicine
-
less efficient proteolytic processing of the Pro370Leu protein by plasmin, coupled with the strong association of this variant with ethnicity, contributes to the differential prevalence of cardiovascular disease across ethnic groups
medicine
-
plasmin activates transforming growth factor beta 2, which has a potential protective role in breast cancer by its inhibitory effect on epithelial cell growth
medicine
-
plasmin can impair hemostasis by partially degrading fibrinogen to fragment X, a product that retains clottability but forms clots with reduced tensile strength that stimulate plasminogen activation by tissue-type plasminogen activator more than fibrin clots. Attenuation of thrombolytic therapy-induced fragment X formation may reduce the risk of bleeding
medicine
-
plasmin generated in atherosclerotic lesion can induce macrophage activation
medicine
-
plasmin generation system plays an important role in tissue repair/remodeling
medicine
-
processing of pro-brain-derived neurotrophic factor by plasmin stimulates neurite outgrowth on TrkB-transfected PC-12 cells to a similar extent than mature wild-type brain-derived neurotrophic factor
medicine
-
the plasminogen/plasmin system decreases Bim(EL) expression and activation of caspase-3 via the ERK1/2 signaling pathway during liver regeneration, resulting in an enhancement of cell survival. Plasmin protects against starvation-induced apoptosis in primary hepatocytes of mice
medicine
-
11% of patients with systemic reactions to Hymenoptera stings display increased serum baseline plasmin level and 70% of these have a history of anaphylaxis. Indication of bone marrow examination for the diagnosis of clonal mast cell disease
medicine
-
16% of patients with a history of systemic reaction to Hymenoptera and Diptera venom show an elevated level of plasmin. These patients report fewer usual skin reactions, more flushing and frequently do not present skin reaction. Mastocytosis was diagnosed in 33% of patients with elevated plasmin level
medicine
-
application of human plasminogen to plasminogen-deficient mice with bacterially induced arthritis. Plasmin protects against Staphylococcus aureus-induced arthritis by activating inflammatory cells, killing bacteria, removing necrotic tissue, and enhancing cytokine expression
medicine
-
comparison of serum plasmin levels and scoring mastocytosis index reveals a positive correlation. Use of scoring mastocytosis index as a tool for evaluating the severity of cutaneous mastocytosis
medicine
-
in presence of plasmin on the bacterial surface, Streptococcus pneumoniae transmigration across epithelial A549 and endothelial EaHy layer increases
medicine
-
antifibrinolytic inhibitors, e.g. aprotinin, of the serine protease plasmin are commonly used to reduce bleeding during surgery
pharmacology
-
construction of a deletion mutant of plasminogen lacking the middle portion of the molecule, resulting in kringle I attachment to the serine protease domain. After expression in Escherichia coli and purification, mutant plasminogen is effectively converted to mutant plasmin by tissue plasminogen activator. Mutant plasmin is rapidly inhibited by alpha2-antiplasmin an alpha2-macroglobulin. It demonstrates fibrinolytic potency comparable to human plasma-derived plasmin and is a potentially safe and effective direct thrombolytic agent
pharmacology
-
development of human plasmin product that is rendered inactive by low pH value of 3.0-4.0 until it is delivered directly to the neutral environment of a thrombus by catheter-assisted administration. The product is extremely pure and has a shelf-life of three years at ambient temperature
medicine
-
role in the course of tissue repair. Plasmin directly influences ERK-mediated signaling leading to epithelial to mesenchymal transition
medicine
-
a mutant, noninhibitory plasminogen activator inhibitor-type 1 reduces pathological ECM accumulation in anti-thy-1 nephritis, in large part through effectively competing with native plasminogen activator inhibitor-type 1, thereby restoring plasmin generation and increasing plasmin-dependent degradation of matrix components
medicine
-
induction of asthma by ovalbumin results in thickening of the airway wall, hypertrophy of smooth muscle cells, infiltration of inflammatory cells, subepithelial fibrosis, epithelial and endothelial lesions. Tissue plasminogen activator activity is significantly decreased in asthmatic animals, and activity of plasmin inhibitor PAI-1 is significantly higher as is alpha2-antiplasmin, consistent with the superiority of plasmin system inhibition over activation in plasma
pharmacology
-
intravitreous injection of plasmin induces partial posterior vitreous detachment in diabetic rats. Combinantion of hyaluronidase and plasmin can induce complete posterior vitreous detachment. It ismore difficult to induce posterior vitreous detachment in diabetic rats than in healthy rats. No obvious toxic reaction was observed in each group
medicine
-
plasmin induces an endothelium-dependent NO-mediated vasorelaxation in the porcine coronary artery, whereas it inhibits the endothelium-dependent relaxation induced by thrombin
medicine
synthetic construct
-
exerts proinflammatory functions. Direct activation of RAW264.7 cell monocytes by plasmin