Center for Bioinformatics
Oxidoreductases | Transferases | Hydrolases | Lyases | Isomerases | Ligases

Basic Information

Enzyme Number

3.4.21.68

Official Name

t-plasminogen activator

Name from literature

tissue type plasminogen activator

Pathway from literature

the fibrinolytic cascade

Pathway from KEGG

Cellular Processes; Immune System; Complement and coagulation cascades; map04610

Organisms

Human (9606)

Genome localization

8p12[5327 ],

Comments

A peptidase of family S1 (trypsin family) from a wide variety of mammalian tissues, especially endothelial cells. Secreted as a single chain precursor which is cleaved to a two-chain form by plasmin. Activity is considerably enhanced by fibrin. Formerly included in EC 3.4.21.31 and EC 3.4.99.26

Rate-limiting Description

"Fibrinolysis was assessed through measurement of the activities of the rate limiting fibrinolytic activator, tissue plasminogen activator, and its inhibitor plasminogen activator inhibitor-1 with amidolytic methods." (10957661)

"For example, tissue type plasminogen activator (t-PA), a trypsin-like enzyme that catalyzes the rate-limiting step of the endogenous fibrinolytic cascade, has only one known substrate in vivo, a single peptide bond (Arg561-Val562) in the proenzyme plasminogen." (8999865)

"The data are consistent with a mechanism for glycosylasparaginase involving rapid formation of a tetrahedral structure upon substrate binding, and a rate-limiting breakdown of the tetrahedral structure to a covalent beta-aspartyl-enzyme intermediate that is dependent on the electronic properties of the substituent group and on the degree of protonation of the leaving group in the transition state by a general acid." (12945771)

"Tissue-type plasminogen activator (t-PA) is a plasma serine protease that catalyzes the initial and rate-limiting step in the fibrinolytic cascade." (8349826)

Regulatory Information

Upstream transcription factor

3146;4790

Regulatory type

Detail

key enzyme;

"Tissue-type plasminogen activator (tPA) is a key enzyme in the fibrinolysis system and the regulation of its expression has been extensively studied in cultured vascular endothelial cells." (11883720)

phosphorylation;PKC

"upregulation of PAI-1, uPA, and tPA after long-term LDL exposure seems to be mediated by a delayed PKC activation associated with an increased PA inhibitory activity" (12167592)

phosphorylation;"PKC,MAPK"

"In thyroid cells, plasminogen activators are regulated via MAPK and protein kinase c-beta pathways." (17458906)

transcriptional factor;NFkappaB(4790)

"IL-1beta stimulates uPA but not tPA production via activation of NFkappaB and tyrosine phosphorylation, and also secretion of the enzyme, and that the uPA/plasmin system appears to be involved in inflammation in human dental pulp." (18202522)

transcriptional factor;HMGB1(3146)

"Interactions of plasminogen and tissue plasminogen activator (t-PA) with amphoterin. Enhancement of t-PA-catalyzed plasminogen activation by amphoterin." (1909331#8366113)

transcriptional factor;HMGB1(3146)

"Interactions of plasminogen and tissue plasminogen activator (t-PA) with amphoterin. Enhancement of t-PA-catalyzed plasminogen activation by amphoterin." (1909331#8366113#16189514)

Gene ontology

Gene ontology

GO:0006508 (P) proteolysis [P00750 ];
GO:0006464 (P) protein modification process [P00750 ];
GO:0005856 (C) cytoskeleton [P00750 ];
GO:0007596 (P) blood coagulation [P00750 ];
GO:0004252 (F) serine-type endopeptidase activity [P00750 ];

Tissue expression

Tissue From HPRD

Vascular endothelial cell [01419 ];
Uterus [01419 ];
Umbilical vein endothelial cell [01419 ];
Fetus [01419 ];

Tissue specificity

Synthesized in numerous tissues (including tumors) and secreted into most extracellular body fluids, such as plasma, uterine fluid, saliva, gingival crevicular fluid, tears, seminal fluid, and milk [P00750 ];

Subcellular localization

Localization

extracellular [P00750 ];

Disease relevance

Disease

Increased activity of TPA is the cause of hyperfibrinolysis [MIM:173370]. Hyperfibrinolysis leads to excessive bleeding. Defective release of TPA causes hypofibrinolysis, leading to thrombosis or embolism [P00750 ];

Links

SwissProt

P00750

Entrez Gene

5327

HPRD

01419



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  Last Modified: 2009-03-24  
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