Catalytic activity:Specific cleavage of Arg-|-Val bond in plasminogen to form plasmin.,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.,Domain:Both FN1 and EGF-like domains are important for binding to LRP1.,Domain:Both FN1 and one of the kringle domains are required for binding to fibrin.,Domain:The FN1 domain mediates binding to annexin A2.,Domain:The second kringle domain is implicated in binding to cytokeratin-8 and to the endothelial cell surface binding site.,Function:Converts the abundant, but inactive, zymogen plasminogen to plasmin by hydrolyzing a single Arg-Val bond in plasminogen. By controlling plasmin-mediated proteolysis, it plays an important role in tissue remodeling and degradation, in cell migration and many other physiopathological events. Play a direct role in facilitating neuronal migration.,online information:Clinical information on Activase,online information:Clinical information on Retavase,online information:The Singapore human mutation and polymorphism database,online information:Tissue plasminogen activator entry,pharmaceutical:Available under the names Activase (Genentech) and Retavase (Centocor and Roche) [Retavase is a fragment of TPA that contains kringle 2 and the protease domain; it was also known as BM 06.022]. Used in Acute Myocardial Infarction (AMI), in Acute Ischemic Stroke (AIS) and Pulmonary Embolism (PE) to initiate fibrinolysis.,PTM:Characterization of O-linked glycan was studied in Bowes melanoma cell line.,PTM:Differential cell-specific N-linked glycosylation gives rise to two glycoforms, type I (glycosylated at Asn-219) and type II (not glycosylated at Asn-219). The single chain type I glycoform is less readily converted into the two-chain form by plasmin, and the two-chain type I glycoform has a lower activity than the two-chain type II glycoform in the presence of fibrin.,PTM:N-glycosylation of Asn-152; the bound oligomannosidic glycan is involved in the interaction with the mannose receptor.,PTM:The single chain, almost fully active enzyme, can be further processed into a two-chain fully active form by a cleavage after Arg-310 catalyzed by plasmin, tissue kallikrein or factor Xa.,similarity:Belongs to the peptidase S1 family.,similarity:Contains 1 EGF-like domain.,similarity:Contains 1 fibronectin type-I domain.,similarity:Contains 1 peptidase S1 domain.,similarity:Contains 2 kringle domains.,subunit:Heterodimer of chain A and chain B held by a disulfide bond. Binds to fibrin with high affinity. This interaction leads to an increase in the catalytic efficiency of the enzyme between 100-fold and 1000-fold, due to an increase in affinity for plasminogen. Similarly, binding to heparin increases the activation of plasminogen. Binds to annexin A2, cytokeratin-8, fibronectin and laminin. Binds to mannose receptor and the low-density lipoprotein receptor-related protein (LRP1); these proteins are involved in TPA clearance. Yet unidentified interactions on endothelial cells and vascular smooth muscle cells (VSMC) lead to a 100-fold stimulation of plasminogen activation. In addition, binding to VSMC reduces TPA inhibition by PAI-1 by 30-fold. Binds LRP1B; binding is followed by internalization and degradation.,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.,
show all