Tpa, Two Chain Recombinant (PLAT) Recombinant Protein

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.

Catalytic activity: Specific cleavage of Arg-|-Val bond in plasminogen to form plasmin.

Enzyme regulation: Inhibited by SERPINA5

By similarity.

Subunit structure: 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 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. Binds LRP1B; binding is followed by internalization and degradation. Forms heterodimer with SERPINA5

By similarity.

Subcellular location: Secreted › extracellular space.

Domain: Both FN1 and one of the kringle domains are required for binding to fibrin

By similarity.Both FN1 and EGF-like domains are important for binding to LRP1

By similarity.The FN1 domain mediates binding to annexin A2

By similarity.The second kringle domain is implicated in binding to cytokeratin-8 and to the endothelial cell surface binding site

By similarity.

Post-translational modification: The single chain, almost fully active enzyme, can be further processed into a two-chain fully active form by a cleavage after Arg-308 catalyzed by plasmin, tissue kallikrein or factor Xa.

Sequence similarities: Belongs to the peptidase S1 family.Contains 1 EGF-like domain.Contains 1 fibronectin type-I domain.Contains 2 kringle domains.Contains 1 peptidase S1 domain.