Recombinant Human Tissue-type plasminogen activator (PLAT), partial

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. During oocyte activation, plays a role in cortical granule reaction in the zona reaction, which contributes to the block to polyspermy (By similarity)

Subcellular Location

Secreted, extracellular space

Disease Association

[Increased activity of TPA results in increased fibrinolysis of fibrin blood clots that is associated with excessive bleeding. Defective release of TPA results in hypofibrinolysis that can lead to thrombosis or embolism]

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

Subunit

Heterodimer of chain A and chain B held by a disulfide bond. Forms a heterodimer with SERPINA5. 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. Interacts with SERPINE1 (PubMed:21925150). In complex with SERPINE1, interacts with SORL1 (PubMed:15053742). Interacts with apyrase from Anopheles gambiae saliva; the interaction results in PLAT activation probably via an allosteric activation mechanism (PubMed:39294191)

• Pennica D. et al. Cloning and expression of human tissue-type plasminogen activator cDNA in E. coli. — Nature (1983)
• Ny T. et al. The structure of the human tissue-type plasminogen activator gene: correlation of intron and exon structures to functional and structural domains. — Proc. Natl. Acad. Sci. U.S.A. (1984)
• Friezner Degen S.J. et al. The human tissue plasminogen activator gene. — J. Biol. Chem. (1986)
• Harris T.J. et al. Cloning of cDNA coding for human tissue-type plasminogen activator and its expression in Escherichia coli. — Mol. Biol. Med. (1986)
• Reddy V.B. et al. Expression of human uterine tissue-type plasminogen activator in mouse cells using BPV vectors. — DNA (1987)
• Sasaki H. et al. Nucleotide sequence of the tissue-type plasminogen activator cDNA from human fetal lung cells. — Nucleic Acids Res. (1988)
• Siebert P.D. et al. Variant tissue-type plasminogen activator (PLAT) cDNA obtained from human endothelial cells. — Nucleic Acids Res. (1990)
• Dou D. et al. A brain-type plasminogen activator. (APR-)