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PLAT

This gene encodes tissue-type plasminogen activator, a secreted serine protease that converts the proenzyme plasminogen to plasmin, a fibrinolytic enzyme. The encoded preproprotein is proteolytically processed by plasmin or trypsin to generate heavy and light chains. These chains associate via disulfide linkages to form the heterodimeric enzyme. This enzyme plays a role in cell migration and tissue remodeling. Increased enzymatic activity causes hyperfibrinolysis, which manifests as excessive bleeding, while decreased activity leads to hypofibrinolysis, which can result in thrombosis or embolism. Alternative splicing of this gene results in multiple transcript variants, at least one of which encodes an isoform that is proteolytically processed. [provided by RefSeq, Jan 2016]
Protein class

Cancer-related genes, Candidate cardiovascular disease genes, Disease related genes, Enzymes, FDA approved drug targets, Plasma proteins

Predicted location

Secreted

Single cell type specificity

Group enriched (Urothelial cells, Basal prostatic cells)

Immune cell specificity

Not detected in immune cells

Cell line specificity

Cell line enhanced (CAPAN-2, HMC-1, hTERT-RPE1, LHCN-M2, U-2197, WM-115)

Interaction

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. In complex with SERPINE1, interacts with SORL1 (PubMed:15053742).

Molecular function

Hydrolase, Protease, Serine protease

More Types Infomation
  • Reteplase (TP-048CL)

    • CAS number: 133652-38-7
  • Alteplase (TP-047CL)

    • CAS number: 105857-23-6

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