Tissue Plasminogen Activator Substrate (PLAT) Protein

This gene encodes tissue-type plasminogen activator, a secreted serine protease which converts the proenzyme plasminogen to plasmin, a fibrinolytic enzyme. Tissue-type plasminogen activator is synthesized as a single chain which is cleaved by plasmin to a two chain disulfide linked protein. This enzyme plays a role in cell migration and tissue remodeling. Increased enzymatic activity causes hyperfibrinolysis, which manifests as excessive bleeding; decreased activity leads to hypofibrinolysis which can result in thrombosis or embolism. Alternative splicing of this gene results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

PLAT: 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. Plays a direct role in facilitating neuronal migration. 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. Belongs to the peptidase S1 family. 4 isoforms of the human protein are produced by alternative splicing.

Protein type: Protease; Cytoskeletal; Secreted; EC 3.4.21.68; Motility/polarity/chemotaxis; Secreted, signal peptide; Vesicle

Chromosomal Location of Human Ortholog: 8p12

Cellular Component: extracellular matrix; extracellular space; cell surface; apical part of cell; cytoplasm; extracellular region; synapse; secretory granule

Molecular Function: protein binding; serine-type endopeptidase activity

Biological Process: negative regulation of proteolysis; response to peptide hormone stimulus; synaptic transmission, glutamatergic; response to cAMP; smooth muscle cell migration; protein modification process; regulation of synaptic plasticity; platelet-derived growth factor receptor signaling pathway; proteolysis; fibrinolysis; response to hypoxia; blood coagulation; transmembrane transport; plasminogen activation

Disease: Thrombophilia, Familial, Due To Decreased Release Of Tissue Plasminogen Activator