Pro-Urokinase (PLAU) Active Protein

This gene encodes a serine protease involved in degradation of the extracellular matrix and possibly tumor cell migration and proliferation. A specific polymorphism in this gene may be associated with late-onset Alzheimer's disease and also with decreased affinity for fibrin-binding. This protein converts plasminogen to plasmin by specific cleavage of an Arg-Val bond in plasminogen. Plasmin in turn cleaves this protein at a Lys-Ile bond to form a two-chain derivative in which a single disulfide bond connects the amino-terminal A-chain to the catalytically active, carboxy-terminal B-chain. This two-chain derivative is also called HMW-uPA (high molecular weight uPA). HMW-uPA can be further processed into LMW-uPA (low molecular weight uPA) by cleavage of chain A into a short chain A (A1) and an amino-terminal fragment. LMW-uPA is proteolytically active but does not bind to the uPA receptor. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2009]

uPA: Specifically cleave the zymogen plasminogen to form the active enzyme plasmin. Defects in PLAU are the cause of Quebec platelet disorder (QPD). QPD is an autosomal dominant bleeding disorder due to a gain-of-function defect in fibrinolysis. Although affected individuals do not exhibit systemic fibrinolysis, they show delayed onset bleeding after challenge, such as surgery. The hallmark of the disorder is markedly increased PLAU levels within platelets, which causes intraplatelet plasmin generation and secondary degradation of alpha-granule proteins. Belongs to the peptidase S1 family. 2 isoforms of the human protein are produced by alternative splicing.

Protein type: Motility/polarity/chemotaxis; Secreted, signal peptide; EC 3.4.21.73; Protease; Secreted

Chromosomal Location of Human Ortholog: 10q22.2

Cellular Component: extracellular space; focal adhesion; cell surface; plasma membrane; extracellular region

Molecular Function: protein binding; serine-type endopeptidase activity

Biological Process: regulation of cell adhesion mediated by integrin; fibrinolysis; regulation of smooth muscle cell migration; smooth muscle cell migration; response to hypoxia; regulation of receptor activity; chemotaxis; signal transduction; proteolysis; blood coagulation; regulation of cell proliferation

Disease: Quebec Platelet Disorder; Alzheimer Disease