PLAU

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]

Full Name

plasminogen activator, urokinase

Function

Specifically cleaves the zymogen plasminogen to form the active enzyme plasmin.

Biological Process

Blood coagulationIEA:UniProtKB-KW
ChemotaxisManual Assertion Based On ExperimentTAS:ProtInc
FibrinolysisManual Assertion Based On ExperimentIBA:GO_Central
Negative regulation of fibrinolysis1 PublicationIC:ComplexPortal
Negative regulation of plasminogen activation1 PublicationIC:ComplexPortal
Plasminogen activationManual Assertion Based On ExperimentIDA:AgBase
Positive regulation of cell migrationManual Assertion Based On ExperimentIDA:MGI
ProteolysisManual Assertion Based On ExperimentIBA:GO_Central
Regulation of cell adhesionManual Assertion Based On ExperimentIDA:ComplexPortal
Regulation of cell adhesion mediated by integrinManual Assertion Based On ExperimentIDA:BHF-UCL
Regulation of cell population proliferationIEA:Ensembl
Regulation of fibrinolysis1 PublicationIC:ComplexPortal
Regulation of plasminogen activation1 PublicationIC:ComplexPortal
Regulation of signaling receptor activityManual Assertion Based On ExperimentIDA:BHF-UCL
Regulation of smooth muscle cell migrationManual Assertion Based On ExperimentIDA:BHF-UCL
Regulation of smooth muscle cell-matrix adhesionManual Assertion Based On ExperimentIDA:BHF-UCL
Regulation of wound healing1 PublicationIC:BHF-UCL
Response to hypoxiaIEA:Ensembl
Signal transductionManual Assertion Based On ExperimentTAS:ProtInc
Smooth muscle cell migrationIEA:Ensembl
Urokinase plasminogen activator signaling pathway1 PublicationIC:ComplexPortal

Cellular Location

Secreted

Involvement in disease

Quebec platelet disorder (QPD):
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.

PTM

Phosphorylation of Ser-158 and Ser-323 abolishes proadhesive ability but does not interfere with receptor binding.
Produced as an inactive single-chain protein (pro-uPA or sc-uPA), is processed into the active disulfide-linked two-chain form of PLAU/uPA by a proteolytic event mediated, at least, by TMPRSS4.

Anti-PLAU antibodies

Fig.3 Signaling pathways in cancers. (Creative Biolabs Authorized)