3bt1

Structural highlights

Disease

[UROK_HUMAN] Defects in PLAU are the cause of Quebec platelet disorder (QPD) [MIM:601709]. 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.^[1]

Function

[UROK_HUMAN] Specifically cleaves the zymogen plasminogen to form the active enzyme plasmin. [UPAR_HUMAN] Acts as a receptor for urokinase plasminogen activator. Plays a role in localizing and promoting plasmin formation. Mediates the proteolysis-independent signal transduction activation effects of U-PA. It is subject to negative-feedback regulation by U-PA which cleaves it into an inactive form. [VTNC_HUMAN] Vitronectin is a cell adhesion and spreading factor found in serum and tissues. Vitronectin interact with glycosaminoglycans and proteoglycans. Is recognized by certain members of the integrin family and serves as a cell-to-substrate adhesion molecule. Inhibitor of the membrane-damaging effect of the terminal cytolytic complement pathway. Somatomedin-B is a growth hormone-dependent serum factor with protease-inhibiting activity.

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

See Also

• Urokinase

References

1. ↑ Paterson AD, Rommens JM, Bharaj B, Blavignac J, Wong I, Diamandis M, Waye JS, Rivard GE, Hayward CP. Persons with Quebec platelet disorder have a tandem duplication of PLAU, the urokinase plasminogen activator gene. Blood. 2010 Feb 11;115(6):1264-6. doi: 10.1182/blood-2009-07-233965. Epub 2009, Dec 9. PMID:20007542 doi:10.1182/blood-2009-07-233965
2. ↑ Huai Q, Zhou A, Lin L, Mazar AP, Parry GC, Callahan J, Shaw DE, Furie B, Furie BC, Huang M. Crystal structures of two human vitronectin, urokinase and urokinase receptor complexes. Nat Struct Mol Biol. 2008 Apr;15(4):422-3. Epub 2008 Mar 23. PMID:18376415 doi:10.1038/nsmb.1404