PAI-1 Human Active Protein

This gene encodes a member of the serine proteinase inhibitor (serpin) superfamily. This member is the principal inhibitor of tissue plasminogen activator (tPA) and urokinase (uPA), and hence is an inhibitor of fibrinolysis. Defects in this gene are the cause of plasminogen activator inhibitor-1 deficiency (PAI-1 deficiency), and high concentrations of the gene product are associated with thrombophilia. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]

Function: Serine protease inhibitor. This inhibitor acts as 'bait' for tissue plasminogen activator, urokinase, protein C and matriptase-3/TMPRSS7. Its rapid interaction with PLAT may function as a major control point in the regulation of fibrinolysis. Ref.18

Subunit structure: Forms protease inhibiting heterodimer with TMPRSS7. Interacts with VTN. Binds LRP1B; binding is followed by internalization and degradation. Ref.15 Ref.17

Subcellular location: Secreted.

Tissue specificity: Found in plasma and platelets and in endothelial, hepatoma and fibrosarcoma cells.

Post-translational modification: Inactivated by proteolytic attack of the urokinase-type (u-PA) and the tissue-type (TPA), cleaving the 369-Arg-|-Met-370 bond.

Involvement in disease: Plasminogen activator inhibitor-1 deficiency (PAI-1D) [MIM:613329]: A hematologic disorder characterized by increased bleeding after trauma, injury, or surgery. Affected females have menorrhagia. The bleeding defect is due to increased fibrinolysis of fibrin blood clots due to deficiency of plasminogen activator inhibitor-1, which inhibits tissue and urinary activators of plasminogen.Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.16High concentrations of SERPINE1 seem to contribute to the development of venous but not arterial occlusions.

Sequence similarities: Belongs to the serpin family.