PAI-1

Plasminogen activator inhibitor 1, also known as PAI-1, Endothelial plasminogen activator inhibitor, SerpinE1 and PLANH1, is a secreted glycoprotein which belongs to the serpin family. SerpinE1 is the primary physiological inhibitor of the two plasminogen activators urokinase (uPA) and tissue plasminogen activator (tPA). Its rapid interaction with TPA may function as a major control point in the regulation of fibrinolysis. Defects in SerpinE1 are the cause of plasminogen activator inhibitor-1 deficiency (PAI-1 deficiency) which is characterized by abnormal bleeding due to SerpinE1 defect in the plasma. High concentrations of SerpinE1 have been associated with thrombophilia which is an autosomal dominant disorder in which affected individuals are prone to develop serious spontaneous thrombosis. Studies of PAI-1 have contributed significantly to the elucidation of the protease inhibitory mechanism of serpins, which is based on a metastable native state becoming stabilised by insertion of the RCL into the central beta-sheet A and formation of covalent complexes with target proteases. Greater expression of PAI-1 has been associated with increased survival of cells and resistance to apoptosis. PAI-1 appears to influence apoptosis by decreasing cell adhesion (anoikis) as well as its effect on intracellular signaling. PAI-1, in its active state, also binds to the extracellular protein vitronectin. When in complex with its target proteases, it binds with high affinity to endocytosis receptors of the low density receptor family. The mechanisms of PAI-1 overexpression during obesity are complex, and it is conceivable that several inducers are involved at the same time at several sites of synthesis. PAI-1 is also implicated in adipose tissue development and in the control of insulin signaling in adipocytes. It suggests that PAI-1 inhibitors serve in the control of atherothrombosis and insulin resistance.

PAI-1 Related Areas

Cancer>>Cancer Biomarkers>>PAI-1/SerpinE1

Enzyme>>Protease & Regulator>>Serine Protease & Regulator>>Serpin Superfamily>>PAI-1/SerpinE1

Immunology>>Innate Immunity>>Coagulation>>PAI-1/SerpinE1

Cardiovascular>>Coagulation>>PAI-1/SerpinE1

PAI-1 Alternative Names

PAI-1, SERPINE1, PAI1, PAI, PLANH1, serpin E1 [Homo sapiens]

PAI-1, Serpine1, PAI1, PAI, Planh1 serpin E1 [Mus musculus]

Summaries for PAI-1

Entrez Gene summary for PAI-1:

SERPINE1 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 SERPINE1 gene are the cause of plasminogen activator inhibitor-1 deficiency (PAI-1 deficiency), and high concentrations of the SERPINE1 gene product are associated with thrombophilia. Alternatively spliced transcript variants encoding different isoforms have been found for SERPINE1 gene. [provided by RefSeq, Sep 2009]

OMIM - description for PAI-1:

The PAI-1 gene encodes endothelial plasminogen activator inhibitor-1 (PAI1), a member of the serine protease inhibitor family that inhibits tissue-type plasminogen activator PLAT and urokinase-type plasminogen activator PLAU. PLAT and PLAU proteolytically activate plasminogen PLG into plasmin, which breaks down fibrin clots. Thus, PAI-1 negatively regulates fibrinolysis and impairs the dissolution of clots (Ginsburg et al., 1986; Mehta and Shapiro, 2008).

Wikipedia summary for PAI-1:

Plasminogen activator inhibitor-1 (PAI-1) also known as endothelial plasminogen activator inhibitor or serpin E1 is a protein that in humans is encoded by the SERPINE1 gene.

PAI-1 is a serine protease inhibitor (serpin) that functions as the principal inhibitor of tissue plasminogen activator (tPA) and urokinase (uPA), the activators of plasminogen and hence fibrinolysis (the physiological breakdown of blood clots). It is a serine protease inhibitor (serpin) protein (SERPINE1).

The other PAI, plasminogen activator inhibitor-2 (PAI-2) is secreted by the placenta and only present in significant amounts during pregnancy. In addition, protease nexin acts as an inhibitor of tPA and urokinase. PAI-1, however, is the main inhibitor of the plasminogen activators.

Human PAI-1 Protein General Information

 

• Protein names: Plasminogen activator inhibitor 1, Short name=PAI ,Short name=PAI-1
• Sequence length: 402 AA.
• Domain: Signal
• Sequence similarities: Belongs to the serpin family.
• 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.
• Subunit structure: Forms protease inhibiting heterodimer with TMPRSS7. Interacts with VTN. Binds LRP1B; binding is followed by internalization and degradation.
• Subcellular location: Secreted.
• Tissue specificity: Found in plasma and platelets and in endothelial, hepatoma and fibrosarcoma cells.
• Involvement in disease: Defects in SERPINE1 are the cause of plasminogen activator inhibitor-1 deficiency (PAI-1D) [MIM:613329]. It is 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=High concentrations of SERPINE1 seem to contribute to the development of venous but not arterial occlusions.

General information above from UniProt

Function for PAI-1 Protein

UniProtKB:

Serine protease inhibitor. This inhibitor acts as 'bait' for tissue plasminogen activator, urokinase, protein C and matriptase-3/TMPRSS7. PAI-1's rapid interaction with PLAT may function as a major control point in the regulation of fibrinolysis.

Genatlas:

• PAI-1 inhibites extracellular matrix degradation by PLAU
• PAI-1 putative upregulated c-Myc target gene
• PAI-1 plays a key role in control of coagulation and tissue remodeling
• PAI-1 plays a role in regulation of angiogenesis

Homology for human PAI-1

• homolog to rattus Serpine1 (80.85 pc)
• homolog to murine Serpine1 (78.61 pc)

Phenotype Information for PAI-1

• Gene/Locus: PAI1, PLANH1, SERPINE1
• Phenotype: Plasminogen activator inhibitor-1 deficiency
  {Transcription of plasminogen activator inhibitor, modulator of}

Phenotype Information for PAI-1 from OMIM (Online Mendelian Inheritance in Man)