SERPINE1

Function

Serine protease inhibitor. Inhibits TMPRSS7 (PubMed:15853774). Is a primary inhibitor of tissue-type plasminogen activator (PLAT) and urokinase-type plasminogen activator (PLAU). As PLAT inhibitor, it is required for fibrinolysis down-regulation and is responsible for the controlled degradation of blood clots (PubMed:8481516, PubMed:9207454, PubMed:17912461). As PLAU inhibitor, it is involved in the regulation of cell adhesion and spreading (PubMed:9175705). Acts as a regulator of cell migration, independently of its role as protease inhibitor (PubMed:15001579, PubMed:9168821). It is required for stimulation of keratinocyte migration during cutaneous injury repair (PubMed:18386027). It is involved in cellular and replicative senescence (PubMed:16862142). Plays a role in alveolar type 2 cells senescence in the lung (By similarity). Is involved in the regulation of cementogenic differentiation of periodontal ligament stem cells, and regulates odontoblast differentiation and dentin formation during odontogenesis (PubMed:25808697, PubMed:27046084).

Involvement in disease

Plasminogen activator inhibitor-1 deficiency

PAI-1D

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.

None

The disease is caused by variants affecting the gene represented in this entry. A rare PAI-1D mutation resulting in a frameshift and protein truncation has been found in an Old Order Amish community. Homozygous mutation carriers suffer from episodes of major hemorrhage, while heterozygous carriers do not manifest abnormal bleeding (PubMed:9207454). Heterozygosity for the mutation is associated with longer leukocyte telomere length, lower fasting insulin levels, lower prevalence of diabetes mellitus, and a longer life span (PubMed:29152572).

Post-translational modifications

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

Sequence similarities

Belongs to the serpin family.

Tissue specificity

Expressed in endothelial cells (PubMed:2430793, PubMed:3097076). Found in plasma, platelets, and hepatoma and fibrosarcoma cells.

Cellular localization

• Secreted

Alternative names

• Plasminogen activator inhibitor 1
• PAI
• PAI-1
• Endothelial plasminogen activator inhibitor
• Serpin E1
• PLANH1
• PAI1
• SERPINE1

Database links

• entrezGene:5054
• entrezGene:5328
• omim:191840
• omim:173360
• swissprot:P05121
• swissprot:P00749

Target type

Proteins

Primary research area

Oncology

Other research areas

• Immunology & Infectious Disease

Molecular weight

45060Da