SERPINE1

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]

Serpin Family E Member 1

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).

Biological Process angiogenesisManual Assertion Based On ExperimentIEP:UniProtKB
Biological Process cellular response to lipopolysaccharideManual Assertion Based On ExperimentIMP:BHF-UCL
Biological Process defense response to Gram-negative bacteriumManual Assertion Based On ExperimentIGI:BHF-UCL
Biological Process dentinogenesisManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process fibrinolysisTAS:Reactome
Biological Process negative regulation of blood coagulation1 PublicationIC:BHF-UCL
Biological Process negative regulation of cell adhesion mediated by integrinManual Assertion Based On ExperimentIDA:BHF-UCL
Biological Process negative regulation of cell migrationManual Assertion Based On ExperimentIDA:BHF-UCL
Biological Process negative regulation of endopeptidase activityManual Assertion Based On ExperimentIDA:BHF-UCL
Biological Process negative regulation of endothelial cell apoptotic processManual Assertion Based On ExperimentIMP:BHF-UCL
Biological Process negative regulation of extrinsic apoptotic signaling pathway via death domain receptorsManual Assertion Based On ExperimentIMP:BHF-UCL
Biological Process negative regulation of fibrinolysisManual Assertion Based On ExperimentIDA:BHF-UCL
Biological Process negative regulation of plasminogen activationManual Assertion Based On ExperimentIDA:BHF-UCL
Biological Process negative regulation of smooth muscle cell migrationManual Assertion Based On ExperimentIDA:BHF-UCL
Biological Process negative regulation of smooth muscle cell-matrix adhesionManual Assertion Based On ExperimentIDA:BHF-UCL
Biological Process negative regulation of vascular wound healingManual Assertion Based On ExperimentIGI:BHF-UCL
Biological Process negative regulation of wound healing1 PublicationIC:BHF-UCL
Biological Process positive regulation of angiogenesisManual Assertion Based On ExperimentIMP:BHF-UCL
Biological Process positive regulation of blood coagulationManual Assertion Based On ExperimentIMP:BHF-UCL
Biological Process positive regulation of inflammatory responseManual Assertion Based On ExperimentIGI:BHF-UCL
Biological Process positive regulation of interleukin-8 productionManual Assertion Based On ExperimentIMP:BHF-UCL
Biological Process positive regulation of leukotriene production involved in inflammatory responseManual Assertion Based On ExperimentIMP:BHF-UCL
Biological Process positive regulation of monocyte chemotaxisManual Assertion Based On ExperimentIMP:BHF-UCL
Biological Process positive regulation of odontoblast differentiationManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process positive regulation of receptor-mediated endocytosisManual Assertion Based On ExperimentIDA:BHF-UCL
Biological Process regulation of signaling receptor activityManual Assertion Based On ExperimentIDA:BHF-UCL
Biological Process replicative senescenceManual Assertion Based On ExperimentIMP:UniProtKB

Secreted

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.

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