Plasminogen activator inhibitor 1

Function

Serine protease inhibitor. Inhibits TMPRSS7. 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. As PLAU inhibitor, it is involved in the regulation of cell adhesion and spreading. Acts as a regulator of cell migration, independently of its role as protease inhibitor. It is required for stimulation of keratinocyte migration during cutaneous injury repair. It is involved in cellular and replicative senescence. 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.

Classification

Family (Pfam)

PF00079 Serpin

InterPro

Serpin_CS, Serpin_dom, Serpin_fam, Serpin_sf, Serpin_sf_1, Serpin_sf_2

Functional cluster

Cytochrome P450 & Heme Enzymes

Experimental structures · PDB · 29

• 1A7C X-ray 1.95A
• 1B3K X-ray 2.99A
• 1C5G X-ray 2.60A
• 1DB2 X-ray 2.70A
• 1DVM X-ray 2.40A
• 1DVN X-ray 2.10A
• 1LJ5 X-ray 1.80A
• 1OC0 X-ray 2.28A
• 3CVM X-ray 2.02A
• 3EOX X-ray 2.61A
• 3PB1 X-ray 2.30A
• 3Q02 X-ray 2.30A
• … and 17 more

A predicted model is available from AlphaFold.

Gene Ontology · 39

• GO:0070062 extracellular exosome
• GO:0031012 extracellular matrix
• GO:0005576 extracellular region
• GO:0005615 extracellular space
• GO:0005886 plasma membrane
• GO:0031093 platelet alpha granule lumen
• GO:0004866 endopeptidase inhibitor activity
• GO:0002020 protease binding
• GO:0004867 serine-type endopeptidase inhibitor activity
• GO:0005102 signaling receptor binding
• GO:0001525 angiogenesis
• GO:0071222 cellular response to lipopolysaccharide
• GO:0050829 defense response to Gram-negative bacterium
• GO:0097187 dentinogenesis
• GO:0042730 fibrinolysis
• GO:0030195 negative regulation of blood coagulation
• GO:0033629 negative regulation of cell adhesion mediated by integrin
• GO:0030336 negative regulation of cell migration
• GO:2000352 negative regulation of endothelial cell apoptotic process
• GO:1902042 negative regulation of extrinsic apoptotic signaling pathway via death domain receptors
• GO:0051918 negative regulation of fibrinolysis
• GO:2001045 negative regulation of integrin-mediated signaling pathway
• GO:0010757 negative regulation of plasminogen activation
• GO:0045861 negative regulation of proteolysis
• GO:0014912 negative regulation of smooth muscle cell migration
• GO:2000098 negative regulation of smooth muscle cell-matrix adhesion
• GO:0070495 negative regulation of thrombin-activated receptor signaling pathway
• GO:0061044 negative regulation of vascular wound healing
• GO:0061045 negative regulation of wound healing
• GO:0045766 positive regulation of angiogenesis
• GO:0030194 positive regulation of blood coagulation
• GO:0050820 positive regulation of coagulation
• GO:0050729 positive regulation of inflammatory response
• GO:0032757 positive regulation of interleukin-8 production
• GO:0035491 positive regulation of leukotriene production involved in inflammatory response
• GO:0090026 positive regulation of monocyte chemotaxis
• GO:1901331 positive regulation of odontoblast differentiation
• GO:0048260 positive regulation of receptor-mediated endocytosis
• GO:0090399 replicative senescence

Disease associations

• congenital plasminogen activator inhibitor type 1 deficiency MONDO:0013227

Drugs targeting this protein · 1

• ALEPLASININ inhibitor

Related proteins · sequence + function similarity

• Plasminogen activator inhibitor 1 0.98
• Plasminogen activator inhibitor 1 0.98
• Plasminogen activator inhibitor 1 0.98
• Plasminogen activator inhibitor 1 0.97
• Plasminogen activator inhibitor 1 0.97
• Probable serpin E3 0.89
• Serpin I2 0.89
• Glia-derived nexin 0.89
• Heparin cofactor 2 0.88
• Heparin cofactor 2 0.88
• Glia-derived nexin 0.88
• Glia-derived nexin 0.88

Co-cited proteins · studied together in the literature

• Plasminogen activator inhibitor 1 1 shared papers
• Urokinase-type plasminogen activator 4 shared papers
• Vitronectin 1 shared papers
• Tissue-type plasminogen activator 3 shared papers
• Low-density lipoprotein receptor-related protein 1B 1 shared papers
• Longistatin 1 shared papers
• Serine/threonine-protein phosphatase PP1-beta catalytic subunit 1 shared papers
• Transmembrane protease serine 7 1 shared papers
• Transmembrane protease serine 7 1 shared papers
• Intercellular adhesion molecule 1 1 shared papers
• Alpha-2-macroglobulin receptor-associated protein 2 shared papers
• Coagulation factor X 1 shared papers

Literature · 38 cited papers

• A null mutation in SERPINE1 protects against biological aging in humans. Sci. Adv. · 2017
• PAI1: a novel PP1-interacting protein that mediates human plasma's anti-apoptotic effect in endothelial cells. J. Cell. Mol. Med. · 2017
• Recombinant human plasminogen activator inhibitor-1 accelerates odontoblastic differentiation of human stem cells from apical papilla. Tissue Eng. Part A · 2016
• Recombinant human plasminogen activator inhibitor-1 promotes cementogenic differentiation of human periodontal ligament stem cells. Tissue Eng. Part A · 2015
• Coagulation factor Xa induces an inflammatory signalling by activation of protease-activated receptors in human atrial tissue. Eur. J. Pharmacol. · 2013
• Resveratrol-induced changes of the human adipocyte secretion profile. J. Proteome Res. · 2012
• Longistatin, a novel plasminogen activator from vector ticks, is resistant to plasminogen activator inhibitor-1. Biochem. Biophys. Res. Commun. · 2011
• SERPINE1 (PAI-1) is deposited into keratinocyte migration 'trails' and required for optimal monolayer wound repair. Arch. Dermatol. Res. · 2008
• Highly stable plasminogen activator inhibitor type one (VLHL PAI-1) protects fibrin clots from tissue plasminogen activator-mediated fibrinolysis. Int. J. Mol. Med. · 2007
• Plasminogen activator inhibitor-1 is a critical downstream target of p53 in the induction of replicative senescence. Nat. Cell Biol. · 2006
• Matriptase-3 is a novel phylogenetically preserved membrane-anchored serine protease with broad serpin reactivity. Biochem. J. · 2005
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
• … and 26 more in the literature graph