SERPINA5 binds activated protein C

Stable Identifier
R-HSA-5591086
Type
Reaction [binding]
Species
Homo sapiens
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SERPINA5, also called Plasma serine protease inhibitor or Protein C inhibitor, inactivates serine proteases by binding irreversibly to their serine activation site. It is involved in the regulation of intravascular and extravascular proteolytic activities, promoting coagulation by inhibiting the anticoagulant complex Activated protein C (APC), but also acts as an anticoagulant factor by inhibiting blood coagulation factors such as prothrombin, factor XI, factor Xa, plasma kallikrein and fibrinolytic enzymes such as tissue- and urinary-type plasminogen activators. Its inhibitory activity is greatly enhanced in the presence of glycosaminoglycans (GAGs), heparin, thrombomodulin and phospholipids vesicles (Suzuki et al. 1985).

SERPINA5 inhibits activated protein C In the blood plasma and inhibits thromibin as part of the thrombin:thrombomodulin complex (Rezaie et al. 1995). On the other hand, PCI can also inhibit coagulation factors (Radtke et al. 2007). The SERPINA5:APC complex is a marker of thrombotic events (Kolbel et al. 2006), which suggests that despite low circulating SERPINA5 concentrations and rates of APC inhibition, its predominant role is procoagulatory (Li & Huntington 2008). This is due to the enhancing effect of GAGs, which line the vascular endothelium. Both SERPINA5 and APC bind to GAGs. The presence of heparin in vitro accelerates the maximal rate of inhibition by over 2000-fold (when accounting for dissociation constants) (Yang et al. 2002).

Literature References
PubMed ID Title Journal Year
6323392 Mechanism of inhibition of activated protein C by protein C inhibitor

Suzuki, K, Nishioka, J, Kusumoto, H, Hashimoto, S

J. Biochem. 1984
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