Protein C inhibitor (SERPINA5)

Protein C inhibitor (SERPINA5, PCI) is a glycoprotein and member of the serine protease inhibitor (serpin) superfamily that plays a central role in regulating blood coagulation and fibrinolysis[1][3][4]. It inhibits several serine proteases, notably protein C, thrombin, factor XI, factor Xa, plasminogen activators, and kallikreins, thereby modulating pathways governing hemostasis and thrombosis in multiple tissues[1][3][4]. PCI can act as both a procoagulant (inhibiting activated protein C) and an anticoagulant (inhibiting thrombin, factor Xa, and plasminogen activators), with activity enhanced by cofactors such as heparin[1][3][4]. It is produced mainly in the liver but also in kidneys and reproductive tissues, and is found in plasma, seminal fluid, and other body fluids[2][3]. Beyond hemostasis, SERPINA5 plays roles in the male reproductive tract (e.g., by inhibiting sperm acrosin and controlling sperm motility and fertilization), suppresses tumor invasion and migration by interacting with fibronectin and regulating fibronectin–integrin β1 signaling, and exhibits antimicrobial activity[2][3]. Altered expression or deficiency of PCI is implicated in thrombotic disease, cancer metastasis (notably in hepatocellular, prostate, breast, and renal cancers), and male infertility[2][3]. An N-terminal PCI fragment is a potential biomarker for prostate cancer[3]. Safety concerns are related to disturbances in hemostasis and potential impacts on fertility or tumor progression if SERPINA5 function is dysregulated. **Note:** There are no currently approved direct-targeting drugs for SERPINA5 in clinical therapeutics, but heparin can modulate its activity in vivo[3].

Other names

Protein C inhibitorSERPINA5PCIPLANH3PROCIPAI-3PAI3plasma serine protease inhibitoracrosomal serine protease inhibitorplasminogen activator inhibitor IIIplasminogen activator inhibitor-3serpin (or cysteine) proteinase inhibitor clade A member 5serpin peptidase inhibitor clade A member 5

Inhibition of serine proteases (e.g., protein C, thrombin, factor Xa, kallikreins), Heparin-mediated enhancement of inhibitor activity, Inhibition of fibrinolytic enzymes (e.g., plasminogen activators), Inhibition of tumor migration via disruption of fibronectin-integrin signaling