Plasma serine protease inhibitor

Definition:

Heparin-dependent serine protease inhibitor acting in body fluids and secretions. Inactivates serine proteases by binding irreversibly to their serine activation site. Involved in the regulation of intravascular and extravascular proteolytic activities. Plays hemostatic roles in the blood plasma. Acts as a procoagulant and pro-inflammatory factor by inhibiting the anticoagulant activated protein C factor as well as the generation of activated protein C factor by the thrombin/thrombomodulin complex. Acts as an anticoagulant factor by inhibiting blood coagulation factors like prothrombin, factor XI, factor Xa, plasma kallikrein and fibrinolytic enzymes such as tissue- and urinary-type plasminogen activators. In seminal plasma, inactivates several serine proteases implicated in the reproductive system. Inhibits the serpin acrosin; indirectly protects component of the male genital tract from being degraded by excessive released acrosin. Inhibits tissue- and urinary-type plasminogen activator, prostate-specific antigen and kallikrein activities; has a control on the sperm motility and fertilization. Inhibits the activated protein C-catalyzed degradation of SEMG1 and SEMG2; regulates the degradation of semenogelin during the process of transfer of spermatozoa from the male reproductive tract into the female tract. In urine, inhibits urinary-type plasminogen activator and kallikrein activities. Inactivates membrane-anchored serine proteases activities such as MPRSS7 and TMPRSS11E. Inhibits urinary-type plasminogen activator-dependent tumor cell invasion and metastasis. May also play a non-inhibitory role in seminal plasma and urine as a hydrophobic hormone carrier by its binding to retinoic acid.

References:

[1]. F España, et al. Functionally active protein C inhibitor/plasminogen activator inhibitor-3 (PCI/PAI-3) is secreted in seminal vesicles, occurs at high concentrations in human seminal plasma and complexes with prostate-specific antigen. Thromb Res. 1991 Nov 1;64(3):309-20. [Content Brief]

[2]. M G Elisen, et al. Protein C inhibitor may modulate human sperm-oocyte interactions. Biol Reprod. 1998 Mar;58(3):670-7. [Content Brief]

[3]. K Suzuki, et al. Mechanism of inhibition of activated protein C by protein C inhibitor. J Biochem. 1984 Jan;95(1):187-95. [Content Brief]

[4]. I Jerabek, et al. Binding of retinoic acid by the inhibitory serpin protein C inhibitor. Eur J Biochem. 2001 Nov;268(22):5989-96. [Content Brief]

[5]. F España, et al. Complexes of tissue kallikrein with protein C inhibitor in human semen and urine. Eur J Biochem. 1995 Dec 1;234(2):641-9. [Content Brief]

[6]. J C Meijers, et al. Inactivation of human plasma kallikrein and factor XIa by protein C inhibitor. Biochemistry. 1988 Jun 14;27(12):4231-7. [Content Brief]

[7]. S T Cooper, et al. Intermolecular interactions between protein C inhibitor and coagulation proteases. Biochemistry. 1995 Oct 10;34(40):12991-7. [Content Brief]

[8]. S He, et al. Functionally inactive protein C inhibitor in seminal plasma may be associated with infertility. Mol Hum Reprod. 1999 Jun;5(6):513-9. [Content Brief]

[9]. X Zheng, et al. Inhibition of acrosin by protein C inhibitor and localization of protein C inhibitor to spermatozoa. Am J Physiol. 1994 Aug;267(2 Pt 1):C466-72. [Content Brief]

[10]. Wei Sun, et al. N-glycans and the N terminus of protein C inhibitor affect the cofactor-enhanced rates of thrombin inhibition. J Biol Chem. 2008 Jul 4;283(27):18601-11. [Content Brief]

[11]. M G Elisen, et al. Protein C inhibitor acts as a procoagulant by inhibiting the thrombomodulin-induced activation of protein C in human plasma. Blood. 1998 Mar 1;91(5):1542-7. [Content Brief]

[12]. Roman Szabo, et al. Matriptase-3 is a novel phylogenetically preserved membrane-anchored serine protease with broad serpin reactivity. Biochem J. 2005 Aug 15;390(Pt 1):231-42. [Content Brief]

[13]. H Kise, et al. Characterization of semenogelin II and its molecular interaction with prostate-specific antigen and protein C inhibitor. Eur J Biochem. 1996 May 15;238(1):88-96. [Content Brief]

[14]. Toshiaki Wakita, et al. Regulation of carcinoma cell invasion by protein C inhibitor whose expression is decreased in renal cell carcinoma. Int J Cancer. 2004 Feb 10;108(4):516-23. [Content Brief]

[15]. T W Stief, et al. Inhibition of urokinase by protein C-inhibitor (PCI). Evidence for identity of PCI and plasminogen activator inhibitor 3. Biol Chem Hoppe Seyler. 1987 Oct;368(10):1427-33. [Content Brief]

[16]. John P Hobson, et al. Mouse DESC1 is located within a cluster of seven DESC1-like genes and encodes a type II transmembrane serine protease that forms serpin inhibitory complexes. J Biol Chem. 2004 Nov 5;279(45):46981-94. [Content Brief]

[17]. T Hayashi, et al. Characterization of a novel human protein C inhibitor (PCI) gene transgenic mouse useful for studying the role of PCI in physiological and pathological conditions. J Thromb Haemost. 2004 Jun;2(6):949-61. [Content Brief]

[18]. J Nishioka, et al. Protein C inhibitor secreted from activated platelets efficiently inhibits activated protein C on phosphatidylethanolamine of platelet membrane and microvesicles. J Biol Chem. 1998 May 1;273(18):11281-7. [Content Brief]

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