2hi9

Structural highlights

Function

IPSP_HUMAN 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 proinflammatory 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.^{[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17] [18]}

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

See Also

• Plasminogen activator inhibitor

References

1. ↑ Suzuki K, Nishioka J, Kusumoto H, Hashimoto S. Mechanism of inhibition of activated protein C by protein C inhibitor. J Biochem. 1984 Jan;95(1):187-95. PMID:6323392
2. ↑ Stief TW, Radtke KP, Heimburger N. 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. PMID:3501295
3. ↑ Meijers JC, Kanters DH, Vlooswijk RA, van Erp HE, Hessing M, Bouma BN. Inactivation of human plasma kallikrein and factor XIa by protein C inhibitor. Biochemistry. 1988 Jun 14;27(12):4231-7. PMID:2844223
4. ↑ Espana F, Gilabert J, Estelles A, Romeu A, Aznar J, Cabo A. 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. PMID:1725227
5. ↑ Zheng X, Geiger M, Ecke S, Bielek E, Donner P, Eberspacher U, Schleuning WD, Binder BR. 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. PMID:7521127
6. ↑ Cooper ST, Whinna HC, Jackson TP, Boyd JM, Church FC. Intermolecular interactions between protein C inhibitor and coagulation proteases. Biochemistry. 1995 Oct 10;34(40):12991-7. PMID:7548057
7. ↑ Espana F, Fink E, Sanchez-Cuenca J, Gilabert J, Estelles A, Witzgall K. Complexes of tissue kallikrein with protein C inhibitor in human semen and urine. Eur J Biochem. 1995 Dec 1;234(2):641-9. PMID:8536714
8. ↑ Kise H, Nishioka J, Kawamura J, Suzuki K. 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. PMID:8665956
9. ↑ Elisen MG, von dem Borne PA, Bouma BN, Meijers JC. 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. PMID:9473218
10. ↑ Elisen MG, van Kooij RJ, Nolte MA, Marquart JA, Lock TM, Bouma BN, Meijers JC. Protein C inhibitor may modulate human sperm-oocyte interactions. Biol Reprod. 1998 Mar;58(3):670-7. PMID:9510955
11. ↑ Nishioka J, Ning M, Hayashi T, Suzuki K. 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. PMID:9556620
12. ↑ He S, Lin YL, Liu YX. Functionally inactive protein C inhibitor in seminal plasma may be associated with infertility. Mol Hum Reprod. 1999 Jun;5(6):513-9. PMID:10340997
13. ↑ Jerabek I, Zechmeister-Machhart M, Binder BR, Geiger M. Binding of retinoic acid by the inhibitory serpin protein C inhibitor. Eur J Biochem. 2001 Nov;268(22):5989-96. PMID:11722589
14. ↑ Wakita T, Hayashi T, Nishioka J, Tamaru H, Akita N, Asanuma K, Kamada H, Gabazza EC, Ido M, Kawamura J, Suzuki K. 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. PMID:14696115 doi:http://dx.doi.org/10.1002/ijc.11594
15. ↑ Hobson JP, Netzel-Arnett S, Szabo R, Rehault SM, Church FC, Strickland DK, Lawrence DA, Antalis TM, Bugge TH. 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. Epub 2004 Aug 24. PMID:15328353 doi:http://dx.doi.org/10.1074/jbc.M403299200
16. ↑ Hayashi T, Nishioka J, Kamada H, Asanuma K, Kondo H, Gabazza EC, Ido M, Suzuki K. 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. PMID:15140131 doi:http://dx.doi.org/10.1111/j.1538-7836.2004.00733.x
17. ↑ Szabo R, Netzel-Arnett S, Hobson JP, Antalis TM, Bugge TH. 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. PMID:15853774 doi:BJ20050299
18. ↑ Sun W, Parry S, Panico M, Morris HR, Kjellberg M, Engstrom A, Dell A, Schedin-Weiss S. 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. doi: 10.1074/jbc.M800608200. Epub 2008 , May 8. PMID:18467335 doi:http://dx.doi.org/10.1074/jbc.M800608200