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Gene Review

SERPINA5  -  serpin peptidase inhibitor, clade A (alpha...

Homo sapiens

Synonyms: Acrosomal serine protease inhibitor, PAI-3, PAI3, PCI, PCI-B, ...
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Disease relevance of SERPINA5


Psychiatry related information on SERPINA5

  • Depressive syndromes and, particularly schizophrenic and paranoid psychoses were more frequent among the PCI than among the PCO subjects [6].
  • Adequate time for thoughtful decision-making, scheduling complexity, informed consent, and physician reimbursement favor PCI on a subsequent day [7].
  • However, treatment of acute myocardial infarction and secondary prevention considerably have been improved within the past years including early revascularization by PCI, the routine use of beta-blockers, statins and ACE-inhibitors as well as cardiac rehabilitation for improving life style measures [8].
  • Pain-coping strategies in chronic pain patients: psychometric characteristics of the pain-coping inventory (PCI) [9].
  • When trials with a symptom duration < 6 hours (median 130 min) were considered, PCI-related delay still correlated with an absolute risk reduction in 30-day mortality with a time to equipoise of 57 min (p = 0.03) [10].

High impact information on SERPINA5


Chemical compound and disease context of SERPINA5


Biological context of SERPINA5


Anatomical context of SERPINA5


Associations of SERPINA5 with chemical compounds

  • Using this assay, time, dose, and heparin-dependent complexes were detected when uPA was incubated with normal plasma or purified urinary PCI, whereas no complexes were measurable using PCI-immunodepleted plasma [24].
  • cis-elements required for expression of human protein C inhibitor gene in HepG2 cells and its androgen-dependent expression in rat reproductive organs [20].
  • The PCI mRNA expression in seminal vesicles was significantly decreased after castration or after 17beta-estradiol treatment [20].
  • Sg II bound to the solid-phase complex of diisopropylfluorophosphate (iPr2FP) and PSA with an apparent dissociation constant (kd) of 41 nM and to PCI with a Kd of 28 nM [25].
  • The protein C inhibitor antigen and activity were unaffected by vitamin K or warfarin treatment [4].
  • A peptide corresponding to the heparin-binding site of PCI abolished the stimulatory effect of PS on aPC inhibition [26].
  • The second-order rate constants (m(-1) min(-1)) of the reaction between HGFA and PCI in the presence or absence of heparin (10 U mL(-1)) were 4.3 x 10(6) and 4.0 x 10(6), respectively [27].
  • Exosite-2 residues (Arg89, Arg93, Glu94, Arg98, Arg245, Arg248, and Gln251) were critical for heparin-accelerated inhibition of thrombin by PCI [28].

Physical interactions of SERPINA5

  • In these plasma samples uPA-PCI complexes were present in a concentration corresponding to 21% to 25% of inactive uPA antigen [24].
  • Recently it was found, using purified proteins, that the anticoagulant thrombin-thrombomodulin complex was also inhibited by PCI [29].
  • Seminal plasma collected in the absence of extrinsic inhibitors contained 1.8 +/- 0.6 nM tKK:PCI complex and 4.7 +/- 2.8 nM immunoreactive tKK (mean +/- SD, n = 10), which indicates that about 28% of the total tKK immunoreactivity is forming complexes with PCI [30].
  • A few per cent of PSA in semen is complexed to the protein C inhibitor [31].
  • A new method to measure plasma levels of activated protein C in complex with protein C inhibitor in patients with acute coronary syndromes [32].

Enzymatic interactions of SERPINA5

  • PCI was found to inhibit the PSA-catalyzed degradation of insoluble coagula Sg I + II by forming a PSA-PCI complex [25].
  • The residues Phe353-Arg354-Ser355 (P2-P1-P1') constitute part of the reactive site loop of PCI with the Arg-Ser peptide bond being cleaved by the proteinase [33].

Regulatory relationships of SERPINA5

  • We conclude that TM enhances the reactivity of PCI with thrombin by providing both a binding site for the serpin and a conformational modulation of the extended binding pocket of thrombin [19].
  • This suggests that PCI can up regulate TAFI activation by inhibiting the protein C activation [34].
  • In blood plasma, PCI is present at ~0.08 muM and inactivates activated protein C and other coagulation and fibrinolytic enzymes [22].
  • These findings strongly suggest that PCI regulates the invasive potential of RCC cells by inhibiting uPA secreted by these cells [1].
  • Purified human PCI inhibited the amidolytic activity of purified boar acrosin with an apparent second-order rate constant of 3.7 x 10(4) M-1.s-1 [35].

Other interactions of SERPINA5

  • The role of PCI for urokinase (uPA) inhibition in vivo was investigated [24].
  • Further studies revealed that the substitution of Arg35 of thrombin with an Ala also resulted in an order of magnitude enhancement in reactivity of the protease with both PCI and AT-PCIH-helix independent of TM [19].
  • Substrates derived from PCI were the most sensitive for both hK1 and hK2 with specificity constants of about 10(7) M-1. s-1 [21].
  • However, alpha 2-PI and PCI seem to have evolved asynchronously from their substrates [36].
  • Addition of PCI to normal plasma and protein C-deficient plasma resulted in a minor prolongation of the clotting time [29].

Analytical, diagnostic and therapeutic context of SERPINA5


  1. Regulation of carcinoma cell invasion by protein C inhibitor whose expression is decreased in renal cell carcinoma. Wakita, T., Hayashi, T., Nishioka, J., Tamaru, H., Akita, N., Asanuma, K., Kamada, H., Gabazza, E.C., Ido, M., Kawamura, J., Suzuki, K. Int. J. Cancer (2004) [Pubmed]
  2. Protein C inhibitor (plasminogen activator inhibitor-3) expression in the CWR22 prostate cancer xenograft. Glasscock, L.N., Réhault, S.M., Gregory, C.W., Cooper, S.T., Jackson, T.P., Hoffman, M., Church, F.C. Exp. Mol. Pathol. (2005) [Pubmed]
  3. Gene organization of human protein C inhibitor, a member of SERPIN family proteins encoded in five exons. Hayashi, T., Suzuki, K. Int. J. Hematol. (1993) [Pubmed]
  4. Biosynthesis and secretion of factor VII, protein C, protein S, and the Protein C inhibitor from a human hepatoma cell line. Fair, D.S., Marlar, R.A. Blood (1986) [Pubmed]
  5. Characterization of a cDNA for human protein C inhibitor. A new member of the plasma serine protease inhibitor superfamily. Suzuki, K., Deyashiki, Y., Nishioka, J., Kurachi, K., Akira, M., Yamamoto, S., Hashimoto, S. J. Biol. Chem. (1987) [Pubmed]
  6. Suicides in close connection with psychiatric care: an analysis of 57 cases in a Swedish county. Sundqvist-Stensman, U.B. Acta psychiatrica Scandinavica. (1987) [Pubmed]
  7. Ad Hoc percutaneous coronary interventions in patients with stable coronary artery disease-A study of prevalence, safety, and variation in use from the American College of Cardiology National Cardiovascular Data Registry (ACC-NCDR(R)). Krone, R.J., Shaw, R.E., Klein, L.W., Blankenship, J.C., Weintraub, W.S. Catheterization and cardiovascular interventions : official journal of the Society for Cardiac Angiography & Interventions. (2006) [Pubmed]
  8. Highly Purified Omega-3 Fatty Acids for Secondary Prevention of Sudden Cardiac Death After Myocardial Infarction-Aims and Methods of the OMEGA-Study. Rauch, B., Schiele, R., Schneider, S., Gohlke, H., Diller, F., Gottwik, M., Steinbeck, G., Heer, T., Katus, H., Zimmer, R., Erdogan, A., Pfafferott, C., Senges For The Omega-Study Group, J. Cardiovascular drugs and therapy / sponsored by the International Society of Cardiovascular Pharmacotherapy (2006) [Pubmed]
  9. Pain-coping strategies in chronic pain patients: psychometric characteristics of the pain-coping inventory (PCI). Kraaimaat, F.W., Evers, A.W. International journal of behavioral medicine. (2003) [Pubmed]
  10. Time delay-adjusted survival benefit of angioplasty over thrombolysis in acute myocardial infarction: influence of time from symptom onset. Tarantini, G., Ramondo, A., Napodano, M., Bilato, C., Buja, P., Isabella, G., Razzolini, R., Iliceto, S. Italian heart journal : official journal of the Italian Federation of Cardiology. (2004) [Pubmed]
  11. Disruption of the protein C inhibitor gene results in impaired spermatogenesis and male infertility. Uhrin, P., Dewerchin, M., Hilpert, M., Chrenek, P., Schöfer, C., Zechmeister-Machhart, M., Krönke, G., Vales, A., Carmeliet, P., Binder, B.R., Geiger, M. J. Clin. Invest. (2000) [Pubmed]
  12. Protein C inhibitor is expressed in tubular cells of human kidney. Radtke, K.P., Fernández, J.A., Greengard, J.S., Tang, W.W., Wilson, C.B., Loskutoff, D.J., Scharrer, I., Griffin, J.H. J. Clin. Invest. (1994) [Pubmed]
  13. Protein C inhibitor and other components of the protein C pathway in patients with acute deep vein thrombosis during heparin treatment. Tabernero, D., España, F., Vicente, V., Estellés, A., Gilabert, J., Aznar, J. Thromb. Haemost. (1990) [Pubmed]
  14. Role of each Asn-linked glycan in the anticoagulant activity of human protein C inhibitor. Fujita, M., Izutani, W., Takahashi, K., Nishizawa, K., Shirono, H., Koga, J. Thromb. Res. (2002) [Pubmed]
  15. Facilitation of primary coronary angioplasty by early start of a glycoprotein 2b/3a inhibitor: results of the ongoing tirofiban in myocardial infarction evaluation (On-TIME) trial. van't Hof, A.W., Ernst, N., de Boer, M.J., de Winter, R., Boersma, E., Bunt, T., Petronio, S., Marcel Gosselink, A.T., Jap, W., Hollak, F., Hoorntje, J.C., Suryapranata, H., Dambrink, J.H., Zijlstra, F. Eur. Heart J. (2004) [Pubmed]
  16. Effect of urinary protein C inhibitor on lipopolysaccharide-induced disseminated intravascular coagulation in rats. Fujita, M., Izutani, W., Komurasaki, Y. Thromb. Haemost. (2000) [Pubmed]
  17. L-arginine attenuates lymphocyte activation and anti-oxidized LDL antibody levels in patients undergoing angioplasty. George, J., Shmuel, S.B., Roth, A., Herz, I., Izraelov, S., Deutsch, V., Keren, G., Miller, H. Atherosclerosis (2004) [Pubmed]
  18. Physical mapping of four serpin genes: alpha 1-antitrypsin, alpha 1-antichymotrypsin, corticosteroid-binding globulin, and protein C inhibitor, within a 280-kb region on chromosome I4q32.1. Billingsley, G.D., Walter, M.A., Hammond, G.L., Cox, D.W. Am. J. Hum. Genet. (1993) [Pubmed]
  19. Thrombomodulin enhances the reactivity of thrombin with protein C inhibitor by providing both a binding site for the serpin and allosterically modulating the activity of thrombin. Yang, L., Manithody, C., Walston, T.D., Cooper, S.T., Rezaie, A.R. J. Biol. Chem. (2003) [Pubmed]
  20. cis-elements required for expression of human protein C inhibitor gene in HepG2 cells and its androgen-dependent expression in rat reproductive organs. Suzuki, K., Hayashi, T. Semin. Thromb. Hemost. (2000) [Pubmed]
  21. Serpin-derived peptide substrates for investigating the substrate specificity of human tissue kallikreins hK1 and hK2. Bourgeois, L., Brillard-Bourdet, M., Deperthes, D., Juliano, M.A., Juliano, L., Tremblay, R.R., Dubé, J.Y., Gauthier, F. J. Biol. Chem. (1997) [Pubmed]
  22. The role of protein C inhibitor in human reproduction. España, F., Navarro, S., Medina, P., Zorio, E., Estellés, A. Semin. Thromb. Hemost. (2007) [Pubmed]
  23. Complex formation between protein C inhibitor and prostate-specific antigen in vitro and in human semen. Christensson, A., Lilja, H. Eur. J. Biochem. (1994) [Pubmed]
  24. Complex formation between urokinase and plasma protein C inhibitor in vitro and in vivo. Geiger, M., Huber, K., Wojta, J., Stingl, L., Espana, F., Griffin, J.H., Binder, B.R. Blood (1989) [Pubmed]
  25. Characterization of semenogelin II and its molecular interaction with prostate-specific antigen and protein C inhibitor. Kise, H., Nishioka, J., Kawamura, J., Suzuki, K. Eur. J. Biochem. (1996) [Pubmed]
  26. Regulation of protein C inhibitor (PCI) activity by specific oxidized and negatively charged phospholipids. Malleier, J.M., Oskolkova, O., Bochkov, V., Jerabek, I., Sokolikova, B., Perkmann, T., Breuss, J., Binder, B.R., Geiger, M. Blood (2007) [Pubmed]
  27. Protein C inhibitor directly and potently inhibits activated hepatocyte growth factor activator. Hayashi, T., Nishioka, J., Nakagawa, N., Kamada, H., Gabazza, E.C., Kobayashi, T., Hattori, A., Suzuki, K. J. Thromb. Haemost. (2007) [Pubmed]
  28. Essential thrombin residues for inhibition by protein C inhibitor with the cofactors heparin and thrombomodulin. Fortenberry, Y.M., Whinna, H.C., Cooper, S.T., Myles, T., Leung, L.L., Church, F.C. J. Thromb. Haemost. (2007) [Pubmed]
  29. Protein C inhibitor acts as a procoagulant by inhibiting the thrombomodulin-induced activation of protein C in human plasma. Elisen, M.G., von dem Borne, P.A., Bouma, B.N., Meijers, J.C. Blood (1998) [Pubmed]
  30. Complexes of tissue kallikrein with protein C inhibitor in human semen and urine. España, F., Fink, E., Sanchez-Cuenca, J., Gilabert, J., Estellés, A., Witzgall, K. Eur. J. Biochem. (1995) [Pubmed]
  31. Biochemistry of prostate specific antigen, PSA. Malm, J., Lilja, H. Scand. J. Clin. Lab. Invest. Suppl. (1995) [Pubmed]
  32. A new method to measure plasma levels of activated protein C in complex with protein C inhibitor in patients with acute coronary syndromes. Strandberg, K., Bhiladvala, P., Holm, J., Stenflo, J. Blood Coagul. Fibrinolysis (2001) [Pubmed]
  33. Mutagenesis of recombinant protein C inhibitor reactive site residues alters target proteinase specificity. Phillips, J.E., Cooper, S.T., Potter, E.E., Church, F.C. J. Biol. Chem. (1994) [Pubmed]
  34. Protein C inhibitor regulates the thrombin-thrombomodulin complex in the up- and down regulation of TAFI activation. Mosnier, L.O., Elisen, M.G., Bouma, B.N., Meijers, J.C. Thromb. Haemost. (2001) [Pubmed]
  35. Inhibition of acrosin by protein C inhibitor and localization of protein C inhibitor to spermatozoa. Zheng, X., Geiger, M., Ecke, S., Bielek, E., Donner, P., Eberspächer, U., Schleuning, W.D., Binder, B.R. Am. J. Physiol. (1994) [Pubmed]
  36. Structure of human alpha 2-plasmin inhibitor deduced from the cDNA sequence. Tone, M., Kikuno, R., Kume-Iwaki, A., Hashimoto-Gotoh, T. J. Biochem. (1987) [Pubmed]
  37. Kininogenase activity of prostate-derived human glandular kallikrein (hK2) purified from seminal fluid. Charlesworth, M.C., Young, C.Y., Miller, V.M., Tindall, D.J. J. Androl. (1999) [Pubmed]
  38. 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. España, F., Gilabert, J., Estellés, A., Romeu, A., Aznar, J., Cabo, A. Thromb. Res. (1991) [Pubmed]
  39. Protein C inhibitor in human body fluids. Seminal plasma is rich in inhibitor antigen deriving from cells throughout the male reproductive system. Laurell, M., Christensson, A., Abrahamsson, P.A., Stenflo, J., Lilja, H. J. Clin. Invest. (1992) [Pubmed]
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