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Gene Review

SERPINA10  -  serpin peptidase inhibitor, clade A (alpha...

Homo sapiens

Synonyms: PZ-dependent protease inhibitor, PZI, Protein Z-dependent protease inhibitor, Serpin A10, UNQ707/PRO1358, ...
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Disease relevance of SERPINA10

  • Inhibition studies in both the presence and absence of PZ revealed that Arg-143, Lys-147, and Arg-154 of the autolysis loop and Lys-96, Lys-169, and Lys-236 of the heparin binding exosite are required for recognition of ZPI, with Arg-143 being essential for the interaction [1].
  • Although further studies are required, all available data support that the ZPI is a candidate to play a significant role in thrombosis and should be evaluated in thrombophilic studies [2].
  • Our study supports that the ZPI Arg67Stop nonsense polymorphism might be an independent genetic risk factor for venous thrombosis [2].

High impact information on SERPINA10

  • ZPI is a 72,000-Mr single-chain protein with an N-terminal amino acid sequence of LAPSPQSPEXXA (X = indeterminate) and an estimated concentration in citrate-treated plasma of 1.0-1.6 microg/ml [3].
  • We have studied 6 genetic modifications affecting the ZPI gene, identifying 5 haplotypes [2].
  • Heparin (0.2 U/mL) enhances the rate (t(1/2) = 25 seconds vs 50 seconds) and the extent (99% vs 93% at 30 minutes) of factor XIa inhibition by ZPI [4].
  • Protein Z-dependent protease inhibitor (ZPI) is a 72-kd member of the serpin superfamily of proteinase inhibitors that produces rapid inhibition of factor Xa in the presence of protein Z (PZ), procoagulant phospholipids, and Ca(++) (t(1/2) less than 10 seconds) [4].
  • 1) FXase incubation mixtures with/without ZPI/protein Z were diluted in EDTA; FXa activity was measured after reversal of its inhibition [5].

Biological context of SERPINA10


Anatomical context of SERPINA10

  • Thus, the AT interaction with the heparin-like glycosaminoglycans on the surface of the endothelium, and the ZPI complex formation with protein Z on membrane phospholipids is required for the physiological regulation of fXa by both serpins [9].
  • Therefore, rabbits diabetic for 3-4 mo (after alloxan injection) were treated with PZI insulin for 3-4 mo, and the mechanical performance of their right ventricular papillary muscles was compared with that of untreated diabetic animals and age-matched controls [10].

Associations of SERPINA10 with chemical compounds

  • Consistent with this notion, rZPI(Y387A), an altered form of ZPI in which tyrosine 387 has been changed to alanine, lacks PZ-dependent factor Xa inhibitory activity [6].
  • Since C4-deficient guinea pig serum is also effective in ZPI formation, the data suggest that ZPI is an alternative pathway intermediate containing both P and C3 [11].
  • The formation of ZPI does not require C1 or C2 and is not diminished by prior absorption of the serum with Z [11].
  • Acute replacement (8 units PZI) 12hr before the measurements resulted in resting and noradrenaline-stimulated values for VO2 that were similar to those of non-diabetic cafeteria rats [12].
  • Comparison of one daily injection of NPH and crystalline PZI insulins on urinary glucose in diabetic children [13].

Analytical, diagnostic and therapeutic context of SERPINA10

  • Surface plasmon resonance binding experiments revealed binding and dissociation of ZPI/FIXa with Kd (app) of 9-12 nm, similar to the concentration of ZPI needed for 50% inhibition [5].
  • The coding region of the ZPI gene was screened for mutations using denaturing high-performance liquid chromatography [14].
  • As PZ deficiency is hypothesized to lead to a prothrombotic state, we performed a case-control study to measure plasma levels of PZ and ZPI in 66 patients with autoimmune aPL and 152 normal controls [15].
  • To clarify the risk, the records of 7,750 cardiac catheterization procedures between 1984 and 1987 were analyzed for presence of NPH or PZI insulin use, protamine administration, and any complications or adverse reactions [16].


  1. Identification of factor Xa residues critical for interaction with protein Z-dependent protease inhibitor: both active site and exosite interactions are required for inhibition. Rezaie, A.R., Manithody, C., Yang, L. J. Biol. Chem. (2005) [Pubmed]
  2. A nonsense polymorphism in the protein Z-dependent protease inhibitor increases the risk for venous thrombosis. Corral, J., González-Conejero, R., Soria, J.M., González-Porras, J.R., Pérez-Ceballos, E., Lecumberri, R., Roldán, V., Souto, J.C., Miñano, A., Hernández-Espinosa, D., Alberca, I., Fontcuberta, J., Vicente, V. Blood (2006) [Pubmed]
  3. Isolation of a protein Z-dependent plasma protease inhibitor. Han, X., Fiehler, R., Broze, G.J. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  4. Characterization of the protein Z-dependent protease inhibitor. Han, X., Fiehler, R., Broze, G.J. Blood (2000) [Pubmed]
  5. Down-regulation of factor IXa in the factor Xase complex by protein Z-dependent protease inhibitor. Heeb, M.J., Cabral, K.M., Ruan, L. J. Biol. Chem. (2005) [Pubmed]
  6. The protein Z-dependent protease inhibitor is a serpin. Han, X., Huang, Z.F., Fiehler, R., Broze, G.J. Biochemistry (1999) [Pubmed]
  7. Contributions of basic amino acids in the autolysis loop of factor XIa to serpin specificity. Rezaie, A.R., Sun, M.F., Gailani, D. Biochemistry (2006) [Pubmed]
  8. Solubilization of four porcine zona pellucida antigens by lithium 3,5-diiodosalicylate. Dietl, J., Czuppon, A., Mettler, L. Hoppe-Seyler's Z. Physiol. Chem. (1982) [Pubmed]
  9. Determinants of specificity of factor xa interaction with its physiological inhibitors. Rezaie, A.R. Mini reviews in medicinal chemistry. (2006) [Pubmed]
  10. Reversibility of diabetic cardiomyopathy with insulin in rabbits. Fein, F.S., Miller-Green, B., Zola, B., Sonnenblick, E.H. Am. J. Physiol. (1986) [Pubmed]
  11. A properdin system intermediate formed by zymosan and serum at 0 degrees C. Yukiyama, Y., Lew, F.T., Waks, H.S., Osler, A.G. J. Immunol. (1976) [Pubmed]
  12. A role for insulin in the diet-induced thermogenesis of cafeteria-fed rats. Rothwell, N.J., Stock, M.J. Metab. Clin. Exp. (1981) [Pubmed]
  13. Comparison of one daily injection of NPH and crystalline PZI insulins on urinary glucose in diabetic children. Mimouni, M., Koivukangas, T., Karp, M., Laron, Z. Acta diabetologica latina. (1979) [Pubmed]
  14. Mutations within the protein Z-dependent protease inhibitor gene are associated with venous thromboembolic disease: a new form of thrombophilia. Water, N., Tan, T., Ashton, F., O'grady, A., Day, T., Browett, P., Ockelford, P., Harper, P. Br. J. Haematol. (2004) [Pubmed]
  15. Autoimmune antiphospholipid antibodies impair the inhibition of activated factor X by protein Z/protein Z-dependent protease inhibitor. Forastiero, R.R., Martinuzzo, M.E., Lu, L., Broze, G.J. J. Thromb. Haemost. (2003) [Pubmed]
  16. Protamine allergy reactions during cardiac catheterization and cardiac surgery: risk in patients taking protamine-insulin preparations. Vincent, G.M., Janowski, M., Menlove, R. Catheterization and cardiovascular diagnosis. (1991) [Pubmed]
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