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Gene Review

SERPINB8  -  serpin peptidase inhibitor, clade B...

Homo sapiens

Synonyms: CAP-2, CAP2, Cytoplasmic antiproteinase 2, PI-8, PI8, ...
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Disease relevance of SERPINB8

  • PI8 inhibited the amidolytic activities of porcine trypsin, human thrombin, human coagulation factor Xa, and the Bacillus subtilis dibasic endoproteinase subtilisin A through different mechanisms but failed to inhibit the Staphylococcus aureus endoproteinase Glu-C [1].

High impact information on SERPINB8

  • The beat frequency of the myogenic heart of the tobacco hawkmoth, Manduca sexta, markedly increases at adult emergence in response to 2 blood-borne peptide neurohormones, known as the cardioacceleratory peptides (CAP1 and CAP2) [2].
  • These results provide strong support for the hypothesis that InsP3 is likely to be the second messenger in the regulation of heart beat activity by CAP2 [2].
  • Thus, PI8 inhibits furin in a rapid, tight binding manner that is characteristic of physiological serpin-proteinase interactions [3].
  • Our identification of multiple sequence homologs of PI-8 and PI-9, and six new ovalbumin serpins, is consonant with the idea that the larger set of granule and other proteinases known to exist in the mouse (compared with human) is balanced by a larger array of serpins [4].
  • The two novel serpins encoded by the two novel cDNA sequences have been designated as proteinase inhibitor 8 (PI8) and proteinase inhibitor 9 (PI9) [5].

Biological context of SERPINB8

  • PI8 is not only the first human ovalbumin-type serpin to demonstrate inhibitory activity toward furin, but it is also the first significant inhibitor of furin identified that is not a serpin reactive site loop mutant, either naturally occurring or engineered [3].
  • In this study, human proteinase inhibitor 8 (PI8), a widely expressed 45-kDa ovalbumin-type serpin that contains two sequences homologous to the minimal sequence for recognition by furin in its reactive site loop, was tested for its ability to inhibit a recombinant soluble form of human furin [3].
  • Furthermore, our findings demonstrate the inhibitory capacity of exogenous PI8 in platelet aggregation assays [6].
  • A slow-binding kinetics approach was used to determine the kinetic constants for the interactions of PI8 with factor Xa and subtilisin A [1].
  • Human ovalbumin serpin evolution: phylogenic analysis, gene organization, and identification of new PI8-related genes suggest that two interchromosomal and several intrachromosomal duplications generated the gene clusters at 18q21-q23 and 6p25 [7].

Anatomical context of SERPINB8

  • PI8 is shown to be a platelet-derived constituent, synthesized by megakaryocytes and stored in platelets prior to its release [6].
  • Two PI8 transcripts of 1.4 kilobases (kb) and 3.8 kb were detected by Northern analysis in equal and greatest abundance in liver and lung, while the 1.4-kb mRNA was in excess over the 3.8-kb mRNA in skeletal muscle and heart [5].
  • Monocytes showed nuclear and cytoplasmic localization of PI-8, whereas neuroendocrine cells showed only cytoplasmic staining [8].
  • In vitro nuclear localization of PI-8 was confirmed by confocal analysis using serpin-transfected HeLa cells [8].
  • PI-8 was also expressed by monocytes and by neuroendocrine cells in the pituitary gland, pancreas, and digestive tract [8].

Associations of SERPINB8 with chemical compounds


Other interactions of SERPINB8

  • Immunoblot analyses using rabbit anti-PI6 IgG indicated the presence of PI8 in the cytosolic fraction of stably transfected cells that formed an SDS-stable 67-kDa complex with human thrombin [5].
  • Here we have identified a new gene (PI8L1) at 6p25 that is 72% identical to the 18q21 gene PI8 [7].
  • Using these data with an ov-serpin phylogenic tree we have constructed, we propose that the ov-serpin gene clusters arose via interchromosomal duplication of PI5 (or a precursor) to 6p25, followed by duplication at 6p25, and a more recent interchromosomal duplication from 6p25 to 18q to yield PI8 [7].

Analytical, diagnostic and therapeutic context of SERPINB8

  • RT-PCR revealed that CAP-2 mRNA was exclusively expressed in the epidermal tissue during the postmolt stage, the site and stage being associated with calcification [10].
  • To elucidate their physiological role(s), we studied the expression of one of these inhibitors, protease inhibitor 8 (PI-8), in normal human tissues by immunohistochemistry using a PI-8-specific monoclonal antibody [8].
  • Relative gene expression level analysis by PCR and by Northern blotting revealed that treatment with TNF-alpha enhanced the expression of PLOD, CAP2 and TTK transcripts which confirmed the results obtained with display gels [9].
  • Biochemical analyses using high-pressure liquid chromatography confirm that the lateral neurons in larvae contain CAP2, one of the CAPs [11].
  • The amino acid composition analysis of the CAP-2 protein calculated from HPLC chromatograms shows that this protein contains around 108 amino acids [12].


  1. Expression, purification, and inhibitory properties of human proteinase inhibitor. Dahlen, J.R., Foster, D.C., Kisiel, W. Biochemistry (1997) [Pubmed]
  2. Insect cardioactive neuropeptides: peptidergic modulation of the intrinsic rhythm of an insect heart is mediated by inositol 1,4,5-trisphosphate. Tublitz, N.J. J. Neurosci. (1988) [Pubmed]
  3. Inhibition of soluble recombinant furin by human proteinase inhibitor 8. Dahlen, J.R., Jean, F., Thomas, G., Foster, D.C., Kisiel, W. J. Biol. Chem. (1998) [Pubmed]
  4. A new family of 10 murine ovalbumin serpins includes two homologs of proteinase inhibitor 8 and two homologs of the granzyme B inhibitor (proteinase inhibitor 9). Sun, J., Ooms, L., Bird, C.H., Sutton, V.R., Trapani, J.A., Bird, P.I. J. Biol. Chem. (1997) [Pubmed]
  5. Molecular cloning, expression, and partial characterization of two novel members of the ovalbumin family of serine proteinase inhibitors. Sprecher, C.A., Morgenstern, K.A., Mathewes, S., Dahlen, J.R., Schrader, S.K., Foster, D.C., Kisiel, W. J. Biol. Chem. (1995) [Pubmed]
  6. The serpin proteinase inhibitor 8: an endogenous furin inhibitor released from human platelets. Leblond, J., Laprise, M.H., Gaudreau, S., Grondin, F., Kisiel, W., Dubois, C.M. Thromb. Haemost. (2006) [Pubmed]
  7. Human ovalbumin serpin evolution: phylogenic analysis, gene organization, and identification of new PI8-related genes suggest that two interchromosomal and several intrachromosomal duplications generated the gene clusters at 18q21-q23 and 6p25. Scott, F.L., Eyre, H.J., Lioumi, M., Ragoussis, J., Irving, J.A., Sutherland, G.A., Bird, P.I. Genomics (1999) [Pubmed]
  8. Distribution of the human intracellular serpin protease inhibitor 8 in human tissues. Strik, M.C., Bladergroen, B.A., Wouters, D., Kisiel, W., Hooijberg, J.H., Verlaan, A.R., Hordijk, P.L., Schneider, P., Hack, C.E., Kummer, J.A. J. Histochem. Cytochem. (2002) [Pubmed]
  9. Tumour necrosis factor alpha enhances the expression of hydroxyl lyase, cytoplasmic antiproteinase-2 and a dual specificity kinase TTK in human chondrocyte-like cells. Ah-Kim, H., Zhang, X., Islam, S., Sofi, J.I., Glickberg, Y., Malemud, C.J., Moskowitz, R.W., Haqqi, T.M. Cytokine (2000) [Pubmed]
  10. A novel calcium-binding peptide from the cuticle of the crayfish, Procambarus clarkii. Inoue, H., Ohira, T., Ozaki, N., Nagasawa, H. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  11. Postembryonic alteration of transmitter phenotype in individually identified peptidergic neurons. Tublitz, N.J., Sylwester, A.W. J. Neurosci. (1990) [Pubmed]
  12. Isolation of a novel tumor protein that induces resistance to natural killer cell lysis. Serrano, R., Yiangos, Y.G., Solana, R., Sachs, J.A., Pena, J. J. Immunol. (1990) [Pubmed]
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