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Gene Review

SERPINB6  -  serpin peptidase inhibitor, clade B...

Homo sapiens

Synonyms: CAP, Cytoplasmic antiproteinase, DFNB91, MSTP057, PI-6, ...
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Disease relevance of SERPINB6

  • In conclusion, SERPINB6 is abundantly expressed by normal mast cells and by mast cells in mastocytoma lesions [1].
  • Identification of a novel complex between human kallikrein 2 and protease inhibitor-6 in prostate cancer tissue [2].
  • To evaluate whether elevated arterial free fatty acids (FFA) increase myocardial oxygen demand and ischemia, 15 fasting patients with coronary artery disease underwent a standardized atrial pacing test before (PTI) and during (PT2) heparin infusion [3].
  • This study was designed to measure the pharmacokinetic parameters of two different preparations of unconjugated soy isoflavones, PTI G-2535 and PTI G-4660 (which contain 43% and 90% genistein, respectively), in human subjects with cancer, to evaluate toxicity and obtain pilot data on in vivo effects on protein-tyrosine phosphorylation [4].
  • Postnatal growth patterns of weight, length/height and head circumference in full-term (FTI), preterm (PTI) and small-for-dates (SFDI) infants, are described by using distance and velocity data together with the concept of growth per unit of body weight [5].

Psychiatry related information on SERPINB6

  • Results showed modest support for the SCZI and PTI but not the MMPI indicators [6].
  • Using a sample of child and adolescent inpatients, we examined the relation of Rorschach variables (PTI, SCZI, M-, and X- %) to thought disorder indexes on a behavior rating scale (Behavior Assessment System for Children; Reynolds & Kamphaus, 1992) and a self-report measure (Personality Inventory for Youth; Lachar & Gruber, 1995) [7].

High impact information on SERPINB6


Biological context of SERPINB6

  • A serpin gene cluster on human chromosome 6p25 contains PI6, PI9 and ELANH2 which have a common structure almost identical to the 18q21 ovalbumin serpin genes [9].
  • Another Ov-serpin gene PI6 (placental thrombin inhibitor) was colocalized to the same region, thus defining an Ov-serpin locus on chromosome 6 in addition to the previously defined PLANH2-containing Ov-serpin locus on chromosome 18 [10].
  • Thus, PI9 joins its close relatives PI6 and PI8 as having the ability to utilize multiple reactive site loop residues as the inhibitory P(1) residue to expand its inhibitory spectrum [11].
  • The degree of amino acid sequence identity between the novel serpins and PI6 (63-68%) significantly exceeds that of any other combination of known intracellular serpins [12].
  • A human placental lambda gt11 cDNA library was screened for sequences encoding proteins related to human proteinase inhibitor 6 (PI6), and two plaques were identified that displayed weak hybridization at high stringency [12].

Anatomical context of SERPINB6


Associations of SERPINB6 with chemical compounds

  • Gel filtration experiments revealed that the latter cells contain a high-molecular-weight form of SERPINB6, which consists of sodium dodecyl sulfate (SDS)-stable complexes of this inhibitor with monomeric beta-tryptase [1].
  • This platelet component is functionally and immunologically indistinguishable from the cytoplasmic antiproteinase (CAP), also known as placental thrombin inhibitor, a recently cloned member of the ovalbumin family of intracellular serpins (serine proteinase inhibitors) [15].
  • The PI-6 cDNA was modified to encode six histidine residues immediately after the initiation codon, and was placed under the control of the P. pastoris alcohol oxidase promoter in the vector pHIL-D2 [16].
  • On the methanol induction, active recombinant PI-6 was produced within the yeast cells, and following cell lysis, was separated from yeast proteins by affinity chromatography using nickel nitrilo-tri-acetic acid (NTA) resin [16].
  • In addition to plasminogen activator inhibitor 1, these included pigment epithelium-derived factor (confirmed by Western immunoblot), placental thrombin inhibitor, pregnancy zone protein, and protease C1 inhibitor [17].

Physical interactions of SERPINB6


Other interactions of SERPINB6


Analytical, diagnostic and therapeutic context of SERPINB6


  1. Intracellular serpin SERPINB6 (PI6) is abundantly expressed by human mast cells and forms complexes with beta-tryptase monomers. Strik, M.C., Wolbink, A., Wouters, D., Bladergroen, B.A., Verlaan, A.R., van Houdt, I.S., Hijlkema, S., Hack, C.E., Kummer, J.A. Blood (2004) [Pubmed]
  2. Identification of a novel complex between human kallikrein 2 and protease inhibitor-6 in prostate cancer tissue. Mikolajczyk, S.D., Millar, L.S., Marker, K.M., Rittenhouse, H.G., Wolfert, R.L., Marks, L.S., Charlesworth, M.C., Tindall, D.J. Cancer Res. (1999) [Pubmed]
  3. Effect of increased free fatty acids on myocardial oxygen extraction and angina threshold during atrial pacing. Dagenais, G.R., Jalbert, B. Circulation (1977) [Pubmed]
  4. Phase I pharmacokinetic and pharmacodynamic analysis of unconjugated soy isoflavones administered to individuals with cancer. Takimoto, C.H., Glover, K., Huang, X., Hayes, S.A., Gallot, L., Quinn, M., Jovanovic, B.D., Shapiro, A., Hernandez, L., Goetz, A., Llorens, V., Lieberman, R., Crowell, J.A., Poisson, B.A., Bergan, R.C. Cancer Epidemiol. Biomarkers Prev. (2003) [Pubmed]
  5. Early postnatal growth evaluation in full-term, preterm and small-for-dates infants. Martell, M., Falkner, F., Bertolini, L.B., Díaz, J.L., Nieto, F., Tenzer, S.M., Belitzky, R. Early Hum. Dev. (1978) [Pubmed]
  6. Association of Rorschach and MMPI psychosis indicators and schizophrenia spectrum diagnoses in a Russian clinical sample. Ritsher, J.B. Journal of personality assessment. (2004) [Pubmed]
  7. Assessment of disordered thinking in children and adolescents: the rorschach perceptual-thinking index. Smith, S.R., Baity, M.R., Knowles, E.S., Hilsenroth, M.J. Journal of personality assessment. (2001) [Pubmed]
  8. Cloning and molecular characterization of a human intracellular serine proteinase inhibitor. Coughlin, P., Sun, J., Cerruti, L., Salem, H.H., Bird, P. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  9. A serpin gene cluster on human chromosome 6p25 contains PI6, PI9 and ELANH2 which have a common structure almost identical to the 18q21 ovalbumin serpin genes. Sun, J., Stephens, R., Mirza, G., Kanai, H., Ragoussis, J., Bird, P.I. Cytogenet. Cell Genet. (1998) [Pubmed]
  10. Characterization and chromosomal localization of ELANH2, the gene encoding human monocyte/neutrophil elastase inhibitor. Evans, E., Cooley, J., Remold-O'Donnell, E. Genomics (1995) [Pubmed]
  11. Inhibition of neutrophil elastase by recombinant human proteinase inhibitor 9. Dahlen, J.R., Foster, D.C., Kisiel, W. Biochim. Biophys. Acta (1999) [Pubmed]
  12. 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]
  13. A cytosolic granzyme B inhibitor related to the viral apoptotic regulator cytokine response modifier A is present in cytotoxic lymphocytes. Sun, J., Bird, C.H., Sutton, V., McDonald, L., Coughlin, P.B., De Jong, T.A., Trapani, J.A., Bird, P.I. J. Biol. Chem. (1996) [Pubmed]
  14. Proteinase inhibitor 6 (PI-6) expression in human skin: induction of PI-6 and a PI-6/proteinase complex during keratinocyte differentiation. Scott, F.L., Paddle-Ledinek, J.E., Cerruti, L., Coughlin, P.B., Salem, H.H., Bird, P.I. Exp. Cell Res. (1998) [Pubmed]
  15. Identification and characterization of the cytoplasmic antiproteinase (CAP) in human platelets. Evidence for the interaction of CAP with endogenous platelet proteins. Riewald, M., Morgenstern, K.A., Schleef, R.R. J. Biol. Chem. (1996) [Pubmed]
  16. Production and characterization of recombinant human proteinase inhibitor 6 expressed in Pichia pastoris. Sun, J., Coughlin, P., Salem, H.H., Bird, P. Biochim. Biophys. Acta (1995) [Pubmed]
  17. Secretome of Primary Cultures of Human Adipose-derived Stem Cells: Modulation of Serpins by Adipogenesis. Zvonic, S., Lefevre, M., Kilroy, G., Floyd, Z.E., Delany, J.P., Kheterpal, I., Gravois, A., Dow, R., White, A., Wu, X., Gimble, J.M. Mol. Cell Proteomics (2007) [Pubmed]
  18. Human kallikrein 2 (hK2), but not prostate-specific antigen (PSA), rapidly complexes with protease inhibitor 6 (PI-6) released from prostate carcinoma cells. Saedi, M.S., Zhu, Z., Marker, K., Liu, R.S., Carpenter, P.M., Rittenhouse, H., Mikolajczyk, S.D. Int. J. Cancer (2001) [Pubmed]
  19. The enigma PAI-2. Gene expression, evolutionary and functional aspects. Bachmann, F. Thromb. Haemost. (1995) [Pubmed]
  20. Chromosomal mapping of the human proteinase inhibitor 6 (PI6) gene to 6p25 by fluorescence in situ hybridization. Coughlin, P., Nicholl, J., Sun, J., Salem, H., Bird, P., Sutherland, G.R. Genomics (1995) [Pubmed]
  21. Gene structure, chromosomal localization, and expression of the murine homologue of human proteinase inhibitor 6 (PI-6) suggests divergence of PI-6 from the ovalbumin serpins. Sun, J., Rose, J.B., Bird, P. J. Biol. Chem. (1995) [Pubmed]
  22. Proteinase inhibitor 6 cannot be secreted, which suggests it is a new type of cellular serpin. Scott, F.L., Coughlin, P.B., Bird, C., Cerruti, L., Hayman, J.A., Bird, P. J. Biol. Chem. (1996) [Pubmed]
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