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Gene Review

Gzma  -  granzyme A

Mus musculus

Synonyms: AW494114, Autocrine thymic lymphoma granzyme-like serine protease, BLT esterase, CTLA-3, Ctla-3, ...
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Disease relevance of Gzma


Psychiatry related information on Gzma


High impact information on Gzma


Chemical compound and disease context of Gzma


Biological context of Gzma


Anatomical context of Gzma


Associations of Gzma with chemical compounds

  • CTLA-1 and CTLA-3 serine esterase transcripts are detected mostly in cytotoxic T cells, but not only and not always [16].
  • A trypsinlike SE activity which cleaves the chromogenic substrate N, alpha-benzyloxycarbonyl-L-lysine thiobenzyl ester was also induced 2- to 4-fold in the presence of the various IL tested [18].
  • This nuclear DNA-releasing (NDR) activity is inhibited by serine esterase inhibitors that also inhibit the granule BLT-esterase activity, and is specifically immunoabsorbed by antibodies to the CTL granule protease granzyme A [19].
  • A combination of Ac-DEVD-CHO and the granzyme A inhibitor IGA (7-(phenyl-ureido)-4-chloro-3-(2-isothioureidoethoxy)-isocoumarin) inhibited long-term cytolysis [20].
  • An expression vector containing antisense cDNA for GA and the gene for hygromycin B resistance was constructed and electroporated into the murine CTL line, AR1 [21].

Physical interactions of Gzma

  • It is proposed that granzyme A interacts with the thrombin receptor found on platelets in a manner that is insufficient to cause aggregation, but sufficient to compete with thrombin for the receptor [22].
  • In contrast, ligation of the CD3/TCR complex could elicit a rapid cytotoxic response and serine esterase release by IEL [23].
  • We previously reported a selective deficiency of NK cells in a C57BL/6 mouse with a transgenic construct consisting of the cDNA for the Ly49A major histocompatibility complex (MHC) class 1-specific inhibitory receptor driven by the granzyme A gene [24].

Enzymatic interactions of Gzma

  • A synthetic peptide spanning the N-terminal thrombin receptor activation sequence was cleaved by granzyme A at the authentic thrombin cleavage site Leu-Asp-Pro-Arg-Ser [25].

Co-localisations of Gzma

  • In PM and IBM, PF positive cells were colocalized with GA positive cells and occasionally invaded into the non-necrotic muscle fibres [3].

Regulatory relationships of Gzma

  • We conclude that GzmK expressed by GzmA-deficient T cells accounts for the remaining Z-Lys-SBzl activity [26].
  • The spontaneous cytotoxic potential of the DN T cells was further corroborated by demonstrating that the lpr DN T cells constitutively transcribed perforin gene but failed to express granzyme A [27].
  • Antibodies to the thrombin receptor inhibited both thrombin and granzyme A-mediated neurite retraction [25].
  • Interestingly, production of granzyme A mRNA was strongly induced by 45 min after Con A stimulation [8].
  • Both CTLL contain a [3H]DFP-labeled protein that migrates with a molecular mass of 60 kDa under nonreducing conditions and with 30 kDa under reducing conditions and which can be inactivated by the TSP-1-specific inhibitor H-D-Pro-Phe-Arg-chloromethylketone [28].

Other interactions of Gzma

  • Apoptotic pathways are selectively activated by granzyme A and/or granzyme B in CTL-mediated target cell lysis [29].
  • While the self peptide was unable to induce serine esterase release from the CTL, it did induce secretion of IFN-gamma [30].
  • CD8 expression positively correlated with perforin and granzyme A, B, and C mRNA, and negatively correlated with IL-4 mRNA levels among these clones [31].
  • The Vla1 locus is located 3.5 cM distal to Ctla-3 and 7.8 cM distal to Htrla [32].
  • Both mutant receptors were able to prevent apoptosis, but only the mutant that activated STAT1 and STAT3 was able to support induction of granzyme A and L-selectin [33].

Analytical, diagnostic and therapeutic context of Gzma


  1. Genes encoding tumor necrosis factor alpha and granzyme A are expressed during development of autoimmune diabetes. Held, W., MacDonald, H.R., Weissman, I.L., Hess, M.W., Mueller, C. Proc. Natl. Acad. Sci. U.S.A. (1990) [Pubmed]
  2. Perforin and Fas act together in the induction of apoptosis, and both are critical in the clearance of lymphocytic choriomeningitis virus infection. Rode, M., Balkow, S., Sobek, V., Brehm, R., Martin, P., Kersten, A., Dumrese, T., Stehle, T., Müllbacher, A., Wallich, R., Simon, M.M. J. Virol. (2004) [Pubmed]
  3. Immunohistochemical analysis of perforin and granzyme A in inflammatory myopathies. Orimo, S., Koga, R., Goto, K., Nakamura, K., Arai, M., Tamaki, M., Sugita, H., Nonaka, I., Arahata, K. Neuromuscul. Disord. (1994) [Pubmed]
  4. Granzyme A is critical for recovery of mice from infection with the natural cytopathic viral pathogen, ectromelia. Müllbacher, A., Ebnet, K., Blanden, R.V., Hla, R.T., Stehle, T., Museteanu, C., Simon, M.M. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  5. Modulation of perforin, granzyme A, and granzyme B in murine natural killer (NK), IL2 stimulated NK, and lymphokine-activated killer cells by alcohol consumption. Spitzer, J.H., Meadows, G.G. Cell. Immunol. (1999) [Pubmed]
  6. A family of serine esterases in lytic granules of cytolytic T lymphocytes. Masson, D., Tschopp, J. Cell (1987) [Pubmed]
  7. Isolation and characterization of a serine esterase from cytolytic T cell granules. Young, J.D., Leong, L.G., Liu, C.C., Damiano, A., Wall, D.A., Cohn, Z.A. Cell (1986) [Pubmed]
  8. Induction by concanavalin A of specific mRNAs and cytolytic function in a CD8-positive T cell hybridoma. Gu, J.J., Harriss, J.V., Ozato, K., Gottlieb, P.D. J. Immunol. (1994) [Pubmed]
  9. Inhibition of bone resorption in vitro by serine-esterase inhibitors. Lerner, U.H., Gustafson, G.T. Biochim. Biophys. Acta (1988) [Pubmed]
  10. Residual cytotoxicity and granzyme K expression in granzyme A-deficient cytotoxic lymphocytes. Shresta, S., Goda, P., Wesselschmidt, R., Ley, T.J. J. Biol. Chem. (1997) [Pubmed]
  11. Concerted action of the FasL/Fas and perforin/granzyme A and B pathways is mandatory for the development of early viral hepatitis but not for recovery from viral infection. Balkow, S., Kersten, A., Tran, T.T., Stehle, T., Grosse, P., Museteanu, C., Utermöhlen, O., Pircher, H., von Weizsäcker, F., Wallich, R., Müllbacher, A., Simon, M.M. J. Virol. (2001) [Pubmed]
  12. The differential contribution of granzyme A and granzyme B in cytotoxic T lymphocyte-mediated apoptosis is determined by the quality of target cells. Pardo, J., Balkow, S., Anel, A., Simon, M.M. Eur. J. Immunol. (2002) [Pubmed]
  13. Granzyme A-deficient mice retain potent cell-mediated cytotoxicity. Ebnet, K., Hausmann, M., Lehmann-Grube, F., Müllbacher, A., Kopf, M., Lamers, M., Simon, M.M. EMBO J. (1995) [Pubmed]
  14. IL-9 induces expression of granzymes and high-affinity IgE receptor in murine T helper clones. Louahed, J., Kermouni, A., Van Snick, J., Renauld, J.C. J. Immunol. (1995) [Pubmed]
  15. Subcellular localization of perforin and serine esterase in lymphokine-activated killer cells and cytotoxic T cells by immunogold labeling. Ojcius, D.M., Zheng, L.M., Sphicas, E.C., Zychlinsky, A., Young, J.D. J. Immunol. (1991) [Pubmed]
  16. CTLA-1 and CTLA-3 serine esterase transcripts are detected mostly in cytotoxic T cells, but not only and not always. Brunet, J.F., Denizot, F., Suzan, M., Haas, W., Mencia-Huerta, J.M., Berke, G., Luciani, M.F., Golstein, P. J. Immunol. (1987) [Pubmed]
  17. Serine esterase in cytolytic T lymphocytes. Pasternack, M.S., Verret, C.R., Liu, M.A., Eisen, H.N. Nature (1986) [Pubmed]
  18. Induction of perforin and serine esterases in a murine cytotoxic T lymphocyte clone. Liu, C.C., Joag, S.V., Kwon, B.S., Young, J.D. J. Immunol. (1990) [Pubmed]
  19. Induction of target cell DNA release by the cytotoxic T lymphocyte granule protease granzyme A. Hayes, M.P., Berrebi, G.A., Henkart, P.A. J. Exp. Med. (1989) [Pubmed]
  20. Inhibition of CPP32-like proteases prevents granzyme B- and Fas-, but not granzyme A-based cytotoxicity exerted by CTL clones. Anel, A., Gamen, S., Alava, M.A., Schmitt-Verhulst, A.M., Piñeiro, A., Naval, J. J. Immunol. (1997) [Pubmed]
  21. Transfection of mouse cytotoxic T lymphocyte with an antisense granzyme A vector reduces lytic activity. Talento, A., Nguyen, M., Law, S., Wu, J.K., Poe, M., Blake, J.T., Patel, M., Wu, T.J., Manyak, C.L., Silberklang, M. J. Immunol. (1992) [Pubmed]
  22. The serine protease granzyme A does not induce platelet aggregation but inhibits responses triggered by thrombin. Suidan, H.S., Clemetson, K.J., Brown-Luedi, M., Niclou, S.P., Clemetson, J.M., Tschopp, J., Monard, D. Biochem. J. (1996) [Pubmed]
  23. Intestinal intraepithelial lymphocytes are activated and cytolytic but do not proliferate as well as other T cells in response to mitogenic signals. Sydora, B.C., Mixter, P.F., Holcombe, H.R., Eghtesady, P., Williams, K., Amaral, M.C., Nel, A., Kronenberg, M. J. Immunol. (1993) [Pubmed]
  24. Arrested natural killer cell development associated with transgene insertion into the Atf2 locus. Kim, S., Song, Y.J., Higuchi, D.A., Kang, H.P., Pratt, J.R., Yang, L., Hong, C.M., Poursine-Laurent, J., Iizuka, K., French, A.R., Sunwoo, J.B., Ishii, S., Reimold, A.M., Yokoyama, W.M. Blood (2006) [Pubmed]
  25. Granzyme A released upon stimulation of cytotoxic T lymphocytes activates the thrombin receptor on neuronal cells and astrocytes. Suidan, H.S., Bouvier, J., Schaerer, E., Stone, S.R., Monard, D., Tschopp, J. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  26. Biological activities of granzyme K are conserved in the mouse and account for residual Z-Lys-SBzl activity in granzyme A-deficient mice. Wilharm, E., Tschopp, J., Jenne, D.E. FEBS Lett. (1999) [Pubmed]
  27. Double-negative T cells from MRL-lpr/lpr mice mediate cytolytic activity when triggered through adhesion molecules and constitutively express perforin gene. Hammond, D.M., Nagarkatti, P.S., Goté, L.R., Seth, A., Hassuneh, M.R., Nagarkatti, M. J. Exp. Med. (1993) [Pubmed]
  28. The T cell-specific serine proteinase TSP-1 is associated with cytoplasmic granules of cytolytic T lymphocytes. Fruth, U., Prester, M., Golecki, J.R., Hengartner, H., Simon, H.G., Kramer, M.D., Simon, M.M. Eur. J. Immunol. (1987) [Pubmed]
  29. Apoptotic pathways are selectively activated by granzyme A and/or granzyme B in CTL-mediated target cell lysis. Pardo, J., Bosque, A., Brehm, R., Wallich, R., Naval, J., Müllbacher, A., Anel, A., Simon, M.M. J. Cell Biol. (2004) [Pubmed]
  30. Selective activation of Fas/Fas ligand-mediated cytotoxicity by a self peptide. Brossart, P., Bevan, M.J. J. Exp. Med. (1996) [Pubmed]
  31. Progressive differentiation and commitment of CD8+ T cells to a poorly cytolytic CD8low phenotype in the presence of IL-4. Kienzle, N., Olver, S., Buttigieg, K., Groves, P., Janas, M.L., Baz, A., Kelso, A. J. Immunol. (2005) [Pubmed]
  32. Genetic mapping of the integrin alpha 1 gene (Vla1) to mouse chromosome 13. Douville, P., Seldin, M.F., Carbonetto, S. Genomics (1992) [Pubmed]
  33. Distinct roles for STAT1, STAT3, and STAT5 in differentiation gene induction and apoptosis inhibition by interleukin-9. Demoulin, J.B., Van Roost, E., Stevens, M., Groner, B., Renauld, J.C. J. Biol. Chem. (1999) [Pubmed]
  34. Accelerated beta-cell destruction in adoptively transferred autoimmune diabetes correlates with an increased expression of the genes coding for TNF-alpha and granzyme A in the intra-islet infiltrates. Mueller, C., Held, W., Imboden, M.A., Carnaud, C. Diabetes (1995) [Pubmed]
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