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Gene Review

Gzmb  -  granzyme B (granzyme 2, cytotoxic T...

Rattus norvegicus

Synonyms: Fragmentin, Granzyme B, Natural killer cell protease 1, RNKP-1
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High impact information on Gzmb


Biological context of Gzmb


Anatomical context of Gzmb

  • From an RNK-16 lambda-gt11 library, we have isolated and sequenced a novel cDNA rat NK cell protease 1 (RNKP-1) that has characteristics unique to serine proteases [8].
  • The induction of RNKP-1 expression in the Con A-cultured spleen cells is accompanied by increases in both NK and lymphokine-activated killer lymphocyte activities [8].
  • RNKP-1 is also expressed in RNK-16 cells, but is not expressed in freshly isolated rat splenocytes, brain, lung, or lymph node tissues [8].
  • Comparison of hydropathic profiles and amino acid sequences of other proteases indicate that RNKP-1 is distinct and belongs to the subfamily of serine proteases of bone marrow origin [8].
  • RESULTS: Paraventricular nucleus administration of beta-EP increased the mRNA and protein expression of granzyme B and mRNA expression of IFN-gamma in pair-fed animals [9].

Associations of Gzmb with chemical compounds

  • Our data further demonstrated how chronic ethanol suppressed NK cell activity by directly disrupting the circadian rhythms of granzyme B, perforin, and IFN-gamma [6].
  • Other serine proteases that were structurally related and have substantial homology with RNKP-1 at the amino acid level showed neither growth inhibitory properties nor affected the morphology of the tumor target cells we used [7].
  • Granzyme B prefers substrates containing P4 to P1 amino acids Ile/Val, Glu/Met/Gln, Pro/Xaa, and aspartic acid N-terminal to the proteolytic cleavage [5].
  • These data suggest that NE and beta-adrenergic agonists may inhibit NK cell cytolytic activity by regulating the production of perforin, granzyme B, and IFN-gamma in splenocytes [10].
  • NE, the beta-adrenergic agonist ISO, and the beta 2-selective-agonist MP all inhibited the protein and mRNA levels of perforin, granzyme B and mRNA levels of IFN-gamma [10].

Physical interactions of Gzmb

  • The results imply that granzyme B (32 kDa) may be transported from the cytoplasm to the nucleus through passive diffusion and accumulate by binding to nuclear/nucleolar factors in a cytosolic factor-mediated process [11].

Enzymatic interactions of Gzmb

  • The caspase substrate poly(ADP)-ribose polymerase is cleaved by granzyme B in a cell-free assay at two sites that resemble the granzyme B specificity determined by the combinatorial methods [12].

Other interactions of Gzmb


Analytical, diagnostic and therapeutic context of Gzmb


  1. Mitochondria-dependent and -independent regulation of Granzyme B-induced apoptosis. MacDonald, G., Shi, L., Vande Velde, C., Lieberman, J., Greenberg, A.H. J. Exp. Med. (1999) [Pubmed]
  2. Granzyme B (GraB) autonomously crosses the cell membrane and perforin initiates apoptosis and GraB nuclear localization. Shi, L., Mai, S., Israels, S., Browne, K., Trapani, J.A., Greenberg, A.H. J. Exp. Med. (1997) [Pubmed]
  3. Synergistic roles of granzymes A and B in mediating target cell death by rat basophilic leukemia mast cell tumors also expressing cytolysin/perforin. Nakajima, H., Park, H.L., Henkart, P.A. J. Exp. Med. (1995) [Pubmed]
  4. Purification of three cytotoxic lymphocyte granule serine proteases that induce apoptosis through distinct substrate and target cell interactions. Shi, L., Kam, C.M., Powers, J.C., Aebersold, R., Greenberg, A.H. J. Exp. Med. (1992) [Pubmed]
  5. Characterization of structural determinants of granzyme B reveals potent mediators of extended substrate specificity. Ruggles, S.W., Fletterick, R.J., Craik, C.S. J. Biol. Chem. (2004) [Pubmed]
  6. Circadian rhythms of granzyme B, perforin, IFN-gamma, and NK cell cytolytic activity in the spleen: effects of chronic ethanol. Arjona, A., Boyadjieva, N., Sarkar, D.K. J. Immunol. (2004) [Pubmed]
  7. Purification of a factor from the granules of a rat natural killer cell line (RNK) that reduces tumor cell growth and changes tumor morphology. Molecular identity with a granule serine protease (RNKP-1). Sayers, T.J., Wiltrout, T.A., Sowder, R., Munger, W.L., Smyth, M.J., Henderson, L.E. J. Immunol. (1992) [Pubmed]
  8. RNKP-1, a novel natural killer-associated serine protease gene cloned from RNK-16 cytotoxic lymphocytes. Zunino, S.J., Bleackley, R.C., Martinez, J., Hudig, D. J. Immunol. (1990) [Pubmed]
  9. Modulation of hypothalamic beta-endorphin-regulated expression of natural killer cell cytolytic activity regulatory factors by ethanol in male Fischer-344 rats. Dokur, M., Boyadjieva, N.I., Advis, J.P., Sarkar, D.K. Alcohol. Clin. Exp. Res. (2004) [Pubmed]
  10. Catecholaminergic control of NK cell cytolytic activity regulatory factors in the spleen. Dokur, M., Boyadjieva, N., Sarkar, D.K. J. Neuroimmunol. (2004) [Pubmed]
  11. Nuclear transport of granzyme B (fragmentin-2). Dependence of perforin in vivo and cytosolic factors in vitro. Jans, D.A., Jans, P., Briggs, L.J., Sutton, V., Trapani, J.A. J. Biol. Chem. (1996) [Pubmed]
  12. Definition and redesign of the extended substrate specificity of granzyme B. Harris, J.L., Peterson, E.P., Hudig, D., Thornberry, N.A., Craik, C.S. J. Biol. Chem. (1998) [Pubmed]
  13. CD8+ cells are not necessary for allograft rejection or the induction of apoptosis in an experimental model of small intestinal transplantation. Krams, S.M., Hayashi, M., Fox, C.K., Villanueva, J.C., Whitmer, K.J., Burns, W., Esquivel, C.O., Martinez, O.M. J. Immunol. (1998) [Pubmed]
  14. Rapamycin treatment depresses intragraft expression of KC/MIP-2, granzyme B, and IFN-gamma in rat recipients of cardiac allografts. Wieder, K.J., Hancock, W.W., Schmidbauer, G., Corpier, C.L., Wieder, I., Kobzik, L., Strom, T.B., Kupiec-Weglinski, J.W. J. Immunol. (1993) [Pubmed]
  15. Steroidogenesis and apoptosis in the mammalian ovary. Amsterdam, A., Keren-Tal, I., Aharoni, D., Dantes, A., Land-Bracha, A., Rimon, E., Sasson, R., Hirsh, L. Steroids (2003) [Pubmed]
  16. Reduction of perforin, granzyme B, and cytokine interferon gamma by ethanol in male Fischer 344 rats. Dokur, M., Boyadjieva, N.I., Sarkar, D.K. Alcohol. Clin. Exp. Res. (2003) [Pubmed]
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