EC Number   |
General Information |
Reference |
|---|
   3.4.21.78 | physiological function |
high functional activity of GzmA in the innate cell-mediated cytotoxicity |
771416 |
| 3.4.21.78 | physiological function |
histone H4 is cleaved by granzyme A during staurosporine-induced cell death in B-lymphoid Raji cells. A fast-migrating histone H4 fragment is detected in cells undergoing staurosporine-induced cell death. Treatment with caspase inhibitors (inhibitors of caspase-6 (Z-VEID-FMK) and caspase-9 (Z-LEHD-FMK)) increases both cell death and histone H4 cleavage. The enzyme cleaves the N-terminal tail pf H4. The cleavage of the histone H4 tail by GzmA contributes to the disintegration of chromosomes during the cell death process. The SET complex is normally located in the endoplasmic reticulum, but it translocates to the nucleus in response to reactive oxygen species produced by GzmA-mediated cleavage of NADH dehydrogenase (ubiquinone) Fe-S protein 3. GzmA is mobilized in the nucleus where many of its known substrates reside. In the nucleus, GzmA digests three components of the SET complex: SET, high-mobility group protein B2, and apurinic/apyrimidinic endonuclease. SET is an inhibitor of the SET complex endonuclease NM23-H1. GzmA degrades the linker histone H1 and removes the tails from core histones H2 and H3, opening up the chromatin and making it accessible to nucleases |
753077 |
| 3.4.21.78 | physiological function |
in filarial infection with Litomosoides sigmodontis, worm loads are significantly reduced in gzmA/gzmB and in gzmB knockout mice during the whole course of infection, but enhanced only early in gzmA knockout compared with wild-type mice. GzmA/gzmB deficiency is associated with a defense-promoting Th2 cytokine and Ab shift, enhanced early inflammatory gene expression, and a trend of reduced alternatively activated macrophage induction, whereas gzmA deficiency is linked with reduced inflammation and a trend toward increased alternatively activated macrophages |
717939 |
| 3.4.21.78 | physiological function |
interleukin-17 induced secretion of the cytokines interleukin-6, interleukin-8 and interleukin-23, whereas GzmA treatment alone does not induce secretion of inflammatory mediators. The combination of GzmA and interleukin-17 significantly increases the release of the proinflammatory chemokines CXCL 1, CXCL 12, and CCL 4 compared to interleukin-17 stimulation alone, but does not alter the levels of interleukin-17-induced cytokines interleukin-6, interleukin-8 and interleukin-23. GzmA neither promotes proliferation nor affects interleukin-17-induced keratinocyte differentiation status as measured by gene expression of MKI67, IVL, KRT16 or KRT10 |
753512 |
| 3.4.21.78 | physiological function |
recombinant GrA promotes release of interleukin IL-8 from A-549 cells, without involvement of protease-activated receptor-1. Release is inhibited by taxol |
708274 |
| 3.4.21.78 | physiological function |
the enzyme is an extracellular modulator of inflammation. The presence and role of extracellular granzyme A (GrA) in several inflammatory diseases and the potential molecular mechanisms of extracellular GrA in augmenting inflammation is summarized |
771430 |
| 3.4.21.78 | physiological function |
the human enzyme shows only slight cytotoxic potential in P815 mastocytoma target cells with streptolysin O |
732177 |
| 3.4.21.78 | physiological function |
the murine enzyme shows a high cytotoxic potential in P815 mastocytoma target cells with streptolysin O |
732177 |
| 3.4.21.78 | physiological function |
wild-type and granzyme A-deficient mice eliminate the mouse pathogen Brucella microti from liver and spleen within 2 or 3 weeks, whereas the bacteria persist in mice lacking perforin or granzyme B as well as in mice depleted of Tc cells. Only gzmA-/- mice exhibit increased survival, which correlated with reduced proinflammatory cytokines, due to depletion of natural killer cells. Infection-related pathology, but not bacterial clearance, appears to require the enzyme |
-, 731617 |
