EC Number   |
General Information |
Reference  |
|---|
   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 |
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 |
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 |
| 3.4.21.78 | evolution |
the enzyme belongs to the granzyme serine protease family, key effector molecules expressed by cytotoxic lymphocytes. Peptide substrate specificity profile of mouse and human granzyme A, overview |
732177 |
| 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 | malfunction |
pneumonia is induced in wild-type and GzmA-deficient (GzmA-/-) mice by intranasal inoculation of Streptococcus pneumoniae. In separate experiments, wild-type and GzmA-/- mice are treated with natural killer (NK) cell depleting antibodies. Upon infection, GzmA-/- mice show a better survival and lower bacterial counts in bronchoalveolar lavage fluid (BALF) and distant body sites compared to the wild-type mice. Although NK cells show strong GzmA expression, NK cell depletion does not influence bacterial loads in either wild-type or GzmA-/- mice. GzmA deficiency has little impact on lung pathology during late stage pneumococcal pneumonia |
-, 752445 |
| 3.4.21.78 | physiological function |
granzyme A contributes to the early inflammatory response in the lung. Granzyme A (GzmA) impairs host defense during Streptococcus pneumoniae pneumonia, role of GzmA on the host response during pneumococcal pneumonia, overview |
752445 |
| 3.4.21.78 | physiological function |
granzyme A contributes to the early inflammatory response in the lung. Granzyme A (GzmA) plays an unfavorable role in host defense during pneumococcal pneumonia by a mechanism that does not depend on natural killer cells. GzmA enhances bacterial dissemination and mortality in pneumococcal pneumonia |
-, 752445 |
| 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 |
