Cloned (Comment) | Organism |
---|---|
recombinant expression of His-tagged enzyme in Escherichia coli | Homo sapiens |
Protein Variants | Comment | Organism |
---|---|---|
additional information | GzmA silencing by siRNA interference | Homo sapiens |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
additional information | histone H4 cleavage is blocked by the GzmA inhibitor nafamostat mesylate and by GzmA knockdown using siRNA. Recombinant histone H4 is treated with trichostatin A, an inhibitor of histone deacetylation, revealing that only untreated histones are digested by GzmA | Homo sapiens | |
nafamostat mesylate | complete inhibition of histone H4 cleavage | Homo sapiens |
Localization | Comment | Organism | GeneOntology No. | Textmining |
---|---|---|---|---|
endoplasmic reticulum | - |
Homo sapiens | 5783 | - |
additional information | GzmA is mobilized in the nucleus | Homo sapiens | - |
- |
nucleus | - |
Homo sapiens | 5634 | - |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
histone H4 + H2O | Homo sapiens | histone H4 is a substrate for GzmA in staurosporine-induced cells | ? | - |
? | |
NADH dehydrogenase (ubiquinone) Fe-S protein 3 + H2O | Homo sapiens | - |
? | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | P12544 | - |
- |
Purification (Comment) | Organism |
---|---|
recombinant His-tagged enzyme from Escherichia coli by nickel affinity chromatography | Homo sapiens |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
B-lymphocyte cell line | - |
Homo sapiens | - |
K-562 cell | - |
Homo sapiens | - |
RAJI cell | - |
Homo sapiens | - |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
histone H4 + H2O | histone H4 is a substrate for GzmA in staurosporine-induced cells | Homo sapiens | ? | - |
? | |
histone H4 + H2O | the histone H4 N-terminal tail is cleaved by GzmA, the enzyme cleaves only deacetylated histone H4 | Homo sapiens | ? | - |
? | |
NADH dehydrogenase (ubiquinone) Fe-S protein 3 + H2O | - |
Homo sapiens | ? | - |
? |
Synonyms | Comment | Organism |
---|---|---|
Gzma | - |
Homo sapiens |
Temperature Optimum [°C] | Temperature Optimum Maximum [°C] | Comment | Organism |
---|---|---|---|
37 | - |
assay at | Homo sapiens |
pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
---|---|---|---|
7.5 | - |
assay at | Homo sapiens |
General Information | Comment | Organism |
---|---|---|
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 | Homo sapiens |