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Literature summary extracted from

  • Lee, P.; Park, B.; Chi, S.; Bae, K.; Kim, S.; Cho, S.; Kang, S.; Kim, J.; Park, S.
    Histone H4 is cleaved by granzyme A during staurosporine-induced cell death in B-lymphoid Raji cells (2016), BMB Rep., 49, 560-565 .
    View publication on PubMedView publication on EuropePMC

Cloned(Commentary)

EC Number Cloned (Comment) Organism
3.4.21.78 recombinant expression of His-tagged enzyme in Escherichia coli Homo sapiens

Protein Variants

EC Number Protein Variants Comment Organism
3.4.21.78 additional information GzmA silencing by siRNA interference Homo sapiens

Inhibitors

EC Number Inhibitors Comment Organism Structure
3.4.21.78 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
3.4.21.78 nafamostat mesylate complete inhibition of histone H4 cleavage Homo sapiens

Localization

EC Number Localization Comment Organism GeneOntology No. Textmining
3.4.21.78 endoplasmic reticulum
-
 Homo sapiens 5783
-
3.4.21.78 additional information GzmA is mobilized in the nucleus Homo sapiens
-
-
3.4.21.78 nucleus
-
 Homo sapiens 5634
-

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
3.4.21.78 histone H4 + H2O Homo sapiens histone H4 is a substrate for GzmA in staurosporine-induced cells ?
-
 ?
3.4.21.78 NADH dehydrogenase (ubiquinone) Fe-S protein 3 + H2O Homo sapiens
-
 ?
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
3.4.21.78 Homo sapiens P12544
-
-

Purification (Commentary)

EC Number Purification (Comment) Organism
3.4.21.78 recombinant His-tagged enzyme from Escherichia coli by nickel affinity chromatography Homo sapiens

Source Tissue

EC Number Source Tissue Comment Organism Textmining
3.4.21.78 B-lymphocyte cell line
-
 Homo sapiens
-
3.4.21.78 K-562 cell
-
 Homo sapiens
-
3.4.21.78 RAJI cell
-
 Homo sapiens
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
3.4.21.78 histone H4 + H2O histone H4 is a substrate for GzmA in staurosporine-induced cells Homo sapiens ?
-
 ?
3.4.21.78 histone H4 + H2O the histone H4 N-terminal tail is cleaved by GzmA, the enzyme cleaves only deacetylated histone H4 Homo sapiens ?
-
 ?
3.4.21.78 NADH dehydrogenase (ubiquinone) Fe-S protein 3 + H2O
-
 Homo sapiens ?
-
 ?

Synonyms

EC Number Synonyms Comment Organism
3.4.21.78 Gzma
-
 Homo sapiens

Temperature Optimum [°C]

EC Number Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
3.4.21.78 37
-
 assay at Homo sapiens

pH Optimum

EC Number pH Optimum Minimum pH Optimum Maximum Comment Organism
3.4.21.78 7.5
-
 assay at Homo sapiens

General Information

EC Number General Information Comment Organism
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 Homo sapiens