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Literature summary for 3.4.21.B59 extracted from

  • Ewen, C.L.; Kane, K.P.; Bleackley, R.C.
    Granzyme H induces cell death primarily via a Bcl-2-sensitive mitochondrial cell death pathway that does not require direct Bid activation (2013), Mol. Immunol., 54, 309-318.
    View publication on PubMed

Cloned(Commentary)

Cloned (Comment) Organism
recombinant expression of enzymatically active enzyme in RBL-2H3 granules Homo sapiens

Protein Variants

Protein Variants Comment Organism
S202A inactive mutant Homo sapiens

Localization

Localization Comment Organism GeneOntology No. Textmining
extracellular
-
Homo sapiens
-
-
mitochondrion
-
Homo sapiens 5739
-

Metals/Ions

Metals/Ions Comment Organism Structure
Mg2+ required Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
DFF45 protein + H2O Homo sapiens
-
?
-
?

Organism

Organism UniProt Comment Textmining
Homo sapiens P20718
-
-

Posttranslational Modification

Posttranslational Modification Comment Organism
proteolytic modification granzyme H is a serine protease, initially produced as a zymogen that requires the activity of granule-resident cathepsin C to become active. Cell death in cytotoxic potential of the enzyme with replication-deficient adenovirus 5 in target cells, i.e. K562 cells, Jurkat cells, and EBV-transformed B cell line RPMI-8866,the enzyme is less effective against tumor cells. Enzyme GrH induces cytochrome C loss from the mitochondrial intermembrane space. Similar to cytochrome C, SMAC/DIABLO is also observed to undergo translocation from the mitochondria to the cytosol after treatment with the enzyme Homo sapiens

Purification (Commentary)

Purification (Comment) Organism
isolation of enzymatically active recombinant wild-type enzyme and of inactive mutant S202A from RBL-2H3 granules Homo sapiens

Source Tissue

Source Tissue Comment Organism Textmining
JURKAT cell
-
Homo sapiens
-
MCF-7 cell
-
Homo sapiens
-
natural killer cell
-
Homo sapiens
-
serum
-
Homo sapiens
-
T-lymphocyte
-
Homo sapiens
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
DFF45 protein + H2O
-
Homo sapiens ?
-
?
DFF45 protein + H2O GrH directly processes DFF45/ICAD to cleavage products of 30 kDa and 15 kDa Homo sapiens ?
-
?
additional information granzyme H does not efficiently process Bid Homo sapiens ?
-
?

Synonyms

Synonyms Comment Organism
Granzyme H
-
Homo sapiens
GrH
-
Homo sapiens

Temperature Optimum [°C]

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

pH Optimum

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

General Information

General Information Comment Organism
additional information Bid is not required for enzyme-mediated cell death Homo sapiens
physiological function the enzyme induces cell death primarily via a Bcl-2-sensitive mitochondrial cell death pathway that does not require direct Bid activation, overview. Neither the apoptosome nor caspase-3 is essential to the induction of GrH-mediated cell death. The enzyme might have pro-apoptotic activity that might be distinct from that of granzyme B and FasL, which can be relevant when Fas/FasL or granzyme B activity or death pathways are impaired. Direct processing of DFF45 by the enzyme may be leading to DNA damage. The enzyme inhibits caspase-3 activation Homo sapiens