BRENDA - Enzyme Database
show all sequences of 3.4.21.B59

Granzyme H induces cell death primarily via a Bcl-2-sensitive mitochondrial cell death pathway that does not require direct Bid activation

Ewen, C.L.; Kane, K.P.; Bleackley, R.C.; Mol. Immunol. 54, 309-318 (2013)

Data extracted from this reference:

Cloned(Commentary)
Commentary
Organism
recombinant expression of enzymatically active enzyme in RBL-2H3 granules
Homo sapiens
Engineering
Amino acid exchange
Commentary
Organism
S202A
inactive mutant
Homo sapiens
Localization
Localization
Commentary
Organism
GeneOntology No.
Textmining
extracellular
-
Homo sapiens
-
-
mitochondrion
-
Homo sapiens
5739
-
Metals/Ions
Metals/Ions
Commentary
Organism
Structure
Mg2+
required
Homo sapiens
Natural Substrates/ Products (Substrates)
Natural Substrates
Organism
Commentary (Nat. Sub.)
Natural Products
Commentary (Nat. Pro.)
Organism (Nat. Pro.)
Reversibility
DFF45 protein + H2O
Homo sapiens
-
?
-
-
?
Organism
Organism
Primary Accession No. (UniProt)
Commentary
Textmining
Homo sapiens
P20718
-
-
Posttranslational Modification
Posttranslational Modification
Commentary
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)
Commentary
Organism
isolation of enzymatically active recombinant wild-type enzyme and of inactive mutant S202A from RBL-2H3 granules
Homo sapiens
Source Tissue
Source Tissue
Commentary
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
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
DFF45 protein + H2O
-
732517
Homo sapiens
?
-
-
-
?
DFF45 protein + H2O
GrH directly processes DFF45/ICAD to cleavage products of 30 kDa and 15 kDa
732517
Homo sapiens
?
-
-
-
?
additional information
granzyme H does not efficiently process Bid
732517
Homo sapiens
?
-
-
-
-
Temperature Optimum [°C]
Temperature Optimum [°C]
Temperature Optimum Maximum [°C]
Commentary
Organism
37
-
assay at
Homo sapiens
pH Optimum
pH Optimum Minimum
pH Optimum Maximum
Commentary
Organism
7.5
-
assay at
Homo sapiens
Cloned(Commentary) (protein specific)
Commentary
Organism
recombinant expression of enzymatically active enzyme in RBL-2H3 granules
Homo sapiens
Engineering (protein specific)
Amino acid exchange
Commentary
Organism
S202A
inactive mutant
Homo sapiens
Localization (protein specific)
Localization
Commentary
Organism
GeneOntology No.
Textmining
extracellular
-
Homo sapiens
-
-
mitochondrion
-
Homo sapiens
5739
-
Metals/Ions (protein specific)
Metals/Ions
Commentary
Organism
Structure
Mg2+
required
Homo sapiens
Natural Substrates/ Products (Substrates) (protein specific)
Natural Substrates
Organism
Commentary (Nat. Sub.)
Natural Products
Commentary (Nat. Pro.)
Organism (Nat. Pro.)
Reversibility
DFF45 protein + H2O
Homo sapiens
-
?
-
-
?
Posttranslational Modification (protein specific)
Posttranslational Modification
Commentary
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) (protein specific)
Commentary
Organism
isolation of enzymatically active recombinant wild-type enzyme and of inactive mutant S202A from RBL-2H3 granules
Homo sapiens
Source Tissue (protein specific)
Source Tissue
Commentary
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) (protein specific)
Substrates
Commentary Substrates
Literature (Substrates)
Organism
Products
Commentary (Products)
Literature (Products)
Organism (Products)
Reversibility
DFF45 protein + H2O
-
732517
Homo sapiens
?
-
-
-
?
DFF45 protein + H2O
GrH directly processes DFF45/ICAD to cleavage products of 30 kDa and 15 kDa
732517
Homo sapiens
?
-
-
-
?
additional information
granzyme H does not efficiently process Bid
732517
Homo sapiens
?
-
-
-
-
Temperature Optimum [°C] (protein specific)
Temperature Optimum [°C]
Temperature Optimum Maximum [°C]
Commentary
Organism
37
-
assay at
Homo sapiens
pH Optimum (protein specific)
pH Optimum Minimum
pH Optimum Maximum
Commentary
Organism
7.5
-
assay at
Homo sapiens
General Information
General Information
Commentary
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
General Information (protein specific)
General Information
Commentary
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
Other publictions for EC 3.4.21.B59
No.
1st author
Pub Med
title
organims
journal
volume
pages
year
Activating Compound
Application
Cloned(Commentary)
Crystallization (Commentary)
Engineering
General Stability
Inhibitors
KM Value [mM]
Localization
Metals/Ions
Molecular Weight [Da]
Natural Substrates/ Products (Substrates)
Organic Solvent Stability
Organism
Oxidation Stability
Posttranslational Modification
Purification (Commentary)
Reaction
Renatured (Commentary)
Source Tissue
Specific Activity [micromol/min/mg]
Storage Stability
Substrates and Products (Substrate)
Subunits
Temperature Optimum [°C]
Temperature Range [°C]
Temperature Stability [°C]
Turnover Number [1/s]
pH Optimum
pH Range
pH Stability
Cofactor
Ki Value [mM]
pI Value
IC50 Value
Activating Compound (protein specific)
Application (protein specific)
Cloned(Commentary) (protein specific)
Cofactor (protein specific)
Crystallization (Commentary) (protein specific)
Engineering (protein specific)
General Stability (protein specific)
IC50 Value (protein specific)
Inhibitors (protein specific)
Ki Value [mM] (protein specific)
KM Value [mM] (protein specific)
Localization (protein specific)
Metals/Ions (protein specific)
Molecular Weight [Da] (protein specific)
Natural Substrates/ Products (Substrates) (protein specific)
Organic Solvent Stability (protein specific)
Oxidation Stability (protein specific)
Posttranslational Modification (protein specific)
Purification (Commentary) (protein specific)
Renatured (Commentary) (protein specific)
Source Tissue (protein specific)
Specific Activity [micromol/min/mg] (protein specific)
Storage Stability (protein specific)
Substrates and Products (Substrate) (protein specific)
Subunits (protein specific)
Temperature Optimum [°C] (protein specific)
Temperature Range [°C] (protein specific)
Temperature Stability [°C] (protein specific)
Turnover Number [1/s] (protein specific)
pH Optimum (protein specific)
pH Range (protein specific)
pH Stability (protein specific)
pI Value (protein specific)
Expression
General Information
General Information (protein specific)
Expression (protein specific)
KCat/KM [mM/s]
KCat/KM [mM/s] (protein specific)
732517
Ewen
Granzyme H induces cell death ...
Homo sapiens
Mol. Immunol.
54
309-318
2013
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