Information on EC 3.4.21.79 - Granzyme B

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The expected taxonomic range for this enzyme is: Eutheria

EC NUMBER
COMMENTARY
3.4.21.79
-
RECOMMENDED NAME
GeneOntology No.
Granzyme B
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
Preferential cleavage: -Asp-/- >> -Asn-/- > -Met-/-, -Ser-/-
show the reaction diagram
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of peptide bond
-
-
-
-
SYNONYMS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
C11
-
-
-
-
CCP1
-
-
-
-
CCPII
-
-
-
-
CTLA1
-
-
-
-
CTSGL1
-
-
-
-
Cytotoxic cell proteinase-1
-
-
-
-
Granzyme G
-
-
-
-
Granzyme H
-
-
-
-
HLp
-
-
-
-
Human lymphocyte protein
-
-
-
-
Lymphocyte protease
-
-
-
-
Proteinase, CCP1
-
-
-
-
SECT
-
-
-
-
T-cell serine protease 1-3E
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
143180-74-9
-
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
encoded by RAH allele
-
-
Manually annotated by BRENDA team
expression in Pichia pastoris
-
-
Manually annotated by BRENDA team
HIV-positive patients and healthy controls
-
-
Manually annotated by BRENDA team
human, YT cells, autonomously proliferating NK line, devoid of granzyme A and K
-
-
Manually annotated by BRENDA team
patients with amyotrophic lateral sclerosis
-
-
Manually annotated by BRENDA team
patients with systemic lupus erythematosus
-
-
Manually annotated by BRENDA team
recombinant expression
-
-
Manually annotated by BRENDA team
129/SvJ mice
-
-
Manually annotated by BRENDA team
B6 background
-
-
Manually annotated by BRENDA team
C57 and Balb/C mice
-
-
Manually annotated by BRENDA team
homozygous deficiency in enzyme
-
-
Manually annotated by BRENDA team
infected with Sendai virus
-
-
Manually annotated by BRENDA team
NOD/Lt, NOD/lpr, NOD.TNFR-/- and C57BL/mice, or strain 129(H-2b) backcrossed onto BL/6 for a minimum of 10 generations
-
-
Manually annotated by BRENDA team
Mus musculus 129/SvJ
129/SvJ mice
-
-
Manually annotated by BRENDA team
Mus musculus B6
B6 background
-
-
Manually annotated by BRENDA team
rat, strain F344
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
-
inhibition or downregulation of GrB suppresses bladder cancer cell invasion in vitro
malfunction
-
knockout GzmB-/- mice which have a small deletion in the granzyme B gene express granzyme C earlier and more abundantly in lymphocytes on a per-cell basis compared to wild-type, suggesting that the deleted 350-bp region in the granzyme B gene is important for the regulation of both granzymes B and granzyme C. Intraepithelial lymphocytes in GzmB-/- knockout mice likewise express granzyme C
physiological function
-
Granzyme B produced by human plasmacytoid dendritic cells suppresses T-cell proliferation in a GrB-dependent, perforin-independent manner
physiological function
-
granzyme B recoverey is closely correlated with clathriin-dependent endocytosis in NK-92 cells stimulated by target cells (primary porcine endothelial cells)
physiological function
-
GrB plays an important role in inflammatory diseases and cancer. Infiltrating immune cells during chronic inflammation results in elevated levels of GrB to diseased tissue and induces apoptosis in damaged and inflamed areas. Extracellular concentrations of GrB in bodily fluids are elevated in various diseases
physiological function
-
GrB, via extracellular matrix degradation, contributes to the establishment of the urothelial carcinoma invasive phenotype
physiological function
-
gzmB-induced cell death is accompanied by a caspase-dependent pathway of extra-mitochondrial reactive oxygen species production, through activation of NADPH oxidase
physiological function
-
in patients with lupus erythematosus, a correlation between GrB+ lymphocyte and the presence of discoid lupus erythematosus form is found, but in dermatomyositis, GrB is poorly expressed
physiological function
-
increased T cell granzyme b production may contribute to Bronchiolitis obliterans syndrome pathogenesis and is not curtailed by current immunosuppressants
physiological function
-
it is investigated how human perforin enhances GzmB uptake in the cell: perforin activates clathrin- and Dyn-dependent endocytosis to remove perforin from the plasma membrane and enhance GzmB uptake. Both perforin and GzmB are endocytosed into giant endosomal antigen-1 endosomes that form after PFN treatment. When endocytosis is inhibited, sublytic perforin or strptolysin-O becomes lytic, causing necrosis. Consequently, inhibiting clathrin or Dyn pathways shifts the balance of target cell death by GzmB and perforin from apoptosis to necrosis
physiological function
-
TCR/CD28 mediated activation of the PI3K-mTOR pathway is important for granyzme B expression but not proliferation in regulatory T cells
physiological function
-
the effect of T-cell activation on neural progenitor cell (NPC) functions: NPC proliferation and neuronal differentiation are impaired by granzyme B released by the T-cells. GrB mediate its effects by the activation of a Gi-protein-coupled receptor leading to decreased intracellular levels of cAMP and subsequent expression of the voltage-dependent potassium channel, Kv1.3. Blocking channel activity with margatoxin or blocking its expression reverses the inhibitory effects of GrB on neural progenitor cells
physiological function
-
antisense morpholino oligonucleotide knock-down leads to arrest of early development at the 2- to 4-cell stages. Only 11.6% of treated embryos overcome 2-cell arrest and develop into 4-cell stage embryos. Embryos exhibited decreased zygotic gene transcription
physiological function
-
granzyme B-deficient mice, and to a lesser extent perforin-deficient mice, exhibit a significant increase in the number of Ag-specific CD8+ T cells in the lungs and draining lymph nodes of virally infected animals. Viral titers in granzyme B-deficient mice are similar to wild-type mice and significantly less than perforin-deficient mice. Regulatory T cells from wild-type mice express high levels of granzyme B in response to infection, and depletion of regulatory T cells from these mice results in an increase in the number of Ag-specific CD8+ T cells, similar to that observed in granzyme B-deficient mice. Granzyme B-deficient regulatory T cells display defective suppression of CD8+ T cell proliferation in vitro
physiological function
-
granzyme B-mediated processing of IL-1alpha potently enhances the biological activity. Granzyme B does not directly influence inflammatory cytokine production by HeLa or HUVEC cells
physiological function
-
GrB is a potent IL-18 converting enzyme. GrB secreted by CTLs and/or NK cells may initiate IL-18 release from target cells, leading to the development of inflammation
physiological function
-
human neurons are selectively susceptible to granzyme B isolated from cytotoxic T cell granules. In vitro, purified human GrB induces neuronal death to the same extent as the whole activated T cell population. Following internalization through various parts of neurons, GrB accumulates in the neuronal soma. Within the cell body, GrB diffuses out of endosomes possibly through a perforin-independent mechanism and induces subsequent activation of caspases and cleavage of a-tubulin. Inhibition of caspase-3, a substrate for GrB, significantly reduces GrB-mediated neurotoxicity. Treatment of neurons with mannose-6-phosphate prevents GrB entry and inhibits GrB-mediated neuronal death
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
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
2-aminobenzoyl-IEPDSSMEK-dnp + H2O
?
show the reaction diagram
-
-
-
?
2-aminobenzoyl-IEPDSSMESK-dinitrophenyl + H2O
?
show the reaction diagram
-
susbtrate is specific for human GrB
-
-
?
2-aminobenzoyl-IEPDSSMESK-dnp + H2O
?
show the reaction diagram
-
-
-
?
2-aminobenzoyl-Val-Val-Ala-Asp-Ser-Ser-Met-Glu-Lys-dnp + H2O
?
show the reaction diagram
-
-
-
?
2-aminobenzoyl-Val-Val-Ala-Glu-Ser-Ser-Met-Glu-Lys-dnp + H2O
?
show the reaction diagram
-
-
-
?
2-aminobenzoyl-VVADSSMASK-dnp + H2O
?
show the reaction diagram
-
-
-
?
2-aminobenzoyl-VVADSSMESK-dnp + H2O
?
show the reaction diagram
-
-
-
?
2-aminobenzoyl-VVAESSMESK-dnp + H2O
?
show the reaction diagram
-
-
-
?
28 kDa heat- and acid-stable phosphoprotein + H2O
?
show the reaction diagram
-
-
-
-
?
28-kDa heat- and acid-stable phosphoprotein + H2O
?
show the reaction diagram
-
-
-
-
?
3110082I17Rik protein + H2O
?
show the reaction diagram
-
-
-
-
?
40 S ribosomal protein S25 + H2O
?
show the reaction diagram
-
-
-
-
?
40 S ribosomal protein S4 + H2O
?
show the reaction diagram
-
X isoform
-
-
?
60 S ribosomal protein L10 + H2O
?
show the reaction diagram
-
-
-
-
?
60 S ribosomal protein L3 + H2O
?
show the reaction diagram
-
-
-
-
?
60 S ribosomal protein L5 + H2O
?
show the reaction diagram
-
-
-
-
?
Abz-IEPDSSMESK-2,4-dinitrophenyl + H2O
?
show the reaction diagram
-
-
-
-
?
Ac-IEPD-p-nitroanilide + H2O
Ac-IEPD + p-nitroaniline
show the reaction diagram
-
-
-
-
-
Ac-IEPD-p-nitroanilide + H2O
Ac-IEPD + p-nitroaniline
show the reaction diagram
-
-
-
-
?
Ac-IEPD-p-nitroanilide + H2O
Ac-IEPD + p-nitroaniline
show the reaction diagram
Q2A6L4
-
-
-
-
AcD3-KSKGVPVISVKTSGSKER + H2O
?
show the reaction diagram
-
-
-
-
?
Ace-Ile-Glu-Pro-Asp-p-nitroanilide + H2O
Ace-Ile-Glu-Pro-Asp + p-nitroaniline
show the reaction diagram
-
-
-
-
?
acetyl-DEVD-7-amido-4-methylcoumarin + H2O
?
show the reaction diagram
-
efficient cleavage by GzmB after K562 cells are exposed to sublytic perforin or streptolysin O. GzmH shows only baseline readings
-
-
?
acetyl-IAPD-7-amino-4-methylcoumarin + H2O
acetyl-IAPD + 7-amino-4-methylcoumarin
show the reaction diagram
P18291
-
-
-
?
acetyl-IEFD-7-amino-4-methylcoumarin + H2O
acetyl-IEFD + 7-amino-4-methylcoumarin
show the reaction diagram
P18291
-
-
-
?
acetyl-IEPD-7-amino-4-methylcoumarin + H2O
acetyl-IEPD + 7-amino-4-methylcoumarin
show the reaction diagram
P18291
-
-
-
?
acetyl-IEPD-p-nitroanilide + H2O
?
show the reaction diagram
-
-
-
-
?
acetyl-IEPD-p-nitroanilide + H2O
?
show the reaction diagram
Q2A6L4
-
-
-
?
acetyl-IETD-7-amido-4-methylcoumarin + H2O
acetyl-IETD + 7-amino-4-methylcoumarin
show the reaction diagram
-
-
-
-
?
acetyl-IETD-7-amido-4-methylcoumarin + H2O
acetyl-IETD + 7-amino-4-methylcoumarin
show the reaction diagram
-
-
-
-
?
acetyl-IETD-7-amido-4-methylcoumarin + H2O
acetyl-IETD-7 + amino-4-methylcoumarin
show the reaction diagram
-
-
-
-
?
acetyl-IETD-7-amino-4-methylcoumarin + H2O
acetyl-IETD + 7-amino-4-methylcoumarin
show the reaction diagram
P18291
-
-
-
?
acetyl-IETD-p-nitroanilide + H2O
?
show the reaction diagram
-
-
-
-
?
acetyl-IKPD-7-amino-4-methylcoumarin + H2O
acetyl-IKPD + 7-amino-4-methylcoumarin
show the reaction diagram
P18291
-
-
-
?
acetyl-Ile-Glu-Pro-Asp-p-nitroanilide + H2O
?
show the reaction diagram
-
-
-
-
?
acetyl-Ile-Glu-Thr-Asp-p-nitroanilide + H2O
?
show the reaction diagram
-
-
-
-
?
acetyl-LEPD-7-amino-4-methylcoumarin + H2O
acetyl-LEPD + 7-amino-4-methylcoumarin
show the reaction diagram
P18291
-
-
-
?
acetyl-VDVADAFC + H2O
acetyl-VDVAD + Ala-Phe-Lys
show the reaction diagram
-
GzmH
-
-
?
acetylcholine receptor
?
show the reaction diagram
-
granzyme B efficiently and specifically cleaves alpha and epsilon subunits of acetylcholine receptor, especially the epsilon subunit
-
-
?
acetylcholine receptor + H2O
?
show the reaction diagram
-
extracellular GrB substrate. Implication: cleavage results in a reduction of the receptor in neuromuscular junctions and yields an autoantigenic fragment
-
-
?
acetylcholine receptor epsilon subunit + H2O
?
show the reaction diagram
-
-
-
-
?
acidic leucine-rich nuclear phosphoprotein 32 family member B + H2O
?
show the reaction diagram
-
-
-
-
?
acidic leucine-rich nuclear phosphoprotein 32 family member E + H2O
?
show the reaction diagram
-
-
-
-
?
actin-like protein 6A + H2O
?
show the reaction diagram
-
-
-
-
?
adenovirus 100K assembly protein + H2O
?
show the reaction diagram
-
gzmB and gzmH
-
-
?
adenovirus DNA-binding protein + H2O
?
show the reaction diagram
-
gzmB and gzmH. Direct cleavage of DNA-binding protein by gzmH is a critical component of the cytotoxic antiviral response against adenovirus, which slows down DNA viral replication. Cleaved by gzmH at multiple sites, most efficient cleavage at Met118, when this site is mutated, gzmH instead cleaves at Phe121
-
-
?
aggrecan + H2O
?
show the reaction diagram
-
extracellular GrB substrate. Implication: Disruption of structural integrity in cartilage
-
-
?
aggrecan proteoglycan + H2O
?
show the reaction diagram
-
-
-
-
?
AHNAK + H2O
?
show the reaction diagram
-
autoantigen cleaved by granzyme B, function of substrate: calcium signalling, associated disease: systemic lupus erythematosus
-
-
?
alanyl tRNA synthetase + H2O
?
show the reaction diagram
-
autoantigen cleaved by granzyme B, function of substrate: translation, associated disease: myositis
-
-
?
alpha-fodrin + H2O
?
show the reaction diagram
-
autoantigen cleaved by granzyme B, function of substrate: cytoskeletal protein, associated disease: Sjrgen's syndrome
-
-
?
alpha-tubulin
?
show the reaction diagram
-
-
-
-
?
alpha-tubulin + H2O
truncated alpha-tubulin
show the reaction diagram
-
alpha-tubulin derived from HeLa S100 extracts or Jurkat S100 extracts is cleaved by grB in a caspase-independent manner. Cleavage occurs at D438. Polymerized and soluble alpha-tubulin can be cleaved
-
-
?
anamorsin + H2O
?
show the reaction diagram
-
-
-
-
?
AQGVISADASNLDDFY + H2O
AQGVISAD + ASNLDDFY
show the reaction diagram
-
-
-
-
?
AQGVISASASNLDDFY + H2O
AQGVISAS + ASNLDDFY
show the reaction diagram
-
-
-
-
?
ARF GTPase-activating protein GIT2 + H2O
?
show the reaction diagram
-
-
-
-
?
ATSY-7-amido-4-methylcoumarin + H2O
ATSY + 7-amino-4-methylcoumarin
show the reaction diagram
-
GzmH
-
-
?
autoantigen + H2O
?
show the reaction diagram
-
-
-
-
?
Bcl-2-associated athano gene-1 + H2O
?
show the reaction diagram
-
GrB proteolysis is independent of caspase activity
-
-
?
BCL2/adenovirus E1B 19 kDa protein-interacting protein 2 + H2O
?
show the reaction diagram
-
generated with similar efficiency by mouse and human recombinant granzyme B
-
-
?
BCL2/adenovirus E1B 19-kDa protein-interacting protein 2 + H2O
?
show the reaction diagram
-
generated with similar efficiency by mouse and human recombinant granzyme B
-
-
?
beta-actin + H2O
?
show the reaction diagram
-
GrB cleavage fragments of beta-actin are detected in medullary carcinoma of the breast tumor lysates, suggesting that CTL-mediated death of medullary carcinoma of the breast tumor cells and actin redistribution may have a function in the generation of autoimmunity to beta-actin
-
-
?
BID + H2O
?
show the reaction diagram
-
-
-
-
?
BID + H2O
truncated BID + ?
show the reaction diagram
-
-
-
-
?
BID + H2O
truncated BID + ?
show the reaction diagram
-
-
-
-
?
BID + H2O
truncated BID + ?
show the reaction diagram
-
efficiently cleaves both human or mouse BID
-
-
?
BID + H2O
truncated BID + ?
show the reaction diagram
-
both human and mouse BID are cleaved efficiently
-
-
?
BID + H2O
truncated BID + ?
show the reaction diagram
-
cleaved in a dose-dependent fashion
-
-
?
BID + H2O
truncated BID + ?
show the reaction diagram
-
efficient cleavage of mouse and human Bid by human granzyme B
-
-
?
BID + H2O
truncated BID + ?
show the reaction diagram
Mus musculus B6
-
-
-
-
?
Boc-Ala-Ala-Asp-SBzl + H2O
?
show the reaction diagram
-
-
-
?
Boc-Ala-Ala-Asp-SBzl + H2O
?
show the reaction diagram
-
-
-
?
Boc-Ala-Ala-Asp-SBzl + H2O
?
show the reaction diagram
-
-
-
?
Boc-Ala-Ala-Asp-SBzl + H2O
?
show the reaction diagram
-
-
-
?
Boc-Ala-Ala-Asp-SBzl + H2O
?
show the reaction diagram
-
-
-
?
Br140 + H2O
?
show the reaction diagram
-
-
-
-
?
cAbl + H2O
?
show the reaction diagram
-
-
-
-
?
cartilage proteoglycans + H2O
?
show the reaction diagram
-
extracellular GrB substrate. Implication: Disruption of structural integrity in cartilage
-
-
?
caspase-3 + H2O
procaspase-3 + ?
show the reaction diagram
-
gzmB
-
-
?
caspase-8 + H2O
?
show the reaction diagram
-
cleaves human caspase-8 but fails to cleave the mouse counterpart of caspase-8. Mouse caspase-8 is processed only upon addition of cytochrome c and dATP to J774 extracts to activate the apoptosome pathway to caspase activation
-
-
?
cell division cycle 5-like protein + H2O
?
show the reaction diagram
-
-
-
-
?
cell division cycle 5-related protein + H2O
?
show the reaction diagram
-
-
-
-
?
centromere protein B + H2O
?
show the reaction diagram
-
autoantigen cleaved by granzyme B, function of substrate: mitosis, associated disease: Scleroderma
-
-
?
centromere protein C + H2O
?
show the reaction diagram
-
autoantigen cleaved by granzyme B, function of substrate: mitosis, associated disease: Scleroderma
-
-
?
chromodomain helicase DNA binding 4 + H2O
?
show the reaction diagram
-
autoantigen cleaved by granzyme B, function of substrate: gene expression, associated disease: myositis
-
-
?
chromodomain-helicase-DNA-binding protein 7 + H2O
?
show the reaction diagram
-
-
-
-
?
dedicator of cytokinesis protein 2 + H2O
?
show the reaction diagram
-
-
-
-
?
DNA binding protein + H2O
?
show the reaction diagram
-
granzyme B and granzyme H (cleavage at Met118 and Phe121)
-
-
?
DNA-PK catalytic subunit + H2O
?
show the reaction diagram
-
autoantigen cleaved by granzyme B, function of substrate: DNA repair, associated disease: myositis
-
-
?
DNA-PKcs + H2O
?
show the reaction diagram
-
-
-
?
DNA-PKcs + H2O
?
show the reaction diagram
-
directly and efficiently cleaved in vitro and in vivo, abolishes kinase activity
-
?
DNA-PKcs + H2O
?
show the reaction diagram
-
directly and efficiently cleaved in vitro and in vivo, abolishes kinase activity
-
?
double strand break repair protein MRE11A + H2O
?
show the reaction diagram
-
-
-
-
?
E3 SUMO-protein ligase RanBP2 + H2O
?
show the reaction diagram
-
-
-
-
?
embryo heart cDNA + H2O
?
show the reaction diagram
-
-
-
-
?
enhancer of mRNA-decapping protein 3 + H2O
?
show the reaction diagram
-
-
-
-
?
eukaryotic translation initiation factor 2 subunit 2 + H2O
?
show the reaction diagram
-
-
-
-
?
exportin-5 + H2O
?
show the reaction diagram
-
-
-
-
?
FGFR1 + H2O
?
show the reaction diagram
-
extracellular GrB substrate. Implication: cleavage activates pro-cell death functions as well as inactivates pro-growth signals
-
-
?
fibrillarin + H2O
?
show the reaction diagram
-
-
-
?
fibrillarin + H2O
?
show the reaction diagram
-
autoantigen cleaved by granzyme B, function of substrate: rRNA processing, associated disease: Scleroderma
-
-
?
Fibrinogen + H2O
?
show the reaction diagram
-
granzyme B is unable to cleave soluble fibrinogen, granzyme B cleaves the matrix form at several sites
-
-
?
Fibrinogen + H2O
?
show the reaction diagram
-
extracellular GrB substrate. Implication: matrix form of fibrinogen is cleaved. The uncleaved protein is responsible for platelet adhesion and thrombus growth. Cleavage results in anti-thrombosis implications
-
-
?
fibroblast growth factor receptor-1 + H2O
?
show the reaction diagram
-
-
-
-
?
Fibronectin + H2O
?
show the reaction diagram
-
-
-
-
?
Fibronectin + H2O
?
show the reaction diagram
-
extracellular GrB substrate. Implication: cell adhesion, migration, and anoikis
-
-
?
gamma-taxilin + H2O
?
show the reaction diagram
-
-
-
-
?
glutamate receptor subunit 3 + H2O
?
show the reaction diagram
-
autoantigen cleaved by granzyme B, function of substrate: Glutamate receptor, associated disease: Rasmussen's encephalitis
-
-
?
Glutamyl 2-naphthylamide + H2O
?
show the reaction diagram
-
-
-
-
-
GTP-binding protein 1 + H2O
?
show the reaction diagram
-
-
-
-
?
hepatitis antigen lamin B + H2O
?
show the reaction diagram
-
cleavage of autoimmune hepatitis antigen lamin B by GrA and B causes disruption of the nuclear lamina, by uncoupling lamin B from its nuclear localisation signal
-
-
?
heterogeneous nuclear ribonucleoprotein H' + H2O
?
show the reaction diagram
-
-
-
-
?
histidyl tRNA synthetase + H2O
?
show the reaction diagram
-
autoantigen cleaved by granzyme B, function of substrate: translation, associated disease: myositis
-
-
?
Hsc70/Hsp70-interacting protein + H2O
?
show the reaction diagram
-
Hsc70/Hsp70-interacting protein is cleaved at both GrB cleavage sites (at sequences IEPD92-TD and INPD180-SA) during NK-mediated cell death in a caspase-independent manner. Hsc70/Hsp70-interacting protein is a substrate unique to GrB
-
-
?
Hsp70 + H2O
?
show the reaction diagram
-
-
-
-
?
Hsp70/Hsp90-organizing protein + H2O
?
show the reaction diagram
-
-
-
-
?
Hsp70/Hsp90-organizing protein + H2O
?
show the reaction diagram
-
directly cleaved at Asp186 in vitro and in cells undergoing GzmB-induced death. Processing by GzmB is caspase-independent. Cleavage by GzmB destroys known functions of Hsp70/Hsp90-organizing protein in Hsp binding and hormone receptor assembly
-
-
?
Hsp90 + H2O
?
show the reaction diagram
-
is proteolyzed at multiple sites by GrB. Cleavage at sequences IDED693-EV and INPD631-PI in Hsp90beta. Cleavage at sequences IDED701-DP, INPD639-HS and VRTD175-TG in Hsp90alpha
-
-
?
human endogenous retrovirus K-10 gag + H2O
?
show the reaction diagram
-
autoantigen cleaved by granzyme B, function of substrate: endogenous retrovirus, associated disease: systemic lupus erythematosus
-
-
?
ICAD + H2O
?
show the reaction diagram
-
cleaves human ICAD but fails to cleave the mouse counterpart
-
-
?
IEPD-p-nitroanilide + H2O
?
show the reaction diagram
-
-
-
-
?
inhibitor of caspase-activated DNase + H2O
caspase-activated DNase
show the reaction diagram
-
cleaved in a dose-dependent fashion
-
-
?
interleukin IL-1alpha + H2O
?
show the reaction diagram
-
cleavage after the motif IAND103, no substrate for caspases -1, -3, -4, -5, and -7
granzyme B-mediated processing of IL-1alpha potently enhances the biological activity
-
?
interleukin proIL-18 + H2O
interleukin IL-18 + ?
show the reaction diagram
-
-
cleavage at residues D35-Y36 of proIL-18, identical to cleavage site of caspase-1
-
?
intersectin-1 + H2O
?
show the reaction diagram
-
-
-
-
?
Ki-67 + H2O
?
show the reaction diagram
-
autoantigen cleaved by granzyme B, function of substrate: proliferation, associated disease: myositis
-
-
?
kinesin family member 21A + H2O
?
show the reaction diagram
-
-
-
-
?
Ku-70 + H2O
?
show the reaction diagram
-
autoantigen cleaved by granzyme B, function of substrate: DNA repair, associated disease: myositis
-
-
?
L4-100k assembly protein + H2O
?
show the reaction diagram
-
granzyme H
-
-
?
La protein + H2O
?
show the reaction diagram
-
La is cleaved by gzmB and gzmH. La is a direct target of gzmH during cytotoxic-mediated cell death. Cleavage of La by gzmH occurs at Phe-364 (P(1) site) and generates a COOH-terminal truncated form of La that loses nuclear localization and decreases hepatitis C virus-internal ribosome entry site-mediated translational activity
-
-
?
La/SS-B + H2O
?
show the reaction diagram
-
-
-
?
La/SSB + H2O
?
show the reaction diagram
-
the SS nuclear autoantigen La/SSB is a substrate for GrB
-
-
?
lamin + H2O
?
show the reaction diagram
-
-
-
-
?
lamin B + H2O
?
show the reaction diagram
-
-
-
-
?
Laminin + H2O
?
show the reaction diagram
-
extracellular GrB substrate. Implication: cell adhesion, anoikis
-
-
?
LEADKGKLEYD + H2O
LEAD + KGKLEYD
show the reaction diagram
-
is a far better substrate for mouse granzyme B as compared with human granzyme B
-
-
?
LEED-p-nitroanilide + H2O
?
show the reaction diagram
-
-
-
-
?
MFLJ00057 protein + H2O
?
show the reaction diagram
-
-
-
-
?
Mi-2 + H2O
?
show the reaction diagram
-
-
-
?
N-acetyl-L-Ile-L-Glu-L-Pro-L-Asp-4-nitroanilide + H2O
?
show the reaction diagram
-
-
-
-
?
Nalpha-tert-Butyloxycarbonyl-Ala-Ala-Asn thiobenzyl ester + H2O
?
show the reaction diagram
-
-
-
-
-
Nalpha-tert-Butyloxycarbonyl-Ala-Ala-Met thiobenzyl ester + H2O
?
show the reaction diagram
-
-
-
-
-
Nalpha-tert-Butyloxycarbonyl-Ala-Ala-Met thiobenzyl ester + H2O
?
show the reaction diagram
-
-
-
-
-
Nalpha-tert-Butyloxycarbonyl-L-Ala-Ala-Ser thiobenzyl ester + H2O
?
show the reaction diagram
-
-
-
-
-
Nalpha-tert-Butyloxycarbonyl-L-Ala-L-Ala-L-Asp thiobenzyl ester + H2O
?
show the reaction diagram
-
-
-
-
-
Nalpha-tert-Butyloxycarbonyl-L-Ala-L-Ala-L-Asp thiobenzyl ester + H2O
?
show the reaction diagram
-
-
-
-
-
negative elongation factor E + H2O
?
show the reaction diagram
-
-
-
-
?
neuronal glutamate receptor + H2O
?
show the reaction diagram
-
extracellular GrB substrate. Implication: GrB cleaves the non-glycosylated form of the receptor into an autoantigenic fragment
-
-
?
nipped-B-like protein + H2O
?
show the reaction diagram
-
-
-
-
?
Notch1 + H2O
?
show the reaction diagram
-
-
-
-
?
Notch1 + H2O
?
show the reaction diagram
-
extracellular GrB substrate. Implication: cleavage results in cell signaling affecting tumor survival and antiviral activities
-
-
?
Notch1 + H2O
?
show the reaction diagram
-
transmembrane receptor, Notch1 is a direct and caspase-independent substrate. GrB cleaves the intracellular Notch1 domain at least twice, at residues D1860 and D1961. GrB cleavage of Notch1 can occur in all subcellular compartments, during maturation of the receptor, at the membrane, and in the nucleus. GrB also displays perforin-independent functions by cleaving the extracellular domain of Notch1
cleavage of Notch1 by GrB results in a loss of transcriptional activity, independent of Notch1 activation. GrB disables Notch1 function, probably resulting in anti-cellular proliferation and cell death signals
-
?
nuclear mitotic apparatus protein 1 + H2O
?
show the reaction diagram
-
autoantigen cleaved by granzyme B, function of substrate: mitosis, associated disease: Sjrgen's syndrome
-
-
?
nuclease-sensitive element-binding protein 1 + H2O
?
show the reaction diagram
-
-
-
-
?
nucleolin + H2O
?
show the reaction diagram
-
-
-
-
?
nucleolus organizing region 90 kDa (NOR-90/UBF) + H2O
?
show the reaction diagram
-
autoantigen cleaved by granzyme B, function of substrate: transcription factor, associated disease: Scleroderma
-
-
?
nucleophosmin (B23) + H2O
?
show the reaction diagram
-
autoantigen cleaved by granzyme B, function of substrate: rRNA processing, associated disease: Scleroderma
-
-
?
nucleophosmin + H2O
?
show the reaction diagram
-
efficiently cleaves nucleophosmin of human origin, does not cleave nucleophosmin within J774 cell free extracts
-
-
?
nucleosome assembly protein 1-like + H2O
?
show the reaction diagram
-
-
-
-
?
NuMA + H2O
?
show the reaction diagram
-
-
-
?
NuMA + H2O
?
show the reaction diagram
-
directly and efficiently cleaved in vitro and in vivo
-
?
p35 + H2O
?
show the reaction diagram
-
GrB-induces phosphorylation of p53
-
-
?
pallidin + H2O
?
show the reaction diagram
-
-
-
-
?
PARP + H2O
?
show the reaction diagram
-
-
-
?
PARP-PKcs + H2O
?
show the reaction diagram
-
-
-
?
PEG-P + H2O
?
show the reaction diagram
-
virtually all soluble PEG-P is cleaved in 3 min, suggesting PEG-P is a sensitive indicator of granzyme B activity. The granzyme can not access PEG-P when encapsulated in 1,2-dioleoyl-sn-glycero-3-phosphocholine large unilamellar vesicles
-
-
?
peptidyl-prolyl cis-trans isomerase G + H2O
?
show the reaction diagram
-
-
-
-
?
peptidyl-prolyl cis-trans isomerase-like 4 + H2O
?
show the reaction diagram
-
-
-
-
?
pericentriolar material 1 protein + H2O
?
show the reaction diagram
-
-
-
-
?
plasmin + H2O
?
show the reaction diagram
-
extracellular GrB substrate. Implication: as plasmin is pro-angiogenic, cleavage results in the reduction of angiogenesis
-
-
?
plasminogen + H2O
?
show the reaction diagram
-
extracellular GrB substrate. Implication: cleavage yields angiostatin, which is anti-angiogenic. Implications in angiogenesis
-
-
?
PMS-1 + H2O
?
show the reaction diagram
-
-
-
?
PMS-2 + H2O
?
show the reaction diagram
-
-
-
?
PMScl/EXOSC10 + H2O
?
show the reaction diagram
-
autoantigen cleaved by granzyme B, function of substrate: mRNA degradation, associated disease: myositis/Scleroderma
-
-
?
poly(ADP)ribose polymerase 1 (PARP1) + H2O
?
show the reaction diagram
-
autoantigen cleaved by granzyme B, function of substrate: ribosylation, associated disease: systemic lupus erythematosus
-
-
?
poly(ADP-ribose) polymerase + H2O
?
show the reaction diagram
-
-
-
-
?
poly(ADP-ribose)polymerase + H2O
?
show the reaction diagram
-
-
-
-
?
poly-a binding protein + H2O
?
show the reaction diagram
-
-
-
-
?
polypyrimidine tract-binding protein + H2O
?
show the reaction diagram
-
2times more efficiently cleaved by mouse versus human recombinant granzyme B
-
-
?
postmeiotic segregation 1 + H2O
?
show the reaction diagram
-
autoantigen cleaved by granzyme B, function of substrate: DNA mismatch repair, associated disease: myositis
-
-
?
postmeiotic segregation 2 + H2O
?
show the reaction diagram
-
autoantigen cleaved by granzyme B, function of substrate: DNA mismatch repair, associated disease: myositis
-
-
?
pro-caspase 3 + H2O
?
show the reaction diagram
-
-
-
-
?
pro-caspase 3 + H2O
p17 + ?
show the reaction diagram
-
-
-
-
?
pro-caspase-10 + H2O
?
show the reaction diagram
-
-
-
?
pro-caspase-10 + H2O
?
show the reaction diagram
-
-
-
?
pro-caspase-3 + H2O
caspase-3 + ?
show the reaction diagram
-
-
-
-
?
pro-caspase-3 + H2O
caspase-3 + ?
show the reaction diagram
-
-
-
-
?
pro-caspase-3 + H2O
caspase-3 + ?
show the reaction diagram
-
cleaves human pro-caspase-3 but only generates a 21-kDa fragment, no autocatalytic removal of the caspase-3 prodomain. Efficiently cleaves and activates mouse procaspase-3, producing predominantly the 17-kDa fragment
-
-
?
pro-caspase-3 + H2O
caspase-3 + ?
show the reaction diagram
-
cleaves human pro-caspase-3 generating a 21-kDa and a 17-kDa fragment (autocatalytic removal of the caspase-3 prodomain)
-
-
?
pro-caspase-3 + H2O
caspase-3 + ?
show the reaction diagram
Mus musculus B6
-
-
-
-
?
pro-caspase-3 + H2O
?
show the reaction diagram
-
-
-
-
?
pro-caspase-3 + H2O
?
show the reaction diagram
-
activates caspase-3, whether of human or murine origin, with a similar efficiency
-
-
?
pro-caspase-3 + H2O
?
show the reaction diagram
-
granzyme B
-
-
?
pro-caspase-7 + H2O
caspase-7 + ?
show the reaction diagram
Mus musculus, Mus musculus B6
-
-
-
-
?
pro-caspase-7 + H2O
?
show the reaction diagram
-
activates caspase-7, whether of human or murine origin, with a similar efficiency
-
-
?
pro-CPP32 + H2O
?
show the reaction diagram
-
processes the caspase into its enzymatically active form
-
?
pro-mCASP-3 + H2O
caspase-3 + ?
show the reaction diagram
-
-
-
?
pro-mCASP-3 + H2O
caspase-3 + ?
show the reaction diagram
-
-
-
?
pro-mCASP-3 + H2O
caspase-3 + ?
show the reaction diagram
-
activational cleavage of the caspase proform
-
?
pro-mCASP-7 + H2O
caspase-7 + ?
show the reaction diagram
-
-
-
?
pro-mCASP-7 + H2O
caspase-7 + ?
show the reaction diagram
-
-
-
?
pro-mCASP-7 + H2O
caspase-7 + ?
show the reaction diagram
-
activational cleavage of the caspase proform
-
?
probable rRNA-processing protein EBP2 + H2O
?
show the reaction diagram
-
-
-
-
?
procaspase-8 + H2O
caspase-8 + ?
show the reaction diagram
-
-
-
-
?
Protease CMH-1 + H2O
?
show the reaction diagram
-
a close homologue of CPP32, granzyme B specifically cleaves at Asp198-Ser199 between the p20 and p12 and activates the cysteine protease
-
-
-
Protease CPP32 + H2O
?
show the reaction diagram
-
CPP32 is the precursor of the protease responsible for cleavage of poly(ADPribose)polymerase
-
-
-
Protease CPP32 + H2O
?
show the reaction diagram
-
granzyme B activates CPP32, which is now able to bind inhibitors and cleave the substrate poly(ADPribose)polymerase whose proteolysis is a marker of apoptosis initiated by several other stimuli
-
-
-
protein phosphatase 1G + H2O
?
show the reaction diagram
-
-
-
-
?
PTSY-7-amido-4-methylcoumarin + H2O
PTSY + 7-amino-4-methylcoumarin
show the reaction diagram
-
GzmH
-
-
?
pyruvate dehydrogenase complex E2 (PDC-E2) + H2O
?
show the reaction diagram
-
autoantigen cleaved by granzyme B, function of substrate: acetyl CoA synthesis, associated disease: primary biliary cirrhosis
-
-
?
RNA polymerase I + H2O
?
show the reaction diagram
-
autoantigen cleaved by granzyme B, function of substrate: transcription, associated disease: Scleroderma
-
-
?
RNA polymerase II + H2O
?
show the reaction diagram
-
autoantigen cleaved by granzyme B, function of substrate: transcription, associated disease: Scleroderma
-
-
?
RNA-binding protein 28 + H2O
?
show the reaction diagram
-
-
-
-
?
scaffold attachment factor B + H2O
?
show the reaction diagram
-
-
-
-
?
serine/arginine-repetitive matrix protein 1 + H2O
?
show the reaction diagram
-
-
-
-
?
serine/arginine-repetitive matrix protein 2 + H2O
?
show the reaction diagram
-
-
-
-
?
serine/threonine protein kinase N1 + H2O
?
show the reaction diagram
-
-
-
-
?
serum deprivation-response protein + H2O
?
show the reaction diagram
-
-
-
-
?
signal recognition particle 72 kDa + H2O
?
show the reaction diagram
-
autoantigen cleaved by granzyme B, function of substrate: translation, associated disease: myositis, systemic lupus erythematosus
-
-
?
smooth muscle cell matrix + H2O
?
show the reaction diagram
-
extracellular GrB substrate. Implication: cell adhesion, anoikis
-
-
?
splicing factor 3B subunit 1 + H2O
?
show the reaction diagram
-
-
-
-
?
squamous cell carcinoma antigen recognized by T-cells 3 + H2O
?
show the reaction diagram
-
-
-
-
?
succinyl-Phe-Leu-Phe-p-nitroanilide + H2O
?
show the reaction diagram
-
-
-
-
?
succinyl-Phe-Leu-Phe-SBzl + H2O
?
show the reaction diagram
-
GzmH
-
-
?
T-complex protein 1 subunit alpha + H2O
?
show the reaction diagram
-
-
-
-
?
testis-specific Y-encoded-like protein 2 + H2O
?
show the reaction diagram
-
-
-
-
?
topoisomerase 1 + H2O
?
show the reaction diagram
-
autoantigen cleaved by granzyme B, function of substrate: transcription, associated disease: Scleroderma
-
-
?
topoisomerase-1 + H2O
?
show the reaction diagram
-
-
-
?
transaldolase + H2O
?
show the reaction diagram
-
specifically cleaved by human GrB. The recognition site is a VVAD motif at aa residue 27
the major C-terminal GrB cleavage product of transaldolase, residues 28-337, has no enzymatic activity but retains the antigenicity of full-length transaldolase, effectively stimulating the proliferation and cytotoxic lymphocyte activity of peripheral blood mononuclear cells and of CD8+ T cell lines from patients with multiple sclerosis. Sera of multiple sclerosis patients exhibit similar binding affinity to wild-type and GrB-cleaved transaldolase
-
?
transcription elongation factor A protein 1 + H2O
?
show the reaction diagram
-
-
-
-
?
U1 small nuclear ribonucleoprotein 70 kDa + H2O
?
show the reaction diagram
-
autoantigen cleaved by granzyme B, function of substrate: RNA processing, associated disease: systemic lupus erythematosus, Scleroderma, myositis
-
-
?
U1-70kD + H2O
?
show the reaction diagram
-
-
-
?
U3 small nucleolar RNA-associated protein 18 homolog + H2O
?
show the reaction diagram
-
-
-
-
?
U4/U6.U5 tri-snRNP-associated protein 1 + H2O
?
show the reaction diagram
-
-
-
-
?
ubiquitin C-terminal hydrolase 10 + H2O
?
show the reaction diagram
-
-
-
-
?
ubiquitin fusion degradation 2 + H2O
?
show the reaction diagram
-
autoantigen cleaved by granzyme B, function of substrate: ubiquitination, associated disease: Scleroderma
-
-
?
ubiquitin thioesterase OTUB1 + H2O
?
show the reaction diagram
-
-
-
-
?
uncharacterized protein KIAA0859 + H2O
?
show the reaction diagram
-
-
-
-
?
VEID-p-nitroanilide + H2O
?
show the reaction diagram
-
-
-
-
?
VGPDFGR + H2O
VGPD + FGR
show the reaction diagram
-
-
-
-
?
Vitronectin + H2O
?
show the reaction diagram
-
-
-
-
?
Vitronectin + H2O
?
show the reaction diagram
-
Grb expressed in human bladder cancer cell lines 1512 and RT112 cleave vitronectin
-
-
?
Vitronectin + H2O
?
show the reaction diagram
-
extracellular GrB substrate. Implication: GrB cleavage site in integrin-binding domain, implications in cell adhesion, migration, and anoikis
-
-
?
von Willebrand factor + H2O
?
show the reaction diagram
-
granzyme B delays ristocetin-induced platelet aggregation and inhibits platelet adhesion and spreading on immobilized von Willebrand factor under static conditions. In vitro, granzyme B cannot cleave the von Willebrand factor conformer in solution, but cleavage is induced when von Willebrand factor is artificially unfolded or presented as a matrix. Granzyme B cleaves von Willebrand factor with comparable efficiency to proteinase ADAMTS-13 and rapidly processes ultra-large von Willebrand factor multimers released from activated endothelial cells under physiological shear. Granzyme B cleaves the A1 and A3 domains of von Willebrand factor
-
-
?
von Willebrand factor + H2O
?
show the reaction diagram
-
extracellular GrB substrate. Implication: GrB cleavage site in the domain of platelet interaction, prevention/delay of thrombosis
-
-
?
microtubule-associated protein 4 + H2O
?
show the reaction diagram
-
-
-
-
?
additional information
?
-
-
the substrate preference of granzyme B is determined by a positive charge in the specificity pocket
-
-
-
additional information
?
-
-
preference for substrates with Glu or Asp as the residue amino-terminal to the scissile bond, little or no activity with oligopeptide substrates for trypsin-like, chymotrypsin-like, and elastase-like proteases
-
-
-
additional information
?
-
-
preference for substrates with Glu or Asp as the residue amino-terminal to the scissile bond, little or no activity with oligopeptide substrates for trypsin-like, chymotrypsin-like, and elastase-like proteases
-
-
-
additional information
?
-
-
induces DNA degradation and apoptosis of cells
-
?
additional information
?
-
-
involved in cell killing by cytotoxic T lymphocytes, activates the apoptotic death pathway in the target cell
-
?
additional information
?
-
-
involved in cell killing by cytotoxic T lymphocytes, activates the apoptotic death pathway in the target cell
-
?
additional information
?
-
-
not able to induce apoptosis on its own
-
?
additional information
?
-
-
processing enzyme, requires extended peptide substrates containing an Asp residue
-
?
additional information
?
-
-
proforms of mCASP-2 and mCASP-1 are not substrates, pro-mCASP-6 is not proteolytically cleaved by granzyme B, mCASP-11 and mCASP-12 are not processed
-
?
additional information
?
-
-
requirement for aspartic acid in the substrate P1 position
-
?
additional information
?
-
-
requirement for aspartic acid in the substrate P1 position
-
?
additional information
?
-
-
requirement for aspartic acid in the substrate P1 position, induces DNA fragmentation in isolated nuclei in the presence of cytosolic factors
-
?
additional information
?
-
-
plays an essential role in cytotoxic T-lymphocyte-mediated cell killing
-
-
-
additional information
?
-
-
the enzyme cleaves and activates CPP32, the precursor of the protease responsible for cleavage of poly(ADPribose)polymerase
-
-
-
additional information
?
-
-
participates in target cell death inflicted by cytotoxic lymphocytes
-
-
-
additional information
?
-
-
induces apoptosis of abnormal cells by cleaving intracellular proteins
-
?
additional information
?
-
-
mediates cell death by cytotoxic lymphocytes
-
?
additional information
?
-
-
protects the organism against intracellular infections and cellular transformation, implicated in the generation of tissue damage in a variety of chronic conditions, including autoimmunity and transplant rejection
-
?
additional information
?
-
-
triggers apoptosis in target cells by activating the caspase pathway, implicated in the etiology of rheumatoid arthritis
-
?
additional information
?
-
-
triggers apoptosis in target cells by activating the caspase pathway, implicated in the etiology of rheumatoid arthritis <6>
-
?
additional information
?
-
-
after prolonged incubation, enzyme causes pronounced morphological changes in human tumor cells, leading to partial loss of contact to the culture support
-
-
-
additional information
?
-
-
compared with granzyme B, granzyme A is minor effector of target cell lysis by natural killer cells
-
-
-
additional information
?
-
-
both human or mouse BID are highly resistant to cleavage by mouse GrB
-
-
-
additional information
?
-
-
BID is a poor substrate for mouse GzmB. Fails to cleave caspase-8 and ICAD from either human or murine origin. Cleaves nucleophosmin of human origin very inefficiently, does not cleave nucleophosmin within J774 cell free extracts
-
-
-
additional information
?
-
-
BID is not cleaved
-
-
-
additional information
?
-
-
both human or mouse BID are highly resistant to cleavage by mouse GrB. It is unable to cleave BID in cell lysates in which caspases are inactivated but induces BID cleavage, albeit inefficiently, in lysates supporting caspase activity. BID pathway is not a prominent primary mediator of the effects of mouse GrB
-
-
-
additional information
?
-
-
caspases 2, 3 and 7 (C285A mutants) and purified BID are not directly cleaved by GzmH. No activity of GzmH toward Ac-LEHD-7-amino-4-methylcouramin
-
-
-
additional information
?
-
-
granzyme H does not cleave BID or inhibitor of caspase-activated death, does not activate caspases
-
-
-
additional information
?
-
-
Hsp27 is resistant to GrB proteolysis
-
-
-
additional information
?
-
-
granzyme B does not bind membrane phospholipids nor has intrinsic membranolytic properties
-
-
-
additional information
?
-
-
granzyme B has no effect on platelet adhesion and spreading on immobilized collagen. Granzyme B does not cleave glycocalicin (extracellular domain of GPIbalpha)
-
-
-
additional information
?
-
-
mediates cleavage at Asn36 (neo-N terminus: LALLEEIEAENR) in the mouse and at Asp37 (neo-N terminus: LALMEEMEAEHR) in the human DNA polymerase delta catalytic subunit
-
-
-
additional information
?
-
-
no efficient cleavage of mouse and human Bid by mouse granzyme B
-
-
-
additional information
?
-
-
platelets from septic granzyme B null (-/-) mice show no lymphotoxicity
-
-
-
additional information
?
-
-
tetrapeptide substrate specificity of human GrB: In addition to the requirement for aspartic acid in the P1 position, P4 is specific for Ile, Val, and Leu, whereas P3 and P2 are able to accommodate a wider range of amino acids, the GrB cleavage sites defined within autoantigens reveal several features: first, all have Ile, Leu, or Val in P4 and are cleaved after the P1 aspartic acid. Second, amino acids in the P2 and P3 positions in autoantigens are almost universally favored by human GrB, but not tolerated by caspases (e.g. proline in P2)
-
-
-
additional information
?
-
-
no substrate: interleukin IL-1beta
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
BID + H2O
truncated BID + ?
show the reaction diagram
-
efficiently cleaves both human or mouse BID
-
-
?
DNA-PKcs + H2O
?
show the reaction diagram
-
-
-
?
DNA-PKcs + H2O
?
show the reaction diagram
-
directly and efficiently cleaved in vitro and in vivo, abolishes kinase activity
-
?
fibrillarin + H2O
?
show the reaction diagram
-
-
-
?
interleukin IL-1alpha + H2O
?
show the reaction diagram
-
cleavage after the motif IAND103, no substrate for caspases -1, -3, -4, -5, and -7
granzyme B-mediated processing of IL-1alpha potently enhances the biological activity
-
?
interleukin proIL-18 + H2O
interleukin IL-18 + ?
show the reaction diagram
-
-
cleavage at residues D35-Y36 of proIL-18, identical to cleavage site of caspase-1
-
?
La/SS-B + H2O
?
show the reaction diagram
-
-
-
?
Notch1 + H2O
?
show the reaction diagram
-
transmembrane receptor, Notch1 is a direct and caspase-independent substrate. GrB cleaves the intracellular Notch1 domain at least twice, at residues D1860 and D1961. GrB cleavage of Notch1 can occur in all subcellular compartments, during maturation of the receptor, at the membrane, and in the nucleus. GrB also displays perforin-independent functions by cleaving the extracellular domain of Notch1
cleavage of Notch1 by GrB results in a loss of transcriptional activity, independent of Notch1 activation. GrB disables Notch1 function, probably resulting in anti-cellular proliferation and cell death signals
-
?
NuMA + H2O
?
show the reaction diagram
-
-
-
?
PARP + H2O
?
show the reaction diagram
-
-
-
?
PMS-1 + H2O
?
show the reaction diagram
-
-
-
?
PMS-2 + H2O
?
show the reaction diagram
-
-
-
?
pro-caspase-10 + H2O
?
show the reaction diagram
-
-
-
?
pro-caspase-10 + H2O
?
show the reaction diagram
-
-
-
?
pro-mCASP-3 + H2O
caspase-3 + ?
show the reaction diagram
-
-
-
?
pro-mCASP-3 + H2O
caspase-3 + ?
show the reaction diagram
-
-
-
?
pro-mCASP-3 + H2O
caspase-3 + ?
show the reaction diagram
-
activational cleavage of the caspase proform
-
?
pro-mCASP-7 + H2O
caspase-7 + ?
show the reaction diagram
-
-
-
?
pro-mCASP-7 + H2O
caspase-7 + ?
show the reaction diagram
-
-
-
?
pro-mCASP-7 + H2O
caspase-7 + ?
show the reaction diagram
-
activational cleavage of the caspase proform
-
?
topoisomerase-1 + H2O
?
show the reaction diagram
-
-
-
?
transaldolase + H2O
?
show the reaction diagram
-
specifically cleaved by human GrB. The recognition site is a VVAD motif at aa residue 27
the major C-terminal GrB cleavage product of transaldolase, residues 28-337, has no enzymatic activity but retains the antigenicity of full-length transaldolase, effectively stimulating the proliferation and cytotoxic lymphocyte activity of peripheral blood mononuclear cells and of CD8+ T cell lines from patients with multiple sclerosis. Sera of multiple sclerosis patients exhibit similar binding affinity to wild-type and GrB-cleaved transaldolase
-
?
U1-70kD + H2O
?
show the reaction diagram
-
-
-
?
Vitronectin + H2O
?
show the reaction diagram
-
Grb expressed in human bladder cancer cell lines 1512 and RT112 cleave vitronectin
-
-
?
Mi-2 + H2O
?
show the reaction diagram
-
-
-
?
additional information
?
-
-
involved in cell killing by cytotoxic T lymphocytes, activates the apoptotic death pathway in the target cell
-
?
additional information
?
-
-
involved in cell killing by cytotoxic T lymphocytes, activates the apoptotic death pathway in the target cell
-
?
additional information
?
-
-
plays an essential role in cytotoxic T-lymphocyte-mediated cell killing
-
-
-
additional information
?
-
-
the enzyme cleaves and activates CPP32, the precursor of the protease responsible for cleavage of poly(ADPribose)polymerase
-
-
-
additional information
?
-
-
participates in target cell death inflicted by cytotoxic lymphocytes
-
-
-
additional information
?
-
-
induces apoptosis of abnormal cells by cleaving intracellular proteins
-
?
additional information
?
-
-
mediates cell death by cytotoxic lymphocytes
-
?
additional information
?
-
-
protects the organism against intracellular infections and cellular transformation, implicated in the generation of tissue damage in a variety of chronic conditions, including autoimmunity and transplant rejection
-
?
additional information
?
-
-
triggers apoptosis in target cells by activating the caspase pathway, implicated in the etiology of rheumatoid arthritis
-
?
additional information
?
-
-
triggers apoptosis in target cells by activating the caspase pathway, implicated in the etiology of rheumatoid arthritis <6>
-
?
additional information
?
-
-
after prolonged incubation, enzyme causes pronounced morphological changes in human tumor cells, leading to partial loss of contact to the culture support
-
-
-
additional information
?
-
-
compared with granzyme B, granzyme A is minor effector of target cell lysis by natural killer cells
-
-
-
additional information
?
-
-
both human or mouse BID are highly resistant to cleavage by mouse GrB
-
-
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Ca2+
-
-
CaCl2
-
50 mM, enhances Nalpha-tert-butyloxycarbonyl-L-Ala-L-Ala-L-Asp thiobenzyl esterase activity
NaCl
-
0.1-1.0 M, highest activity with Nalpha-tert-butyloxycarbonyl-Ala-Ala-Met thiobenzyl ester
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(2S,5S)-N-((1H-1,2,3-triazol-4-yl)methyl)-5-((3S,4S)-3-(2-(benzo[b]thiophen-3-yl)acetamido)-4-methyl-2-oxohexylamino)-4-oxo-1,2,4,5,6,7-hexahydroazepino[3,2,1-hi]indole-2-carboxamide
-
specific granzyme B inhibitor
(S)-3-((2S,5S)-5-((2S,3S)-2-acetamido-3-methylpentanamido)-4-oxo-1,2,4,5,6,7-hexahydroazepino[3,2,1-hi]indole-2-carboxamido)-4-oxobutanoic acid
-
-
(S)-3-((2S,5S)-5-((2S,3S)-2-acetamido-3-methylpentanamido)-4-oxo-1,2,4,5,6,7-hexahydroazepino[3,2,1-hi]indole-2-carboxamido)-4-oxobutanoic acid
-
GzmB inhibitor
(S)-3-((2S,5S)-5-((2S,3S)-2-acetamido-3-methylpentanamido)-4-oxo-1,2,4,5,6,7-hexahydroazepino[3,2,1-hi]indole-2-carboxamido)-4-oxobutanoic acid
-
peptide-mimetic analog of IEPD-aldehyde
100 kDa assembly protein (Ad5-100K)
-
no inhibition is seen in mouse or rat
-
100K assembly protein of human adenovirus type 5
-
potent and specific inhibitor
-
Ac-IETD-CHO
Q2A6L4
reduces activity about 6fold
Ac-Ile-Glu-Thr-Asp-CHO
-
specific granzyme B oligopeptide inhibitor
adenovirus 100K assembly protein
-
inhibits gzmB, gzmH relieves gzmB inhibition
-
benzamidine
-
-
benzyloxycarbonyl-Ala-Ala-Asp-chloromethylketone
-
GrB-specific inhibitor. Addition completely blocks reaction with interleukin proIL-18
Bio-x-IEPDp-(Oph)2
-
specific and irreversible inhibition both in vitro and in cells
Boc-Ile-Glu-Ala-Asp-CONH(CH2)2-Ph
-
granB specific inhibitor
Bovine aprotinin
-
-
-
Bovine aprotinin
-
-
-
chymostatin
-
-
chymostatin
-
-
cytokine response modifier A (CrmA) of poxyvirus
-
virally encoded serpin
-
ecotin[81-84IEPD]
-
-
EGTA
-
inhibits granular granzyme B-mediated killing
EGTA
-
-
guanidinium hydrochloride
-
-
Human plasma alpha1-protease inhibitor
-
-
-
Human plasma alpha1-protease inhibitor
-
-
-
Human plasma alpha2-protease macroglobulin
-
-
-
Human plasma alpha2-protease macroglobulin
-
-
-
IETD-CHO
Q2A6L4
reduces activity about 6fold
interleukin-10
-
granzyme B release from both alloreactive cytotoxic T cell clones and an Epstein-Barr virus-specific cytotoxic T cell clone is inhibited in the presence of interleukin-10 serum
-
interleukin-4
-
significantly suppresses granzyme B synthesis. Interleukin-4-mediated suppression of granzyme B leads to impaired cytotoxicity of adaptive regulatory T cells against K562 target cells
-
L4-100k assembly protein
-
acts as a sink that binds to and inhibits granzyme B, preventing target cell death
-
Lima-bean trypsin inhibitor
-
-
-
Nalpha-tert-Butyloxycarbonyl-Ala-Ala-Asp-CH2Cl
-
-
phosphoramidon
-
-
phosphoramidon
-
-
PI-9
-
granzyme B forms a specific SDS-stable complex with its cognate inhibitor, PI-9
-
protease inhibitor-9
-
endogenous human inhibitor
-
proteinase inhibitor 9 (PI-9)
-
-
-
serine protease inhibitor 6 (Spi6)
-
-
-
serpin inhibitor PI-9
-
granzyme B specific serpin inhibitor, complexation of enzyme with inhibitor prevents recognition by receptor importin beta and eliminates requirement of importin alpha for nuclear import
-
serpin proteinase inhibitor 9
-
-
-
serpina3n
-
inhibitor for human and mouse GrB, expressed by Sertoli cells. Inhibitor shares homology with human alpha-1-anti-chymotrypsin
-
Soybean trypsin inhibitor
-
-
-
Soybean trypsin inhibitor
-
-
-
z-AAD-chloromethylketone
-
-
Z-Ala-Ala-Asp-CH2Cl
-
-
Lima-bean trypsin inhibitor
-
-
-
additional information
-
no inhibition with 100K assembly protein of human adenovirus type 5
-
additional information
-
zVAD-fmk completely inhibits GzmB induced executioner caspase activity
-
additional information
-
treatment of T1 cells with pifithrin-alpha results in inhibition of p53 phosphorylation and in a significant decrease in GrB-induced apoptotic T1 cell death. siRNA targeting p53 induces inhibition of streptolysin-O/GrB-mediated apoptotic T1 cell death
-
additional information
-
inhibition of caspases does not clonogenically rescue cells from human GzmB
-
additional information
-
inhibition of caspases may clonogenically rescue cells from mouse GzmB
-
additional information
-
to protect beta cells from allogeneic CTL attack, one needs to inhibit the perforin/granzyme and probably also the TNFalpha pathway. Granzyme B-dependent death of NIT-1 cells is not inhibited by Bcl-2 overexpression
-
additional information
-
natural killer cells stimulated in vitro with interleukin-2 reduce their granzyme H levels over 3-4 days
-
additional information
-
no significant difference of granzyme B between patients without immunologic treatment and patients after introduction of immunologic treatment, this may be attributed to the variety of clinical stage at the introduction of immunologic treatment and the variety of immunologic treatment
-
additional information
-
back salt progressively inhibits granzyme B-mediated von Willebrand factor cleavage
-
additional information
-
induced hypoacetylation in GZMB gene loci by a HAT inhibitor (curcumin) results in decreased expressions of GZMB in memory cells in response to in vitro stimulation
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
A23187
-
induces granzyme B expression in mast cell lines HMC-1 and LAD2 and cord blood-derived mast cells
cathepsin C
-
proteolytically activates in cytotoxic granules
-
compound 48/80
-
induces granzyme B expression in mast cell line LAD2 and cord blood-derived mast cells
PMA
-
stimulates
PMA
Q2A6L4
stimulates
SERPINB9
-
-
-
Substance P
-
induces granzyme B expression in mast cell line LAD2 and cord blood-derived mast cells
ionomycin
Q2A6L4
stimulates
additional information
-
CMV/EBV/influenza peptide pool peptides do not induce GzB release in CD8+ cells from healthy donors within 24 h. Purified CD8+ cells after CMV/EBV/influenza peptide pool peptide stimulation show induction of GzB after 72 h in vitro. HIV peptides induce GzB secretion in HIV-infected individuals directly ex vivo
-
additional information
-
induction of granzyme B by a DNase1 hypersensitive site 3.9 kb upstream of the transcription start site of granzyme B
-
additional information
-
secreted after Fcepsilon-receptor-mediated activation in cytoplasmic granules of bone marrow-derived mast cells
-
additional information
-
GzB is not induced in purified CD8+ cells by CEF peptides ex vivo. Low frequencies of GzB producing CD8+ cells after mitogen stimulation. IFN-gamma positive, GzB negative CD8+ memory cells convert into GzB producing cells within 2 days after antigen stimulation. Induction of GzB producing CD8+ cells after Vaccinia virus booster immunization. HIV peptides induce GzB production in HIV-infected individuals directly ex vivo
-
additional information
-
granzyme B expression in Treg cells is activated by syngeneic tumor cell line
-
additional information
-
no GzB activity in CTL or NK92 effector cells, but activity rapidly becomes detectable throughout the target cytoplasm after effector-target engagement. Lack of GzB activity in Jurkat cells following intrinsic and extrinsic apoptotic stimuli
-
additional information
-
mature skin-derived mast cells only produce granzyme B upon IgE-dependent stimulation by FcepsilonRI
-
additional information
-
natural killer cells stimulated in vitro with interleukin-2 express progressively greater amounts of perforin and granzyme B
-
additional information
-
sepsis induces platelet granzyme B expression. In septic mice, granzyme B expression significantly increases by 24 h in megakaryocytes and platelets
-
additional information
-
in the presence of perforin, modest cleavage of the encapsulated PEG-P at large unilamellar vesicles/perforin molar ratio of 1000 at acidic and neutral pH. Granzyme B requires a translocation agent to enter the target cell. Granzyme B readily accesses PEG-P only when a membrane disrupting agent, e.g. TX-100, streptolysin O or perforin, is present
-
additional information
-
plasma level of granzyme B increases significantly by day 14, with a peak at day 7 after onset of acute myocardial infarction. Significant positive correlation between the plasma granzyme B level on day 14 and the increase in left ventricular end-diastolic volume index over 6 months after acute myocardial infarction
-
additional information
-
granzyme B level is elevated in the early stage of Rasmussen syndrome around the onset of epilepsy and remains slightly elevated even in the progressed stage, and declines within a few months to more or less constant levels
-
additional information
-
an extracellular activator of granzyme B may exist
-
additional information
-
activation of CD4+ T cells with anti-CD3 and anti-CD28 or anti-CD46 induces granzyme B expression in all cells. Granzyme B expression in anti-CD3/anti-CD46 activated CD4+ T cells is much higher than granzyme B expression induced by usual activation (anti-CD3/anti-CD28)
-
additional information
-
ristocetin does not increase granzyme B cleavage in the presence or absence of salt
-
additional information
-
in vitro stimulation increases the mRNA levels of GZMB in both naive and memory cells. Activation-induced GZMB expression increases significantly faster and higher in memory cells than in naive cells for the first 24-32 h. At 72 h after stimulation, naive cells express higher levels of GZMB than do memory cells
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0058
2-aminobenzoyl-IEPDSSMEK-dnp
-
pH 7.4, 37C, wild-type
0.0068
2-aminobenzoyl-IEPDSSMEK-dnp
-
pH 7.4, 37C, mutant K24A
0.0387
2-aminobenzoyl-IEPDSSMEK-dnp
-
pH 7.4, 37C, mutant K27A
0.0058
2-aminobenzoyl-IEPDSSMESK-dnp
-
pH 7.4, 37C
0.0701
2-aminobenzoyl-VVADSSMASK-dnp
-
pH 7.4, 37C
0.013
2-aminobenzoyl-VVADSSMESK-dnp
-
pH 7.4, 37C
0.0643
2-aminobenzoyl-VVAESSMESK-dnp
-
pH 7.4, 37C
0.0057
Abz-IEPDSSMESK-DNP
-
mutant Q48R/P88A/Y245H, 37C
0.0058
Abz-IEPDSSMESK-DNP
-
wild-type, 37C
0.1512
Ac-IEPD-p-nitroanilide
Q2A6L4
-
0.447
Ac-IEPD-p-nitroanilide
-
-
0.15
acetyl-IEFD-7-amino-4-methylcoumarin
P18291
wild-type
0.88
acetyl-IEFD-7-amino-4-methylcoumarin
P18291
mutant I99A
0.89
acetyl-IEFD-7-amino-4-methylcoumarin
P18291
mutant I99A/N218A
0.93
acetyl-IEFD-7-amino-4-methylcoumarin
P18291
mutant I99R
1.3
acetyl-IEFD-7-amino-4-methylcoumarin
P18291
mutant I99A/N218A
0.37
acetyl-IEPD-7-amino-4-methylcoumarin
P18291
wild-type
2.7
acetyl-IEPD-7-amino-4-methylcoumarin
P18291
mutant I99A/N218A
0.25
acetyl-IETD-7-amino-4-methylcoumarin
P18291
wild-type
6.16
acetyl-IETD-p-nitroanilide
-
recombinant enzyme, pH 7.4, 37C
7.38
acetyl-IETD-p-nitroanilide
-
native enzyme, pH 7.4, 37C
1.18
acetyl-IKPD-7-amino-4-methylcoumarin
P18291
mutant N218T
1.6
acetyl-IKPD-7-amino-4-methylcoumarin
P18291
wild-type
1.8
acetyl-IKPD-7-amino-4-methylcoumarin
P18291
mutant N218A
0.6
acetyl-LEFD-7-amino-4-methylcoumarin
P18291
wild-type
1.1
acetyl-LEPD-7-amino-4-methylcoumarin
P18291
wild-type
0.082
Boc-Ala-Ala-Asp-SBzl
-
pH 7.5, 25C, recombinant enzyme
0.15
Boc-Ala-Ala-Asp-SBzl
-
pH 7.5, 25C, native enzyme
0.355
Boc-Ala-Ala-Asp-SBzl
-
pH 7.5, 23C
0.683
Boc-Ala-Ala-Asp-SBzl
-
pH 7.5, 23C>
0.027
IEPD-p-nitroanilide
-
pH 7.75
0.067
IEPD-p-nitroanilide
-
pH 7.75
0.082
LEED-p-nitroanilide
-
pH 7.75
0.117
LEED-p-nitroanilide
-
pH 7.75
0.5
Nalpha-tert-butyloxycarbonyl-Ala-Ala-Asp thiobenzyl ester
-
mouse
0.55
Nalpha-tert-Butyloxycarbonyl-Ala-Ala-Met thiobenzyl ester
-
mouse
0.088
VEID-p-nitroanilide
-
pH 7.75
0.17
VEID-p-nitroanilide
-
pH 7.75
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.7
2-aminobenzoyl-IEPDSSMEK-dnp
-
pH 7.4, 37C, mutant K27A
4.2
2-aminobenzoyl-IEPDSSMEK-dnp
-
pH 7.4, 37C, mutant K24A
4.4
2-aminobenzoyl-IEPDSSMEK-dnp
-
pH 7.4, 37C, wild-type
4.4
2-aminobenzoyl-IEPDSSMESK-dnp
-
pH 7.4, 37C
3.7
2-aminobenzoyl-VVADSSMASK-dnp
-
pH 7.4, 37C
1.5
2-aminobenzoyl-VVADSSMESK-dnp
-
pH 7.4, 37C
0.6
2-aminobenzoyl-VVAESSMESK-dnp
-
pH 7.4, 37C
4.4
Abz-IEPDSSMESK-2,4-dinitrophenyl
-
wild-type, 37C
4.6
Abz-IEPDSSMESK-2,4-dinitrophenyl
-
mutant Q48R/P88A/Y245H, 37C
4.34
acetyl-IETD-p-nitroanilide
-
native enzyme, pH 7.4, 37C
5.23
acetyl-IETD-p-nitroanilide
-
recombinant enzyme, pH 7.4, 37C
11
Boc-Ala-Ala-Asp-SBzl
-
pH 7.5, 25C, native enzyme
12
Boc-Ala-Ala-Asp-SBzl
-
pH 7.5, 25C, recombinant enzyme
16
Boc-Ala-Ala-Asp-SBzl
-
pH 7.5, 23C
18
Boc-Ala-Ala-Asp-SBzl
-
pH 7.5, 23C
4.9
IEPD-p-nitroanilide
-
pH 7.75
5
IEPD-p-nitroanilide
-
pH 7.75
0.15
LEED-p-nitroanilide
-
pH 7.75
0.22
LEED-p-nitroanilide
-
pH 7.75
116
Nalpha-tert-butyloxycarbonyl-Ala-Ala-Asp thiobenzyl ester
-
mouse
24
Nalpha-tert-Butyloxycarbonyl-Ala-Ala-Met thiobenzyl ester
-
mouse
11
Nalpha-tert-Butyloxycarbonyl-L-Ala-L-Ala-L-Asp thiobenzyl ester
-
-
0.3
VEID-p-nitroanilide
-
pH 7.75
0.72
VEID-p-nitroanilide
-
pH 7.75
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.000008
(S)-3-((2S,5S)-5-((2S,3S)-2-acetamido-3-methylpentanamido)-4-oxo-1,2,4,5,6,7-hexahydroazepino[3,2,1-hi]indole-2-carboxamido)-4-oxobutanoic acid
-
-
0.000025
(S)-3-((2S,5S)-5-((2S,3S)-2-acetamido-3-methylpentanamido)-4-oxo-1,2,4,5,6,7-hexahydroazepino[3,2,1-hi]indole-2-carboxamido)-4-oxobutanoic acid
-
-
0.0084
Boc-Ile-Glu-Ala-Asp-CONH(CH2)2-Ph
-
pH 7.5, 23C
0.0123
Boc-Ile-Glu-Ala-Asp-CONH(CH2)2-Ph
-
pH 7.5, 23C
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
29
-
native wild-type, 37C
82
-
recombinant wild-type, 37C
131
-
mutant Q48R/P88A/Y245H, 37C
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7 - 7.5
-
Nalpha-tert-butyloxycarbonyl-L-Ala-L-Ala-L-Asp thiobenzyl ester
7 - 7.5
-
Nalpha-tert-butyloxycarbonyl-L-Ala-L-Ala-L-Asp thiobenzyl ester
7 - 7.5
-
Nalpha-tert-butyloxycarbonyl-L-Ala-L-Ala-L-Asp thiobenzyl ester
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6 - 8.5
-
pH 6: about 60% of activity maximum, pH 8.5: about 45% of activity maximum
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
-
assay at
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
Epstein-Barr virus-transformed autologous B lymphoblastoid cell line
Manually annotated by BRENDA team
-
IL-21 and GzmB serum levels are highly correlated in subjects with systemic lupus erythematosus and freshly isolated CD51 systemic lupus erythematosus B cells constitutively express GzmB
Manually annotated by BRENDA team
-
GrB is expressed in 7 out of 12 bladder cancer cell lines
Manually annotated by BRENDA team
-
granzyme B expression is increased in lung transplant patients
Manually annotated by BRENDA team
-
granzyme B mRNA expression is increased 2.9fold in a severe septic human subject
Manually annotated by BRENDA team
-
septic megakaryocytes produce platelets with acutely altered mRNA profiles, and these platelets mediate lymphotoxicity via granzyme B
Manually annotated by BRENDA team
-
in stroke samples, Gra-b co-localizes with Annexin-V+/TUNEL+ in degenerating neurons
Manually annotated by BRENDA team
-
expressed in the bronchoalveolar lavage of patients with chronic obstructive pulmonary disease and lung inflammation
Manually annotated by BRENDA team
-
granzyme B expression is increased in lung transplant patients
Manually annotated by BRENDA team
-
expressed in the cerebrospinal fluid of multiple sclerosis and Rasmussen encephalitis patients
Manually annotated by BRENDA team
-
between smooth muscle cells
Manually annotated by BRENDA team
-
of activated CTL lines, grown in the presence of recombinant interleukin 2
Manually annotated by BRENDA team
-
expresses gzmB. Positive gzmB cytotoxic T-lymphocyte cells abrogate target cell proliferation by inducing cell death, independent of caspases and mitochondrial signaling. Positive gzmB cytotoxic T-lymphocyte cells independently induce pro-apoptotic processes either via caspase-3/-7, leading to plasma membrane perturbance and ROS production or via Bid/Bak/Bax, resulting in cytochrome c release, whereby both pathways elicit loss of mitochondrial membrane potential
Manually annotated by BRENDA team
-
a proportion of granzyme B is constitutively secreted by cytotoxic T lymphocytes in the absence of target cell engagement. Cytotoxic T lymphocyte primarily secrete inactive granzyme B zymogen, bypassing the granules. They produce less granzyme B than natural killer cells, but secrete much more (58%) than they store
Manually annotated by BRENDA team
Mus musculus B6
-
expresses gzmB. Positive gzmB cytotoxic T-lymphocyte cells abrogate target cell proliferation by inducing cell death, independent of caspases and mitochondrial signaling. Positive gzmB cytotoxic T-lymphocyte cells independently induce pro-apoptotic processes either via caspase-3/-7, leading to plasma membrane perturbance and ROS production or via Bid/Bak/Bax, resulting in cytochrome c release, whereby both pathways elicit loss of mitochondrial membrane potential
-
Manually annotated by BRENDA team
-
transcripts of the granzyme G gene are detected at the 2-cell stage, but are absent at the oocyte, 1-cell, 96 hr, and later stages. Spatial expression is confined to the extra-embryonic trophoblasts during the middle implantation stage of the mouse placenta
Manually annotated by BRENDA team
-
mitogen-stimulated
Manually annotated by BRENDA team
-
cytotoxic lymphocyte subsets and T regulatory cells, most circulating CD56+8- NK cells and half of circulating CD8+ T lymphocytes coexpress both granzymes A and B. Activation of CD8+ T-lymphocytes with concanavalin A and of CD4+ T-lymphocytes with antibodies to CD3/CD28 or CD3/CD46 induces substantial expression of granzyme B, but not of granzyme A. Granzyme B-expressing CD4+ Tr1 cells are capable of killing target cells in a perforin-dependent manner
Manually annotated by BRENDA team
-
wild-type CD8alpha+ intraepithelial lymphocytes constitutively express granzyme B
Manually annotated by BRENDA team
-
activated macrophages
Manually annotated by BRENDA team
-
cord blood- and mature skin-derived mast cells. Majority of lesional mast cells express abundant GrB
Manually annotated by BRENDA team
-
skin-, but not lung-associated primary mast cells as well as in vitro-differentiated bone marrow-derived mast cells express GzmB
Manually annotated by BRENDA team
-
in medullary carcinoma of the breast (MCB), GrB-expressing cytotoxic T cells are found in large numbers, often nearby apoptotic tumor cells
Manually annotated by BRENDA team
-
express high levels of granzyme H but relatively low levels of granzyme B
Manually annotated by BRENDA team
-
only the YT cell line, which is a poor killer expresses low levels of GzmH
Manually annotated by BRENDA team
-
a proportion of granzyme B is constitutively secreted by natural killer cells in the absence of target cell engagement. The protease is primarily released in an active form through secretory granules except in YT cells that mainly release inactive granzyme B zymogen. A-NK and NK92 cells secrete a comparatively small proportion of their granzyme B (ca. 10 and 0.3% of the total per hour, respectively), whereas YT cells release about 29%
Manually annotated by BRENDA team
-
is constitutively expressed
Manually annotated by BRENDA team
-
natural killer cells expressing CD16, generally express gA, gB and perforin simultaneously
Manually annotated by BRENDA team
-
alloreactive cytotoxic T cell clones
Manually annotated by BRENDA team
-
cells that do not express either granzyme (gA- or gB-) rarely express perforin and generally express little or no CD57. Granzyme B is never expressed without granzyme A. gA- gB- cells can only express low levels of perforin, as high perforin content requires expression of gA and gB. Less differentiated, naive T cells express no cytotoxic enzymes (gA- gB- Perf-), and nearly all highly differentiated effector T cells (which are largely terminally differentiated CD57 bright cells) express the three cytotoxic enzymes simultaneously. The majority of CMV-specific T cells express gA, gB, and perforin, whereas EBV-specific T cells mostly express gA but not gB and HIV-specific T cells express gA, gB but low levels of perforin
Manually annotated by BRENDA team
-
perforin-independent expression
Manually annotated by BRENDA team
-
elevated expression of granzyme B
Manually annotated by BRENDA team
-
regulatory T cells (Tregs) freshly isolated from the peripheral blood of normal adults lack granzyme B expression. Tregs subjected to prolonged TCR and CD28 triggering, in the presence of IL-2, express high levels of granzyme B but CD3 stimulation alone or IL-2 treatment alone fail to induce granzyme B. Treatment of Tregs with the mammalian target of rapamycin (mTOR) inhibitor, rapamycin or the PI3 kinase (PI3K) inhibitor LY294002 markedly suppressed granzyme B expression
Manually annotated by BRENDA team
-
levels of GrB in the serum and synovial fluid of rheumatoid arthritis patients is strikingly associated with the severity of erosive joint disease
Manually annotated by BRENDA team
-
around skin appendages
Manually annotated by BRENDA team
-
low levels of granzyme B mRNA within non-lesional skin, significant increase in granzyme B expression within lichen planus lesions. Positive correlation between levels of mRNA of granzyme B and granulysin within lesions of lichen planus
Manually annotated by BRENDA team
-
perforin-independent expression
Manually annotated by BRENDA team
-
expressed in the synovial fluid of rheumatoid arthritis patients
Manually annotated by BRENDA team
-
levels of GrB in the serum and synovial fluid of rheumatoid arthritis patients is strikingly associated with the severity of erosive joint disease
Manually annotated by BRENDA team
-
granzyme B and granzyme C expression is detected in CD4+ and CD8+ T cells activated with CD3/CD28 beads or MLRs
Manually annotated by BRENDA team
-
highly expressed in CD8+ T cells
Manually annotated by BRENDA team
-
peripheral CD4+CD8+ T cells express granzyme B
Manually annotated by BRENDA team
-
perforin-independent expression
Manually annotated by BRENDA team
-
granzyme B is present in thymus glands from myasthenia patients, but is absent in thymus from normal adult subjects
Manually annotated by BRENDA team
-
granzyme B and its substrate acetylcholin receptor epsilon subunit are aberrantly expressed in thymus from patients with Myasthenia gravis
Manually annotated by BRENDA team
-
around small vessels
Manually annotated by BRENDA team
-
GrB is expressed, in absence of perforin in urothelial carcinoma cells. Significant differences are found between GrB expression and both increasing pathological tumor spreading and high-grade vs. low-grade pTa tumors
Manually annotated by BRENDA team
-
septic megakaryocytes produce platelets with acutely altered mRNA profiles, and these platelets mediate lymphotoxicity via granzyme B
Manually annotated by BRENDA team
additional information
-
CD8+ T cell
Manually annotated by BRENDA team
additional information
-
granzyme B is not expressed in naive Treg cells but is highly expressed in 5%-30% of CD4(+)Foxp3(+) Treg cells in the tumor environment
Manually annotated by BRENDA team
additional information
-
in activated but not resting primary CD8+ T cells, a DNase1 hypersensitive site pesent upstream of the granzyme B gene. Thymocytes do not express granzyme B. MTL 2.8.2 cell line constitutively expresses granzyme B at a high level. CTLL R8 cell line constitutively expresses endogenous granzyme B gene
Manually annotated by BRENDA team
additional information
-
increased protein levels in all regions of vessels with advanced atherosclerosis, i.e., superficial intima, deep intima, and the media. In the intima granzyme B is present within lipid-rich regions in which it localizes to TUNEL-positive foam cells of atherosclerotic plaques. In allograft vasculopathy increase of protein levels only in the deep intima
Manually annotated by BRENDA team
additional information
-
LAK cells, gzmB and gzmH present
Manually annotated by BRENDA team
additional information
-
neither monocytes nor activated CD8+ CTLs show any GzmH expression
Manually annotated by BRENDA team
additional information
-
no GzB activity in CTL or NK92 effector cells. Lack of GzB activity in Jurkat cells
Manually annotated by BRENDA team
additional information
-
Treg cell
Manually annotated by BRENDA team
additional information
-
unstimulted HMC-1 cells and LAD 2 cells show no Grb mRNA and protein, expression upon stimulation with non-physiological stimuli
Manually annotated by BRENDA team
additional information
-
YAC-1 cell
Manually annotated by BRENDA team
additional information
-
YT-Indy cell line
Manually annotated by BRENDA team
additional information
-
absent in K562 cells
Manually annotated by BRENDA team
additional information
-
alphabeta T cell and gammabeta T cell express gA, gB and perforin simultaneously
Manually annotated by BRENDA team
additional information
-
CD4+ adaptive regulatory T cells generated by co-ligation of CD3 and CD46 express high amounts of granzyme B
Manually annotated by BRENDA team
additional information
-
CD8+ T cell, granzyme B-secreting cell
Manually annotated by BRENDA team
additional information
-
granzyme B is not detectable in K562 cell-conditioned medium
Manually annotated by BRENDA team
additional information
-
low levels of GZMB mRNA and no detectable levels of granzyme B protein in resting naive or memory CD8 T cells
Manually annotated by BRENDA team
additional information
-
large airway brushing: granzyme B expression is increased in lung transplant patients
Manually annotated by BRENDA team
additional information
Mus musculus 129/SvJ
-
granzyme B is not expressed in naive Treg cells but is highly expressed in 5%-30% of CD4(+)Foxp3(+) Treg cells in the tumor environment
-
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
cytoplasmic granules of cytotoxic T lymphocytes and natural killer cells
Manually annotated by BRENDA team
-
cytoplasmic granules of cytotoxic T lymphocytes anf natural killer cells
Manually annotated by BRENDA team
-
cytoplasmic granules of cytotoxic T lymphocytes anf natural killer cells
Manually annotated by BRENDA team
-
cytoplasmic granules of cytotoxic T lymphocytes anf natural killer cells
Manually annotated by BRENDA team
-
rapid uptake of external enzyme by HeLa cells and accumulation in cytoplasm in inactive form, uptake does not depend on enzyme activity or on mannose 6-phosphate receptor
Manually annotated by BRENDA team
-
active in cytoplasmic granules, mainly located in the dense core, partially colocalizes with tryptase in granules with both lysosomal and secretory features
Manually annotated by BRENDA team
-
is associated with cytoplasmic granules of bone marrow-derived mast cells
Manually annotated by BRENDA team
-
in thymus glands from myasthenia patients
Manually annotated by BRENDA team
-
of 2-cell stage, protein completely disappears by the 16-cell stage
Manually annotated by BRENDA team
-
for nuclear import, receptor importin alpha is required, while receptor importin beta inhibits import
Manually annotated by BRENDA team
-
both perforin and GzmB are endocytosed into giant endosomal antigen-1 endosomes that form after perforin treatment
Manually annotated by BRENDA team
additional information
-
GrB cleavage of Notch1 can occur in all subcellular compartments, during maturation of the receptor, at the membrane, and in the nucleus
-
Manually annotated by BRENDA team
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
27000 - 29000
-
-
653125
27000 - 32000
-
-
653125
27000
-
predicted from cDNA
649536
28000 - 33000
-
immunoblotting
649536
30000
-
Western blot analysis
679099
32000 - 34000
-
-
653125
32000
-
immunoblotting
699669
35000
Q2A6L4
Western blot analysis
682965
35000
-
Western blot analysis
708765
45000
-
recombinant GzmH
681968
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
?
-
x * 35000, human, SDS-PAGE, x * 45000, human, SDS-PAGE with reducing agents
?
-
x * 27400, calculated for non-activated recombinant fusion protein pro-rGBr-H6
dimer
-
-
monomer
-
1 * 25000 Da
additional information
-
enzyme interacts with either of the nuclear import receptor family members importin alpha and beta, but in addition exogenous cytosol is required for nuclear import of enzyme
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
glycoprotein
-
-
proteolytic modification
-
first expressed as an inactive proenzyme
proteolytic modification
-
GrB is synthesized as a zymogen (proGrB) and activated in cytotoxic granules by the lysosomal cysteine protease cathepsin C which removes the N-terminal dipeptide Gly-Glu. Cathepsin H is an additional convertase of proGrB
proteolytic modification
-
GrB is synthesized as a zymogen (proGrB) and activated in cytotoxic granules by cathepsin C and cathepsin H. Mice lacking both cathepsin C and cathepsin H show reduced convertase activity. Despite this, cytotoxic lymphocytes from transgenic mice retain cytotoxic activity and some residual GrB activity, indicating that other proteases must also possess convertase activity
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
space group P2(1)2(1)2(1), cell constants a = 41.74 A, b = 114.31 A, c = 135.52, in complex with a tetrapeptide aldehyde inhibitor
-
crystals by hanging drop vapor diffusion, in complex with a macromolecular inhibitor ecotin, space group P2(1), a = 56.64 A, b = 154.6 A, c = 57.24 A
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-20C, pH 4.5, stable for more than 6 months
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
active GzmH and mutant S182A purified by Ni-affinity chromatography
-
by nickel affinity chromatography
-
granzyme H
-
gzmB and gzmH
-
recombinant enzyme
-
to homogeneity
-
with B-specific monoclonal antibodies
-
by nickel affinity chromatography
-
expressed in Pichia pastoris
-
recombinant enzyme
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
293TT cells transiently transfected with plasmids encoding either for wild-type or mutant GrzmB. cDNA subcloned into the mammalian expression vector pcDNA3.1(+) or into the insect cell expression vector pVL1392. Expressed in H5 and Sf9 insect cells. Mutagenesis PCR-products transformed into Escherichia coli TOP 10
Q2A6L4
active GzmH and mutant S182A with a C-terminal 6 x His-tag coding sequence subcloned into vector pPICZalpha and expressed in Pichia pastoris. Jurkat or HeLa cells loaded with GzmH
-
cDNA subcloned from pPIC-9-GrzmB yeast-expression vector into pcDNA3.1(+)
-
commercial preparation
-
expressed in bacteria and eukaryotic cells. The large scale production of recombinant GzmB in bacteria may necessitate refolding, but this is easily achieved in optimized detergent-free refolding buffers
-
expressed in Pichia pastoris
-
expression in HEK-293 cells
-
expression in Pichia pastoris
-
expression of active GrB in yeast and by baculovirus expression
-
expression of recombinant GrB using a baculovirus expression system
-
expression of recombinant human granzyme B in COS cells
-
leukocyte cDNA amplified by PCR, expressed in a baculovirus system in Sf9 cells
-
recombinant granzyme B expressed in Pichia pastoris as a chimeric zymogen comprising the alpha-factor signal sequence, a prodomain including an enterokinase cleavage site, and the mature granzyme B sequence followed by a hexahistidine tag, cloned and expressed in Escherichia coli, resulting fusion protein is insoluble and folded incorrectly
-
recombinant human ProGrB is produced in Pichia pastoris
-
recombinant, nonglycosylated GzmH and GzmH mutant expressed in Escherichia coli
-
recombinantly expressed
-
CTLL R8 cell line stably transfected with GFP reporter constructs
-
into vector pPIC6alpha and expressed in Pichia pastoris X-33 cells
-
recombinant granzyme B expressed from baculovirus in Sf9 cells
-
cloned and expressed in Pichia pastoris
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
treatment of regulatory T cells (Tregs) with the mammalian target of rapamycin (mTOR) inhibitor, rapamycin or the PI3 kinase (PI3K) inhibitor LY294002 markedly suppresses granzyme B expression
-
expression of granzyme B is higher in patients with Bronchiolitis obliterans syndrome than in patients with acute lung transplant rejection
-
GrB expression in plasmacytoid dendritic cells is strictly regulated on a transcriptional level involving Janus kinase 1 (JAK1), signal transducer and activator of transcription 3 (STAT3), and STAT5. Interleukin-3 (IL-3), secreted by activated T cells, plays a central role for GrB induction
-
GrB in urothelial cancer tissues is concentrated at the cancer invasion front and is expressed in neoplastic cells undergoing epithelial-mesenchymal transition, a key event in carcinoma invasion
-
IL-21 directly induces GzmB expression and secretion by CD51 B cells
-
in blood, bronchoalveolar lavage (BAL) and large airway brushing expression of granzyme B is significantly increased in lung transplant patients
-
regulatory T cells (Tregs) freshly isolated from the peripheral blood of normal adults lack granzyme B expression. Tregs subjected to prolonged TCR and CD28 triggering, in the presence of IL-2, express high levels of granzyme B but CD3 stimulation alone or IL-2 treatment alone fail to induce granzyme B
-
serum levels of GrB are elevated in several diseases such as human immunodeficiency virus-1 infection, Epstein-Barr virus infection, arthritis and others
-
expression of GrB mRNA is upregulated in active lesions of multiple sclerosis patients and in activated T cells
-
stimulation of NK cells in vitro with IL-15 induce expression of granzyme C
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
D108A
Q2A6L4
complete loss of enzyme activity
S203A
Q2A6L4
complete loss of enzyme activity
A339G
-
site-directed mutagenesis
C228F
-
fusion protein pro-rGrB-H6, activity with Ac-IEPD-p-nitroanilide substrate as wild-type
C228T
-
fusion protein pro-rGrB-H6, activity with Ac-IEPD-p-nitroanilide substrate slightly lower than wild-type
C228V
-
fusion protein pro-rGrB-H6, activity with Ac-IEPD-p-nitroanilide substrate slightly lower than wild-type
C335A
-
site-directed mutagenesis
C341A
-
site-directed mutagenesis
C341S
-
site-directed mutagenesis
E340A
-
site-directed mutagenesis
E340D
-
site-directed mutagenesis
E344A
-
site-directed mutagenesis
E344D
-
site-directed mutagenesis
F336A
-
site-directed mutagenesis
Q48R/P88A/Y245H
-
common allele termed RAH, mutant enzmye has essentially identical proteolytic and cytotoxic properties to wild-type
R226G
-
replacing Arg-226 by a glycine yields an enzyme with chymase-like activity cleaving like cathepsin G after Phe
S182A
-
inactive
S183A
-
no catalytic activity
S183A
-
granzyme B active site mutant
S195A
-
GzmH mutant, catalytically inactive
S334A
-
site-directed mutagenesis
S345A
-
site-directed mutagenesis
T327R
-
site-directed mutagenesis
V337A
-
site-directed mutagenesis
I99A
P18291
substrate acetyl-IEPD-7-amino-4-methylcoumarin, drastic reduction in ratio kcat/Km
I99A/N218A
P18291
6fold increase in Km-value, substrate acetyl-IEFD-7-amino-4-methylcoumarin
I99F
P18291
substrate acetyl-IEPD-7-amino-4-methylcoumarin, 6fold reduction in ratio kcat/Km
I99R
P18291
substrate acetyl-IEPD-7-amino-4-methylcoumarin, 10fold reduction in ratio kcat/Km
N218A
P18291
substrate acetyl-IEPD-7-amino-4-methylcoumarin, 30% reduction in ratio kcat/Km
N218A/R192A
P18291
substrate acetyl-IEPD-7-amino-4-methylcoumarin, drastic reduction in ratio kcat/Km
N218A/R192E
P18291
substrate acetyl-IEPD-7-amino-4-methylcoumarin, drastic reduction in ratio kcat/Km
N218T
P18291
substrate acetyl-IEPD-7-amino-4-methylcoumarin, almost 2fold increase in ratio kcat/Km
Y174A
P18291
substrate acetyl-IEPD-7-amino-4-methylcoumarin, 6fold reduction in ratio kcat/Km
H64A
Q2A6L4
complete loss of enzyme activity
additional information
Q2A6L4
deletion of the activation di-peptide leads to a strong increase in enzyme activity
M343A
-
site-directed mutagenesis
additional information
-
expression of His-tagged enzyme, pro-rGrB-H6, dependent on activation by blood coagulation factor Xa, and of pro(IEPD)-rGrB-H6, engineered for self-activation, and of their C228 mutants
additional information
-
expression system for the production of high yields of enzymatic and biologically active human grB by transfection of HEK-293 with grB. The HEK-293 host cells are protected from apoptotic cell death by fusing an inactivation site coupled to a (His)6 tag to the gene sequence of GrB. Inactive grB which is actively released from HEK-293 cells by insertion of a Igkappa leader sequence is purified on a nickel column utilizing the (His)6 tag. After enterokinase digestion and heparin affinity chromatography, high yields of enzymatic and biologically active human grB are obtained
V338A
-
site-directed mutagenesis
additional information
-
deletion of the DNase1 hypersensitive site upstream of the granzyme B gene results in a 10fold reduction in expression
additional information
-
granzyme A/B-deficient mice exhibit significantly reduced survival compared to wild-type mice. Granzyme B-deficient mice clear both allogeneic and syngeneic tumor cell lines more efficiently than do wild-type mice. NK and CD8+ T cell death in tumor ascites of granzyme B-deficient mice is reduced after Treg cell depletion
additional information
-
granzyme B deficient mice lack expression of linked granzyme-loci, due to accidental effects of the thymidine kinase enhancer integrated into the granzyme locus on mouse Chromosome 14
additional information
-
granzyme B-deficient mice possess a normal phenotype, with the exception of reduced CTL-mediated target cell apoptosis, antiviral responses, and tumor cell clearance. Treg cells from granzyme B-deficient mice can not suppress immune responses as effectively as Treg cells from wild-type mice. Granzyme B-deficient recipient mice exhibit reduced allograft vasculopathy and increased susceptibility to allgergen-induced asthma. Hearts from 129J donor mice transplanted into granzyme B-KO mice exhibit significantly smaller lesions and luminal narrowing compared with wild-type recipients
additional information
-
gzmB-/-CTL cells, no cleavage of Bid
additional information
-
gzmB-deficient mice do not cause cell death in susceptible adherent target cells
additional information
-
mice deficient in granzyme B are up to 100000fold more sensitive to the natural mouse proxivirus pathogen ectromelia than are wild-type mice
additional information
-
target cells with reduced levels of Hsp70/Hsp90-organizing protein are no more susceptible than control target cells to GzmB-/-/deltaPGK-neo and GzmB-/-/+PGK-neo natural killer effectors. GzmA-/- x GzmB-/-/deltaPGK-neo and GzmA-/- x GzmB-/-/+PGK-neo doubly deficient natural killer effectors, likewise, show no differences in susceptibility between control and Hsp70/Hsp90-organizing protein knockdown target cells
R226G
-
replacing Arg-226 by a glycine yields an enzyme with chymase-like activity cleaving like cathepsin G after Phe
additional information
Mus musculus 129/SvJ
-
granzyme A/B-deficient mice exhibit significantly reduced survival compared to wild-type mice. Granzyme B-deficient mice clear both allogeneic and syngeneic tumor cell lines more efficiently than do wild-type mice. NK and CD8+ T cell death in tumor ascites of granzyme B-deficient mice is reduced after Treg cell depletion
-
additional information
Mus musculus B6
-
gzmB-/-CTL cells, no cleavage of Bid
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
analysis
-
caution in the design and interpretation of experiments using GrBs from different species due to distinct tetrapeptide specificities and abilities to recruit the BID pathway
biotechnology
-
engineering of mutant enzyme suitable for cleavage of fusion proteins
degradation
-
human and murine GzmB are distinct enzymes with different substrate preferences. Subtle differences in enzyme structure can radically affect substrate selection. Caspases are not essential for apoptosis initiated by human GzmB
medicine
-
A streptolysin-O/GrB combination results in the induction of p53 accumulation and transcriptional activity associated with strong induction of apoptotic cell death in T1 cells
medicine
-
can induce rapid apoptosis of target cells, which is dependent on caspase activation and mitochondrial damage. GzmH-induced death is characterized by phosphatidylserine externalization, nuclear condensation, DNA fragmentation, caspase activation and cytochrome c release. GzmH may play an essential role in caspase-dependent pathogen clearance in the innate immunity that may complement the proapoptotic function of GzmB in human natural killer cells
medicine
-
detection of target GzB activity followed by caspase 3 activation provides a unique readout of a potentially lethal injury delivered by cytotoxic lymphocytes
medicine
-
ELISPOT measurements of granzyme B permit the identification of actively ongoing CD8+ cell responses. Importance for immune diagnostic of infections, transplantation, allergies, autoimmune diseases, tumors and vaccine development
medicine
-
expression of granzyme B by peripheral CD8+ T lymphocytes does not vary between emphysematous smokers, smokers and non-smokers with normal lung function
medicine
-
extension of the present standard of IFN-gamma measurements to the analysis of GzB and perforin release in functional T cell assays will provide new insights into CD8+ effector T cell function in HIV infection
medicine
-
granzyme B may play a key role in ateromatous diseases. Role in cardiac allograft vasculopathy and atherosclerosis
medicine
-
granzyme B plays a role in the cytotoxic response in lichen planus. It is a probable target for future immunomodulator therapy
medicine
-
granzyme H participates in the anti-adenovirus response by both inhibiting virus replication directly and simultaneously re-sensitizing infected cell to granzyme B-induced cell death
medicine
-
granzymes can mediate antiviral activity through direct cleavage of viral substrates. Different granzymes have synergistic functions to outflank viral defenses that block host antiviral activities
medicine
-
GrB proteolysis of Hsc70/Hsp70-interacting protein is important to the efficiency of death induction
medicine
-
GzmH induces cell death, it is nearly as potent as GzmB. Exhibits an alternative cell death pathway in innate immunity. In contrast to GzmB, GzmH achieves cell death by acting on mitochondrial and nuclear targets but not through the activation of hallmark apoptotic substrates
medicine
-
key role of plasticity in the granzyme B mediated cell death pathway in the killing of changed tumor cells, resulting in keratoacanthoma regression through apoptosis or direct damage of tumor cells. Insufficient activation of cytotoxic T lymphocytes and decreased release or activity of granzyme B may be responsible for squamous cell-carcinoma progression and occasional aggressive behavior in keratoacanthomas. Targeted delivery of granzyme B to squamous cell, carcinoma cells may be a new agent that may have an additive or synergic effect with conventional therapeutic modalities, since there are still no known cellular resistance mechanisms capable of protecting cells against all granzyme B mediated pathways
medicine
-
extracellular granzyme B may help control localized coagulation during inflammation
medicine
-
granzyme B level may contribute to a diagnosis of immune-mediated epilepsy including Rasmussen syndrome
medicine
-
granzyme B may be the limiting factor in adaptive regulatory T cell-mediated K562 target cell killing
medicine
-
plasma granzyme B level on day 14 is a significant predicting factor for left ventricular remodeling after acute myocardial infarction
medicine
-
potential role for granzyme B in the process of initiation of myasthenia gravis
medicine
-
the release of granzyme B through two routes from unconjugated cytotoxic lymphocytes suggests that it functions outside the cell and may contribute to pathology in cases of immune dysregulation, such as familial hemophagocytic lymphohistiocytosis
medicine
-
granzyme B GrB labels a subpopulation of effector cells involved in ongoing cytotoxic action should be considered as a specific marker showing the extent of the direct local cytotoxic damage in patients with lupus erythematosus
medicine
-
modified versions of GzmB with lower isoelectric points can be utilized without loss of apoptosis-inducing potential but fewer side activities, since GzmB is very effective in killing human tumor cell lines that are resistant against cytotoxic drugs GrzmB is used as an effector domain in potential immunoconjugates
medicine
-
both GzmA and GzmB levels are significantly increased in serum of patients with patients with amyotrophic lateral sclerosis. There is a significant correlation of serum GzmB levels with severity of clinical state of amyotrophic lateral sclerosis patients
medicine
-
human neurons are selectively susceptible to granzyme B isolated from cytotoxic T cell granules. In vitro, purified human GrB induces neuronal death to the same extent as the whole activated T cell population. Following internalization through various parts of neurons, GrB accumulates in the neuronal soma. Within the cell body, GrB diffuses out of endosomes possibly through a perforin-independent mechanism and induces subsequent activation of caspases and cleavage of a-tubulin. Inhibition of caspase-3, a substrate for GrB, significantly reduces GrB-mediated neurotoxicity. Treatment of neurons with mannose-6-phosphate prevents GrB entry and inhibits GrB-mediated neuronal death
medicine
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internalization of grB by membrane Hsp70 positive tumor cells is dependent on mammalian glycosylation of GrB. Neuraminic acid blocks binding of GrB to CT26 tumor cells
medicine
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ischemic brain samples after stroke contain significantly higher levels of Gra-b and interferon-gamma inducible protein-10 than non-ischemic controls. In stroke, poly(ADP-ribose) polymerase-1 and heat shock protein-70 are cleaved to canonical proteolytic signature fragments by Gra-b. Gra-b also binds to Bid and caspase-3 and colocalizesw with Annexin-V+/TUNEL+ in degenerating neurons. Gra-b inhibition protects both normal and ischemia-reperfused neurons against in vitro neurotoxicity mediated by activated CG-SH cells and supernatants. Increased leukocyte infiltration and elevated Gra-b levels in the post-stroke brain can induce contact-dependent and independent post-ischemic neuronal death to aggravate stroke injury
medicine
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the precursor frequency and cytotoxic lymphocyte activity of HLA-A2-restricted transaldolase 168-176-specific CD8+ T cells is increased in multiple sclerosis patients. The major C-terminal GrB cleavage product of transaldolase, residues 28-337, has no enzymatic activity but retains the antigenicity of full-length transaldolase, effectively stimulating the proliferation and cytotoxic lymphocyte activity of peripheral blood mononuclear cells and of CD8+ T cell lines from patients with multiple sclerosis. Sera of multiple sclerosis patients exhibit similar binding affinity to wild-type and GrB-cleaved transaldolase
synthesis
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expression system for the production of high yields of enzymatic and biologically active human grB by transfection of HEK-293 with grB. The HEK-293 host cells are protected from apoptotic cell death by fusing an inactivation site coupled to a (His)6 tag to the gene sequence of GrB. Inactive grB which is actively released from HEK-293 cells by insertion of a Igkappa leader sequence is purified on a nickel column utilizing the (His)6 tag. After enterokinase digestion and heparin affinity chromatography, high yields of enzymatic and biologically active human grB are obtained
analysis
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caution in the design and interpretation of experiments using GrBs from different species due to distinct tetrapeptide specificities and abilities to recruit the BID pathway
degradation
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human and murine GzmB are distinct enzymes with different substrate preferences. Subtle differences in enzyme structure can radically affect substrate selection. Caspases are essential for apoptosis initiated by mouse GzmB
medicine
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cytolytic T-lymphocytes from enzyme or granzyme A deficient mice similarly induce early proapoptotic features such as phosphatidyl serine exposure on plasma membrane, or reactive oxygen radical generation, though with distinct kinetics. Cytolytic T-lymphocytes from granzyme A, but not granzyme B deficient animals activate caspase 3 and 9. All granzyme-induced apoptotic features depend critically on perforin
medicine
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activated mast cells contribute, via secreted gzmB, to cell death, increased vascular permeability, leukocyte extravasation and subsequent inflammatory processes in affected tissues. GzmB-induced detachment of adherent mouse embryonic fibroblasts leads to anoikis. GzmB induces a disorganization of endothelial cell-cell contacts
medicine
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granzyme B may play a key role in ateromatous diseases. Role in cardiac allograft vasculopathy and atherosclerosis
medicine
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Hsp70/Hsp90-organizing protein per se does not set the threshold for susceptibility to GzmB-induced apoptosis
medicine
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pleiotropic pro-apoptotic function of gzmB presumably to counteract evasion strategies of pathogens and to control tumors
medicine
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Treg cells derived from the tumor environment can induce NK and CD8(+) T cell death in a granzyme B- and perforin-dependent fashion. Granzyme B and perforin are relevant for Treg cell-mediated suppression of tumor clearance in vivo
medicine
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platelets are lymphotoxic effectors in sepsis via granzyme B
medicine
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granzyme B-deficient mice, and to a lesser extent perforin-deficient mice, exhibit a significant increase in the number of Ag-specific CD8+ T cells in the lungs and draining lymph nodes of virally infected animals. Viral titers in granzyme B-deficient mice are similar to wild-type mice and significantly less than perforin-deficient mice. Regulatory T cells from wild-type mice express high levels of granzyme B in response to infection, and depletion of regulatory T cells from these mice results in an increase in the number of Ag-specific CD8+ T cells, similar to that observed in granzyme B-deficient mice. Granzyme B-deficient regulatory T cells display defective suppression of CD8+ T cell proliferation in vitro
medicine
Mus musculus 129/SvJ
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Treg cells derived from the tumor environment can induce NK and CD8(+) T cell death in a granzyme B- and perforin-dependent fashion. Granzyme B and perforin are relevant for Treg cell-mediated suppression of tumor clearance in vivo
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medicine
Mus musculus B6
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pleiotropic pro-apoptotic function of gzmB presumably to counteract evasion strategies of pathogens and to control tumors
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additional information
Q2A6L4
Equine granzyme B shows close proximity to putative equine mast cell protease and to granzyme B from mouse, rat, and human. Equine granzyme B may be useful in the development of immunological assays for the activity of equine lymphocytes
medicine
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The soluble granzyme B levels are higher in systemic lupus erythematosus patients and associated with various clinical features like reduced complement components, C3 and C4, and skin lesion. The soluble granzyme B levels are also sturdily related with severity of the disease. Excessive secretion of soluble granzyme B and enhanced activity of cytotoxic T lymphocyte may play a vital role in the pathogenesis of systemic lupus erythematosus and organ damage
additional information
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role for granzyme B as mediator in mast cell biology
additional information
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role for granzyme B in the dismantling of the cytoskeleton. In the execution phase of apoptosis it may modify key structural proteins thus enabling the cell to be properly dismantled and eliminated by phagocytosis
additional information
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ability of gzmH to cleave host proteins involved in essential viral functions provides a novel mechanism by which granzymes can mediate direct antiviral activities
medicine
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proinflammatory gzmA and anti-inflammatory gzmB are novel modulators of the Th1/2 balance and defense in helminth infection
additional information
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cytotoxic granule-mediated death of both primary and transformed beta cells requires granzyme B. Early cell death is completely dependent on granzyme B. Death induced by granzyme B is dependent on cosecretion with perforin