3.4.21.79: granzyme B
This is an abbreviated version!
For detailed information about granzyme B, go to the full flat file.
Word Map on EC 3.4.21.79
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3.4.21.79
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perforin
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t-cells
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cd8
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cytolytic
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immunotherapy
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vaccine
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lymphoma
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rejection
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tnf
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dendritic
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cell-mediated
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ifn-gamma
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allograft
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tregs
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tia-1
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fasl
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foxp3
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autologous
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interferon-gamma
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caspases
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degranulation
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allogeneic
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epstein-barr
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antigen-specific
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virus-specific
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immunophenotype
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ctla-4
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anti-cd3
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tumor-infiltrating
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nk-cell
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extranodal
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elispot
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synthesis
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eomes
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graft-versus-leukemia
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cd45ro
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alcls
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biotechnology
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death-1
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analysis
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intragraft
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lag-3
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hiv-specific
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medicine
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diagnostics
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degradation
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alloreactive
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lymphocyte-mediated
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lymphokine-activated
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crma
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b-mediated
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pharmacology
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ag-specific
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banff
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hepatosplenic
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anti-pd-1
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interleukin-15
- 3.4.21.79
- perforin
- t-cells
- cd8
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cytolytic
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immunotherapy
- vaccine
- lymphoma
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rejection
- tnf
- dendritic
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cell-mediated
- ifn-gamma
-
allograft
-
tregs
- tia-1
- fasl
- foxp3
-
autologous
- interferon-gamma
-
caspases
-
degranulation
-
allogeneic
-
epstein-barr
-
antigen-specific
-
virus-specific
-
immunophenotype
-
ctla-4
-
anti-cd3
-
tumor-infiltrating
-
nk-cell
-
extranodal
-
elispot
- synthesis
-
eomes
-
graft-versus-leukemia
-
cd45ro
-
alcls
- biotechnology
-
death-1
- analysis
-
intragraft
- lag-3
-
hiv-specific
- medicine
- diagnostics
- degradation
-
alloreactive
-
lymphocyte-mediated
-
lymphokine-activated
- crma
-
b-mediated
- pharmacology
-
ag-specific
-
banff
-
hepatosplenic
-
anti-pd-1
- interleukin-15
Reaction
preferential cleavage: -Asp-/- >> -Asn-/- > -Met-/-, -Ser-/- =
Synonyms
Asp-ase, C11, CCP1, CCPII, CTLA1, CTSGL1, Cytotoxic cell proteinase-1, cytotoxic lymphocyte-associated protease, cytotoxic lymphocyte-specific protein, cytotoxic serine protease granzyme B, cytotoxic T-lymphocyte-associated gene transcript-1, gB, Gra-b, granzyme B, Granzyme G, Granzyme H, GrB, GrzmB, GzB, Gzm, Gzm B, GzmB, GzmB-like enzyme, GzmH, HLp, Human lymphocyte protein, Lymphocyte protease, natural killer cell protease 1, pro-apoptotic serine protease, proGrB, Proteinase, CCP1, rat grB[N66Q], SECT, T-cell serine protease 1-3E
ECTree
3.4.21.79 granzyme BAdvanced search results
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results (Engineering
Engineering on EC 3.4.21.79 - granzyme B
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PROTEIN VARIANTS 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
C228F
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fusion protein pro-rGrB-H6, activity with Ac-IEPD-p-nitroanilide substrate as wild-type
C228T
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fusion protein pro-rGrB-H6, activity with Ac-IEPD-p-nitroanilide substrate slightly lower than wild-type
C228V
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fusion protein pro-rGrB-H6, activity with Ac-IEPD-p-nitroanilide substrate slightly lower than wild-type
Q48R/P88A/Y245H
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common allele termed RAH, mutant enzmye has essentially identical proteolytic and cytotoxic properties to wild-type
R226G
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replacing Arg-226 by a glycine yields an enzyme with chymase-like activity cleaving like cathepsin G after Phe
S183A
R226G
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replacing Arg-226 by a glycine yields an enzyme with chymase-like activity cleaving like cathepsin G after Phe
I99A
substrate acetyl-IEPD-7-amino-4-methylcoumarin, drastic reduction in ratio kcat/Km
I99A/N218A
6fold increase in Km-value, substrate acetyl-IEFD-7-amino-4-methylcoumarin
I99F
substrate acetyl-IEPD-7-amino-4-methylcoumarin, 6fold reduction in ratio kcat/Km
I99R
substrate acetyl-IEPD-7-amino-4-methylcoumarin, 10fold reduction in ratio kcat/Km
N218A
substrate acetyl-IEPD-7-amino-4-methylcoumarin, 30% reduction in ratio kcat/Km
N218A/R192A
substrate acetyl-IEPD-7-amino-4-methylcoumarin, drastic reduction in ratio kcat/Km
N218A/R192E
substrate acetyl-IEPD-7-amino-4-methylcoumarin, drastic reduction in ratio kcat/Km
N218T
substrate acetyl-IEPD-7-amino-4-methylcoumarin, almost 2fold increase in ratio kcat/Km
Y174A
substrate acetyl-IEPD-7-amino-4-methylcoumarin, 6fold reduction in ratio kcat/Km
additional information
additional information
deletion of the activation di-peptide leads to a strong increase in enzyme activity
additional information
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deletion of the activation di-peptide leads to a strong increase in enzyme activity
additional information
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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
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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
additional information
generation of a recombinant chimeric enzyme by fusion of the pre-pro-granzyme B to the epidermal growth factor receptor peptide ligand transforming growth factor alpha. Activation of the genetically modified natural killer cells by cognate target cells resulted in the release of chimeric enzyme GrB-TGFalpha together with endogenous granzymes and perforin, which augments the effector cells natural cytotoxicity against NK-sensitive tumor cells. The chimeric enzyme GrB-TGFalpha is released into the extracellular space upon induction of degranulation with phspbol-12-myristate-13-acetate and ionomycin. The secreted GrB-TGFalpha chimeric enzyme displays specific binding to EGFR-overexpressing tumor cells, enzymatic activity, and selective target cell killing in the presence of an endosomolytic activity. Release of GrB-TGFalpha protein from NKL/GrB-TGFalpha cells upon activation-induced degranulation
additional information
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generation of a recombinant chimeric enzyme by fusion of the pre-pro-granzyme B to the epidermal growth factor receptor peptide ligand transforming growth factor alpha. Activation of the genetically modified natural killer cells by cognate target cells resulted in the release of chimeric enzyme GrB-TGFalpha together with endogenous granzymes and perforin, which augments the effector cells natural cytotoxicity against NK-sensitive tumor cells. The chimeric enzyme GrB-TGFalpha is released into the extracellular space upon induction of degranulation with phspbol-12-myristate-13-acetate and ionomycin. The secreted GrB-TGFalpha chimeric enzyme displays specific binding to EGFR-overexpressing tumor cells, enzymatic activity, and selective target cell killing in the presence of an endosomolytic activity. Release of GrB-TGFalpha protein from NKL/GrB-TGFalpha cells upon activation-induced degranulation
additional information
construction of a protein-based therapeutic platform, termed cytoplasmic oncoprotein verifier and response trigger (COVERT), which enables the interrogation of intracellular proteases to trigger targeted cytotoxicity. COVERT molecules consist of the cytotoxic protein granzyme B (GrB) fused to an inhibitory N-terminal peptide, which can be removed by researcher-specified proteases to activate GrB function. Fusion of a small ubiquitin-like modifier 1 (SUMO1) protein to GrB yields a SUMO-GrB molecule that is specifically activated by the cancer-associated sentrin-specific protease 1 (SENP1). SUMO-GrB selectively triggers apoptotic phenotypes in HEK293T cells that overexpress SENP1, and it is highly sensitive to different SENP1 levels across cell lines. The rational design of additional COVERT molecules responsive to enterokinase (EK) and tobacco etch virus protease (TEVp) highlight the COVERT platform's modularity and adaptability to diverse protease targets. Primary human T cells (Jurkat cells) can express, package, traffic, and deliver engineered GrB molecules in response to antigen stimulation. The COVERT platform, ENLYFQ-GrB is evaluated for its ability to selectively mediate cytotoxicity against HEK293T cells expressing TEVp. In contrast to SENP1, TEVp is not mammalian in origin, and its forced expression mimics a state of viral infection. Transient expression of GrB in HEK293T cells resulted in marked changes in cell physiology regardless of whether the cells co-expressed TEVp. Method evaluation supporting the modularity and versatility of the COVERT platform for targeting proteolytic markers of a variety of disease states, overview
additional information
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construction of a protein-based therapeutic platform, termed cytoplasmic oncoprotein verifier and response trigger (COVERT), which enables the interrogation of intracellular proteases to trigger targeted cytotoxicity. COVERT molecules consist of the cytotoxic protein granzyme B (GrB) fused to an inhibitory N-terminal peptide, which can be removed by researcher-specified proteases to activate GrB function. Fusion of a small ubiquitin-like modifier 1 (SUMO1) protein to GrB yields a SUMO-GrB molecule that is specifically activated by the cancer-associated sentrin-specific protease 1 (SENP1). SUMO-GrB selectively triggers apoptotic phenotypes in HEK293T cells that overexpress SENP1, and it is highly sensitive to different SENP1 levels across cell lines. The rational design of additional COVERT molecules responsive to enterokinase (EK) and tobacco etch virus protease (TEVp) highlight the COVERT platform's modularity and adaptability to diverse protease targets. Primary human T cells (Jurkat cells) can express, package, traffic, and deliver engineered GrB molecules in response to antigen stimulation. The COVERT platform, ENLYFQ-GrB is evaluated for its ability to selectively mediate cytotoxicity against HEK293T cells expressing TEVp. In contrast to SENP1, TEVp is not mammalian in origin, and its forced expression mimics a state of viral infection. Transient expression of GrB in HEK293T cells resulted in marked changes in cell physiology regardless of whether the cells co-expressed TEVp. Method evaluation supporting the modularity and versatility of the COVERT platform for targeting proteolytic markers of a variety of disease states, overview
additional information
creation and synthesis of an antimalarial fusion protein consisting of granzyme B fused to a merozoite surface protein 4 (MSP4)-specific single-chain Fv protein (scFv), which targets the enzyme to infected erythrocytes, with up to an 8fold reduction in the IC50 of 176 nM compared to wild-type granzyme B against schizont-stage Plasmodium falciparum strain 3D7A, method, overview. Generation of a single-chain variable fragment (scFv) from an MSP4EGF-like domain-specific murine antibody, 2.44IgG1
additional information
synthesis of the GrB-superparamagnetic nanocarriers (SPIONs): preparation of superparamagnetic iron oxide nanoparticles from salt solutions FeSO4 and FeCl3 by coprecipitation, dextran is added to the nanosuspension for prevention of sedimentation. The dextran coating of the synthesized nanoparticles is cross-linked with epichlorohydrin and aminated. Activated by carbodiimide aminated-dextran is coupled to the carboxyl groups of proteins. The hydrodynamic size and electrophoretic properties of the nanoparticles are estimated. Functionalized superparamagnetic iron oxide nanoparticles (SPIONs) have emerged as potential clinical tools for cancer theranostics. GrB-functionalized SPIONs act as a contrast enhancement agent for magnetic resonance imaging and induce specific tumor cell apoptosis. Combinatorial regimens employing stereotactic radiotherapy and/or magnetic targeting are found to further enhance the therapeutic efficacy of GrB-SPIONs in different tumor mouse models. Magnetic targeting of the nanoparticles in vivo with a magnet placed on top of orthotopic U87 glioblastoma in NMRU nu/nu mice and C6 glioma in Wistar rats drastically enhances the accumulation of nanoparticles to the location of the magnet
additional information
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deletion of the DNase1 hypersensitive site upstream of the granzyme B gene results in a 10fold reduction in expression
additional information
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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
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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
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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
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gzmB-deficient mice do not cause cell death in susceptible adherent target cells
additional information
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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
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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
additional information
construction of functional fluorescent chimeric GZMB-Tomato (GZMB-Tom) fusion protein. The GZMB-Tom knock-in mice in which GZMB-Tom faithfully reproduce GZMB expression, provide useful tools to dissect mechanisms leading to the development of anti-bacterial effector and memory CD8+ T-cells and reactivation of the memory response to cognate antigen or inflammatory signals. The use of CD8+ T-cells from knock in mice expressing a functional fluorescent chimeric GZMB-Tom protein in place of GZMB allow the evaluation of the induction of GZMB during CD8+ T-cell differentiation as a function of T-cell division. Mice homozygous for GZMB-Tom and heterozygous for the OT1 (GZMB-Tom-OT1) or OT2 (GZMB-Tom-OT2) transgenic T-cell receptors are used. Congenic C57BL/6 (CD45.1) mice are used as recipients
additional information
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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
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additional information
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construction of functional fluorescent chimeric GZMB-Tomato (GZMB-Tom) fusion protein. The GZMB-Tom knock-in mice in which GZMB-Tom faithfully reproduce GZMB expression, provide useful tools to dissect mechanisms leading to the development of anti-bacterial effector and memory CD8+ T-cells and reactivation of the memory response to cognate antigen or inflammatory signals. The use of CD8+ T-cells from knock in mice expressing a functional fluorescent chimeric GZMB-Tom protein in place of GZMB allow the evaluation of the induction of GZMB during CD8+ T-cell differentiation as a function of T-cell division. Mice homozygous for GZMB-Tom and heterozygous for the OT1 (GZMB-Tom-OT1) or OT2 (GZMB-Tom-OT2) transgenic T-cell receptors are used. Congenic C57BL/6 (CD45.1) mice are used as recipients
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