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 hide
3.4.21.79
-
RECOMMENDED NAME
GeneOntology No.
Granzyme B
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
preferential cleavage: -Asp-/- >> -Asn-/- > -Met-/-, -Ser-/-
show the reaction diagram
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
hydrolysis of peptide bond
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-
-
-
CAS REGISTRY NUMBER
COMMENTARY hide
143180-74-9
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
SwissProt
Manually annotated by BRENDA team
Mus musculus 129/SvJ
129/SvJ mice
-
-
Manually annotated by BRENDA team
gene gzmB
SwissProt
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
metabolism
physiological function
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
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
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
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-amido-4-methylcoumarin + H2O
acetyl-IAPD + 7-amino-4-methylcoumarin
show the reaction diagram
-
-
-
?
acetyl-IEFD-7-amido-4-methylcoumarin + H2O
acetyl-IEFD + 7-amino-4-methylcoumarin
show the reaction diagram
-
-
-
?
acetyl-IEPD-7-amido-4-methylcoumarin + H2O
acetyl-IEPD + 7-amino-4-methylcoumarin
show the reaction diagram
-
-
-
?
acetyl-IEPD-p-nitroanilide + H2O
?
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-p-nitroanilide + H2O
?
show the reaction diagram
-
-
-
-
?
acetyl-IKPD-7-amido-4-methylcoumarin + H2O
acetyl-IKPD + 7-amino-4-methylcoumarin
show the reaction diagram
-
-
-
?
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-amido-4-methylcoumarin + H2O
acetyl-LEPD + 7-amino-4-methylcoumarin
show the reaction diagram
-
-
-
?
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
-
-
?
beta-glycan + H2O
?
show the reaction diagram
BID + H2O
?
show the reaction diagram
-
-
-
-
?
BID + H2O
truncated BID + ?
show the reaction diagram
biglycan + 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
decorin + 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
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
fibrillin-1 + H2O
?
show the reaction diagram
-
-
-
-
?
Fibrinogen + H2O
?
show the reaction diagram
fibroblast growth factor receptor-1 + H2O
?
show the reaction diagram
-
-
-
-
?
Fibronectin + H2O
?
show the reaction diagram
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
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
LEED-p-nitroanilide + H2O
?
show the reaction diagram
-
-
-
-
?
MFLJ00057 protein + H2O
?
show the reaction diagram
-
-
-
-
?
Mi-2 + H2O
?
show the reaction diagram
-
-
-
?
microtubule-associated protein 4 + 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-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
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
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
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
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-3 + H2O
?
show the reaction diagram
pro-caspase-3 + H2O
caspase-3 + ?
show the reaction diagram
pro-caspase-7 + H2O
?
show the reaction diagram
pro-caspase-7 + H2O
caspase-7 + ?
show the reaction diagram
-
-
-
-
?
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-7 + H2O
caspase-7 + ?
show the reaction diagram
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
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
von Willebrand factor + H2O
?
show the reaction diagram
additional information
?
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
beta-glycan + H2O
?
show the reaction diagram
-
-
-
-
?
BID + H2O
truncated BID + ?
show the reaction diagram
-
efficiently cleaves both human or mouse BID
-
-
?
biglycan + H2O
?
show the reaction diagram
-
-
-
-
?
decorin + H2O
?
show the reaction diagram
-
-
-
-
?
DNA-PKcs + H2O
?
show the reaction diagram
fibrillarin + H2O
?
show the reaction diagram
-
-
-
?
fibrillin-1 + 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
-
-
-
?
Mi-2 + 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-mCASP-3 + H2O
caspase-3 + ?
show the reaction diagram
pro-mCASP-7 + H2O
caspase-7 + ?
show the reaction diagram
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
-
-
?
additional information
?
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Ca2+
-
-
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(2S,5S)-4-oxo-5-[[N-(phenylacetyl)-L-isoleucyl]amino]-N-(1H-1,2,3-triazol-4-ylmethyl)-1,2,4,5,6,7-hexahydroazepino[3,2,1-hi]indole-2-carboxamide
-
-
(2S,5S)-5-[(N-acetyl-L-isoleucyl)amino]-4-oxo-N-(1H-1,2,3-triazol-4-ylmethyl)-1,2,4,5,6,7-hexahydroazepino[3,2,1-hi]indole-2-carboxamide
-
-
(2S,5S)-5-[[N-(1-benzothiophen-3-ylacetyl)-L-isoleucyl]amino]-4-oxo-N-(1H-1,2,3-triazol-4-ylmethyl)-1,2,4,5,6,7-hexahydroazepino[3,2,1-hi]indole-2-carboxamide
-
-
(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
(3R)-N-cyclopropyl-1-(3-[[(3-methoxyphenyl)sulfonyl]amino]benzoyl)piperidine-3-carboxamide
-
-
(3S)-N-cycloheptyl-3-methyl-1-oxo-2-(pyridin-2-ylmethyl)-10-(1H-pyrrol-1-yl)-1,2,3,4-tetrahydropyrazino[1,2-a]indole-3-carboxamide
-
-
(5R)-4-(3-methoxybenzyl)-10-methyl-N-(3-methylbutyl)-3-oxo-3,4,5,5a,10,10a-hexahydro-2H-[1,4]thiazepino[7,6-b]indole-5-carboxamide
-
-
(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
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
-
2-[(4E)-4-[3-methoxy-4-(prop-2-yn-1-yloxy)benzylidene]-2,5-dioxoimidazolidin-1-yl]-N-(4-methylphenyl)acetamide
-
-
2-[(5E)-5-[4-(2-amino-2-oxoethoxy)-3-methoxybenzylidene]-2,4-dioxo-1,3-thiazolidin-3-yl]-N-(3,4-dimethylphenyl)acetamide
-
-
3-(4-chlorophenyl)-2-([[5-(2,3-dihydro-1,4-benzodioxin-2-yl)-4-phenyl-4,5-dihydro-3H-1,2,4-triazol-3-yl]sulfanyl]methyl)quinazolin-4(3H)-one
-
-
5-[2-(4-chlorophenoxy)ethoxy]-1-cyclohexyl-1H-tetrazole
-
-
Ac-IETD-CHO
reduces activity about 6fold
Ac-Ile-Glu-Thr-Asp-CHO
adenovirus 100K assembly protein
-
inhibits gzmB, gzmH relieves gzmB inhibition
-
antipain
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
Bovine aprotinin
chymostatin
cytokine response modifier A (CrmA) of poxyvirus
-
virally encoded serpin
-
ecotin[81-84IEPD]
-
-
guanidinium hydrochloride
Human plasma alpha1-protease inhibitor
Human plasma alpha2-protease macroglobulin
hydroxy(6-[2-methoxy-4-[(E)-(3-[2-[(4-methylphenyl)amino]-2-oxoethyl]-2,4-dioxo-1,3-thiazolidin-5-ylidene)methyl]phenoxy]pyridin-3-yl)oxoammonium
-
-
IEPD-CHO
-
a tetrapeptide aldehyde inhibitor, binding structure analysis from crystal structure, PDB ID 1IAU
-
IETD-CHO
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
N-acetyl-L-isoleucyl-L-alpha-glutamyl-N-[(2S)-1-carboxy-3-oxopropan-2-yl]-L-prolinamide
-
-
Nalpha-tert-Butyloxycarbonyl-Ala-Ala-Asp-CH2Cl
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
Soybean trypsin inhibitor
z-AAD-chloromethylketone
-
-
Z-Ala-Ala-Asp-CH2Cl
-
-
additional information
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
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
ionomycin
stimulates
SERPINB9
-
-
-
Substance P
-
induces granzyme B expression in mast cell line LAD2 and cord blood-derived mast cells
additional information
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0058 - 0.0387
2-aminobenzoyl-IEPDSSMEK-dnp
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 - 0.0058
Abz-IEPDSSMESK-DNP
0.1512 - 0.447
Ac-IEPD-p-nitroanilide
0.15 - 1.3
acetyl-IEFD-7-amido-4-methylcoumarin
0.37 - 2.7
acetyl-IEPD-7-amido-4-methylcoumarin
0.25
acetyl-IETD-4-methylcoumarin-7-amide
wild-type
6.16 - 7.38
acetyl-IETD-p-nitroanilide
1.18 - 1.8
acetyl-IKPD-7-amido-4-methylcoumarin
0.6
acetyl-LEFD-7-amido-4-methylcoumarin
wild-type
1.1
acetyl-LEPD-7-amido-4-methylcoumarin
wild-type
0.082 - 0.683
Boc-Ala-Ala-Asp-SBzl
0.027 - 0.067
IEPD-p-nitroanilide
0.082 - 0.117
LEED-p-nitroanilide
0.5
Nalpha-tert-butyloxycarbonyl-Ala-Ala-Asp thiobenzyl ester
-
mouse
0.55
Nalpha-tert-Butyloxycarbonyl-Ala-Ala-Met thiobenzyl ester
-
mouse
0.088 - 0.17
VEID-p-nitroanilide
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.7 - 4.4
2-aminobenzoyl-IEPDSSMEK-dnp
4.4
2-aminobenzoyl-IEPDSSMESK-dnp
Homo sapiens
-
pH 7.4, 37C
3.7
2-aminobenzoyl-VVADSSMASK-dnp
Homo sapiens
-
pH 7.4, 37C
1.5
2-aminobenzoyl-VVADSSMESK-dnp
Homo sapiens
-
pH 7.4, 37C
0.6
2-aminobenzoyl-VVAESSMESK-dnp
Homo sapiens
-
pH 7.4, 37C
4.4 - 4.6
Abz-IEPDSSMESK-2,4-dinitrophenyl
4.34 - 5.23
acetyl-IETD-p-nitroanilide
11 - 18
Boc-Ala-Ala-Asp-SBzl
4.9 - 5
IEPD-p-nitroanilide
0.15 - 0.22
LEED-p-nitroanilide
116
Nalpha-tert-butyloxycarbonyl-Ala-Ala-Asp thiobenzyl ester
Mus musculus
-
mouse
24
Nalpha-tert-Butyloxycarbonyl-Ala-Ala-Met thiobenzyl ester
Mus musculus
-
mouse
11
Nalpha-tert-Butyloxycarbonyl-L-Ala-L-Ala-L-Asp thiobenzyl ester
Homo sapiens
-
-
0.3 - 0.72
VEID-p-nitroanilide
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
5.9
beta-glycan
Homo sapiens
-
pH 7.4, 37C
202538
1.7
biglycan
Homo sapiens
-
pH 7.4, 37C
25180
1
decorin
Homo sapiens
-
pH 7.4, 37C
17574
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.013
(2S,5S)-4-oxo-5-[[N-(phenylacetyl)-L-isoleucyl]amino]-N-(1H-1,2,3-triazol-4-ylmethyl)-1,2,4,5,6,7-hexahydroazepino[3,2,1-hi]indole-2-carboxamide
-
pH 7.4, 30C
0.038
(2S,5S)-5-[(N-acetyl-L-isoleucyl)amino]-4-oxo-N-(1H-1,2,3-triazol-4-ylmethyl)-1,2,4,5,6,7-hexahydroazepino[3,2,1-hi]indole-2-carboxamide
-
pH 7.4, 30C
0.000007
(2S,5S)-5-[[N-(1-benzothiophen-3-ylacetyl)-L-isoleucyl]amino]-4-oxo-N-(1H-1,2,3-triazol-4-ylmethyl)-1,2,4,5,6,7-hexahydroazepino[3,2,1-hi]indole-2-carboxamide
-
pH 7.4, 30C
0.000008 - 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 - 0.0123
Boc-Ile-Glu-Ala-Asp-CONH(CH2)2-Ph
0.08
N-acetyl-L-isoleucyl-L-alpha-glutamyl-N-[(2S)-1-carboxy-3-oxopropan-2-yl]-L-prolinamide
-
pH 7.4, 30C
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.045
(3R)-N-cyclopropyl-1-(3-[[(3-methoxyphenyl)sulfonyl]amino]benzoyl)piperidine-3-carboxamide
Homo sapiens
-
pH 7.4, 30C
0.044
2-[(4E)-4-[3-methoxy-4-(prop-2-yn-1-yloxy)benzylidene]-2,5-dioxoimidazolidin-1-yl]-N-(4-methylphenyl)acetamide
Homo sapiens
-
pH 7.4, 30C
0.025
2-[(5E)-5-[4-(2-amino-2-oxoethoxy)-3-methoxybenzylidene]-2,4-dioxo-1,3-thiazolidin-3-yl]-N-(3,4-dimethylphenyl)acetamide
Homo sapiens
-
pH 7.4, 30C
0.044
3-(4-chlorophenyl)-2-([[5-(2,3-dihydro-1,4-benzodioxin-2-yl)-4-phenyl-4,5-dihydro-3H-1,2,4-triazol-3-yl]sulfanyl]methyl)quinazolin-4(3H)-one
Homo sapiens
-
pH 7.4, 30C
0.035
5-[2-(4-chlorophenoxy)ethoxy]-1-cyclohexyl-1H-tetrazole
Homo sapiens
-
pH 7.4, 30C
0.028
hydroxy(6-[2-methoxy-4-[(E)-(3-[2-[(4-methylphenyl)amino]-2-oxoethyl]-2,4-dioxo-1,3-thiazolidin-5-ylidene)methyl]phenoxy]pyridin-3-yl)oxoammonium
Homo sapiens
-
pH 7.4, 30C
0.00008
IEPD-CHO
Homo sapiens
-
pH 7.4, 30C
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
29
-
native wild-type, 37C
82
-
recombinant wild-type, 37C
131
-
mutant Q48R/P88A/Y245H, 37C
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7 - 7.5
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6 - 8.5
-
pH 6: about 60% of activity maximum, pH 8.5: about 45% of activity maximum
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
30
-
assay at
37
-
assay at
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
type II
Manually annotated by BRENDA team
-
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
-
in stroke samples, Gra-b co-localizes with Annexin-V+/TUNEL+ in degenerating neurons
Manually annotated by BRENDA team
-
between smooth muscle cells
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
-
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
-
septic megakaryocytes produce platelets with acutely altered mRNA profiles, and these platelets mediate lymphotoxicity via granzyme B
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
-
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
-
perforin-independent expression
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
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
-
both perforin and GzmB are endocytosed into giant endosomal antigen-1 endosomes that form after perforin treatment
Manually annotated by BRENDA team
-
for nuclear import, receptor importin alpha is required, while receptor importin beta inhibits import
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 hide
LITERATURE
27000 - 29000
-
-
27000 - 32000
-
-
27000
-
predicted from cDNA
28000 - 33000
-
immunoblotting
30000
-
Western blot analysis
32000 - 34000
-
-
32000
-
immunoblotting
45000
-
recombinant GzmH
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
dimer
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monomer
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1 * 25000 Da
additional information
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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 hide
LITERATURE
glycoprotein
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proteolytic modification
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
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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
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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
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by nickel affinity chromatography
expressed in Pichia pastoris
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granzyme H
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gzmB and gzmH
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recombinant enzyme
recombinant GST-tagged enzyme from Escherichia coli strain BL21(DE3) by ultracentrifugation, glutathione affinity chromatography and dialysis to 97% purity
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to homogeneity
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with B-specific monoclonal antibodies
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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
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
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cDNA subcloned from pPIC-9-GrzmB yeast-expression vector into pcDNA3.1(+)
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cloned and expressed in Pichia pastoris
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commercial preparation
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CTLL R8 cell line stably transfected with GFP reporter constructs
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ectopic expression of granzyme B-epidermal growth factor receptor peptide ligand transforming growth factor alpha chimeric enzyme GrB-TGFalpha in natural killer cells from a lentiviral vector, the fusion enzyme shows enhanced natural cytotoxicity and increased specific killing of tumor cells
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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
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expressed in Pichia pastoris
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expression in HEK-293 cells
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expression in Pichia pastoris
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expression of active GrB in yeast and by baculovirus expression
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expression of recombinant GrB using a baculovirus expression system
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expression of recombinant human granzyme B in COS cells
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functional recombinant expression of GST-tagged enzyme in Escherichia coli strain BL21(DE3)
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into vector pPIC6alpha and expressed in Pichia pastoris X-33 cells
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leukocyte cDNA amplified by PCR, expressed in a baculovirus system in Sf9 cells
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recombinant granzyme B expressed from baculovirus in Sf9 cells
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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
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recombinant human ProGrB is produced in Pichia pastoris
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recombinant, nonglycosylated GzmH and GzmH mutant expressed in Escherichia coli
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recombinantly expressed
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
enzyme expression is decreased in natural killer cells following immunosuppressive therapy
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expression of granzyme B is higher in patients with Bronchiolitis obliterans syndrome than in patients with acute lung transplant rejection; in blood, bronchoalveolar lavage (BAL) and large airway brushing expression of granzyme B is significantly increased in lung transplant patients
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expression of GrB mRNA is upregulated in active lesions of multiple sclerosis patients and in activated T cells
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extracellular levels of the ezyme are elevated in the bodily fluids in chronic inflammatory diseases such as atherosclerosis and rheumatoid arthritis
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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
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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
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IL-21 directly induces GzmB expression and secretion by CD51 B cells
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interleukin-6 induces CD4 T cells to express the enzyme
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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
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serum levels of GrB are elevated in several diseases such as human immunodeficiency virus-1 infection, Epstein-Barr virus infection, arthritis and others
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stimulation of NK cells in vitro with IL-15 induce expression of granzyme C
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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
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
D108A
complete loss of enzyme activity
H64A
complete loss of enzyme activity
S203A
complete loss of enzyme activity
A339G
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site-directed mutagenesis
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
C335A
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site-directed mutagenesis
C341A
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site-directed mutagenesis
C341S
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site-directed mutagenesis
E340A
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site-directed mutagenesis
E340D
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site-directed mutagenesis
E344A
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site-directed mutagenesis
E344D
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site-directed mutagenesis
F336A
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site-directed mutagenesis
M343A
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site-directed mutagenesis
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
S182A
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inactive
S195A
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GzmH mutant, catalytically inactive
S334A
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site-directed mutagenesis
S345A
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site-directed mutagenesis
T327R
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site-directed mutagenesis
V337A
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site-directed mutagenesis
V338A
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site-directed mutagenesis
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