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Synonyms
2apro, 2a protease, usp2a, protease 2a, 2a proteinase, proteinase 2a, poliovirus 2apro, poliovirus 2a protease, ubiquitin-specific protease 2a, poliovirus protease 2a,
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eukaryotic initiation factor 4G + H2O
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Bid protein + H2O
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cAMP-regulated response element binding protein + H2O
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CVB1 protein + H2O
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death-associated protein 5 + H2O
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dystrophin + H2O
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eIF4G + H2O
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eukaryotic initiation factor-4G
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eukaryotic translation initiation factor 4G + H2O
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eIF4G
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eukaryotic translation initiation factor 4gamma + H2O
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eukaryotic translation initiation factor 4Gl + H2O
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Grb2-associated binding protein 1 + H2O
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GAB1 is cleaved during CV-B3 infection by viral proteinase 2A
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Grb2-associated binding protein 2 + H2O
GAB2-N1-237 + GAB2-C238-676
MAVS + H2O
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a cellular protein
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MDA5 + H2O
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a cellular protein
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nuclear factor of activated T cells 5/tonicity enhancer binding protein
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picornavirus polyprotein + H2O
hydrolyzed picornavirus polyprotein
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poly-(ADP-ribose) polymerase + H2O
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pro-caspase 3 + H2O
caspase 3 + ?
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serum response factor + H2O
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additional information
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death-associated protein 5 + H2O
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DAP5
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death-associated protein 5 + H2O
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DAP5, generation of 45 kDa N-terminal (DAP5-N) and 52 kDa C-terminal (DAP5-C) fragments, respectively. DAP5 is cleaved at amino acid G434
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Grb2-associated binding protein 2 + H2O
GAB2-N1-237 + GAB2-C238-676
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GAB2 is cleaved at G238 during CV-B3 infection by viral proteinase 2A, generating two cleaved fragments of GAB2-N1-237 and GAB2-C238-676
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Grb2-associated binding protein 2 + H2O
GAB2-N1-237 + GAB2-C238-676
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GAB2 is cleaved at G238 during CV-B3 infection by viral proteinase 2A, generating two cleaved fragments of GAB2-N1-237 and GAB2-C238-676. mutant GAB2G238E is non-cleavable for the enzyme
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nuclear factor of activated T cells 5/tonicity enhancer binding protein
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NFAT5/TonEBP, a cellular transcription factor, the protein is cleaved by CVB3 protease 2A at Gly503, inactivation of NFAT5
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nuclear factor of activated T cells 5/tonicity enhancer binding protein
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NFAT5/TonEBP, a cellular transcription factor, the protein is cleaved by CVB3 protease 2A at Gly503, which is the only CVB3 protease 2A cleavage site on NFAT5, leading to inactivation of NFAT5
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additional information
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does not cleave death-associated protein 5
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additional information
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DAP5 is cleaved during CVB3 infection in tissue culture and in mouse heart
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additional information
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in vivo assays by expression of GAB2 proteins in virus-infected HeLa cells
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eukaryotic initiation factor 4G + H2O
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CVB1 protein + H2O
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death-associated protein 5 + H2O
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DAP5
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dystrophin + H2O
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eIF4G + H2O
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eukaryotic initiation factor-4G
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eukaryotic translation initiation factor 4G + H2O
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eIF4G
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eukaryotic translation initiation factor 4gamma + H2O
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Grb2-associated binding protein 1 + H2O
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GAB1 is cleaved during CV-B3 infection by viral proteinase 2A
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?
Grb2-associated binding protein 2 + H2O
GAB2-N1-237 + GAB2-C238-676
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GAB2 is cleaved at G238 during CV-B3 infection by viral proteinase 2A, generating two cleaved fragments of GAB2-N1-237 and GAB2-C238-676
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MAVS + H2O
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a cellular protein
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?
MDA5 + H2O
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a cellular protein
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?
nuclear factor of activated T cells 5/tonicity enhancer binding protein
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NFAT5/TonEBP, a cellular transcription factor, the protein is cleaved by CVB3 protease 2A at Gly503, inactivation of NFAT5
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serum response factor + H2O
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additional information
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additional information
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DAP5 is cleaved during CVB3 infection in tissue culture and in mouse heart
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additional information
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in vivo assays by expression of GAB2 proteins in virus-infected HeLa cells
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?
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physiological function
2A protease is the key viral component that triggers stress granule formation
malfunction
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a catalytic mutant of 2A (2Amut) fails to cleave GAB2. Deletion of GAB1 causes a decrease in phosphorylated ERK1/2, but knockdown of GAB2 has no effect on virus-mediated ERK1/2 phosphorylation
malfunction
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CVB3 mutants, that arise with passage in polyamine-depleted conditions, contain mutations in the 2A protease (EC 3.4.22.29) and 3C protease (EC 3.4.22.28). These mutant proteases confer resistance to polyamine depletion. The 2A and 3C protease mutations also enhance reporter protease activity in polyamine-depleted conditions. The mutations promote cleavage of cellular eIF4G during infection of polyamine-depleted cells
malfunction
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overexpression of these DAP5 truncates (45 kDa N-terminal (DAP5-N) and 52 kDa C-terminal (DAP5-C) fragments) demonstrates that DAP5-N retains the capability of initiating IRES-driven translation of apoptosis-associated p53, but not the prosurvival Bcl-2 (B-cell lymphoma 2) when compared with the full-length DAP5
physiological function
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cleavage of serum response factor mediated by enteroviral protease 2A contributes to impaired cardiac function in mice
physiological function
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death-associated protein 5 (DAP5) is cleaved during CVB3 infection by coxsackievirus B3 2A protease. Viral protease 2A but not 3C (EC 3.4.22.28) is responsible for DAP5 cleavage generating 45 kDa N-terminal (DAP5-N) and 52 kDa C-terminal (DAP5-C) fragments, respectively. Cleavage of DAP5 facilitates viral replication and enhances apoptosis by altering translation of IRES-containing genes. Also eukaryotic translation initiation factor 4G (eIF4G) is cleaved during infection by the enterovirus protease leading to the shutoff of cellular cap-dependent translation, but it does not affect the initiation of cap-independent translation of mRNAs containing an internal ribosome entry site (IRES). DAP5 is cleaved at amino acid G434. Upon cleavage, DAP5-N largely translocates to the nucleus at the later time points of infection, whereas the DAP5-C largely remains in the cytoplasm. DAP5-N expression promotes CVB3 replication and progeny release. On the other hand, DAP5-C exerts a dominant-negative effect on cap-dependent translation. DAP5 is cleaved into N- and C-terminal-truncated forms during CVB3 infection in vitro and in vivo and is transcriptionally downregulated. DAP5-N and DAP5-C differentially regulate translation of p53 and Bcl-2 and result in apoptotic cell death. DAP5-N and DAP5-C differentially alter translation but not transcription of IRES-containing genes p53 and Bcl-2
physiological function
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enterovirus 2Apro plays a key role in inhibiting innate antiviral cellular responses. The direct cleavage of eIF4G by 2Apro contributes to the suppression of stress granule (SG) formation. Cleavage of eIF4G impairs the recruitment of 40S ribosomes to mRNAs, thereby altering the composition of mRNPs, which, in turn, may affect their recruitment to SGs. The observation that 2Apro triggers SG formation by cleavage of eIF4G. During enterovirus infection, several signaling molecules in the RLR pathway have been suggested to be cleaved by 2Apro and 3Cpro (EC 3.4.22.28). Enzyme 2Apro is the viral protease responsible for cleaving MAVS. Addition of recombinant 2Apro, but not 3Cpro, to cell lysates results in the appearance of MAVS cleavage products of the same size as those observed in infected cells. These cleavage products are also observed when 2Apro, but not 3Cpro, is expressed by a recombinant encephalomyocarditis virus (EMCV), a picornavirus that by itself does not cleave components of the RLR pathway. Enterovirus 2Apro, but not 3Cpro, suppresses the induction of IFN-alpha/beta gene transcription in HeLa cells. Heterologous expression of 2Apro during EMCV infection (EMCV-2Apro) nearly completely blocks IFN-beta gene transcription (about 500fold reduction) indicates that it is unlikely that suppression of SG formation by 2Apro is the major contributing factor in the viral suppression of IFN-beta gene transcription. 2Apro is a major enteroviral security protein
physiological function
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Grb2-associated binding protein 2 (GAB2) is cleaved at G238 during CV-B3 infection by viral proteinase 2A. Knockdown of GAB2 significantly inhibits the synthesis of viral protein and subsequent viral progeny production, accompanied by reduced levels of phosphorylated p38, suggesting a pro-viral function for GAB2 linked to p38 activation. Expression of the cleavage products of GAB2 does not further enhance viral replication, indicating that GAB2 cleavage results in its loss-of-function, rather than gain-of-function in supporting viral replication that represents a distinct host defense mechanism
physiological function
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the 2A and 3C picornaviral proteases function to cleave both host and viral proteins. 3C protease is responsible for the majority of viral polyprotein cleavage, while 2A facilitates the cleavage between the P1 and P2 protein segments. Polyamines are crucial to protease function during picornavirus infection
physiological function
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the enzyme cleaves cellular transcription factor nuclear factor of activated T cells 5/tonicity enhancer binding protein (NFAT5/TonEBP). The 70-kDa N-terminal cleavage product (p70-NFAT5, amino acid residues 175-471 within the N-terminal fragment of NFAT5) exerts a dominant negative effect on the full-length NFAT5 protein. Elevated expression of NFAT5 to counteract viral protease cleavage, especially overexpression of a non-cleavable mutant of NFAT5, significantly inhibits CVB3 replication. Ectopic expression of NFAT5 results in elevated expression of inducible nitric oxide synthase (iNOS), a factor reported to inhibit CVB3 replication. The anti-CVB3 activity of NFAT5 is impaired during CVB3 infection due to 2A-mediated cleavage of NFAT5
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D136N
the mutant shows wild type cleavage efficiency toward eukaryotic initiation factor 4G
D39E
the mutant shows wild type cleavage efficiency toward eukaryotic initiation factor 4G
G122E
the mutant exhibits very low cleavage efficiency toward eukaryotic initiation factor 4G
L40F
the mutant shows wild type cleavage efficiency toward eukaryotic initiation factor 4G
S67F
the mutant shows reduced cleavage efficiency toward eukaryotic initiation factor 4G
V120M
the mutant shows wild type cleavage efficiency toward eukaryotic initiation factor 4G
Y89L
the mutant shows wild type cleavage efficiency toward eukaryotic initiation factor 4G
Y90L
the mutant shows reduced cleavage efficiency toward eukaryotic initiation factor 4G
additional information
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generation of inactive mutant 2A29K through site-directed mutagenesis
additional information
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overexpression of these DAP5 truncates (45 kDa N-terminal (DAP5-N) and 52 kDa C-terminal (DAP5-C) fragments) demonstrates that DAP5-N retains the capability of initiating IRES-driven translation of apoptosis-associated p53, but not the prosurvival Bcl-2 (B-cell lymphoma 2) when compared with the full-length DAP5
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
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Chau, D.H.; Yuan, J.; Zhang, H.; Cheung, P.; Lim, T.; Liu, Z.; Sall, A.; Yang, D.
Coxsackievirus B3 proteases 2A and 3C induce apoptotic cell death through mitochondrial injury and cleavage of eIF4GI but not DAP5/p97/NAT1
Apoptosis
12
513-524
2007
Coxsackievirus B3
brenda
Maghsoudi, N.; Tafreshi, N.K.h.; Khodagholi, F.; Zakeri, Z.; Esfandiarei, M.; Hadi-Alijanvand, H.; Sabbaghian, M.; Maghsoudi, A.H.; Sajadi, M.; Zohri, M.; Moosavi, M.; Zeinoddini, M.
Targeting enteroviral 2A protease by a 16-mer synthetic peptide: inhibition of 2Apro-induced apoptosis in a stable Tet-on HeLa cell line
Virology
399
39-45
2010
Coxsackievirus B3
brenda
Wong, J.; Zhang, J.; Yanagawa, B.; Luo, Z.; Yang, X.; Chang, J.; McManus, B.; Luo, H.
Cleavage of serum response factor mediated by enteroviral protease 2A contributes to impaired cardiac function
Cell Res.
22
360-371
2012
Coxsackievirus B3
brenda
Wu, S.; Wang, Y.; Lin, L.; Si, X.; Wang, T.; Zhong, X.; Tong, L.; Luan, Y.; Chen, Y.; Li, X.; Zhang, F.; Zhao, W.; Zhong, Z.
Protease 2A induces stress granule formation during coxsackievirus B3 and enterovirus 71 infections
Virol. J.
11
192
2015
Coxsackievirus B3 (Q66282), Coxsackievirus B3, Coxsackievirus B3 Woodruff (Q66282), Enterovirus A71 (Q66478), Enterovirus A71
brenda
Hanson, P.J.; Ye, X.; Qiu, Y.; Zhang, H.M.; Hemida, M.G.; Wang, F.; Lim, T.; Gu, A.; Cho, B.; Kim, H.; Fung, G.; Granville, D.J.; Yang, D.
Cleavage of DAP5 by coxsackievirus B3 2A protease facilitates viral replication and enhances apoptosis by altering translation of IRES-containing genes
Cell Death Differ.
23
828-840
2016
Coxsackievirus B3
brenda
Deng, H.; Fung, G.; Qiu, Y.; Wang, C.; Zhang, J.; Jin, Z.G.; Luo, H.
Cleavage of Grb2-associated binding protein 2 by viral proteinase 2A during coxsackievirus infection
Front. Cell. Infect. Microbiol.
7
85
2017
Coxsackievirus B3
brenda
Visser, L.J.; Langereis, M.A.; Rabouw, H.H.; Wahedi, M.; Muntjewerff, E.M.; de Groot, R.J.; van Kuppeveld, F.J.M.
Essential role of enterovirus 2A protease in counteracting stress granule formation and the induction of type I Interferon
J. Virol.
93
e00222-19
2019
Coxsackievirus A21, Coxsackievirus B3, Enterovirus A71, Enterovirus D68, no activity in Encephalomyocarditis virus
brenda
Qiu, Y.; Ye, X.; Zhang, H.M.; Hanson, P.; Zhao, G.; Tong, L.; Xie, R.; Yang, D.
Cleavage of osmosensitive transcriptional factor NFAT5 by Coxsackieviral protease 2A promotes viral replication
PLoS Pathog.
13
e1006744
2017
Coxsackievirus B3
brenda
Dial, C.N.; Tate, P.M.; Kicmal, T.M.; Mounce, B.C.
Coxsackievirus B3 responds to polyamine depletion via enhancement of 2A and 3C protease activity
Viruses
11
403
2019
Coxsackievirus B3, Coxsackievirus B3 Nancy
brenda