SARS-CoV-2 nsp3 deISGylates ISGylated IRF3

Stable Identifier
R-HSA-9729725
Type
Reaction [transition]
Species
Homo sapiens
Related Species
Severe acute respiratory syndrome coronavirus 2
Compartment
cytosol
ReviewStatus
5/5
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SARS-CoV-2 nsp3 deISGylates ISGylated IRF3
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The endopeptidase activity of SARS-CoV-2 nsp3 (PLpro) includes cleavage of ISG15 from ISGylated proteins, so called deISGylation (Leite et al, 2021). Since interferon responsive factor 3 (IRF3) is ISGylated this activity contributes to the cleavage of IRF3 and attenuates type I interferon responses (Freitas et al, 2020; Shin et al, 2020).
Literature References
PubMed ID Title Journal Year
33024073 Main protease of SARS-CoV-2 serves as a bifunctional molecule in restricting type I interferon antiviral signaling

Zhang, J, Ma, L, Zhao, J, Zhao, Z, Cai, S, Zhou, L, Cui, J, Wang, PH, Wu, Y, Zhuang, Z

Signal Transduct Target Ther 2020
32726803 Papain-like protease regulates SARS-CoV-2 viral spread and innate immunity

Schulz, L, Ciesek, S, Müller, S, Baek, K, Grewe, D, Geurink, PP, Schulman, BA, Bhattacharya, A, Tascher, G, Mehdipour, AR, Bojkova, D, Shin, D, Dikic, I, Cinatl, J, Ovaa, H, Hummer, G, Rajalingam, K, Knobeloch, KP, Wilhelm, A, Widera, M, van der Heden van Noort, GJ, Mukherjee, R

Nature 2020
32428392 Characterization and Noncovalent Inhibition of the Deubiquitinase and deISGylase Activity of SARS-CoV-2 Papain-Like Protease

Pegan, SD, Durie, IA, Tripp, RA, Longo, JE, Freitas, BT, Hogan, RJ, Crich, D, Murray, J, Miller, HC

ACS Infect Dis 2020
34110168 Conformational Dynamics in the Interaction of SARS-CoV-2 Papain-like Protease with Human Interferon-Stimulated Gene 15 Protein

Leite, WC, Weiss, KL, Qian, S, Phillips, G, Coates, L, Tsutakawa, SE, O'Neill, H, Zhang, Q

J Phys Chem Lett 2021
Participants
Input
Output
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as an event of
Catalyst Activity

ISG15-specific peptidase activity of N-glycan nsp3 [endoplasmic reticulum membrane]

Physical Entity
N-glycan nsp3 [endoplasmic reticulum membrane] (Severe acute respiratory syndrome coronavirus 2)
Activity
ISG15-specific peptidase activity (GO:0019785)
Disease
Name Identifier Synonyms
COVID-19 DOID:0080600 2019 Novel Coronavirus (2019-nCoV), Wuhan seafood market pneumonia virus infection, 2019-nCoV infection, Wuhan coronavirus infection
Authored
Stephan, R  (2021-06-11)
Reviewed
Messina, F  (2022-02-18)
Created
Stephan, R  (2021-05-03)
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