SARS-CoV-1 nsp3 deubiquinates K63-linked pUb-STING

Stable Identifier
R-HSA-9711016
Type
Reaction [omitted]
Species
Homo sapiens
Related Species
Human SARS coronavirus
Compartment
cytosol, endoplasmic reticulum membrane
ReviewStatus
5/5
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SARS-CoV-1 nsp3 deubiquinates K63-linked pUb-STING
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Severe acute respiratory syndrome coronavirus type 1 (SARS-CoV-1) 1a-encoded papain-like protease (PLPro or nsp3) processes the viral replicase polyprotein and interacts with other viral proteins as well as RNA to form the replication/transcription complex (RTC) (Imbert I et al. 2008; reviewed in Báez-Santos YM et al. 2015; Lei J et al. 2018). In addition, viral nsp3 processes polyubiquitin (polyUb) chains and ISG15 substrates on host cell proteins by recognizing a consensus motif LXGG (Lindner HA et al. 2005; Barretto N et al. 2005; Ratia K et al. 2006; reviewed in Lei J et al. 2018). De-ubiquitinating and deISGylating activities of SARS-CoV-1 nsp3 (PLpro) antagonize the innate immune response during SARS-CoV-1 infection. Co-immunoprecipitation experiments revealed that nsp3 interacted with STING, TRAF3 and TBK1 and disrupted the formation of the STING:TRAF3:TBK1 complex in human embryonic kidney HEK293T cells upon coexpression of tagged human proteins and nsp3 (Chen X et al. 2014). STING dimerization was also substantially reduced in cells infected with SARS-CoV-1 (Sun L et al. 2012). Studies with truncated STING proteins showed that viral nsp3 interacted with STING through the transmembrane (TM) domains. As a de-ubiquitinating enzyme, viral nsp3 inhibited the ubiquitination of RIG-I, TRAF3, STING, TBK1, and IRF3 (Sun L et al. 2012; Chen X et al. 2014). The ubiquitination of these signaling proteins controls the formation of signaling complexes and the activation of IRF3 which leads to the production of type I IFN.

The Reactome event describes nsp3-mediated removal of K63-linked polyUb on STING.

Literature References
PubMed ID Title Journal Year
22312431 Coronavirus papain-like proteases negatively regulate antiviral innate immune response through disruption of STING-mediated signaling

Clementz, MA, Chen, X, Xing, Y, Baker, SC, Banach, BS, Nichols, DB, Li, K, Zheng, Y, Chen, Z, Yang, Y, Sun, L

PLoS One 2012
24622840 SARS coronavirus papain-like protease inhibits the type I interferon signaling pathway through interaction with the STING-TRAF3-TBK1 complex

Chen, X, Xing, Y, Zheng, Y, Yang, X, Chen, Z, Yang, Y

Protein Cell 2014
Participants
Input
Output
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as an event of
Event Information
Go Biological Process
symbiont-mediated perturbation of host ubiquitin-like protein modification (0039648)
Catalyst Activity

K63-linked deubiquitinase activity of N-glycan pp1a-nsp3 [endoplasmic reticulum membrane]

Physical Entity
N-glycan pp1a-nsp3 [endoplasmic reticulum membrane] (Human SARS coronavirus)
Activity
K63-linked deubiquitinase activity (GO:0061578)
Disease
Name Identifier Synonyms
severe acute respiratory syndrome DOID:2945 SARS-CoV infection, SARS
Authored
Shamovsky, V  (2020-06-25)
Reviewed
D'Eustachio, P  (2021-01-26)
Created
Shamovsky, V  (2021-01-07)
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