SARS-CoV-2 M binds TBK1

Stable Identifier
R-HSA-9754827
Type
Reaction [omitted]
Species
Homo sapiens
Related Species
Severe acute respiratory syndrome coronavirus 2
Compartment
endoplasmic reticulum-Golgi intermediate compartment membrane, mitochondrial outer membrane
ReviewStatus
5/5
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SARS-CoV-2 M binds TBK1
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Ectopic expression of the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) membrane (M) protein was found to suppress production of type I and III IFNs in human embryonic kidney 293T cells (HEK293 cells) induced by Sendai virus infection or overexpression of RIG-I (DDX58), MDA5 (IFIH1), MAVS, TBK1 and IKKε (IKBKE) proteins (Zheng Y et al. 2020; Sui L et al. 2021). The inhibitory effect of viral M on the production of type I and III IFNs was also observed in human alveolar basal epithelial (A549) cells (Zheng Y et al. 2020). Co-immunoprecipitation experiments showed the interaction between SARS-CoV-2 M and human TBK1 upon co-expression in HEK293T (Zheng Y et al. 2020; Sui L et al. 2021). The interaction of viral M with TBK1 is thought to induce ubiquitin-mediated degradation of TBK1 thus inhibiting IRF3 activation in HEK293T cells (Sui L et al. 2021). Besides interacting with TBK1, the viral M co-immunoprecipitated with DDX58, MAVS, IKBKE (Zheng Y et al. 2020) and MDA5 (IFIH1), TRAF3, but not DDX58 (Sui L et al. 2021). SARS‑CoV‑2 M protein is thought to prevent the formation of the TRAF3:TANK:TBK1/IKBKE complex and thereby inhibit TBK1/IKBKE‑dependent activation of IRF3/IRF7 transcription factors downstream of MAVS (Zheng Y et al. 2020; Sui L et al. 2021). Similar results were reported for the SARS-CoV-1 M protein (Siu KL et al. 2009; 2014).

This Reactome event shows binding of the ER-localized SARS-CoV-2 M protein to TBK1.

Literature References
PubMed ID Title Journal Year
33372174 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) membrane (M) protein inhibits type I and III interferon production by targeting RIG-I/MDA-5 signaling

Zhang, J, Kang, D, Nan, ML, Zhan, P, Han, L, Zheng, Y, Wang, PH, Zhuang, MW, Liu, X, Gao, C

Signal Transduct Target Ther 2020
34084167 SARS-CoV-2 Membrane Protein Inhibits Type I Interferon Production Through Ubiquitin-Mediated Degradation of TBK1

Hou, Z, Wang, W, Tan, G, Zhao, Y, Liu, Q, Yu, Y, Wu, P, Sui, L, Wang, Z

Front Immunol 2021
Participants
Input
Output
Participates
as an event of
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
Shamovsky, V  (2021-10-27)
Reviewed
Messina, F  (2022-02-18)
Created
Shamovsky, V  (2021-10-05)
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