| + |
Papain-like proteinase | down-regulates activity 
binding
|
STING1 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-260247 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 22312431 |
Here we show that human coronavirus (HCoV) NL63 and severe acute respiratory syndrome (SARS) CoV papain-like proteases (PLP) antagonize innate immune signaling mediated by STING (stimulator of interferon genes, also known as MITA/ERIS/MYPS). STING resides in the endoplasmic reticulum and upon activation, forms dimers which assemble with MAVS, TBK-1 and IKKε, leading to IRF-3 activation and subsequent induction of interferon (IFN). We found that expression of the membrane anchored PLP domain from human HCoV-NL63 (PLP2-TM) or SARS-CoV (PLpro-TM) inhibits STING-mediated activation of IRF-3 nuclear translocation and induction of IRF-3 dependent promoters. Both catalytically active and inactive forms of CoV PLPs co-immunoprecipitated with STING |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | COVID-19 Causal Network, SARS-CoV INNATE RESPONSE TO dsRNA |
| + |
Papain-like proteinase | down-regulates activity
binding, deubiquitination
|
IRF3 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-260276 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 17761676 |
PLpro interacts with IRF-3, and inhibits the phosphorylation and nuclear translocation of IRF-3, thereby disrupting the activation of type I IFN responses through either Toll-like receptor 3 or retinoic acid inducible gene I/melanoma differentiation-associated gene 5 pathways. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-260249 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 25481026 |
Here we show that PLpro also inhibits IRF3 activation at a step after phosphorylation and that this inhibition is dependent on the de-ubiquitination (DUB) activity of PLpro. We found that PLpro is able to block the type I IFN induction of a constitutively active IRF3, but does not inhibit IRF3 dimerization, nuclear localization or DNA binding. However, inhibition of PLpro’s DUB activity by mutagenesis blocked the IRF3 inhibition activity of PLpro, suggesting a role for IRF3 ubiquitination in induction of a type I IFN innate immune response. |
|
| Publications: |
2 |
Organism: |
Homo Sapiens |
| Pathways: | COVID-19 Causal Network, SARS-CoV ATTACHMENT AND ENTRY, SARS-CoV INFLAMMATORY RESPONSE, SARS-CoV INNATE RESPONSE TO dsRNA, SARS-CoV STRESS GRANULES |
| + |
Papain-like proteinase | down-regulates activity
deubiquitination
|
TRAF6 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-260248 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 31226023 |
Also, SARS-CoVPLPro catalyzed deubiquitination ofTNF-receptor-associatedfactor3(TRAF3)and TRAF6, thereby suppressing IFN-I and proinflammatory cytokines induced by TLR7 agonist |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | COVID-19 Causal Network, SARS-CoV INFLAMMATORY RESPONSE |
| + |
Papain-like proteinase | down-regulates activity
deubiquitination
|
TRAF3 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-260246 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 31226023 |
Overexpressing PLPro of SARS-CoV or MERS-CoV significantly reduced the expression of IFN-β and proinflammatory cytokines in MDA5-stimulated 293T cells (83).Also, SARS-CoVPLPro catalyzed deubiquitination of TNF-receptor-associated factor3 (TRAF3) and TRAF6, thereby suppressing IFN-I and proinflammatory cytokines induced by TLR7 agonist (63). The deubiquitinating activity of SARS-CoV PLPro also suppressed a constitutively active phosphomimetic IRF3, suggesting its involvement in the postactivation signaling of IRF3 |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | COVID-19 Causal Network, SARS-CoV INFLAMMATORY RESPONSE |
3.0
Papain-like proteinase
- 
- 