| + |
NSD3 | up-regulates activity 
methylation
|
IRF3 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-259198 |
Lys366 |
RLVMVLysVVPTC |
Homo sapiens |
HEK-293T Cell |
| pmid |
sentence |
| 29101251 |
We found that lysine methyltransferase NSD3 interacts with and directly monomethylates IRF3 in the nucleus, leading to the enhanced IRF3 transcriptional activity and antiviral immune responses. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
BGLF4 | down-regulates activity 
phosphorylation
|
IRF3 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-266647 |
Ser123 |
DFSQPDTsPDTNGGG |
Homo sapiens |
HEK-293T Cell |
| pmid |
sentence |
| 19052084 |
BGLF4 kinase interacts physically with and phosphorylates IRF3, which is the initial activator of transcription in the innate immune response. BGLF4 suppresses IRF3-dependent transcriptional activation. Data here suggest that Ser123, Ser173, and Thr180 contribute additively to the BGLF4-mediated repression of the IRF3 transactivation activity. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-266648 |
Ser173 |
PCPQPLRsPSLDNPT |
Homo sapiens |
HEK-293T Cell |
| pmid |
sentence |
| 19052084 |
BGLF4 kinase interacts physically with and phosphorylates IRF3, which is the initial activator of transcription in the innate immune response. BGLF4 suppresses IRF3-dependent transcriptional activation. Data here suggest that Ser123, Ser173, and Thr180 contribute additively to the BGLF4-mediated repression of the IRF3 transactivation activity. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-266649 |
Thr180 |
SPSLDNPtPFPNLGP |
Homo sapiens |
HEK-293T Cell |
| pmid |
sentence |
| 19052084 |
BGLF4 kinase interacts physically with and phosphorylates IRF3, which is the initial activator of transcription in the innate immune response. BGLF4 suppresses IRF3-dependent transcriptional activation. Data here suggest that Ser123, Ser173, and Thr180 contribute additively to the BGLF4-mediated repression of the IRF3 transactivation activity. |
|
| Publications: |
3 |
Organism: |
Homo Sapiens |
| Pathways: | EBV infection |
| + |
MAPK8 | up-regulates
phosphorylation
|
IRF3 |
0.55 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-183489 |
Ser173 |
PCPQPLRsPSLDNPT |
Homo sapiens |
|
| pmid |
sentence |
| 19153595 |
In this study, we show that another kinase, c-jun-nh(2)-terminal kinase (jnk), phosphorylates irf3 on its n-terminal serine 173 residuejnk1 can synergize the action of irf3(5d), but not the s173a-irf3(5d) mutant |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | COVID-19 Causal Network, SARS-CoV ATTACHMENT AND ENTRY, Toll like receptors |
| + |
IKBKE | up-regulates activity
phosphorylation
|
IRF3 |
0.732 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-178363 |
Ser385 |
MARVGGAsSLENTVD |
in vitro |
|
| pmid |
sentence |
| 18440553 |
Virus-induced phosphoactivation of irf-3, thought to be mediated directly or indirectly by ikkepsilon And/or tbk1 occurs in the c-terminal region of irf-3 at seven ser/thr residues, 385sslentvdlhisnshplslts405 (fig. 1a).Within This region, irf-3 has two phosphorylation sites: site 1 includes ser385 and ser386, whereas site 2 includes ser396, ser398, ser402, ser405, and thr404. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-178367 |
Ser386 |
ARVGGASsLENTVDL |
in vitro |
|
| pmid |
sentence |
| 18440553 |
Virus-induced phosphoactivation of irf-3, thought to be mediated directly or indirectly by ikk? And/or tbk1 occurs in the c-terminal region of irf-3 at seven ser/thr residues, 385sslentvdlhisnshplslts405 (fig. 1a).Within This region, irf-3 has two phosphorylation sites: site 1 includes ser385 and ser386, whereas site 2 includes ser396, ser398, ser402, ser405, and thr404. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-178371 |
Ser396 |
NTVDLHIsNSHPLSL |
in vitro |
|
| pmid |
sentence |
| 18440553 |
Virus-induced phosphoactivation of irf-3, thought to be mediated directly or indirectly by ikk? And/or tbk1 occurs in the c-terminal region of irf-3 at seven ser/thr residues, 385sslentvdlhisnshplslts405 (fig. 1a).Within This region, irf-3 has two phosphorylation sites: site 1 includes ser385 and ser386, whereas site 2 includes ser396, ser398, ser402, ser405, and thr404. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-178375 |
Ser398 |
VDLHISNsHPLSLTS |
in vitro |
|
| pmid |
sentence |
| 18440553 |
Virus-induced phosphoactivation of irf-3, thought to be mediated directly or indirectly by ikk? And/or tbk1 occurs in the c-terminal region of irf-3 at seven ser/thr residues, 385sslentvdlhisnshplslts405 (fig. 1a).Within This region, irf-3 has two phosphorylation sites: site 1 includes ser385 and ser386, whereas site 2 includes ser396, ser398, ser402, ser405, and thr404. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-178379 |
Ser402 |
ISNSHPLsLTSDQYK |
in vitro |
|
| pmid |
sentence |
| 18440553 |
Virus-induced phosphoactivation of irf-3, thought to be mediated directly or indirectly by ikk? And/or tbk1 occurs in the c-terminal region of irf-3 at seven ser/thr residues, 385sslentvdlhisnshplslts405 (fig. 1a).Within This region, irf-3 has two phosphorylation sites: site 1 includes ser385 and ser386, whereas site 2 includes ser396, ser398, ser402, ser405, and thr404. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-178383 |
Ser405 |
SHPLSLTsDQYKAYL |
in vitro |
|
| pmid |
sentence |
| 18440553 |
Virus-induced phosphoactivation of irf-3, thought to be mediated directly or indirectly by ikk? And/or tbk1 occurs in the c-terminal region of irf-3 at seven ser/thr residues, 385sslentvdlhisnshplslts405 (fig. 1a).Within This region, irf-3 has two phosphorylation sites: site 1 includes ser385 and ser386, whereas site 2 includes ser396, ser398, ser402, ser405, and thr404. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-178387 |
Thr404 |
NSHPLSLtSDQYKAY |
in vitro |
|
| pmid |
sentence |
| 18440553 |
Virus-induced phosphoactivation of irf-3, thought to be mediated directly or indirectly by ikk? And/or tbk1 occurs in the c-terminal region of irf-3 at seven ser/thr residues, 385sslentvdlhisnshplslts405 (fig. 1a).Within This region, irf-3 has two phosphorylation sites: site 1 includes ser385 and ser386, whereas site 2 includes ser396, ser398, ser402, ser405, and thr404. |
|
| Publications: |
7 |
Organism: |
In Vitro |
| Pathways: | COVID-19 Causal Network, Innate Immune Response, SARS-CoV INNATE RESPONSE TO dsRNA, Toll like receptors |
| + |
TBK1 | up-regulates activity
phosphorylation
|
IRF3 |
0.817 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-178391 |
Ser385 |
MARVGGAsSLENTVD |
in vitro |
|
| pmid |
sentence |
| 18440553 |
Virus-induced phosphoactivation of irf-3, thought to be mediated directly or indirectly by ikk? And/or tbk1 occurs in the c-terminal region of irf-3 at seven ser/thr residues, 385sslentvdlhisnshplslts405 (fig. 1a).Within This region, irf-3 has two phosphorylation sites: site 1 includes ser385 and ser386, whereas site 2 includes ser396, ser398, ser402, ser405, and thr404. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-178395 |
Ser386 |
ARVGGASsLENTVDL |
in vitro |
|
| pmid |
sentence |
| 18440553 |
Virus-induced phosphoactivation of irf-3, thought to be mediated directly or indirectly by ikk? And/or tbk1 occurs in the c-terminal region of irf-3 at seven ser/thr residues, 385sslentvdlhisnshplslts405 (fig. 1a).Within This region, irf-3 has two phosphorylation sites: site 1 includes ser385 and ser386, whereas site 2 includes ser396, ser398, ser402, ser405, and thr404. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-178399 |
Ser396 |
NTVDLHIsNSHPLSL |
in vitro |
|
| pmid |
sentence |
| 18440553 |
Virus-induced phosphoactivation of irf-3, thought to be mediated directly or indirectly by ikk? And/or tbk1 occurs in the c-terminal region of irf-3 at seven ser/thr residues, 385sslentvdlhisnshplslts405 (fig. 1a).Within This region, irf-3 has two phosphorylation sites: site 1 includes ser385 and ser386, whereas site 2 includes ser396, ser398, ser402, ser405, and thr404. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-178403 |
Ser398 |
VDLHISNsHPLSLTS |
in vitro |
|
| pmid |
sentence |
| 18440553 |
Virus-induced phosphoactivation of irf-3, thought to be mediated directly or indirectly by ikk? And/or tbk1 occurs in the c-terminal region of irf-3 at seven ser/thr residues, 385sslentvdlhisnshplslts405 (fig. 1a).Within This region, irf-3 has two phosphorylation sites: site 1 includes ser385 and ser386, whereas site 2 includes ser396, ser398, ser402, ser405, and thr404. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-178407 |
Ser402 |
ISNSHPLsLTSDQYK |
in vitro |
|
| pmid |
sentence |
| 18440553 |
Virus-induced phosphoactivation of irf-3, thought to be mediated directly or indirectly by ikk? And/or tbk1 occurs in the c-terminal region of irf-3 at seven ser/thr residues, 385sslentvdlhisnshplslts405 (fig. 1a).Within This region, irf-3 has two phosphorylation sites: site 1 includes ser385 and ser386, whereas site 2 includes ser396, ser398, ser402, ser405, and thr404. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-178411 |
Ser405 |
SHPLSLTsDQYKAYL |
in vitro |
|
| pmid |
sentence |
| 18440553 |
Virus-induced phosphoactivation of irf-3, thought to be mediated directly or indirectly by ikk? And/or tbk1 occurs in the c-terminal region of irf-3 at seven ser/thr residues, 385sslentvdlhisnshplslts405 (fig. 1a).Within This region, irf-3 has two phosphorylation sites: site 1 includes ser385 and ser386, whereas site 2 includes ser396, ser398, ser402, ser405, and thr404. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-178420 |
Thr404 |
NSHPLSLtSDQYKAY |
in vitro |
|
| pmid |
sentence |
| 18440553 |
Virus-induced phosphoactivation of irf-3, thought to be mediated directly or indirectly by ikk? And/or tbk1 occurs in the c-terminal region of irf-3 at seven ser/thr residues, 385sslentvdlhisnshplslts405 (fig. 1a).Within This region, irf-3 has two phosphorylation sites: site 1 includes ser385 and ser386, whereas site 2 includes ser396, ser398, ser402, ser405, and thr404. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-260154 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 24622840 |
STING recruits TBK1 and IKKε and forms the TBK1-IKKε complex via the association with TRAF3. The TBK1 complex induces the phosphorylation, dimerization, and nuclear translocation of IRF3. |
|
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-120355 |
|
|
Homo sapiens |
T-lymphocyte |
| pmid |
sentence |
| 14679297 |
We show that purified recombinant ikk-epsilon and tbk1 directly phosphorylate the critical serine residues in irf3 allowing its translocation into the nucleus and production of interferon type i. |
|
| Publications: |
9 |
Organism: |
In Vitro, Homo Sapiens |
| Pathways: | COVID-19 Causal Network, EBV infection, Innate Immune Response, Inflammosome Activation, SARS-CoV INFLAMMATORY RESPONSE, SARS-CoV INNATE RESPONSE TO dsRNA, Toll like receptors |
| + |
PTEN | up-regulates activity
dephosphorylation
|
IRF3 |
0.259 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-277025 |
Ser97 |
LRLAEDRsKDPHDPH |
Homo sapiens |
|
| pmid |
sentence |
| 32394474 |
PTEN can dephosphorylate IRF-3 S97 residue and facilitate its nuclear import for the IFN signaling pathway (7).|PTEN expression directly increases activated IRF-3 nuclear import and subsequent interferon (IFN) synthesis. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
PRKDC | up-regulates
phosphorylation
|
IRF3 |
0.406 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-115331 |
Thr135 |
GGGSTSDtQEDILDE |
Homo sapiens |
|
| pmid |
sentence |
| 11867762 |
Phosphorylation of irf-3 by dna-pk after virus infection results in its nuclear retention and delayed proteolysis |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
ABL1 | up-regulates activity
phosphorylation
|
IRF3 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-277440 |
Tyr292 |
RLGHCHTyWAVSEEL |
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 30842273 |
The data in this study show that IRF3 is physically associated with c-Abl in vivo and directly binds to c-Abl in vitro. IRF3 is phosphorylated by c-Abl and c-Abl-related kinase, Arg, mainly at Y292. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
ABL2 | up-regulates activity
phosphorylation
|
IRF3 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-277441 |
Tyr292 |
RLGHCHTyWAVSEEL |
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 30842273 |
The data in this study show that IRF3 is physically associated with c-Abl in vivo and directly binds to c-Abl in vitro. IRF3 is phosphorylated by c-Abl and c-Abl-related kinase, Arg, mainly at Y292. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
IRF3 | up-regulates 
|
Interferon_Production |
0.7 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-126962 |
|
|
Mus musculus |
MEF Cell |
| pmid |
sentence |
| 20610653 |
Type 1 IFNs are induced in a cell type-specific manner through Toll-like receptor and RIG-I-like receptor pathways, both of which activate interferon regulatory factors (IRFs) and nuclear factor _B (NF-_B) transcription factors. |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| Pathways: | EBV infection, Toll like receptors |
| + |
PPP2CA | down-regulates activity
dephosphorylation
|
IRF3 |
0.318 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-260944 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 24726876 |
RACK1 Negatively Regulates the Type I IFN pathway. Here we report that IRF3 is deactivated via dephosphorylation mediated by the serine and threonine phosphatase PP2A and its adaptor protein RACK1. The PP2A-RACK1 complex negatively regulated the IRF3 pathway after LPS or poly(I:C) stimulation or Sendai virus (SeV) infection. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | COVID-19 Causal Network, SARS-CoV STRESS GRANULES |
| + |
IRF3 | up-regulates quantity by expression
transcriptional regulation
|
Interferon-type-I |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-260330 |
|
|
Mus musculus |
|
| pmid |
sentence |
| 20610653 |
Type 1 IFNs are induced in a cell type-specific manner through Toll-like receptor and RIG-I-like receptor pathways, both of which activate interferon regulatory factors (IRFs) and nuclear factor _B (NF-_B) transcription factors. |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| Pathways: | COVID-19 Causal Network, EBV infection, Innate Immune Response, Inflammosome Activation, SARS-CoV ATTACHMENT AND ENTRY, SARS-CoV INFLAMMATORY RESPONSE, SARS-CoV INNATE RESPONSE TO dsRNA |
| + |
TRIM26 | down-regulates quantity by destabilization
polyubiquitination
|
IRF3 |
0.659 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-272440 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 25763818 |
TRIM26 bound to IRF3 and promoted its K48-linked polyubiquitination and degradation in nucleus. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
CDH8 | up-regulates quantity
transcriptional regulation
|
IRF3 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-266898 |
|
|
Homo sapiens |
HeLa Cell |
| pmid |
sentence |
| 17938208 |
CHD8 binds to histone H3 di- and trimethylated on lysine 4. It resides on the human U6 promoter as well as the mRNA IRF3 promoter in vivo and contributes to efficient transcription from both these promoters |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
BRLF1 | down-regulates quantity by repression
transcriptional regulation
|
IRF3 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-266644 |
|
|
Homo sapiens |
HEK-293T Cell |
| pmid |
sentence |
| 20381110 |
EBV Rta selectively down-regulates the expression of IRF3 and IRF7, the main regulators of the Type I IFNs. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | EBV infection |
| + |
N | down-regulates activity 
|
IRF3 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-260337 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 17108024 |
The data presented here indicate that N protein inhibits interferon production, while ORF 3b and ORF 6 proteins are able to inhibit both interferon production and interferon signaling. IRF-3 activation is inhibited in cells that express ORF 3b, ORF 6, or N protein, and NF-κB is inhibited in cells expressing N protein.ORF 3b, ORF 6, and N proteins all effectively inhibit phosphorylation of IRF-3.SARS-CoV ORF 3b, ORF 6, and N proteins all inhibit activation of IRF-3 by phosphorylation and binding of IRF-3 to a promoter with IRF-3 binding sites. |
|
| Publications: |
1 |
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 |
| + |
3b | down-regulates activity
|
IRF3 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-260338 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 17108024 |
The data presented here indicate that N protein inhibits interferon production, while ORF 3b and ORF 6 proteins are able to inhibit both interferon production and interferon signaling. IRF-3 activation is inhibited in cells that express ORF 3b, ORF 6, or N protein, and NF-κB is inhibited in cells expressing N protein.ORF 3b, ORF 6, and N proteins all effectively inhibit phosphorylation of IRF-3.SARS-CoV ORF 3b, ORF 6, and N proteins all inhibit activation of IRF-3 by phosphorylation and binding of IRF-3 to a promoter with IRF-3 binding sites. |
|
| Publications: |
1 |
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 |
| + |
6 | down-regulates activity
|
IRF3 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-260339 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 17108024 |
The data presented here indicate that N protein inhibits interferon production, while ORF 3b and ORF 6 proteins are able to inhibit both interferon production and interferon signaling. IRF-3 activation is inhibited in cells that express ORF 3b, ORF 6, or N protein, and NF-κB is inhibited in cells expressing N protein.ORF 3b, ORF 6, and N proteins all effectively inhibit phosphorylation of IRF-3.SARS-CoV ORF 3b, ORF 6, and N proteins all inhibit activation of IRF-3 by phosphorylation and binding of IRF-3 to a promoter with IRF-3 binding sites. |
|
| Publications: |
1 |
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 |
| + |
8a | down-regulates activity
binding
|
IRF3 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-260239 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 29294448 |
Accessory proteins 8b and 8ab of severe acute respiratory syndrome coronavirus suppress the interferon signaling pathway by mediating ubiquitin-dependent rapid degradation of interferon regulatory factor 3.We also found that proteins 8b and 8ab could physically interact with IRF3. Overexpression of 8b and 8ab resulted in the reduction of poly (I:C)-induced IRF3 dimerization and inhibition of the IFN-β signaling pathway. |
|
| Publications: |
1 |
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 |
| + |
8b | down-regulates activity
binding
|
IRF3 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-260240 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 29294448 |
Accessory proteins 8b and 8ab of severe acute respiratory syndrome coronavirus suppress the interferon signaling pathway by mediating ubiquitin-dependent rapid degradation of interferon regulatory factor 3.We also found that proteins 8b and 8ab could physically interact with IRF3. This counteracting effect was partially mediated by protein 8b/8ab-induced degradation of IRF3 in a ubiquitin-proteasome-dependent manner. Taken together, we propose that SARS-CoV may exploit the unique functions of proteins 8b and 8ab as novel mechanisms to overcome the effect of IFN response during virus infection.. |
|
| Publications: |
1 |
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 |
| + |
IRF3 | up-regulates
|
Immune_response |
0.7 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-216316 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 12692549 |
The transcription factors interferon regulatory factor 3 (IRF3) and NF-B are required for the expression of many genes involved in the innate immune response. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | COVID-19 Causal Network, EBV infection, Innate Immune Response, Inflammosome Activation, SARS-CoV ATTACHMENT AND ENTRY, SARS-CoV INFLAMMATORY RESPONSE, SARS-CoV INNATE RESPONSE TO dsRNA, SARS-CoV STRESS GRANULES, Toll like receptors |
| + |
DUSP10 | down-regulates activity
dephosphorylation
|
IRF3 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-277146 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 26305722 |
The inactivation of IRF3 by MKP5 is dependent on MKP5 phosphatase activity or its binding to IRF3.|This is confirmed since MKP5 phosphatasedeficient mutant is unable to dephosphorylate IRF3 and MKP5 mutant lacking IRF3 binding motifs fails to suppress IRF3 nuclear translocation upon virus infection. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
IRF3 | up-regulates quantity by expression
transcriptional regulation
|
IL6 |
0.418 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-251721 |
|
|
Mus musculus |
Macrophage |
| pmid |
sentence |
| 27337441 |
Recent reports show that in mice the microbiome, comprising commensal microorganisms that colonize body surfaces, promotes a partial and low-grade M1-like phenotype in macrophages throughout the body, including those in lymphoid organs (119, 120). This M1-like priming of macrophages induces chromatin remodeling with increased H3K4me3 marks at Ifnb, Il6, and Tnf promoters, which is associated with increased binding of NF-κB p65, IRF3, and Pol II upon cell stimulation |
|
| Publications: |
1 |
Organism: |
Mus Musculus |
| Pathways: | COVID-19 Causal Network |
| + |
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 |
| + |
IRF3 | up-regulates quantity by expression
transcriptional regulation
|
IFNB1 |
0.653 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-252257 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 16699525 |
Similarly, exogenous expression of wild-type Pin1 suppressed TLR3-mediated, IRF3-dependent activation of the IFN-beta promoter and reduced IFN-beta secretion in culture supernatants |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | EBV infection |
| + |
MAVS | up-regulates activity
binding
|
IRF3 |
0.794 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-260143 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 25636800 |
Phosphorylated MAVS and STING then bind to a positively charged surface of interferon regulatory factor 3 (IRF3) and thereby recruit IRF3 for its phosphorylation and activation by TBK1. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | COVID-19 Causal Network, Innate Immune Response, SARS-CoV INNATE RESPONSE TO dsRNA, SARS-CoV STRESS GRANULES |
| + |
Host translation inhibitor nsp1 | down-regulates activity
|
IRF3 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-262503 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 17715225 |
SARS-CoV nsp1 inhibits virus-dependent activation of IRF3 and IRF7. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | SARS-CoV ATTACHMENT AND ENTRY, SARS-CoV INFLAMMATORY RESPONSE, SARS-CoV INNATE RESPONSE TO dsRNA, SARS-CoV STRESS GRANULES |
| + |
PPM1A | down-regulates activity
dephosphorylation
|
IRF3 |
0.25 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-277152 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 27419230 |
In contrast, coexpression of wild-type PPM1A, but not its D239N or R174G mutant, abolished IRF3 activation (XREF_FIG).|We found that PPM1A abolished the C-terminal phosphorylation of IRF3 (XREF_FIG), whereas depletion of PPM1A expression improved virus induced pIRF3 level (XREF_FIG and XREF_FIG). |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
IRF3 | up-regulates quantity by expression
transcriptional regulation
|
SOCS2 |
0.372 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-254495 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 22291912 |
SOCS2 induction by LPS was dependent on the type I IFN regulated transcription factors IRF1 and IRF3 as shown by using silencing RNAs for IRFs. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
IRF3 | up-regulates quantity by expression
transcriptional regulation
|
ABCC2 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-254533 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 15185298 |
Expression of recombinant human IRF3 increased MRP2 promoter activity. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
KPNA2 | up-regulates activity
relocalization
|
IRF3 |
0.2 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-262514 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 32979938 |
The results from Figure 1C suggest that ORF6 inhibits IFN-β production through IRF3 or a component downstream of IRF3. Thus, we examined the effect of ORF6 on IRF3 nuclear translocation. Upon poly(I:C) treatment, IRF3 translocated to the cell nucleus in the absence of ORF6, whereas the expression of ORF6 blocked its nuclear translocation (Figure 2D). Karyopherin α 1–6 (KPNA1–6) are importing factors for nuclear translocation of cargos, including IRF3, IRF7, and STAT1 (Chook and Blobel, 2001). Co-immunoprecipitation showed that ORF6 selectively interacted with KPNA2, but not the other KPNAs (Figure 2E), suggesting that ORF6 inhibits IFN-β production by binding to KPNA2 to block IRF3 nuclear translocation (Figure 2F). |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| Pathways: | SARS-CoV INFLAMMATORY RESPONSE |
| + |
PIN1 | down-regulates quantity by destabilization
binding
|
IRF3 |
0.627 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-252256 |
|
|
Homo sapiens |
|
| pmid |
sentence |
| 16699525 |
Here we report that activation of IRF3 is negatively regulated by the peptidyl-prolyl isomerase Pin1. After stimulation by double-stranded RNA, induced phosphorylation of the Ser339–Pro340 motif of IRF3 led to its interaction with Pin1 and finally polyubiquitination and then proteasome-dependent degradation of IRF3. Suppression of Pin1 by RNA interference or genetic deletion resulted in enhanced IRF-3-dependent production of interferon-beta, with consequent reduction of virus replication. |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
TRIM59 | down-regulates activity
|
IRF3 |
0.264 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-260373 |
|
|
Homo sapiens |
HeLa Cell, HEK-293T Cell |
| pmid |
sentence |
| 22588174 |
TRIM59 also inhibited the phosphorylation of IRF3 and IRF7, which induces dimerization, suggesting that TRIM59 negatively regulates kinases for IRF3/7 (IKKe/TBK1) or their upstream signal |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
| + |
RBCK1 | down-regulates quantity by destabilization
polyubiquitination
|
IRF3 |
0.331 |
| Identifier |
Residue |
Sequence |
Organism |
Cell Line |
| SIGNOR-271737 |
|
|
Homo sapiens |
HEK-293 Cell |
| pmid |
sentence |
| 18711448 |
Here we show that the E3 ubiquitin ligase RBCC protein interacting with PKC1 (RBCK1) catalyzes the ubiquitination and degradation of IRF3. We transfected 293 cells with expression plasmids for Flag-IRF3, HA-ubiquitin, and HA-RBCK1. Coimmunoprecipitation and western blot analysis indicated that RBCK1 significantly polyubiquitinated IRF3 (Figure 4D). |
|
| Publications: |
1 |
Organism: |
Homo Sapiens |
3.0
IRF3
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