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IRF3

GeneName

IRF3

Summary

IRF3, also known as interferon regulatory factor 3, is a 47 kDa transcription factor that plays a pivotal role in the antiviral innate immune response. It is predominantly expressed in the cytoplasm and translocates to the nucleus upon activation. IRF3 is involved in the regulation of genes that produce type I interferons and other cytokines, which are crucial for the immune response to viral infections. It binds to specific DNA sequences to activate or repress transcription, thereby influencing various immune processes including the cellular response to viruses and the regulation of inflammatory responses. IRF3 is also implicated in the cGAS/STING and TLR signalling pathways, which are essential for detecting viral pathogens and initiating immune responses.

Importance

IRF3 is relevant to: - The regulation of antiviral responses through its role in type I interferon production, which is essential for controlling viral infections. - The modulation of inflammatory responses, impacting conditions such as autoimmune diseases and chronic inflammation. - The interplay between apoptosis and immune responses, particularly in macrophage function and the resolution of inflammation. - The understanding of signalling pathways like cGAS/STING and TLR, which are critical for innate immunity and therapeutic targets in infectious diseases.

Top Products

For researchers investigating IRF3, we highly recommend the top-selling recombinant monoclonal antibody, Anti-IRF3 antibody [EPR2418Y] (ab68481). This antibody has been validated in knockout models, ensuring reliable performance in various applications, including Western blotting (WB), immunocytochemistry (ICC), immunohistochemistry (IHC), and flow cytometry (FC). With 110 citations, it is well-regarded in the research community, making it an excellent choice for those seeking dependable IRF3 detection in their studies.

Abcam Product Citation Summary

The data indicates that IRF3 is a significant target in studies related to apoptosis, Type I IFN signalling, and immune responses. The use of various Abcam antibodies in both mouse and human cell lines highlights the relevance of IRF3 in different biological contexts, including responses to treatments and signalling pathways.

Abcam Product Citation Table

Product Code
Species
Application
Study Context
PMID
ab25950
Mouse
WB
Apoptosis inhibition
24551175
ab25950
Mouse
WB
Type I IFN signalling pathway activation
28542569
ab25950
Mouse
WB
Effects of sodium arsenate treatment
24551175
ab25950
Human
WB
Kinase activity
31455651
ab25950
Human
WB
Effects of IFI44 on IKKβ and IKKε activation
31455651
ab25950
Human
WB
Patient-derived fibroblasts
30672142
ab68481
Mouse
IF
cGAMP treatment
26754564
ab76409
Human
WB
TLR3/TRIF signalling
27504984
ab76409
Human
WB
IFN pathway activation
22629479

Function

Key transcriptional regulator of type I interferon (IFN)-dependent immune responses which plays a critical role in the innate immune response against DNA and RNA viruses (PubMed:22394562, PubMed:24049179, PubMed:25636800, PubMed:27302953, PubMed:31340999, PubMed:36603579, PubMed:8524823). Regulates the transcription of type I IFN genes (IFN-alpha and IFN-beta) and IFN-stimulated genes (ISG) by binding to an interferon-stimulated response element (ISRE) in their promoters (PubMed:11846977, PubMed:16846591, PubMed:16979567, PubMed:20049431, PubMed:32972995, PubMed:36603579, PubMed:8524823). Acts as a more potent activator of the IFN-beta (IFNB) gene than the IFN-alpha (IFNA) gene and plays a critical role in both the early and late phases of the IFNA/B gene induction (PubMed:16846591, PubMed:16979567, PubMed:20049431, PubMed:36603579). Found in an inactive form in the cytoplasm of uninfected cells and following viral infection, double-stranded RNA (dsRNA), or toll-like receptor (TLR) signaling, is phosphorylated by IKBKE and TBK1 kinases (PubMed:22394562, PubMed:25636800, PubMed:27302953, PubMed:36603579). This induces a conformational change, leading to its dimerization and nuclear localization and association with CREB binding protein (CREBBP) to form dsRNA-activated factor 1 (DRAF1), a complex which activates the transcription of the type I IFN and ISG genes (PubMed:16154084, PubMed:27302953, PubMed:33440148, PubMed:36603579). Can activate distinct gene expression programs in macrophages and can induce significant apoptosis in primary macrophages (PubMed:16846591). In response to Sendai virus infection, is recruited by TOMM70:HSP90AA1 to mitochondrion and forms an apoptosis complex TOMM70IRF3:BAX inducing apoptosis (PubMed:25609812). Key transcription factor regulating the IFN response during SARS-CoV-2 infection (PubMed:33440148).

Involvement in disease

Encephalopathy, acute, infection-induced, 7, herpes-specific

IIAE7

A rare complication of human herpesvirus 1 (HHV-1) infection, occurring in only a small minority of HHV-1 infected individuals. It is characterized by hemorrhagic necrosis of parts of the temporal and frontal lobes. Onset is over several days and involves fever, headache, seizures, stupor, and often coma, frequently with a fatal outcome.

None

Disease susceptibility is associated with variants affecting the gene represented in this entry.

Post-translational modifications

Constitutively phosphorylated on many Ser/Thr residues (PubMed:22394562, PubMed:23478265, PubMed:23746807). Activated following phosphorylation by TBK1 and IKBKE (PubMed:23478265, PubMed:23746807, PubMed:25636800, PubMed:36603579). Innate adapter proteins, such as MAVS, STING1 or TICAM1, are first activated by viral RNA, cytosolic DNA, and bacterial lipopolysaccharide (LPS), respectively, leading to activation of the kinases TBK1 and IKBKE (PubMed:25636800). These kinases then phosphorylate the adapter proteins on the pLxIS motif, leading to recruitment of IRF3, thereby licensing IRF3 for phosphorylation by TBK1 (PubMed:25636800). Phosphorylation at Ser-386 is followed by pyrophosphorylation at the same residue, promoting phosphorylation at Ser-396 (PubMed:36603579). Phosphorylated IRF3 dissociates from the adapter proteins, dimerizes, and then enters the nucleus to induce IFNs (PubMed:25636800, PubMed:36603579).

Pyrophosphorylated by UAP1 following phosphorylation at Ser-386 by TBK1 (PubMed:36603579). Pyrophosphorylation promotes subsequent phosphorylation at Ser-396, leading to homodimerization of IRF3 (PubMed:36603579).

Acetylation at Lys-366 by KAT8 inhibits recruimtent to promoters and transcription factor activity. Acetylation by KAT8 is promoted by phosphorylation at Ser-396.

Ubiquitinated; ubiquitination involves RBCK1 leading to proteasomal degradation (PubMed:18711448). Polyubiquitinated; ubiquitination involves TRIM21 leading to proteasomal degradation (PubMed:18641315). Ubiquitinated by UBE3C, leading to its degradation (PubMed:21167755).

ISGylated by HERC5 resulting in sustained IRF3 activation and in the inhibition of IRF3 ubiquitination by disrupting PIN1 binding. The phosphorylation state of IRF3 does not alter ISGylation.

Proteolytically cleaved by apoptotic caspases during apoptosis, leading to its inactivation (PubMed:30878284). Cleavage by CASP3 during virus-induced apoptosis inactivates it, preventing cytokine overproduction (PubMed:30878284).

(Microbial infection) ISGylated. ISGylation is cleaved and removed by SARS-COV-2 nsp3 which attenuates type I interferon responses.

(Microbial infection) Phosphorylation and subsequent activation of IRF3 is inhibited by vaccinia virus protein E3.

(Microbial infection) Phosphorylated by herpes simplex virus 1/HHV-1 US3 at Ser-175 to prevent IRF3 activation.

Sequence Similarities

Belongs to the IRF family.

Tissue Specificity

Expressed constitutively in a variety of tissues.

Cellular localization

Alternative names

Interferon regulatory factor 3, IRF-3, IRF3

swissprot:Q14653 entrezGene:3661 omim:603734

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