Interferon regulatory factor 3, also known as IRF3, is an
interferon regulatory factor.
Function
IRF3 is a member of the interferon regulatory transcription factor (IRF) family.
IRF3 was originally discovered as a
homolog
In biology, homology is similarity in anatomical structures or genes between organisms of different taxa due to shared ancestry, ''regardless'' of current functional differences. Evolutionary biology explains homologous structures as retained her ...
of
IRF1
Interferon regulatory factor 1 is a protein that in humans is encoded by the ''IRF1'' gene.
Function
Interferon regulatory factor 1 was the first member of the interferon regulatory transcription factor (IRF) family identified. Initially desc ...
and
IRF2. IRF3 has been further characterized and shown to contain several functional domains including a nuclear export signal, a
DNA-binding domain
A DNA-binding domain (DBD) is an independently folded protein domain that contains at least one structural motif that recognizes double- or single-stranded DNA. A DBD can recognize a specific DNA sequence (a recognition sequence) or have a gener ...
, a
C-terminal
The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, carboxy tail, C-terminal end, or COOH-terminus) is the end of an amino acid chain (protein or polypeptide), terminated by a free carboxyl group (-COOH). When t ...
IRF association domain and several regulatory
phosphorylation
In biochemistry, phosphorylation is described as the "transfer of a phosphate group" from a donor to an acceptor. A common phosphorylating agent (phosphate donor) is ATP and a common family of acceptor are alcohols:
:
This equation can be writ ...
sites.
IRF3 is found in an inactive cytoplasmic form that upon serine/threonine phosphorylation forms a complex with
CREBBP.
The complex
translocates into the nucleus for the transcriptional activation of interferons alpha and beta, and further interferon-induced genes.
IRF3 plays an important role in the
innate immune system
The innate immune system or nonspecific immune system is one of the two main immunity strategies in vertebrates (the other being the adaptive immune system). The innate immune system is an alternate defense strategy and is the dominant immune s ...
's response to
viral infection
A viral disease (or viral infection) occurs when an organism's body is invaded by pathogenic viruses, and infectious virus particles (virions) attach to and enter susceptible cells.
Examples include the common cold, gastroenteritis, COVID-19, t ...
.
Aggregated
MAVS have been found to activate IRF3 dimerization. A 2015 study shows phosphorylation of innate immune adaptor proteins MAVS, STING and TRIF at a conserved pLxIS motif recruits and specifies IRF3 phosphorylation and activation by the Serine/threonine-protein kinase TBK1, thereby activating the production of type-I interferons.
Another study has shown that IRF3-/- knockouts protect from myocardial infarction.
The same study identified IRF3 and the type I IFN response as a potential therapeutic target for post-
myocardial infarction
A myocardial infarction (MI), commonly known as a heart attack, occurs when Ischemia, blood flow decreases or stops in one of the coronary arteries of the heart, causing infarction (tissue death) to the heart muscle. The most common symptom ...
cardioprotection.
Interactions
IRF3 has been shown to
interact with
IRF7.
References
Further reading
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External links
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{{JAK-STAT signaling pathway
Transcription factors