Interferon regulatory factor 3, also known as IRF3, is an
interferon regulatory factor
Interferon regulatory factors (IRF) are proteins which regulate transcription of interferons (see regulation of gene expression). Interferon regulatory factors contain a conserved N-terminal region of about 120 amino acids, which folds into a s ...
.
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 due to shared ancestry between a pair of structures or genes in different taxa. A common example of homologous structures is the forelimbs of vertebrates, where the wings of bats and birds, the arms of prima ...
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 descr ...
and
IRF2
Interferon regulatory factor 2 is a protein that in humans is encoded by the ''IRF2'' gene.
Function
IRF2 encodes interferon regulatory factor 2, a member of the interferon regulatory transcription factor (IRF) family. IRF2 competitively inhib ...
. 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, 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 the protein is ...
IRF association domain and several regulatory
phosphorylation sites.
IRF3 is found in an inactive cytoplasmic form that upon serine/threonine phosphorylation forms a complex with
CREBBP
Cyclic adenosine monophosphate Response Element Binding protein Binding Protein (CREB-binding protein), also known as CREBBP or CBP or KAT3A, is a coactivator encoded by the ''CREBBP'' gene in humans, located on chromosome 16p13.3. CBP has intri ...
.
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'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.
Structural Characteristics
Basic structural characteristics, ...
.
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 blood flow decreases or stops to the coronary artery of the heart, causing damage to the heart muscle. The most common symptom is chest pain or discomfort which may ...
cardioprotection.
Interactions
IRF3 has been shown to
interact
Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization using innovative strategies to advocate for the legal and human rights of children with intersex traits. The organizati ...
with
IRF7
Interferon regulatory factor 7, also known as IRF7, is a member of the interferon regulatory factor family of transcription factors.
Function
IRF7 encodes interferon regulatory factor 7, a member of the interferon regulatory transcription fact ...
.
References
Further reading
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External links
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{{JAK-STAT signaling pathway
Transcription factors