Mus musculus Gene: Irf3
Summary
InnateDB Gene IDBG-181123.6
Last Modified 2014-10-13 [Report errors or provide feedback]
Gene Symbol Irf3
Gene Name interferon regulatory factor 3
Synonyms C920001K05Rik; IRF-3;
Species Mus musculus
Ensembl Gene ENSMUSG00000003184
Encoded Proteins
interferon regulatory factor 3
interferon regulatory factor 3
interferon regulatory factor 3
Protein Structure
Useful resources Stemformatics EHFPI ImmGen
InnateDB Annotation
Summary
Irf3 is strongly phosphorylated at the late stages of a Sindbis virus infection to mount antiviral responses in human embryonic kidney cells. (Demonstrated in human)
Irf3 is involved in the innate immune recognition of Plasmodium falciparum AT-rich DNA and in the subsequent induction of type I IFNs. Mice lacking Irf3/Irf7 are resistant to otherwise lethal cerebral malaria.
Irf3 suppresses neuroinflammation through regulation of immunomodulatory mmu-mir-155 microRNA expression in astrocytes. (Demonstrated in human)
HIV accessory protein Vpu targets Irf3 to endolysosome for proteolytic degradation to avoid antiviral immune responses. (Demonstrated in human)
Endoplasmic reticulum stress primes macrophages to respond to innate immunity stimuli by activating IRF3.
Plasmodium RNA is a pathogen-associated molecular pattern (PAMP) capable of activating a type I IFN response via the cytosolic pattern recognition receptors Ifih1 and Mavs, as well as via transcription factors Irf3 and Irf7.
Il28ra (Ifnlr1), Stat1 and Irf3 are required for antibiotics to prevent persistent murine norovirus infection.
The innate immune system plays a role in immunogenic tumour recognition. Tumor-cell-derived DNA triggers Ifnb1 production and dendritic cell activation via Tmem173 and Irf3 cytosolic DNA sensing pathways.
Aberrant mitochondrial DNA (mtDNA) packaging promotes escape of mtDNA into the cytosol, where it engages the DNA sensor Mb21d1 and promotes Tmem173-Irf3-dependent signalling to elevate IFN-stimulated gene expression, potentiate type I IFN responses and confer broad viral resistance.
Ppp4c, a serine/threonine phosphatase, directly binds to Tbk1 upon virus infection to dephosphorylate Tbk1 and inhibit Tbk1 activation, and subsequently restrain Irf3 activation, resulting in suppressed production of type I IFN and IFN-stimulated genes.
InnateDB Annotation from Orthologs
Summary
[Homo sapiens] IRF3 is a transcription factor that activates type-1 interferon (IFN) and IFN responsive genes.
[Homo sapiens] IRF3 is directly activated after virus infection and functions as a key activator of the intermediate/early alpha/beta interferon (IFN) genes as well as the RANTES chemokine gene.
[Homo sapiens] IRF3 transcription factor induces type I interferons (IFNs) and elicits innate antiviral response. TMEM173 (MITA) is a critical mediator of virus-triggered IRF3 activation and IFN expression.
[Homo sapiens] IRF3 phosphorylation is virus-inducible and results in IRF3 alteration of protein conformation to permit nuclear translocation, association with transcriptional partners, and primary activation of interferon (IFN)- and IFN-responsive genes.
[Homo sapiens] IRF3 is strongly phosphorylated at the late stages of a Sindbis virus infection to mount antiviral responses in human embryonic kidney cells.
[Homo sapiens] IRF3 is involved in the innate immune recognition of Plasmodium falciparum AT-rich DNA and in the subsequent induction of type I IFNs. Mice lacking Irf3/Irf7 are resistant to otherwise lethal cerebral malaria. (Demonstrated in mouse)
[Homo sapiens] IRF3 suppresses neuroinflammation through regulation of immunomodulatory MIR155 microRNA expression in astrocytes.
[Homo sapiens] HIV accessory protein Vpu targets IRF3 to endolysosome for proteolytic degradation to avoid antiviral immune responses.
[Homo sapiens] During the transcriptional response to Sendai virus infection, POLR2F(RNA Pol II) is recruited by IRF3 and NFκB to control virus induced gene activation.
[Homo sapiens] Vpu, an accessory protein encoded by HIV-1, contributes to the attenuation of the anti-viral response by partial inactivation of IRF3 while host cells undergo apoptosis.
[Homo sapiens] Hepatitis B virus (HBV) polymerase inhibits TMEM173-stimulated IRF3 activation and IFNB1 induction.
[Homo sapiens] Stimulation of TMEM173-dependent IRF3 activation by ultraviolet radiation is due to apoptotic signalling-dependent disruption of ULK1, a pro-autophagic protein that negatively regulates TMEM173.
[Homo sapiens] PQBP1 directly binds to reverse-transcribed HIV-1 DNA and interacts with MB21D1 to initiate an IRF3-dependent innate response
[Homo sapiens] 4-(2-chloro-6-fluorobenzyl)-N-(furan-2-ylmethyl)-3-oxo-3,4-dihydro-2H-benzo[b][1,4]thiazine-6-carboxamide (G10) requires STING to trigger IRF3/IFN-associated transcription in human fibroblasts and subsequently blocking replication of Chikungunya virus, Venezuelan Encephalitis virus, and Sindbis virus.
[Homo sapiens] Influenza B virus induces IRF3 activation and IL29 (IFNL1) gene expression without a requirement for viral protein synthesis or replication and DDX58 is the critical pattern recognition receptor needed for IRF3 activation.
Entrez Gene
Summary This gene does not have any Entrez summary - the following is the summary from its human ortholog ENSG00000126456:
This gene encodes a member of the interferon regulatory transcription factor (IRF) family. The encoded protein is found in an inactive cytoplasmic form that upon serine/threonine phosphorylation forms a complex with CREBBP. This complex translocates to the nucleus and activates the transcription of interferons alpha and beta, as well as other interferon-induced genes. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Nov 2011]
Gene Information
Type Protein coding
Genomic Location Chromosome 7:44997648-45002848
Strand Forward strand
Band B3
Transcripts
ENSMUST00000003284 ENSMUSP00000003284
ENSMUST00000107835 ENSMUSP00000103466
ENSMUST00000107834 ENSMUSP00000103465
ENSMUST00000124069
ENSMUST00000130610
ENSMUST00000145728
ENSMUST00000145233
ENSMUST00000127011
ENSMUST00000146355
Interactions
Number of Interactions This gene and/or its encoded proteins are associated with 41 experimentally validated interaction(s) in this database.
They are also associated with 79 interaction(s) predicted by orthology.
Experimentally validated
Total 41 [view]
Protein-Protein 27 [view]
Protein-DNA 12 [view]
Protein-RNA 2 [view]
DNA-DNA 0
RNA-RNA 0
DNA-RNA 0
Predicted by orthology
Total 79 [view]
Gene Ontology

Molecular Function
Accession GO Term
GO:0000975 regulatory region DNA binding
GO:0003700 sequence-specific DNA binding transcription factor activity
GO:0005515 protein binding
GO:0042802 identical protein binding
GO:0042803 protein homodimerization activity
GO:0044212 transcription regulatory region DNA binding
Biological Process
GO:0000122 negative regulation of transcription from RNA polymerase II promoter
GO:0006351 transcription, DNA-templated
GO:0006355 regulation of transcription, DNA-templated
GO:0009617 response to bacterium
GO:0031663 lipopolysaccharide-mediated signaling pathway
GO:0032496 response to lipopolysaccharide
GO:0032727 positive regulation of interferon-alpha production
GO:0032728 positive regulation of interferon-beta production
GO:0043123 positive regulation of I-kappaB kinase/NF-kappaB signaling
GO:0043330 response to exogenous dsRNA
GO:0045087 innate immune response (InnateDB)
GO:0045351 type I interferon biosynthetic process
GO:0045358 negative regulation of interferon-beta biosynthetic process
GO:0050689 negative regulation of defense response to virus by host
GO:0050715 positive regulation of cytokine secretion
GO:0051607 defense response to virus
GO:0060340 positive regulation of type I interferon-mediated signaling pathway
GO:0071359 cellular response to dsRNA
GO:0097300 programmed necrotic cell death
Cellular Component
GO:0005634 nucleus
GO:0005737 cytoplasm
GO:0005829 cytosol
Orthologs
Species
Homo sapiens
Bos taurus
Gene ID
Gene Order
Method
Confidence
Comments
SSD Ortholog
Ortholog supports species divergence
Not yet available
SSD Ortholog
Ortholog supports species divergence
Pathways
NETPATH
REACTOME
Toll Like Receptor 3 (TLR3) Cascade pathway
Innate Immune System pathway
Hemostasis pathway
Cytokine Signaling in Immune system pathway
IRF3 mediated activation of type 1 IFN pathway
Antiviral mechanism by IFN-stimulated genes pathway
Negative regulators of RIG-I/MDA5 signaling pathway
ISG15 antiviral mechanism pathway
ZBP1(DAI) mediated induction of type I IFNs pathway
Immune System pathway
LRR FLII-interacting protein 1 (LRRFIP1) activates type I IFN production pathway
TRAF6 mediated IRF7 activation pathway
Factors involved in megakaryocyte development and platelet production pathway
Interferon gamma signaling pathway
Interferon Signaling pathway
IRF3-mediated induction of type I IFN pathway
Toll-Like Receptors Cascades pathway
Cytosolic sensors of pathogen-associated DNA pathway
STING mediated induction of host immune responses pathway
Regulation of innate immune responses to cytosolic DNA pathway
Activated TLR4 signalling pathway
MyD88-independent cascade pathway
RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways pathway
TRIF-mediated TLR3/TLR4 signaling pathway
TRAF3-dependent IRF activation pathway pathway
Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon pathway
Toll Like Receptor 4 (TLR4) Cascade pathway
KEGG
Toll-like receptor signaling pathway pathway
RIG-I-like receptor signaling pathway pathway
Cytosolic DNA-sensing pathway pathway
Hepatitis C pathway
INOH
PID BIOCARTA
PID NCI
Pathway Predictions based on Human Orthology Data
NETPATH
REACTOME
STING mediated induction of host immune responses pathway
IRF3-mediated induction of type I IFN pathway
Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon pathway
LRR FLII-interacting protein 1 (LRRFIP1) activates type I IFN production pathway
Antiviral mechanism by IFN-stimulated genes pathway
Interferon alpha/beta signaling pathway
ZBP1(DAI) mediated induction of type I IFNs pathway
IRF3 mediated activation of type 1 IFN pathway
Cytokine Signaling in Immune system pathway
Innate Immune System pathway
Toll Like Receptor 3 (TLR3) Cascade pathway
TRAF6 mediated IRF7 activation pathway
Toll-Like Receptors Cascades pathway
RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways pathway
Interferon Signaling pathway
Regulation of innate immune responses to cytosolic DNA pathway
Immune System pathway
MyD88-independent cascade pathway
TRAF3-dependent IRF activation pathway pathway
Interferon gamma signaling pathway
Factors involved in megakaryocyte development and platelet production pathway
Toll Like Receptor 4 (TLR4) Cascade pathway
Activated TLR4 signalling pathway
ISG15 antiviral mechanism pathway
TRIF-mediated TLR3/TLR4 signaling pathway
Cytosolic sensors of pathogen-associated DNA pathway
Negative regulators of RIG-I/MDA5 signaling pathway
Hemostasis pathway
STING mediated induction of host immune responses pathway
Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon pathway
TRIF-mediated TLR3/TLR4 signaling pathway
Toll Like Receptor 3 (TLR3) Cascade pathway
Factors involved in megakaryocyte development and platelet production pathway
ISG15 antiviral mechanism pathway
Activated TLR4 signalling pathway
MyD88-independent cascade pathway
Cytosolic sensors of pathogen-associated DNA pathway
RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways pathway
Cytokine Signaling in Immune system pathway
Hemostasis pathway
Immune System pathway
Antiviral mechanism by IFN-stimulated genes pathway
IRF3-mediated induction of type I IFN pathway
IRF3 mediated activation of type 1 IFN pathway
Toll-Like Receptors Cascades pathway
Negative regulators of RIG-I/MDA5 signaling pathway
TRAF3-dependent IRF activation pathway pathway
Interferon Signaling pathway
LRR FLII-interacting protein 1 (LRRFIP1) activates type I IFN production pathway
TRAF6 mediated IRF7 activation pathway
Innate Immune System pathway
ZBP1(DAI) mediated induction of type I IFNs pathway
Toll Like Receptor 4 (TLR4) Cascade pathway
KEGG
Toll-like receptor signaling pathway pathway
RIG-I-like receptor signaling pathway pathway
Cytosolic DNA-sensing pathway pathway
Hepatitis C pathway
INOH
PID BIOCARTA
The information processing pathway at the ifn beta enhancer [Biocarta view]
PID NCI
Cross-References
SwissProt
TrEMBL
UniProt Splice Variant
Entrez Gene
UniGene
RefSeq NM_016849
OMIM
CCDS CCDS21224
HPRD
IMGT
MGI ID
MGI Symbol
EMBL
GenPept
RNA Seq Atlas