Homo sapiens Gene: IRF3
Summary
InnateDB Gene IDBG-63225.6
Last Modified 2014-10-13 [Report errors or provide feedback]
Gene Symbol IRF3
Gene Name interferon regulatory factor 3
Synonyms
Species Homo sapiens
Ensembl Gene ENSG00000126456
Encoded Proteins
interferon regulatory factor 3
interferon regulatory factor 3
interferon regulatory factor 3
interferon regulatory factor 3
Protein Structure
Useful resources Stemformatics EHFPI ImmGen
InnateDB Annotation
Summary
IRF3 is a transcription factor that activates type-1 interferon (IFN) and IFN responsive genes.
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.
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.
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.
IRF3 is strongly phosphorylated at the late stages of a Sindbis virus infection to mount antiviral responses in human embryonic kidney cells.
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)
IRF3 suppresses neuroinflammation through regulation of immunomodulatory MIR155 microRNA expression in astrocytes.
HIV accessory protein Vpu targets IRF3 to endolysosome for proteolytic degradation to avoid antiviral immune responses.
During the transcriptional response to Sendai virus infection, POLR2F(RNA Pol II) is recruited by IRF3 and NFκB to control virus induced gene activation.
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.
Hepatitis B virus (HBV) polymerase inhibits TMEM173-stimulated IRF3 activation and IFNB1 induction.
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.
PQBP1 directly binds to reverse-transcribed HIV-1 DNA and interacts with MB21D1 to initiate an IRF3-dependent innate response
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.
InnateDB Annotation from Orthologs
Summary
[Mus musculus] 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)
[Mus musculus] 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.
[Mus musculus] Irf3 suppresses neuroinflammation through regulation of immunomodulatory mmu-mir-155 microRNA expression in astrocytes. (Demonstrated in human)
[Mus musculus] HIV accessory protein Vpu targets Irf3 to endolysosome for proteolytic degradation to avoid antiviral immune responses. (Demonstrated in human)
[Mus musculus] Endoplasmic reticulum stress primes macrophages to respond to innate immunity stimuli by activating IRF3.
[Mus musculus] 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.
[Mus musculus] Il28ra (Ifnlr1), Stat1 and Irf3 are required for antibiotics to prevent persistent murine norovirus infection.
[Mus musculus] 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.
[Mus musculus] 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.
Entrez Gene
Summary 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 19:49659569-49665875
Strand Reverse strand
Band q13.33
Transcripts
ENST00000309877 ENSP00000310127
ENST00000377139 ENSP00000366344
ENST00000377135 ENSP00000366339
ENST00000442265 ENSP00000400378
ENST00000600022 ENSP00000472700
ENST00000595034 ENSP00000469067
ENST00000597636 ENSP00000470436
ENST00000597198 ENSP00000469113
ENST00000597180
ENST00000602190
ENST00000598808 ENSP00000472582
ENST00000596788 ENSP00000473232
ENST00000595240
ENST00000596765 ENSP00000470512
ENST00000600453 ENSP00000470905
ENST00000601291 ENSP00000471896
ENST00000596822 ENSP00000468911
ENST00000597369
ENST00000601373 ENSP00000471402
ENST00000600911 ENSP00000470431
ENST00000599144 ENSP00000470069
ENST00000593818 ENSP00000471517
ENST00000598108 ENSP00000472223
ENST00000593922 ENSP00000472601
ENST00000599223 ENSP00000471358
ENST00000596644
ENST00000596756 ENSP00000473128
ENST00000593337 ENSP00000473176
ENST00000594387
ENST00000601809 ENSP00000470140
ENST00000599680
Interactions
Number of Interactions This gene and/or its encoded proteins are associated with 156 experimentally validated interaction(s) in this database.
They are also associated with 21 interaction(s) predicted by orthology.
Experimentally validated
Total 156 [view]
Protein-Protein 105 [view]
Protein-DNA 51 [view]
Protein-RNA 0
DNA-DNA 0
RNA-RNA 0
DNA-RNA 0
Predicted by orthology
Total 21 [view]
Gene Ontology

Molecular Function
Accession GO Term
GO:0000975 regulatory region DNA binding
GO:0003677 DNA binding
GO:0003700 sequence-specific DNA binding transcription factor activity
GO:0003712 transcription cofactor 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:0002224 toll-like receptor signaling pathway
GO:0002756 MyD88-independent toll-like receptor signaling pathway
GO:0006355 regulation of transcription, DNA-templated
GO:0006366 transcription from RNA polymerase II promoter
GO:0006915 apoptotic process
GO:0006974 cellular response to DNA damage stimulus
GO:0009617 response to bacterium
GO:0016032 viral process
GO:0019221 cytokine-mediated signaling pathway
GO:0031663 lipopolysaccharide-mediated signaling pathway
GO:0032480 negative regulation of type I interferon production
GO:0032481 positive regulation of type I interferon production
GO:0032496 response to lipopolysaccharide
GO:0032727 positive regulation of interferon-alpha production
GO:0032728 positive regulation of interferon-beta production
GO:0034138 toll-like receptor 3 signaling pathway
GO:0034142 toll-like receptor 4 signaling pathway
GO:0035666 TRIF-dependent toll-like receptor signaling pathway
GO:0039530 MDA-5 signaling pathway
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:0060333 interferon-gamma-mediated signaling pathway
GO:0060337 type I interferon signaling pathway
GO:0060340 positive regulation of type I interferon-mediated signaling pathway
GO:0071359 cellular response to dsRNA
GO:0071888 macrophage apoptotic process
GO:0097300 programmed necrotic cell death
Cellular Component
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005737 cytoplasm
GO:0005829 cytosol
Orthologs
Species
Mus musculus
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
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
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 M0QXC8 M0R0R8 M0R0X9
UniProt Splice Variant
Entrez Gene 3661
UniGene Hs.660040 Hs.75254
RefSeq NM_001197122 NM_001197123 NM_001197124 NM_001197125 NM_001197126 NM_001197127 NM_001197128 NM_001571 XM_006723197 XM_006723198 XM_006723200 XM_006723201
HUGO HGNC:6118
OMIM 603734
CCDS CCDS12775 CCDS56099 CCDS59407 CCDS59408 CCDS59409
HPRD 04769
IMGT
EMBL AC011495
GenPept
RNA Seq Atlas 3661