Homo sapiens Gene: IRF3
Summary
InnateDB Gene IDBG-110976.1
Last Modified 2018-06-05 [Report errors or provide feedback]
Gene Symbol IRF3
Gene Name interferon regulatory factor 3
Synonyms IIAE7;
Species Homo sapiens
Ensembl Gene ENSG00000126456
Encoded Proteins
interferon regulatory factor 3
interferon regulatory factor 3
interferon regulatory factor 3
interferon regulatory factor 3
interferon regulatory factor 3
interferon regulatory factor 3
interferon regulatory factor 3
interferon regulatory factor 3
interferon regulatory factor 3
interferon regulatory factor 3
interferon regulatory factor 3
interferon regulatory factor 3
interferon regulatory factor 3
interferon regulatory factor 3
interferon regulatory factor 3
interferon regulatory factor 3
interferon regulatory factor 3
interferon regulatory factor 3
interferon regulatory factor 3
interferon regulatory factor 3
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.
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 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
ENST00000377135 ENSP00000366339
ENST00000377139 ENSP00000366344
ENST00000442265 ENSP00000400378
ENST00000593337 ENSP00000473176
ENST00000593818 ENSP00000471517
ENST00000593922 ENSP00000472601
ENST00000594387
ENST00000595034 ENSP00000469067
ENST00000595240
ENST00000596644
ENST00000596756 ENSP00000473128
ENST00000596765 ENSP00000470512
ENST00000596788 ENSP00000473232
ENST00000596822 ENSP00000468911
ENST00000597180
ENST00000597198 ENSP00000469113
ENST00000597369
ENST00000597636 ENSP00000470436
ENST00000598108 ENSP00000472223
ENST00000598808 ENSP00000472582
ENST00000599144 ENSP00000470069
ENST00000599223 ENSP00000471358
ENST00000599680
ENST00000600022 ENSP00000472700
ENST00000600453 ENSP00000470905
ENST00000600911 ENSP00000470431
ENST00000601291 ENSP00000471896
ENST00000601373 ENSP00000471402
ENST00000601809 ENSP00000470140
ENST00000602190
Interactions
Number of Interactions This gene and/or its encoded proteins are associated with 199 experimentally validated interaction(s) in this database.
They are also associated with 24 interaction(s) predicted by orthology.
Experimentally validated
Total 199 [view]
Protein-Protein 150 [view]
Protein-DNA 49 [view]
Protein-RNA 0
DNA-DNA 0
RNA-RNA 0
DNA-RNA 0
Predicted by orthology
Total 24 [view]
Gene Ontology

Molecular Function
Accession GO Term
GO:0000978 RNA polymerase II proximal promoter sequence-specific DNA binding
GO:0000981 RNA polymerase II transcription factor activity, sequence-specific DNA binding
GO:0001077 transcriptional activator activity, RNA polymerase II proximal promoter sequence-specific DNA binding
GO:0001078 transcriptional repressor activity, RNA polymerase II proximal promoter sequence-specific DNA binding
GO:0001228 transcriptional activator activity, RNA polymerase II transcription regulatory region sequence-specific DNA binding
GO:0003677 DNA binding
GO:0003700 DNA binding transcription factor activity
GO:0003712 transcription cofactor activity
GO:0005515 protein binding
GO:0019904 protein domain specific binding
GO:0042802 identical protein binding
GO:0042803 protein homodimerization activity
GO:0043565 sequence-specific DNA binding
GO:0044212 transcription regulatory region DNA binding
Biological Process
GO:0000122 negative regulation of transcription from RNA polymerase II promoter
GO:0002376 immune system process
GO:0006351 transcription, DNA-templated
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:0031663 lipopolysaccharide-mediated signaling pathway
GO:0032479 regulation of type I interferon production
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: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:0045944 positive regulation of transcription from RNA polymerase II promoter
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:0071222 cellular response to lipopolysaccharide
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
No orthologs found for this gene
Pathways
NETPATH
REACTOME
Toll Like Receptor 3 (TLR3) Cascade pathway
TRAF3-dependent IRF activation pathway pathway
Regulation of innate immune responses to cytosolic DNA pathway
Toll-Like Receptors Cascades pathway
Negative regulators of DDX58/IFIH1 signaling pathway
Toll Like Receptor 4 (TLR4) Cascade pathway
TICAM1-dependent activation of IRF3/IRF7 pathway
STING mediated induction of host immune responses pathway
Immune System pathway
Antiviral mechanism by IFN-stimulated genes pathway
ZBP1(DAI) mediated induction of type I IFNs pathway
ISG15 antiviral mechanism pathway
TRIF(TICAM1)-mediated TLR4 signaling pathway
Interferon Signaling pathway
Innate Immune System pathway
Interferon alpha/beta signaling pathway
IRF3 mediated activation of type 1 IFN pathway
Cytosolic sensors of pathogen-associated DNA pathway
DDX58/IFIH1-mediated induction of interferon-alpha/beta pathway
MyD88-independent TLR4 cascade pathway
Cytokine Signaling in Immune system pathway
Interferon gamma signaling pathway
LRR FLII-interacting protein 1 (LRRFIP1) activates type I IFN production pathway
IRF3-mediated induction of type I IFN pathway
Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon pathway
TRAF6 mediated IRF7 activation pathway
KEGG
Toll-like receptor signaling pathway pathway
NOD-like receptor signaling pathway pathway
RIG-I-like receptor signaling pathway pathway
Cytosolic DNA-sensing pathway pathway
Pertussis pathway
Hepatitis C pathway
Hepatitis B pathway
Measles pathway
Influenza A pathway
Human papillomavirus infection pathway
Kaposi's sarcoma-associated herpesvirus infection pathway
Herpes simplex infection pathway
Epstein-Barr virus infection pathway
Viral carcinogenesis pathway
INOH
PID BIOCARTA
PID NCI
Cross-References
SwissProt
TrEMBL
UniProt Splice Variant
Entrez Gene
UniGene
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 XM_006723202 XM_017026766 XM_017026767
HUGO
OMIM
CCDS CCDS12775 CCDS56099 CCDS59407 CCDS59408 CCDS59409
HPRD
IMGT
EMBL
GenPept
RNA Seq Atlas