InnateDB: Systems Biology of the Innate Immune Response

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.

PMID 18818105

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.

PMID 9566918

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.

PMID 21768204

IRF3 is strongly phosphorylated at the late stages of a Sindbis virus infection to mount antiviral responses in human embryonic kidney cells.

PMID 21820332

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)

PMID 22170100

IRF3 suppresses neuroinflammation through regulation of immunomodulatory MIR155 microRNA expression in astrocytes.

PMID 22593165

HIV accessory protein Vpu targets IRF3 to endolysosome for proteolytic degradation to avoid antiviral immune responses.

PMID 23994473

During the transcriptional response to Sendai virus infection, POLR2F(RNA Pol II) is recruited by IRF3 and NFκB to control virus induced gene activation.

PMID 25352594

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.

PMID 25505063

Hepatitis B virus (HBV) polymerase inhibits TMEM173-stimulated IRF3 activation and IFNB1 induction.

PMID 25792739

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.

PMID 26046437

PQBP1 directly binds to reverse-transcribed HIV-1 DNA and interacts with MB21D1 to initiate an IRF3-dependent innate response

PMID 26646986

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.

PMID 26378160

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.

InnateDB Annotation from Orthologs

Summary

PMID 21768204

[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)

PMID 21820332

[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.

PMID 22170100

[Mus musculus] Irf3 suppresses neuroinflammation through regulation of immunomodulatory mmu-mir-155 microRNA expression in astrocytes. (Demonstrated in human)

PMID 22593165

[Mus musculus] HIV accessory protein Vpu targets Irf3 to endolysosome for proteolytic degradation to avoid antiviral immune responses. (Demonstrated in human)

PMID 23028052

[Mus musculus] Endoplasmic reticulum stress primes macrophages to respond to innate immunity stimuli by activating IRF3.

PMID 24362933

[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.

PMID 25431490

[Mus musculus] Il28ra (Ifnlr1), Stat1 and Irf3 are required for antibiotics to prevent persistent murine norovirus infection.

PMID 25517615

[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.

PMID 25642965

[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.

PMID 26363053

[Mus musculus] 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.

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

ENSMUSG00000003184

View Gene Order

ENSBTAG00000006633

Not yet available

Pathways

NETPATH

REACTOME

REACT_118811

IRF3 mediated activation of type 1 IFN pathway

REACT_118764

ZBP1(DAI) mediated induction of type I IFNs pathway

REACT_147841

STING mediated induction of host immune responses pathway

REACT_24938

TRAF6 mediated IRF7 activation pathway

REACT_25271

Negative regulators of RIG-I/MDA5 signaling pathway

REACT_25026

TRAF3-dependent IRF activation pathway pathway

REACT_25359

RIG-I/MDA5 mediated induction of IFN-alpha/beta pathways pathway

REACT_25148

Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon pathway

REACT_6809

MyD88-independent cascade pathway

REACT_6783

Toll Like Receptor 3 (TLR3) Cascade pathway

REACT_6894

Toll Like Receptor 4 (TLR4) Cascade pathway

REACT_25162

Interferon alpha/beta signaling pathway

REACT_115831

ISG15 antiviral mechanism pathway

REACT_25078

Interferon gamma signaling pathway

REACT_24970

Factors involved in megakaryocyte development and platelet production pathway

REACT_163993

IRF3-mediated induction of type I IFN pathway

REACT_163743

LRR FLII-interacting protein 1 (LRRFIP1) activates type I IFN production pathway

REACT_115676

Antiviral mechanism by IFN-stimulated genes pathway

REACT_75790

Cytokine Signaling in Immune system pathway

REACT_6802

Innate Immune System pathway

REACT_6966

Toll-Like Receptors Cascades pathway

REACT_25229

Interferon Signaling pathway

REACT_163977

Regulation of innate immune responses to cytosolic DNA pathway

REACT_6900

Immune System pathway

REACT_6890

Activated TLR4 signalling pathway

REACT_25281

TRIF-mediated TLR3/TLR4 signaling pathway

REACT_118823

Cytosolic sensors of pathogen-associated DNA pathway

REACT_604

Hemostasis pathway

KEGG

hsa04620

Toll-like receptor signaling pathway pathway

hsa04622

RIG-I-like receptor signaling pathway pathway

hsa04623

Cytosolic DNA-sensing pathway pathway

hsa05160

Hepatitis C pathway

INOH

PID NCI

Cross-References

SwissProt

TrEMBL

UniProt Splice Variant

Entrez Gene

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

OMIM

CCDS

CCDS12775 CCDS56099 CCDS59407 CCDS59408 CCDS59409

HPRD

04769

IMGT

EMBL

GenPept

RNA Seq Atlas