Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Interferon regulatory factor 3

Gene

Irf3

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Key transcriptional regulator of type I interferon (IFN)-dependent immune responses which plays a critical role in the innate immune response against DNA and RNA viruses. Regulates the transcription of type I IFN genes (IFN-alpha and IFN-beta) and IFN-stimulated genes (ISG) by binding to an interferon-stimulated response element (ISRE) in their promoters. Acts as a more potent activator of the IFN-beta (IFNB) gene than the IFN-alpha (IFNA) gene and plays a critical role in both the early and late phases of the IFNA/B gene induction. Found in an inactive form in the cytoplasm of uninfected cells and following viral infection, double-stranded RNA (dsRNA), or toll-like receptor (TLR) signaling, is phosphorylated by IKBKE and TBK1 kinases. This induces a conformational change, leading to its dimerization and nuclear localization and association with CREB binding protein (CREBBP) to form dsRNA-activated factor 1 (DRAF1), a complex which activates the transcription of the type I IFN and ISG genes. Can activate distinct gene expression programs in macrophages and can induce significant apoptosis in primary macrophages.1 Publication

Enzyme regulationi

In the absence of viral infection, maintained as a monomer in an autoinhibited state and phosphorylation disrupts this autoinhibition leading to the liberation of the DNA-binding and dimerization activities and its nuclear localization where it can activate type I IFN and ISG genes.By similarity

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
DNA bindingi5 – 111IRF tryptophan pentad repeatPROSITE-ProRule annotationAdd BLAST107

GO - Molecular functioni

GO - Biological processi

  • cellular response to dsRNA Source: Ensembl
  • cellular response to lipopolysaccharide Source: MGI
  • defense response to virus Source: UniProtKB
  • innate immune response Source: UniProtKB-KW
  • lipopolysaccharide-mediated signaling pathway Source: MGI
  • positive regulation of cytokine secretion Source: Ensembl
  • positive regulation of I-kappaB kinase/NF-kappaB signaling Source: Ensembl
  • positive regulation of interferon-alpha production Source: UniProtKB
  • positive regulation of interferon-beta production Source: UniProtKB
  • positive regulation of transcription from RNA polymerase II promoter Source: MGI
  • positive regulation of type I interferon-mediated signaling pathway Source: MGI
  • programmed necrotic cell death Source: MGI
  • response to bacterium Source: MGI
  • response to exogenous dsRNA Source: MGI
  • response to lipopolysaccharide Source: MGI
  • type I interferon biosynthetic process Source: MGI

Keywordsi

Molecular functionActivator, DNA-binding
Biological processAntiviral defense, Immunity, Innate immunity, Transcription, Transcription regulation

Enzyme and pathway databases

ReactomeiR-MMU-1169408. ISG15 antiviral mechanism.
R-MMU-1606341. IRF3 mediated activation of type 1 IFN.
R-MMU-3134973. LRR FLII-interacting protein 1 (LRRFIP1) activates type I IFN production.
R-MMU-3134975. Regulation of innate immune responses to cytosolic DNA.
R-MMU-3270619. IRF3-mediated induction of type I IFN.
R-MMU-918233. TRAF3-dependent IRF activation pathway.
R-MMU-933541. TRAF6 mediated IRF7 activation.
R-MMU-936440. Negative regulators of DDX58/IFIH1 signaling.
R-MMU-936964. Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon.
R-MMU-983231. Factors involved in megakaryocyte development and platelet production.

Names & Taxonomyi

Protein namesi
Recommended name:
Interferon regulatory factor 3
Short name:
IRF-3
Gene namesi
Name:Irf3
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 7

Organism-specific databases

MGIiMGI:1859179. Irf3.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Disruption phenotypei

Double knockout with TREX1 does not show a visible phenotype.1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001545541 – 419Interferon regulatory factor 3Add BLAST419

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei3PhosphothreonineBy similarity1
Modified residuei14PhosphoserineBy similarity1
Modified residuei75PhosphothreonineBy similarity1
Modified residuei97PhosphoserineBy similarity1
Modified residuei123PhosphoserineCombined sources1
Modified residuei135PhosphoserineCombined sources1
Cross-linki188Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15)By similarity
Modified residuei230PhosphothreonineBy similarity1
Modified residuei237PhosphothreonineBy similarity1
Modified residuei246PhosphothreonineBy similarity1
Cross-linki353Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15)By similarity
Cross-linki359Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15)By similarity
Modified residuei379Phosphoserine; by TBK1By similarity1
Modified residuei388Phosphoserine; by IKKEBy similarity1
Modified residuei390PhosphoserineBy similarity1
Modified residuei396PhosphothreonineBy similarity1

Post-translational modificationi

Constitutively phosphorylated on many Ser/Thr residues. C-terminal serine/threonine cluster is phosphorylated in response of induction by IKBKE and TBK1. Phosphorylated at Ser-388 by IKBKE upon ssRNA viral infection. Ser-378 and Ser-379 may be specifically phosphorylated in response to induction. Phosphorylation at Ser-379 by TBK1 results in oligomerization. An alternate model propose that the five serine/threonine residues between 388 and 397 are phosphorylated in response to a viral infection.1 Publication
Ubiquitinated; ubiquitination involves RBCK1 leading to proteasomal degradation. Polyubiquitinated; ubiquitination involves TRIM21 leading to proteasomal degradation.By similarity
ISGylated by HERC5 resulting in sustained IRF3 activation and in the inhibition of IRF3 ubiquitination by disrupting PIN1 binding. The phosphorylation state of IRF3 does not alter ISGylation.By similarity

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP70671.
PaxDbiP70671.
PeptideAtlasiP70671.
PRIDEiP70671.

PTM databases

iPTMnetiP70671.
PhosphoSitePlusiP70671.

Expressioni

Gene expression databases

BgeeiENSMUSG00000003184.
CleanExiMM_IRF3.
ExpressionAtlasiP70671. baseline and differential.
GenevisibleiP70671. MM.

Interactioni

Subunit structurei

Monomer. Homodimer; phosphorylation-induced. Heterodimer with IRF7. Interacts with CREBBP. May interact with MAVS. Interacts with IKBKE and TBK1. Interacts with TICAM1 and TICAM2. Interacts with RBCK1. Interacts with HERC5. Interacts with DDX3X (phosphorylated at 'Ser-102'); the interaction allows the phosphorylation and activation of IRF3 by IKBKE. Interacts with TRIM21 and ULK1, in the presence of TRIM21; this interaction leads to IRF3 degradation by autophagy. Interacts with RIOK3; RIOK3 probybly mediates the interaction of TBK1 with IRF3.By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
itself3EBI-7947049,EBI-7947049

GO - Molecular functioni

  • identical protein binding Source: IntAct
  • protein domain specific binding Source: MGI
  • protein homodimerization activity Source: MGI

Protein-protein interaction databases

BioGridi207570. 5 interactors.
DIPiDIP-29881N.
IntActiP70671. 4 interactors.
MINTiMINT-2737174.
STRINGi10090.ENSMUSP00000003284.

Structurei

3D structure databases

ProteinModelPortaliP70671.
SMRiP70671.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the IRF family.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiENOG410IXD8. Eukaryota.
ENOG410YA4B. LUCA.
GeneTreeiENSGT00760000119093.
HOGENOMiHOG000033705.
HOVERGENiHBG105601.
InParanoidiP70671.
KOiK05411.
OMAiCHTYWAV.
OrthoDBiEOG091G067P.
PhylomeDBiP70671.
TreeFamiTF328512.

Family and domain databases

CDDicd00103. IRF. 1 hit.
Gene3Di1.10.10.10. 1 hit.
2.60.200.10. 1 hit.
InterProiView protein in InterPro
IPR019817. Interferon_reg_fac_CS.
IPR001346. Interferon_reg_fact_DNA-bd_dom.
IPR019471. Interferon_reg_factor-3.
IPR017855. SMAD_dom-like.
IPR008984. SMAD_FHA_domain.
IPR036388. WH-like_DNA-bd_sf.
IPR036390. WH_DNA-bd_sf.
PANTHERiPTHR11949. PTHR11949. 1 hit.
PfamiView protein in Pfam
PF00605. IRF. 1 hit.
PF10401. IRF-3. 1 hit.
PRINTSiPR00267. INTFRNREGFCT.
SMARTiView protein in SMART
SM00348. IRF. 1 hit.
SM01243. IRF-3. 1 hit.
SUPFAMiSSF46785. SSF46785. 1 hit.
SSF49879. SSF49879. 1 hit.
PROSITEiView protein in PROSITE
PS00601. IRF_1. 1 hit.
PS51507. IRF_2. 1 hit.

Sequencei

Sequence statusi: Complete.

P70671-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
METPKPRILP WLVSQLDLGQ LEGVAWLDES RTRFRIPWKH GLRQDAQMAD
60 70 80 90 100
FGIFQAWAEA SGAYTPGKDK PDVSTWKRNF RSALNRKEVL RLAADNSKDP
110 120 130 140 150
YDPHKVYEFV TPGARDFVHL GASPDTNGKS SLPHSQENLP KLFDGLILGP
160 170 180 190 200
LKDEGSSDLA IVSDPSQQLP SPNVNNFLNP APQENPLKQL LAEEQWEFEV
210 220 230 240 250
TAFYRGRQVF QQTLFCPGGL RLVGSTADMT LPWQPVTLPD PEGFLTDKLV
260 270 280 290 300
KEYVGQVLKG LGNGLALWQA GQCLWAQRLG HSHAFWALGE ELLPDSGRGP
310 320 330 340 350
DGEVHKDKDG AVFDLRPFVA DLIAFMEGSG HSPRYTLWFC MGEMWPQDQP
360 370 380 390 400
WVKRLVMVKV VPTCLKELLE MAREGGASSL KTVDLHISNS QPISLTSDQY
410
KAYLQDLVED MDFQATGNI
Length:419
Mass (Da):46,852
Last modified:February 1, 1997 - v1
Checksum:i1FF67C4E0FC7F027
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U75839 mRNA. Translation: AAB36924.1.
U75840 mRNA. Translation: AAB36925.1.
BC050882 mRNA. Translation: AAH50882.1.
CCDSiCCDS21224.1.
RefSeqiNP_058545.1. NM_016849.4.
XP_006541058.1. XM_006540995.3.
XP_006541059.1. XM_006540996.2.
UniGeneiMm.3960.
Mm.489648.

Genome annotation databases

EnsembliENSMUST00000003284; ENSMUSP00000003284; ENSMUSG00000003184.
ENSMUST00000107834; ENSMUSP00000103465; ENSMUSG00000003184.
ENSMUST00000209066; ENSMUSP00000146773; ENSMUSG00000003184.
GeneIDi54131.
KEGGimmu:54131.
UCSCiuc009gsm.2. mouse.

Similar proteinsi

Entry informationi

Entry nameiIRF3_MOUSE
AccessioniPrimary (citable) accession number: P70671
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: February 1, 1997
Last modified: October 25, 2017
This is version 152 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families