ID IRF3_MOUSE Reviewed; 419 AA.
AC P70671;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1997, sequence version 1.
DT 29-MAY-2013, entry version 110.
DE RecName: Full=Interferon regulatory factor 3;
DE Short=IRF-3;
GN Name=Irf3;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Sciurognathi;
OC Muroidea; Muridae; Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=BALB/c; TISSUE=Liver;
RA Hakem R., Grossman A., Antonio L., Suggs S., Mak T.W.;
RL Submitted (NOV-1996) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6; TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP FUNCTION.
RX PubMed=15800576; DOI=10.1038/nature03464;
RA Honda K., Yanai H., Negishi H., Asagiri M., Sato M., Mizutani T.,
RA Shimada N., Ohba Y., Takaoka A., Yoshida N., Taniguchi T.;
RT "IRF-7 is the master regulator of type-I interferon-dependent immune
RT responses.";
RL Nature 434:772-777(2005).
RN [4]
RP REVIEW ON FUNCTION.
RX PubMed=16846591; DOI=10.1016/j.bcp.2006.06.002;
RA Solis M., Goubau D., Romieu-Mourez R., Genin P., Civas A., Hiscott J.;
RT "Distinct functions of IRF-3 and IRF-7 in IFN-alpha gene regulation
RT and control of anti-tumor activity in primary macrophages.";
RL Biochem. Pharmacol. 72:1469-1476(2006).
RN [5]
RP REVIEW ON FUNCTION.
RX PubMed=16979567; DOI=10.1016/j.immuni.2006.08.009;
RA Honda K., Takaoka A., Taniguchi T.;
RT "Type I interferon gene induction by the interferon regulatory factor
RT family of transcription factors.";
RL Immunity 25:349-360(2006).
RN [6]
RP ERRATUM.
RA Honda K., Takaoka A., Taniguchi T.;
RL Immunity 25:849-849(2006).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-123 AND SER-135, AND
RP MASS SPECTROMETRY.
RC TISSUE=Melanoma;
RX PubMed=19367708; DOI=10.1021/pr800599n;
RA Zanivan S., Gnad F., Wickstroem S.A., Geiger T., Macek B., Cox J.,
RA Faessler R., Mann M.;
RT "Solid tumor proteome and phosphoproteome analysis by high resolution
RT mass spectrometry.";
RL J. Proteome Res. 7:5314-5326(2008).
RN [8]
RP REVIEW ON FUNCTION.
RX PubMed=20049431; DOI=10.1007/s00262-009-0804-6;
RA Savitsky D., Tamura T., Yanai H., Taniguchi T.;
RT "Regulation of immunity and oncogenesis by the IRF transcription
RT factor family.";
RL Cancer Immunol. Immunother. 59:489-510(2010).
CC -!- FUNCTION: Key transcriptional regulator of type I interferon
CC (IFN)-dependent immune responses and plays a critical role in the
CC innate immune response against DNA and RNA viruses. Regulates the
CC transcription of type I IFN genes (IFN-alpha and IFN-beta) and
CC IFN-stimulated genes (ISG) by binding to an interferon-stimulated
CC response element (ISRE) in their promoters. Acts as a more potent
CC activator of the IFN-beta (IFNB) gene than the IFN-alpha (IFNA)
CC gene and plays a critical role in both the early and late phases
CC of the IFNA/B gene induction. Found in an inactive form in the
CC cytoplasm of uninfected cells and following viral infection,
CC double-stranded RNA (dsRNA), or toll-like receptor (TLR)
CC signaling, becomes phosphorylated by IKBKE and TBK1 kinases. This
CC induces a conformational change, leading to its dimerization and
CC nuclear localization and association with CREB binding protein
CC (CREBBP) to form dsRNA-activated factor 1 (DRAF1), a complex which
CC activates the transcription of the type I IFN and ISG genes. Can
CC activate distinct gene expression programs in macrophages and can
CC induce significant apoptosis in primary macrophages.
CC -!- ENZYME REGULATION: In the absence of viral infection, maintained
CC as a monomer in an autoinhibited state and phosphorylation
CC disrupts this autoinhibition leading to the liberation of the DNA-
CC binding and dimerization activities and its nuclear localization
CC where it can activate type I IFN and ISG genes (By similarity).
CC -!- SUBUNIT: Monomer. Homodimer; phosphorylation-induced. Heterodimer
CC with IRF7. Interacts with CREBBP. May interact with MAVS.
CC Interacts with IKBKE and TBK1. Interacts with TICAM1 and TICAM2.
CC Interacts with RBCK1. Interacts with TRIM21 (By similarity).
CC -!- SUBCELLULAR LOCATION: Cytoplasm (By similarity). Nucleus (By
CC similarity). Note=Shuttles between cytoplasmic and nuclear
CC compartments, with export being the prevailing effect. When
CC activated, IRF3 interaction with CREBBP prevents its export to the
CC cytoplasm (By similarity).
CC -!- PTM: Constitutively phosphorylated on many serines residues. C-
CC terminal serine/threonine cluster is phosphorylated in response of
CC induction by IKBKE and TBK1 (By similarity).
CC -!- PTM: Ubiquitinated; ubiquitination involves RBCK1 leading to
CC proteasomal degradation. Polyubiquitinated; ubiquitination
CC involves TRIM21 leading to proteasomal degradation (By
CC similarity).
CC -!- PTM: ISGylated resulting in sustained IRF3 activation and in the
CC inhibition of IRF3 ubiquitination by disrupting PIN1 binding. The
CC phosphorylation state of IRF3 does not alter ISGylation (By
CC similarity).
CC -!- SIMILARITY: Belongs to the IRF family.
CC -!- SIMILARITY: Contains 1 IRF tryptophan pentad repeat DNA-binding
CC domain.
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DR EMBL; U75839; AAB36924.1; -; mRNA.
DR EMBL; U75840; AAB36925.1; -; mRNA.
DR EMBL; BC050882; AAH50882.1; -; mRNA.
DR IPI; IPI00111836; -.
DR RefSeq; NP_058545.1; NM_016849.4.
DR UniGene; Mm.3960; -.
DR UniGene; Mm.489648; -.
DR ProteinModelPortal; P70671; -.
DR SMR; P70671; 4-110, 184-417.
DR DIP; DIP-29881N; -.
DR MINT; MINT-2737174; -.
DR STRING; 10090.ENSMUSP00000103466; -.
DR PhosphoSite; P70671; -.
DR PaxDb; P70671; -.
DR PRIDE; P70671; -.
DR Ensembl; ENSMUST00000003284; ENSMUSP00000003284; ENSMUSG00000003184.
DR Ensembl; ENSMUST00000107834; ENSMUSP00000103465; ENSMUSG00000003184.
DR Ensembl; ENSMUST00000107835; ENSMUSP00000103466; ENSMUSG00000003184.
DR GeneID; 54131; -.
DR KEGG; mmu:54131; -.
DR UCSC; uc009gsm.2; mouse.
DR CTD; 3661; -.
DR MGI; MGI:1859179; Irf3.
DR eggNOG; NOG42868; -.
DR HOGENOM; HOG000033705; -.
DR HOVERGEN; HBG105601; -.
DR InParanoid; P70671; -.
DR KO; K05411; -.
DR OMA; EGVAWLD; -.
DR OrthoDB; EOG4X6C90; -.
DR Reactome; REACT_107772; Immune System.
DR ChiTaRS; IRF3; mouse.
DR NextBio; 310937; -.
DR ArrayExpress; P70671; -.
DR Bgee; P70671; -.
DR CleanEx; MM_IRF3; -.
DR Genevestigator; P70671; -.
DR GermOnline; ENSMUSG00000003184; Mus musculus.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:MGI.
DR GO; GO:0000975; F:regulatory region DNA binding; IEA:InterPro.
DR GO; GO:0003700; F:sequence-specific DNA binding transcription factor activity; IEA:InterPro.
DR GO; GO:0044212; F:transcription regulatory region DNA binding; IDA:MGI.
DR GO; GO:0071359; P:cellular response to dsRNA; IEA:Compara.
DR GO; GO:0051607; P:defense response to virus; IMP:UniProtKB.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0031663; P:lipopolysaccharide-mediated signaling pathway; IDA:MGI.
DR GO; GO:0050689; P:negative regulation of defense response to virus by host; IDA:MGI.
DR GO; GO:0045358; P:negative regulation of interferon-beta biosynthetic process; IDA:MGI.
DR GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IDA:MGI.
DR GO; GO:0050715; P:positive regulation of cytokine secretion; IEA:Compara.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB cascade; IEA:Compara.
DR GO; GO:0032727; P:positive regulation of interferon-alpha production; IMP:UniProtKB.
DR GO; GO:0032728; P:positive regulation of interferon-beta production; IMP:UniProtKB.
DR GO; GO:0060340; P:positive regulation of type I interferon-mediated signaling pathway; IMP:MGI.
DR GO; GO:0043330; P:response to exogenous dsRNA; IDA:MGI.
DR GO; GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW.
DR GO; GO:0045351; P:type I interferon biosynthetic process; IGI:MGI.
DR Gene3D; 1.10.10.10; -; 1.
DR Gene3D; 2.60.200.10; -; 1.
DR InterPro; IPR019817; Interferon_reg_fac_CS.
DR InterPro; IPR001346; Interferon_reg_fact_DNA-bd_dom.
DR InterPro; IPR019471; Interferon_reg_factor-3.
DR InterPro; IPR017855; SMAD_dom-like.
DR InterPro; IPR008984; SMAD_FHA_domain.
DR InterPro; IPR011991; WHTH_DNA-bd_dom.
DR Pfam; PF00605; IRF; 1.
DR Pfam; PF10401; IRF-3; 1.
DR PRINTS; PR00267; INTFRNREGFCT.
DR SMART; SM00348; IRF; 1.
DR SUPFAM; SSF49879; SMAD_FHA; 1.
DR PROSITE; PS00601; IRF_1; 1.
DR PROSITE; PS51507; IRF_2; 1.
PE 1: Evidence at protein level;
KW Activator; Antiviral defense; Complete proteome; Cytoplasm;
KW DNA-binding; Immunity; Innate immunity; Isopeptide bond; Nucleus;
KW Phosphoprotein; Reference proteome; Transcription;
KW Transcription regulation; Ubl conjugation.
FT CHAIN 1 419 Interferon regulatory factor 3.
FT /FTId=PRO_0000154554.
FT DNA_BIND 5 111 IRF tryptophan pentad repeat.
FT MOD_RES 123 123 Phosphoserine.
FT MOD_RES 135 135 Phosphoserine.
FT CROSSLNK 188 188 Glycyl lysine isopeptide (Lys-Gly)
FT (interchain with G-Cter in ISG15) (By
FT similarity).
FT CROSSLNK 353 353 Glycyl lysine isopeptide (Lys-Gly)
FT (interchain with G-Cter in ISG15) (By
FT similarity).
FT CROSSLNK 359 359 Glycyl lysine isopeptide (Lys-Gly)
FT (interchain with G-Cter in ISG15) (By
FT similarity).
SQ SEQUENCE 419 AA; 46852 MW; 1FF67C4E0FC7F027 CRC64;
METPKPRILP WLVSQLDLGQ LEGVAWLDES RTRFRIPWKH GLRQDAQMAD FGIFQAWAEA
SGAYTPGKDK PDVSTWKRNF RSALNRKEVL RLAADNSKDP YDPHKVYEFV TPGARDFVHL
GASPDTNGKS SLPHSQENLP KLFDGLILGP LKDEGSSDLA IVSDPSQQLP SPNVNNFLNP
APQENPLKQL LAEEQWEFEV TAFYRGRQVF QQTLFCPGGL RLVGSTADMT LPWQPVTLPD
PEGFLTDKLV KEYVGQVLKG LGNGLALWQA GQCLWAQRLG HSHAFWALGE ELLPDSGRGP
DGEVHKDKDG AVFDLRPFVA DLIAFMEGSG HSPRYTLWFC MGEMWPQDQP WVKRLVMVKV
VPTCLKELLE MAREGGASSL KTVDLHISNS QPISLTSDQY KAYLQDLVED MDFQATGNI
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