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Database: UniProt
Entry: P70671
LinkDB: P70671
Original site: P70671 
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-OCT-2014, entry version 124.
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   DISRUPTION PHENOTYPE.
RX   PubMed=18724932; DOI=10.1016/j.cell.2008.06.032;
RA   Stetson D.B., Ko J.S., Heidmann T., Medzhitov R.;
RT   "Trex1 prevents cell-intrinsic initiation of autoimmunity.";
RL   Cell 134:587-598(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).
RN   [9]
RP   PHOSPHORYLATION UPON SSRNA VIRAL INFECTION.
RX   PubMed=22065572; DOI=10.1074/jbc.M111.285205;
RA   Perwitasari O., Cho H., Diamond M.S., Gale M. Jr.;
RT   "Inhibitor of kappaB kinase epsilon (IKK(epsilon)), STAT1, and IFIT2
RT   proteins define novel innate immune effector pathway against West Nile
RT   virus infection.";
RL   J. Biol. Chem. 286:44412-44423(2011).
CC   -!- FUNCTION: Key transcriptional regulator of type I interferon
CC       (IFN)-dependent immune responses which plays a critical role in
CC       the innate immune response against DNA and RNA viruses. Regulates
CC       the 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, is 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       {ECO:0000269|PubMed:15800576}.
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. {ECO:0000250}.
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 rotavirus A NSP1 (via C-terminus); this interaction
CC       leads to the proteasome-dependent degradation of IRF3. Interacts
CC       with RBCK1. Interacts with TRIM21. Interacts with HERC5. InteractS
CC       with DDX3X; the interaction allows the phosphorylation and
CC       activation of IRF3 by IKBKE.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Nucleus
CC       {ECO:0000250}. 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). {ECO:0000250}.
CC   -!- PTM: Constitutively phosphorylated on many Ser/Thr residues. C-
CC       terminal serine/threonine cluster is phosphorylated in response of
CC       induction by IKBKE and TBK1. Phosphorylated at Ser-388 by IKBKE
CC       upon ssRNA viral infection. Ser-378 and Ser-379 may be
CC       specifically phosphorylated in response to induction.
CC       Phosphorylation at Ser-379 by TBK1 results in oligomerization. An
CC       alternate model propose that the five serine/threonine residues
CC       between 388 and 397 are phosphorylated in response to a viral
CC       infection. {ECO:0000269|PubMed:22065572}.
CC   -!- PTM: Ubiquitinated; ubiquitination involves RBCK1 leading to
CC       proteasomal degradation. Polyubiquitinated; ubiquitination
CC       involves TRIM21 leading to proteasomal degradation (By
CC       similarity). {ECO:0000250}.
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). {ECO:0000250}.
CC   -!- DISRUPTION PHENOTYPE: Double knockout with TREX1 does not show a
CC       visible phenotype. {ECO:0000269|PubMed:18724932}.
CC   -!- SIMILARITY: Belongs to the IRF family. {ECO:0000255|PROSITE-
CC       ProRule:PRU00840}.
CC   -!- SIMILARITY: Contains 1 IRF tryptophan pentad repeat DNA-binding
CC       domain. {ECO:0000255|PROSITE-ProRule:PRU00840}.
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DR   EMBL; U75839; AAB36924.1; -; mRNA.
DR   EMBL; U75840; AAB36925.1; -; mRNA.
DR   EMBL; BC050882; AAH50882.1; -; mRNA.
DR   CCDS; CCDS21224.1; -.
DR   RefSeq; NP_058545.1; NM_016849.4.
DR   RefSeq; XP_006541058.1; XM_006540995.1.
DR   RefSeq; XP_006541059.1; XM_006540996.1.
DR   UniGene; Mm.3960; -.
DR   UniGene; Mm.489648; -.
DR   ProteinModelPortal; P70671; -.
DR   SMR; P70671; 4-110, 184-417.
DR   BioGrid; 207570; 4.
DR   DIP; DIP-29881N; -.
DR   IntAct; P70671; 2.
DR   MINT; MINT-2737174; -.
DR   STRING; 10090.ENSMUSP00000103466; -.
DR   PhosphoSite; P70671; -.
DR   MaxQB; 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; CHTYWAV; -.
DR   OrthoDB; EOG7CCBR1; -.
DR   PhylomeDB; P70671; -.
DR   TreeFam; TF328512; -.
DR   Reactome; REACT_196447; IRF3-mediated induction of type I IFN.
DR   Reactome; REACT_196519; Regulation of innate immune responses to cytosolic DNA.
DR   Reactome; REACT_198521; TRAF6 mediated IRF7 activation.
DR   Reactome; REACT_198532; Negative regulators of RIG-I/MDA5 signaling.
DR   Reactome; REACT_198533; ISG15 antiviral mechanism.
DR   Reactome; REACT_198649; Factors involved in megakaryocyte development and platelet production.
DR   Reactome; REACT_198660; Interferon gamma signaling.
DR   Reactome; REACT_198980; IRF3 mediated activation of type 1 IFN.
DR   Reactome; REACT_223626; LRR FLII-interacting protein 1 (LRRFIP1) activates type I IFN production.
DR   Reactome; REACT_225463; Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon.
DR   ChiTaRS; IRF3; mouse.
DR   NextBio; 310937; -.
DR   PRO; PR:P70671; -.
DR   Bgee; P70671; -.
DR   CleanEx; MM_IRF3; -.
DR   ExpressionAtlas; P70671; baseline and differential.
DR   Genevestigator; P70671; -.
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: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:Ensembl.
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:Ensembl.
DR   GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; IEA:Ensembl.
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:0097300; P:programmed necrotic cell death; IMP:MGI.
DR   GO; GO:0009617; P:response to bacterium; IDA:MGI.
DR   GO; GO:0043330; P:response to exogenous dsRNA; IDA:MGI.
DR   GO; GO:0032496; P:response to lipopolysaccharide; IDA:MGI.
DR   GO; GO:0006351; P:transcription, DNA-templated; 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; SSF49879; 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                                {ECO:0000255|PROSITE-ProRule:PRU00840}.
FT   MOD_RES       3      3       Phosphothreonine. {ECO:0000250}.
FT   MOD_RES      14     14       Phosphoserine. {ECO:0000250}.
FT   MOD_RES      75     75       Phosphothreonine. {ECO:0000250}.
FT   MOD_RES      97     97       Phosphoserine. {ECO:0000250}.
FT   MOD_RES     230    230       Phosphothreonine. {ECO:0000250}.
FT   MOD_RES     237    237       Phosphothreonine. {ECO:0000250}.
FT   MOD_RES     246    246       Phosphothreonine. {ECO:0000250}.
FT   MOD_RES     379    379       Phosphoserine; by TBK1. {ECO:0000250}.
FT   MOD_RES     388    388       Phosphoserine; by IKKE. {ECO:0000250}.
FT   MOD_RES     390    390       Phosphoserine. {ECO:0000250}.
FT   MOD_RES     396    396       Phosphothreonine. {ECO:0000250}.
FT   CROSSLNK    188    188       Glycyl lysine isopeptide (Lys-Gly)
FT                                (interchain with G-Cter in ISG15).
FT                                {ECO:0000250}.
FT   CROSSLNK    353    353       Glycyl lysine isopeptide (Lys-Gly)
FT                                (interchain with G-Cter in ISG15).
FT                                {ECO:0000250}.
FT   CROSSLNK    359    359       Glycyl lysine isopeptide (Lys-Gly)
FT                                (interchain with G-Cter in ISG15).
FT                                {ECO:0000250}.
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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