ID IRF7_MOUSE Reviewed; 457 AA.
AC P70434;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1997, sequence version 1.
DT 29-MAY-2013, entry version 103.
DE RecName: Full=Interferon regulatory factor 7;
DE Short=IRF-7;
GN Name=Irf7;
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=Spleen;
RA Grossman A., Nicholl J., Antonio L., Luethy R., Suggs S.,
RA Sutherland G.R., Mak T.W.;
RL Submitted (OCT-1996) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP REVIEW ON FUNCTION.
RX PubMed=11846980; DOI=10.1089/107999002753452700;
RA Zhang L., Pagano J.S.;
RT "Structure and function of IRF-7.";
RL J. Interferon Cytokine Res. 22:95-101(2002).
RN [3]
RP FUNCTION, PHOSPHORYLATION AT SER-429; SER-431; SER-437; SER-438 AND
RP SER-441, AND MUTAGENESIS OF SER-425; SER-426; LEU-427; SER-429;
RP SER-431; SER-437; SER-438 AND SER-441.
RX PubMed=15743772; DOI=10.1074/jbc.M411389200;
RA Caillaud A., Hovanessian A.G., Levy D.E., Marie I.J.;
RT "Regulatory serine residues mediate phosphorylation-dependent and
RT phosphorylation-independent activation of interferon regulatory factor
RT 7.";
RL J. Biol. Chem. 280:17671-17677(2005).
RN [4]
RP FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION, UBIQUITINATION, AND
RP INTERACTION WITH MYD88 AND TRAF6.
RX PubMed=15361868; DOI=10.1038/ni1118;
RA Kawai T., Sato S., Ishii K.J., Coban C., Hemmi H., Yamamoto M.,
RA Terai K., Matsuda M., Inoue J., Uematsu S., Takeuchi O., Akira S.;
RT "Interferon-alpha induction through Toll-like receptors involves a
RT direct interaction of IRF7 with MyD88 and TRAF6.";
RL Nat. Immunol. 5:1061-1068(2004).
RN [5]
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 [6]
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 [7]
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 [8]
RP ERRATUM.
RA Honda K., Takaoka A., Taniguchi T.;
RL Immunity 25:849-849(2006).
RN [9]
RP FUNCTION.
RX PubMed=18562536; DOI=10.1128/JVI.00918-08;
RA Daffis S., Samuel M.A., Suthar M.S., Keller B.C., Gale M. Jr.,
RA Diamond M.S.;
RT "Interferon regulatory factor IRF-7 induces the antiviral alpha
RT interferon response and protects against lethal West Nile virus
RT infection.";
RL J. Virol. 82:8465-8475(2008).
RN [10]
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 [11]
RP REVIEW ON FUNCTION.
RX PubMed=21490621; DOI=10.1038/gene.2011.21;
RA Ning S., Pagano J.S., Barber G.N.;
RT "IRF7: activation, regulation, modification and function.";
RL Genes Immun. 12:399-414(2011).
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. Can efficiently
CC activate both the IFN-beta (IFNB) and the IFN-alpha (IFNA) genes
CC and mediate their induction via both the virus-activated, MyD88-
CC independent pathway and the TLR-activated, MyD88-dependent
CC pathway. Required during both the early and late phases of the IFN
CC gene induction but is more critical for the late than for the
CC early phase. Exists in an inactive form in the cytoplasm of
CC uninfected cells and following viral infection, double-stranded
CC RNA (dsRNA), or toll-like receptor (TLR) signaling, becomes
CC phosphorylated by IKBKE and TBK1 kinases. This induces a
CC conformational change, leading to its dimerization and nuclear
CC localization where along with other coactivators it can activate
CC transcription of the type I IFN and ISG genes. Can also play a
CC role in regulating adaptive immune responses by inducing
CC PSMB9/LMP2 expression, either directly or through induction of
CC IRF1. Binds to the Q promoter (Qp) of EBV nuclear antigen 1 a
CC (EBNA1) and may play a role in the regulation of EBV latency. Can
CC activate distinct gene expression programs in macrophages and
CC regulate the anti-tumor properties of 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.
CC -!- SUBUNIT: Monomer. Homodimer; phosphorylation-induced. Heterodimer
CC with IRF3. Interacts with TICAM1 and TICAM2. Interacts with
CC rotavirus A NSP1; this interaction leads to the proteasome-
CC dependent degradation of IRF7. Interacts with Epstein-Barr virus
CC LF2. Interacts with MYD88 AND TRAF6.
CC -!- INTERACTION:
CC Q60680:Chuk; NbExp=3; IntAct=EBI-997907, EBI-646245;
CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Note=The phosphorylated
CC and active form accumulates selectively in the nucleus.
CC -!- INDUCTION: By type I interferon (IFN) and viruses.
CC -!- PTM: Acetylation inhibits its DNA-binding ability and activity (By
CC similarity).
CC -!- PTM: In response to a viral infection, phosphorylated by TBK1 and
CC IKBKE1. Phosphorylation, and subsequent activation is inhibited by
CC vaccinia virus protein E3. In TLR7- and TLR9-mediated signaling
CC pathway, phosphorylated by IRAK1 (By similarity).
CC -!- PTM: TRAF6-mediated ubiquitination is required for IRF7
CC activation.
CC -!- PTM: Sumoylated by TRIM28, which inhibits its transactivation
CC activity (By 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; U73037; AAB18626.1; -; mRNA.
DR IPI; IPI00109286; -.
DR RefSeq; NP_058546.1; NM_016850.3.
DR UniGene; Mm.3233; -.
DR PDB; 3QU3; X-ray; 1.30 A; A/B/C=1-134.
DR PDBsum; 3QU3; -.
DR ProteinModelPortal; P70434; -.
DR SMR; P70434; 9-130, 243-417.
DR IntAct; P70434; 3.
DR PhosphoSite; P70434; -.
DR PaxDb; P70434; -.
DR PRIDE; P70434; -.
DR Ensembl; ENSMUST00000026571; ENSMUSP00000026571; ENSMUSG00000025498.
DR GeneID; 54123; -.
DR KEGG; mmu:54123; -.
DR UCSC; uc009kkg.2; mouse.
DR CTD; 3665; -.
DR MGI; MGI:1859212; Irf7.
DR eggNOG; NOG39245; -.
DR HOGENOM; HOG000111812; -.
DR HOVERGEN; HBG105600; -.
DR InParanoid; P70434; -.
DR KO; K09447; -.
DR OMA; ELPDQKQ; -.
DR OrthoDB; EOG4Z8XWR; -.
DR NextBio; 310909; -.
DR ArrayExpress; P70434; -.
DR Bgee; P70434; -.
DR CleanEx; MM_IRF7; -.
DR Genevestigator; P70434; -.
DR GermOnline; ENSMUSG00000025498; Mus musculus.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0003677; F:DNA binding; ISS:UniProtKB.
DR GO; GO:0000982; F:RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity; IEA:Compara.
DR GO; GO:0000979; F:RNA polymerase II core promoter sequence-specific DNA binding; IEA:Compara.
DR GO; GO:0016064; P:immunoglobulin mediated immune response; IMP:MGI.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0032607; P:interferon-alpha production; IMP:UniProtKB.
DR GO; GO:0032608; P:interferon-beta production; IMP:UniProtKB.
DR GO; GO:0032727; P:positive regulation of interferon-alpha production; TAS:UniProtKB.
DR GO; GO:0032728; P:positive regulation of interferon-beta production; TAS:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; ISS:UniProtKB.
DR GO; GO:0060340; P:positive regulation of type I interferon-mediated signaling pathway; IMP:MGI.
DR GO; GO:0006473; P:protein acetylation; IEA:Compara.
DR GO; GO:0006468; P:protein phosphorylation; IEA:Compara.
DR GO; GO:0002819; P:regulation of adaptive immune response; ISS:UniProtKB.
DR GO; GO:0034124; P:regulation of MyD88-dependent toll-like receptor signaling pathway; IMP:UniProtKB.
DR GO; GO:0034127; P:regulation of MyD88-independent toll-like receptor signaling pathway; IMP:UniProtKB.
DR GO; GO:0045351; P:type I interferon biosynthetic process; IMP: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 3D-structure; Acetylation; Activator; Complete proteome; Cytoplasm;
KW DNA-binding; Immunity; Innate immunity; Isopeptide bond; Nucleus;
KW Phosphoprotein; Reference proteome; Transcription;
KW Transcription regulation; Ubl conjugation.
FT CHAIN 1 457 Interferon regulatory factor 7.
FT /FTId=PRO_0000154563.
FT DNA_BIND 9 126 IRF tryptophan pentad repeat.
FT MOD_RES 92 92 N6-acetyllysine; by KAT2A and KAT2B (By
FT similarity).
FT MOD_RES 425 425 Phosphoserine (Probable).
FT MOD_RES 426 426 Phosphoserine (Probable).
FT MOD_RES 429 429 Phosphoserine (Probable).
FT MOD_RES 431 431 Phosphoserine; by TBK1 and IKKE (By
FT similarity).
FT MOD_RES 437 437 Phosphoserine (Probable).
FT MOD_RES 438 438 Phosphoserine (Probable).
FT CROSSLNK 398 398 Glycyl lysine isopeptide (Lys-Gly)
FT (interchain with G-Cter in SUMO) (By
FT similarity).
FT CROSSLNK 400 400 Glycyl lysine isopeptide (Lys-Gly)
FT (interchain with G-Cter in SUMO) (By
FT similarity).
FT MUTAGEN 425 425 S->A: Strongly decreased transcriptional
FT activation in response to viral
FT infection; when associated with A-426.
FT MUTAGEN 425 425 S->D: Strongly decreased transcriptional
FT activation in response to viral
FT infection; when associated with D-426.
FT MUTAGEN 426 426 S->A: Strongly decreased transcriptional
FT activation in response to viral
FT infection; when associated with A-425.
FT MUTAGEN 426 426 S->D: Strongly decreased transcriptional
FT activation in response to viral
FT infection; when associated with D-425.
FT MUTAGEN 427 427 L->A: Strongly decreased transcriptional
FT activation in response to viral
FT infection.
FT MUTAGEN 427 427 L->D: No effect on transcriptional
FT activation in response to viral
FT infection.
FT MUTAGEN 429 429 S->A: Almost no effect on transcriptional
FT activation in response to viral
FT infection; when associated with A-430 and
FT A-431.
FT MUTAGEN 429 429 S->D: Strongly increased transcriptional
FT activation in response to viral
FT infection; when associated with D-430 and
FT A-431.
FT MUTAGEN 430 430 S->A: Almost no effect on transcriptional
FT activation in response to viral
FT infection; when associated with A-429 and
FT A-431.
FT MUTAGEN 430 430 S->D: Strongly increased transcriptional
FT activation in response to viral
FT infection; when associated with D-429 and
FT A-431.
FT MUTAGEN 431 431 S->A: Almost no effect on transcriptional
FT activation in response to viral
FT infection; when associated with A-429 and
FT A-430.
FT MUTAGEN 431 431 S->D: Strongly increased transcriptional
FT activation in response to viral
FT infection; when associated with D-429 and
FT A-430.
FT MUTAGEN 437 437 S->A: Almost complete loss of
FT transcriptional activation; when
FT associated with A-438.
FT MUTAGEN 437 437 S->D: Increased transcriptional
FT activation; when associated with D-438.
FT MUTAGEN 438 438 S->A: Almost complete loss of
FT transcriptional activation; when
FT associated with A-437.
FT MUTAGEN 438 438 S->D: Increased transcriptional
FT activation; when associated with D-437.
FT MUTAGEN 441 441 S->A: Almost no effect on transcriptional
FT activation in response to viral
FT infection.
FT HELIX 12 22
FT STRAND 29 32
FT STRAND 37 41
FT HELIX 52 55
FT HELIX 56 64
FT HELIX 77 85
FT HELIX 88 100
FT STRAND 105 111
FT STRAND 119 124
SQ SEQUENCE 457 AA; 51222 MW; 30B102C668F56142 CRC64;
MAEVRGVQRV LFGDWLLGEV SSGQYEGLQW LNEARTVFRV PWKHFGRRDL DEEDAQIFKA
WAVARGRWPP SGVNLPPPEA EAAERRERRG WKTNFRCALH STGRFILRQD NSGDPVDPHK
VYELSRELGS TVGPATENRE EVSLSNALPT QGVSPGSFLA RENAGLQTPS PLLSSDAGDL
LLQVLQYSHI LESESGADPV PPQAPGQEQD RVYEEPYAAW QVEAVPSPRP QQPALTERSL
GFLDVTIMYK GRTVLQAVVG HPRCVFLYSP MAPAVRTSEP QPVIFPSPAE LPDQKQLHYT
ETLLQHVSPG LQLELRGPSL WALRMGKCKV YWEVGSPMGT TGPSTPPQLL ERNRHTPIFD
FSTFFRELEE FRARRRQGSP HYTIYLGFGQ DLSAGRPKEK TLILVKLEPW VCKAYLEGVQ
REGVSSLDSS SLGLCLSSTN SLYEDIEHFL MDLGQWP
//
