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Database: UniProt
Entry: P70434
LinkDB: P70434
Original site: P70434 
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   26-NOV-2014, entry version 117.
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-425; SER-426; SER-429; SER-431;
RP   SER-437; SER-438 AND SER-441, AND MUTAGENESIS OF SER-425; SER-426;
RP   LEU-427; SER-429; 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       {ECO:0000269|PubMed:15361868, ECO:0000269|PubMed:15743772,
CC       ECO:0000269|PubMed:15800576, ECO:0000269|PubMed:18562536}.
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       {ECO:0000269|PubMed:15361868}.
CC   -!- INTERACTION:
CC       Q60680:Chuk; NbExp=3; IntAct=EBI-997907, EBI-646245;
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:15361868}.
CC       Cytoplasm {ECO:0000269|PubMed:15361868}. 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.
CC       {ECO:0000250}.
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). {ECO:0000250}.
CC   -!- PTM: TRAF6-mediated ubiquitination is required for IRF7
CC       activation. {ECO:0000269|PubMed:15361868}.
CC   -!- PTM: Sumoylated by TRIM28, which inhibits its transactivation
CC       activity. {ECO:0000250}.
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; U73037; AAB18626.1; -; mRNA.
DR   CCDS; CCDS22005.1; -.
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   BioGrid; 207563; 9.
DR   IntAct; P70434; 4.
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; GWKTNFR; -.
DR   PhylomeDB; P70434; -.
DR   TreeFam; TF328512; -.
DR   Reactome; REACT_198521; TRAF6 mediated IRF7 activation.
DR   Reactome; REACT_198527; TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling.
DR   Reactome; REACT_198649; Factors involved in megakaryocyte development and platelet production.
DR   Reactome; REACT_198660; Interferon gamma signaling.
DR   Reactome; REACT_225463; Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon.
DR   Reactome; REACT_231481; TRAF3-dependent IRF activation pathway.
DR   NextBio; 310909; -.
DR   PRO; PR:P70434; -.
DR   Bgee; P70434; -.
DR   CleanEx; MM_IRF7; -.
DR   ExpressionAtlas; P70434; baseline and differential.
DR   Genevestigator; P70434; -.
DR   GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-KW.
DR   GO; GO:0005634; C:nucleus; IEA:UniProtKB-KW.
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; IDA:MGI.
DR   GO; GO:0000979; F:RNA polymerase II core promoter sequence-specific DNA binding; IEA:Ensembl.
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:0045893; P:positive regulation of transcription, DNA-templated; ISS:UniProtKB.
DR   GO; GO:0060340; P:positive regulation of type I interferon-mediated signaling pathway; IMP:MGI.
DR   GO; GO:0002819; P:regulation of adaptive immune response; ISS:UniProtKB.
DR   GO; GO:0045088; P:regulation of innate immune response; TAS: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:0006366; P:transcription from RNA polymerase II promoter; IDA:GOC.
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; SSF49879; 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                                {ECO:0000255|PROSITE-ProRule:PRU00840}.
FT   MOD_RES      92     92       N6-acetyllysine; by KAT2A and KAT2B.
FT                                {ECO:0000250}.
FT   MOD_RES     425    425       Phosphoserine.
FT                                {ECO:0000305|PubMed:15743772}.
FT   MOD_RES     426    426       Phosphoserine.
FT                                {ECO:0000305|PubMed:15743772}.
FT   MOD_RES     429    429       Phosphoserine.
FT                                {ECO:0000305|PubMed:15743772}.
FT   MOD_RES     431    431       Phosphoserine; by TBK1 and IKKE.
FT                                {ECO:0000250}.
FT   MOD_RES     437    437       Phosphoserine.
FT                                {ECO:0000305|PubMed:15743772}.
FT   MOD_RES     438    438       Phosphoserine.
FT                                {ECO:0000305|PubMed:15743772}.
FT   MOD_RES     441    441       Phosphoserine.
FT                                {ECO:0000305|PubMed:15743772}.
FT   CROSSLNK    398    398       Glycyl lysine isopeptide (Lys-Gly)
FT                                (interchain with G-Cter in SUMO).
FT                                {ECO:0000250}.
FT   CROSSLNK    400    400       Glycyl lysine isopeptide (Lys-Gly)
FT                                (interchain with G-Cter in SUMO).
FT                                {ECO:0000250}.
FT   MUTAGEN     425    425       S->A: Strongly decreased transcriptional
FT                                activation in response to viral
FT                                infection; when associated with A-426.
FT                                {ECO:0000269|PubMed:15743772}.
FT   MUTAGEN     425    425       S->D: Strongly decreased transcriptional
FT                                activation in response to viral
FT                                infection; when associated with D-426.
FT                                {ECO:0000269|PubMed:15743772}.
FT   MUTAGEN     426    426       S->A: Strongly decreased transcriptional
FT                                activation in response to viral
FT                                infection; when associated with A-425.
FT                                {ECO:0000269|PubMed:15743772}.
FT   MUTAGEN     426    426       S->D: Strongly decreased transcriptional
FT                                activation in response to viral
FT                                infection; when associated with D-425.
FT                                {ECO:0000269|PubMed:15743772}.
FT   MUTAGEN     427    427       L->A: Strongly decreased transcriptional
FT                                activation in response to viral
FT                                infection. {ECO:0000269|PubMed:15743772}.
FT   MUTAGEN     427    427       L->D: No effect on transcriptional
FT                                activation in response to viral
FT                                infection. {ECO:0000269|PubMed:15743772}.
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. {ECO:0000269|PubMed:15743772}.
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. {ECO:0000269|PubMed:15743772}.
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. {ECO:0000269|PubMed:15743772}.
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. {ECO:0000269|PubMed:15743772}.
FT   MUTAGEN     437    437       S->A: Almost complete loss of
FT                                transcriptional activation; when
FT                                associated with A-438.
FT                                {ECO:0000269|PubMed:15743772}.
FT   MUTAGEN     437    437       S->D: Increased transcriptional
FT                                activation; when associated with D-438.
FT                                {ECO:0000269|PubMed:15743772}.
FT   MUTAGEN     438    438       S->A: Almost complete loss of
FT                                transcriptional activation; when
FT                                associated with A-437.
FT                                {ECO:0000269|PubMed:15743772}.
FT   MUTAGEN     438    438       S->D: Increased transcriptional
FT                                activation; when associated with D-437.
FT                                {ECO:0000269|PubMed:15743772}.
FT   MUTAGEN     441    441       S->A: Almost no effect on transcriptional
FT                                activation in response to viral
FT                                infection. {ECO:0000269|PubMed:15743772}.
FT   HELIX        12     22       {ECO:0000244|PDB:3QU3}.
FT   STRAND       29     32       {ECO:0000244|PDB:3QU3}.
FT   STRAND       37     41       {ECO:0000244|PDB:3QU3}.
FT   HELIX        52     55       {ECO:0000244|PDB:3QU3}.
FT   HELIX        56     64       {ECO:0000244|PDB:3QU3}.
FT   HELIX        77     85       {ECO:0000244|PDB:3QU3}.
FT   HELIX        88    100       {ECO:0000244|PDB:3QU3}.
FT   STRAND      105    111       {ECO:0000244|PDB:3QU3}.
FT   STRAND      119    124       {ECO:0000244|PDB:3QU3}.
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
//
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