IRF7_MOUSE
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 03-AUG-2022, entry version 172.
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; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=BALB/cJ; TISSUE=Spleen;
RA Grossman A., Nicholl J., Antonio L., Luethy R., Suggs S., Sutherland G.R.,
RA 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; SER-437;
RP SER-438 AND SER-441, AND MUTAGENESIS OF SER-425; SER-426; LEU-427;
RP 429-SER--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 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., Terai K.,
RA Matsuda M., Inoue J., Uematsu S., Takeuchi O., Akira S.;
RT "Interferon-alpha induction through Toll-like receptors involves a direct
RT 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 and
RT 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 OF PUBMED:16979567.
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 interferon
RT response and protects against lethal West Nile virus 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 factor
RT 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).
RN [12]
RP INTERACTION WITH NMI, UBIQUITINATION, REGION, AND MUTAGENESIS OF
RP 1-MET--GLU-237; 1-MET--VAL-132; 238-ARG--PRO-457; 238-ARG--TRP-410 AND
RP 411-VAL--PRO-457.
RX PubMed=23956435; DOI=10.4049/jimmunol.1300740;
RA Wang J., Yang B., Hu Y., Zheng Y., Zhou H., Wang Y., Ma Y., Mao K.,
RA Yang L., Lin G., Ji Y., Wu X., Sun B.;
RT "Negative regulation of Nmi on virus-triggered type I IFN production by
RT targeting IRF7.";
RL J. Immunol. 191:3393-3399(2013).
RN [13]
RP FUNCTION, AND INDUCTION.
RX PubMed=27129230; DOI=10.1074/jbc.m116.718080;
RA Ren Y., Zhao Y., Lin D., Xu X., Zhu Q., Yao J., Shu H.B., Zhong B.;
RT "The Type I Interferon-IRF7 Axis Mediates Transcriptional Expression of
RT Usp25 Gene.";
RL J. Biol. Chem. 291:13206-13215(2016).
CC -!- FUNCTION: Key transcriptional regulator of type I interferon (IFN)-
CC dependent immune responses and plays a critical role in the innate
CC immune response against DNA and RNA viruses (PubMed:27129230).
CC Regulates the transcription of type I IFN genes (IFN-alpha and IFN-
CC beta) and IFN-stimulated genes (ISG) by binding to an interferon-
CC stimulated response element (ISRE) in their promoters. Can efficiently
CC activate both the IFN-beta (IFNB) and the IFN-alpha (IFNA) genes and
CC mediate their induction via both the virus-activated, MyD88-independent
CC pathway and the TLR-activated, MyD88-dependent pathway. Induces
CC transcription of ubiquitin hydrolase USP25 mRNA in response to
CC lipopolysaccharide (LPS) or viral infection in a type I IFN-dependent
CC manner (PubMed:27129230). Required during both the early and late
CC phases of the IFN gene induction but is more critical for the late than
CC for the early phase. Exists in an inactive form in the cytoplasm of
CC uninfected cells and following viral infection, double-stranded RNA
CC (dsRNA), or toll-like receptor (TLR) signaling, becomes phosphorylated
CC by IKBKE and TBK1 kinases. This induces a conformational change,
CC leading to its dimerization and nuclear localization where along with
CC other coactivators it can activate transcription of the type I IFN and
CC ISG genes. Can also play a role in regulating adaptive immune responses
CC by inducing PSMB9/LMP2 expression, either directly or through induction
CC of 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 regulate
CC 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 ECO:0000269|PubMed:27129230}.
CC -!- ACTIVITY REGULATION: In the absence of viral infection, maintained as a
CC monomer in an autoinhibited state and phosphorylation disrupts this
CC autoinhibition leading to the liberation of the DNA-binding and
CC dimerization activities and its nuclear localization where it can
CC activate type I IFN and ISG genes.
CC -!- SUBUNIT: Monomer. Homodimer; phosphorylation-induced. Heterodimer with
CC IRF3. Interacts with TICAM1 and TICAM2. Interacts with MYD88 AND TRAF6.
CC Interacts with NMI; the interaction is direct and leads to the
CC inhibition of IRF7-mediated type I IFN production (PubMed:23956435).
CC {ECO:0000269|PubMed:15361868, ECO:0000269|PubMed:23956435}.
CC -!- INTERACTION:
CC P70434; Q60680: Chuk; NbExp=3; IntAct=EBI-997907, EBI-646245;
CC P70434; Q8C006: Trim35; NbExp=2; IntAct=EBI-997907, EBI-2536044;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:15361868}. Cytoplasm
CC {ECO:0000269|PubMed:15361868}. Note=The phosphorylated and active form
CC accumulates selectively in the nucleus.
CC -!- INDUCTION: Induced by lipopolysaccharide (LPS) (PubMed:27129230).
CC Induced by type I interferon (IFN) and viruses (HIV-1 and SeV viruses)
CC (PubMed:27129230). {ECO:0000269|PubMed:27129230}.
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 activation
CC (PubMed:15361868). TRIM35 mediates IRF7 'Lys-48'-linked
CC polyubiquitination and subsequent proteasomal degradation (By
CC similarity). 'Lys-48'-linked polyubiquitination and subsequent
CC proteasomal degradation is NMI-dependent in response to Sendai virus
CC infection (PubMed:23956435). Ubiquitinated by UBE3C, leading to its
CC degradation (By similarity). {ECO:0000250|UniProtKB:Q92985,
CC ECO:0000269|PubMed:15361868, ECO:0000269|PubMed:23956435}.
CC -!- PTM: Sumoylated by TRIM28, which inhibits its transactivation activity.
CC {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the IRF family. {ECO:0000255|PROSITE-
CC 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 PDB; 3QU3; X-ray; 1.30 A; A/B/C=1-134.
DR PDBsum; 3QU3; -.
DR AlphaFoldDB; P70434; -.
DR SMR; P70434; -.
DR BioGRID; 207563; 9.
DR DIP; DIP-37903N; -.
DR IntAct; P70434; 8.
DR MINT; P70434; -.
DR STRING; 10090.ENSMUSP00000026571; -.
DR iPTMnet; P70434; -.
DR PhosphoSitePlus; P70434; -.
DR PaxDb; P70434; -.
DR PRIDE; P70434; -.
DR ProteomicsDB; 269505; -.
DR Antibodypedia; 4325; 617 antibodies from 41 providers.
DR DNASU; 54123; -.
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 VEuPathDB; HostDB:ENSMUSG00000025498; -.
DR eggNOG; ENOG502R2I9; Eukaryota.
DR GeneTree; ENSGT00940000160931; -.
DR InParanoid; P70434; -.
DR OMA; WLDEAHT; -.
DR OrthoDB; 648909at2759; -.
DR PhylomeDB; P70434; -.
DR TreeFam; TF328512; -.
DR Reactome; R-MMU-3134963; DEx/H-box helicases activate type I IFN and inflammatory cytokines production.
DR Reactome; R-MMU-9013973; TICAM1-dependent activation of IRF3/IRF7.
DR Reactome; R-MMU-918233; TRAF3-dependent IRF activation pathway.
DR Reactome; R-MMU-933541; TRAF6 mediated IRF7 activation.
DR Reactome; R-MMU-936964; Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon.
DR Reactome; R-MMU-975110; TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling.
DR BioGRID-ORCS; 54123; 1 hit in 78 CRISPR screens.
DR PRO; PR:P70434; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; P70434; protein.
DR Bgee; ENSMUSG00000025498; Expressed in small intestine Peyer's patch and 105 other tissues.
DR ExpressionAtlas; P70434; baseline and differential.
DR Genevisible; P70434; MM.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0000987; F:cis-regulatory region sequence-specific DNA binding; IDA:UniProtKB.
DR GO; GO:0003677; F:DNA binding; ISS:UniProtKB.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IDA:MGI.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISO:MGI.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:MGI.
DR GO; GO:0051607; P:defense response to virus; IMP:UniProtKB.
DR GO; GO:0002376; P:immune system process; IBA:GO_Central.
DR GO; GO:0016064; P:immunoglobulin mediated immune response; IMP:MGI.
DR GO; GO:0032727; P:positive regulation of interferon-alpha production; ISO:MGI.
DR GO; GO:0032728; P:positive regulation of interferon-beta production; ISO:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IMP:UniProtKB.
DR GO; GO:0032481; P:positive regulation of type I interferon production; IGI:MGI.
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:0010468; P:regulation of gene expression; IGI:MGI.
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:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0060337; P:type I interferon signaling pathway; IMP:UniProtKB.
DR CDD; cd00103; IRF; 1.
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-like_dom_sf.
DR InterPro; IPR008984; SMAD_FHA_dom_sf.
DR InterPro; IPR036388; WH-like_DNA-bd_sf.
DR InterPro; IPR036390; WH_DNA-bd_sf.
DR Pfam; PF00605; IRF; 1.
DR Pfam; PF10401; IRF-3; 1.
DR PRINTS; PR00267; INTFRNREGFCT.
DR SMART; SM00348; IRF; 1.
DR SMART; SM01243; IRF-3; 1.
DR SUPFAM; SSF46785; SSF46785; 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; Cytoplasm; DNA-binding; Immunity;
KW Innate immunity; Isopeptide bond; Nucleus; Phosphoprotein;
KW Reference proteome; Transcription; Transcription regulation;
KW Ubl conjugation.
FT CHAIN 1..457
FT /note="Interferon regulatory factor 7"
FT /id="PRO_0000154563"
FT DNA_BIND 9..126
FT /note="IRF tryptophan pentad repeat"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00840"
FT REGION 238..410
FT /note="Necessary for the interaction with NMI"
FT /evidence="ECO:0000269|PubMed:23956435"
FT MOD_RES 92
FT /note="N6-acetyllysine; by KAT2A and KAT2B"
FT /evidence="ECO:0000250|UniProtKB:Q92985"
FT MOD_RES 425
FT /note="Phosphoserine"
FT /evidence="ECO:0000305|PubMed:15743772"
FT MOD_RES 426
FT /note="Phosphoserine"
FT /evidence="ECO:0000305|PubMed:15743772"
FT MOD_RES 429
FT /note="Phosphoserine"
FT /evidence="ECO:0000305|PubMed:15743772"
FT MOD_RES 431
FT /note="Phosphoserine; by TBK1 and IKKE"
FT /evidence="ECO:0000250|UniProtKB:Q92985"
FT MOD_RES 437
FT /note="Phosphoserine"
FT /evidence="ECO:0000305|PubMed:15743772"
FT MOD_RES 438
FT /note="Phosphoserine"
FT /evidence="ECO:0000305|PubMed:15743772"
FT MOD_RES 441
FT /note="Phosphoserine"
FT /evidence="ECO:0000305|PubMed:15743772"
FT CROSSLNK 398
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000250"
FT CROSSLNK 400
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000250"
FT MUTAGEN 425
FT /note="S->A: Strongly decreased transcriptional activation
FT in response to viral infection; when associated with A-
FT 426."
FT /evidence="ECO:0000269|PubMed:15743772"
FT MUTAGEN 425
FT /note="S->D: Strongly decreased transcriptional activation
FT in response to viral infection; when associated with D-
FT 426."
FT /evidence="ECO:0000269|PubMed:15743772"
FT MUTAGEN 426
FT /note="S->A: Strongly decreased transcriptional activation
FT in response to viral infection; when associated with A-
FT 425."
FT /evidence="ECO:0000269|PubMed:15743772"
FT MUTAGEN 426
FT /note="S->D: Strongly decreased transcriptional activation
FT in response to viral infection; when associated with D-
FT 425."
FT /evidence="ECO:0000269|PubMed:15743772"
FT MUTAGEN 427
FT /note="L->A: Strongly decreased transcriptional activation
FT in response to viral infection."
FT /evidence="ECO:0000269|PubMed:15743772"
FT MUTAGEN 427
FT /note="L->D: No effect on transcriptional activation in
FT response to viral infection."
FT /evidence="ECO:0000269|PubMed:15743772"
FT MUTAGEN 429..431
FT /note="SSS->AAA: Almost no effect on transcriptional
FT activation in response to viral infection."
FT /evidence="ECO:0000269|PubMed:15743772"
FT MUTAGEN 429..431
FT /note="SSS->DDD: Strongly increased transcriptional
FT activation in response to viral infection."
FT /evidence="ECO:0000269|PubMed:15743772"
FT MUTAGEN 437
FT /note="S->A: Almost complete loss of transcriptional
FT activation; when associated with A-438."
FT /evidence="ECO:0000269|PubMed:15743772"
FT MUTAGEN 437
FT /note="S->D: Increased transcriptional activation; when
FT associated with D-438."
FT /evidence="ECO:0000269|PubMed:15743772"
FT MUTAGEN 438
FT /note="S->A: Almost complete loss of transcriptional
FT activation; when associated with A-437."
FT /evidence="ECO:0000269|PubMed:15743772"
FT MUTAGEN 438
FT /note="S->D: Increased transcriptional activation; when
FT associated with D-437."
FT /evidence="ECO:0000269|PubMed:15743772"
FT MUTAGEN 441
FT /note="S->A: Almost no effect on transcriptional activation
FT in response to viral infection."
FT /evidence="ECO:0000269|PubMed:15743772"
FT HELIX 12..22
FT /evidence="ECO:0007829|PDB:3QU3"
FT STRAND 29..32
FT /evidence="ECO:0007829|PDB:3QU3"
FT STRAND 37..41
FT /evidence="ECO:0007829|PDB:3QU3"
FT HELIX 52..55
FT /evidence="ECO:0007829|PDB:3QU3"
FT HELIX 56..64
FT /evidence="ECO:0007829|PDB:3QU3"
FT HELIX 77..85
FT /evidence="ECO:0007829|PDB:3QU3"
FT HELIX 88..100
FT /evidence="ECO:0007829|PDB:3QU3"
FT STRAND 105..111
FT /evidence="ECO:0007829|PDB:3QU3"
FT STRAND 119..124
FT /evidence="ECO:0007829|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
