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P70434 (IRF7_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 111. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Interferon regulatory factor 7

Short name=IRF-7
Gene names
Name:Irf7
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length457 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Key transcriptional regulator of type I interferon (IFN)-dependent immune responses and plays a critical role in the innate immune response against DNA and RNA viruses. Regulates the transcription of type I IFN genes (IFN-alpha and IFN-beta) and IFN-stimulated genes (ISG) by binding to an interferon-stimulated response element (ISRE) in their promoters. Can efficiently activate both the IFN-beta (IFNB) and the IFN-alpha (IFNA) genes and mediate their induction via both the virus-activated, MyD88-independent pathway and the TLR-activated, MyD88-dependent pathway. Required during both the early and late phases of the IFN gene induction but is more critical for the late than for the early phase. Exists in an inactive form in the cytoplasm of uninfected cells and following viral infection, double-stranded RNA (dsRNA), or toll-like receptor (TLR) signaling, becomes phosphorylated by IKBKE and TBK1 kinases. This induces a conformational change, leading to its dimerization and nuclear localization where along with other coactivators it can activate transcription of the type I IFN and ISG genes. Can also play a role in regulating adaptive immune responses by inducing PSMB9/LMP2 expression, either directly or through induction of IRF1. Binds to the Q promoter (Qp) of EBV nuclear antigen 1 a (EBNA1) and may play a role in the regulation of EBV latency. Can activate distinct gene expression programs in macrophages and regulate the anti-tumor properties of primary macrophages. Ref.3 Ref.4 Ref.5 Ref.9

Enzyme regulation

In the absence of viral infection, maintained as a monomer in an autoinhibited state and phosphorylation disrupts this autoinhibition leading to the liberation of the DNA-binding and dimerization activities and its nuclear localization where it can activate type I IFN and ISG genes.

Subunit structure

Monomer. Homodimer; phosphorylation-induced. Heterodimer with IRF3. Interacts with TICAM1 and TICAM2. Interacts with rotavirus A NSP1; this interaction leads to the proteasome-dependent degradation of IRF7. Interacts with Epstein-Barr virus LF2. Interacts with MYD88 AND TRAF6. Ref.4

Subcellular location

Nucleus. Cytoplasm. Note: The phosphorylated and active form accumulates selectively in the nucleus. Ref.4

Induction

By type I interferon (IFN) and viruses.

Post-translational modification

Acetylation inhibits its DNA-binding ability and activity By similarity.

In response to a viral infection, phosphorylated by TBK1 and IKBKE1. Phosphorylation, and subsequent activation is inhibited by vaccinia virus protein E3. In TLR7- and TLR9-mediated signaling pathway, phosphorylated by IRAK1 By similarity. Ref.3 Ref.4

TRAF6-mediated ubiquitination is required for IRF7 activation.

Sumoylated by TRIM28, which inhibits its transactivation activity By similarity.

Sequence similarities

Belongs to the IRF family.

Contains 1 IRF tryptophan pentad repeat DNA-binding domain.

Ontologies

Keywords
   Biological processImmunity
Innate immunity
Transcription
Transcription regulation
   Cellular componentCytoplasm
Nucleus
   LigandDNA-binding
   Molecular functionActivator
   PTMAcetylation
Isopeptide bond
Phosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processimmunoglobulin mediated immune response

Inferred from mutant phenotype Ref.5. Source: MGI

innate immune response

Inferred from electronic annotation. Source: UniProtKB-KW

interferon-alpha production

Inferred from mutant phenotype Ref.5. Source: UniProtKB

interferon-beta production

Inferred from mutant phenotype Ref.5. Source: UniProtKB

positive regulation of interferon-alpha production

Traceable author statement Ref.7. Source: UniProtKB

positive regulation of interferon-beta production

Traceable author statement Ref.7. Source: UniProtKB

positive regulation of transcription from RNA polymerase II promoter

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of transcription, DNA-templated

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of type I interferon-mediated signaling pathway

Inferred from mutant phenotype PubMed 17618271. Source: MGI

regulation of MyD88-dependent toll-like receptor signaling pathway

Inferred from mutant phenotype Ref.5. Source: UniProtKB

regulation of MyD88-independent toll-like receptor signaling pathway

Inferred from mutant phenotype Ref.5. Source: UniProtKB

regulation of adaptive immune response

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of innate immune response

Traceable author statement Ref.5. Source: UniProtKB

transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 23042151. Source: GOC

type I interferon biosynthetic process

Inferred from mutant phenotype Ref.5. Source: MGI

   Cellular_componentcytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

nucleus

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionDNA binding

Inferred from sequence or structural similarity. Source: UniProtKB

RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity

Inferred from direct assay PubMed 23042151. Source: MGI

RNA polymerase II core promoter sequence-specific DNA binding

Inferred from electronic annotation. Source: Ensembl

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

ChukQ606803EBI-997907,EBI-646245

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 457457Interferon regulatory factor 7
PRO_0000154563

Regions

DNA binding9 – 126118IRF tryptophan pentad repeat

Amino acid modifications

Modified residue921N6-acetyllysine; by KAT2A and KAT2B By similarity
Modified residue4251Phosphoserine Probable
Modified residue4261Phosphoserine Probable
Modified residue4291Phosphoserine Probable
Modified residue4311Phosphoserine; by TBK1 and IKKE By similarity
Modified residue4371Phosphoserine Probable
Modified residue4381Phosphoserine Probable
Modified residue4411Phosphoserine Probable
Cross-link398Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity
Cross-link400Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity

Experimental info

Mutagenesis4251S → A: Strongly decreased transcriptional activation in response to viral infection; when associated with A-426. Ref.3
Mutagenesis4251S → D: Strongly decreased transcriptional activation in response to viral infection; when associated with D-426. Ref.3
Mutagenesis4261S → A: Strongly decreased transcriptional activation in response to viral infection; when associated with A-425. Ref.3
Mutagenesis4261S → D: Strongly decreased transcriptional activation in response to viral infection; when associated with D-425. Ref.3
Mutagenesis4271L → A: Strongly decreased transcriptional activation in response to viral infection. Ref.3
Mutagenesis4271L → D: No effect on transcriptional activation in response to viral infection. Ref.3
Mutagenesis4291S → A: Almost no effect on transcriptional activation in response to viral infection; when associated with A-430 and A-431. Ref.3
Mutagenesis4291S → D: Strongly increased transcriptional activation in response to viral infection; when associated with D-430 and A-431. Ref.3
Mutagenesis4301S → A: Almost no effect on transcriptional activation in response to viral infection; when associated with A-429 and A-431.
Mutagenesis4301S → D: Strongly increased transcriptional activation in response to viral infection; when associated with D-429 and A-431.
Mutagenesis4311S → A: Almost no effect on transcriptional activation in response to viral infection; when associated with A-429 and A-430. Ref.3
Mutagenesis4311S → D: Strongly increased transcriptional activation in response to viral infection; when associated with D-429 and A-430. Ref.3
Mutagenesis4371S → A: Almost complete loss of transcriptional activation; when associated with A-438. Ref.3
Mutagenesis4371S → D: Increased transcriptional activation; when associated with D-438. Ref.3
Mutagenesis4381S → A: Almost complete loss of transcriptional activation; when associated with A-437. Ref.3
Mutagenesis4381S → D: Increased transcriptional activation; when associated with D-437. Ref.3
Mutagenesis4411S → A: Almost no effect on transcriptional activation in response to viral infection. Ref.3

Secondary structure

.................. 457
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P70434 [UniParc].

Last modified February 1, 1997. Version 1.
Checksum: 30B102C668F56142

FASTA45751,222
        10         20         30         40         50         60 
MAEVRGVQRV LFGDWLLGEV SSGQYEGLQW LNEARTVFRV PWKHFGRRDL DEEDAQIFKA 

        70         80         90        100        110        120 
WAVARGRWPP SGVNLPPPEA EAAERRERRG WKTNFRCALH STGRFILRQD NSGDPVDPHK 

       130        140        150        160        170        180 
VYELSRELGS TVGPATENRE EVSLSNALPT QGVSPGSFLA RENAGLQTPS PLLSSDAGDL 

       190        200        210        220        230        240 
LLQVLQYSHI LESESGADPV PPQAPGQEQD RVYEEPYAAW QVEAVPSPRP QQPALTERSL 

       250        260        270        280        290        300 
GFLDVTIMYK GRTVLQAVVG HPRCVFLYSP MAPAVRTSEP QPVIFPSPAE LPDQKQLHYT 

       310        320        330        340        350        360 
ETLLQHVSPG LQLELRGPSL WALRMGKCKV YWEVGSPMGT TGPSTPPQLL ERNRHTPIFD 

       370        380        390        400        410        420 
FSTFFRELEE FRARRRQGSP HYTIYLGFGQ DLSAGRPKEK TLILVKLEPW VCKAYLEGVQ 

       430        440        450 
REGVSSLDSS SLGLCLSSTN SLYEDIEHFL MDLGQWP 

« Hide

References

[1]Grossman A., Nicholl J., Antonio L., Luethy R., Suggs S., Sutherland G.R., Mak T.W.
Submitted (OCT-1996) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Strain: BALB/c.
Tissue: Spleen.
[2]"Structure and function of IRF-7."
Zhang L., Pagano J.S.
J. Interferon Cytokine Res. 22:95-101(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON FUNCTION.
[3]"Regulatory serine residues mediate phosphorylation-dependent and phosphorylation-independent activation of interferon regulatory factor 7."
Caillaud A., Hovanessian A.G., Levy D.E., Marie I.J.
J. Biol. Chem. 280:17671-17677(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, PHOSPHORYLATION AT SER-425; SER-426; SER-429; SER-431; SER-437; SER-438 AND SER-441, MUTAGENESIS OF SER-425; SER-426; LEU-427; SER-429; SER-431; SER-437; SER-438 AND SER-441.
[4]"Interferon-alpha induction through Toll-like receptors involves a direct interaction of IRF7 with MyD88 and TRAF6."
Kawai T., Sato S., Ishii K.J., Coban C., Hemmi H., Yamamoto M., Terai K., Matsuda M., Inoue J., Uematsu S., Takeuchi O., Akira S.
Nat. Immunol. 5:1061-1068(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION, UBIQUITINATION, INTERACTION WITH MYD88 AND TRAF6.
[5]"IRF-7 is the master regulator of type-I interferon-dependent immune responses."
Honda K., Yanai H., Negishi H., Asagiri M., Sato M., Mizutani T., Shimada N., Ohba Y., Takaoka A., Yoshida N., Taniguchi T.
Nature 434:772-777(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[6]"Distinct functions of IRF-3 and IRF-7 in IFN-alpha gene regulation and control of anti-tumor activity in primary macrophages."
Solis M., Goubau D., Romieu-Mourez R., Genin P., Civas A., Hiscott J.
Biochem. Pharmacol. 72:1469-1476(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON FUNCTION.
[7]"Type I interferon gene induction by the interferon regulatory factor family of transcription factors."
Honda K., Takaoka A., Taniguchi T.
Immunity 25:349-360(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON FUNCTION.
[8]Erratum
Honda K., Takaoka A., Taniguchi T.
Immunity 25:849-849(2006)
[9]"Interferon regulatory factor IRF-7 induces the antiviral alpha interferon response and protects against lethal West Nile virus infection."
Daffis S., Samuel M.A., Suthar M.S., Keller B.C., Gale M. Jr., Diamond M.S.
J. Virol. 82:8465-8475(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[10]"Regulation of immunity and oncogenesis by the IRF transcription factor family."
Savitsky D., Tamura T., Yanai H., Taniguchi T.
Cancer Immunol. Immunother. 59:489-510(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON FUNCTION.
[11]"IRF7: activation, regulation, modification and function."
Ning S., Pagano J.S., Barber G.N.
Genes Immun. 12:399-414(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON FUNCTION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U73037 mRNA. Translation: AAB18626.1.
RefSeqNP_058546.1. NM_016850.3.
UniGeneMm.3233.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3QU3X-ray1.30A/B/C1-134[»]
ProteinModelPortalP70434.
SMRP70434. Positions 9-130, 238-455.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid207563. 9 interactions.
IntActP70434. 4 interactions.

PTM databases

PhosphoSiteP70434.

Proteomic databases

PaxDbP70434.
PRIDEP70434.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000026571; ENSMUSP00000026571; ENSMUSG00000025498.
GeneID54123.
KEGGmmu:54123.
UCSCuc009kkg.2. mouse.

Organism-specific databases

CTD3665.
MGIMGI:1859212. Irf7.

Phylogenomic databases

eggNOGNOG39245.
HOGENOMHOG000111812.
HOVERGENHBG105600.
InParanoidP70434.
KOK09447.
OMAGWKTNFR.
PhylomeDBP70434.
TreeFamTF328512.

Gene expression databases

ArrayExpressP70434.
BgeeP70434.
CleanExMM_IRF7.
GenevestigatorP70434.

Family and domain databases

Gene3D1.10.10.10. 1 hit.
2.60.200.10. 1 hit.
InterProIPR019817. Interferon_reg_fac_CS.
IPR001346. Interferon_reg_fact_DNA-bd_dom.
IPR019471. Interferon_reg_factor-3.
IPR017855. SMAD_dom-like.
IPR008984. SMAD_FHA_domain.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]
PfamPF00605. IRF. 1 hit.
PF10401. IRF-3. 1 hit.
[Graphical view]
PRINTSPR00267. INTFRNREGFCT.
SMARTSM00348. IRF. 1 hit.
[Graphical view]
SUPFAMSSF49879. SSF49879. 1 hit.
PROSITEPS00601. IRF_1. 1 hit.
PS51507. IRF_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio310909.
PROP70434.
SOURCESearch...

Entry information

Entry nameIRF7_MOUSE
AccessionPrimary (citable) accession number: P70434
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: February 1, 1997
Last modified: April 16, 2014
This is version 111 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot