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Protein

Interferon regulatory factor 7

Gene

Irf7

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.4 Publications

Enzyme regulationi

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.

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
DNA bindingi9 – 126118IRF tryptophan pentad repeatPROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

GO - Biological processi

  • immunoglobulin mediated immune response Source: MGI
  • innate immune response Source: UniProtKB-KW
  • interferon-alpha production Source: UniProtKB
  • interferon-beta production Source: UniProtKB
  • positive regulation of interferon-alpha production Source: UniProtKB
  • positive regulation of interferon-beta production Source: UniProtKB
  • positive regulation of transcription, DNA-templated Source: UniProtKB
  • positive regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  • positive regulation of type I interferon-mediated signaling pathway Source: MGI
  • positive regulation of type I interferon production Source: MGI
  • regulation of adaptive immune response Source: UniProtKB
  • regulation of innate immune response Source: UniProtKB
  • regulation of MyD88-dependent toll-like receptor signaling pathway Source: UniProtKB
  • regulation of MyD88-independent toll-like receptor signaling pathway Source: UniProtKB
  • transcription, DNA-templated Source: UniProtKB-KW
  • type I interferon biosynthetic process Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Activator

Keywords - Biological processi

Immunity, Innate immunity, Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding

Enzyme and pathway databases

ReactomeiREACT_280010. Factors involved in megakaryocyte development and platelet production.
REACT_297122. TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling.
REACT_311325. TRAF3-dependent IRF activation pathway.
REACT_311354. TRAF6 mediated IRF7 activation.
REACT_332303. Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon.
REACT_343658. DEx/H-box helicases activate type I IFN and inflammatory cytokines production.
REACT_349056. Interferon gamma signaling.

Names & Taxonomyi

Protein namesi
Recommended name:
Interferon regulatory factor 7
Short name:
IRF-7
Gene namesi
Name:Irf7
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589 Componenti: Chromosome 7

Organism-specific databases

MGIiMGI:1859212. Irf7.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi425 – 4251S → A: Strongly decreased transcriptional activation in response to viral infection; when associated with A-426. 1 Publication
Mutagenesisi425 – 4251S → D: Strongly decreased transcriptional activation in response to viral infection; when associated with D-426. 1 Publication
Mutagenesisi426 – 4261S → A: Strongly decreased transcriptional activation in response to viral infection; when associated with A-425. 1 Publication
Mutagenesisi426 – 4261S → D: Strongly decreased transcriptional activation in response to viral infection; when associated with D-425. 1 Publication
Mutagenesisi427 – 4271L → A: Strongly decreased transcriptional activation in response to viral infection. 1 Publication
Mutagenesisi427 – 4271L → D: No effect on transcriptional activation in response to viral infection. 1 Publication
Mutagenesisi429 – 4291S → A: Almost no effect on transcriptional activation in response to viral infection; when associated with A-430 and A-431. 1 Publication
Mutagenesisi429 – 4291S → D: Strongly increased transcriptional activation in response to viral infection; when associated with D-430 and A-431. 1 Publication
Mutagenesisi430 – 4301S → A: Almost no effect on transcriptional activation in response to viral infection; when associated with A-429 and A-431.
Mutagenesisi430 – 4301S → D: Strongly increased transcriptional activation in response to viral infection; when associated with D-429 and A-431.
Mutagenesisi431 – 4311S → A: Almost no effect on transcriptional activation in response to viral infection; when associated with A-429 and A-430. 1 Publication
Mutagenesisi431 – 4311S → D: Strongly increased transcriptional activation in response to viral infection; when associated with D-429 and A-430. 1 Publication
Mutagenesisi437 – 4371S → A: Almost complete loss of transcriptional activation; when associated with A-438. 1 Publication
Mutagenesisi437 – 4371S → D: Increased transcriptional activation; when associated with D-438. 1 Publication
Mutagenesisi438 – 4381S → A: Almost complete loss of transcriptional activation; when associated with A-437. 1 Publication
Mutagenesisi438 – 4381S → D: Increased transcriptional activation; when associated with D-437. 1 Publication
Mutagenesisi441 – 4411S → A: Almost no effect on transcriptional activation in response to viral infection. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 457457Interferon regulatory factor 7PRO_0000154563Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei92 – 921N6-acetyllysine; by KAT2A and KAT2BBy similarity
Cross-linki398 – 398Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity
Cross-linki400 – 400Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity
Modified residuei425 – 4251Phosphoserine1 Publication
Modified residuei426 – 4261Phosphoserine1 Publication
Modified residuei429 – 4291Phosphoserine1 Publication
Modified residuei431 – 4311Phosphoserine; by TBK1 and IKKEBy similarity
Modified residuei437 – 4371Phosphoserine1 Publication
Modified residuei438 – 4381Phosphoserine1 Publication
Modified residuei441 – 4411Phosphoserine1 Publication

Post-translational modificationi

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).By similarity
TRAF6-mediated ubiquitination is required for IRF7 activation.1 Publication
Sumoylated by TRIM28, which inhibits its transactivation activity.By similarity

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiP70434.
PRIDEiP70434.

PTM databases

PhosphoSiteiP70434.

Expressioni

Inductioni

By type I interferon (IFN) and viruses.

Gene expression databases

BgeeiP70434.
CleanExiMM_IRF7.
ExpressionAtlasiP70434. baseline and differential.
GenevisibleiP70434. MM.

Interactioni

Subunit structurei

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 TRAF6.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
ChukQ606803EBI-997907,EBI-646245

Protein-protein interaction databases

BioGridi207563. 8 interactions.
DIPiDIP-37903N.
IntActiP70434. 4 interactions.
STRINGi10090.ENSMUSP00000026571.

Structurei

Secondary structure

1
457
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi12 – 2211Combined sources
Beta strandi29 – 324Combined sources
Beta strandi37 – 415Combined sources
Helixi52 – 554Combined sources
Helixi56 – 649Combined sources
Helixi77 – 859Combined sources
Helixi88 – 10013Combined sources
Beta strandi105 – 1117Combined sources
Beta strandi119 – 1246Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3QU3X-ray1.30A/B/C1-134[»]
ProteinModelPortaliP70434.
SMRiP70434. Positions 9-130, 243-417.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the IRF family.PROSITE-ProRule annotation
Contains 1 IRF tryptophan pentad repeat DNA-binding domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiNOG39245.
GeneTreeiENSGT00760000119093.
HOGENOMiHOG000111812.
HOVERGENiHBG105600.
InParanoidiP70434.
OMAiGWKTNFR.
PhylomeDBiP70434.
TreeFamiTF328512.

Family and domain databases

Gene3Di1.10.10.10. 1 hit.
2.60.200.10. 1 hit.
InterProiIPR019817. 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]
PfamiPF00605. IRF. 1 hit.
PF10401. IRF-3. 1 hit.
[Graphical view]
PRINTSiPR00267. INTFRNREGFCT.
SMARTiSM00348. IRF. 1 hit.
[Graphical view]
SUPFAMiSSF49879. SSF49879. 1 hit.
PROSITEiPS00601. IRF_1. 1 hit.
PS51507. IRF_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P70434-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAEVRGVQRV LFGDWLLGEV SSGQYEGLQW LNEARTVFRV PWKHFGRRDL
60 70 80 90 100
DEEDAQIFKA WAVARGRWPP SGVNLPPPEA EAAERRERRG WKTNFRCALH
110 120 130 140 150
STGRFILRQD NSGDPVDPHK VYELSRELGS TVGPATENRE EVSLSNALPT
160 170 180 190 200
QGVSPGSFLA RENAGLQTPS PLLSSDAGDL LLQVLQYSHI LESESGADPV
210 220 230 240 250
PPQAPGQEQD RVYEEPYAAW QVEAVPSPRP QQPALTERSL GFLDVTIMYK
260 270 280 290 300
GRTVLQAVVG HPRCVFLYSP MAPAVRTSEP QPVIFPSPAE LPDQKQLHYT
310 320 330 340 350
ETLLQHVSPG LQLELRGPSL WALRMGKCKV YWEVGSPMGT TGPSTPPQLL
360 370 380 390 400
ERNRHTPIFD FSTFFRELEE FRARRRQGSP HYTIYLGFGQ DLSAGRPKEK
410 420 430 440 450
TLILVKLEPW VCKAYLEGVQ REGVSSLDSS SLGLCLSSTN SLYEDIEHFL

MDLGQWP
Length:457
Mass (Da):51,222
Last modified:February 1, 1997 - v1
Checksum:i30B102C668F56142
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U73037 mRNA. Translation: AAB18626.1.
CCDSiCCDS22005.1.
RefSeqiNP_058546.1. NM_016850.3.
UniGeneiMm.3233.

Genome annotation databases

EnsembliENSMUST00000026571; ENSMUSP00000026571; ENSMUSG00000025498.
GeneIDi54123.
UCSCiuc009kkg.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U73037 mRNA. Translation: AAB18626.1.
CCDSiCCDS22005.1.
RefSeqiNP_058546.1. NM_016850.3.
UniGeneiMm.3233.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3QU3X-ray1.30A/B/C1-134[»]
ProteinModelPortaliP70434.
SMRiP70434. Positions 9-130, 243-417.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi207563. 8 interactions.
DIPiDIP-37903N.
IntActiP70434. 4 interactions.
STRINGi10090.ENSMUSP00000026571.

PTM databases

PhosphoSiteiP70434.

Proteomic databases

PaxDbiP70434.
PRIDEiP70434.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000026571; ENSMUSP00000026571; ENSMUSG00000025498.
GeneIDi54123.
UCSCiuc009kkg.2. mouse.

Organism-specific databases

CTDi3665.
MGIiMGI:1859212. Irf7.

Phylogenomic databases

eggNOGiNOG39245.
GeneTreeiENSGT00760000119093.
HOGENOMiHOG000111812.
HOVERGENiHBG105600.
InParanoidiP70434.
OMAiGWKTNFR.
PhylomeDBiP70434.
TreeFamiTF328512.

Enzyme and pathway databases

ReactomeiREACT_280010. Factors involved in megakaryocyte development and platelet production.
REACT_297122. TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling.
REACT_311325. TRAF3-dependent IRF activation pathway.
REACT_311354. TRAF6 mediated IRF7 activation.
REACT_332303. Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon.
REACT_343658. DEx/H-box helicases activate type I IFN and inflammatory cytokines production.
REACT_349056. Interferon gamma signaling.

Miscellaneous databases

NextBioi310909.
PROiP70434.
SOURCEiSearch...

Gene expression databases

BgeeiP70434.
CleanExiMM_IRF7.
ExpressionAtlasiP70434. baseline and differential.
GenevisibleiP70434. MM.

Family and domain databases

Gene3Di1.10.10.10. 1 hit.
2.60.200.10. 1 hit.
InterProiIPR019817. 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]
PfamiPF00605. IRF. 1 hit.
PF10401. IRF-3. 1 hit.
[Graphical view]
PRINTSiPR00267. INTFRNREGFCT.
SMARTiSM00348. IRF. 1 hit.
[Graphical view]
SUPFAMiSSF49879. SSF49879. 1 hit.
PROSITEiPS00601. IRF_1. 1 hit.
PS51507. IRF_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  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. 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.

Entry informationi

Entry nameiIRF7_MOUSE
AccessioniPrimary (citable) accession number: P70434
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: February 1, 1997
Last modified: July 22, 2015
This is version 124 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.