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P70434

- IRF7_MOUSE

UniProt

P70434 - IRF7_MOUSE

Protein

Interferon regulatory factor 7

Gene

Irf7

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 115 (01 Oct 2014)
      Sequence version 1 (01 Feb 1997)
      Previous versions | rss
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    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

    1. DNA binding Source: UniProtKB
    2. protein binding Source: IntAct
    3. RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity Source: MGI
    4. RNA polymerase II core promoter sequence-specific DNA binding Source: Ensembl

    GO - Biological processi

    1. immunoglobulin mediated immune response Source: MGI
    2. innate immune response Source: UniProtKB-KW
    3. interferon-alpha production Source: UniProtKB
    4. interferon-beta production Source: UniProtKB
    5. positive regulation of interferon-alpha production Source: UniProtKB
    6. positive regulation of interferon-beta production Source: UniProtKB
    7. positive regulation of transcription, DNA-templated Source: UniProtKB
    8. positive regulation of transcription from RNA polymerase II promoter Source: UniProtKB
    9. positive regulation of type I interferon-mediated signaling pathway Source: MGI
    10. regulation of adaptive immune response Source: UniProtKB
    11. regulation of innate immune response Source: UniProtKB
    12. regulation of MyD88-dependent toll-like receptor signaling pathway Source: UniProtKB
    13. regulation of MyD88-independent toll-like receptor signaling pathway Source: UniProtKB
    14. transcription from RNA polymerase II promoter Source: GOC
    15. type I interferon biosynthetic process Source: MGI

    Keywords - Molecular functioni

    Activator

    Keywords - Biological processi

    Immunity, Innate immunity, Transcription, Transcription regulation

    Keywords - Ligandi

    DNA-binding

    Enzyme and pathway databases

    ReactomeiREACT_198521. TRAF6 mediated IRF7 activation.
    REACT_198527. TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling.
    REACT_198649. Factors involved in megakaryocyte development and platelet production.
    REACT_198660. Interferon gamma signaling.
    REACT_225463. Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon.

    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: Chromosome 7

    Organism-specific databases

    MGIiMGI:1859212. Irf7.

    Subcellular locationi

    Nucleus 1 Publication. Cytoplasm 1 Publication
    Note: The phosphorylated and active form accumulates selectively in the nucleus.

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB-SubCell
    2. nucleus Source: UniProtKB-SubCell

    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 – 4251Phosphoserine2 Publications
    Modified residuei426 – 4261Phosphoserine2 Publications
    Modified residuei429 – 4291Phosphoserine2 Publications
    Modified residuei431 – 4311Phosphoserine; by TBK1 and IKKEBy similarity
    Modified residuei437 – 4371Phosphoserine2 Publications
    Modified residuei438 – 4381Phosphoserine2 Publications
    Modified residuei441 – 4411Phosphoserine2 Publications

    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

    ArrayExpressiP70434.
    BgeeiP70434.
    CleanExiMM_IRF7.
    GenevestigatoriP70434.

    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. 9 interactions.
    IntActiP70434. 4 interactions.

    Structurei

    Secondary structure

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

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    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.
    HOGENOMiHOG000111812.
    HOVERGENiHBG105600.
    InParanoidiP70434.
    KOiK09447.
    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

    MAEVRGVQRV LFGDWLLGEV SSGQYEGLQW LNEARTVFRV PWKHFGRRDL    50
    DEEDAQIFKA WAVARGRWPP SGVNLPPPEA EAAERRERRG WKTNFRCALH 100
    STGRFILRQD NSGDPVDPHK VYELSRELGS TVGPATENRE EVSLSNALPT 150
    QGVSPGSFLA RENAGLQTPS PLLSSDAGDL LLQVLQYSHI LESESGADPV 200
    PPQAPGQEQD RVYEEPYAAW QVEAVPSPRP QQPALTERSL GFLDVTIMYK 250
    GRTVLQAVVG HPRCVFLYSP MAPAVRTSEP QPVIFPSPAE LPDQKQLHYT 300
    ETLLQHVSPG LQLELRGPSL WALRMGKCKV YWEVGSPMGT TGPSTPPQLL 350
    ERNRHTPIFD FSTFFRELEE FRARRRQGSP HYTIYLGFGQ DLSAGRPKEK 400
    TLILVKLEPW VCKAYLEGVQ REGVSSLDSS SLGLCLSSTN SLYEDIEHFL 450
    MDLGQWP 457
    Length:457
    Mass (Da):51,222
    Last modified:February 1, 1997 - v1
    Checksum:i30B102C668F56142
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U73037 mRNA. Translation: AAB18626.1.
    CCDSiCCDS22005.1.
    RefSeqiNP_058546.1. NM_016850.3.
    UniGeneiMm.3233.

    Genome annotation databases

    EnsembliENSMUST00000026571; ENSMUSP00000026571; ENSMUSG00000025498.
    GeneIDi54123.
    KEGGimmu:54123.
    UCSCiuc009kkg.2. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U73037 mRNA. Translation: AAB18626.1 .
    CCDSi CCDS22005.1.
    RefSeqi NP_058546.1. NM_016850.3.
    UniGenei Mm.3233.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    3QU3 X-ray 1.30 A/B/C 1-134 [» ]
    ProteinModelPortali P70434.
    SMRi P70434. Positions 9-130, 243-417.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 207563. 9 interactions.
    IntActi P70434. 4 interactions.

    PTM databases

    PhosphoSitei P70434.

    Proteomic databases

    PaxDbi P70434.
    PRIDEi P70434.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000026571 ; ENSMUSP00000026571 ; ENSMUSG00000025498 .
    GeneIDi 54123.
    KEGGi mmu:54123.
    UCSCi uc009kkg.2. mouse.

    Organism-specific databases

    CTDi 3665.
    MGIi MGI:1859212. Irf7.

    Phylogenomic databases

    eggNOGi NOG39245.
    HOGENOMi HOG000111812.
    HOVERGENi HBG105600.
    InParanoidi P70434.
    KOi K09447.
    OMAi GWKTNFR.
    PhylomeDBi P70434.
    TreeFami TF328512.

    Enzyme and pathway databases

    Reactomei REACT_198521. TRAF6 mediated IRF7 activation.
    REACT_198527. TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling.
    REACT_198649. Factors involved in megakaryocyte development and platelet production.
    REACT_198660. Interferon gamma signaling.
    REACT_225463. Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon.

    Miscellaneous databases

    NextBioi 310909.
    PROi P70434.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P70434.
    Bgeei P70434.
    CleanExi MM_IRF7.
    Genevestigatori P70434.

    Family and domain databases

    Gene3Di 1.10.10.10. 1 hit.
    2.60.200.10. 1 hit.
    InterProi IPR019817. 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 ]
    Pfami PF00605. IRF. 1 hit.
    PF10401. IRF-3. 1 hit.
    [Graphical view ]
    PRINTSi PR00267. INTFRNREGFCT.
    SMARTi SM00348. IRF. 1 hit.
    [Graphical view ]
    SUPFAMi SSF49879. SSF49879. 1 hit.
    PROSITEi PS00601. IRF_1. 1 hit.
    PS51507. IRF_2. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    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: October 1, 2014
    This is version 115 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