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P15314

- IRF1_MOUSE

UniProt

P15314 - IRF1_MOUSE

Protein

Interferon regulatory factor 1

Gene

Irf1

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 120 (01 Oct 2014)
      Sequence version 1 (01 Apr 1990)
      Previous versions | rss
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    Functioni

    Transcriptional regulator which displays a remarkable functional diversity in the regulation of cellular responses. These include the regulation of IFN and IFN-inducible genes, host response to viral and bacterial infections, regulation of many genes expressed during hematopoiesis, inflammation, immune responses and cell proliferation and differentiation, regulation of the cell cycle and induction of growth arrest and programmed cell death following DNA damage. Stimulates both innate and acquired immune responses through the activation of specific target genes and can act as a transcriptional activator and repressor regulating target genes by binding to an interferon-stimulated response element (ISRE) in their promoters. Its target genes for transcriptional activation activity are: genes involved in anti-viral response, such as IFN-alpha/beta, DDX58/RIG-I, TNFSF10/TRAIL, OAS1/2, PIAS1/GBP, EIF2AK2/PKR and RSAD2/viperin; antibacterial response, such as NOS2/INOS; anti-proliferative response, such as p53/TP53, LOX and CDKN1A; apoptosis, such as BBC3/PUMA, CASP1, CASP7 and CASP8; immune response, such as IL7, IL12A/B and IL15, PTGS2/COX2 and CYBB; DNA damage responses and DNA repair, such as POLQ/POLH; MHC class I expression, such as TAP1, PSMB9/LMP2, PSME1/PA28A, PSME2/PA28B and B2M and MHC class II expression, such as CIITA. Represses genes involved in anti-proliferative response, such as BIRC5/survivin, CCNB1, CCNE1, CDK1, CDK2 and CDK4 and in immune response, such as FOXP3, IL4, ANXA2 and TLR4. Stimulates p53/TP53-dependent transcription through enhanced recruitment of EP300 leading to increased acetylation of p53/TP53. Plays an important role in immune response directly affecting NK maturation and activity, macrophage production of IL12, Th1 development and maturation of CD8+ T-cells. Also implicated in the differentiation and maturation of dendritic cells and in the suppression of regulatory T (Treg) cells development. Acts as a tumor suppressor and plays a role not only in antagonism of tumor cell growth but also in stimulating an immune response against tumor cells.6 Publications

    Enzyme regulationi

    Activated by MYD88.

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    DNA bindingi5 – 113109IRF tryptophan pentad repeatPROSITE-ProRule annotationAdd
    BLAST

    GO - Molecular functioni

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

    GO - Biological processi

    1. apoptotic process Source: UniProtKB
    2. CD8-positive, alpha-beta T cell differentiation Source: MGI
    3. cell cycle arrest Source: UniProtKB
    4. cellular response to interferon-beta Source: Ensembl
    5. cellular response to mechanical stimulus Source: Ensembl
    6. defense response to virus Source: UniProtKB
    7. interferon-gamma-mediated signaling pathway Source: UniProtKB
    8. negative regulation of regulatory T cell differentiation Source: UniProtKB
    9. negative regulation of T-helper 2 cell differentiation Source: UniProtKB
    10. negative regulation of transcription, DNA-templated Source: UniProtKB
    11. positive regulation of interferon-beta production Source: UniProtKB
    12. positive regulation of interleukin-12 biosynthetic process Source: MGI
    13. positive regulation of natural killer cell differentiation Source: UniProtKB
    14. positive regulation of T-helper 1 cell differentiation Source: UniProtKB
    15. positive regulation of transcription, DNA-templated Source: UniProtKB
    16. positive regulation of transcription from RNA polymerase II promoter Source: MGI
    17. positive regulation of type I interferon production Source: UniProtKB
    18. regulation of adaptive immune response Source: UniProtKB
    19. regulation of CD8-positive, alpha-beta T cell proliferation Source: UniProtKB
    20. regulation of gene expression Source: MGI
    21. regulation of innate immune response Source: UniProtKB
    22. regulation of MyD88-dependent toll-like receptor signaling pathway Source: UniProtKB
    23. transcription, DNA-templated Source: UniProtKB-KW

    Keywords - Molecular functioni

    Activator, Repressor

    Keywords - Biological processi

    Antiviral defense, Immunity, Innate immunity, Transcription, Transcription regulation

    Keywords - Ligandi

    DNA-binding

    Enzyme and pathway databases

    ReactomeiREACT_198521. TRAF6 mediated IRF7 activation.
    REACT_198649. Factors involved in megakaryocyte development and platelet production.
    REACT_198660. Interferon gamma signaling.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Interferon regulatory factor 1
    Short name:
    IRF-1
    Gene namesi
    Name:Irf1
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 11

    Organism-specific databases

    MGIiMGI:96590. Irf1.

    Subcellular locationi

    Nucleus 1 Publication. Cytoplasm 1 Publication
    Note: MYD88-associated IRF1 migrates into the nucleus more efficiently than non-MYD88-associated IRF1.

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB
    2. nuclear chromatin Source: Ensembl
    3. nucleus Source: UniProtKB

    Keywords - Cellular componenti

    Cytoplasm, Nucleus

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 329329Interferon regulatory factor 1PRO_0000154546Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei78 – 781N6-acetyllysineBy similarity
    Cross-linki276 – 276Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity
    Cross-linki300 – 300Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity

    Post-translational modificationi

    Phosphorylated by CK2 and this positively regulates its activity.By similarity
    Sumoylation represses the transcriptional activity and displays enhanced resistance to protein degradation. Inactivates the tumor suppressor activity. Elevated levels in tumor cells. Major site is Lys-276. Sumoylation is enhanced by PIAS3. Desumoylated by SENP1 in tumor cells and appears to compete with ubiquitination on C-terminal sites By similarity.By similarity
    Ubiquitinated. Appears to compete with sumoylation on C-terminal sites By similarity.By similarity

    Keywords - PTMi

    Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

    Proteomic databases

    PRIDEiP15314.

    PTM databases

    PhosphoSiteiP15314.

    Expressioni

    Inductioni

    By viruses and IFN-gamma.

    Gene expression databases

    ArrayExpressiP15314.
    BgeeiP15314.
    CleanExiMM_IRF1.
    GenevestigatoriP15314.

    Interactioni

    Subunit structurei

    Monomer. Homodimer. Interacts with EP300 By similarity. Interacts with MYD88 and PIAS3.By similarity2 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    KEAP1Q141452EBI-6115486,EBI-751001From a different organism.
    TRAF3Q131142EBI-6115486,EBI-357631From a different organism.

    Protein-protein interaction databases

    BioGridi200784. 6 interactions.
    IntActiP15314. 5 interactions.

    Structurei

    Secondary structure

    1
    329
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi12 – 209
    Beta strandi21 – 255
    Beta strandi29 – 346
    Turni48 – 503
    Beta strandi51 – 533
    Helixi54 – 618
    Helixi74 – 8714
    Beta strandi89 – 935
    Beta strandi100 – 1023
    Beta strandi107 – 1093

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1IF1X-ray3.00A/B1-113[»]
    ProteinModelPortaliP15314.
    SMRiP15314. Positions 7-111.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP15314.

    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

    eggNOGiNOG42582.
    HOGENOMiHOG000037937.
    HOVERGENiHBG003455.
    InParanoidiP15314.
    KOiK09444.
    OMAiCKEEPEV.
    OrthoDBiEOG72ZCFD.
    PhylomeDBiP15314.
    TreeFamiTF328512.

    Family and domain databases

    Gene3Di1.10.10.10. 1 hit.
    InterProiIPR017431. Interferon_reg_fac-1/2.
    IPR019817. Interferon_reg_fac_CS.
    IPR001346. Interferon_reg_fact_DNA-bd_dom.
    IPR011991. WHTH_DNA-bd_dom.
    [Graphical view]
    PfamiPF00605. IRF. 1 hit.
    [Graphical view]
    PIRSFiPIRSF038196. IFN_RF1/2. 1 hit.
    PRINTSiPR00267. INTFRNREGFCT.
    SMARTiSM00348. IRF. 1 hit.
    [Graphical view]
    PROSITEiPS00601. IRF_1. 1 hit.
    PS51507. IRF_2. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    P15314-1 [UniParc]FASTAAdd to Basket

    « Hide

    MPITRMRMRP WLEMQINSNQ IPGLIWINKE EMIFQIPWKH AAKHGWDINK    50
    DACLFRSWAI HTGRYKAGEK EPDPKTWKAN FRCAMNSLPD IEEVKDQSRN 100
    KGSSAVRVYR MLPPLTRNQR KERKSKSSRD TKSKTKRKLC GDVSPDTFSD 150
    GLSSSTLPDD HSSYTTQGYL GQDLDMERDI TPALSPCVVS SSLSEWHMQM 200
    DIIPDSTTDL YNLQVSPMPS TSEAATDEDE EGKIAEDLMK LFEQSEWQPT 250
    HIDGKGYLLN EPGTQLSSVY GDFSCKEEPE IDSPRGDIGI GIQHVFTEMK 300
    NMDSIMWMDS LLGNSVRLPP SIQAIPCAP 329
    Length:329
    Mass (Da):37,319
    Last modified:April 1, 1990 - v1
    Checksum:i0E5DD23C0D977B34
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M21065 mRNA. Translation: AAA39334.1.
    BC003821 mRNA. Translation: AAH03821.1.
    CCDSiCCDS24686.1.
    PIRiA31595.
    RefSeqiNP_001152868.1. NM_001159396.1.
    NP_032416.1. NM_008390.2.
    UniGeneiMm.105218.

    Genome annotation databases

    EnsembliENSMUST00000019043; ENSMUSP00000019043; ENSMUSG00000018899.
    ENSMUST00000108920; ENSMUSP00000104548; ENSMUSG00000018899.
    GeneIDi16362.
    KEGGimmu:16362.
    UCSCiuc007iww.2. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M21065 mRNA. Translation: AAA39334.1 .
    BC003821 mRNA. Translation: AAH03821.1 .
    CCDSi CCDS24686.1.
    PIRi A31595.
    RefSeqi NP_001152868.1. NM_001159396.1.
    NP_032416.1. NM_008390.2.
    UniGenei Mm.105218.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1IF1 X-ray 3.00 A/B 1-113 [» ]
    ProteinModelPortali P15314.
    SMRi P15314. Positions 7-111.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 200784. 6 interactions.
    IntActi P15314. 5 interactions.

    PTM databases

    PhosphoSitei P15314.

    Proteomic databases

    PRIDEi P15314.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000019043 ; ENSMUSP00000019043 ; ENSMUSG00000018899 .
    ENSMUST00000108920 ; ENSMUSP00000104548 ; ENSMUSG00000018899 .
    GeneIDi 16362.
    KEGGi mmu:16362.
    UCSCi uc007iww.2. mouse.

    Organism-specific databases

    CTDi 3659.
    MGIi MGI:96590. Irf1.

    Phylogenomic databases

    eggNOGi NOG42582.
    HOGENOMi HOG000037937.
    HOVERGENi HBG003455.
    InParanoidi P15314.
    KOi K09444.
    OMAi CKEEPEV.
    OrthoDBi EOG72ZCFD.
    PhylomeDBi P15314.
    TreeFami TF328512.

    Enzyme and pathway databases

    Reactomei REACT_198521. TRAF6 mediated IRF7 activation.
    REACT_198649. Factors involved in megakaryocyte development and platelet production.
    REACT_198660. Interferon gamma signaling.

    Miscellaneous databases

    EvolutionaryTracei P15314.
    NextBioi 289466.
    PROi P15314.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P15314.
    Bgeei P15314.
    CleanExi MM_IRF1.
    Genevestigatori P15314.

    Family and domain databases

    Gene3Di 1.10.10.10. 1 hit.
    InterProi IPR017431. Interferon_reg_fac-1/2.
    IPR019817. Interferon_reg_fac_CS.
    IPR001346. Interferon_reg_fact_DNA-bd_dom.
    IPR011991. WHTH_DNA-bd_dom.
    [Graphical view ]
    Pfami PF00605. IRF. 1 hit.
    [Graphical view ]
    PIRSFi PIRSF038196. IFN_RF1/2. 1 hit.
    PRINTSi PR00267. INTFRNREGFCT.
    SMARTi SM00348. IRF. 1 hit.
    [Graphical view ]
    PROSITEi PS00601. IRF_1. 1 hit.
    PS51507. IRF_2. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Regulated expression of a gene encoding a nuclear factor, IRF-1, that specifically binds to IFN-beta gene regulatory elements."
      Miyamoto M., Fujita T., Kimura Y., Maruyama M., Harada H., Sudo Y., Miyata T., Taniguchi T.
      Cell 54:903-913(1988) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    2. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Strain: FVB/N.
      Tissue: Mammary gland.
    3. "Degradation of transcription factor IRF-1 by the ubiquitin-proteasome pathway. The C-terminal region governs the protein stability."
      Nakagawa K., Yokosawa H.
      Eur. J. Biochem. 267:1680-1686(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: UBIQUITINATION.
    4. "IRF family of transcription factors as regulators of host defense."
      Taniguchi T., Ogasawara K., Takaoka A., Tanaka N.
      Annu. Rev. Immunol. 19:623-655(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW ON FUNCTION.
    5. "PIAS3 induces SUMO-1 modification and transcriptional repression of IRF-1."
      Nakagawa K., Yokosawa H.
      FEBS Lett. 530:204-208(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH PIAS3, SUMOYLATION, FUNCTION.
    6. Cited for: REVIEW ON FUNCTION.
    7. Cited for: REVIEW ON FUNCTION.
    8. "IRFs: master regulators of signalling by Toll-like receptors and cytosolic pattern-recognition receptors."
      Honda K., Taniguchi T.
      Nat. Rev. Immunol. 6:644-658(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW ON FUNCTION.
    9. "Evidence for licensing of IFN-gamma-induced IFN regulatory factor 1 transcription factor by MyD88 in Toll-like receptor-dependent gene induction program."
      Negishi H., Fujita Y., Yanai H., Sakaguchi S., Ouyang X., Shinohara M., Takayanagi H., Ohba Y., Taniguchi T., Honda K.
      Proc. Natl. Acad. Sci. U.S.A. 103:15136-15141(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH MYD88.
    10. "Ubc9-mediated sumoylation leads to transcriptional repression of IRF-1."
      Kim E.-J., Park J.-S., Um S.-J.
      Biochem. Biophys. Res. Commun. 377:952-956(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUMOYLATION, FUNCTION.
    11. "IFN regulatory factor-1 negatively regulates CD4+ CD25+ regulatory T cell differentiation by repressing Foxp3 expression."
      Fragale A., Gabriele L., Stellacci E., Borghi P., Perrotti E., Ilari R., Lanciotti A., Remoli A.L., Venditti M., Belardelli F., Battistini A.
      J. Immunol. 181:1673-1682(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    12. "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.
    13. "IFN regulatory factor-1 bypasses IFN-mediated antiviral effects through viperin gene induction."
      Stirnweiss A., Ksienzyk A., Klages K., Rand U., Grashoff M., Hauser H., Kroeger A.
      J. Immunol. 184:5179-5185(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    14. "Interferon regulatory factor-1 (IRF-1) shapes both innate and CD8(+) T cell immune responses against West Nile virus infection."
      Brien J.D., Daffis S., Lazear H.M., Cho H., Suthar M.S., Gale M. Jr., Diamond M.S.
      PLoS Pathog. 7:E1002230-E1002230(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    15. "Structure of IRF-1 with bound DNA reveals determinants of interferon regulation."
      Escalante C.R., Yie J., Thanos D., Aggarwal A.K.
      Nature 391:103-106(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 7-111.

    Entry informationi

    Entry nameiIRF1_MOUSE
    AccessioniPrimary (citable) accession number: P15314
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: April 1, 1990
    Last sequence update: April 1, 1990
    Last modified: October 1, 2014
    This is version 120 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