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Q02556

- IRF8_HUMAN

UniProt

Q02556 - IRF8_HUMAN

Protein

Interferon regulatory factor 8

Gene

IRF8

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 133 (01 Oct 2014)
      Sequence version 2 (15 Jul 1999)
      Previous versions | rss
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    Functioni

    Specifically binds to the upstream regulatory region of type I IFN and IFN-inducible MHC class I genes (the interferon consensus sequence (ICS)). Plays a negative regulatory role in cells of the immune system. Involved in CD8+ dendritic cell differentiation by forming a complex with the BATF-JUNB heterodimer in immune cells, leading to recognition of AICE sequence (5'-TGAnTCA/GAAA-3'), an immune-specific regulatory element, followed by cooperative binding of BATF and IRF8 and activation of genes By similarity.By similarity

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    DNA bindingi7 – 114108IRF tryptophan pentad repeatPROSITE-ProRule annotationAdd
    BLAST

    GO - Molecular functioni

    1. protein binding Source: IntAct
    2. regulatory region DNA binding Source: InterPro
    3. RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity Source: ProtInc

    GO - Biological processi

    1. cellular response to lipopolysaccharide Source: Ensembl
    2. cytokine-mediated signaling pathway Source: Reactome
    3. defense response to bacterium Source: Ensembl
    4. defense response to protozoan Source: Ensembl
    5. immune response Source: ProtInc
    6. interferon-gamma-mediated signaling pathway Source: Reactome
    7. myeloid cell differentiation Source: Ensembl
    8. negative regulation of growth of symbiont in host Source: Ensembl
    9. negative regulation of transcription from RNA polymerase II promoter Source: ProtInc
    10. phagocytosis Source: Ensembl
    11. positive regulation of interferon-gamma production Source: Ensembl
    12. positive regulation of interleukin-12 production Source: Ensembl
    13. positive regulation of transcription initiation from RNA polymerase II promoter Source: Ensembl
    14. transcription from RNA polymerase II promoter Source: GOC
    15. type I interferon signaling pathway Source: Reactome

    Keywords - Biological processi

    Transcription, Transcription regulation

    Keywords - Ligandi

    DNA-binding

    Enzyme and pathway databases

    ReactomeiREACT_25078. Interferon gamma signaling.
    REACT_25162. Interferon alpha/beta signaling.
    SignaLinkiQ02556.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Interferon regulatory factor 8
    Short name:
    IRF-8
    Alternative name(s):
    Interferon consensus sequence-binding protein
    Short name:
    H-ICSBP
    Short name:
    ICSBP
    Gene namesi
    Name:IRF8
    Synonyms:ICSBP1
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 16

    Organism-specific databases

    HGNCiHGNC:5358. IRF8.

    Subcellular locationi

    Nucleus 1 Publication

    GO - Cellular componenti

    1. cytosol Source: Reactome
    2. nucleus Source: HPA

    Keywords - Cellular componenti

    Nucleus

    Pathology & Biotechi

    Involvement in diseasei

    IRF8 deficiency, autosomal dominant (IRF8DD) [MIM:614893]: An immunologic disorder characterized by abnormal peripheral blood myeloid phenotype with a marked loss of CD11C-positive/CD1C dendritic cells, resulting in selective susceptibility to mycobacterial infections.1 Publication
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti80 – 801T → A in IRF8DD; impairs transcriptional activity by disrupting the interaction between IRF8 and DNA. 1 Publication
    VAR_070084
    IRF8 deficiency, autosomal recessive (IRF8DR) [MIM:614894]: A life-threatening pediatric disease characterized by monocyte and dendritic cell deficiency, myeloproliferation, and susceptibility to severe opportunistic infections, including disseminated BCG infection and oral candidiasis.1 Publication
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti108 – 1081K → E in IRF8DR; impairs transcriptional activity by disrupting the interaction between IRF8 and DNA. 1 Publication
    VAR_070085

    Keywords - Diseasei

    Disease mutation

    Organism-specific databases

    MIMi614893. phenotype.
    614894. phenotype.
    Orphaneti319600. Mendelian susceptibility to mycobacterial diseases due to partial IRF8 deficiency.
    PharmGKBiPA29606.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 426426Interferon regulatory factor 8PRO_0000154564Add
    BLAST

    Post-translational modificationi

    Ubiquitinated. Ubiquitination by TRIM21 in macrophages, a process that is strongly increased upon interferon gamma stimulation, leds to the enhanced transcriptional activity of target cytokine genes By similarity.By similarity

    Keywords - PTMi

    Ubl conjugation

    Proteomic databases

    MaxQBiQ02556.
    PaxDbiQ02556.
    PRIDEiQ02556.

    PTM databases

    PhosphoSiteiQ02556.

    Expressioni

    Tissue specificityi

    Predominantly expressed in lymphoid tissues.2 Publications

    Inductioni

    By IFNG/IFN-gamma. Negatively regulated by microRNA-155 (miR155).2 Publications

    Gene expression databases

    ArrayExpressiQ02556.
    BgeeiQ02556.
    CleanExiHS_IRF8.
    GenevestigatoriQ02556.

    Organism-specific databases

    HPAiCAB013480.
    HPA002267.
    HPA002531.

    Interactioni

    Subunit structurei

    Interacts (via C-terminus) with TRIM21 (via C-terminus). Interacts with the BATF-JUNB heterodimer. Interacts with BATF (via bZIP domain); the interaction is direct By similarity. Interacts with COPS2.By similarity1 Publication

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    IRF6O148963EBI-2866563,EBI-6115643

    Protein-protein interaction databases

    BioGridi109621. 24 interactions.
    IntActiQ02556. 10 interactions.
    STRINGi9606.ENSP00000268638.

    Structurei

    3D structure databases

    ProteinModelPortaliQ02556.
    SMRiQ02556. Positions 9-115, 198-379.
    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

    eggNOGiNOG42878.
    HOGENOMiHOG000010107.
    HOVERGENiHBG003072.
    InParanoidiQ02556.
    KOiK10155.
    OMAiRELQQFY.
    OrthoDBiEOG7CCBR1.
    PhylomeDBiQ02556.
    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.

    Q02556-1 [UniParc]FASTAAdd to Basket

    « Hide

    MCDRNGGRRL RQWLIEQIDS SMYPGLIWEN EEKSMFRIPW KHAGKQDYNQ    50
    EVDASIFKAW AVFKGKFKEG DKAEPATWKT RLRCALNKSP DFEEVTDRSQ 100
    LDISEPYKVY RIVPEEEQKC KLGVATAGCV NEVTEMECGR SEIDELIKEP 150
    SVDDYMGMIK RSPSPPEACR SQLLPDWWAQ QPSTGVPLVT GYTTYDAHHS 200
    AFSQMVISFY YGGKLVGQAT TTCPEGCRLS LSQPGLPGTK LYGPEGLELV 250
    RFPPADAIPS ERQRQVTRKL FGHLERGVLL HSSRQGVFVK RLCQGRVFCS 300
    GNAVVCKGRP NKLERDEVVQ VFDTSQFFRE LQQFYNSQGR LPDGRVVLCF 350
    GEEFPDMAPL RSKLILVQIE QLYVRQLAEE AGKSCGAGSV MQAPEEPPPD 400
    QVFRMFPDIC ASHQRSFFRE NQQITV 426
    Length:426
    Mass (Da):48,356
    Last modified:July 15, 1999 - v2
    Checksum:i1535D1B7C83E0355
    GO

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti80 – 801T → A in IRF8DD; impairs transcriptional activity by disrupting the interaction between IRF8 and DNA. 1 Publication
    VAR_070084
    Natural varianti81 – 811R → K in a breast cancer sample; somatic mutation. 1 Publication
    VAR_036490
    Natural varianti108 – 1081K → E in IRF8DR; impairs transcriptional activity by disrupting the interaction between IRF8 and DNA. 1 Publication
    VAR_070085
    Natural varianti197 – 1971A → T in a breast cancer sample; somatic mutation. 1 Publication
    VAR_036491

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M91196 mRNA. Translation: AAB63813.1.
    BC126247 mRNA. Translation: AAI26248.1.
    CCDSiCCDS10956.1.
    PIRiA45064.
    RefSeqiNP_002154.1. NM_002163.2.
    UniGeneiHs.137427.

    Genome annotation databases

    EnsembliENST00000268638; ENSP00000268638; ENSG00000140968.
    GeneIDi3394.
    KEGGihsa:3394.
    UCSCiuc002fjh.3. human.

    Polymorphism databases

    DMDMi6016308.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M91196 mRNA. Translation: AAB63813.1 .
    BC126247 mRNA. Translation: AAI26248.1 .
    CCDSi CCDS10956.1.
    PIRi A45064.
    RefSeqi NP_002154.1. NM_002163.2.
    UniGenei Hs.137427.

    3D structure databases

    ProteinModelPortali Q02556.
    SMRi Q02556. Positions 9-115, 198-379.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 109621. 24 interactions.
    IntActi Q02556. 10 interactions.
    STRINGi 9606.ENSP00000268638.

    PTM databases

    PhosphoSitei Q02556.

    Polymorphism databases

    DMDMi 6016308.

    Proteomic databases

    MaxQBi Q02556.
    PaxDbi Q02556.
    PRIDEi Q02556.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000268638 ; ENSP00000268638 ; ENSG00000140968 .
    GeneIDi 3394.
    KEGGi hsa:3394.
    UCSCi uc002fjh.3. human.

    Organism-specific databases

    CTDi 3394.
    GeneCardsi GC16P085932.
    HGNCi HGNC:5358. IRF8.
    HPAi CAB013480.
    HPA002267.
    HPA002531.
    MIMi 601565. gene.
    614893. phenotype.
    614894. phenotype.
    neXtProti NX_Q02556.
    Orphaneti 319600. Mendelian susceptibility to mycobacterial diseases due to partial IRF8 deficiency.
    PharmGKBi PA29606.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG42878.
    HOGENOMi HOG000010107.
    HOVERGENi HBG003072.
    InParanoidi Q02556.
    KOi K10155.
    OMAi RELQQFY.
    OrthoDBi EOG7CCBR1.
    PhylomeDBi Q02556.
    TreeFami TF328512.

    Enzyme and pathway databases

    Reactomei REACT_25078. Interferon gamma signaling.
    REACT_25162. Interferon alpha/beta signaling.
    SignaLinki Q02556.

    Miscellaneous databases

    GeneWikii IRF8.
    GenomeRNAii 3394.
    NextBioi 13414.
    PROi Q02556.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q02556.
    Bgeei Q02556.
    CleanExi HS_IRF8.
    Genevestigatori Q02556.

    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. "Human interferon consensus sequence binding protein is a negative regulator of enhancer elements common to interferon-inducible genes."
      Weisz A., Marx P., Sharf R., Appella E., Driggers P.H., Ozato K., Levi B.-Z.
      J. Biol. Chem. 267:25589-25596(1992) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, INDUCTION BY IFNG.
      Tissue: Lung and Monocyte.
    2. Schmidt M.
      Submitted (JUL-1997) to the EMBL/GenBank/DDBJ databases
      Cited for: SEQUENCE REVISION.
    3. "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].
      Tissue: Brain.
    4. "Interaction between interferon consensus sequence-binding protein and COP9/signalosome subunit CSN2 (Trip15). A possible link between interferon regulatory factor signaling and the COP9/signalosome."
      Cohen H., Azriel A., Cohen T., Meraro D., Hashmueli S., Bech-Otschir D., Kraft R., Dubiel W., Levi B.Z.
      J. Biol. Chem. 275:39081-39089(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH COPS2.
    5. "BCL6 positively regulates AID and germinal center gene expression via repression of miR-155."
      Basso K., Schneider C., Shen Q., Holmes A.B., Setty M., Leslie C., Dalla-Favera R.
      J. Exp. Med. 209:2455-2465(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: INDUCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
    6. Cited for: VARIANTS [LARGE SCALE ANALYSIS] LYS-81 AND THR-197.
    7. Cited for: VARIANT IRF8DD ALA-80, VARIANT IRF8DR GLU-108, CHARACTERIZATION OF VARIANT IRF8DD ALA-80, CHARACTERIZATION OF VARIANT IRF8DR GLU-108.

    Entry informationi

    Entry nameiIRF8_HUMAN
    AccessioniPrimary (citable) accession number: Q02556
    Secondary accession number(s): A0AV82
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 1, 1993
    Last sequence update: July 15, 1999
    Last modified: October 1, 2014
    This is version 133 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. Human chromosome 16
      Human chromosome 16: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3