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O14879

- IFIT3_HUMAN

UniProt

O14879 - IFIT3_HUMAN

Protein

Interferon-induced protein with tetratricopeptide repeats 3

Gene

IFIT3

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 134 (01 Oct 2014)
      Sequence version 1 (01 Jan 1998)
      Previous versions | rss
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    Functioni

    IFN-induced antiviral protein which acts as an inhibitor of cellular as well as viral processes, cell migration, proliferation, signaling, and viral replication. Enhances MAVS-mediated host antiviral responses by serving as an adapter bridging TBK1 to MAVS which leads to the activation of TBK1 and phosphorylation of IRF3 and phosphorylated IRF3 translocates into nucleus to promote antiviral gene transcription. Exihibits an antiproliferative activity via the up-regulation of cell cycle negative regulators CDKN1A/p21 and CDKN1B/p27. Normally, CDKN1B/p27 turnover is regulated by COPS5, which binds CDKN1B/p27 in the nucleus and exports it to the cytoplasm for ubiquitin-dependent degradation. IFIT3 sequesters COPS5 in the cytoplasm, thereby increasing nuclear CDKN1B/p27 protein levels. Upregulates CDKN1A/p21 by downregulating MYC, a repressor of CDKN1A/p21. Can negatively regulate the apoptotic effects of IFIT2.5 Publications

    GO - Molecular functioni

    1. identical protein binding Source: IntAct
    2. protein binding Source: UniProtKB

    GO - Biological processi

    1. cellular response to interferon-alpha Source: InterPro
    2. cytokine-mediated signaling pathway Source: Reactome
    3. defense response to virus Source: UniProtKB-KW
    4. negative regulation of apoptotic process Source: UniProtKB
    5. negative regulation of cell proliferation Source: UniProtKB
    6. response to virus Source: UniProtKB
    7. type I interferon signaling pathway Source: Reactome

    Keywords - Biological processi

    Antiviral defense, Immunity, Innate immunity

    Enzyme and pathway databases

    ReactomeiREACT_25162. Interferon alpha/beta signaling.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Interferon-induced protein with tetratricopeptide repeats 3
    Short name:
    IFIT-3
    Alternative name(s):
    CIG49
    ISG-60
    Interferon-induced 60 kDa protein
    Short name:
    IFI-60K
    Interferon-induced protein with tetratricopeptide repeats 4
    Short name:
    IFIT-4
    Retinoic acid-induced gene G protein
    Short name:
    P60
    Short name:
    RIG-G
    Gene namesi
    Name:IFIT3
    Synonyms:CIG-49, IFI60, IFIT4, ISG60
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 10

    Organism-specific databases

    HGNCiHGNC:5411. IFIT3.

    Subcellular locationi

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB
    2. cytosol Source: Reactome
    3. mitochondrion Source: UniProtKB

    Keywords - Cellular componenti

    Cytoplasm, Mitochondrion

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA29651.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 490490Interferon-induced protein with tetratricopeptide repeats 3PRO_0000106349Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei203 – 2031Phosphoserine3 Publications
    Modified residuei237 – 2371Phosphoserine1 Publication
    Modified residuei478 – 4781Phosphoserine1 Publication

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    MaxQBiO14879.
    PaxDbiO14879.
    PeptideAtlasiO14879.
    PRIDEiO14879.

    PTM databases

    PhosphoSiteiO14879.

    Expressioni

    Tissue specificityi

    Expression significantly higher in peripheral blood mononuclear cells (PBMCs) and monocytes from systemic lupus erythematosus (SLE) patients than in those from healthy individuals (at protein level). Spleen, lung, leukocytes, lymph nodes, placenta, bone marrow and fetal liver.1 Publication

    Inductioni

    By type I interferons, dsRNAs and viruses.1 Publication

    Gene expression databases

    ArrayExpressiO14879.
    BgeeiO14879.
    CleanExiHS_IFIT3.
    GenevestigatoriO14879.

    Organism-specific databases

    HPAiHPA059914.

    Interactioni

    Subunit structurei

    Component of an interferon-dependent multiprotein complex, at least composed of IFIT1, IFIT2 and IFIT3. Interacts with IFIT1 and IFIT2. Interacts (via N-terminus) with MAVS, TBK1, TRAF6 and DDX58. Interacts with COPS5.4 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    itself3EBI-745127,EBI-745127
    CDC37Q165434EBI-745127,EBI-295634
    IFIT1P099145EBI-745127,EBI-745117
    IFIT2P099134EBI-745127,EBI-3507167

    Protein-protein interaction databases

    BioGridi109660. 51 interactions.
    IntActiO14879. 50 interactions.
    MINTiMINT-1448195.
    STRINGi9606.ENSP00000360876.

    Structurei

    3D structure databases

    ProteinModelPortaliO14879.
    SMRiO14879. Positions 2-440.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Repeati51 – 8434TPR 1Add
    BLAST
    Repeati94 – 12734TPR 2Add
    BLAST
    Repeati136 – 16934TPR 3Add
    BLAST
    Repeati172 – 20635TPR 4Add
    BLAST
    Repeati207 – 24034TPR 5Add
    BLAST
    Repeati241 – 27434TPR 6Add
    BLAST
    Repeati415 – 44834TPR 7Add
    BLAST
    Repeati450 – 48132TPR 8Add
    BLAST

    Sequence similaritiesi

    Belongs to the IFIT family.Curated
    Contains 8 TPR repeats.PROSITE-ProRule annotation

    Keywords - Domaini

    Repeat, TPR repeat

    Phylogenomic databases

    eggNOGiNOG284690.
    HOGENOMiHOG000001558.
    HOVERGENiHBG066330.
    InParanoidiO14879.
    OMAiHQIGCCY.
    OrthoDBiEOG71K62V.
    PhylomeDBiO14879.
    TreeFamiTF342671.

    Family and domain databases

    Gene3Di1.25.40.10. 2 hits.
    InterProiIPR024122. Interferon-induced_IFIT3.
    IPR013026. TPR-contain_dom.
    IPR011990. TPR-like_helical.
    IPR001440. TPR_1.
    IPR019734. TPR_repeat.
    [Graphical view]
    PANTHERiPTHR10271:SF3. PTHR10271:SF3. 1 hit.
    PfamiPF00515. TPR_1. 1 hit.
    PF13181. TPR_8. 1 hit.
    [Graphical view]
    SMARTiSM00028. TPR. 4 hits.
    [Graphical view]
    PROSITEiPS50005. TPR. 5 hits.
    PS50293. TPR_REGION. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    O14879-1 [UniParc]FASTAAdd to Basket

    « Hide

    MSEVTKNSLE KILPQLKCHF TWNLFKEDSV SRDLEDRVCN QIEFLNTEFK    50
    ATMYNLLAYI KHLDGNNEAA LECLRQAEEL IQQEHADQAE IRSLVTWGNY 100
    AWVYYHLGRL SDAQIYVDKV KQTCKKFSNP YSIEYSELDC EEGWTQLKCG 150
    RNERAKVCFE KALEEKPNNP EFSSGLAIAM YHLDNHPEKQ FSTDVLKQAI 200
    ELSPDNQYVK VLLGLKLQKM NKEAEGEQFV EEALEKSPCQ TDVLRSAAKF 250
    YRRKGDLDKA IELFQRVLES TPNNGYLYHQ IGCCYKAKVR QMQNTGESEA 300
    SGNKEMIEAL KQYAMDYSNK ALEKGLNPLN AYSDLAEFLE TECYQTPFNK 350
    EVPDAEKQQS HQRYCNLQKY NGKSEDTAVQ HGLEGLSISK KSTDKEEIKD 400
    QPQNVSENLL PQNAPNYWYL QGLIHKQNGD LLQAAKCYEK ELGRLLRDAP 450
    SGIGSIFLSA SELEDGSEEM GQGAVSSSPR ELLSNSEQLN 490
    Length:490
    Mass (Da):55,985
    Last modified:January 1, 1998 - v1
    Checksum:iB9F042D4DF7151D2
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti44 – 441F → S in AAH04977. (PubMed:15489334)Curated
    Sequence conflicti359 – 3591Q → QQ in AAB40606. (PubMed:9828129)Curated
    Sequence conflicti435 – 4351Missing in AAB40606. (PubMed:9828129)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF026939 mRNA. Translation: AAB95160.1.
    AF083470 mRNA. Translation: AAC63524.1.
    U52513 mRNA. Translation: AAB40606.1.
    BT007284 mRNA. Translation: AAP35948.1.
    BC001383 mRNA. Translation: AAH01383.1.
    BC004977 mRNA. Translation: AAH04977.1.
    CCDSiCCDS31241.1.
    CCDS7402.1.
    RefSeqiNP_001026853.1. NM_001031683.3.
    NP_001540.2. NM_001549.5.
    UniGeneiHs.47338.
    Hs.744072.

    Genome annotation databases

    EnsembliENST00000371811; ENSP00000360876; ENSG00000119917.
    ENST00000371818; ENSP00000360883; ENSG00000119917.
    GeneIDi3437.
    KEGGihsa:3437.
    UCSCiuc001kgf.3. human.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF026939 mRNA. Translation: AAB95160.1 .
    AF083470 mRNA. Translation: AAC63524.1 .
    U52513 mRNA. Translation: AAB40606.1 .
    BT007284 mRNA. Translation: AAP35948.1 .
    BC001383 mRNA. Translation: AAH01383.1 .
    BC004977 mRNA. Translation: AAH04977.1 .
    CCDSi CCDS31241.1.
    CCDS7402.1.
    RefSeqi NP_001026853.1. NM_001031683.3.
    NP_001540.2. NM_001549.5.
    UniGenei Hs.47338.
    Hs.744072.

    3D structure databases

    ProteinModelPortali O14879.
    SMRi O14879. Positions 2-440.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 109660. 51 interactions.
    IntActi O14879. 50 interactions.
    MINTi MINT-1448195.
    STRINGi 9606.ENSP00000360876.

    PTM databases

    PhosphoSitei O14879.

    Proteomic databases

    MaxQBi O14879.
    PaxDbi O14879.
    PeptideAtlasi O14879.
    PRIDEi O14879.

    Protocols and materials databases

    DNASUi 3437.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000371811 ; ENSP00000360876 ; ENSG00000119917 .
    ENST00000371818 ; ENSP00000360883 ; ENSG00000119917 .
    GeneIDi 3437.
    KEGGi hsa:3437.
    UCSCi uc001kgf.3. human.

    Organism-specific databases

    CTDi 3437.
    GeneCardsi GC10P091077.
    HGNCi HGNC:5411. IFIT3.
    HPAi HPA059914.
    MIMi 604650. gene.
    neXtProti NX_O14879.
    PharmGKBi PA29651.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG284690.
    HOGENOMi HOG000001558.
    HOVERGENi HBG066330.
    InParanoidi O14879.
    OMAi HQIGCCY.
    OrthoDBi EOG71K62V.
    PhylomeDBi O14879.
    TreeFami TF342671.

    Enzyme and pathway databases

    Reactomei REACT_25162. Interferon alpha/beta signaling.

    Miscellaneous databases

    GeneWikii IFIT3.
    GenomeRNAii 3437.
    NextBioi 13544.
    PROi O14879.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi O14879.
    Bgeei O14879.
    CleanExi HS_IFIT3.
    Genevestigatori O14879.

    Family and domain databases

    Gene3Di 1.25.40.10. 2 hits.
    InterProi IPR024122. Interferon-induced_IFIT3.
    IPR013026. TPR-contain_dom.
    IPR011990. TPR-like_helical.
    IPR001440. TPR_1.
    IPR019734. TPR_repeat.
    [Graphical view ]
    PANTHERi PTHR10271:SF3. PTHR10271:SF3. 1 hit.
    Pfami PF00515. TPR_1. 1 hit.
    PF13181. TPR_8. 1 hit.
    [Graphical view ]
    SMARTi SM00028. TPR. 4 hits.
    [Graphical view ]
    PROSITEi PS50005. TPR. 5 hits.
    PS50293. TPR_REGION. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Use of differential display analysis to assess the effect of human cytomegalovirus infection on the accumulation of cellular RNAs: induction of interferon-responsive RNAs."
      Zhu H., Cong J.-P., Shenk T.
      Proc. Natl. Acad. Sci. U.S.A. 94:13985-13990(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Tissue: Foreskin.
    2. "IFI60/ISG60/IFIT4, a new member of the human IFI54/IFIT2 family of interferon-stimulated genes."
      de Veer M.J., Sim H., Whisstock J.C., Devenish R.J., Ralph S.J.
      Genomics 54:267-277(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    3. "RIG-G, a novel gene induced by ATRA in acute promyelocytic leukemia cells, is a new member of the ISG family."
      Yu M., Tong J., Mao M., Chen S., Chen Z.
      Submitted (MAR-1996) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    4. "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
      Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
      Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    5. "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: Skin.
    6. "RIG-G as a key mediator of the antiproliferative activity of interferon-related pathways through enhancing p21 and p27 proteins."
      Xiao S., Li D., Zhu H.Q., Song M.G., Pan X.R., Jia P.M., Peng L.L., Dou A.X., Chen G.Q., Chen S.J., Chen Z., Tong J.H.
      Proc. Natl. Acad. Sci. U.S.A. 103:16448-16453(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INDUCTION, SUBCELLULAR LOCATION, INTERACTION WITH COPS5.
    7. "Interferon-induced protein IFIT4 is associated with systemic lupus erythematosus and promotes differentiation of monocytes into dendritic cell-like cells."
      Huang X., Shen N., Bao C., Gu Y., Wu L., Chen S.
      Arthritis Res. Ther. 10:R91-R91(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
    8. "Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."
      Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M.
      Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-203 AND SER-237, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    9. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-203 AND SER-478, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    10. "Identification of alpha interferon-induced genes associated with antiviral activity in Daudi cells and characterization of IFIT3 as a novel antiviral gene."
      Schmeisser H., Mejido J., Balinsky C.A., Morrow A.N., Clark C.R., Zhao T., Zoon K.C.
      J. Virol. 84:10671-10680(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    11. "Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
      Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
      Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-203, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    12. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    13. "The interferon stimulated gene 54 promotes apoptosis."
      Stawowczyk M., Van Scoy S., Kumar K.P., Reich N.C.
      J. Biol. Chem. 286:7257-7266(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH IFIT2.
    14. "IFN-induced TPR protein IFIT3 potentiates antiviral signaling by bridging MAVS and TBK1."
      Liu X.Y., Chen W., Wei B., Shan Y.F., Wang C.
      J. Immunol. 187:2559-2568(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH MAVS; TBK1; TRAF6 AND DDX58.
    15. Cited for: REVIEW.
    16. Cited for: FUNCTION, INTERACTION WITH IFIT1 AND IFIT2.

    Entry informationi

    Entry nameiIFIT3_HUMAN
    AccessioniPrimary (citable) accession number: O14879
    Secondary accession number(s): Q99634, Q9BSK7
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: May 30, 2000
    Last sequence update: January 1, 1998
    Last modified: October 1, 2014
    This is version 134 of the entry and version 1 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 10
      Human chromosome 10: entries, gene names and cross-references to MIM
    2. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    3. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3