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P09913

- IFIT2_HUMAN

UniProt

P09913 - IFIT2_HUMAN

Protein

Interferon-induced protein with tetratricopeptide repeats 2

Gene

IFIT2

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 137 (01 Oct 2014)
      Sequence version 1 (01 Jul 1989)
      Previous versions | rss
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    Functioni

    IFN-induced antiviral protein which inhibits expression of viral messenger RNAs lacking 2'-O-methylation of the 5' cap. The ribose 2'-O-methylation would provide a molecular signature to distinguish between self and non-self mRNAs by the host during viral infection. Viruses evolved several ways to evade this restriction system such as encoding their own 2'-O-methylase for their mRNAs or by stealing host cap containing the 2'-O-methylation (cap snatching mechanism). Binds AU-rich viral RNAs, with or without 5' triphosphorylation, RNA-binding is required for antiviral activity. Can promote apoptosis.1 Publication

    GO - Molecular functioni

    1. poly(A) RNA binding Source: UniProtKB
    2. protein binding Source: UniProtKB

    GO - Biological processi

    1. apoptotic mitochondrial changes Source: UniProtKB
    2. cellular response to interferon-alpha Source: Ensembl
    3. cytokine-mediated signaling pathway Source: Reactome
    4. defense response to virus Source: UniProtKB-KW
    5. negative regulation of protein binding Source: BHF-UCL
    6. positive regulation of apoptotic process Source: UniProtKB
    7. response to virus Source: UniProtKB
    8. type I interferon signaling pathway Source: Reactome

    Keywords - Biological processi

    Antiviral defense, Apoptosis, Immunity, Innate immunity

    Keywords - Ligandi

    RNA-binding

    Enzyme and pathway databases

    ReactomeiREACT_25162. Interferon alpha/beta signaling.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Interferon-induced protein with tetratricopeptide repeats 2
    Short name:
    IFIT-2
    Alternative name(s):
    ISG-54 K
    Interferon-induced 54 kDa protein
    Short name:
    IFI-54K
    Short name:
    P54
    Gene namesi
    Name:IFIT2
    Synonyms:CIG-42, G10P2, IFI54, ISG54
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 10

    Organism-specific databases

    HGNCiHGNC:5409. IFIT2.

    Subcellular locationi

    Cytoplasm 1 Publication. Endoplasmic reticulum 1 Publication

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB
    2. cytosol Source: Reactome
    3. endoplasmic reticulum Source: UniProtKB

    Keywords - Cellular componenti

    Cytoplasm, Endoplasmic reticulum

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi184 – 1841R → E: Abolishes RNA-binding. 1 Publication
    Mutagenesisi255 – 2551K → E: Significantly impairs RNA-binding; when associated with Glu-259. 1 Publication
    Mutagenesisi259 – 2591R → E: Significantly impairs RNA-binding; when associated with Glu-255. 1 Publication
    Mutagenesisi292 – 2921R → E: Abolishes RNA-binding. 1 Publication
    Mutagenesisi410 – 4101K → E: Abolishes RNA-binding. 1 Publication

    Organism-specific databases

    PharmGKBiPA29650.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Initiator methioninei1 – 11Removed1 Publication
    Chaini2 – 472471Interferon-induced protein with tetratricopeptide repeats 2PRO_0000106347Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei2 – 21N-acetylserine1 Publication

    Keywords - PTMi

    Acetylation

    Proteomic databases

    MaxQBiP09913.
    PaxDbiP09913.
    PRIDEiP09913.

    PTM databases

    PhosphoSiteiP09913.

    Expressioni

    Inductioni

    By type I interferons, dsRNAs and viruses.1 Publication

    Gene expression databases

    BgeeiP09913.
    CleanExiHS_IFIT2.
    GenevestigatoriP09913.

    Organism-specific databases

    HPAiHPA003408.

    Interactioni

    Subunit structurei

    Domain-swapped homodimer. Component of an interferon-dependent multiprotein complex, at least composed of IFIT1, IFIT2 and IFIT3. Interacts with IFIT1 and IFIT3. Interacts with TMEM173/MITA and disrupts its interaction with MAVS or TBK1. Interacts with EIF3E and EIF3C.5 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    IFIT1P099145EBI-3507167,EBI-745117
    IFIT3O148794EBI-3507167,EBI-745127

    Protein-protein interaction databases

    BioGridi109658. 37 interactions.
    DIPiDIP-48848N.
    IntActiP09913. 32 interactions.
    MINTiMINT-1479068.
    STRINGi9606.ENSP00000360891.

    Structurei

    Secondary structure

    1
    472
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi9 – 146
    Turni19 – 213
    Turni24 – 274
    Helixi31 – 4111
    Helixi52 – 6312
    Helixi67 – 8418
    Helixi86 – 883
    Turni90 – 934
    Helixi94 – 10613
    Helixi110 – 12617
    Helixi136 – 14914
    Helixi153 – 16715
    Helixi172 – 18716
    Helixi195 – 20410
    Helixi209 – 22113
    Helixi231 – 24212
    Helixi247 – 25913
    Helixi263 – 27614
    Helixi281 – 30020
    Helixi309 – 32921
    Turni331 – 3333
    Helixi337 – 34610
    Helixi350 – 36213
    Helixi367 – 38317
    Helixi388 – 40013
    Helixi406 – 42520
    Helixi432 – 44514

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    4G1TX-ray2.80A/B1-472[»]
    ProteinModelPortaliP09913.
    SMRiP09913. Positions 8-452.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Repeati51 – 8939TPR 11 PublicationPROSITE-ProRule annotationAdd
    BLAST
    Repeati90 – 13546TPR 21 PublicationPROSITE-ProRule annotationAdd
    BLAST
    Repeati136 – 17136TPR 31 PublicationPROSITE-ProRule annotationAdd
    BLAST
    Repeati172 – 20837TPR 41 PublicationPROSITE-ProRule annotationAdd
    BLAST
    Repeati247 – 28034TPR 51 PublicationPROSITE-ProRule annotationAdd
    BLAST
    Repeati281 – 33555TPR 61 PublicationPROSITE-ProRule annotationAdd
    BLAST
    Repeati336 – 36631TPR 71 PublicationPROSITE-ProRule annotationAdd
    BLAST
    Repeati367 – 40539TPR 81 PublicationPROSITE-ProRule annotationAdd
    BLAST
    Repeati406 – 44843TPR 91 PublicationPROSITE-ProRule annotationAdd
    BLAST

    Domaini

    The C-terminal part folds into a super-helical structure and has an extensively positively-charged nucleotide-binding channel on its inner surface.

    Sequence similaritiesi

    Belongs to the IFIT family.Curated
    Contains 9 TPR repeats.PROSITE-ProRule annotation

    Keywords - Domaini

    Repeat, TPR repeat

    Phylogenomic databases

    eggNOGiNOG309012.
    HOVERGENiHBG066330.
    InParanoidiP09913.
    OMAiKCEDKAI.
    OrthoDBiEOG71K62V.
    PhylomeDBiP09913.
    TreeFamiTF342671.

    Family and domain databases

    Gene3Di1.25.40.10. 4 hits.
    InterProiIPR024124. Interferon-induced_IFIT2.
    IPR013026. TPR-contain_dom.
    IPR011990. TPR-like_helical.
    IPR019734. TPR_repeat.
    [Graphical view]
    PANTHERiPTHR10271:SF4. PTHR10271:SF4. 1 hit.
    PfamiPF13181. TPR_8. 1 hit.
    [Graphical view]
    SMARTiSM00028. TPR. 3 hits.
    [Graphical view]
    PROSITEiPS50005. TPR. 1 hit.
    PS50293. TPR_REGION. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    P09913-1 [UniParc]FASTAAdd to Basket

    « Hide

    MSENNKNSLE SSLRQLKCHF TWNLMEGENS LDDFEDKVFY RTEFQNREFK    50
    ATMCNLLAYL KHLKGQNEAA LECLRKAEEL IQQEHADQAE IRSLVTWGNY 100
    AWVYYHMGRL SDVQIYVDKV KHVCEKFSSP YRIESPELDC EEGWTRLKCG 150
    GNQNERAKVC FEKALEKKPK NPEFTSGLAI ASYRLDNWPP SQNAIDPLRQ 200
    AIRLNPDNQY LKVLLALKLH KMREEGEEEG EGEKLVEEAL EKAPGVTDVL 250
    RSAAKFYRRK DEPDKAIELL KKALEYIPNN AYLHCQIGCC YRAKVFQVMN 300
    LRENGMYGKR KLLELIGHAV AHLKKADEAN DNLFRVCSIL ASLHALADQY 350
    EDAEYYFQKE FSKELTPVAK QLLHLRYGNF QLYQMKCEDK AIHHFIEGVK 400
    INQKSREKEK MKDKLQKIAK MRLSKNGADS EALHVLAFLQ ELNEKMQQAD 450
    EDSERGLESG SLIPSASSWN GE 472
    Length:472
    Mass (Da):54,632
    Last modified:July 1, 1989 - v1
    Checksum:i3CF11319A5008FB9
    GO

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti79 – 791E → A.
    Corresponds to variant rs17468739 [ dbSNP | Ensembl ].
    VAR_052615
    Natural varianti121 – 1211K → R.
    Corresponds to variant rs2070845 [ dbSNP | Ensembl ].
    VAR_052616
    Natural varianti352 – 3521D → E.
    Corresponds to variant rs1727 [ dbSNP | Ensembl ].
    VAR_014490

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M14660, M14659 Genomic DNA. Translation: AAA59191.1.
    AL353751 Genomic DNA. Translation: CAI12238.1.
    X07557 Genomic DNA. Translation: CAA30438.1.
    CCDSiCCDS41548.1.
    PIRiI59087.
    RefSeqiNP_001538.4. NM_001547.4.
    UniGeneiHs.437609.

    Genome annotation databases

    EnsembliENST00000371826; ENSP00000360891; ENSG00000119922.
    GeneIDi3433.
    KEGGihsa:3433.
    UCSCiuc009xts.3. human.

    Polymorphism databases

    DMDMi124488.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M14660 , M14659 Genomic DNA. Translation: AAA59191.1 .
    AL353751 Genomic DNA. Translation: CAI12238.1 .
    X07557 Genomic DNA. Translation: CAA30438.1 .
    CCDSi CCDS41548.1.
    PIRi I59087.
    RefSeqi NP_001538.4. NM_001547.4.
    UniGenei Hs.437609.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    4G1T X-ray 2.80 A/B 1-472 [» ]
    ProteinModelPortali P09913.
    SMRi P09913. Positions 8-452.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 109658. 37 interactions.
    DIPi DIP-48848N.
    IntActi P09913. 32 interactions.
    MINTi MINT-1479068.
    STRINGi 9606.ENSP00000360891.

    PTM databases

    PhosphoSitei P09913.

    Polymorphism databases

    DMDMi 124488.

    Proteomic databases

    MaxQBi P09913.
    PaxDbi P09913.
    PRIDEi P09913.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000371826 ; ENSP00000360891 ; ENSG00000119922 .
    GeneIDi 3433.
    KEGGi hsa:3433.
    UCSCi uc009xts.3. human.

    Organism-specific databases

    CTDi 3433.
    GeneCardsi GC10P091051.
    H-InvDB HIX0025911.
    HGNCi HGNC:5409. IFIT2.
    HPAi HPA003408.
    MIMi 147040. gene.
    neXtProti NX_P09913.
    PharmGKBi PA29650.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG309012.
    HOVERGENi HBG066330.
    InParanoidi P09913.
    OMAi KCEDKAI.
    OrthoDBi EOG71K62V.
    PhylomeDBi P09913.
    TreeFami TF342671.

    Enzyme and pathway databases

    Reactomei REACT_25162. Interferon alpha/beta signaling.

    Miscellaneous databases

    GeneWikii IFIT2.
    GenomeRNAii 3433.
    NextBioi 13536.
    PROi P09913.
    SOURCEi Search...

    Gene expression databases

    Bgeei P09913.
    CleanExi HS_IFIT2.
    Genevestigatori P09913.

    Family and domain databases

    Gene3Di 1.25.40.10. 4 hits.
    InterProi IPR024124. Interferon-induced_IFIT2.
    IPR013026. TPR-contain_dom.
    IPR011990. TPR-like_helical.
    IPR019734. TPR_repeat.
    [Graphical view ]
    PANTHERi PTHR10271:SF4. PTHR10271:SF4. 1 hit.
    Pfami PF13181. TPR_8. 1 hit.
    [Graphical view ]
    SMARTi SM00028. TPR. 3 hits.
    [Graphical view ]
    PROSITEi PS50005. TPR. 1 hit.
    PS50293. TPR_REGION. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Interferon-stimulated transcription: isolation of an inducible gene and identification of its regulatory region."
      Levy D., Larner A., Chaudhuri A., Babiss L.E., Darnell J.E. Jr.
      Proc. Natl. Acad. Sci. U.S.A. 83:8929-8933(1986) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    2. "The DNA sequence and comparative analysis of human chromosome 10."
      Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J.
      , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.
      Nature 429:375-381(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    3. "Regulation of two interferon-inducible human genes by interferon, poly(rI).poly(rC) and viruses."
      Wathelet M.G., Clauss I.M., Content J., Huez G.A.
      Eur. J. Biochem. 174:323-329(1988) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-2.
    4. "The IFI-56K and IFI-54K interferon-inducible human genes belong to the same gene family."
      Wathelet M.G., Clauss I.M., Content J., Huez G.A.
      FEBS Lett. 231:164-171(1988) [PubMed] [Europe PMC] [Abstract]
      Cited for: SIMILARITY TO IFI-56K.
    5. "Distinct induction patterns and functions of two closely related interferon-inducible human genes, ISG54 and ISG56."
      Terenzi F., Hui D.J., Merrick W.C., Sen G.C.
      J. Biol. Chem. 281:34064-34071(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: INDUCTION, INTERACTION WITH EIF3E AND EIF3C.
    6. "ISG56 is a negative-feedback regulator of virus-triggered signaling and cellular antiviral response."
      Li Y., Li C., Xue P., Zhong B., Mao A.P., Ran Y., Chen H., Wang Y.Y., Yang F., Shu H.B.
      Proc. Natl. Acad. Sci. U.S.A. 106:7945-7950(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH TMEM173/MITA.
    7. "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, SUBCELLULAR LOCATION, INTERACTION WITH IFIT1 AND IFIT3.
    8. Cited for: REVIEW.
    9. Cited for: INTERACTION WITH IFIT1 AND IFIT3.
    10. Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS], CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS].
    11. "Crystal structure of ISG54 reveals a novel RNA binding structure and potential functional mechanisms."
      Yang Z., Liang H., Zhou Q., Li Y., Chen H., Ye W., Chen D., Fleming J., Shu H., Liu Y.
      Cell Res. 22:1328-1338(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS), TPR REPEATS, SUBUNIT, MUTAGENESIS OF ARG-184; LYS-255; ARG-259; ARG-292 AND LYS-410.

    Entry informationi

    Entry nameiIFIT2_HUMAN
    AccessioniPrimary (citable) accession number: P09913
    Secondary accession number(s): Q5T767
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 1, 1989
    Last sequence update: July 1, 1989
    Last modified: October 1, 2014
    This is version 137 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

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 10
      Human chromosome 10: 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. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3