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A4GBY3

- NS1_I77AA

UniProt

A4GBY3 - NS1_I77AA

Protein

Non-structural protein 1

Gene

NS

Organism
Influenza A virus (strain A/Brazil/11/1978 H1N1)
Status
Reviewed - Annotation score: 3 out of 5- Protein inferred from homologyi
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    • History
      Entry version 39 (01 Oct 2014)
      Sequence version 1 (17 Apr 2007)
      Previous versions | rss
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    Functioni

    Inhibits post-transcriptional processing of cellular pre-mRNA, by binding and inhibiting two cellular proteins that are required for the 3'-end processing of cellular pre-mRNAs: the 30 kDa cleavage and polyadenylation specificity factor (CPSF4) and the poly(A)-binding protein 2 (PABPN1). This results in the accumulation of unprocessed 3' end pre-mRNAs which can't be exported from the nucleus. Cellular protein synthesis is thereby shut off very early after virus infection. Viral protein synthesis is not affected by the inhibition of the cellular 3' end processing machinery because the poly(A) tails of viral mRNAs are produced by the viral polymerase through a stuttering mechanism By similarity.By similarity
    Prevents the establishment of the cellular antiviral state by inhibiting TRIM25-mediated DDX58 ubiquitination, which normally triggers the antiviral transduction signal that leads to the activation of type I IFN genes by transcription factors like IRF3 and IRF7. Prevents human EIF2AK2/PKR activation, either by binding double-strand RNA, or by interacting directly with EIF2AK2/PKR. This function may be important at the very beginning of the infection, when NS1 is mainly present in the cytoplasm. Also binds poly(A) and U6 snRNA. Suppresses the RNA silencing-based antiviral response in Drosophila cells By similarity.By similarity

    GO - Molecular functioni

    1. RNA binding Source: UniProtKB-KW

    GO - Biological processi

    1. suppression by virus of host mRNA processing Source: UniProtKB-KW
    2. suppression by virus of host PKR activity Source: UniProtKB-KW
    3. suppression by virus of host RIG-I activity Source: UniProtKB-KW
    4. suppression by virus of host type I interferon-mediated signaling pathway Source: UniProtKB-KW

    Keywords - Biological processi

    Eukaryotic host gene expression shutoff by virus, Host gene expression shutoff by virus, Host mRNA suppression by virus, Host-virus interaction, Inhibition of host innate immune response by virus, Inhibition of host interferon signaling pathway by virus, Inhibition of host PKR by virus, Inhibition of host pre-mRNA processing by virus, Inhibition of host RIG-I by virus, Inhibition of host RLR pathway by virus, Interferon antiviral system evasion, Viral immunoevasion

    Keywords - Ligandi

    RNA-binding

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Non-structural protein 1
    Short name:
    NS1
    Alternative name(s):
    NS1A
    Gene namesi
    Name:NS
    OrganismiInfluenza A virus (strain A/Brazil/11/1978 H1N1)
    Taxonomic identifieri393560 [NCBI]
    Taxonomic lineageiVirusesssRNA negative-strand virusesOrthomyxoviridaeInfluenzavirus A
    Virus hostiAves [TaxID: 8782]
    Homo sapiens (Human) [TaxID: 9606]
    Sus scrofa (Pig) [TaxID: 9823]
    ProteomesiUP000008025: Genome

    Subcellular locationi

    Host nucleus. Host cytoplasm
    Note: In uninfected, transfected cells, NS1 is localized in the nucleus. Only in virus infected cells, the nuclear export signal is unveiled, presumably by a viral protein, and a fraction of NS1 is exported in the cytoplasm By similarity.By similarity

    GO - Cellular componenti

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

    Keywords - Cellular componenti

    Host cytoplasm, Host nucleus

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 237237Non-structural protein 1PRO_0000372989Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Cross-linki20 – 20Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15); in band I form; by hostBy similarity
    Cross-linki41 – 41Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15); in band I form; by hostBy similarity
    Cross-linki108 – 108Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15); in band II form; by hostBy similarity
    Cross-linki110 – 110Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15); in band II form; by hostBy similarity
    Cross-linki126 – 126Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15); in band II form; by hostBy similarity
    Cross-linki217 – 217Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15); in band I form; by hostBy similarity
    Cross-linki219 – 219Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15); in band I form; by hostBy similarity

    Post-translational modificationi

    Upon interferon induction, ISGylated via host HERC5; this results in the impairment of NS1 interaction with RNA targets due to its inability to form homodimers and to interact with host EIF2AK2/PKR. There are two ISGylated forms: one form is ISGylated at Lys-20, Lys-41, Lys-217, and Lys-219, and another one at Lys-108, Lys-110, and Lys-126, they represent band I and II respectively. Lys-126 and Lys-217 are critical for host antiviral response in vivo By similarity.By similarity

    Keywords - PTMi

    Isopeptide bond, Ubl conjugation

    Interactioni

    Subunit structurei

    Homodimer. Interacts with host TRIM25 (via coiled coil); this interaction specifically inhibits TRIM25 multimerization and TRIM25-mediated DDX58 CARD ubiquitination. Interacts with human EIF2AK2/PKR, CPSF4, IVNS1ABP and PABPN1 By similarity.By similarity

    Structurei

    3D structure databases

    ProteinModelPortaliA4GBY3.
    SMRiA4GBY3. Positions 1-73, 79-205.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni1 – 7373RNA-binding and homodimerizationBy similarityAdd
    BLAST
    Regioni180 – 21536CPSF4-bindingBy similarityAdd
    BLAST
    Regioni223 – 23715PABPN1-bindingBy similarityAdd
    BLAST

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi34 – 385Nuclear localization signal 1By similarity
    Motifi137 – 14610Nuclear export signalBy similarity
    Motifi216 – 2216Nuclear localization signal 2By similarity

    Domaini

    The dsRNA-binding region is required for suppression of RNA silencing.By similarity

    Sequence similaritiesi

    Belongs to the influenza A viruses NS1 family.Curated

    Family and domain databases

    Gene3Di1.10.287.10. 1 hit.
    InterProiIPR000256. Flu_NS1.
    IPR009068. S15_NS1_RNA-bd.
    [Graphical view]
    PfamiPF00600. Flu_NS1. 1 hit.
    [Graphical view]
    SUPFAMiSSF47060. SSF47060. 1 hit.

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform NS1 (identifier: A4GBY3-1) [UniParc]FASTAAdd to Basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MDPNTVSSFQ VDCFLWHVRK QVADQELGDA PFLDRLRRDQ KSLRGRGSTL    50
    GLNIETATCV GKQIVERILK EESDEALKMT MASAPASRYL TDMTIEEMSR 100
    DWFMLMPKQK VAGPLCIRMD QAIMDKNIIL KANFSVIFDR LETLILLRAF 150
    TEEGAIVGEI SPLPSLPGHT NEDVKNAIGV LIGGLEWNDN TVRVSKTLQR 200
    FAWRSSNENG RPPLTPKQKR KMARTIRSEV RRNKMAD 237
    Length:237
    Mass (Da):26,890
    Last modified:April 17, 2007 - v1
    Checksum:iD5759FEBE558E268
    GO
    Isoform NEP (identifier: A4GBY2-1) [UniParc]FASTAAdd to Basket

    Also known as: NS2

    The sequence of this isoform can be found in the external entry A4GBY2.
    Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.
    Length:121
    Mass (Da):14,379
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    CY020297 Viral cRNA. Translation: ABO38070.1.

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    CY020297 Viral cRNA. Translation: ABO38070.1 .

    3D structure databases

    ProteinModelPortali A4GBY3.
    SMRi A4GBY3. Positions 1-73, 79-205.
    ModBasei Search...
    MobiDBi Search...

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Family and domain databases

    Gene3Di 1.10.287.10. 1 hit.
    InterProi IPR000256. Flu_NS1.
    IPR009068. S15_NS1_RNA-bd.
    [Graphical view ]
    Pfami PF00600. Flu_NS1. 1 hit.
    [Graphical view ]
    SUPFAMi SSF47060. SSF47060. 1 hit.
    ProtoNeti Search...

    Publicationsi

    1. Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
    2. The NIAID Influenza Genome Sequencing Consortium
      Submitted (MAR-2007) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].

    Entry informationi

    Entry nameiNS1_I77AA
    AccessioniPrimary (citable) accession number: A4GBY3
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: May 5, 2009
    Last sequence update: April 17, 2007
    Last modified: October 1, 2014
    This is version 39 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programViral Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome

    Documents

    1. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3