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P03496

- NS1_I34A1

UniProt

P03496 - NS1_I34A1

Protein

Non-structural protein 1

Gene

NS

Organism
Influenza A virus (strain A/Puerto Rico/8/1934 H1N1)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 105 (01 Oct 2014)
      Sequence version 1 (21 Jul 1986)
      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. protein binding Source: IntAct
    2. RNA binding Source: UniProtKB-KW

    GO - Biological processi

    1. cytokine-mediated signaling pathway Source: Reactome
    2. evasion or tolerance by virus of host immune response Source: Reactome
    3. modification by virus of host mRNA processing Source: Reactome
    4. modulation by virus of host morphology or physiology Source: Reactome
    5. modulation by virus of host process Source: Reactome
    6. suppression by virus of host mRNA processing Source: UniProtKB-KW
    7. suppression by virus of host PKR activity Source: UniProtKB-KW
    8. suppression by virus of host RIG-I activity Source: UniProtKB-KW
    9. suppression by virus of host type I interferon-mediated signaling pathway Source: UniProtKB-KW
    10. viral life cycle Source: Reactome
    11. viral process Source: Reactome
    12. viral transcription Source: Reactome

    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

    Enzyme and pathway databases

    ReactomeiREACT_115831. ISG15 antiviral mechanism.
    REACT_6173. Inhibition of Host mRNA Processing and RNA Silencing.
    REACT_6320. Inhibition of IFN-beta.
    REACT_6350. Inhibition of PKR.
    REACT_9491. Viral mRNA Translation.

    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/Puerto Rico/8/1934 H1N1)
    Taxonomic identifieri211044 [NCBI]
    Taxonomic lineageiVirusesssRNA negative-strand virusesOrthomyxoviridaeInfluenzavirus A
    Virus hostiAves [TaxID: 8782]
    Homo sapiens (Human) [TaxID: 9606]
    Sus scrofa (Pig) [TaxID: 9823]
    ProteomesiUP000009255: 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. cytosol Source: Reactome
    2. host cell cytoplasm Source: UniProtKB-SubCell
    3. host cell nucleus Source: UniProtKB-SubCell
    4. nucleoplasm Source: Reactome

    Keywords - Cellular componenti

    Host cytoplasm, Host nucleus

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi20 – 201K → A: No of ISGylation of band I form; when associated with K-41; K-217 and K-219. 1 Publication
    Mutagenesisi38 – 381R → A: Complete loss of inhibition of DDX58 CARD ubiquitination; when associated with A-41. 1 Publication
    Mutagenesisi41 – 411K → A: Complete loss of inhibition of DDX58 CARD ubiquitination; when associated with A-38. 2 Publications
    Mutagenesisi41 – 411K → A: No of ISGylation of band I form; when associated with K-20; K-217 and K-219. 2 Publications
    Mutagenesisi96 – 961E → A: Complete loss of inhibition of DDX58 CARD ubiquitination; when associated with A-97. 1 Publication
    Mutagenesisi97 – 971E → A: Complete loss of inhibition of DDX58 CARD ubiquitination; when associated with A-96. 1 Publication
    Mutagenesisi108 – 1081K → A: No of ISGylation of band II form; when associated with K-110 and K-126. 1 Publication
    Mutagenesisi110 – 1101K → A: No of ISGylation of band II form; when associated with K-108 and K-126. 1 Publication
    Mutagenesisi126 – 1261K → A: No of ISGylation of band II form; when associated with K-108 and K-110. 1 Publication
    Mutagenesisi217 – 2171K → A: No of ISGylation of band I form; when associated with K-20; K-41 and K-219. 1 Publication
    Mutagenesisi219 – 2191K → A: No of ISGylation of band I form; when associated with K-20; K-41 and K-217. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 230230Non-structural protein 1PRO_0000078945Add
    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 host
    Cross-linki41 – 41Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15); in band I form; by host
    Cross-linki108 – 108Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15); in band II form; by host
    Cross-linki110 – 110Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15); in band II form; by host
    Cross-linki126 – 126Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15); in band II form; by host
    Cross-linki217 – 217Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15); in band I form; by host
    Cross-linki219 – 219Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15); in band I form; by host

    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.1 Publication

    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

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    PIK3R2O004598EBI-2547442,EBI-346930From a different organism.
    STAU1O957933EBI-2547442,EBI-358174From a different organism.
    TRIM25Q142583EBI-2547442,EBI-2341129From a different organism.

    Protein-protein interaction databases

    DIPiDIP-29081N.
    IntActiP03496. 172 interactions.
    MINTiMINT-3381930.

    Structurei

    Secondary structure

    1
    230
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi3 – 2422
    Helixi30 – 5021
    Helixi54 – 6916
    Beta strandi88 – 936
    Helixi95 – 995
    Beta strandi105 – 1128
    Beta strandi115 – 1206
    Beta strandi127 – 13711
    Beta strandi140 – 15112
    Beta strandi156 – 1627
    Helixi171 – 18717
    Beta strandi191 – 1944
    Helixi196 – 2016

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    2GX9X-ray2.10A/B79-207[»]
    2ZKOX-ray1.70A/B1-70[»]
    3L4QX-ray2.30A/B73-230[»]
    3O9QX-ray2.50A/B79-230[»]
    3O9RX-ray2.00A/B79-230[»]
    3O9SX-ray2.48A/B79-230[»]
    3O9TX-ray2.20A/B79-230[»]
    3O9UX-ray3.20A/B/C/D/E/F/G/H79-230[»]
    3RVCX-ray1.80A79-230[»]
    ProteinModelPortaliP03496.
    SMRiP03496. Positions 1-72, 79-205.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP03496.

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni1 – 7373RNA-binding and homodimerizationBy similarityAdd
    BLAST
    Regioni180 – 21536CPSF4-bindingBy similarityAdd
    BLAST
    Regioni223 – 2308PABPN1-bindingBy similarity

    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: P03496-1) [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 RVADQELGDA PFLDRLRRDQ KSLRGRGSTL    50
    GLDIETATRA GKQIVERILK EESDEALKMT MASVPASRYL TDMTLEEMSR 100
    DWSMLIPKQK VAGPLCIRMD QAIMDKNIIL KANFSVIFDR LETLILLRAF 150
    TEEGAIVGEI SPLPSLPGHT AEDVKNAVGV LIGGLEWNDN TVRVSETLQR 200
    FAWRSSNENG RPPLTPKQKR EMAGTIRSEV 230
    Length:230
    Mass (Da):25,868
    Last modified:July 21, 1986 - v1
    Checksum:i2F7EC18E3EE7A4BE
    GO
    Isoform NEP (identifier: P03508-1) [UniParc]FASTAAdd to Basket

    Also known as: NS2

    The sequence of this isoform can be found in the external entry P03508.
    Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.
    Length:121
    Mass (Da):14,380
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti55 – 551E → K in ABD77680. 1 PublicationCurated
    Sequence conflicti101 – 1011D → E in AAA43536. (PubMed:11779399)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    V01104 Genomic RNA. Translation: CAA24292.1. Sequence problems.
    J02150 Genomic RNA. Translation: AAA43536.1.
    AF389122 Genomic RNA. Translation: AAM75163.1.
    EF467817 Genomic RNA. Translation: ABO21703.1.
    CY009448 Genomic RNA. Translation: ABD77680.1.
    RefSeqiNP_040984.1. NC_002020.1.

    Genome annotation databases

    GeneIDi956533.

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    V01104 Genomic RNA. Translation: CAA24292.1 . Sequence problems.
    J02150 Genomic RNA. Translation: AAA43536.1 .
    AF389122 Genomic RNA. Translation: AAM75163.1 .
    EF467817 Genomic RNA. Translation: ABO21703.1 .
    CY009448 Genomic RNA. Translation: ABD77680.1 .
    RefSeqi NP_040984.1. NC_002020.1.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    2GX9 X-ray 2.10 A/B 79-207 [» ]
    2ZKO X-ray 1.70 A/B 1-70 [» ]
    3L4Q X-ray 2.30 A/B 73-230 [» ]
    3O9Q X-ray 2.50 A/B 79-230 [» ]
    3O9R X-ray 2.00 A/B 79-230 [» ]
    3O9S X-ray 2.48 A/B 79-230 [» ]
    3O9T X-ray 2.20 A/B 79-230 [» ]
    3O9U X-ray 3.20 A/B/C/D/E/F/G/H 79-230 [» ]
    3RVC X-ray 1.80 A 79-230 [» ]
    ProteinModelPortali P03496.
    SMRi P03496. Positions 1-72, 79-205.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    DIPi DIP-29081N.
    IntActi P03496. 172 interactions.
    MINTi MINT-3381930.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    GeneIDi 956533.

    Enzyme and pathway databases

    Reactomei REACT_115831. ISG15 antiviral mechanism.
    REACT_6173. Inhibition of Host mRNA Processing and RNA Silencing.
    REACT_6320. Inhibition of IFN-beta.
    REACT_6350. Inhibition of PKR.
    REACT_9491. Viral mRNA Translation.

    Miscellaneous databases

    EvolutionaryTracei P03496.

    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. "Complete nucleotide sequence of the influenza A/PR/8/34 virus NS gene and comparison with the NS genes of the A/Udorn/72 and A/FPV/Rostock/34 strains."
      Baez M., Taussig R., Zazra J.J., Young J.F., Palese P., Reisfeld A., Skalka A.M.
      Nucleic Acids Res. 8:5845-5858(1980) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
    2. Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
    3. "Efficient generation and growth of influenza virus A/PR/8/34 from eight cDNA fragments."
      de Wit E., Spronken M.I.J., Bestebroer T.M., Rimmelzwaan G.F., Osterhaus A.D.M.E., Fouchier R.A.M.
      Virus Res. 103:155-161(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA], REVERSE GENETICS.
    4. Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
    5. "Intracellular warfare between human influenza viruses and human cells: the roles of the viral NS1 protein."
      Krug R.M., Yuan W., Noah D.L., Latham A.G.
      Virology 309:181-189(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW.
    6. "Influenza A virus NS1 targets the ubiquitin ligase TRIM25 to evade recognition by the host viral RNA sensor RIG-I."
      Gack M.U., Albrecht R.A., Urano T., Inn K.-S., Huang I.-C., Carnero E., Farzan M., Inoue S., Jung J.U., Garcia-Sastre A.
      Cell Host Microbe 5:439-449(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH HUMAN TRIM25, MUTAGENESIS OF ARG-38; LYS-41; GLU-96 AND GLU-97.
    7. "Herc5 attenuates influenza A virus by catalyzing ISGylation of viral NS1 protein."
      Tang Y., Zhong G., Zhu L., Liu X., Shan Y., Feng H., Bu Z., Chen H., Wang C.
      J. Immunol. 184:5777-5790(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: ISGYLATION AT LYS-20; LYS-41; LYS-108; LYS-110; LYS-126; LYS-217 AND LYS-219, MUTAGENESIS OF LYS-20; LYS-41; LYS-108; LYS-110; LYS-126; LYS-217 AND LYS-219.

    Entry informationi

    Entry nameiNS1_I34A1
    AccessioniPrimary (citable) accession number: P03496
    Secondary accession number(s): Q20N32, Q67267, Q71QT3
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 21, 1986
    Last sequence update: July 21, 1986
    Last modified: October 1, 2014
    This is version 105 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

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    2. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3