ID   NS1_I07A0               Reviewed;         230 AA.
AC   A8C8K0;
DT   05-MAY-2009, integrated into UniProtKB/Swiss-Prot.
DT   13-NOV-2007, sequence version 1.
DT   08-NOV-2023, entry version 58.
DE   RecName: Full=Non-structural protein 1 {ECO:0000255|HAMAP-Rule:MF_04066};
DE            Short=NS1 {ECO:0000255|HAMAP-Rule:MF_04066};
DE   AltName: Full=NS1A {ECO:0000255|HAMAP-Rule:MF_04066};
GN   Name=NS {ECO:0000255|HAMAP-Rule:MF_04066};
OS   Influenza A virus (strain A/USA:Texas/UR06-0195/2007 H1N1).
OC   Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina;
OC   Insthoviricetes; Articulavirales; Orthomyxoviridae; Alphainfluenzavirus;
OC   Alphainfluenzavirus influenzae; Influenza A virus.
OX   NCBI_TaxID=455880;
OH   NCBI_TaxID=8782; Aves.
OH   NCBI_TaxID=9606; Homo sapiens (Human).
OH   NCBI_TaxID=9823; Sus scrofa (Pig).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RA   Spiro D., Sengamalay N., Boyne A., Bera J., Zaborsky J., Subbu V.,
RA   Sparenborg J., Gallagher T., Overton L., Althoff R., Liu X., Ghedin E.,
RA   Sitz J., Katzel D., Neupane R., Shumway M., Koo H., Edelman L., Menegus M.,
RA   Mayer C., Dale S., Bao Y., Bolotov P., Dernovoy D., Kiryutin B.,
RA   Lipman D.J., Tatusova T.;
RT   "The NIAID influenza genome sequencing project.";
RL   Submitted (SEP-2007) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RG   The NIAID Influenza Genome Sequencing Consortium;
RL   Submitted (SEP-2007) to the EMBL/GenBank/DDBJ databases.
CC   -!- FUNCTION: Inhibits post-transcriptional processing of cellular pre-
CC       mRNA, by binding and inhibiting two cellular proteins that are required
CC       for the 3'-end processing of cellular pre-mRNAs: the 30 kDa cleavage
CC       and polyadenylation specificity factor/CPSF4 and the poly(A)-binding
CC       protein 2/PABPN1. In turn, unprocessed 3' end pre-mRNAs accumulate in
CC       the host nucleus and are no longer exported to the cytoplasm. Cellular
CC       protein synthesis is thereby shut off very early after virus infection.
CC       Viral protein synthesis is not affected by the inhibition of the
CC       cellular 3' end processing machinery because the poly(A) tails of viral
CC       mRNAs are produced by the viral polymerase through a stuttering
CC       mechanism. Prevents the establishment of the cellular antiviral state
CC       by inhibiting TRIM25-mediated RIGI ubiquitination, which normally
CC       triggers the antiviral transduction signal that leads to the activation
CC       of type I IFN genes by transcription factors IRF3 and IRF7. Also binds
CC       poly(A) and U6 snRNA. Inhibits the integrated stress response (ISR) in
CC       the infected cell by blocking dsRNA binding by EIF2AK2/PKR and further
CC       phosphorylation of EIF2S1/EIF-2ALPHA. Stress granule formation is thus
CC       inhibited, which allows protein synthesis and viral replication.
CC       {ECO:0000255|HAMAP-Rule:MF_04066}.
CC   -!- SUBUNIT: Homodimer. Interacts with host TRIM25 (via coiled coil); this
CC       interaction specifically inhibits TRIM25 multimerization and TRIM25-
CC       mediated RIGI CARD ubiquitination. Interacts with human EIF2AK2/PKR,
CC       CPSF4, IVNS1ABP and PABPN1. {ECO:0000255|HAMAP-Rule:MF_04066}.
CC   -!- SUBCELLULAR LOCATION: Host nucleus {ECO:0000255|HAMAP-Rule:MF_04066}.
CC       Host cytoplasm {ECO:0000255|HAMAP-Rule:MF_04066}. Note=In uninfected,
CC       transfected cells, NS1 is localized in the nucleus. Only in virus
CC       infected cells, the nuclear export signal is unveiled, presumably by a
CC       viral protein, and a fraction of NS1 is exported in the cytoplasm.
CC       {ECO:0000255|HAMAP-Rule:MF_04066}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=NS1;
CC         IsoId=A8C8K0-1; Sequence=Displayed;
CC       Name=NEP; Synonyms=NS2;
CC         IsoId=A8C8J9-1; Sequence=External;
CC   -!- DOMAIN: The dsRNA-binding region is required for suppression of RNA
CC       silencing. {ECO:0000255|HAMAP-Rule:MF_04066}.
CC   -!- PTM: Upon interferon induction, ISGylated via host HERC5; this results
CC       in the impairment of NS1 interaction with RNA targets due to its
CC       inability to form homodimers and to interact with host EIF2AK2/PKR.
CC       {ECO:0000255|HAMAP-Rule:MF_04066}.
CC   -!- SIMILARITY: Belongs to the influenza A viruses NS1 family.
CC       {ECO:0000255|HAMAP-Rule:MF_04066}.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; CY026215; ABV45931.1; -; Viral_cRNA.
DR   SMR; A8C8K0; -.
DR   GO; GO:0030430; C:host cell cytoplasm; IEA:UniProtKB-SubCell.
DR   GO; GO:0042025; C:host cell nucleus; IEA:UniProtKB-SubCell.
DR   GO; GO:0030291; F:protein serine/threonine kinase inhibitor activity; IEA:UniProtKB-KW.
DR   GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
DR   GO; GO:0039524; P:suppression by virus of host mRNA processing; IEA:UniProtKB-KW.
DR   GO; GO:0039580; P:suppression by virus of host PKR signaling; IEA:UniProtKB-KW.
DR   GO; GO:0039502; P:suppression by virus of host type I interferon-mediated signaling pathway; IEA:UniProtKB-KW.
DR   GO; GO:0039540; P:suppression by virus of host viral-induced cytoplasmic pattern recognition receptor signaling pathway via inhibition of host RIG-I activity; IEA:UniProtKB-KW.
DR   Gene3D; 3.30.420.330; Influenza virus non-structural protein, effector domain; 1.
DR   Gene3D; 1.10.287.10; S15/NS1, RNA-binding; 1.
DR   HAMAP; MF_04066; INFV_NS1; 1.
DR   InterPro; IPR004208; NS1.
DR   InterPro; IPR000256; NS1A.
DR   InterPro; IPR038064; NS1A_effect_dom-like_sf.
DR   InterPro; IPR009068; uS15_NS1_RNA-bd_sf.
DR   Pfam; PF00600; Flu_NS1; 1.
DR   SUPFAM; SSF143021; Ns1 effector domain-like; 1.
DR   SUPFAM; SSF47060; S15/NS1 RNA-binding domain; 1.
PE   3: Inferred from homology;
KW   Alternative splicing; Eukaryotic host gene expression shutoff by virus;
KW   Host cytoplasm; Host gene expression shutoff by virus;
KW   Host mRNA suppression by virus; Host nucleus; Host-virus interaction;
KW   Inhibition of host innate immune response by virus;
KW   Inhibition of host interferon signaling pathway by virus;
KW   Inhibition of host PKR by virus;
KW   Inhibition of host pre-mRNA processing by virus;
KW   Inhibition of host RIG-I by virus; Inhibition of host RLR pathway by virus;
KW   Interferon antiviral system evasion; RNA-binding; Ubl conjugation;
KW   Viral immunoevasion.
FT   CHAIN           1..230
FT                   /note="Non-structural protein 1"
FT                   /id="PRO_0000372979"
FT   REGION          1..73
FT                   /note="RNA-binding and homodimerization"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04066"
FT   REGION          180..215
FT                   /note="CPSF4-binding"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04066"
FT   REGION          205..230
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          223..230
FT                   /note="PABPN1-binding"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04066"
FT   MOTIF           34..38
FT                   /note="Nuclear localization signal"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04066"
FT   MOTIF           137..146
FT                   /note="Nuclear export signal"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04066"
FT   COMPBIAS        205..223
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ   SEQUENCE   230 AA;  25815 MW;  EB0B53149B12F196 CRC64;
     MDSHTVSSFQ VDCFLWHVRK QVADQDLGDA PFLDRLRRDQ KSLKGRGSTL GLNIETATCV
     GKQIVERILK EESDEALKMT MASALASRYL TDMTVEEMSR DWFMLMPKQK VAGPLCVRMD
     QAIMDKNIIL KANFSVIFDR LENLTLLRAF TEEGAIVGEI SPLPSFPGHT NEDVKNAIGV
     LIGGLEWNDN TVRVSETLQR FAWRSSNETG GPPFTTTQKR KMAGTTRSEI
//