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NS1_I83A1
ID   NS1_I83A1               Reviewed;         237 AA.
AC   P11618; A4GCI1;
DT   01-OCT-1989, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1990, sequence version 2.
DT   23-FEB-2022, entry version 104.
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/Chile/1/1983 H1N1).
OC   Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina;
OC   Insthoviricetes; Articulavirales; Orthomyxoviridae; Alphainfluenzavirus.
OX   NCBI_TaxID=380985;
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].
RX   PubMed=2762132; DOI=10.1093/nar/17.13.5381;
RA   Schreier E., Roeske H., Michel S.;
RT   "Nucleotide sequence of the NS gene of influenza virus A/Chile/1/83
RT   (H1N1).";
RL   Nucleic Acids Res. 17:5381-5381(1989).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RA   Ghedin E., Spiro D., Miller N., Zaborsky J., Feldblyum T., Subbu V.,
RA   Shumway M., Sparenborg J., Groveman L., Halpin R., Sitz J., Koo H.,
RA   Salzberg S.L., Webster R.G., Hoffmann E., Krauss S., Naeve C., Bao Y.,
RA   Bolotov P., Dernovoy D., Kiryutin B., Lipman D.J., Tatusova T.;
RT   "The NIAID influenza genome sequencing project.";
RL   Submitted (MAR-2007) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RG   The NIAID Influenza Genome Sequencing Consortium;
RL   Submitted (MAR-2007) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   REVIEW.
RX   PubMed=12758165; DOI=10.1016/s0042-6822(03)00119-3;
RA   Krug R.M., Yuan W., Noah D.L., Latham A.G.;
RT   "Intracellular warfare between human influenza viruses and human cells: the
RT   roles of the viral NS1 protein.";
RL   Virology 309:181-189(2003).
CC   -!- FUNCTION: Prevents the establishment of the cellular antiviral state by
CC       inhibiting TRIM25-mediated DDX58 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. Prevents
CC       human EIF2AK2/PKR activation, either by binding double-strand RNA, or
CC       by interacting directly with EIF2AK2/PKR. This function may be
CC       important at the very beginning of the infection, when NS1 is mainly
CC       present in the cytoplasm. Also binds poly(A) and U6 snRNA.
CC       {ECO:0000255|HAMAP-Rule:MF_04066}.
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. {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 DDX58 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=P11618-1; Sequence=Displayed;
CC       Name=NEP; Synonyms=NS2;
CC         IsoId=P11619-1; 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}.
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DR   EMBL; X15282; CAA33355.2; -; Genomic_RNA.
DR   EMBL; CY020441; ABO38345.1; -; Viral_cRNA.
DR   SMR; P11618; -.
DR   Proteomes; UP000008582; Genome.
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; -; 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; S15_NS1_RNA-bd.
DR   Pfam; PF00600; Flu_NS1; 1.
DR   SUPFAM; SSF143021; SSF143021; 1.
DR   SUPFAM; SSF47060; SSF47060; 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..237
FT                   /note="Non-structural protein 1"
FT                   /id="PRO_0000078920"
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..237
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"
SQ   SEQUENCE   237 AA;  26819 MW;  C33A9E3D0386E752 CRC64;
     MDPNTVSSFQ VDCFLWHVRK QVADQELGDA PFLDRLRRDQ KSLKGRGSTL GLDIETATCV
     GKQIVERILK EESDEALKMT MASAPASRYL TDMTIEEMSR DWFMLMPKQK VAGPLCVRMD
     QAIMDKNIIL KANFSVIFDR LETLILLRAF TEEGAIVGEI SPLPSLPGHT NEDVKNAIGV
     LIGGLEWNDN TVRVSKTLQR FAWRSSNENG RPPLTPKQKR KMARAIRSEV RRNKMAD
 
 
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