ID   NS1_I57A4               Reviewed;          89 AA.
AC   Q84056; P03497;
DT   21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1996, sequence version 1.
DT   03-AUG-2022, entry version 87.
DE   RecName: Full=Non-structural protein 1;
DE            Short=NS1;
DE   AltName: Full=NS1A;
DE   Flags: Fragment;
GN   Name=NS;
OS   Influenza A virus (strain A/RI/5-/1957 H2N2).
OC   Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina;
OC   Insthoviricetes; Articulavirales; Orthomyxoviridae; Alphainfluenzavirus.
OX   NCBI_TaxID=382828;
OH   NCBI_TaxID=8782; Aves.
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX   PubMed=7241645; DOI=10.1128/jvi.38.1.1-7.1981;
RA   Hall R.M., Air G.M.;
RT   "Variation in nucleotide sequences coding for the N-terminal regions of the
RT   matrix and nonstructural proteins of influenza A viruses.";
RL   J. Virol. 38:1-7(1981).
RN   [2]
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: 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). This results in the accumulation of unprocessed 3'
CC       end pre-mRNAs which can't be exported from the nucleus. 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 (By similarity). {ECO:0000250}.
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 like IRF3 and IRF7.
CC       Prevents human EIF2AK2/PKR activation, either by binding double-strand
CC       RNA, or 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. Suppresses
CC       the RNA silencing-based antiviral response in Drosophila cells (By
CC       similarity). {ECO:0000250}.
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 (By similarity). {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Host nucleus. Host cytoplasm. 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 (By
CC       similarity). {ECO:0000250}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=NS1;
CC         IsoId=Q84056-1; Sequence=Displayed;
CC       Name=NEP; Synonyms=NS2;
CC         IsoId=Q84056-2; Sequence=Not described;
CC   -!- DOMAIN: The dsRNA-binding region is required for suppression of RNA
CC       silencing. {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the influenza A viruses NS1 family.
CC       {ECO:0000305}.
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DR   EMBL; J02157; AAA43532.1; -; Genomic_RNA.
DR   SMR; Q84056; -.
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:0003723; F:RNA binding; IEA:UniProtKB-KW.
DR   GO; GO:0039524; P:suppression by virus of host mRNA processing; IEA:UniProtKB-KW.
DR   InterPro; IPR000256; NS1A.
DR   InterPro; IPR009068; S15_NS1_RNA-bd.
DR   Pfam; PF00600; Flu_NS1; 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 pre-mRNA processing by virus;
KW   Interferon antiviral system evasion; RNA-binding.
FT   CHAIN           1..>89
FT                   /note="Non-structural protein 1"
FT                   /id="PRO_0000078946"
FT   REGION          1..73
FT                   /note="RNA-binding and homodimerization"
FT                   /evidence="ECO:0000250"
FT   MOTIF           34..38
FT                   /note="Nuclear localization signal 1"
FT                   /evidence="ECO:0000250"
FT   NON_TER         89
SQ   SEQUENCE   89 AA;  10080 MW;  757E281C10352DC9 CRC64;
     MDPNTVSSFQ VDCFLWHVRK QVADQELGDA PFLDRLRRDQ KSLRGRGSTL GLNIETATRV
     GKQIVERILK EESDEALKMT MASAPASRY