ID   H8XZV3_9INFA            Unreviewed;       230 AA.
AC   H8XZV3;
DT   16-MAY-2012, integrated into UniProtKB/TrEMBL.
DT   16-MAY-2012, sequence version 1.
DT   08-NOV-2023, entry version 48.
DE   RecName: Full=Non-structural protein 1 {ECO:0000256|RuleBase:RU362113};
DE            Short=NS1 {ECO:0000256|RuleBase:RU362113};
GN   Name=NS1 {ECO:0000313|EMBL:ADV39803.1};
GN   Synonyms=NS {ECO:0000256|RuleBase:RU362113};
OS   Influenza A virus (A/KOL/964/2007(H1N1)).
OC   Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina;
OC   Insthoviricetes; Articulavirales; Orthomyxoviridae; Alphainfluenzavirus;
OC   Alphainfluenzavirus influenzae; Influenza A virus.
OX   NCBI_TaxID=943998 {ECO:0000313|EMBL:ADV39803.1};
RN   [1] {ECO:0000313|EMBL:ADV39803.1}
RP   NUCLEOTIDE SEQUENCE.
RC   STRAIN=A/KOL/964/2007 {ECO:0000313|EMBL:ADV39803.1};
RA   Sarkar-Dutta M., Chawla-Sarkar M.;
RL   Submitted (JAN-2011) to the EMBL/GenBank/DDBJ databases.
RN   [2] {ECO:0000313|EMBL:ADV39803.1}
RP   NUCLEOTIDE SEQUENCE.
RC   STRAIN=A/KOL/964/2007 {ECO:0000313|EMBL:ADV39803.1};
RX   PubMed=22217077;
RA   Sarkar M., Chanda S., Chakrabarti S., Mazumdar J., Ganguly A., Chadha M.S.,
RA   Mishra A.C., Chawla-Sarkar M.;
RT   "Surveillance in eastern India (2007-2009) revealed reassortment event
RT   involving ns and PB1-F2 gene segments among co-circulating influenza a
RT   subtypes.";
RL   Virol. J. 9:3-3(2012).
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:0000256|RuleBase:RU362113}.
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:0000256|RuleBase:RU362113}.
CC   -!- SUBCELLULAR LOCATION: Host nucleus {ECO:0000256|RuleBase:RU362113}.
CC       Host cytoplasm {ECO:0000256|RuleBase:RU362113}.
CC   -!- DOMAIN: The dsRNA-binding region is required for suppression of RNA
CC       silencing. {ECO:0000256|RuleBase:RU362113}.
CC   -!- SIMILARITY: Belongs to the influenza A viruses NS1 family.
CC       {ECO:0000256|RuleBase:RU362113}.
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DR   EMBL; HQ853511; ADV39803.1; -; Viral_cRNA.
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-UniRule.
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   Eukaryotic host gene expression shutoff by virus
KW   {ECO:0000256|ARBA:ARBA00023247, ECO:0000256|RuleBase:RU362113};
KW   Host cytoplasm {ECO:0000256|ARBA:ARBA00023200,
KW   ECO:0000256|RuleBase:RU362113};
KW   Host gene expression shutoff by virus {ECO:0000256|ARBA:ARBA00022995,
KW   ECO:0000256|RuleBase:RU362113};
KW   Host mRNA suppression by virus {ECO:0000256|ARBA:ARBA00022557,
KW   ECO:0000256|RuleBase:RU362113};
KW   Host nucleus {ECO:0000256|ARBA:ARBA00022562,
KW   ECO:0000256|RuleBase:RU362113};
KW   Host-virus interaction {ECO:0000256|ARBA:ARBA00022581,
KW   ECO:0000256|RuleBase:RU362113};
KW   Inhibition of host innate immune response by virus
KW   {ECO:0000256|ARBA:ARBA00022632};
KW   Inhibition of host interferon signaling pathway by virus
KW   {ECO:0000256|ARBA:ARBA00022830};
KW   Inhibition of host PKR by virus {ECO:0000256|ARBA:ARBA00023041};
KW   Inhibition of host pre-mRNA processing by virus
KW   {ECO:0000256|ARBA:ARBA00022834, ECO:0000256|RuleBase:RU362113};
KW   Inhibition of host RIG-I by virus {ECO:0000256|ARBA:ARBA00023090};
KW   Inhibition of host RLR pathway by virus {ECO:0000256|ARBA:ARBA00022482};
KW   Interferon antiviral system evasion {ECO:0000256|ARBA:ARBA00023258,
KW   ECO:0000256|RuleBase:RU362113};
KW   RNA-binding {ECO:0000256|ARBA:ARBA00022884, ECO:0000256|RuleBase:RU362113};
KW   Ubl conjugation {ECO:0000256|ARBA:ARBA00022843};
KW   Viral immunoevasion {ECO:0000256|ARBA:ARBA00023280}.
FT   REGION          205..230
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ   SEQUENCE   230 AA;  25786 MW;  F99B5310CA12F196 CRC64;
     MDSHTVSSFQ VDCFLWHVRK QVADQDLGDA PFLDRLRRDQ KSLKGRGSTL GLNIETATCV
     GKQIVERILK EESDEALKMT MASALASRYL TDMTVEEMSR DWFMLMPKQK VAGPLCVRMD
     QAIMDKNIIL KANFSVIFDR LENLTLLRAF TEEGAIVGEI SPLPSFPGHT NEDVKNAIGV
     LIGGLEWNDN TVRVSETLQR FAWRSSNETG GPPFTTTQNR KMAGTTRSEV
//