ID D9N0J5_9INFA Unreviewed; 230 AA. AC D9N0J5; DT 05-OCT-2010, integrated into UniProtKB/TrEMBL. DT 05-OCT-2010, sequence version 1. DT 07-OCT-2020, entry version 44. DE RecName: Full=Non-structural protein 1 {ECO:0000256|RuleBase:RU362113}; DE Short=NS1 {ECO:0000256|RuleBase:RU362113}; DE Flags: Fragment; GN Name=NS1 {ECO:0000313|EMBL:ADK20197.1}; GN Synonyms=NS {ECO:0000256|RuleBase:RU362113}; OS Influenza A virus (A/Pavia/4538/2009(H3N2)). OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina; OC Insthoviricetes; Articulavirales; Orthomyxoviridae; Alphainfluenzavirus. OX NCBI_TaxID=863179 {ECO:0000313|EMBL:ADK20197.1}; RN [1] {ECO:0000313|EMBL:ADK20197.1} RP NUCLEOTIDE SEQUENCE. RC STRAIN=A/Pavia/4538/2009 {ECO:0000313|EMBL:ADK20197.1}; RX PubMed=20809948; RA Campanini G., Piralla A., Paolucci S., Rovida F., Percivalle E., Maga G., RA Baldanti F.; RT "Genetic divergence of influenza A NS1 gene in pandemic 2009 H1N1 isolates RT with respect to H1N1 and H3N2 isolates from previous seasonal epidemics."; RL Virol. J. 7:209-209(2010). 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:0000256|RuleBase:RU362113}. 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:0000256|RuleBase:RU362113}. 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: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}. 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; HM745170; ADK20197.1; -; 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: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 activity; IEA:UniProtKB-KW. DR GO; GO:0039540; P:suppression by virus of host RIG-I activity; IEA:UniProtKB-KW. DR GO; GO:0039502; P:suppression by virus of host type I interferon-mediated signaling pathway; 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 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" FT NON_TER 230 FT /evidence="ECO:0000313|EMBL:ADK20197.1" SQ SEQUENCE 230 AA; 26147 MW; 2867C5F5B245CB27 CRC64; MDSNTVSSFQ VDCFLWHIRK QVVDQEMSDA PFLDRLRRDQ RSLRGRGNTL GLDIKVATHV GKQIVEKILK EESDEALKMT MVSTPASRYI TDMTIEELSR NWFMLMPKQK VEGPLCIRMD QAIMEKNITL KANFSVIFDR LETIVLLRAF TEEGAIVGEI SPLPSFPGHT IEDVKNAIGV LIGGLEWNDN TVRVSKNLQR FAWRSSNENG GPPLTPKQKR EMARTARSKV //