ID D9N0J5_9INFA Unreviewed; 230 AA. AC D9N0J5; DT 05-OCT-2010, integrated into UniProtKB/TrEMBL. DT 05-OCT-2010, sequence version 1. DT 20-DEC-2017, entry version 33. DE RecName: Full=Non-structural protein 1 {ECO:0000256|RuleBase:RU362113, ECO:0000256|SAAS:SAAS00965123}; 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; ssRNA viruses; ssRNA negative-strand viruses; OC Orthomyxoviridae; Influenzavirus A. 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., RA Maga G., Baldanti F.; RT "Genetic divergence of influenza A NS1 gene in pandemic 2009 H1N1 RT isolates with respect to H1N1 and H3N2 isolates from previous seasonal RT epidemics."; RL Virol. J. 7:209-209(2010). CC -!- FUNCTION: Inhibits post-transcriptional processing of cellular CC pre-mRNA, by binding and inhibiting two cellular proteins that are CC required for the 3'-end processing of cellular pre-mRNAs: the 30 CC kDa cleavage and polyadenylation specificity factor/CPSF4 and the CC poly(A)-binding protein 2/PABPN1. In turn, unprocessed 3' end pre- CC mRNAs accumulate in the host nucleus and are no longer exported to CC the cytoplasm. Cellular protein synthesis is thereby shut off very CC early after virus infection. Viral protein synthesis is not CC affected by the inhibition of the cellular 3' end processing CC machinery because the poly(A) tails of viral mRNAs are produced by CC the viral polymerase through a stuttering mechanism. CC {ECO:0000256|RuleBase:RU362113, ECO:0000256|SAAS:SAAS00845460}. CC -!- FUNCTION: Prevents the establishment of the cellular antiviral CC state by inhibiting TRIM25-mediated DDX58 ubiquitination, which CC normally triggers the antiviral transduction signal that leads to CC the activation of type I IFN genes by transcription factors IRF3 CC and IRF7. Prevents human EIF2AK2/PKR activation, either by binding CC double-strand RNA, or by interacting directly with EIF2AK2/PKR. CC This function may be important at the very beginning of the CC infection, when NS1 is mainly present in the cytoplasm. Also binds CC poly(A) and U6 snRNA. {ECO:0000256|RuleBase:RU362113, CC ECO:0000256|SAAS:SAAS00845430}. CC -!- SUBUNIT: Homodimer. Interacts with host TRIM25 (via coiled coil); CC this interaction specifically inhibits TRIM25 multimerization and CC TRIM25-mediated DDX58 CARD ubiquitination. Interacts with human CC EIF2AK2/PKR, CPSF4, IVNS1ABP and PABPN1. CC {ECO:0000256|RuleBase:RU362113, ECO:0000256|SAAS:SAAS00141396}. CC -!- SUBCELLULAR LOCATION: Host cytoplasm CC {ECO:0000256|RuleBase:RU362113, ECO:0000256|SAAS:SAAS00965118}. CC Host nucleus {ECO:0000256|RuleBase:RU362113}. CC -!- DOMAIN: The dsRNA-binding region is required for suppression of CC RNA silencing. {ECO:0000256|RuleBase:RU362113}. CC -!- SIMILARITY: Belongs to the influenza A viruses NS1 family. CC {ECO:0000256|RuleBase:RU362113, ECO:0000256|SAAS:SAAS00596488}. 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; 1.10.287.10; -; 1. DR HAMAP; MF_04066; INFV_NS1; 1. DR InterPro; IPR004208; Flu_B_NS1. DR InterPro; IPR000256; Flu_NS1. DR InterPro; IPR009068; S15_NS1_RNA-bd. DR Pfam; PF00600; Flu_NS1; 1. DR SUPFAM; SSF47060; SSF47060; 1. PE 3: Inferred from homology; KW Eukaryotic host gene expression shutoff by virus KW {ECO:0000256|RuleBase:RU362113, ECO:0000256|SAAS:SAAS00490754}; KW Host cytoplasm {ECO:0000256|RuleBase:RU362113, KW ECO:0000256|SAAS:SAAS00965142}; KW Host gene expression shutoff by virus {ECO:0000256|RuleBase:RU362113, KW ECO:0000256|SAAS:SAAS00490948}; KW Host mRNA suppression by virus {ECO:0000256|RuleBase:RU362113, KW ECO:0000256|SAAS:SAAS00141209}; KW Host nucleus {ECO:0000256|RuleBase:RU362113, KW ECO:0000256|SAAS:SAAS00965098}; KW Host-virus interaction {ECO:0000256|RuleBase:RU362113, KW ECO:0000256|SAAS:SAAS00965144}; KW Inhibition of host innate immune response by virus KW {ECO:0000256|SAAS:SAAS00965111}; KW Inhibition of host interferon signaling pathway by virus KW {ECO:0000256|SAAS:SAAS00965146}; KW Inhibition of host PKR by virus {ECO:0000256|SAAS:SAAS00491222}; KW Inhibition of host pre-mRNA processing by virus KW {ECO:0000256|RuleBase:RU362113, ECO:0000256|SAAS:SAAS00141362}; KW Inhibition of host RIG-I by virus {ECO:0000256|SAAS:SAAS00491268}; KW Inhibition of host RLR pathway by virus KW {ECO:0000256|SAAS:SAAS00141185}; KW Interferon antiviral system evasion {ECO:0000256|RuleBase:RU362113, KW ECO:0000256|SAAS:SAAS00965145}; KW RNA-binding {ECO:0000256|RuleBase:RU362113, KW ECO:0000256|SAAS:SAAS00965112}; KW Viral immunoevasion {ECO:0000256|SAAS:SAAS00491222}. FT NON_TER 230 230 {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 //