ID D9N0J5_9INFA Unreviewed; 230 AA. AC D9N0J5; DT 05-OCT-2010, integrated into UniProtKB/TrEMBL. DT 05-OCT-2010, sequence version 1. DT 31-OCT-2012, entry version 6. DE SubName: Full=Nonstructural protein 1; DE Flags: Fragment; GN Name=NS1; OS Influenza A virus (A/Pavia/4538/2009(H3N2)). OC Viruses; ssRNA negative-strand viruses; Orthomyxoviridae; OC Influenzavirus A. OX NCBI_TaxID=863179; RN [1] RP NUCLEOTIDE SEQUENCE. RC STRAIN=A/Pavia/4538/2009; 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 CC the poly(A)-binding protein 2 (PABPN1). This results in the CC accumulation of unprocessed 3' end pre-mRNAs which can't be CC exported from the nucleus. Cellular protein synthesis is thereby CC shut off very early after virus infection. Viral protein synthesis CC is not affected by the inhibition of the cellular 3' end CC processing machinery because the poly(A) tails of viral mRNAs are CC produced by the viral polymerase through a stuttering mechanism CC (By similarity). 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 like CC IRF3 and IRF7. Prevents human EIF2AK2/PKR activation, either by CC binding double-strand RNA, or by interacting directly with CC EIF2AK2/PKR. This function may be important at the very beginning CC of the infection, when NS1 is mainly present in the cytoplasm. CC Also binds poly(A) and U6 snRNA. Suppresses the RNA silencing- CC based antiviral response in Drosophila cells (By similarity). 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 (By similarity). 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-KW. DR GO; GO:0042025; C:host cell nucleus; IEA:UniProtKB-KW. DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW. DR GO; GO:0030683; P:evasion or tolerance by virus of host immune response; IEA:UniProtKB-KW. DR GO; GO:0039524; P:suppression by virus of host mRNA processing; IEA:UniProtKB-KW. DR Gene3D; G3DSA:1.10.287.10; S15_NS1_RNA_bd; 1. DR InterPro; IPR000256; Flu_NS1. DR InterPro; IPR009068; S15_NS1_RNA-bd. DR Pfam; PF00600; Flu_NS1; 1. DR SUPFAM; SSF47060; S15/NS1_bind; 1. PE 3: Inferred from homology; 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; KW Suppressor of RNA silencing. FT NON_TER 230 230 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 //