ID Q6E3U7_9INFA Unreviewed; 228 AA. AC Q6E3U7; DT 16-AUG-2004, integrated into UniProtKB/TrEMBL. DT 16-AUG-2004, sequence version 1. DT 28-NOV-2012, entry version 42. DE SubName: Full=Nonstructural protein 1; DE Flags: Fragment; GN Name=NS1; OS Influenza A virus (A/duck/Fujian/01/2002(H5N1)). OC Viruses; ssRNA negative-strand viruses; Orthomyxoviridae; OC Influenzavirus A. OX NCBI_TaxID=274827; RN [1] RP NUCLEOTIDE SEQUENCE. RC STRAIN=A/Duck/Fujian/01/2002; RX PubMed=15235128; DOI=10.1073/pnas.0403212101; RA Chen H., Deng G., Li Z., Tian G., Li Y., Jiao P., Zhang L., Liu Z., RA Webster R.G., Yu K.; RT "The evolution of H5N1 influenza viruses in ducks in southern China."; RL Proc. Natl. Acad. Sci. U.S.A. 101:10452-10457(2004). RN [2] RP NUCLEOTIDE SEQUENCE. RC STRAIN=A/Duck/Fujian/01/2002; RA Chen H.L., Deng G.H., Li Z.J., Tian G.B., Li Y.B., Jiao P., Zhang L., RA Webster R.G., Yu K.; RL Submitted (MAR-2004) to the EMBL/GenBank/DDBJ databases. 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; AY585441; AAT12106.1; -; mRNA. DR ProteinModelPortal; Q6E3U7; -. 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; 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 2: Evidence at transcript level; 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 228 228 SQ SEQUENCE 228 AA; 25969 MW; 073C0B09E174938A CRC64; MDSNTVSSFQ VDCFLWHVRK RFADQELGDA PFLDRLRRDQ KSLRGRGSTL GLDIETATRA GKQIVERILE EESDEALKMT IASLPAPRYL TEMTIEEMTR DWYMLMPRQK VTGSLWVRMD QAIMDKTIIF KANFSVIFDR LETLIPLRAF TEGGAIVGEI SPLPSVPGHT NEDVKNAIGV LIGGLEWNDN TVRVSETLQR FAWRSSDEDG RPPLPPKQKR KMARTIES //