ID A0A0U2SS25_9INFA Unreviewed; 230 AA. AC A0A0U2SS25; DT 16-MAR-2016, integrated into UniProtKB/TrEMBL. DT 16-MAR-2016, sequence version 1. DT 08-JUN-2016, entry version 4. DE RecName: Full=Non-structural protein 1 {ECO:0000256|RuleBase:RU362113, ECO:0000256|SAAS:SAAS00141112}; DE Short=NS1 {ECO:0000256|RuleBase:RU362113}; GN Name=NS1 {ECO:0000313|EMBL:ALR82593.1}; GN Synonyms=NS {ECO:0000256|RuleBase:RU362113}; OS Influenza A virus (A/wild bird/Wuhan/WHHN58/2014(H1N1)). OC Viruses; ssRNA viruses; ssRNA negative-strand viruses; OC Orthomyxoviridae; Influenzavirus A. OX NCBI_TaxID=1756090 {ECO:0000313|EMBL:ALR82593.1}; RN [1] {ECO:0000313|EMBL:ALR82593.1} RP NUCLEOTIDE SEQUENCE. RC STRAIN=A/wild bird/Wuhan/WHHN58/2014 {ECO:0000313|EMBL:ALR82593.1}; RA Chen L.-J., Lin X.-D., Guo W.-P., Tian J.-H., Zhang Y.-Z.; RT "Diversity and evolution of avian influenza viruses in live poultry RT markets, free range poultry and wetland regions in China."; RL Submitted (NOV-2015) 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. CC {ECO:0000256|RuleBase:RU362113}. 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 {ECO:0000256|SAAS:SAAS00141143}. 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. {ECO:0000256|RuleBase:RU362113}. 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. CC {ECO:0000256|SAAS:SAAS00141179}. 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|SAAS:SAAS00596549}. CC -!- SUBCELLULAR LOCATION: Host nucleus CC {ECO:0000256|SAAS:SAAS00596446}. CC -!- SUBCELLULAR LOCATION: Host nucleus CC {ECO:0000256|RuleBase:RU362113}. Host cytoplasm CC {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; KU143424; ALR82593.1; -; 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-KW. 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 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:SAAS00491311}; 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:SAAS00491234}; KW Host nucleus {ECO:0000256|RuleBase:RU362113, KW ECO:0000256|SAAS:SAAS00491032}; KW Host-virus interaction {ECO:0000256|RuleBase:RU362113, KW ECO:0000256|SAAS:SAAS00491141}; KW Inhibition of host innate immune response by virus KW {ECO:0000256|SAAS:SAAS00491089}; KW Inhibition of host interferon signaling pathway by virus KW {ECO:0000256|SAAS:SAAS00490748}; 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:SAAS00491387}; KW Inhibition of host RIG-I by virus {ECO:0000256|SAAS:SAAS00491268}; KW Inhibition of host RLR pathway by virus KW {ECO:0000256|SAAS:SAAS00491356}; KW Interferon antiviral system evasion {ECO:0000256|RuleBase:RU362113, KW ECO:0000256|SAAS:SAAS00490884}; KW RNA-binding {ECO:0000256|RuleBase:RU362113, KW ECO:0000256|SAAS:SAAS00491002}; KW Viral immunoevasion {ECO:0000256|SAAS:SAAS00491222}. SQ SEQUENCE 230 AA; 26071 MW; 4514E86F929B5EC3 CRC64; MDSNTVSSFQ VDCFLWHVRK RFADQELGDA PFLDRLRRDQ KSLRGRGSTL GLDIETATRA GKQIVERILE EESDEALKMT IASVPASRYL TDMTLEEMSR DWFMLMPKQK VAGSLCIRMD QAIMDKNITL KANFSVIFDR LETLILLRAF TEEGAIVGEI SPLPSLPGHT DEDVKNAIGV LIGGLEWNDN TVRVSETLQR FAWRSSNEDG RPPLPPKQKR KMARTIESEV //