ID A0A0U2SS25_9INFA Unreviewed; 230 AA. AC A0A0U2SS25; DT 16-MAR-2016, integrated into UniProtKB/TrEMBL. DT 16-MAR-2016, sequence version 1. DT 13-SEP-2023, entry version 30. DE RecName: Full=Non-structural protein 1 {ECO:0000256|RuleBase:RU362113}; 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; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina; OC Insthoviricetes; Articulavirales; Orthomyxoviridae; Alphainfluenzavirus. OX NCBI_TaxID=1756090 {ECO:0000313|EMBL:ALR82593.1, ECO:0000313|Proteomes:UP000119134}; RN [1] {ECO:0000313|EMBL:ALR82593.1, ECO:0000313|Proteomes:UP000119134} RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. 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 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. Prevents the establishment of the cellular antiviral state CC by inhibiting TRIM25-mediated RIGI 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. Also binds CC poly(A) and U6 snRNA. Inhibits the integrated stress response (ISR) in CC the infected cell by blocking dsRNA binding by EIF2AK2/PKR and further CC phosphorylation of EIF2S1/EIF-2ALPHA. Stress granule formation is thus CC inhibited, which allows protein synthesis and viral replication. 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 RIGI 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; KU143424; ALR82593.1; -; Viral_cRNA. DR Proteomes; UP000119134; Genome. 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:0030291; F:protein serine/threonine kinase inhibitor activity; IEA:UniProtKB-KW. 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 signaling; IEA:UniProtKB-KW. DR GO; GO:0039502; P:suppression by virus of host type I interferon-mediated signaling pathway; IEA:UniProtKB-KW. DR GO; GO:0039540; P:suppression by virus of host viral-induced cytoplasmic pattern recognition receptor signaling pathway via inhibition of host RIG-I activity; IEA:UniProtKB-KW. DR Gene3D; 3.30.420.330; Influenza virus non-structural protein, effector domain; 1. DR Gene3D; 1.10.287.10; S15/NS1, RNA-binding; 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; Ns1 effector domain-like; 1. DR SUPFAM; SSF47060; S15/NS1 RNA-binding domain; 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 COMPBIAS 213..230 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" 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 //