AC MF_04066; DC Protein; auto TR HAMAP; MF_04066; -; 1; level=0 XX Names: INFV_NS1 XX ID NS1 DE RecName: Full=Non-structural protein 1; DE Short=NS1; DE AltName: Full=NS1A; GN Name=NS; XX case 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 -!- SUBUNIT: Homodimer. Interacts with host TRIM25 (via coiled coil); this CC interaction specifically inhibits TRIM25 multimerization and TRIM25- CC mediated DDX58 CARD ubiquitination. Interacts with human EIF2AK2/PKR, CC CPSF4, IVNS1ABP and PABPN1. CC -!- SUBCELLULAR LOCATION: Host nucleus. Host cytoplasm. Note=In uninfected, CC transfected cells, NS1 is localized in the nucleus. Only in virus CC infected cells, the nuclear export signal is unveiled, presumably by a CC viral protein, and a fraction of NS1 is exported in the cytoplasm. CC -!- DOMAIN: The dsRNA-binding region is required for suppression of RNA CC silencing. CC -!- PTM: Upon interferon induction, ISGylated via host HERC5; this results CC in the impairment of NS1 interaction with RNA targets due to its CC inability to form homodimers and to interact with host EIF2AK2/PKR. CC -!- SIMILARITY: Belongs to the influenza A viruses NS1 family. else case CC -!- FUNCTION: Binds and inhibits the conjugation of the ubiquitin-like CC G1P2/ISG15 protein to its target proteins. Since G1P2/ISG15 is an early CC antiviral protein, NS1 may inhibit the host antiviral response. CC Prevents EIF2AK2/PKR activation, either by binding double strand RNA or CC by interacting directly with EIF2AK2/PKR. Also binds poly(A) and U6 CC snRNA. CC -!- SUBUNIT: Homodimer. Interacts with and inhibits human G1P2 conjugation CC by UBE1L. CC -!- SUBCELLULAR LOCATION: Host cytoplasm. Host nucleus. CC -!- SIMILARITY: Belongs to the influenza B viruses NS1 family. else case CC -!- FUNCTION: Prevents the establishment of the cellular antiviral state CC initiated by host DDX58, which normally triggers the antiviral CC transduction signal that leads to the activation of type I IFN genes by CC transcription factors IRF3 and IRF7. Participates also in the CC upregulation of the splicing of viral mRNAs. CC -!- SUBCELLULAR LOCATION: Host cytoplasm. Host nucleus. CC -!- SIMILARITY: Belongs to the influenza C viruses NS1 family. end case XX DR Pfam; PF00600; Flu_NS1; 1; trigger=no DR Pfam; PF02942; Flu_B_NS1; 1; trigger=no DR Pfam; PF03506; Flu_C_NS1; 1; trigger=no DR Pfam; PF03555; Flu_C_NS2; 1; trigger=no DR PIRSF; PIRSF003938; Flu_B_NS1; 1; trigger=no XX KW Host cytoplasm KW Host nucleus KW Host-virus interaction KW Viral immunoevasion KW Interferon antiviral system evasion KW Inhibition of host innate immune response by virus KW RNA-binding KW Inhibition of host interferon signaling pathway by virus case KW Eukaryotic host gene expression shutoff by virus KW Host gene expression shutoff by virus KW Host mRNA suppression by virus KW Inhibition of host PKR by virus KW Inhibition of host pre-mRNA processing by virus KW Inhibition of host RIG-I by virus KW Inhibition of host RLR pathway by virus KW Ubl conjugation else case KW Inhibition of host ISG15 by virus KW Inhibition of host PKR by virus else case KW Inhibition of host RIG-I by virus KW Inhibition of host RLR pathway by virus end case XX GO GO:0030430; C:host cell cytoplasm GO GO:0042025; C:host cell nucleus GO GO:0003723; F:RNA binding GO GO:0039502; P:suppression by virus of host type I interferon-mediated signaling pathway case GO GO:0039524; P:suppression by virus of host mRNA processing end case case and GO GO:0039540; P:suppression by virus of host viral-induced cytoplasmic pattern recognition receptor signaling pathway via inhibition of host RIG-I activity end case case and GO GO:0039580; P:suppression by virus of host PKR signaling end case XX FT From: NS1_I34A1 (P03496) case FT REGION Nter..73 FT /note="RNA-binding and homodimerization" FT REGION 180..215 FT /note="CPSF4-binding" FT REGION 223..230 FT /note="PABPN1-binding" FT MOTIF 34..38 FT /note="Nuclear localization signal" FT MOTIF 137..146 FT /note="Nuclear export signal" end case FT From: NS1_INBLE (P03502) case FT REGION Nter..93 FT /note="RNA-binding and homodimerization" FT MOTIF 50..55 FT /note="Nuclear localization signal" end case XX Size: 202-281; Related: None; Template: P03496; P03502; Scope: Viruses; Orthomyxoviridae Fusion: Nter: None Cter: None Duplicate: None Plasmid: None Comments: None XX # Revision 1.6 2023/03/07 //