ID NS1_I05A1 Reviewed; 219 AA. AC Q2F4N6; DT 13-NOV-2007, integrated into UniProtKB/Swiss-Prot. DT 21-MAR-2006, sequence version 1. DT 25-APR-2018, entry version 54. DE RecName: Full=Non-structural protein 1 {ECO:0000255|HAMAP-Rule:MF_04066}; DE Short=NS1 {ECO:0000255|HAMAP-Rule:MF_04066}; DE AltName: Full=NS1A {ECO:0000255|HAMAP-Rule:MF_04066}; DE Flags: Fragment; GN Name=NS {ECO:0000255|HAMAP-Rule:MF_04066}; OS Influenza A virus (strain A/Goose/Guangxi/345/2005 H5N1 genotype G). OC Viruses; ssRNA viruses; ssRNA negative-strand viruses; OC Orthomyxoviridae; Alphainfluenzavirus. OX NCBI_TaxID=365089; OH NCBI_TaxID=8782; Aves. OH NCBI_TaxID=9685; Felis catus (Cat) (Felis silvestris catus). OH NCBI_TaxID=9606; Homo sapiens (Human). OH NCBI_TaxID=9691; Panthera pardus (Leopard) (Felis pardus). OH NCBI_TaxID=9694; Panthera tigris (Tiger). OH NCBI_TaxID=9823; Sus scrofa (Pig). RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC RNA]. RX PubMed=17075062; DOI=10.1073/pnas.0608157103; RA Smith G.J., Fan X.H., Wang J., Li K.S., Qin K., Zhang J.X., RA Vijaykrishna D., Cheung C.L., Huang K., Rayner J.M., Peiris J.S., RA Chen H., Webster R.G., Guan Y.; RT "Emergence and predominance of an H5N1 influenza variant in China."; RL Proc. Natl. Acad. Sci. U.S.A. 103:16936-16941(2006). 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 IRF3 CC and IRF7. Prevents human EIF2AK2/PKR activation, either by binding CC double-strand RNA, or by interacting directly with EIF2AK2/PKR. CC This function may be important at the very beginning of the CC infection, when NS1 is mainly present in the cytoplasm. Also binds CC poly(A) and U6 snRNA. {ECO:0000255|HAMAP-Rule:MF_04066}. 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 the CC poly(A)-binding protein 2/PABPN1. In turn, unprocessed 3' end pre- CC mRNAs accumulate in the host nucleus and are no longer exported to CC the cytoplasm. Cellular protein synthesis is thereby shut off very CC early after virus infection. Viral protein synthesis is not CC affected by the inhibition of the cellular 3' end processing CC machinery because the poly(A) tails of viral mRNAs are produced by CC the viral polymerase through a stuttering mechanism. CC {ECO:0000255|HAMAP-Rule:MF_04066}. 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. {ECO:0000255|HAMAP- CC Rule:MF_04066}. CC -!- SUBCELLULAR LOCATION: Host nucleus {ECO:0000255|HAMAP- CC Rule:MF_04066}. Host cytoplasm {ECO:0000255|HAMAP-Rule:MF_04066}. CC Note=In uninfected, transfected cells, NS1 is localized in the CC nucleus. Only in virus infected cells, the nuclear export signal CC is unveiled, presumably by a viral protein, and a fraction of NS1 CC is exported in the cytoplasm. {ECO:0000255|HAMAP-Rule:MF_04066}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=NS1; CC IsoId=Q2F4N6-1; Sequence=Displayed; CC Name=NEP; Synonyms=NS2; CC IsoId=P0C5U4-1; Sequence=External; CC -!- DOMAIN: The dsRNA-binding region is required for suppression of CC RNA silencing. {ECO:0000255|HAMAP-Rule:MF_04066}. CC -!- PTM: Upon interferon induction, ISGylated via host HERC5; this CC results in the impairment of NS1 interaction with RNA targets due CC to its inability to form homodimers and to interact with host CC EIF2AK2/PKR. {ECO:0000255|HAMAP-Rule:MF_04066}. CC -!- SIMILARITY: Belongs to the influenza A viruses NS1 family. CC {ECO:0000255|HAMAP-Rule:MF_04066}. 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; DQ321159; ABC68544.1; -; Genomic_RNA. DR ProteinModelPortal; Q2F4N6; -. DR SMR; Q2F4N6; -. 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; 3.30.420.330; -; 1. DR HAMAP; MF_04066; INFV_NS1; 1. DR InterPro; IPR004208; NS1. DR InterPro; IPR000256; NS1A. DR InterPro; IPR038064; NS1A_effect_dom_like_sp. DR InterPro; IPR009068; S15_NS1_RNA-bd. DR Pfam; PF00600; Flu_NS1; 1. DR SUPFAM; SSF143021; SSF143021; 1. DR SUPFAM; SSF47060; SSF47060; 1. PE 3: Inferred from homology; KW Alternative splicing; KW Eukaryotic host gene expression shutoff by virus; Host cytoplasm; KW Host gene expression shutoff by virus; Host mRNA suppression by virus; KW Host nucleus; Host-virus interaction; KW Inhibition of host innate immune response by virus; KW Inhibition of host interferon signaling pathway 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 Interferon antiviral system evasion; RNA-binding; Ubl conjugation; KW Viral immunoevasion. FT CHAIN <1 219 Non-structural protein 1. FT /FTId=PRO_0000311756. FT REGION 171 206 CPSF4-binding. {ECO:0000255|HAMAP- FT Rule:MF_04066}. FT MOTIF 30 34 Nuclear localization signal. FT {ECO:0000255|HAMAP-Rule:MF_04066}. FT MOTIF 128 137 Nuclear export signal. FT {ECO:0000255|HAMAP-Rule:MF_04066}. FT NON_TER 1 1 SQ SEQUENCE 219 AA; 24878 MW; 229E9B3CA4102752 CRC64; TVSSFQVDCF LWHVRKRFAD QELGDAPFLD RLRRDQKSLR GRGNTLGLDI ETATRAGKQI VERILEEESD EALKMPASRY LTDMTLEEMS RDWFMLMPKQ KVAGSLSIKM DQAIMDKNIT LKANFNVIFD RLETLILLRA FTEEGAIVGE ISPLPSLPGH TDEDVKNAIG VLIGGLEWND NTVRVSEALQ RFAWRSSDKN GRPPLPSNQK RKMARTIES //