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 14-DEC-2022, entry version 64. 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; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina; OC Insthoviricetes; Articulavirales; 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., Chen H., RA 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 state by CC inhibiting TRIM25-mediated RIGI ubiquitination, which normally triggers CC the antiviral transduction signal that leads to the activation of type CC I IFN genes by transcription factors IRF3 and IRF7. Prevents human CC EIF2AK2/PKR activation, either by binding double-strand RNA, or by CC interacting directly with EIF2AK2/PKR. This function may be important CC at the very beginning of the infection, when NS1 is mainly present in CC the cytoplasm. Also binds poly(A) and U6 snRNA. {ECO:0000255|HAMAP- CC Rule:MF_04066}. 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. {ECO:0000255|HAMAP-Rule:MF_04066}. 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:0000255|HAMAP-Rule:MF_04066}. CC -!- SUBCELLULAR LOCATION: Host nucleus {ECO:0000255|HAMAP-Rule:MF_04066}. CC Host cytoplasm {ECO:0000255|HAMAP-Rule:MF_04066}. 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 {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 RNA CC silencing. {ECO:0000255|HAMAP-Rule:MF_04066}. 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 {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 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: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-KW. 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; -; 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 Alternative splicing; Eukaryotic host gene expression shutoff by virus; KW Host cytoplasm; Host gene expression shutoff by virus; KW Host mRNA suppression by virus; 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; Inhibition of host RLR pathway by virus; KW Interferon antiviral system evasion; RNA-binding; Ubl conjugation; KW Viral immunoevasion. FT CHAIN <1..219 FT /note="Non-structural protein 1" FT /id="PRO_0000311756" FT REGION 171..206 FT /note="CPSF4-binding" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04066" FT REGION 196..219 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 30..34 FT /note="Nuclear localization signal" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04066" FT MOTIF 128..137 FT /note="Nuclear export signal" FT /evidence="ECO:0000255|HAMAP-Rule:MF_04066" FT NON_TER 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 //