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 31-OCT-2012, entry version 31. DE RecName: Full=Non-structural protein 1; DE Short=NS1; DE AltName: Full=NS1A; DE Flags: Fragment; GN Name=NS; OS Influenza A virus (strain A/Goose/Guangxi/345/2005 H5N1 genotype G). OC Viruses; ssRNA negative-strand viruses; Orthomyxoviridae; OC Influenzavirus A. 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). 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: 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 (By similarity). 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 (By similarity). 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 (By similarity). CC -!- SUBCELLULAR LOCATION: Host nucleus. Host cytoplasm. Note=In CC uninfected, transfected cells, NS1 is localized in the nucleus. CC Only in virus infected cells, the nuclear export signal is CC unveiled, presumably by a viral protein, and a fraction of NS1 is CC exported in the cytoplasm (By similarity). 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 (By similarity). CC -!- SIMILARITY: Belongs to the influenza A viruses NS1 family. 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; 1-68, 75-196. 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:0030683; P:evasion or tolerance by virus of host immune response; IEA:UniProtKB-KW. DR GO; GO:0039524; P:suppression by virus of host mRNA processing; IEA:UniProtKB-KW. DR Gene3D; G3DSA:1.10.287.10; S15_NS1_RNA_bd; 1. DR InterPro; IPR000256; Flu_NS1. DR InterPro; IPR009068; S15_NS1_RNA-bd. DR Pfam; PF00600; Flu_NS1; 1. DR SUPFAM; SSF47060; S15/NS1_bind; 1. PE 3: Inferred from homology; KW Alternative splicing; Host cytoplasm; KW Host gene expression shutoff by virus; Host mRNA suppression by virus; KW Host nucleus; Host-virus interaction; KW Inhibition of host pre-mRNA processing by virus; KW Interferon antiviral system evasion; RNA-binding; KW Suppressor of RNA silencing. FT CHAIN <1 219 Non-structural protein 1. FT /FTId=PRO_0000311756. FT REGION <1 69 RNA-binding (By similarity). FT REGION 171 206 CPSF4-binding (By similarity). FT MOTIF 30 34 Nuclear localization signal 1 (By FT similarity). FT MOTIF 128 137 Nuclear export signal (By similarity). FT MOTIF 207 212 Nuclear localization signal 2 (By FT similarity). 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 //