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-NOV-2008, entry version 18. 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 silvestris catus (Cat). 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. This protein synthesis CC shut off is presumably necessary for the virus to escape CC interferon synthesis after activation of the IRF3 pathway, and CC therefore prevents establishment of cellular antiviral state. CC Viral protein synthesis is not affected by the inhibition of the CC cellular 3' end processing machinery because the poly(A) tails of CC viral mRNAs are produced by the viral polymerase, through a CC stuttering mechanism (By similarity). CC -!- FUNCTION: 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 (By similarity). Suppresses the RNA CC silencing-based antiviral response in Drosophila cells. CC -!- SUBUNIT: Homodimer. Interacts with human EIF2AK2/PKR, CPSF4, CC IVNS1ABP and PABPN1 (By similarity). CC -!- SUBCELLULAR LOCATION: Nucleus. 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 CC by a viral protein, and a fraction of NS1 is exported in the CC 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 SMR; Q2F4N6; 1-66. DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-KW. DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-KW. DR GO; GO:0003723; F:RNA binding; IEA:InterPro. DR GO; GO:0030683; P:evasion by virus of host immune response; IEA:UniProtKB-KW. DR InterPro; IPR000256; Flu_NS1. DR InterPro; IPR009068; S15_NS1_RNA_bd. DR Gene3D; G3DSA:1.10.287.10; S15_NS1_RNA_bd; 1. DR Pfam; PF00600; Flu_NS1; 1. DR ProDom; PD000613; Flu_NS1; 1. PE 3: Inferred from homology; KW Alternative splicing; Cytoplasm; Host-virus interaction; KW Interferon antiviral system evasion; Nucleus; 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 //