ID NS1_I96A0 Reviewed; 230 AA.
AC Q9Q0L6;
DT 18-MAR-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 08-NOV-2023, entry version 102.
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};
GN Name=NS {ECO:0000255|HAMAP-Rule:MF_04066};
OS Influenza A virus (strain A/Goose/Guangdong/1/1996 H5N1 genotype Gs/Gd).
OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina;
OC Insthoviricetes; Articulavirales; Orthomyxoviridae; Alphainfluenzavirus;
OC Alphainfluenzavirus influenzae; Influenza A virus.
OX NCBI_TaxID=93838;
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=10484749; DOI=10.1006/viro.1999.9820;
RA Xu X., Subbarao K., Cox N.J., Guo Y.;
RT "Genetic characterization of the pathogenic influenza
RT A/Goose/Guangdong/1/96 (H5N1) virus: similarity of its hemagglutinin gene
RT to those of H5N1 viruses from the 1997 outbreaks in Hong Kong.";
RL Virology 261:15-19(1999).
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 {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=Q9Q0L6-1; Sequence=Displayed;
CC Name=NEP; Synonyms=NS2;
CC IsoId=Q9Q0L7-1; 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}.
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DR EMBL; AF144307; AAD51930.1; -; Genomic_RNA.
DR RefSeq; YP_308673.1; NC_007364.1. [Q9Q0L6-1]
DR SMR; Q9Q0L6; -.
DR IntAct; Q9Q0L6; 1.
DR GeneID; 8656648; -.
DR KEGG; vg:8656648; -.
DR OrthoDB; 8721at10239; -.
DR Proteomes; UP000131152; Genome.
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; Influenza virus non-structural protein, effector domain; 1.
DR Gene3D; 1.10.287.10; S15/NS1, RNA-binding; 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; uS15_NS1_RNA-bd_sf.
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; Reference proteome; RNA-binding;
KW Ubl conjugation; Viral immunoevasion.
FT CHAIN 1..230
FT /note="Non-structural protein 1"
FT /id="PRO_0000324282"
FT REGION 1..73
FT /note="RNA-binding and homodimerization"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04066"
FT REGION 180..215
FT /note="CPSF4-binding"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04066"
FT REGION 223..230
FT /note="PABPN1-binding"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04066"
FT MOTIF 34..38
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04066"
FT MOTIF 137..146
FT /note="Nuclear export signal"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04066"
SQ SEQUENCE 230 AA; 26095 MW; C4174DF7B731D442 CRC64;
MDSNTITSFQ VDCYLWHIRK LLSMRDMCDA PFDDRLRRDQ KALKGRGSTL GLDLRVATME
GKKIVEDILK SETNENLKIA IASSPAPRYI TDMSIEEMSR EWYMLMPRQK ITGGLMVKMD
QAIMDKRIIL KANFSVLFDQ LETLVSLRAF TESGAIVAEI FPIPSVPGHF TEDVKNAIGI
LIGGLEWNDN SIRASENIQR FAWGIHDENG GPSLPPKQKR YMAKRVESEV
//
