NS1_I02A3
ID NS1_I02A3 Reviewed; 230 AA.
AC Q6DP66;
DT 13-NOV-2007, integrated into UniProtKB/Swiss-Prot.
DT 16-AUG-2004, sequence version 1.
DT 23-FEB-2022, entry version 67.
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/Chicken/Hong Kong/37.4/2002 H5N1 genotype X2).
OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina;
OC Insthoviricetes; Articulavirales; Orthomyxoviridae; Alphainfluenzavirus.
OX NCBI_TaxID=284172;
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=15241415; DOI=10.1038/nature02746;
RA Li K.S., Guan Y., Wang J., Smith G.J.D., Xu K.M., Duan L., Rahardjo A.P.,
RA Puthavathana P., Buranathai C., Nguyen T.D., Estoepangestie A.T.S.,
RA Chaisingh A., Auewarakul P., Long H.T., Hanh N.T.H., Webby R.J.,
RA Poon L.L.M., Chen H., Shortridge K.F., Yuen K.Y., Webster R.G.,
RA Peiris J.S.M.;
RT "Genesis of a highly pathogenic and potentially pandemic H5N1 influenza
RT virus in eastern Asia.";
RL Nature 430:209-213(2004).
CC -!- FUNCTION: Prevents the establishment of the cellular antiviral state by
CC inhibiting TRIM25-mediated DDX58 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. Prevents
CC human EIF2AK2/PKR activation, either by binding double-strand RNA, or
CC by interacting directly with EIF2AK2/PKR. This function may be
CC important at the very beginning of the infection, when NS1 is mainly
CC present in the cytoplasm. Also binds poly(A) and U6 snRNA.
CC {ECO:0000255|HAMAP-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 DDX58 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=Q6DP66-1; Sequence=Displayed;
CC Name=NEP; Synonyms=NS2;
CC IsoId=Q6DP67-1; 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; AY651566; AAT73421.1; -; Genomic_RNA.
DR SMR; Q6DP66; -.
DR PRIDE; Q6DP66; -.
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; SSF143021; 1.
DR SUPFAM; SSF47060; SSF47060; 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..230
FT /note="Non-structural protein 1"
FT /id="PRO_0000311749"
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 205..230
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
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; 26029 MW; D14D92BC1F9CB1F5 CRC64;
MDSNTVSSFQ VDCFLWHVRK RFADQELGDA PFLDRLRRDQ KSLRGRGSTL GLDIETATRA
GKQIVERILE KESDEALKMT IASLPALRYL TDMTLEEMSR DWFMLMPKQK VAGSLCIRMD
QAIMDKTIIL KANFSVIFDR LETLILLRAF TEEGAIVGEI SPLPSLPGHT DEDVKNAIGV
LIGGLEWNDN TVRVSETLQR FAWRSSNEGG RPSLPPKQKR KMARTTESEV
