NS1_I82A2
ID NS1_I82A2 Reviewed; 90 AA.
AC P26148;
DT 01-MAY-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1992, sequence version 1.
DT 03-AUG-2022, entry version 89.
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/Camel/Mongolia/1982 H1N1).
OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina;
OC Insthoviricetes; Articulavirales; Orthomyxoviridae; Alphainfluenzavirus.
OX NCBI_TaxID=387191;
OH NCBI_TaxID=8782; Aves.
OH NCBI_TaxID=9606; Homo sapiens (Human).
OH NCBI_TaxID=9823; Sus scrofa (Pig).
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=8249279; DOI=10.1006/viro.1993.1629;
RA Yamnikova S.S., Mandler J., Bekh-Ochir Z.H., Dachtzeren P., Ludwig S.,
RA Lvov D.K., Scholtissek C.;
RT "A reassortant H1N1 influenza A virus caused fatal epizootics among camels
RT in Mongolia.";
RL Virology 197:558-563(1993).
RN [2]
RP REVIEW.
RX PubMed=12758165; DOI=10.1016/s0042-6822(03)00119-3;
RA Krug R.M., Yuan W., Noah D.L., Latham A.G.;
RT "Intracellular warfare between human influenza viruses and human cells: the
RT roles of the viral NS1 protein.";
RL Virology 309:181-189(2003).
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). This results in the accumulation of unprocessed 3'
CC end pre-mRNAs which can't be exported from the nucleus. 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 (By similarity). {ECO:0000250}.
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 like IRF3 and IRF7.
CC Prevents human EIF2AK2/PKR activation, either by binding double-strand
CC RNA, or 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. Suppresses
CC the RNA silencing-based antiviral response in Drosophila cells (By
CC similarity). {ECO:0000250}.
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 (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Host nucleus. Host 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 by a
CC viral protein, and a fraction of NS1 is exported in the cytoplasm (By
CC similarity). {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=NS1;
CC IsoId=P26148-1; Sequence=Displayed;
CC Name=NEP; Synonyms=NS2;
CC IsoId=P26148-2; Sequence=Not described;
CC -!- DOMAIN: The dsRNA-binding region is required for suppression of RNA
CC silencing. {ECO:0000250}.
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 There are two ISGylated forms (By similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the influenza A viruses NS1 family.
CC {ECO:0000305}.
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; M73977; AAA16908.2; -; mRNA.
DR SMR; P26148; -.
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:0039524; P:suppression by virus of host mRNA processing; IEA:UniProtKB-KW.
DR Gene3D; 3.30.420.330; -; 1.
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 2: Evidence at transcript level;
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 pre-mRNA processing by virus;
KW Interferon antiviral system evasion; Isopeptide bond; RNA-binding;
KW Ubl conjugation.
FT CHAIN <1..>90
FT /note="Non-structural protein 1"
FT /id="PRO_0000078919"
FT REGION <1..61
FT /note="RNA-binding and homodimerization"
FT /evidence="ECO:0000250"
FT MOTIF 22..26
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000250"
FT CROSSLNK 8
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ISG15); in band I form; by host"
FT /evidence="ECO:0000250"
FT CROSSLNK 29
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ISG15); in band I form; by host"
FT /evidence="ECO:0000250"
FT NON_TER 1
FT NON_TER 90
SQ SEQUENCE 90 AA; 10396 MW; 5F11F851E5CE0037 CRC64;
CFLWHVRKRV ADQELGDAPF LDRLRRDQKS LRGRGSTLGL DIKTATRAGK QIVERILKEE
SDEALKMTMA SVPASRYLTD MTLEEMSRDW
