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A8C8K0 - NS1_I07A0

UniProt

A8C8K0 - NS1_I07A0

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Protein

Non-structural protein 1

Gene

NS

Organism
Influenza A virus (strain A/USA:Texas/UR06-0195/2007 H1N1)
Status
Reviewed-Annotation score: Annotation score: 3 out of 5-Protein inferred from homologyi

Functioni

Inhibits post-transcriptional processing of cellular pre-mRNA, by binding and inhibiting two cellular proteins that are required for the 3'-end processing of cellular pre-mRNAs: the 30 kDa cleavage and polyadenylation specificity factor (CPSF4) and the poly(A)-binding protein 2 (PABPN1). This results in the accumulation of unprocessed 3' end pre-mRNAs which can't be exported from the nucleus. Cellular protein synthesis is thereby shut off very early after virus infection. Viral protein synthesis is not affected by the inhibition of the cellular 3' end processing machinery because the poly(A) tails of viral mRNAs are produced by the viral polymerase through a stuttering mechanism (By similarity).By similarity
Prevents the establishment of the cellular antiviral state by inhibiting TRIM25-mediated DDX58 ubiquitination, which normally triggers the antiviral transduction signal that leads to the activation of type I IFN genes by transcription factors like IRF3 and IRF7. Prevents human EIF2AK2/PKR activation, either by binding double-strand RNA, or by interacting directly with EIF2AK2/PKR. This function may be important at the very beginning of the infection, when NS1 is mainly present in the cytoplasm. Also binds poly(A) and U6 snRNA. Suppresses the RNA silencing-based antiviral response in Drosophila cells (By similarity).By similarity

GO - Molecular functioni

  1. RNA binding Source: UniProtKB-KW

GO - Biological processi

  1. suppression by virus of host mRNA processing Source: UniProtKB-KW
  2. suppression by virus of host PKR activity Source: UniProtKB-KW
  3. suppression by virus of host RIG-I activity Source: UniProtKB-KW
  4. suppression by virus of host type I interferon-mediated signaling pathway Source: UniProtKB-KW
Complete GO annotation...

Keywords - Biological processi

Eukaryotic host gene expression shutoff by virus, Host gene expression shutoff by virus, Host mRNA suppression by virus, Host-virus interaction, Inhibition of host innate immune response by virus, Inhibition of host interferon signaling pathway by virus, Inhibition of host PKR by virus, Inhibition of host pre-mRNA processing by virus, Inhibition of host RIG-I by virus, Inhibition of host RLR pathway by virus, Interferon antiviral system evasion, Viral immunoevasion

Keywords - Ligandi

RNA-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Non-structural protein 1
Short name:
NS1
Alternative name(s):
NS1A
Gene namesi
Name:NS
OrganismiInfluenza A virus (strain A/USA:Texas/UR06-0195/2007 H1N1)
Taxonomic identifieri455880 [NCBI]
Taxonomic lineageiViruses › ssRNA negative-strand viruses › Orthomyxoviridae › Influenzavirus A ›
Virus hostiAves [TaxID: 8782]
Homo sapiens (Human) [TaxID: 9606]
Sus scrofa (Pig) [TaxID: 9823]

Subcellular locationi

Host nucleus. Host cytoplasm
Note: In uninfected, transfected cells, NS1 is localized in the nucleus. Only in virus infected cells, the nuclear export signal is unveiled, presumably by a viral protein, and a fraction of NS1 is exported in the cytoplasm (By similarity).By similarity

GO - Cellular componenti

  1. host cell cytoplasm Source: UniProtKB-SubCell
  2. host cell nucleus Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Host cytoplasm, Host nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 230230Non-structural protein 1PRO_0000372979Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Cross-linki20 – 20Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15); in band I form; by hostBy similarity
Cross-linki41 – 41Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15); in band I form; by hostBy similarity
Cross-linki108 – 108Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15); in band II form; by hostBy similarity
Cross-linki110 – 110Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15); in band II form; by hostBy similarity
Cross-linki126 – 126Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15); in band II form; by hostBy similarity
Cross-linki219 – 219Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ISG15); in band I form; by hostBy similarity

Post-translational modificationi

Upon interferon induction, ISGylated via host HERC5; this results in the impairment of NS1 interaction with RNA targets due to its inability to form homodimers and to interact with host EIF2AK2/PKR. There are two ISGylated forms: one form is ISGylated at Lys-20, Lys-41 and Lys-219, and another one at Lys-108, Lys-110, and Lys-126, they represent band I and II respectively. Lys-126 is critical for host antiviral response in vivo (By similarity).By similarity

Keywords - PTMi

Isopeptide bond, Ubl conjugation

Interactioni

Subunit structurei

Homodimer. Interacts with host TRIM25 (via coiled coil); this interaction specifically inhibits TRIM25 multimerization and TRIM25-mediated DDX58 CARD ubiquitination. Interacts with human EIF2AK2/PKR, CPSF4, IVNS1ABP and PABPN1 (By similarity).By similarity

Structurei

3D structure databases

ProteinModelPortaliA8C8K0.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 7373RNA-binding and homodimerizationBy similarityAdd
BLAST
Regioni180 – 21536CPSF4-bindingBy similarityAdd
BLAST
Regioni223 – 2308PABPN1-bindingBy similarity

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi34 – 385Nuclear localization signal 1By similarity
Motifi137 – 14610Nuclear export signalBy similarity
Motifi216 – 2216Nuclear localization signal 2By similarity

Domaini

The dsRNA-binding region is required for suppression of RNA silencing.By similarity

Sequence similaritiesi

Belongs to the influenza A viruses NS1 family.Curated

Family and domain databases

Gene3Di1.10.287.10. 1 hit.
InterProiIPR000256. Flu_NS1.
IPR009068. S15_NS1_RNA-bd.
[Graphical view]
PfamiPF00600. Flu_NS1. 1 hit.
[Graphical view]
SUPFAMiSSF47060. SSF47060. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. Align

Isoform NS1 (identifier: A8C8K0-1) [UniParc]FASTAAdd to Basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MDSHTVSSFQ VDCFLWHVRK QVADQDLGDA PFLDRLRRDQ KSLKGRGSTL 
        60         70         80         90        100
GLNIETATCV GKQIVERILK EESDEALKMT MASALASRYL TDMTVEEMSR 
       110        120        130        140        150
DWFMLMPKQK VAGPLCVRMD QAIMDKNIIL KANFSVIFDR LENLTLLRAF 
       160        170        180        190        200
TEEGAIVGEI SPLPSFPGHT NEDVKNAIGV LIGGLEWNDN TVRVSETLQR 
       210        220        230
FAWRSSNETG GPPFTTTQKR KMAGTTRSEI
Length:230
Mass (Da):25,815
Last modified:November 13, 2007 - v1
Checksum:iEB0B53149B12F196
GO
Isoform NEP (identifier: A8C8J9-1) [UniParc]FASTAAdd to Basket

Also known as: NS2

The sequence of this isoform can be found in the external entry A8C8J9.
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.
Length:121
Mass (Da):14,285
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
CY026215 Viral cRNA. Translation: ABV45931.1.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
CY026215 Viral cRNA. Translation: ABV45931.1.

3D structure databases

ProteinModelPortaliA8C8K0.
ModBaseiSearch...
MobiDBiSearch...

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Family and domain databases

Gene3Di1.10.287.10. 1 hit.
InterProiIPR000256. Flu_NS1.
IPR009068. S15_NS1_RNA-bd.
[Graphical view]
PfamiPF00600. Flu_NS1. 1 hit.
[Graphical view]
SUPFAMiSSF47060. SSF47060. 1 hit.
ProtoNetiSearch...

Publicationsi

  1. Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
  2. The NIAID Influenza Genome Sequencing Consortium
    Submitted (SEP-2007) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].

Entry informationi

Entry nameiNS1_I07A0
AccessioniPrimary (citable) accession number: A8C8K0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 5, 2009
Last sequence update: November 13, 2007
Last modified: January 7, 2015
This is version 38 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Miscellaneousi

Documents

  1. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.