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UniProtKB - Q0HD54 (NS1_I40A0)

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Protein

Non-structural protein 1

Gene

NS

Organism
Influenza A virus (strain A/Hickox/1940 H1N1)
Status
Reviewed-Annotation score: Annotation score: 3 out of 5-Protein inferred from homologyi

Functioni

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 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.UniRule annotation
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. In turn, unprocessed 3' end pre-mRNAs accumulate in the host nucleus and are no longer exported to the cytoplasm. 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.UniRule annotation

GO - Molecular functioni

Complete GO annotation...

GO - Biological processi

Complete GO annotation...

Keywordsi

Molecular functionRNA-binding
Biological processEukaryotic 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

Names & Taxonomyi

Protein namesi
Recommended name:
Non-structural protein 1UniRule annotation
Short name:
NS1UniRule annotation
Alternative name(s):
NS1AUniRule annotation
Gene namesi
Name:NSUniRule annotation
OrganismiInfluenza A virus (strain A/Hickox/1940 H1N1)
Taxonomic identifieri383543 [NCBI]
Taxonomic lineageiViruses › ssRNA viruses › ssRNA negative-strand viruses › Orthomyxoviridae › Influenzavirus A ›
Virus hostiAves [TaxID: 8782]
Homo sapiens (Human) [TaxID: 9606]
Sus scrofa (Pig) [TaxID: 9823]
Proteomesi
  • UP000156248 Componenti: Genome

Subcellular locationi

  • Host nucleus UniRule annotation
  • Host cytoplasm UniRule annotation

    • 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.UniRule annotation

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Host cytoplasm, Host nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003729821 – 237Non-structural protein 1Add BLAST237

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.UniRule annotation

Keywords - PTMi

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.UniRule annotation

Protein-protein interaction databases

IntActiQ0HD54. 70 interactors.

Structurei

3D structure databases

ProteinModelPortaliQ0HD54.
SMRiQ0HD54.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 73RNA-binding and homodimerizationUniRule annotationAdd BLAST73
Regioni180 – 215CPSF4-bindingUniRule annotationAdd BLAST36
Regioni223 – 230PABPN1-bindingUniRule annotation8

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi34 – 38Nuclear localization signalUniRule annotation5
Motifi137 – 146Nuclear export signalUniRule annotation10

Domaini

The dsRNA-binding region is required for suppression of RNA silencing.UniRule annotation

Sequence similaritiesi

Belongs to the influenza A viruses NS1 family.UniRule annotation

Phylogenomic databases

OrthoDBiVOG090000NT.

Family and domain databases

HAMAPiMF_04066. INFV_NS1. 1 hit.
InterProiView protein in InterPro
IPR000256. Flu_NS1.
IPR009068. S15_NS1_RNA-bd.
PfamiView protein in Pfam
PF00600. Flu_NS1. 1 hit.
SUPFAMiSSF47060. SSF47060. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform NS1 (identifier: Q0HD54-1) [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
MDPNTVSSFQ VDCFLWHVRK RVADQELGDA PFLDRLRRDQ KSLKGRGSTL 
        60         70         80         90        100
GLNIETATRV GKQIVERILK EESDEALKMT MASAPASRYL TDMTIEEMSR 
       110        120        130        140        150
DWFMLMPKQK VAGPLCIRMD QAVMDKSIIL KANFSVIFDR LETLILLRAF 
       160        170        180        190        200
TEEGAIVGEI SPLPSLPGHT NEDVKNAIGV LIGGLEWNDN TVRVSKTLQR 
       210        220        230 
FAWRSSNENG GPPLTPKQKR KMARTIRSEV RRNKMVD
Length:237
Mass (Da):26,831
Last modified:October 3, 2006 - v1
Checksum:iE419A374F7DF4E34
GO
Isoform NEP (identifier: Q0HD55-1) [UniParc]FASTAAdd to basket
Also known as: NS2
The sequence of this isoform can be found in the external entry Q0HD55.
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.
Length:121
Mass (Da):14,452
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
CY013275 Other RNA. Translation: ABI20831.1.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
CY013275 Other RNA. Translation: ABI20831.1.

3D structure databases

ProteinModelPortaliQ0HD54.
SMRiQ0HD54.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ0HD54. 70 interactors.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Phylogenomic databases

OrthoDBiVOG090000NT.

Family and domain databases

HAMAPiMF_04066. INFV_NS1. 1 hit.
InterProiView protein in InterPro
IPR000256. Flu_NS1.
IPR009068. S15_NS1_RNA-bd.
PfamiView protein in Pfam
PF00600. Flu_NS1. 1 hit.
SUPFAMiSSF47060. SSF47060. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiNS1_I40A0
AccessioniPrimary (citable) accession number: Q0HD54
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 5, 2009
Last sequence update: October 3, 2006
Last modified: June 7, 2017
This is version 51 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

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 one 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.