P13137 · NS1_I76A5

Function

function

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. Prevents the establishment of the cellular antiviral state by inhibiting TRIM25-mediated RIGI ubiquitination, which normally triggers the antiviral transduction signal that leads to the activation of type I IFN genes by transcription factors IRF3 and IRF7. Also binds poly(A) and U6 snRNA. Inhibits the integrated stress response (ISR) in the infected cell by blocking dsRNA binding by EIF2AK2/PKR and further phosphorylation of EIF2S1/EIF-2ALPHA. Stress granule formation is thus inhibited, which allows protein synthesis and viral replication.

GO annotations

all annotationsall molecular functionvirus receptor activitydna bindingrna bindingcytoskeletal motor activitycatalytic activitygtpase activitystructural molecule activitytransporter activitycytoskeletal protein bindinglipid bindingcyclase activityantioxidant activityoxidoreductase activitytransferase activityhydrolase activitylyase activityisomerase activityligase activityprotein tag activitycargo receptor activityhistone bindingprotein folding chaperonetranslation regulator activitynutrient reservoir activityreceptor ligand activitymolecular transducer activitymolecular adaptor activitytoxin activitycell adhesion mediator activitymolecular function regulator activityvirus coreceptor activitycatalytic activity, acting on a proteincatalytic activity, acting on dnacatalytic activity, acting on rnamolecular carrier activitytranscription regulator activitygeneral transcription initiation factor activitymolecular sensor activitymolecular sequestering activityatp-dependent activityother molecular functionall biological processmitotic cell cyclecytokinesiscytoplasmic translationimmune system processmuscle system processcirculatory system processrenal system processrespiratory system processcarbohydrate metabolic processgeneration of precursor metabolites and energydna replicationdna repairdna recombinationchromatin organizationdna-templated transcriptionregulation of dna-templated transcriptiontrna metabolic processprotein foldingprotein glycosylationamino acid metabolic processmodified amino acid metabolic processlipid metabolic processvitamin metabolic processsulfur compound metabolic processintracellular protein transportnucleocytoplasmic transportautophagyinflammatory responsemitochondrion organizationcytoskeleton organizationmicrotubule-based movementperoxisome organizationlysosome organizationchromosome segregationcell adhesionestablishment or maintenance of cell polarityprogrammed cell deathphotosynthesismrna metabolic processsnrna metabolic processvesicle-mediated transportreproductive processdigestive system processsignalingcell differentiationprotein catabolic processextracellular matrix organizationregulatory ncrna-mediated gene silencingtelomere organizationcell junction organizationwound healingribosome biogenesiscilium organizationanatomical structure developmentcell motilitynervous system processendocrine processprotein maturationtransmembrane transportnucleobase-containing small molecule metabolic processhepaticobiliary system processmembrane organizationprotein-containing complex assemblycell wall organization or biogenesisnitrogen cycle metabolic processprotein localization to plasma membranedefense response to other organismdetoxificationmeiotic nuclear divisionmitotic nuclear divisionmitochondrial gene expressioncarbohydrate derivative metabolic processother biological processall cellular componentnuclear chromosomeextracellular regionextracellular spacecell wallnucleusnuclear envelopenucleoplasmchromosomenucleolusmitochondrionlysosomeendosomevacuoleperoxisomeendoplasmic reticulumgolgi apparatuslipid dropletmicrotubule organizing centercytosolribosomecytoskeletonplasma membraneciliumplastidthylakoidexternal encapsulating structureextracellular matrixcytoplasmic vesicleorganelleother cellular component
Cell color indicative of number of GO terms
AspectTerm
Cellular Componenthost cell cytoplasm
Cellular Componenthost cell nucleus
Molecular Functionprotein serine/threonine kinase inhibitor activity
Molecular FunctionRNA binding
Biological Processsymbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of RIG-I activity
Biological Processsymbiont-mediated suppression of host mRNA processing
Biological Processsymbiont-mediated suppression of host PKR/eIFalpha signaling
Biological Processsymbiont-mediated suppression of host type I interferon-mediated signaling pathway
Biological Processvirus-mediated perturbation of host defense response

Keywords

Names & Taxonomy

Protein names

  • Recommended name
    Non-structural protein 1
  • Short names
    NS1
  • Alternative names
    • NS1A

Gene names

    • Name
      NS

Organism names

Accessions

  • Primary accession
    P13137

Subcellular Location

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.

Keywords

PTM/Processing

Features

Showing features for chain.

TypeIDPosition(s)Description
ChainPRO_00000789361-230Non-structural protein 1

Post-translational modification

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.

Keywords

Interaction

Subunit

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

Structure

3D structure databases

Family & Domains

Features

Showing features for region, motif.

TypeIDPosition(s)Description
Region1-73RNA-binding and homodimerization
Motif34-38Nuclear localization signal
Motif137-146Nuclear export signal
Region180-215CPSF4-binding
Region209-230Disordered
Region223-230PABPN1-binding

Domain

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

Sequence similarities

Belongs to the influenza A viruses NS1 family.

Family and domain databases

Sequence & Isoform

Align isoforms (2)
  • Sequence status
    Complete

This entry describes 2 isoforms produced by Alternative splicing.

P13137-1

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.

  • Name
    NS1
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Length
    230
  • Mass (Da)
    26,021
  • Last updated
    1991-05-01 v2
  • Checksum
    39BC9521FAFA9590
MDSNTVTSFQVDCYLWHIRKLLSMRDMCDAPFDDRLRRDQKALKGRGSTLGLDLRVATMEGKKVVEDILKSETDENLKIAIASSPAPRYITDMSIEEISREWYMLMPRQKITGGLMVKMDQAIMDKRITLKANFSVLFDQLETLVSLRAFTDDGAIVAEISPIPSMPGHSTEDVKNAIGILIGGLEWNDNSIRASENIQRFAWGIRDENGGPPLPPKQKRYMARRVESEV

P13145-1

The sequence of this isoform can be found in the external entry linked below. Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.

View isoform
  • Name
    NEP
  • Synonyms
    NS2
  • See also
    sequence in UniParc or sequence clusters in UniRef

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
M25373
EMBL· GenBank· DDBJ
AAA43531.1
EMBL· GenBank· DDBJ
Genomic RNA

Similar Proteins

Disclaimer

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