P13137 · NS1_I76A5
- ProteinNon-structural protein 1
- GeneNS
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids230 (go to sequence)
- Protein existenceInferred from homology
- Annotation score3/5
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 annotations | all molecular function | virus receptor activity | dna binding | rna binding | cytoskeletal motor activity | catalytic activity | gtpase activity | structural molecule activity | transporter activity | cytoskeletal protein binding | lipid binding | cyclase activity | antioxidant activity | oxidoreductase activity | transferase activity | hydrolase activity | lyase activity | isomerase activity | ligase activity | protein tag activity | cargo receptor activity | histone binding | protein folding chaperone | translation regulator activity | nutrient reservoir activity | receptor ligand activity | molecular transducer activity | molecular adaptor activity | toxin activity | cell adhesion mediator activity | molecular function regulator activity | virus coreceptor activity | catalytic activity, acting on a protein | catalytic activity, acting on dna | catalytic activity, acting on rna | molecular carrier activity | transcription regulator activity | general transcription initiation factor activity | molecular sensor activity | molecular sequestering activity | atp-dependent activity | other molecular function | all biological process | mitotic cell cycle | cytokinesis | cytoplasmic translation | immune system process | muscle system process | circulatory system process | renal system process | respiratory system process | carbohydrate metabolic process | generation of precursor metabolites and energy | dna replication | dna repair | dna recombination | chromatin organization | dna-templated transcription | regulation of dna-templated transcription | trna metabolic process | protein folding | protein glycosylation | amino acid metabolic process | modified amino acid metabolic process | lipid metabolic process | vitamin metabolic process | sulfur compound metabolic process | intracellular protein transport | nucleocytoplasmic transport | autophagy | inflammatory response | mitochondrion organization | cytoskeleton organization | microtubule-based movement | peroxisome organization | lysosome organization | chromosome segregation | cell adhesion | establishment or maintenance of cell polarity | programmed cell death | photosynthesis | mrna metabolic process | snrna metabolic process | vesicle-mediated transport | reproductive process | digestive system process | signaling | cell differentiation | protein catabolic process | extracellular matrix organization | regulatory ncrna-mediated gene silencing | telomere organization | cell junction organization | wound healing | ribosome biogenesis | cilium organization | anatomical structure development | cell motility | nervous system process | endocrine process | protein maturation | transmembrane transport | nucleobase-containing small molecule metabolic process | hepaticobiliary system process | membrane organization | protein-containing complex assembly | cell wall organization or biogenesis | nitrogen cycle metabolic process | protein localization to plasma membrane | defense response to other organism | detoxification | meiotic nuclear division | mitotic nuclear division | mitochondrial gene expression | carbohydrate derivative metabolic process | other biological process | all cellular component | nuclear chromosome | extracellular region | extracellular space | cell wall | nucleus | nuclear envelope | nucleoplasm | chromosome | nucleolus | mitochondrion | lysosome | endosome | vacuole | peroxisome | endoplasmic reticulum | golgi apparatus | lipid droplet | microtubule organizing center | cytosol | ribosome | cytoskeleton | plasma membrane | cilium | plastid | thylakoid | external encapsulating structure | extracellular matrix | cytoplasmic vesicle | organelle | other cellular component | |||
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Aspect | Term | |
---|---|---|
Cellular Component | host cell cytoplasm | |
Cellular Component | host cell nucleus | |
Molecular Function | protein serine/threonine kinase inhibitor activity | |
Molecular Function | RNA binding | |
Biological Process | symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of RIG-I activity | |
Biological Process | symbiont-mediated suppression of host mRNA processing | |
Biological Process | symbiont-mediated suppression of host PKR/eIFalpha signaling | |
Biological Process | symbiont-mediated suppression of host type I interferon-mediated signaling pathway | |
Biological Process | virus-mediated perturbation of host defense response |
Keywords
- Molecular function
- Biological process
Names & Taxonomy
Protein names
- Recommended nameNon-structural protein 1
- Short namesNS1
- Alternative names
Gene names
Organism names
- Taxonomic lineageViruses > Riboviria > Orthornavirae > Negarnaviricota > Polyploviricotina > Insthoviricetes > Articulavirales > Orthomyxoviridae > Alphainfluenzavirus > Alphainfluenzavirus influenzae > Influenza A virus
- Virus hosts
Accessions
- Primary accessionP13137
Subcellular Location
UniProt Annotation
GO 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.
Keywords
- Cellular component
PTM/Processing
Features
Showing features for chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000078936 | 1-230 | Non-structural protein 1 | |||
Sequence: MDSNTVTSFQVDCYLWHIRKLLSMRDMCDAPFDDRLRRDQKALKGRGSTLGLDLRVATMEGKKVVEDILKSETDENLKIAIASSPAPRYITDMSIEEISREWYMLMPRQKITGGLMVKMDQAIMDKRITLKANFSVLFDQLETLVSLRAFTDDGAIVAEISPIPSMPGHSTEDVKNAIGILIGGLEWNDNSIRASENIQRFAWGIRDENGGPPLPPKQKRYMARRVESEV |
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
- PTM
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.
Family & Domains
Features
Showing features for region, motif.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-73 | RNA-binding and homodimerization | ||||
Sequence: MDSNTVTSFQVDCYLWHIRKLLSMRDMCDAPFDDRLRRDQKALKGRGSTLGLDLRVATMEGKKVVEDILKSET | ||||||
Motif | 34-38 | Nuclear localization signal | ||||
Sequence: DRLRR | ||||||
Motif | 137-146 | Nuclear export signal | ||||
Sequence: LFDQLETLVS | ||||||
Region | 180-215 | CPSF4-binding | ||||
Sequence: ILIGGLEWNDNSIRASENIQRFAWGIRDENGGPPLP | ||||||
Region | 209-230 | Disordered | ||||
Sequence: NGGPPLPPKQKRYMARRVESEV | ||||||
Region | 223-230 | PABPN1-binding | ||||
Sequence: ARRVESEV |
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
- Sequence statusComplete
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.
- NameNS1
- Length230
- Mass (Da)26,021
- Last updated1991-05-01 v2
- Checksum39BC9521FAFA9590
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- NameNEP
- SynonymsNS2
Keywords
- Coding sequence diversity