UniProtKB - Q38SQ2 (NS1_I83A8)
Non-structural protein 1
NS
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 annotationInhibits 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 annotationGO - Molecular functioni
- protein serine/threonine kinase inhibitor activity Source: UniProtKB-KW
- RNA binding Source: UniProtKB-KW
GO - Biological processi
- suppression by virus of host mRNA processing Source: UniProtKB-KW
- suppression by virus of host PKR signaling Source: UniProtKB-KW
- suppression by virus of host type I interferon-mediated signaling pathway Source: UniProtKB-KW
- suppression by virus of host viral-induced cytoplasmic pattern recognition receptor signaling pathway via inhibition of host RIG-I activity Source: UniProtKB-KW
Keywordsi
Names & Taxonomyi
Protein namesi | Recommended name: Non-structural protein 1UniRule annotationShort name: NS1UniRule annotation Alternative name(s): NS1AUniRule annotation |
Gene namesi | Name:NSUniRule annotation |
Organismi | Influenza A virus (strain A/Hong Kong/5/1983 H3N2) |
Taxonomic identifieri | 387159 [NCBI] |
Taxonomic lineagei | Viruses › Riboviria › Orthornavirae › Negarnaviricota › Polyploviricotina › Insthoviricetes › Articulavirales › Orthomyxoviridae › Alphainfluenzavirus › |
Virus hosti | Aves [TaxID: 8782] Cetacea (whales) [TaxID: 9721] Homo sapiens (Human) [TaxID: 9606] Phocidae (true seals) [TaxID: 9709] Sus scrofa (Pig) [TaxID: 9823] |
Proteomesi |
|
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
Keywords - Cellular componenti
Host cytoplasm, Host nucleusPTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000324274 | 1 – 237 | Non-structural protein 1Add BLAST | 237 |
Post-translational modificationi
Keywords - PTMi
Ubl conjugationInteractioni
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 annotationFamily & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 1 – 73 | RNA-binding and homodimerizationUniRule annotationAdd BLAST | 73 | |
Regioni | 180 – 215 | CPSF4-bindingUniRule annotationAdd BLAST | 36 | |
Regioni | 205 – 237 | DisorderedSequence analysisAdd BLAST | 33 | |
Regioni | 223 – 230 | PABPN1-bindingUniRule annotation | 8 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 34 – 38 | Nuclear localization signalUniRule annotation | 5 | |
Motifi | 137 – 146 | Nuclear export signalUniRule annotation | 10 |
Domaini
Sequence similaritiesi
Family and domain databases
Gene3Di | 3.30.420.330, 1 hit |
HAMAPi | MF_04066, INFV_NS1, 1 hit |
IDEALi | IID90024 |
InterProi | View protein in InterPro IPR004208, NS1 IPR000256, NS1A IPR038064, NS1A_effect_dom-like_sf IPR009068, S15_NS1_RNA-bd |
Pfami | View protein in Pfam PF00600, Flu_NS1, 1 hit |
SUPFAMi | SSF143021, SSF143021, 1 hit SSF47060, SSF47060, 1 hit |
s (2)i Sequence
Sequence statusi: Complete.
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MDSNTVSSFQ VDCFLWHVRK QVVDQELSDA PFLDRLRRDQ RSLRGRGSTL
60 70 80 90 100
GLDIKAATHV GKQIVEKILK EESDEALKMT MASTPASRYI TDMTIEELSR
110 120 130 140 150
NWFMLMPKQK VEGPLCIRMD QAIMEKNIML KANFSVIFDR LETLVLLRAF
160 170 180 190 200
TEEGAIVGEI SPLPSFPGHT IEDVKNAIGV LIGGLEWNDN TVRVSKTLQR
210 220 230
FAWGSSNENG GPPLTPKQKR KMARTARSKV RRDKMAD
Isoforms of the same protein are often annotated in two different entries if their sequences differ significantly.
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | CY003740 Genomic RNA Translation: ABB04944.1 |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | CY003740 Genomic RNA Translation: ABB04944.1 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
4O42 | X-ray | 1.87 | B | 216-230 | [»] | |
SMRi | Q38SQ2 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Family and domain databases
Gene3Di | 3.30.420.330, 1 hit |
HAMAPi | MF_04066, INFV_NS1, 1 hit |
IDEALi | IID90024 |
InterProi | View protein in InterPro IPR004208, NS1 IPR000256, NS1A IPR038064, NS1A_effect_dom-like_sf IPR009068, S15_NS1_RNA-bd |
Pfami | View protein in Pfam PF00600, Flu_NS1, 1 hit |
SUPFAMi | SSF143021, SSF143021, 1 hit SSF47060, SSF47060, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | NS1_I83A8 | |
Accessioni | Q38SQ2Primary (citable) accession number: Q38SQ2 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | March 18, 2008 |
Last sequence update: | November 22, 2005 | |
Last modified: | February 23, 2022 | |
This is version 72 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Viral Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
3D-structureDocuments
- PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families