UniProtKB - 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
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
- RNA binding Source: UniProtKB-KW
GO - Biological processi
- suppression by virus of host mRNA processing Source: UniProtKB-KW
- suppression by virus of host PKR activity Source: UniProtKB-KW
- suppression by virus of host RIG-I activity Source: UniProtKB-KW
- suppression by virus of host type I interferon-mediated signaling pathway 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/USA:Texas/UR06-0195/2007 H1N1) |
Taxonomic identifieri | 455880 [NCBI] |
Taxonomic lineagei | Viruses › ssRNA viruses › ssRNA negative-strand viruses › Orthomyxoviridae › Influenzavirus A › |
Virus hosti | Aves [TaxID: 8782] Homo sapiens (Human) [TaxID: 9606] Sus scrofa (Pig) [TaxID: 9823] |
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
- host cell cytoplasm Source: UniProtKB-SubCell
- host cell nucleus Source: UniProtKB-SubCell
Keywords - Cellular componenti
Host cytoplasm, Host nucleusPTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000372979 | 1 – 230 | Non-structural protein 1Add BLAST | 230 |
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 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 annotation
Structurei
3D structure databases
ProteinModelPortali | A8C8K0. |
SMRi | A8C8K0. |
ModBasei | Search... |
MobiDBi | Search... |
Family & 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 | 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
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
Family and domain databases
Gene3Di | 3.30.420.330. 1 hit. |
HAMAPi | MF_04066. INFV_NS1. 1 hit. |
InterProi | View protein in InterPro IPR004208. NS1. IPR000256. NS1A. IPR038064. NS1A_effect_dom_like_sp. 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 basket
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.
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
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.
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 | CY026215 Viral cRNA. Translation: ABV45931.1. |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Entry informationi
Entry namei | NS1_I07A0 | |
Accessioni | A8C8K0Primary (citable) accession number: A8C8K0 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | May 5, 2009 |
Last sequence update: | November 13, 2007 | |
Last modified: | March 28, 2018 | |
This is version 46 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Viral Protein Annotation Program |