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HAMAP rule MF_04066

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General rule information [?]

Accession MF_04066
Dates 10-APR-2017 (Created)
28-OCT-2021 (Last updated, Version 5)
Name INFV_NS1
Scope
Viruses; Orthomyxoviridae
Templates P03496 (NS1_I34A1); P03502 (NS1_INBLE): [Recover all]
Triggered by

Propagated annotation [?]


Identifier, protein and gene names [?]

Identifier
NS1
Protein name
RecName: Full=Non-structural protein 1;
Short=NS1;
AltName: Full=NS1A;
Gene name
NS

Comments [?]

case <OC:Alphainfluenzavirus>
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 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.
Subunit 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.
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.
Domain The dsRNA-binding region is required for suppression of RNA silencing.
Ptm 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.
Similarity Belongs to the influenza A viruses NS1 family.
else case <OC:Betainfluenzavirus>
Function Binds and inhibits the conjugation of the ubiquitin-like G1P2/ISG15 protein to its target proteins. Since G1P2/ISG15 is an early antiviral protein, NS1 may inhibit the host antiviral response. Prevents EIF2AK2/PKR activation, either by binding double strand RNA or by interacting directly with EIF2AK2/PKR. Also binds poly(A) and U6 snRNA.
Subunit Homodimer. Interacts with and inhibits human G1P2 conjugation by UBE1L.
Subcellular location Host cytoplasm. Host nucleus.
Similarity Belongs to the influenza B viruses NS1 family.
else case <OC:Gammainfluenzavirus>
Function Prevents the establishment of the cellular antiviral state initiated by host DDX58, which normally triggers the antiviral transduction signal that leads to the activation of type I IFN genes by transcription factors IRF3 and IRF7. Participates also in the upregulation of the splicing of viral mRNAs.
Subcellular location Host cytoplasm. Host nucleus.
Similarity Belongs to the influenza C viruses NS1 family.
end case

Keywords [?]

Host cytoplasm
Host nucleus
Host-virus interaction
Viral immunoevasion
Interferon antiviral system evasion
Inhibition of host innate immune response by virus
RNA-binding
Inhibition of host interferon signaling pathway by virus
case <OC:Alphainfluenzavirus>
Eukaryotic host gene expression shutoff by virus
Host gene expression shutoff by virus
Host mRNA suppression 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
Ubl conjugation
else case <OC:Betainfluenzavirus>
Inhibition of host ISG15 by virus
Inhibition of host PKR by virus
else case <OC:Gammainfluenzavirus>
Inhibition of host RIG-I by virus
Inhibition of host RLR pathway by virus
end case

Gene Ontology [?]

GO:0030430; Cellular component: host cell cytoplasm.
GO:0042025; Cellular component: host cell nucleus.
GO:0003723; Molecular function: RNA binding.
GO:0039502; Biological process: suppression by virus of host type I interferon-mediated signaling pathway.
case <OC:Alphainfluenzavirus>
GO:0039524; Biological process: suppression by virus of host mRNA processing.
end case
case <OC:Alphainfluenzavirus> and <OC:Gammainfluenzavirus>
GO:0039540; Biological process: suppression by virus of host viral-induced cytoplasmic pattern recognition receptor signaling pathway via inhibition of host RIG-I activity.
end case
case <OC:Alphainfluenzavirus> and <OC:Betainfluenzavirus>
GO:0039580; Biological process: suppression by virus of host PKR signaling.
end case

Cross-references [?]

Pfam PF00600; Flu_NS1; 1;
PF02942; Flu_B_NS1; 1;
PF03506; Flu_C_NS1; 1;
PF03555; Flu_C_NS2; 1;
PIRSF PIRSF003938; Flu_B_NS1; 1;

Features [?]

case <OC:Alphainfluenzavirus>
From: NS1_I34A1 (P03496)
Key     From     To       Description   Tag   Condition   FTGroup
REGION     Nter     73       RNA-binding and homodimerization        
REGION     180     215       CPSF4-binding        
REGION     223     230       PABPN1-binding        
MOTIF     34     38       Nuclear localization signal        
MOTIF     137     146       Nuclear export signal        
end case
case <OC:Betainfluenzavirus>
From: NS1_INBLE (P03502)
REGION     Nter     93       RNA-binding and homodimerization        
MOTIF     50     55       Nuclear localization signal        
end case

Additional information [?]

Size range 202-281 amino acids
Related rules None
Fusion None


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