HAMAP rule MF_04066
General rule information
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| Accession | MF_04066 |
| Dates | 10-APR-2017 (Created)
7-MAR-2023 (Last updated, Version 6) |
| Name | INFV_NS1 |
| Scope(s) |
Viruses Orthomyxoviridae |
| Template(s) | P03496 (NS1_I34A1); P03502 (NS1_INBLE); [ Recover all ] |
| Triggered by |
HAMAP; MF_04066 (Get profile general information and statistics) |
Propagated annotation
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Identifier, protein and gene names
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| Identifier | NS1 |
| Protein name | RecName: Full=Non-structural protein 1; Short=NS1; AltName: Full=NS1A; |
| Gene name | Name=NS; |
Comments
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| 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 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. |
| 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
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Gene Ontology
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| 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 <OCellular component:Alphainfluenzavirus> | |
| GO:0039524; Biological process:suppression by virus of host mRNA processing | |
| end case | |
| case <OCellular component: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 <OCellular component:Alphainfluenzavirus> and <OC:Betainfluenzavirus> | |
| GO:0039580; Biological process:suppression by virus of host PKR signaling | |
| end case | |
Cross-references
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| Pfam | PF00600; Flu_NS1; 1; |
| Pfam | PF02942; Flu_B_NS1; 1; |
| Pfam | PF03506; Flu_C_NS1; 1; |
| Pfam | PF03555; Flu_C_NS2; 1; |
| PIRSF | PIRSF003938; Flu_B_NS1; 1; |
Features
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| From: NS1_I34A1 (P03496) | ||||||||||||
| Key | From | To | Description | Tag | Condition | FTGroup | ||||||
| case <OC:Alphainfluenzavirus> | ||||||||||||
| REGION | Nter | 73 | /note="RNA-binding and homodimerization" | |||||||||
| REGION | 180 | 215 | /note="CPSF4-binding" | |||||||||
| REGION | 223 | 230 | /note="PABPN1-binding" | |||||||||
| MOTIF | 34 | 38 | /note="Nuclear localization signal" | |||||||||
| MOTIF | 137 | 146 | /note="Nuclear export signal" | |||||||||
| end case | ||||||||||||
| From: NS1_INBLE (P03502) | ||||||||||||
| Key | From | To | Description | Tag | Condition | FTGroup | ||||||
| case <OC:Betainfluenzavirus> | ||||||||||||
| REGION | Nter | 93 | /note="RNA-binding and homodimerization" | |||||||||
| MOTIF | 50 | 55 | /note="Nuclear localization signal" | |||||||||
| end case | ||||||||||||
Additional information
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| Size range | 202-281 amino acids |
| Related rules |
None |
| Fusion | Nter: None Cter: None |