Query author contributions in Reactome
Reactome depends on collaboration between our curation team and outside experts to assemble and peer-review its pathway modules. The integration of ORCID within Reactome enables us to meet a key challenge with authoring, curating and reviewing biological information by incentivizing and crediting the external experts that contribute their expertise and time to the Reactome curation process. More information is available at ORCID and Reactome.
If you have an ORCID ID that is not listed on this page, please forward this information to us and we will update your Reactome pathway records.
Details on Person UniProt:P03496 NS
| Class:Id | ReferenceGeneProduct:169060 |
|---|---|
| _chainChangeLog | chain:1-230 added on Fri February 6 2015 |
| _displayName | UniProt:P03496 NS |
| _timestamp | 2023-11-03 18:03:07 |
| chain | chain:1-230 |
| checksum | 2F7EC18E3EE7A4BE |
| comment | 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 (PubMed:33766561). Stress granule formation is thus inhibited, which allows protein synthesis and viral replication (PubMed:33766561).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.INTERACTION 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.ALTERNATIVE PRODUCTS 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. There are two ISGylated forms: one form is ISGylated at Lys-20, Lys-41, Lys-217, and Lys-219, and another one at Lys-108, Lys-110, and Lys-126, they represent band I and II respectively. Lys-126 and Lys-217 are critical for host antiviral response in vivo.SIMILARITY Belongs to the influenza A viruses NS1 family. |
| created | [InstanceEdit:169110] Gillespie, ME, 2005-11-22 21:39:50 |
| description | recommendedName: fullName evidence="1"Non-structural protein 1 shortName evidence="1"NS1 alternativeName: fullName evidence="1"NS1A |
| geneName | NS |
| identifier | P03496 |
| isSequenceChanged | FALSE |
| keyword | 3D-structure Alternative splicing Eukaryotic host gene expression shutoff by virus Host cytoplasm Host gene expression shutoff by virus Host mRNA suppression by virus Host nucleus Host-virus interaction Inhibition of host innate immune response by virus Inhibition of host interferon signaling pathway 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 Interferon antiviral system evasion Isopeptide bond Reference proteome RNA-binding Ubl conjugation Viral immunoevasion |
| modified | [InstanceEdit:169470] Gillespie, ME, 2005-11-29 19:12:13 [InstanceEdit:169470] Gillespie, ME, 2005-11-29 19:12:13 [InstanceEdit:169470] Gillespie, ME, 2005-11-29 19:12:13 [InstanceEdit:169470] Gillespie, ME, 2005-11-29 19:12:13 [InstanceEdit:169483] Gillespie, ME, 2005-11-29 19:34:47 [InstanceEdit:217385] Schmidt, EE, 2008-03-27 06:23:53 [InstanceEdit:354386] Schmidt, EE, 2008-06-18 04:45:12 [InstanceEdit:384350] Kanapin, AA, 2008-11-26 14:00:39 [InstanceEdit:392885] Kanapin, AA, 2009-03-09 12:07:18 [InstanceEdit:400710] Schmidt, EE, 2009-03-25 05:33:35 [InstanceEdit:423310] Kanapin, AA [InstanceEdit:435478] Kanapin, AA [InstanceEdit:435871] Kanapin, AA [InstanceEdit:447347] Kanapin, AA [InstanceEdit:525883] Kanapin, AA [InstanceEdit:613449] Kanapin, AA [InstanceEdit:797602] Kanapin, AA [InstanceEdit:937368] Yung, CK [InstanceEdit:1042053] Yung, CK [InstanceEdit:1220657] Yung, CK [InstanceEdit:1300696] Yung, CK [InstanceEdit:1301627] Yung, CK [InstanceEdit:1551960] Weiser, JD [InstanceEdit:1995863] Weiser, JD [InstanceEdit:2132304] Weiser, JD [InstanceEdit:2265580] Weiser, JD [InstanceEdit:2587579] Weiser, JD [InstanceEdit:5263031] Weiser, JD [InstanceEdit:5433710] Weiser, JD [InstanceEdit:5618415] Weiser, JD [InstanceEdit:5634237] Weiser, JD [InstanceEdit:5673015] Weiser, JD [InstanceEdit:9015733] Weiser, JD [InstanceEdit:9031715] D'Eustachio, Peter, 2017-12-01 [InstanceEdit:9031717] D'Eustachio, Peter, 2017-12-01 [InstanceEdit:9037114] Weiser, JD [InstanceEdit:9637257] Weiser, JD [InstanceEdit:9676415] Weiser, JD [InstanceEdit:9730071] Weiser, JD [InstanceEdit:9829221] Weiser, Joel [InstanceEdit:9841277] Weiser, Joel [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 |
| name | NS |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| secondaryIdentifier | NS1_I34A1 Q20N32 Q67267 Q71QT3 |
| sequenceLength | 230 |
| species | [Species:9031716] Influenza A virus |
| (isoformParent) | [ReferenceIsoform:402336] UniProt:P03496-1 NS [Influenza A virus] [ReferenceIsoform:402351] UniProt:P03508-1 NS [Influenza A virus] |
| (referenceEntity) | [EntityWithAccessionedSequence:169113] NS1 [nucleoplasm] [Influenza A virus] [EntityWithAccessionedSequence:169118] NS1 [cytosol] [Influenza A virus] |
| [Change default viewing format] | |
No pathways have been reviewed or authored by UniProt:P03496 NS (169060)
