20210801 20180803 20180425 20210801 IID90024 Non-structural protein 1 NS1A Influenza A virus (strain A/Hong Kong/5/1983 H3N2) 237 Q38SQ2 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. 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. Nuclear localization signal 34 38 Nuclear export signal 137 146 0 0 NS NS1_I83A8 MDSNTVSSFQVDCFLWHVRKQVVDQELSDAPFLDRLRRDQRSLRGRGSTLGLDIKAATHVGKQIVEKILKEESDEALKMTMASTPASRYITDMTIEELSRNWFMLMPKQKVEGPLCIRMDQAIMEKNIMLKANFSVIFDRLETLVLLRAFTEEGAIVGEISPLPSFPGHTIEDVKNAIGVLIGGLEWNDNTVRVSKTLQRFAWGSSNENGGPPLTPKQKRKMARTARSKVRRDKMAD 1 4o42B 216 223 disorder 1 2 4o42B 224 230 order 1 1 4o42 X-RAY 291K 7 24853335 S.QIN,Y.LIU,W.TEMPEL,M.S.ERAM,C.BIAN,K.LIU,G.SENISTERRA,L.CROMBET,M.VEDADI,J.MIN 2014 NAT COMMUN 5 3952 x-ray 4o42 B 216 230 100 1 216 223 1 4o42 3817 Hetero dimer 4o42B Q38SQ2 IID90024 4o42A O14646 IID00003 4o42B-4o42A ProS 1 possible 2 224 230 Same region of homolog (P03496, 740dentity) is disordered in the free state. 2-72,86-203,216-217,219-221 1-1,73-85,204-215,218-218,222-237 4-209 1-3,210-237 210-237 34-48