The following text describes a protein:
Function:
[Polyprotein P1234]: Inactive precursor of the viral replicase, which is activated by cleavages carried out by the viral protease nsP2; [Polyprotein P123]: The early replication complex formed by the polyprotein P123 and nsP4 synthesizes minus-strand RNAs. Polyprotein P123 is a short-lived polyprotein that accumulates during early stage of infection. As soon P123 is cleaved into mature proteins, the plus-strand RNAs synthesis begins; [Polyprotein P123']: The early replication complex formed by the polyprotein P123' and nsP4 synthesizes minus-strand RNAs (Probable). Polyprotein P123' is a short-lived polyprotein that accumulates during early stage of infection (Probable). As soon P123' is cleaved into mature proteins, the plus-strand RNAs synthesis begins (Probable); [mRNA-capping enzyme nsP1]: Cytoplasmic capping enzyme that catalyzes two virus-specific reactions: methyltransferase and nsP1 guanylyltransferase. mRNA-capping is necessary since all viral RNAs are synthesized in the cytoplasm, and host capping enzymes are restricted to the nucleus (Probable). The enzymatic reaction involves a covalent link between 7-methyl-GMP and nsP1, whereas eukaryotic capping enzymes form a covalent complex only with GMP (Probable). nsP1 capping consists in the following reactions: GTP is first methylated into 7-methyl-GMP and then is covalently linked to nsP1 to form the m7GMp-nsP1 complex from which 7-methyl-GMP complex is transferred to the mRNA to create the cap structure (Probable). NsP1 is needed for the initiation of the minus-strand RNAs synthesis. Probably serves as a membrane anchor for the replication complex composed of nsP1-nsP4 (By similarity). Palmitoylated nsP1 is remodeling host cell cytoskeleton, and induces filopodium-like structure formation at the surface of the host cell (By similarity); [Protease nsP2]: Multifunctional protein whose N-terminus is part of the RNA polymerase complex and displays NTPase, RNA triphosphatase and helicase activities (By similarity). NTPase and RNA triphosphatase are involved in viral RNA capping and helicase keeps a check on the dsRNA replication intermediates (By similarity). The C-terminus harbors a protease that specifically cleaves the polyproteins and releases the mature proteins (By similarity). Required for the shutoff of minus-strand RNAs synthesis. Specifically inhibits the host IFN response by promoting the nuclear export of host STAT1 (By similarity). Also inhibits host transcription by inducing rapid proteasome-dependent degradation of POLR2A, a catalytic subunit of the RNAPII complex. The resulting inhibition of cellular protein synthesis serves to ensure maximal viral gene expression and to evade host immune response (Probable); [Non-structural protein 3]: Seems to be essential for minus-strand RNAs and subgenomic 26S mRNAs synthesis. Displays mono-ADP-ribosylhydrolase activity. ADP-ribosylation is a post-translantional modification that controls various processes of the host cell and the virus probably needs to revert it for optimal viral replication. Binds proteins of G3BP family and sequesters them into the viral RNA replication complexes thereby inhibiting the formation of host stress granules on viral mRNAs. The nsp3-G3BP complexes bind viral RNAs and probably orchestrate the assembly of viral replication complexes, thanks to the ability of G3BP family members to self-assemble and bind DNA (By similarity); [Non-structural protein 3']: Seems to be essential for minus-strand RNAs and subgenomic 26S mRNAs synthesis (Probable). Displays mono-ADP-ribosylhydrolase activity (Probable). ADP-ribosylation is a post-translational modification that controls various processes of the host cell and the virus probably needs to revert it for optimal viral replication (Probable). Binds proteins of G3BP family and sequesters them into the viral RNA replication complexes thereby inhibiting the formation of host stress granules on viral mRNAs (Probable). The nsp3'-G3BP complexes bind viral RNAs and probably orchestrate the assembly of viral replication complexes, thanks to the ability of G3BP family members to self-assemble and bind DNA (By similarity); [RNA-directed RNA polymerase nsP4]: RNA dependent RNA polymerase. Replicates genomic and antigenomic RNA by recognizing replications specific signals. The early replication complex formed by the polyprotein P123 and nsP4 synthesizes minus-strand RNAs. The late replication complex composed of fully processed nsP1-nsP4 is responsible for the production of genomic and subgenomic plus-strand RNAs. The core catalytic domain of nsP4 also possesses terminal adenylyltransferase (TATase) activity that is probably involved in maintenance and repair of the poly(A) tail, an element required for replication of the viral genome.
Miscellaneous:
MISCELLANEOUS: Viral replication produces dsRNA in the late phase of infection, resulting in a strong activation of host EIF2AK2/PKR, leading to almost complete phosphorylation of EIF2A. This inactivates completely cellular translation initiation, resulting shutoff of host proteins synthesis. However, phosphorylation of EIF2A is probably not the only mechanism responsible for the host translation shutoff. The viral translation can still occur normally because it relies on a hairpin structure in the coding region of sgRNA and is EIF2A-, EIF2D-, EIF4G- EIF4A-independent; MISCELLANEOUS: The genome codes for P123, but readthrough of a terminator codon UGA occurs between the codons for Tyr-1896 and Leu-1898 giving rise to P1234. P1234 is cleaved quickly by nsP2 into P123' and nsP4 (By similarity). Further processing of p123' gives nsP1, nsP2 and nsP3' which is 6 amino acids longer than nsP3 since the cleavage site is after the readthrough (By similarity). This unusual molecular mechanism ensures that few nsP4 are produced compared to other non-structural proteins (By similarity). Mutant viruses with no alternative termination site grow significantly slower than wild-type virus. The opal termination codon is frequently mutated to a sense codon on passage in cell culture (By similarity). The presence of the opal codon may be a requirement for viral maintenance in both vertebrate and invertebrate hosts and a selective advantage may be conferred in cell culture for the sense codon (By similarity).
Subcellular Localization:
[Polyprotein P1234]: Host cytoplasmic vesicle membrane; Peripheral membrane protein. Note=Part of cytoplasmic vesicles, which are probably formed at the plasma membrane and internalized leading to late endosomal/lysosomal spherules containing the replication complex; [Polyprotein P123']: Host cytoplasmic vesicle membrane; Peripheral membrane protein. Note=Part of cytoplasmic vesicles, which are probably formed at the plasma membrane and internalized leading to late endosomal/lysosomal spherules containing the replication complex; [Polyprotein P123]: Host cytoplasmic vesicle membrane; Peripheral membrane protein. Note=Part of cytoplasmic vesicles, which are probably formed at the plasma membrane and internalized leading to late endosomal/lysosomal spherules containing the replication complex; [mRNA-capping enzyme nsP1]: Host cytoplasmic vesicle membrane; Lipid-anchor. Host cell membrane; Lipid-anchor; Cytoplasmic side. Host cell projection, host filopodium. Note=In the late phase of infection, the polyprotein is quickly cleaved before localization to cellular membranes. Then a fraction of nsP1 localizes to the inner surface of the plasma membrane and its filopodial extensions. Only the palmitoylated nsP1 localizes to the host filopodia (By similarity). NsP1 is also part of cytoplasmic vesicles, which are probably formed at the plasma membrane and internalized leading to late endosomal/lysosomal spherules containing the replication complex (By similarity); [Protease nsP2]: Host cytoplasmic vesicle membrane; Peripheral membrane protein. Host nucleus. Host cytoplasm. Note=In the late phase of infection, the polyprotein is quickly cleaved before localization to cellular membranes. Then approximately half of nsP2 is found in the nucleus (By similarity). Shuttles between cytoplasm and nucleus (By similarity). NsP2 is also part of cytoplasmic vesicles, which are probably formed at the plasma membrane and internalized leading to late endosomal/lysosomal spherules containing the replication complex (By similarity); [Non-structural protein 3]: Host cytoplasmic vesicle membrane; Peripheral membrane protein. Note=In the late phase of infection, the polyprotein is quickly cleaved before localization to cellular membranes. Then nsP3 and nsP3' form aggregates in cytoplasm. NsP3 is also part of cytoplasmic vesicles, which are probably formed at the plasma membrane and internalized leading to late endosomal/lysosomal spherules containing the replication complex; [Non-structural protein 3']: Host cytoplasmic vesicle membrane; Peripheral membrane protein. Note=In the late phase of infection, the polyprotein is quickly cleaved before localization to cellular membranes. Then nsP3 and nsP3' form aggregates in cytoplasm (Probable). NsP3' is also part of cytoplasmic vesicles, which are probably formed at the plasma membrane and internalized leading to late endosomal/lysosomal spherules containing the replication complex (Probable); [RNA-directed RNA polymerase nsP4]: Host cytoplasmic vesicle membrane; Peripheral membrane protein. Note=NsP4 is part of cytoplasmic vesicles, which are probably formed at the plasma membrane and internalized leading to late endosomal/lysosomal spherules containing the replication complex.
Domain:
[Protease nsP2]: The N-terminus exhibits NTPase and RNA triphosphatase activities and is proposed to have helicase activity, whereas the C-terminus possesses protease activity (By similarity). Contains a nuclear localization signal and a nuclear export signal, these two motifs are probably involved in the shuttling between the cytoplasm and the nucleus of nsP2 (By similarity). The C-terminus is required for promoting the export of host STAT1 (By similarity); [Non-structural protein 3]: In the N-terminus, the macro domain displays a mono-ADP-ribosylhydrolase activity. The central part has a zinc-binding function. The C-terminus contains two FGDF motifs necessary and sufficient for formation of the nsP3/G3BP1 complex (By similarity); [Non-structural protein 3']: In the N-terminus, the macro domain displays a mono-ADP-ribosylhydrolase activity (Probable). The central part has a zinc-binding function (Probable). The C-terminus contains two FGDF motifs necessary and sufficient for formation of the nsP3'/G3BP1 complex (By similarity).
Sequence:
MEKPVVNVDVDPQSPFVVQLQKSFPQFEVVAQQVTPNDHANARAFSHLASKLIELEVPTTATILDIGSAPARRMFSEHQYHCVCPMRSPEDPDRMMKYASKLAEKACKITNKNLHEKIKDLRTVLDTPDAETPSLCFHNDVTCNMRAEYSVMQDVYINAPGTIYHQAMKGVRTLYWIGFDTTQFMFSAMAGSYPAYNTNWADEKVLEARNIGLCSTKLSEGRTGKLSIMRKKELKPGSRVYFSVGSTLYPEHRASLQSWHLPSVFHLNGKQSYTCRCDTVVSCEGYVVKKITISPGITGETVGYAVTHNSEGFLLCKVTDTVKGERVSFPVCTYIPATICDQMTGIMATDISPDDAQKLLVGLNQRIVINGRTNRNTNTMQNYLLPIIAQGFSKWAKERKDDLDNEKMLGTRERKLTYGCLWAFRTKKVHSFYRPPGTQTCVKVPASFSAFPMSSVWTTSLPMSLRQKLKLALQPKKEEKLLQVSEELVMEAKAAFEDAQEEARAEKLREALPPLVADKGIEAAAEVVCEVEGLQADIGAALVETPRGHVRIIPQANDRMIGQYIVVSPNSVLKNAKLAPAHPLADQVKIITHSGRSGRYAVEPYDAKVLMPAGGAVPWPEFLALSESATLVYNEREFVNRKLYHIAMHGPAKNTEEEQYKVTKAELAETEYVFDVDKKRCVKKEEASGLVLSGELTNPPYHELALEGLKTRPAVPYKVETIGVIGTPGSGKSAIIKSTVTARDLVTSGKKENCREIEADVLRLRGMQITSKTVDSVMLNGCHKAVEVLYVDEAFACHAGALLALIAIVRPRKKVVLCGDPMQCGFFNMMQLKVHFNHPEKDICTKTFYKYISRRCTQPVTAIVSTLHYDGKMKTTNPCKKNIEIDITGATKPKPGDIILTCFRGWVKQLQIDYPGHEVMTAAASQGLTRKGVYAVRQKVNENPLYAITSEHVNVLLTRTEDRLVWKTLQGDPWIKQPTNIPKGNFQATIEDWEAEHKGIIAAINSPTPRANPFSCKTNVCWAKALEPILATAGIVLTGCQWSELFPQFADDKPHSAIYALDVICIKFFGMDLTSGLFSKQSIPLTYHPADSARPVAHWDNSPGTRKYGYDHAIAAELSRRFPVFQLAGKGTQLDLQTGRTRVISAQHNLVPVNRNLPHALVPEYKEKQPGPVKKFLNQFKHHSVLVVSEEKIEAPRKRIEWIAPIGIAGADKNYNLAFGFPPQARYDLVFINIGTKYRNHHFQQCEDHAATLKTLSRSALNCLNPGGTLVVKSYGYADRNSEDVVTALARKFVRVSAARPDCVSSNTEMYLIFRQLDNSRTRQFTPHHLNCVISSVYEGTRDGVGAAPSYRTKRENIADCQEEAVVNAANPLGRPGEGVCRAIYKRWPTSFTDSATETGTARMTVCLGKKVIHAVGPDFRKHPEAEALKLLQNAYHAVADLVNEHNIKSVAIPLLSTGIYAAGKDRLEVSLNCLTTALDRTDADVTIYCLDKKWKERIDAALQLKESVTELKDEDMEIDDELVWIHPDSCLKGRKGFSTTKGKLYSYFEGTKFHQAAKDMAEIKVLFPNDQESNEQLCAYILGETMEAIREKCPVDHNPSSSPPKTLPCLCMYAMTPERVHRLRSNNVKEVTVCSSTPLPKHKIKNVQKVQCTKVVLFNPHTPAFVPARKYIEVPEQPTAPPAQAEEAPEVVATPSPSTADNTSLDVTDISLDMDDSSEGSLFSSFSGSDNSITSMDSWSSGPSSLEIVDRRQVVVADVHAVQEPAPIPPPRLKKMARLAAARKEPTPPASNSSESLHLSFGGVSMSLGSIFDGETARQAAVQPLATGPTDVPMSFGSFSDGEIDELSRRVTESEPVLFGSFEPGEVNSIISSRSAVSFPLRKQRRRRRSRRTEYXLTGVGGYIFSTDTGPGHLQKKSVLQNQLTEPTLERNVLERIHAPVLDTSKEEQLKLRYQMMPTEANKSRYQSRKVENQKAITTERLLSGLRLYNSATDQPECYKITYPKPLYSSSVPANYSDPQFAVAVCNNYLHENYPTVASYQITDEYDAYLDMVDGTVACLDTATFCPAKLRSYPKKHEYRAPNIRSAVPSAMQNTLQNVLIAATKRNCNVTQMRELPTLDSATFNVECFRKYACNDEYWEEFARKPIRITTEFVTAYVARLKGPKAAALFAKTYNLVPLQEVPMDRFVMDMKRDVKVTPGTKHTEERPKVQVIQAAEPLATAYLCGIHRELVRRLTAVLLPNIHTLFDMSAEDFDAIIAEHFKQGDPVLETDIASFDKSQDDAMALTGLMILEDLGVDQPLLDLIECAFGEISSTHLPTGTRFKFGAMMKSGMFLTLFVNTVLNVVIASRVLEERLKTSRCAAFIGDDNIIHGVVSDKEMAERCATWLNMEVKIIDAVIGERPPYFCGGFILQDSVTSTACRVADPLKRLFKLGKPLPADDEQDEDRRRALLDETKAWFRVGITGTLAVAVTTRYEVDNITPVLLALRTFAQSKRAFQAIRGEIKHLYGGPK