| IED ID | IndEnz0002001713 |
| Enzyme Type ID | protease001713 |
| Protein Name |
Polyprotein P1234 P1234 Non-structural polyprotein Cleaved into: Polyprotein P123 P123 ; mRNA-capping enzyme nsP1 EC 2.1.1.- EC 2.7.7.- Non-structural protein 1 ; Protease nsP2 EC 3.1.3.33 EC 3.4.22.- EC 3.6.1.15 EC 3.6.4.13 Non-structural protein 2 nsP2 ; Non-structural protein 3 nsP3 EC 3.1.3.84 ; RNA-directed RNA polymerase nsP4 EC 2.7.7.19 EC 2.7.7.48 Non-structural protein 4 nsP4 |
| Gene Name | |
| Organism | Chikungunya virus (strain S27-African prototype) (CHIKV) |
| Taxonomic Lineage | Viruses Riboviria Orthornavirae Kitrinoviricota Alsuviricetes Martellivirales Togaviridae Alphavirus (arboviruses group A) Chikungunya virus (CHIKV) Chikungunya virus (strain S27-African prototype) (CHIKV) |
| Enzyme Sequence | MDPVYVDIDADSAFLKALQRAYPMFEVEPRQVTPNDHANARAFSHLAIKLIEQEIDPDSTILDIGSAPARRMMSDRKYHCVCPMRSAEDPERLANYARKLASAAGKVLDRNISGKIGDLQAVMAVPDTETPTFCLHTDVSCRQRADVAIYQDVYAVHAPTSLYHQAIKGVRLAYWVGFDTTPFMYNAMAGAYPSYSTNWADEQVLKAKNIGLCSTDLTEGRRGKLSIMRGKKLEPCDRVLFSVGSTLYPESRKLLKSWHLPSVFHLKGKLSFTCRCDTVVSCEGYVVKRITMSPGLYGKTTGYAVTHHADGFLMCKTTDTVDGERVSFSVCTYVPATICDQMTGILATEVTPEDAQKLLVGLNQRIVVNGRTQRNTNTMKNYMIPVVAQAFSKWAKECRKDMEDEKLLGVRERTLTCCCLWAFKKQKTHTVYKRPDTQSIQKVQAEFDSFVVPSLWSSGLSIPLRTRIKWLLSKVPKTDLTPYSGDAQEARDAEKEAEEEREAELTLEALPPLQAAQEDVQVEIDVEQLEDRAGAGIIETPRGAIKVTAQPTDHVVGEYLVLSPQTVLRSQKLSLIHALAEQVKTCTHSGRAGRYAVEAYDGRVLVPSGYAISPEDFQSLSESATMVYNEREFVNRKLHHIAMHGPALNTDEESYELVRAERTEHEYVYDVDQRRCCKKEEAAGLVLVGDLTNPPYHEFAYEGLKIRPACPYKIAVIGVFGVPGSGKSAIIKNLVTRQDLVTSGKKENCQEITTDVMRQRGLEISARTVDSLLLNGCNRPVDVLYVDEAFACHSGTLLALIALVRPRQKVVLCGDPKQCGFFNMMQMKVNYNHNICTQVYHKSISRRCTLPVTAIVSSLHYEGKMRTTNEYNKPIVVDTTGSTKPDPGDLVLTCFRGWVKQLQIDYRGHEVMTAAASQGLTRKGVYAVRQKVNENPLYASTSEHVNVLLTRTEGKLVWKTLSGDPWIKTLQNPPKGNFKATIKEWEVEHASIMAGICSHQMTFDTFQNKANVCWAKSLVPILETAGIKLNDRQWSQIIQAFKEDKAYSPEVALNEICTRMYGVDLDSGLFSKPLVSVYYADNHWDNRPGGKMFGFNPEAASILERKYPFTKGKWNINKQICVTTRRIEDFNPTTNIIPANRRLPHSLVAEHRPVKGERMEWLVNKINGHHVLLVSGCSLALPTKRVTWVAPLGVRGADYTYNLELGLPATLGRYDLVVINIHTPFRIHHYQQCVDHAMKLQMLGGDSLRLLKPGGSLLIRAYGYADRTSERVICVLGRKFRSSRALKPPCVTSNTEMFFLFSNFDNGRRNFTTHVMNNQLNAAFVGQATRAGCAPSYRVKRMDIAKNDEECVVNAANPRGLPGDGVCKAVYKKWPESFKNSATPVGTAKTVMCGTYPVIHAVGPNFSNYSESEGDRELAAAYREVAKEVTRLGVNSVAIPLLSTGVYSGGKDRLTQSLNHLFTAMDSTDADVVIYCRDKEWEKKISEAIQMRTQVELLDEHISIDCDVVRVHPDSSLAGRKGYSTTEGALYSYLEGTRFHQTAVDMAEIYTMWPKQTEANEQVCLYALGESIESIRQKCPVDDADASSPPKTVPCLCRYAMTPERVTRLRMNHVTSIIVCSSFPLPKYKIEGVQKVKCSKVMLFDHNVPSRVSPREYRPSQESVQEASTTTSLTHSQFDLSVDGKILPVPSDLDADAPALEPALDDGAIHTLPSATGNLAAVSDWVMSTVPVAPPRRRRGRNLTVTCDEREGNITPMASVRFFRAELCPVVQETAETRDTAMSLQAPPSTATELSHPPISFGAPSETFPITFGDFNEGEIESLSSELLTFGDFLPGEVDDLTDSDWSTCSDTDDELRLDRAGGYIFSSDTGPGHLQQKSVRQSVLPVNTLEEVHEEKCYPPKLDEAKEQLLLKKLQESASMANRSRYQSRKVENMKATIIQRLKRGCRLYLMSETPKVPTYRTTYPAPVYSPPINVRLSNPESAVAACNEFLARNYPTVSSYQITDEYDAYLDMVDGSESCLDRATFNPSKLRSYPKQHAYHAPSIRSAVPSPFQNTLQNVLAAATKRNCNVTQMRELPTLDSAVFNVECFKKFACNQEYWEEFAASPIRITTENLTTYVTKLKGPKAAALFAKTHNLLPLQEVPMDRFTVDMKRDVKVTPGTKHTEERPKVQVIQAAEPLATAYLCGIHRELVRRLNAVLLPNVHTLFDMSAEDFDAIIAAHFKPGDTVLETDIASFDKSQDDSLALTALMLLEDLGVDHSLLDLIEAAFGEISSCHLPTGTRFKFGAMMKSGMFLTLFVNTLLNITIASRVLEDRLTKSACAAFIGDDNIIHGVVSDELMAARCATWMNMEVKIIDAVVSQKAPYFCGGFILHDIVTGTACRVADPLKRLFKLGKPLAAGDEQDEDRRRALADEVVRWQRTGLIDELEKAVYSRYEVQGISVVVMSMATFASSRSNFEKLRGPVVTLYGGPK |
| Enzyme Length | 2474 |
| Uniprot Accession Number | Q8JUX6 |
| Absorption | |
| Active Site | ACT_SITE 37; /note=For mRNA-capping enzyme nsP1 activity; /evidence=ECO:0000269|PubMed:33730549; ACT_SITE 1013; /note=For cysteine protease nsP2 activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU00853; ACT_SITE 1083; /note=For cysteine protease nsP2 activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU00853 |
| Activity Regulation | |
| Binding Site | BINDING 1343; /note=ADP-ribose; /evidence=ECO:0000269|PubMed:19386706; BINDING 1357; /note=ADP-ribose; /evidence=ECO:0000269|PubMed:19386706; BINDING 1365; /note=ADP-ribose; /evidence=ECO:0000269|PubMed:19386706; BINDING 1445; /note=ADP-ribose; /evidence=ECO:0000269|PubMed:19386706; BINDING 1446; /note=ADP-ribose; /evidence=ECO:0000269|PubMed:19386706; BINDING 1447; /note=ADP-ribose; /evidence=ECO:0000269|PubMed:19386706 |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=GTP + S-adenosyl-L-methionine = N(7)-methyl-GTP + S-adenosyl-L-homocysteine; Xref=Rhea:RHEA:46948, ChEBI:CHEBI:37565, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:87133; Evidence={ECO:0000250|UniProtKB:P27282}; CATALYTIC ACTIVITY: Reaction=[nsP1 protein]-L-histidine + N(7)-methyl-GTP = [nsP1 protein]-N(tele)-(N(7)-methylguanosine 5'-phospho)-L-histidine + diphosphate; Xref=Rhea:RHEA:54792, Rhea:RHEA-COMP:13994, Rhea:RHEA-COMP:13995, ChEBI:CHEBI:29979, ChEBI:CHEBI:33019, ChEBI:CHEBI:87133, ChEBI:CHEBI:138334; Evidence={ECO:0000250|UniProtKB:P27282};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:54793; Evidence={ECO:0000250|UniProtKB:P27282}; CATALYTIC ACTIVITY: Reaction=[nsP1 protein]-N(tele)-(N(7)-methylguanosine 5'-phospho)-L-histidine + a 5'-end diphospho-(purine-ribonucleoside) in mRNA + H(+) = [nsP1 protein]-L-histidine + a 5'-end (N(7)-methyl 5'-triphosphoguanosine)-(purine-ribonucleoside) in mRNA; Xref=Rhea:RHEA:54800, Rhea:RHEA-COMP:12925, Rhea:RHEA-COMP:13929, Rhea:RHEA-COMP:13994, Rhea:RHEA-COMP:13995, ChEBI:CHEBI:15378, ChEBI:CHEBI:29979, ChEBI:CHEBI:133968, ChEBI:CHEBI:138276, ChEBI:CHEBI:138334; Evidence={ECO:0000250|UniProtKB:P27282}; CATALYTIC ACTIVITY: Reaction=a 5'-end triphospho-(purine-ribonucleoside) in mRNA + H2O = a 5'-end diphospho-(purine-ribonucleoside) in mRNA + H(+) + phosphate; Xref=Rhea:RHEA:11008, Rhea:RHEA-COMP:13929, Rhea:RHEA-COMP:13942, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:43474, ChEBI:CHEBI:138276, ChEBI:CHEBI:138288; EC=3.1.3.33; Evidence={ECO:0000269|PubMed:21811589}; CATALYTIC ACTIVITY: Reaction=a ribonucleoside 5'-triphosphate + H2O = a ribonucleoside 5'-diphosphate + H(+) + phosphate; Xref=Rhea:RHEA:23680, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:43474, ChEBI:CHEBI:57930, ChEBI:CHEBI:61557; EC=3.6.1.15; Evidence={ECO:0000269|PubMed:21811589, ECO:0000269|PubMed:24407286}; CATALYTIC ACTIVITY: Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=3.6.4.13; Evidence={ECO:0000269|PubMed:21811589, ECO:0000269|PubMed:24407286}; CATALYTIC ACTIVITY: Reaction=a ribonucleoside 5'-triphosphate + RNA(n) = diphosphate + RNA(n+1); Xref=Rhea:RHEA:21248, Rhea:RHEA-COMP:14527, Rhea:RHEA-COMP:17342, ChEBI:CHEBI:33019, ChEBI:CHEBI:61557, ChEBI:CHEBI:140395; EC=2.7.7.48; Evidence={ECO:0000255|PROSITE-ProRule:PRU00539}; CATALYTIC ACTIVITY: Reaction=4-O-(ADP-D-ribosyl)-L-aspartyl-[protein] + H2O = ADP-D-ribose + H(+) + L-aspartyl-[protein]; Xref=Rhea:RHEA:54428, Rhea:RHEA-COMP:9867, Rhea:RHEA-COMP:13832, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:29961, ChEBI:CHEBI:57967, ChEBI:CHEBI:138102; Evidence={ECO:0000269|PubMed:28143925, ECO:0000269|PubMed:28150709};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:54429; Evidence={ECO:0000269|PubMed:28143925, ECO:0000269|PubMed:28150709}; CATALYTIC ACTIVITY: Reaction=5-O-(ADP-D-ribosyl)-L-glutamyl-[protein] + H2O = ADP-D-ribose + H(+) + L-glutamyl-[protein]; Xref=Rhea:RHEA:58248, Rhea:RHEA-COMP:10208, Rhea:RHEA-COMP:15089, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:29973, ChEBI:CHEBI:57967, ChEBI:CHEBI:142540; Evidence={ECO:0000269|PubMed:28143925, ECO:0000269|PubMed:28150709};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:58249; Evidence={ECO:0000269|PubMed:28143925, ECO:0000269|PubMed:28150709}; CATALYTIC ACTIVITY: Reaction=ATP + RNA(n) = diphosphate + RNA(n)-3'-adenine ribonucleotide; Xref=Rhea:RHEA:11332, Rhea:RHEA-COMP:14527, Rhea:RHEA-COMP:17347, ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:140395, ChEBI:CHEBI:173115; EC=2.7.7.19; Evidence={ECO:0000250|UniProtKB:P03317}; CATALYTIC ACTIVITY: Reaction=ADP-D-ribose 1''-phosphate + H2O = ADP-D-ribose + phosphate; Xref=Rhea:RHEA:25029, ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:57967, ChEBI:CHEBI:58753; EC=3.1.3.84; Evidence={ECO:0000269|PubMed:19386706};PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25030; Evidence={ECO:0000269|PubMed:19386706}; |
| DNA Binding | |
| EC Number | 2.1.1.-; 2.7.7.-; 3.1.3.33; 3.4.22.-; 3.6.1.15; 3.6.4.13; 3.1.3.84; 2.7.7.19; 2.7.7.48 |
| Enzyme Function | FUNCTION: [Polyprotein P1234]: Inactive precursor of the viral replicase, which is activated by cleavages carried out by the viral protease nsP2. {ECO:0000269|PubMed:27845418}.; FUNCTION: [Polyprotein P123]: The early replication complex formed by the polyprotein P123 and nsP4 synthesizes minus-strand RNAs (By similarity). As soon P123 is cleaved into mature proteins, the plus-strand RNAs synthesis begins (By similarity). {ECO:0000250|UniProtKB:P03317}.; FUNCTION: [mRNA-capping enzyme nsP1]: Cytoplasmic capping enzyme that catalyzes two virus-specific reactions: methyltransferase and guanylyltransferase (By similarity). 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 (By similarity). 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 (By similarity). NsP1 is also needed for the initiation of the minus-strand RNAs synthesis (By similarity). At the initiation of virus replication, mediates the assembly of the viral replication complex made of the non-structural proteins, the association of this complex with the inner face of the plasma membrane and the formation of membranous spherules that serve as replication complex factories (PubMed:33730549). Forms the neck of these spherules with a central channel for mediating communication and the passage of RNA, nucleotides, and small proteins between the viral replication complex and the host cytoplasm (PubMed:33730549). Palmitoylated nsP1 is remodeling host cell cytoskeleton, and induces filopodium-like structure formation at the surface of the host cell (PubMed:30404808). {ECO:0000250|UniProtKB:P03317, ECO:0000269|PubMed:30404808, ECO:0000269|PubMed:33730549}.; FUNCTION: [Protease nsP2]: Multifunctional protein whose N-terminus is part of the RNA polymerase complex and displays NTPase, RNA triphosphatase and helicase activities (PubMed:21811589, PubMed:24407286). 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 (PubMed:27845418, PubMed:26597768). Required for the shutoff of minus-strand RNAs synthesis (By similarity). Specifically inhibits the host IFN response by promoting the nuclear export of host STAT1 (PubMed:29925658). Also inhibits host transcription by inducing the rapid proteasome-dependent degradation of POLR2A, a catalytic subunit of the RNAPII complex (PubMed:22514352). The resulting inhibition of cellular protein synthesis serves to ensure maximal viral gene expression and to evade host immune response (Probable). {ECO:0000250|UniProtKB:P03317, ECO:0000250|UniProtKB:P08411, ECO:0000269|PubMed:21811589, ECO:0000269|PubMed:22514352, ECO:0000269|PubMed:24407286, ECO:0000269|PubMed:26597768, ECO:0000269|PubMed:27845418, ECO:0000269|PubMed:29925658, ECO:0000305|PubMed:22514352}.; FUNCTION: [Non-structural protein 3]: Seems to be essential for minus-strand RNAs and subgenomic 26S mRNAs synthesis (By similarity). Displays mono-ADP-ribosylhydrolase activity (PubMed:28143925, PubMed:28150709). 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 (PubMed:28143925, PubMed:28150709). 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 (PubMed:25653451). 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 (PubMed:27509095, PubMed:27383630) (Probable). {ECO:0000250|UniProtKB:P03317, ECO:0000269|PubMed:25653451, ECO:0000269|PubMed:27383630, ECO:0000269|PubMed:27509095, ECO:0000269|PubMed:28143925, ECO:0000269|PubMed:28150709, ECO:0000305|PubMed:25653451}.; FUNCTION: [RNA-directed RNA polymerase nsP4]: RNA dependent RNA polymerase (By similarity). 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 (By similarity). The late replication complex composed of fully processed nsP1-nsP4 is responsible for the production of genomic and subgenomic plus-strand RNAs (By similarity). {ECO:0000250|UniProtKB:P03317}. |
| Temperature Dependency | BIOPHYSICOCHEMICAL PROPERTIES: Temperature dependence: Optimum temperature is 37 degrees Celsius for nsP2 NTPase. {ECO:0000269|PubMed:21811589}; |
| PH Dependency | BIOPHYSICOCHEMICAL PROPERTIES: pH dependence: Optimum pH is 7.2 for nsP2 NTPase. {ECO:0000269|PubMed:21811589, ECO:0000269|PubMed:24407286}; |
| Pathway | |
| nucleotide Binding | NP_BIND 721..728; /note=NTP; /evidence=ECO:0000255|PROSITE-ProRule:PRU00990 |
| Features | Active site (3); Beta strand (17); Binding site (6); Chain (6); Compositional bias (2); Domain (6); Helix (21); Lipidation (2); Metal binding (8); Motif (4); Mutagenesis (22); Nucleotide binding (1); Region (9); Site (4); Turn (2) |
| Keywords | 3D-structure;ATP-binding;Eukaryotic host gene expression shutoff by virus;Eukaryotic host transcription shutoff by virus;GTP-binding;Helicase;Host cell membrane;Host cell projection;Host cytoplasm;Host cytoplasmic vesicle;Host gene expression shutoff by virus;Host membrane;Host nucleus;Host-virus interaction;Hydrolase;Inhibition of host RNA polymerase II by virus;Inhibition of host STAT1 by virus;Inhibition of host innate immune response by virus;Inhibition of host interferon signaling pathway by virus;Lipoprotein;Membrane;Metal-binding;Methyltransferase;Multifunctional enzyme;Nucleotide-binding;Nucleotidyltransferase;Palmitate;Phosphoprotein;Protease;RNA suppression of termination;RNA-binding;RNA-directed RNA polymerase;Reference proteome;S-adenosyl-L-methionine;Thiol protease;Transferase;Ubl conjugation;Viral RNA replication;Viral immunoevasion;Zinc;mRNA capping;mRNA processing |
| Interact With | |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: [Polyprotein P1234]: Host cytoplasmic vesicle membrane {ECO:0000305}; Peripheral membrane protein {ECO:0000305}. 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. {ECO:0000305}.; SUBCELLULAR LOCATION: [Polyprotein P123]: Host cytoplasmic vesicle membrane {ECO:0000305}; Peripheral membrane protein {ECO:0000305}. 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. {ECO:0000305}.; SUBCELLULAR LOCATION: [mRNA-capping enzyme nsP1]: Host cytoplasmic vesicle membrane {ECO:0000250|UniProtKB:P08411}; Lipid-anchor {ECO:0000250|UniProtKB:P08411}. Host cell membrane {ECO:0000250|UniProtKB:P08411}; Lipid-anchor {ECO:0000250|UniProtKB:P08411}; Cytoplasmic side {ECO:0000250|UniProtKB:P08411}. Host cell projection, host filopodium {ECO:0000269|PubMed:30404808}. 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 (PubMed:30404808). 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). {ECO:0000250|UniProtKB:P08411, ECO:0000269|PubMed:30404808}.; SUBCELLULAR LOCATION: [Protease nsP2]: Host cytoplasmic vesicle membrane {ECO:0000250|UniProtKB:P08411}; Peripheral membrane protein {ECO:0000250|UniProtKB:P08411}. Host nucleus {ECO:0000250|UniProtKB:P27282}. Host cytoplasm {ECO:0000250|UniProtKB:P27282}. 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). {ECO:0000250|UniProtKB:P08411, ECO:0000250|UniProtKB:P27282}.; SUBCELLULAR LOCATION: [Non-structural protein 3]: Host cytoplasmic vesicle membrane {ECO:0000250|UniProtKB:P03317}; Peripheral membrane protein {ECO:0000305}. Note=In the late phase of infection, the polyprotein is quickly cleaved before localization to cellular membranes. Then nsP3 forms aggregates in cytoplasm (By similarity). 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 (By similarity). {ECO:0000250|UniProtKB:P03317}.; SUBCELLULAR LOCATION: [RNA-directed RNA polymerase nsP4]: Host cytoplasmic vesicle membrane; Peripheral membrane protein {ECO:0000250|UniProtKB:P08411}. 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. {ECO:0000250|UniProtKB:P08411}. |
| Modified Residue | |
| Post Translational Modification | PTM: [Polyprotein P1234]: Specific enzymatic cleavages in vivo yield mature proteins (PubMed:27845418). The processing of the polyprotein is temporally regulated (By similarity). In early stages (1.7 hpi), P1234 is first cleaved in trans through its nsP2 protease activity, releasing P123 and nsP4, which associate to form the early replication complex (By similarity). At the same time, P1234 is also cut at the nsP1/nsP2 site early in infection but with lower efficiency (By similarity). After replication of the viral minus-strand RNAs (4 hpi), the polyproteins are cut at the nsP1/nsP2 and nsP2/nsP3 sites very efficiently, preventing accumulation of P123 and P1234 and allowing the formation of the late replication complex (By similarity). NsP3/nsP4 site is not cleaved anymore and P34 is produced rather than nsP4 (By similarity). {ECO:0000250|UniProtKB:P03317, ECO:0000269|PubMed:27845418}.; PTM: [Polyprotein P123]: Specific enzymatic cleavages in vivo yield mature proteins (By similarity). The processing of the polyprotein is temporally regulated (By similarity). In early stages (1.7 hpi), P123 is cleaved at the nsP1/nsP2 site with low efficiency (By similarity). After replication of the viral minus-strand RNAs (4 hpi), the polyproteins are cut at the nsP1/nsP2 and nsP2/nsP3 sites very efficiently, preventing accumulation of P123 and allowing the formation of the late replication complex (By similarity). {ECO:0000250|UniProtKB:P03317}.; PTM: [mRNA-capping enzyme nsP1]: Palmitoylated by host palmitoyltransferases ZDHHC2 and ZDHHC19 (PubMed:30404808). Palmitoylation is increased by the interacton with host STING1 (PubMed:33057424). {ECO:0000269|PubMed:30404808, ECO:0000269|PubMed:33057424}.; PTM: [Non-structural protein 3]: Phosphorylated by host on serines and threonines. {ECO:0000250|UniProtKB:P08411}.; PTM: [RNA-directed RNA polymerase nsP4]: Ubiquitinated; targets the protein for rapid degradation via the ubiquitin system (By similarity). Nsp4 is present in extremely low quantities due to low frequency of translation through the amber stop-codon and the degradation by the ubiquitin pathway (By similarity). {ECO:0000250|UniProtKB:P03317}. |
| Signal Peptide | |
| Structure 3D | NMR spectroscopy (1); Electron microscopy (3); X-ray crystallography (5) |
| Cross Reference PDB | 3GPG; 3GPO; 3GPQ; 3TRK; 4TU0; 5I22; 6Z0U; 6Z0V; 7DOP; |
| Mapped Pubmed ID | - |
| Motif | MOTIF 1058..1067; /note=Nuclear export signal; /evidence=ECO:0000250|UniProtKB:P27282; MOTIF 1182..1186; /note=Nuclear localization signal; /evidence=ECO:0000250|UniProtKB:P08411; MOTIF 1812..1815; /note=FGDF; binding to host G3BP1; /evidence=ECO:0000305|PubMed:24623412; MOTIF 1830..1833; /note=FGDF; binding to host G3BP1; /evidence=ECO:0000305|PubMed:24623412 |
| Gene Encoded By | |
| Mass | 275,652 |
| Kinetics | |
| Metal Binding | METAL 79; /note=Zinc; /evidence=ECO:0000269|PubMed:33730549; METAL 129; /note=Zinc; /evidence=ECO:0000269|PubMed:33730549; METAL 134; /note=Zinc; /evidence=ECO:0000269|PubMed:33730549; METAL 141; /note=Zinc; /evidence=ECO:0000269|PubMed:33730549; METAL 1595; /note=Zinc; /evidence=ECO:0000250|UniProtKB:P03317; METAL 1597; /note=Zinc; /evidence=ECO:0000250|UniProtKB:P03317; METAL 1620; /note=Zinc; /evidence=ECO:0000250|UniProtKB:P03317; METAL 1638; /note=Zinc; /evidence=ECO:0000250|UniProtKB:P03317 |
| Rhea ID | RHEA:46948; RHEA:54792; RHEA:54793; RHEA:54800; RHEA:11008; RHEA:23680; RHEA:13065; RHEA:21248; RHEA:54428; RHEA:54429; RHEA:58248; RHEA:58249; RHEA:11332; RHEA:25029; RHEA:25030 |
| Cross Reference Brenda | 3.2.2.B6;3.4.22.B79; |