| Identification |
|---|
| HMDB Protein ID
| HMDBP12381 |
| Secondary Accession Numbers
| None |
| Name
| Polyprotein P1234 |
| Synonyms
|
- P1234
- Non-structural polyprotein
|
| Gene Name
| Not Available |
| Protein Type
| Unknown |
| Biological Properties |
|---|
| General Function
| Not Available |
| Specific Function
| Inactive precursor of the viral replicase, which is activated by cleavages carried out by the viral protease nsP2.The early replication complex formed by the polyprotein P123 and nsP4 synthesizes the minus-strand RNAs (antigenome) (By similarity). 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 (By similarity).The early replication complex formed by the polyprotein P123' and nsP4 synthesizes minus-strand RNAs (antigenome) (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).Cytoplasmic capping enzyme that catalyzes two virus-specific reactions: methyltransferase and nsP1 guanylyltransferase (PubMed:26041283). 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 (PubMed:26041283). NsP1 is also needed for the initiation of the minus-strand RNAs synthesis (By similarity). Probably serves as a membrane anchor for the replication complex composed of nsP1-nsP4 (By similarity). Nsp1 is needed for the initiation of the minus-strand RNAs synthesis (By similarity). Palmitoylated nsP1 is remodeling host cell cytoskeleton, and induces filopodium-like structure formation at the surface of the host cell (By similarity).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 (By similarity). Inhibits host translation to ensure maximal viral gene expression and evade host immune response (PubMed:27318152).Seems to be essential for minus-strand RNAs and subgenomic 26S mRNAs synthesis (By similarity). Displays mono-ADP-ribosylhydrolase activity (PubMed:28150709, PubMed:27440879). 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:28150709). Binds proteins of FXR family and sequesters them into the viral RNA replication complexes thereby inhibiting the formation of host stress granules on viral mRNAs (PubMed:27509095). The nsp3-FXR complexes bind viral RNAs and probably orchestrate the assembly of viral replication complexes, thanks to the ability of FXR family members to self-assemble and bind DNA (PubMed:27509095).Seems to be essential for minus-strand RNAs and subgenomic 26S mRNAs synthesis (By similarity). 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 FXR family and sequesters them into the viral RNA replication complexes thereby inhibiting the formation of host stress granules on viral mRNAs (Probable). The nsp3'-FXR complexes bind viral RNAs and probably orchestrate the assembly of viral replication complexes, thanks to the ability of FXR family members to self-assemble and bind DNA (Probable).RNA dependent RNA polymerase (By similarity). Replicates genomic and antigenomic RNA by recognizing replications specific signals. The early replication complex formed by the polyproteins P123/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). |
| Pathways
|
Not Available
|
| Reactions
| Not Available |
| GO Classification
|
| Biological Process |
| viral RNA genome replication |
| transcription, DNA-dependent |
| suppression by virus of host RNA polymerase II activity |
| 7-methylguanosine mRNA capping |
| Cellular Component |
| membrane |
| host cell plasma membrane |
| host cell nucleus |
| host cell filopodium |
| host cell cytoplasmic vesicle membrane |
| Molecular Function |
| polynucleotide 5'-phosphatase activity |
| ADP-ribosyl-[dinitrogen reductase] hydrolase activity |
| mRNA methyltransferase activity |
| cysteine-type peptidase activity |
| RNA-directed RNA polymerase activity |
| metal ion binding |
| polynucleotide adenylyltransferase activity |
| nucleoside-triphosphatase activity |
| RNA helicase activity |
| GTP binding |
| RNA binding |
| ATP binding |
|
| Cellular Location
|
Not Available
|
| Gene Properties |
|---|
| Chromosome Location
| Not Available |
| Locus
| Not Available |
| SNPs
| Not Available |
| Gene Sequence
|
Not Available
|
| Protein Properties |
|---|
| Number of Residues
| Not Available |
| Molecular Weight
| Not Available |
| Theoretical pI
| Not Available |
| Pfam Domain Function
|
|
| Signals
|
Not Available
|
|
Transmembrane Regions
|
Not Available
|
| Protein Sequence
|
Not Available
|
| External Links |
|---|
| GenBank ID Protein
| Not Available |
| UniProtKB/Swiss-Prot ID
| P27282 |
| UniProtKB/Swiss-Prot Entry Name
| POLN_EEVVT |
| PDB IDs
|
|
| GenBank Gene ID
| Not Available |
| GeneCard ID
| Not Available |
| GenAtlas ID
| Not Available |
| HGNC ID
| Not Available |
| References |
|---|
| General References
| - Kinney RM, Johnson BJ, Welch JB, Tsuchiya KR, Trent DW: The full-length nucleotide sequences of the virulent Trinidad donkey strain of Venezuelan equine encephalitis virus and its attenuated vaccine derivative, strain TC-83. Virology. 1989 May;170(1):19-30. [PubMed:2524126 ]
- Kinney RM, Tsuchiya KR, Sneider JM, Trent DW: Molecular evidence for the origin of the widespread Venezuelan equine encephalitis epizootic of 1969 to 1972. J Gen Virol. 1992 Dec;73 ( Pt 12):3301-5. [PubMed:1469368 ]
- Eckei L, Krieg S, Butepage M, Lehmann A, Gross A, Lippok B, Grimm AR, Kummerer BM, Rossetti G, Luscher B, Verheugd P: The conserved macrodomains of the non-structural proteins of Chikungunya virus and other pathogenic positive strand RNA viruses function as mono-ADP-ribosylhydrolases. Sci Rep. 2017 Feb 2;7:41746. doi: 10.1038/srep41746. [PubMed:28150709 ]
- Kim DY, Reynaud JM, Rasalouskaya A, Akhrymuk I, Mobley JA, Frolov I, Frolova EI: New World and Old World Alphaviruses Have Evolved to Exploit Different Components of Stress Granules, FXR and G3BP Proteins, for Assembly of Viral Replication Complexes. PLoS Pathog. 2016 Aug 10;12(8):e1005810. doi: 10.1371/journal.ppat.1005810. eCollection 2016 Aug. [PubMed:27509095 ]
- Montgomery SA, Johnston RE: Nuclear import and export of Venezuelan equine encephalitis virus nonstructural protein 2. J Virol. 2007 Oct;81(19):10268-79. doi: 10.1128/JVI.00371-07. Epub 2007 Jul 25. [PubMed:17652399 ]
- Kim DY, Atasheva S, Frolova EI, Frolov I: Venezuelan equine encephalitis virus nsP2 protein regulates packaging of the viral genome into infectious virions. J Virol. 2013 Apr;87(8):4202-13. doi: 10.1128/JVI.03142-12. Epub 2013 Jan 30. [PubMed:23365438 ]
- Li C, Guillen J, Rabah N, Blanjoie A, Debart F, Vasseur JJ, Canard B, Decroly E, Coutard B: mRNA Capping by Venezuelan Equine Encephalitis Virus nsP1: Functional Characterization and Implications for Antiviral Research. J Virol. 2015 Aug;89(16):8292-303. doi: 10.1128/JVI.00599-15. Epub 2015 Jun 3. [PubMed:26041283 ]
- Amaya M, Brooks-Faulconer T, Lark T, Keck F, Bailey C, Raman V, Narayanan A: Venezuelan equine encephalitis virus non-structural protein 3 (nsP3) interacts with RNA helicases DDX1 and DDX3 in infected cells. Antiviral Res. 2016 Jul;131:49-60. doi: 10.1016/j.antiviral.2016.04.008. Epub 2016 Apr 20. [PubMed:27105836 ]
- Bhalla N, Sun C, Metthew Lam LK, Gardner CL, Ryman KD, Klimstra WB: Host translation shutoff mediated by non-structural protein 2 is a critical factor in the antiviral state resistance of Venezuelan equine encephalitis virus. Virology. 2016 Sep;496:147-165. doi: 10.1016/j.virol.2016.06.005. Epub 2016 Jun 15. [PubMed:27318152 ]
- Li C, Debing Y, Jankevicius G, Neyts J, Ahel I, Coutard B, Canard B: Viral Macro Domains Reverse Protein ADP-Ribosylation. J Virol. 2016 Sep 12;90(19):8478-86. doi: 10.1128/JVI.00705-16. Print 2016 Oct 1. [PubMed:27440879 ]
- Hu X, Compton JR, Leary DH, Olson MA, Lee MS, Cheung J, Ye W, Ferrer M, Southall N, Jadhav A, Morazzani EM, Glass PJ, Marugan J, Legler PM: Kinetic, Mutational, and Structural Studies of the Venezuelan Equine Encephalitis Virus Nonstructural Protein 2 Cysteine Protease. Biochemistry. 2016 May 31;55(21):3007-19. doi: 10.1021/acs.biochem.5b00992. Epub 2016 May 19. [PubMed:27030368 ]
- Compton JR, Mickey MJ, Hu X, Marugan JJ, Legler PM: Mutation of Asn-475 in the Venezuelan Equine Encephalitis Virus nsP2 Cysteine Protease Leads to a Self-Inhibited State. Biochemistry. 2017 Nov 28;56(47):6221-6230. doi: 10.1021/acs.biochem.7b00746. Epub 2017 Nov 9. [PubMed:29064679 ]
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