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Showing Protein Polyprotein P1234 (HMDBP12372)

IdentificationBiological propertiesGene propertiesProtein propertiesExternal linksReferencesXMLShow 0 metabolites
Identification
HMDB Protein ID HMDBP12372
Secondary Accession Numbers None
Name Polyprotein P1234
Synonyms
  1. P1234
  2. Non-structural polyprotein
Gene Name (REFSEQ) CHIKUNGUNYA VIRUS; NONSTRUCTURAL POLYPROTEIN
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 minus-strand RNAs (By similarity). As soon P123 is cleaved into mature proteins, the plus-strand RNAs synthesis begins (By similarity).Cytoplasmic capping enzyme that catalyzes two virus-specific reactions: methyltransferase and nsP1 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). 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 (PubMed:30404808).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).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).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).
Pathways Not Available
Reactions Not Available
GO Classification
Biological Process
suppression by virus of host STAT activity
stress granule disassembly
regulation of cytoskeleton organization
transcription, DNA-dependent
suppression by virus of host type I interferon-mediated signaling pathway
suppression by virus of host STAT1 activity
positive stranded viral RNA replication
viral RNA genome replication
7-methylguanosine mRNA capping
suppression by virus of host RNA polymerase II activity
Cellular Component
host cell filopodium
host cell plasma membrane
host cell nucleus
host cell cytoplasmic vesicle membrane
membrane
Molecular Function
metal ion binding
RNA-directed RNA polymerase activity
polynucleotide 5'-phosphatase activity
cysteine-type peptidase activity
mRNA methyltransferase activity
polynucleotide adenylyltransferase activity
nucleoside-triphosphatase activity
ADP-ribosyl-[dinitrogen reductase] hydrolase activity
RNA helicase activity
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 2474
Molecular Weight 275649.415
Theoretical pI 7.232
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence Not Available
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID Q8JUX6
UniProtKB/Swiss-Prot Entry Name POLN_CHIKS
PDB IDs
GenBank Gene ID Not Available
GeneCard ID Not Available
GenAtlas ID Not Available
HGNC ID Not Available
References
General References
  1. Khan AH, Morita K, Parquet Md Mdel C, Hasebe F, Mathenge EG, Igarashi A: Complete nucleotide sequence of chikungunya virus and evidence for an internal polyadenylation site. J Gen Virol. 2002 Dec;83(Pt 12):3075-84. [PubMed:12466484 ]
  2. Akhrymuk I, Kulemzin SV, Frolova EI: Evasion of the innate immune response: the Old World alphavirus nsP2 protein induces rapid degradation of Rpb1, a catalytic subunit of RNA polymerase II. J Virol. 2012 Jul;86(13):7180-91. doi: 10.1128/JVI.00541-12. Epub 2012 Apr 18. [PubMed:22514352 ]
  3. 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 ]
  4. Karpe YA, Aher PP, Lole KS: NTPase and 5'-RNA triphosphatase activities of Chikungunya virus nsP2 protein. PLoS One. 2011;6(7):e22336. doi: 10.1371/journal.pone.0022336. Epub 2011 Jul 19. [PubMed:21811589 ]
  5. Sreejith R, Rana J, Dudha N, Kumar K, Gabrani R, Sharma SK, Gupta A, Vrati S, Chaudhary VK, Gupta S: Mapping interactions of Chikungunya virus nonstructural proteins. Virus Res. 2012 Oct;169(1):231-6. doi: 10.1016/j.virusres.2012.08.006. Epub 2012 Aug 19. [PubMed:22951312 ]
  6. Das PK, Merits A, Lulla A: Functional cross-talk between distant domains of chikungunya virus non-structural protein 2 is decisive for its RNA-modulating activity. J Biol Chem. 2014 Feb 28;289(9):5635-53. doi: 10.1074/jbc.M113.503433. Epub 2014 Jan 9. [PubMed:24407286 ]
  7. Saisawang C, Saitornuang S, Sillapee P, Ubol S, Smith DR, Ketterman AJ: Chikungunya nsP2 protease is not a papain-like cysteine protease and the catalytic dyad cysteine is interchangeable with a proximal serine. Sci Rep. 2015 Nov 24;5:17125. doi: 10.1038/srep17125. [PubMed:26597768 ]
  8. Scholte FE, Tas A, Albulescu IC, Zusinaite E, Merits A, Snijder EJ, van Hemert MJ: Stress granule components G3BP1 and G3BP2 play a proviral role early in Chikungunya virus replication. J Virol. 2015 Apr;89(8):4457-69. doi: 10.1128/JVI.03612-14. Epub 2015 Feb 4. [PubMed:25653451 ]
  9. Schulte T, Liu L, Panas MD, Thaa B, Dickson N, Gotte B, Achour A, McInerney GM: Combined structural, biochemical and cellular evidence demonstrates that both FGDF motifs in alphavirus nsP3 are required for efficient replication. Open Biol. 2016 Jul;6(7). pii: rsob.160078. doi: 10.1098/rsob.160078. [PubMed:27383630 ]
  10. 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 ]
  11. McPherson RL, Abraham R, Sreekumar E, Ong SE, Cheng SJ, Baxter VK, Kistemaker HA, Filippov DV, Griffin DE, Leung AK: ADP-ribosylhydrolase activity of Chikungunya virus macrodomain is critical for virus replication and virulence. Proc Natl Acad Sci U S A. 2017 Feb 14;114(7):1666-1671. doi: 10.1073/pnas.1621485114. Epub 2017 Jan 31. [PubMed:28143925 ]
  12. Jones JE, Long KM, Whitmore AC, Sanders W, Thurlow LR, Brown JA, Morrison CR, Vincent H, Peck KM, Browning C, Moorman N, Lim JK, Heise MT: Disruption of the Opal Stop Codon Attenuates Chikungunya Virus-Induced Arthritis and Pathology. mBio. 2017 Nov 14;8(6). pii: mBio.01456-17. doi: 10.1128/mBio.01456-17. [PubMed:29138302 ]
  13. Goertz GP, McNally KL, Robertson SJ, Best SM, Pijlman GP, Fros JJ: The Methyltransferase-Like Domain of Chikungunya Virus nsP2 Inhibits the Interferon Response by Promoting the Nuclear Export of STAT1. J Virol. 2018 Aug 16;92(17). pii: JVI.01008-18. doi: 10.1128/JVI.01008-18. Print 2018 Sep 1. [PubMed:29925658 ]
  14. Zhang N, Zhao H, Zhang L: Fatty Acid Synthase Promotes the Palmitoylation of Chikungunya Virus nsP1. J Virol. 2019 Jan 17;93(3). pii: JVI.01747-18. doi: 10.1128/JVI.01747-18. Print 2019 Feb 1. [PubMed:30404808 ]
  15. Tossavainen H, Aitio O, Hellman M, Saksela K, Permi P: Structural Basis of the High Affinity Interaction between the Alphavirus Nonstructural Protein-3 (nsP3) and the SH3 Domain of Amphiphysin-2. J Biol Chem. 2016 Jul 29;291(31):16307-17. doi: 10.1074/jbc.M116.732412. Epub 2016 Jun 6. [PubMed:27268056 ]