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Showing Protein Polyprotein P1234 (HMDBP12367)

IdentificationBiological propertiesGene propertiesProtein propertiesExternal linksReferencesXMLShow 0 metabolites
Identification
HMDB Protein ID HMDBP12367
Secondary Accession Numbers None
Name Polyprotein P1234
Synonyms
  1. P1234
  2. Non-structural polyprotein
  3. p270 nonstructural polyprotein
Gene Name (REFSEQ) SINDBIS VIRUS; HYPOTHETICAL PROTEIN
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 (PubMed:8107248, PubMed:7517863). Polyprotein P123 is a short-lived polyprotein that accumulates during early stage of infection (PubMed:8107248, PubMed:7517863). As soon P123 is cleaved into mature proteins, the plus-strand RNAs synthesis begins (PubMed:8107248, PubMed:7517863).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).Cytoplasmic capping enzyme that catalyzes two virus-specific reactions: methyltransferase and nsP1 guanylyltransferase (PubMed:7831320). 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 (PubMed:1824787). 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).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 (PubMed:8627744). 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 (PubMed:22514352, PubMed:17108023, PubMed:30232189). 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 (PubMed:8057460). Displays mono-ADP-ribosylhydrolase activity (PubMed:28150709). 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 (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:18684830). 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).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 dependent RNA polymerase (PubMed:8107248, PubMed:7517863, PubMed:19036396). 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 (PubMed:8107248, PubMed:7517863, PubMed:2529379). The late replication complex composed of fully processed nsP1-nsP4 is responsible for the production of genomic and subgenomic plus-strand RNAs (PubMed:8107248, PubMed:7517863). 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 (PubMed:17005674).
Pathways Not Available
Reactions Not Available
GO Classification
Biological Process
7-methylguanosine mRNA capping
suppression by virus of host RNA polymerase II activity
negative regulation of stress granule assembly
positive stranded viral RNA replication
suppression by virus of host STAT1 activity
suppression by virus of host transcription
suppression by virus of host type I interferon-mediated signaling pathway
transcription, DNA-dependent
Cellular Component
host cell cytoplasmic vesicle membrane
host cell filopodium
host cell nucleus
host cell plasma membrane
membrane
Molecular Function
RNA-directed RNA polymerase activity
metal ion binding
RNA helicase activity
nucleoside-triphosphatase activity
ATP binding
RNA binding
cysteine-type peptidase activity
GTP binding
mRNA methyltransferase activity
polynucleotide 5'-phosphatase activity
adenylyltransferase activity
ADP-ribosyl-[dinitrogen reductase] hydrolase activity
polynucleotide adenylyltransferase activity
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 2513
Molecular Weight Not Available
Theoretical pI 8.003
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence Not Available
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID P03317
UniProtKB/Swiss-Prot Entry Name POLN_SINDV
PDB IDs
GenBank Gene ID Not Available
GeneCard ID Not Available
GenAtlas ID Not Available
HGNC ID Not Available
References
General References
  1. Strauss EG, Rice CM, Strauss JH: Complete nucleotide sequence of the genomic RNA of Sindbis virus. Virology. 1984 Feb;133(1):92-110. [PubMed:6322438 ]
  2. Ou JH, Strauss EG, Strauss JH: The 5'-terminal sequences of the genomic RNAs of several alphaviruses. J Mol Biol. 1983 Jul 25;168(1):1-15. [PubMed:6308269 ]
  3. Strauss EG, Rice CM, Strauss JH: Sequence coding for the alphavirus nonstructural proteins is interrupted by an opal termination codon. Proc Natl Acad Sci U S A. 1983 Sep;80(17):5271-5. [PubMed:6577423 ]
  4. Ou JH, Rice CM, Dalgarno L, Strauss EG, Strauss JH: Sequence studies of several alphavirus genomic RNAs in the region containing the start of the subgenomic RNA. Proc Natl Acad Sci U S A. 1982 Sep;79(17):5235-9. [PubMed:6291034 ]
  5. Froshauer S, Kartenbeck J, Helenius A: Alphavirus RNA replicase is located on the cytoplasmic surface of endosomes and lysosomes. J Cell Biol. 1988 Dec;107(6 Pt 1):2075-86. [PubMed:2904446 ]
  6. Hardy WR, Strauss JH: Processing the nonstructural polyproteins of sindbis virus: nonstructural proteinase is in the C-terminal half of nsP2 and functions both in cis and in trans. J Virol. 1989 Nov;63(11):4653-64. [PubMed:2529379 ]
  7. Li GP, Rice CM: Mutagenesis of the in-frame opal termination codon preceding nsP4 of Sindbis virus: studies of translational readthrough and its effect on virus replication. J Virol. 1989 Mar;63(3):1326-37. [PubMed:2521676 ]
  8. de Groot RJ, Hardy WR, Shirako Y, Strauss JH: Cleavage-site preferences of Sindbis virus polyproteins containing the non-structural proteinase. Evidence for temporal regulation of polyprotein processing in vivo. EMBO J. 1990 Aug;9(8):2631-8. [PubMed:2142454 ]
  9. de Groot RJ, Rumenapf T, Kuhn RJ, Strauss EG, Strauss JH: Sindbis virus RNA polymerase is degraded by the N-end rule pathway. Proc Natl Acad Sci U S A. 1991 Oct 15;88(20):8967-71. [PubMed:1924357 ]
  10. Strauss EG, De Groot RJ, Levinson R, Strauss JH: Identification of the active site residues in the nsP2 proteinase of Sindbis virus. Virology. 1992 Dec;191(2):932-40. [PubMed:1448929 ]
  11. Lemm JA, Rumenapf T, Strauss EG, Strauss JH, Rice CM: Polypeptide requirements for assembly of functional Sindbis virus replication complexes: a model for the temporal regulation of minus- and plus-strand RNA synthesis. EMBO J. 1994 Jun 15;13(12):2925-34. [PubMed:7517863 ]
  12. Shirako Y, Strauss JH: Regulation of Sindbis virus RNA replication: uncleaved P123 and nsP4 function in minus-strand RNA synthesis, whereas cleaved products from P123 are required for efficient plus-strand RNA synthesis. J Virol. 1994 Mar;68(3):1874-85. [PubMed:8107248 ]
  13. Wang HL, O'Rear J, Stollar V: Mutagenesis of the Sindbis virus nsP1 protein: effects on methyltransferase activity and viral infectivity. Virology. 1996 Mar 15;217(2):527-31. [PubMed:8610444 ]
  14. Shirako Y, Strauss JH: Requirement for an aromatic amino acid or histidine at the N terminus of Sindbis virus RNA polymerase. J Virol. 1998 Mar;72(3):2310-5. [PubMed:9499091 ]
  15. Ahola T, Kujala P, Tuittila M, Blom T, Laakkonen P, Hinkkanen A, Auvinen P: Effects of palmitoylation of replicase protein nsP1 on alphavirus infection. J Virol. 2000 Aug;74(15):6725-33. [PubMed:10888610 ]
  16. Ventoso I, Sanz MA, Molina S, Berlanga JJ, Carrasco L, Esteban M: Translational resistance of late alphavirus mRNA to eIF2alpha phosphorylation: a strategy to overcome the antiviral effect of protein kinase PKR. Genes Dev. 2006 Jan 1;20(1):87-100. [PubMed:16391235 ]
  17. Ahola T, Kaariainen L: Reaction in alphavirus mRNA capping: formation of a covalent complex of nonstructural protein nsP1 with 7-methyl-GMP. Proc Natl Acad Sci U S A. 1995 Jan 17;92(2):507-11. [PubMed:7831320 ]
  18. Shirako Y, Strauss JH: Cleavage between nsP1 and nsP2 initiates the processing pathway of Sindbis virus nonstructural polyprotein P123. Virology. 1990 Jul;177(1):54-64. doi: 10.1016/0042-6822(90)90459-5. [PubMed:2141206 ]
  19. Wang YF, Sawicki SG, Sawicki DL: Sindbis virus nsP1 functions in negative-strand RNA synthesis. J Virol. 1991 Feb;65(2):985-8. doi: 10.1128/JVI.65.2.985-988.1991. [PubMed:1824787 ]
  20. LaStarza MW, Lemm JA, Rice CM: Genetic analysis of the nsP3 region of Sindbis virus: evidence for roles in minus-strand and subgenomic RNA synthesis. J Virol. 1994 Sep;68(9):5781-91. doi: 10.1128/JVI.68.9.5781-5791.1994. [PubMed:8057460 ]
  21. De I, Sawicki SG, Sawicki DL: Sindbis virus RNA-negative mutants that fail to convert from minus-strand to plus-strand synthesis: role of the nsP2 protein. J Virol. 1996 May;70(5):2706-19. doi: 10.1128/JVI.70.5.2706-2719.1996. [PubMed:8627744 ]
  22. Frolova E, Gorchakov R, Garmashova N, Atasheva S, Vergara LA, Frolov I: Formation of nsP3-specific protein complexes during Sindbis virus replication. J Virol. 2006 Apr;80(8):4122-34. doi: 10.1128/JVI.80.8.4122-4134.2006. [PubMed:16571828 ]
  23. Tomar S, Hardy RW, Smith JL, Kuhn RJ: Catalytic core of alphavirus nonstructural protein nsP4 possesses terminal adenylyltransferase activity. J Virol. 2006 Oct;80(20):9962-9. doi: 10.1128/JVI.01067-06. [PubMed:17005674 ]
  24. Garmashova N, Gorchakov R, Volkova E, Paessler S, Frolova E, Frolov I: The Old World and New World alphaviruses use different virus-specific proteins for induction of transcriptional shutoff. J Virol. 2007 Mar;81(5):2472-84. doi: 10.1128/JVI.02073-06. Epub 2006 Nov 15. [PubMed:17108023 ]
  25. Gorchakov R, Garmashova N, Frolova E, Frolov I: Different types of nsP3-containing protein complexes in Sindbis virus-infected cells. J Virol. 2008 Oct;82(20):10088-101. doi: 10.1128/JVI.01011-08. Epub 2008 Aug 6. [PubMed:18684830 ]
  26. Rubach JK, Wasik BR, Rupp JC, Kuhn RJ, Hardy RW, Smith JL: Characterization of purified Sindbis virus nsP4 RNA-dependent RNA polymerase activity in vitro. Virology. 2009 Feb 5;384(1):201-8. doi: 10.1016/j.virol.2008.10.030. Epub 2008 Nov 25. [PubMed:19036396 ]
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  28. 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 ]
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  31. Shin G, Yost SA, Miller MT, Elrod EJ, Grakoui A, Marcotrigiano J: Structural and functional insights into alphavirus polyprotein processing and pathogenesis. Proc Natl Acad Sci U S A. 2012 Oct 9;109(41):16534-9. doi: 10.1073/pnas.1210418109. Epub 2012 Sep 25. [PubMed:23010928 ]