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UniProtKB/Swiss-Prot entry P08411

[Entry info] [Name and origin] [References] [Comments] [Cross-references] [Keywords] [Features] [Sequence] [Tools]

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Entry information
Entry name POLN_SFV
Primary accession number P08411
Secondary accession numbers Q3LRQ3 Q3LRQ4 Q3LRQ6 Q3LRQ7 Q3LRQ9 Q3LRR0 Q3LRR1 Q3LRR2 Q8JMP6 Q9QBM1
Integrated into Swiss-Prot on August 1, 1988
Sequence was last modified on March 21, 2006 (Sequence version 2)
Annotations were last modified on    September 2, 2008 (Entry version 82)
Name and origin of the protein
Protein name Non-structural polyprotein
Synonyms Polyprotein nsP1234
P1234
Contains P123
mRNA-capping enzyme nsP1
     (EC 2.1.1.-)
     (EC 2.7.7.-)
     (Non-structural protein 1)
Protease/triphosphatase/NTPase/helicase nsP2
     (EC 3.4.22.-)
     (EC 3.1.3.33)
     (EC 3.6.1.15)
     (EC 3.6.1.-)
     (Non-structural protein 2)
     (nsP2)
Non-structural protein 3
     (nsP3)
RNA-directed RNA polymerase nsP4
     (EC 2.7.7.48)
     (Non-structural protein 4)
     (nsP4)
Gene name None
From
Semliki forest virus (SFV) [TaxID: 11033] 
Taxonomy Viruses; ssRNA positive-strand viruses, no DNA stage; Togaviridae; Alphavirus; SFV complex.
Virus hosts Aedes [TaxID: 7158]
Atelerix albiventris (Middle-African hedgehog) [TaxID: 9368]
Culex tritaeniorhynchus [TaxID: 7178]
Halcyon [TaxID: 170865]
Homo sapiens (Human) [TaxID: 9606]
Quelea [TaxID: 158617]
Rhipicephalus [TaxID: 34630]
Protein existence 1: Evidence at protein level;
References
[1]
 NUCLEOTIDE SEQUENCE [GENOMIC RNA].
STRAIN=Isolate Garoff/Takkinen;
DOI=10.1093/nar/14.14.5667; PubMed=3488539 [NCBI, ExPASy, EBI, Israel, Japan]
Takkinen K.;
"Complete nucleotide sequence of the nonstructural protein genes of Semliki Forest virus.";
Nucleic Acids Res. 14:5667-5682(1986).
[2]
 NUCLEOTIDE SEQUENCE [GENOMIC RNA].
STRAIN=Isolate L10 clone SFV4;
DOI=10.1128/JVI.74.10.4579-4589.2000; PubMed=10775594 [NCBI, ExPASy, EBI, Israel, Japan]
Tuittila M.T., Santagati M.G., Roeyttae M., Maeaettae J.A., Hinkkanen A.E.;
"Replicase complex genes of Semliki Forest virus confer lethal neurovirulence.";
J. Virol. 74:4579-4589(2000).
[3]
 NUCLEOTIDE SEQUENCE [GENOMIC RNA].
STRAIN=Isolate L10;
Logue C., Mooney D., Shanley R., Atkins G.J.;
"Semliki Forest virus -- L10 strain complete genome.";
Submitted (MAY-2002) to the EMBL/GenBank/DDBJ databases.
[4]
 NUCLEOTIDE SEQUENCE [GENOMIC RNA].
STRAIN=Isolate Ts1, Isolate Ts10, Isolate TS11, Isolate Ts13, Isolate Ts14, Isolate Ts6, and Isolate Ts9;
DOI=10.1128/JVI.80.6.3108-3111.2006; PubMed=16501123 [NCBI, ExPASy, EBI, Israel, Japan]
Lulla V., Merits A., Sarin P., Kaariainen L., Keranen S., Ahola T.;
"Identification of mutations causing temperature-sensitive defects in Semliki Forest virus RNA synthesis.";
J. Virol. 80:3108-3111(2006).
[5]
 SUBCELLULAR LOCATION OF NON-STRUCTURAL PROTEINS.
DOI=10.1083/jcb.107.6.2075; PubMed=2904446 [NCBI, ExPASy, EBI, Israel, Japan]
Froshauer S., Kartenbeck J., Helenius A.;
"Alphavirus RNA replicase is located on the cytoplasmic surface of endosomes and lysosomes.";
J. Cell Biol. 107:2075-2086(1988).
[6]
 SUBCELLULAR LOCATION OF NSP2.
DOI=10.1016/0042-6822(92)90570-F; PubMed=1386484 [NCBI, ExPASy, EBI, Israel, Japan]
Rikkonen M., Peraenen J., Kaeaeriaeinen L.;
"Nuclear and nucleolar targeting signals of Semliki Forest virus nonstructural protein nsP2.";
Virology 189:462-473(1992).
[7]
 FUNCTION OF NSP2.
PubMed=8057461 [NCBI, ExPASy, EBI, Israel, Japan]
Rikkonen M., Peraenen J., Kaeaeriaeinen L.;
"ATPase and GTPase activities associated with Semliki Forest virus nonstructural protein nsP2.";
J. Virol. 68:5804-5810(1994).
[8]
 SUBCELLULAR LOCATION OF NSP1.
DOI=10.1006/viro.1995.1192; PubMed=7747433 [NCBI, ExPASy, EBI, Israel, Japan]
Peraenen J., Laakkonen P., Hyvoenen M., Kaeaeriaeinen L.;
"The alphavirus replicase protein nsP1 is membrane-associated and has affinity to endocytic organelles.";
Virology 208:610-620(1995).
[9]
 CHARACTERIZATION OF MRNA GUANYLYLTRANSFERASE FUNCTION OF NSP1.
PubMed=7831320 [NCBI, ExPASy, EBI, Israel, Japan]
Ahola T., Kaeaeriaeinen 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. 92:507-511(1995).
[10]
 PALMITOYLATION AT CYS-418 AND CYS-420, AND MUTAGENESIS OF 418-CYS--CYS-420.
DOI=10.1074/jbc.271.45.28567; PubMed=8910486 [NCBI, ExPASy, EBI, Israel, Japan]
Laakkonen P., Ahola T., Kaeaeriaeinen L.;
"The effects of palmitoylation on membrane association of Semliki forest virus RNA capping enzyme.";
J. Biol. Chem. 271:28567-28571(1996).
[11]
 SUBCELLULAR LOCATION OF NPS2, AND MUTAGENESIS OF ARG-1186.
DOI=10.1006/viro.1996.0204; PubMed=8610462 [NCBI, ExPASy, EBI, Israel, Japan]
Rikkonen M.;
"Functional significance of the nuclear-targeting and NTP-binding motifs of Semliki Forest virus nonstructural protein nsP2.";
Virology 218:352-361(1996).
[12]
 FUNCTION OF NSP1, AND MUTAGENESIS OF LEU-19; HIS-38; ASP-64; 81-CYS--CYS-83; ASP-90; ARG-93; CYS-135; CYS-142; ASP-153; LYS-169; ASP-180; GLU-203; CYS-214; TYR-249 AND LYS-317.
PubMed=8985362 [NCBI, ExPASy, EBI, Israel, Japan]
Ahola T., Laakkonen P., Vihinen H., Kaeaeriaeinen L.;
"Critical residues of Semliki Forest virus RNA capping enzyme involved in methyltransferase and guanylyltransferase-like activities.";
J. Virol. 71:392-397(1997).
[13]
 FUNCTION OF NSP1.
PubMed=9811773 [NCBI, ExPASy, EBI, Israel, Japan]
Laakkonen P., Auvinen P., Kujala P., Kaeaeriaeinen L.;
"Alphavirus replicase protein NSP1 induces filopodia and rearrangement of actin filaments.";
J. Virol. 72:10265-10269(1998).
[14]
 MEMBRANE-BINDING OF NSP1.
DOI=10.1093/emboj/18.11.3164; PubMed=10357827 [NCBI, ExPASy, EBI, Israel, Japan]
Ahola T., Lampio A., Auvinen P., Kaeaeriaeinen L.;
"Semliki Forest virus mRNA capping enzyme requires association with anionic membrane phospholipids for activity.";
EMBO J. 18:3164-3172(1999).
[15]
 FUNCTION OF NSP2, AND MUTAGENESIS OF LYS-729.
DOI=10.1016/S0014-5793(99)00321-X; PubMed=10217401 [NCBI, ExPASy, EBI, Israel, Japan]
Gomez de Cedron M., Ehsani N., Mikkola M.L., Garcia J.A., Kaeaeriaeinen L.;
"RNA helicase activity of Semliki Forest virus replicase protein NSP2.";
FEBS Lett. 448:19-22(1999).
[16]
 PALMITOYLATION AT CYS-418 AND CYS-420, AND MUTAGENESIS OF 418-CYS--CYS-420.
DOI=10.1128/JVI.74.15.6725-6733.2000; PubMed=10888610 [NCBI, ExPASy, EBI, Israel, Japan]
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. 74:6725-6733(2000).
[17]
 FUNCTION, AND BIOPHYSICOCHEMICAL PROPERTIES OF NSP2.
DOI=10.1074/jbc.M910340199; PubMed=10748213 [NCBI, ExPASy, EBI, Israel, Japan]
Vasiljeva L., Merits A., Auvinen P., Kaeaeriaeinen L.;
"Identification of a novel function of the alphavirus capping apparatus. RNA 5'-triphosphatase activity of Nsp2.";
J. Biol. Chem. 275:17281-17287(2000).
[18]
 ACTIVE SITE OF NSP2 PROTEASE, AND MUTAGENESIS OF CYS-1015 AND ASP-1824.
PubMed=11257180 [NCBI, ExPASy, EBI, Israel, Japan]
Merits A., Vasiljeva L., Ahola T., Kaeaeriaeinen L., Auvinen P.;
"Proteolytic processing of Semliki Forest virus-specific non-structural polyprotein by nsP2 protease.";
J. Gen. Virol. 82:765-773(2001).
[19]
 PHOSPHORYLATION AT THR-1680 AND THR-1681, AND MUTAGENESIS OF THR-1680 AND THR-1681.
DOI=10.1074/jbc.M006077200; PubMed=11104756 [NCBI, ExPASy, EBI, Israel, Japan]
Vihinen H., Ahola T., Tuittila M., Merits A., Kaeaeriaeinen L.;
"Elimination of phosphorylation sites of Semliki Forest virus replicase protein nsP3.";
J. Biol. Chem. 276:5745-5752(2001).
[20]
 PROTEOLYTIC PROCESSING OF POLYPROTEIN.
DOI=10.1074/jbc.M307481200; PubMed=12917405 [NCBI, ExPASy, EBI, Israel, Japan]
Vasiljeva L., Merits A., Golubtsov A., Sizemskaja V., Kaeaeriaeinen L., Ahola T.;
"Regulation of the sequential processing of Semliki Forest virus replicase polyprotein.";
J. Biol. Chem. 278:41636-41645(2003).
[21]
 INDUCTION.
DOI=10.1091/mbc.E05-02-0124; PubMed=15930128 [NCBI, ExPASy, EBI, Israel, Japan]
McInerney G.M., Kedersha N.L., Kaufman R.J., Anderson P., Liljestrom P.;
"Importance of eIF2alpha phosphorylation and stress granule assembly in alphavirus translation regulation.";
Mol. Biol. Cell 16:3753-3763(2005).
[22]
 INDUCTION.
DOI=10.1101/gad.357006; PubMed=16391235 [NCBI, ExPASy, EBI, Israel, Japan]
Ventoso I., Sanz M.A., Molina S., Berlanga J.J., 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. 20:87-100(2006).
[23]
 FUNCTION OF NSP2.
DOI=10.1128/JVI.80.1.360-371.2006; PubMed=16352561 [NCBI, ExPASy, EBI, Israel, Japan]
Sawicki D.L., Perri S., Polo J.M., Sawicki S.G.;
"Role for nsP2 proteins in the cessation of alphavirus minus-strand synthesis by host cells.";
J. Virol. 80:360-371(2006).
[24]
 STRUCTURE BY NMR OF 245-264.
DOI=10.1074/jbc.M004865200; PubMed=10984480 [NCBI, ExPASy, EBI, Israel, Japan]
Lampio A., Kilpelainen I., Pesonen S., Karhi K., Auvinen P., Somerharju P., Kaeaeriaeinen L.;
"Membrane binding mechanism of an RNA virus-capping enzyme.";
J. Biol. Chem. 275:37853-37859(2000).
Comments
  • FUNCTION: P123 is short-lived polyproteins, accumulating during early stage of infection. It localizes the viral replication complex to the cytoplasmic surface of modified endosomes and lysosomes. By interacting with nsP4, it starts viral genome replication into antigenome. After these early events, P123 is cleaved sequentially into nsP1, nsP2 and nsP3. This sequence of delayed processing would allow correct assembly and membrane association of the RNA polymerase complex.
  • FUNCTION: nsP1 is a cytoplasmic capping enzyme. This function is necessary since all viral RNAs are synthesized in the cytoplasm, and host capping enzymes are restricted to the nucleus. The enzymatic reaction involves a covalent link between 7-methyl-GMP and nsP1, whereas eukaryotic capping enzymes form a covalent complex only with GMP. nsP1 capping would consist in the following reactions: GTP is first methylated and then forms the m7GMp-nsP1 complex, from which 7-methyl-GMP complex is transferred to the mRNA to create the cap structure. Palmitoylated nsP1 is remodeling host cell cytoskeleton, and induces filopodium-like structure formation at the surface of the host cell.
  • FUNCTION: nsP2 has two separate domain with different biological activities. The N-terminal section is part of the RNA polymerase complex and has RNA trisphosphatase and RNA helicase activity. The C-terminal section harbors a protease that specifically cleaves and releases the four mature proteins.
  • FUNCTION: nsP3 is essential for minus strand and subgenomic 26S mRNA synthesis.
  • FUNCTION: nsP4 is a RNA dependent RNA polymerase. It replicates genomic and antigenomic RNA by recognizing replications specific signals. Transcribes also a 26S subgenomic mRNA by initiating RNA synthesis internally on antigenomic RNA. This 26S mRNA encodes for structural proteins.
  • CATALYTIC ACTIVITY: S-adenosyl-L-methionine + GTP = m7GTP.
  • CATALYTIC ACTIVITY: m7GTP + (5')pp-Pur-mRNA = diphosphate + m7G(5')ppp-Pur-mRNA.
  • CATALYTIC ACTIVITY: (5')ppp-mRNA + H2O = (5')pp-mRNA + phosphate.
  • CATALYTIC ACTIVITY: A 5'-phosphopolynucleotide + H2O = a polynucleotide + phosphate.
  • CATALYTIC ACTIVITY: NTP + H2O = NDP + phosphate.
  • CATALYTIC ACTIVITY: Nucleoside triphosphate + RNA(n) = diphosphate + RNA(n+1).
  • BIOPHYSICOCHEMICAL PROPERTIES:
    Kinetic parameters:   KM=2.99 mM for triphosphatase (at pH 8.0);
    KM=90 mM for NTPase (at pH 7.5);
  • SUBUNIT: P123 interacts with nsP4; nsP1, nsP2, nsP3 and nsP4 interact with each other, and with uncharacterized host factors.
  • SUBCELLULAR LOCATION: Non-structural polyprotein: Endosome membrane; Peripheral membrane protein; Cytoplasmic side. Lysosome membrane; Peripheral membrane protein; Cytoplasmic side. Note=Located on the cytoplasmic surface of modified endosomes and lysosomes, also called cytopathic vacuoles type I (CPVI). These vacuoles contain numerous small circular invaginations (spherules) which may be the sites of RNA synthesis.
  • SUBCELLULAR LOCATION: P123: Endosome membrane; Peripheral membrane protein; Cytoplasmic side. Lysosome membrane; Peripheral membrane protein; Cytoplasmic side.
  • SUBCELLULAR LOCATION: mRNA-capping enzyme nsP1: Endosome membrane; Peripheral membrane protein; Cytoplasmic side. Lysosome membrane; Peripheral membrane protein; Cytoplasmic side. Cell membrane; Peripheral membrane protein; Cytoplasmic side. Cell projection, 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.
  • SUBCELLULAR LOCATION: Protease/triphosphatase/NTPase/helicase nsP2: Endosome membrane; Peripheral membrane protein; Cytoplasmic side. Lysosome membrane; Peripheral membrane protein; Cytoplasmic side. Nucleus. 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.
  • SUBCELLULAR LOCATION: Non-structural protein 3: Endosome membrane; Peripheral membrane protein; Cytoplasmic side. Lysosome membrane; Peripheral membrane protein; Cytoplasmic side. Cytoplasm. Note=In the late phase of infection, the polyprotein is quickly cleaved before localization to cellular membranes. Then nsP3 and nsP3' seems to aggregate in cytoplasm.
  • SUBCELLULAR LOCATION: RNA-directed RNA polymerase nsP4: Endosome membrane; Peripheral membrane protein; Cytoplasmic side. Lysosome membrane; Peripheral membrane protein; Cytoplasmic side.
  • INDUCTION: Viral replication produces dsRNA in the late phsae 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 in a dramatic shutoff of proteins synthesis. Translation of viral non-structural polyprotein and all cellular proteins are stopped in infected cell between 2 and 4 hours post infection. Only the 26S mRNA is still translated into viral structural proteins, presumably through a unique mechanism of enhancer element which counteract the translation inhibition mediated by EIF2A. By doing this, the virus uses the cellular defense for its own advantage: shutoff of cellular translation allows to produce big amounts of structural proteins needed for the virus to bud out of the doomed cell.
  • PTM: Specific enzymatic cleavages in vivo yield mature proteins. The polyprotein is synthesized as P1234 by stop codon readthrough. This polyprotein is processed differently depending on the stage of infection. In early stages, P1234 is first cleaved in trans, through its nsP2 protease activity, releasing P123 and nsP4. P123 and nsP4 start to replicate the viral genome into its antigenome. After these early events, nsP1 is cleaved in cis by nsP2 protease, releasing P23 polyprotein. Cleavage of nsP1 exposes an 'activator' at the N-terminus of P23 which induces its cleavage into nsP2 and nsP3 by the viral protease. This sequence of delayed processing would allow correct assembly and membrane association of the RNA-polymerase complex. In the late stage of infection, the presence of free nsP2 in the cytoplasm cleaves P1234 quickly into P12 and P34, then into the four nsP.
  • PTM: nsP1 is palmitoylated by host.
  • PTM: nsP3 is phosphorylated by host on serines and threonines.
  • PTM: nsP4 is ubiquitinated; targets the protein for rapid degradation via the ubiquitin system (By similarity).
  • SIMILARITY: Contains 1 Macro domain.
  • SIMILARITY: Contains 1 peptidase C9 domain [view classification].
  • SIMILARITY: Contains 1 RdRp catalytic domain.
  • CAUTION: There is no stop codon readthrough before nsp4.
Copyright
Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.
Cross-references
Sequence databases
EMBL
X04129; CAA27741.1; -; Genomic_RNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AJ251359; CAB62256.1; -; Genomic_RNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AY112987; AAM64226.1; -; Genomic_RNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
DQ189079; ABA29023.1; -; Genomic_RNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
DQ189080; ABA29024.1; -; Genomic_RNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
DQ189081; ABA29025.1; -; Genomic_RNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
DQ189082; ABA29026.1; -; Genomic_RNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
DQ189083; ABA29028.1; -; Genomic_RNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
DQ189084; ABA29029.1; -; Genomic_RNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
DQ189085; ABA29031.1; -; Genomic_RNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
DQ189086; ABA29032.1; -; Genomic_RNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
PIR A23592; MNWVSF.
RefSeq NP_463457.1; -.
3D structure databases
PDB
1FW5; NMR; -; A=245-264.[ExPASy / RCSB / EBI]
PDBsum 1FW5; -.
ModBase P08411.
Protein family/group databases
MEROPS C09.001; -.
Ontologies
GO
GO:0005765; Cellular component: lysosomal membrane (inferred from electronic annotation from UniProtKB-SubCell).
QuickGo view.
Family and domain databases
InterPro IPR002589; A1pp.
IPR002620; Peptidase_C9.
IPR001788; RNA-dep_RNA_pol_vir-typ.
IPR000606; RNA_helicase1_vir.
IPR007094; RNA_pol_PSvir.
Graphical view of domain structure.
Pfam PF01661; A1pp; 1.
PF01707; Peptidase_C9; 1.
PF00978; RdRP_2; 1.
PF01443; Viral_helicase1; 1.
Pfam graphical view of domain structure.
SMART SM00506; A1pp; 1.
SMART graphical view of domain structure.
PROSITE PS51154; MACRO; 1.
PS50507; RDRP_SSRNA_POS; 1.
PROSITE graphical view of domain structure (profiles).
BLOCKS P08411.
Genome annotation databases
GeneID 922350; -.
Other
ProtoNet P08411.
UniRef View cluster of proteins with at least 50% / 90% / 100% identity.
Keywords
3D-structure; ATP-binding; Cell membrane; Cell projection; Cytoplasm; Endosome; Helicase; Hydrolase; Lipoprotein; Lysosome; Membrane; Methyltransferase; mRNA capping; mRNA processing; Multifunctional enzyme; Nucleotide-binding; Nucleotidyltransferase; Nucleus; Palmitate; Phosphoprotein; Protease; RNA replication; RNA-binding; RNA-directed RNA polymerase; Thiol protease; Transferase; Ubl conjugation.
Features
SEVIEWER logo Feature table viewer FT aligner logo Feature aligner
KeyFrom    To Length Description FTId
CHAIN   1   2432  2432     Non-structural polyprotein. PRO_0000308403
CHAIN   1   1818  1818     P123. PRO_0000227770
CHAIN   1    537  537     mRNA-capping enzyme nsP1. PRO_0000041228
CHAIN   538   1336  799     Protease/triphosphatase/NTPase/helicase nsP2. PRO_0000041229
CHAIN   1337   1818  482     Non-structural protein 3. PRO_0000041230
CHAIN   1819   2431  613     RNA-directed RNA polymerase nsP4. PRO_0000041231
DOMAIN   966   1167  202     Peptidase C9. 
DOMAIN   1337   1495  159     Macro. 
DOMAIN   2182   2297  116     RdRp catalytic. 
NP_BIND   723    730  8     ATP (Potential). 
REGION   245    264  20     nsP1 membrane-binding. 
REGION   1007   1026  20     Nucleolus localization signal. 
MOTIF   1184   1188  5     Nuclear localization signal. 
ACT_SITE   1015   1015        For cysteine protease nsP2 activity (By similarity). 
ACT_SITE   1085   1085        For cysteine protease nsP2 activity (By similarity). 
SITE   537    538  2     Cleavage; by nsP2. 
SITE   1336   1337  2     Cleavage; by nsP2. 
SITE   1818   1819  2     Cleavage; by nsP2. 
MOD_RES   1680   1680        Phosphothreonine; by host. 
MOD_RES   1681   1681        Phosphothreonine; by host. 
LIPID   418    418        S-palmitoyl cysteine; by host. 
LIPID   420    420        S-palmitoyl cysteine; by host. 
VARIANT   6      6  1     H -> Y (in strain: Isolate L10). 
VARIANT   95     96  2     VC -> DS (in strain: Isolate Garoff/Takkinen). 
VARIANT   119    119  1     D -> N (in strain: Isolate Ts14). 
VARIANT   311    311  1     E -> K (in strain: Isolate L10). 
VARIANT   529    529  1     E -> D (in strain: Isolate Ts10). 
VARIANT   596    596  1     R -> G (in strain: Isolate Garoff/Takkinen). 
VARIANT   764    771  8     LDIQAKTV -> KGTSRENS (in strain: Isolate Garoff/Takkinen). 
VARIANT   764    771  8     LDIQAKTV -> NWTSRKNS (in strain: Isolate L10). 
VARIANT   817    817  1     D -> N (in strain: Isolate L10). 
VARIANT   826    826  1     M -> T (in strain: Isolate L10). 
VARIANT   843    843  1     H -> N (in strain: Isolate L10). 
VARIANT   845    845  1     S -> N (in strain: Isolate Ts1). 
VARIANT   859    859  1     S -> C (in strain: Isolate L10). 
VARIANT   869    869  1     T -> S (in strain: Isolate Ts13). 
VARIANT   901    901  1     V -> A (in strain: Isolate Garoff/Takkinen). 
VARIANT   1114   1114  1     G -> R (in strain: Isolate Ts11). 
VARIANT   1199   1199  1     A -> T (in strain: Isolate Ts6). 
VARIANT   1258   1259  2     SL -> I (in strain: Isolate Garoff/Takkinen and Isolate L10). 
VARIANT   1384   1384  1     A -> E (in strain: Isolate L10 clone SFV4). 
VARIANT   1565   1565  1     Q -> R (in strain: Isolate Garoff/Takkinen). 
VARIANT   1579   1579  1     R -> G (in strain: Isolate Garoff/Takkinen). 
VARIANT   1644   1644  1     G -> V (in strain: Isolate Garoff/Takkinen, Isolate L10 and Isolate L10 clone SFV4). 
VARIANT   1849   1849  1     E -> Q (in strain: Isolate Garoff/Takkinen). 
VARIANT   1921   1921  1     P -> R (in strain: Isolate L10). 
VARIANT   1938   1938  1     V -> A (in strain: Isolate L10). 
VARIANT   2060   2060  1     A -> V (in strain: Isolate Ts13). 
VARIANT   2088   2088  1     A -> D (in strain: Isolate L10). 
VARIANT   2405   2405  1     A -> T (in strain: Isolate Garoff/Takkinen). 
MUTAGEN   19     19        L->E: Complete loss of guanylyltransferase and guanine-7-methyl transferase activity in vitro. 
MUTAGEN   38     38        H->A: Complete loss of guanylyltransferase and guanine-7-methyl transferase activity in vitro. 
MUTAGEN   64     64        D->A: 60% increase of guanine-7-methyl transferase activity in vitro. Complete loss of guanylyltransferase activity in vitro. 
MUTAGEN   81     83        CVC->AVA: 60% loss of guanine-7-methyl transferase activity and complete loss of guanylyltransferase activity in vitro. 
MUTAGEN   90     90        D->A: Complete loss of guanylyltransferase and guanine-7-methyl transferase activity in vitro. 
MUTAGEN   93     93        R->A: Complete loss of guanylyltransferase and guanine-7-methyl transferase activity in vitro. 
MUTAGEN   135    135        C->A: 90% loss of guanine-7-methyl transferase activity and complete loss of guanylyltransferase activity in vitro. 
MUTAGEN   142    142        C->A: Complete loss of guanylyltransferase and guanine-7-methyl transferase activity in vitro. 
MUTAGEN   153    153        D->A: No effect on guanylyltransferase and guanine-7-methyl transferase activity in vitro. 
MUTAGEN   169    169        K->A: 50% loss of guanine-7-methyl transferase activity and no effect on guanylyltransferase activity in vitro. 
MUTAGEN   180    180        D->A: No effect on guanine-7-methyl transferase activity in vitro. 
MUTAGEN   203    203        E->A: No effect on guanylyltransferase and guanine-7-methyl transferase activity in vitro. 
MUTAGEN   214    214        C->A: 90% loss of guanylyltransferase and guanine-7-methyl transferase activity in vitro. 
MUTAGEN   249    249        Y->A: 97% loss of guanine-7-methyl transferase activity and complete loss of guanylyltransferase activity in vitro. 
MUTAGEN   317    317        K->A: 95% loss of guanine-7-methyl transferase activity and 98% loss of guanylyltransferase activity in vitro. 
MUTAGEN   418    420        CCC->AAA: Complete loss of palmitoylation. Complete loss of pathogenicity in mice. 
MUTAGEN   729    729        K->N: Complete loss of NTPase and helicase activity. 
MUTAGEN   1015   1015        C->A: Complete loss of polyprotein processing. 
MUTAGEN   1186   1186        R->D: Complete loss of nuclear localization for nsP2. 
MUTAGEN   1680   1680        T->A: Complete loss of threonine phosphorylation. 
MUTAGEN   1681   1681        T->A: Complete loss of threonine phosphorylation. 
MUTAGEN   1824   1824        D->A: No effect on polyprotein processing. 
HELIX   246    259  14      
Sequence information
Length: 2432 AA [This is the length of the unprocessed precursor] Molecular weight: 269512 Da [This is the MW of the unprocessed precursor] CRC64: BE7104A1EC3EF6EE [This is a checksum on the sequence] 
        10         20         30         40         50         60 
MAAKVHVDIE ADSPFIKSLQ KAFPSFEVES LQVTPNDHAN ARAFSHLATK LIEQETDKDT 

        70         80         90        100        110        120 
LILDIGSAPS RRMMSTHKYH CVCPMRSAED PERLVCYAKK LAAASGKVLD REIAGKITDL 

       130        140        150        160        170        180 
QTVMATPDAE SPTFCLHTDV TCRTAAEVAV YQDVYAVHAP TSLYHQAMKG VRTAYWIGFD 

       190        200        210        220        230        240 
TTPFMFDALA GAYPTYATNW ADEQVLQARN IGLCAASLTE GRLGKLSILR KKQLKPCDTV 

       250        260        270        280        290        300 
MFSVGSTLYT ESRKLLRSWH LPSVFHLKGK QSFTCRCDTI VSCEGYVVKK ITMCPGLYGK 

       31<