POLN_SFV
ID POLN_SFV Reviewed; 2432 AA.
AC P08411; B3TP00; Q3LRQ3; Q3LRQ4; Q3LRQ6; Q3LRQ7; Q3LRQ9; Q3LRR0; Q3LRR1;
AC Q3LRR2; Q8JMP6; Q9QBM1;
DT 01-AUG-1988, integrated into UniProtKB/Swiss-Prot.
DT 21-MAR-2006, sequence version 2.
DT 03-AUG-2022, entry version 170.
DE RecName: Full=Polyprotein P1234;
DE Short=P1234;
DE AltName: Full=Non-structural polyprotein;
DE Contains:
DE RecName: Full=Polyprotein P123';
DE Short=P123';
DE Contains:
DE RecName: Full=Polyprotein P123;
DE Short=P123;
DE Contains:
DE RecName: Full=mRNA-capping enzyme nsP1;
DE EC=2.1.1.- {ECO:0000250|UniProtKB:P27282};
DE EC=2.7.7.- {ECO:0000250|UniProtKB:P27282};
DE AltName: Full=Non-structural protein 1;
DE Contains:
DE RecName: Full=Protease nsP2;
DE EC=3.1.3.33 {ECO:0000269|PubMed:10748213};
DE EC=3.4.22.- {ECO:0000250|UniProtKB:Q8JUX6};
DE EC=3.6.1.15 {ECO:0000269|PubMed:8057461};
DE EC=3.6.4.13 {ECO:0000269|PubMed:10217401};
DE AltName: Full=Non-structural protein 2;
DE Short=nsP2;
DE Contains:
DE RecName: Full=Non-structural protein 3;
DE Short=nsP3;
DE EC=3.1.3.84 {ECO:0000250|UniProtKB:Q8JUX6};
DE Contains:
DE RecName: Full=Non-structural protein 3';
DE Short=nsP3';
DE EC=3.1.3.84 {ECO:0000250|UniProtKB:Q8JUX6};
DE Contains:
DE RecName: Full=RNA-directed RNA polymerase nsP4;
DE EC=2.7.7.19 {ECO:0000250|UniProtKB:P03317};
DE EC=2.7.7.48 {ECO:0000255|PROSITE-ProRule:PRU00539};
DE AltName: Full=Non-structural protein 4;
DE Short=nsP4;
OS Semliki forest virus (SFV).
OC Viruses; Riboviria; Orthornavirae; Kitrinoviricota; Alsuviricetes;
OC Martellivirales; Togaviridae; Alphavirus.
OX NCBI_TaxID=11033;
OH NCBI_TaxID=7158; Aedes.
OH NCBI_TaxID=9368; Atelerix albiventris (Middle-African hedgehog) (Four-toed hedgehog).
OH NCBI_TaxID=7178; Culex tritaeniorhynchus (Mosquito).
OH NCBI_TaxID=170865; Halcyon.
OH NCBI_TaxID=9606; Homo sapiens (Human).
OH NCBI_TaxID=158617; Quelea.
OH NCBI_TaxID=34630; Rhipicephalus.
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RC STRAIN=Isolate Garoff/Takkinen;
RX PubMed=3488539; DOI=10.1093/nar/14.14.5667;
RA Takkinen K.;
RT "Complete nucleotide sequence of the nonstructural protein genes of Semliki
RT Forest virus.";
RL Nucleic Acids Res. 14:5667-5682(1986).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RC STRAIN=Isolate L10 clone SFV4;
RX PubMed=10775594; DOI=10.1128/jvi.74.10.4579-4589.2000;
RA Tuittila M.T., Santagati M.G., Roeyttae M., Maeaettae J.A., Hinkkanen A.E.;
RT "Replicase complex genes of Semliki Forest virus confer lethal
RT neurovirulence.";
RL J. Virol. 74:4579-4589(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RC STRAIN=Isolate L10;
RA Logue C., Mooney D., Shanley R., Atkins G.J.;
RT "Semliki Forest virus -- L10 strain complete genome.";
RL Submitted (MAY-2002) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RC STRAIN=Isolate Ts1, Isolate Ts10, Isolate Ts11, Isolate Ts13, Isolate Ts14,
RC Isolate Ts6, and Isolate Ts9;
RX PubMed=16501123; DOI=10.1128/jvi.80.6.3108-3111.2006;
RA Lulla V., Merits A., Sarin P., Kaariainen L., Keranen S., Ahola T.;
RT "Identification of mutations causing temperature-sensitive defects in
RT Semliki Forest virus RNA synthesis.";
RL J. Virol. 80:3108-3111(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA] (POLYPROTEIN P123).
RC STRAIN=Isolate Me Tri virus;
RX PubMed=18753222; DOI=10.1099/vir.0.2008/002121-0;
RA Tan le V., Ha do Q., Hien V.M., van der Hoek L., Farrar J., de Jong M.D.;
RT "Me Tri virus: a Semliki Forest virus strain from Vietnam?";
RL J. Gen. Virol. 89:2132-2135(2008).
RN [6]
RP SUBCELLULAR LOCATION (RNA-DIRECTED RNA POLYMERASE NSP4).
RX PubMed=2904446; DOI=10.1083/jcb.107.6.2075;
RA Froshauer S., Kartenbeck J., Helenius A.;
RT "Alphavirus RNA replicase is located on the cytoplasmic surface of
RT endosomes and lysosomes.";
RL J. Cell Biol. 107:2075-2086(1988).
RN [7]
RP SUBCELLULAR LOCATION (PROTEASE NSP2), AND NUCLEAR LOCALIZATION SIGNAL.
RX PubMed=1386484; DOI=10.1016/0042-6822(92)90570-f;
RA Rikkonen M., Peraenen J., Kaeaeriaeinen L.;
RT "Nuclear and nucleolar targeting signals of Semliki Forest virus
RT nonstructural protein nsP2.";
RL Virology 189:462-473(1992).
RN [8]
RP FUNCTION (PROTEASE NSP2), CATALYTIC ACTIVITY (PROTEASE NSP2), AND
RP MUTAGENESIS OF LYS-729.
RX PubMed=8057461; DOI=10.1128/jvi.68.9.5804-5810.1994;
RA Rikkonen M., Peraenen J., Kaeaeriaeinen L.;
RT "ATPase and GTPase activities associated with Semliki Forest virus
RT nonstructural protein nsP2.";
RL J. Virol. 68:5804-5810(1994).
RN [9]
RP SUBCELLULAR LOCATION (MRNA-CAPPING ENZYME NSP1).
RX PubMed=7747433; DOI=10.1006/viro.1995.1192;
RA Peraenen J., Laakkonen P., Hyvoenen M., Kaeaeriaeinen L.;
RT "The alphavirus replicase protein nsP1 is membrane-associated and has
RT affinity to endocytic organelles.";
RL Virology 208:610-620(1995).
RN [10]
RP FUNCTION (MRNA-CAPPING ENZYME NSP1).
RX PubMed=7831320; DOI=10.1073/pnas.92.2.507;
RA Ahola T., Kaeaeriaeinen L.;
RT "Reaction in alphavirus mRNA capping: formation of a covalent complex of
RT nonstructural protein nsP1 with 7-methyl-GMP.";
RL Proc. Natl. Acad. Sci. U.S.A. 92:507-511(1995).
RN [11]
RP PALMITOYLATION AT CYS-418 AND CYS-420, MUTAGENESIS OF 418-CYS--CYS-420, AND
RP SUBCELLULAR LOCATION (MRNA-CAPPING ENZYME NSP1).
RX PubMed=8910486; DOI=10.1074/jbc.271.45.28567;
RA Laakkonen P., Ahola T., Kaeaeriaeinen L.;
RT "The effects of palmitoylation on membrane association of Semliki forest
RT virus RNA capping enzyme.";
RL J. Biol. Chem. 271:28567-28571(1996).
RN [12]
RP SUBCELLULAR LOCATION (PROTEASE NSP2), MUTAGENESIS OF LYS-729 AND ARG-1186,
RP AND NUCLEAR LOCALIZATION SIGNAL.
RX PubMed=8610462; DOI=10.1006/viro.1996.0204;
RA Rikkonen M.;
RT "Functional significance of the nuclear-targeting and NTP-binding motifs of
RT Semliki Forest virus nonstructural protein nsP2.";
RL Virology 218:352-361(1996).
RN [13]
RP FUNCTION (MRNA-CAPPING ENZYME NSP1), AND MUTAGENESIS OF LEU-19; HIS-38;
RP ASP-64; 81-CYS--CYS-83; ASP-90; ARG-93; CYS-135; CYS-142; ASP-153; LYS-169;
RP ASP-180; GLU-203; CYS-214; TYR-249 AND LYS-317.
RX PubMed=8985362; DOI=10.1128/jvi.71.1.392-397.1997;
RA Ahola T., Laakkonen P., Vihinen H., Kaeaeriaeinen L.;
RT "Critical residues of Semliki Forest virus RNA capping enzyme involved in
RT methyltransferase and guanylyltransferase-like activities.";
RL J. Virol. 71:392-397(1997).
RN [14]
RP FUNCTION (MRNA-CAPPING ENZYME NSP1).
RX PubMed=9811773; DOI=10.1128/jvi.72.12.10265-10269.1998;
RA Laakkonen P., Auvinen P., Kujala P., Kaeaeriaeinen L.;
RT "Alphavirus replicase protein NSP1 induces filopodia and rearrangement of
RT actin filaments.";
RL J. Virol. 72:10265-10269(1998).
RN [15]
RP MEMBRANE-BINDING (MRNA-CAPPING ENZYME NSP1).
RX PubMed=10357827; DOI=10.1093/emboj/18.11.3164;
RA Ahola T., Lampio A., Auvinen P., Kaeaeriaeinen L.;
RT "Semliki Forest virus mRNA capping enzyme requires association with anionic
RT membrane phospholipids for activity.";
RL EMBO J. 18:3164-3172(1999).
RN [16]
RP FUNCTION (PROTEASE NSP2), AND MUTAGENESIS OF LYS-729.
RX PubMed=10217401; DOI=10.1016/s0014-5793(99)00321-x;
RA Gomez de Cedron M., Ehsani N., Mikkola M.L., Garcia J.A., Kaeaeriaeinen L.;
RT "RNA helicase activity of Semliki Forest virus replicase protein NSP2.";
RL FEBS Lett. 448:19-22(1999).
RN [17]
RP PALMITOYLATION AT CYS-418 AND CYS-420, AND MUTAGENESIS OF 418-CYS--CYS-420.
RX PubMed=10888610; DOI=10.1128/jvi.74.15.6725-6733.2000;
RA Ahola T., Kujala P., Tuittila M., Blom T., Laakkonen P., Hinkkanen A.,
RA Auvinen P.;
RT "Effects of palmitoylation of replicase protein nsP1 on alphavirus
RT infection.";
RL J. Virol. 74:6725-6733(2000).
RN [18]
RP FUNCTION (PROTEASE NSP2), BIOPHYSICOCHEMICAL PROPERTIES (PROTEASE NSP2),
RP CATALYTIC ACTIVITY (PROTEASE NSP2), AND MUTAGENESIS OF LYS-729.
RX PubMed=10748213; DOI=10.1074/jbc.m910340199;
RA Vasiljeva L., Merits A., Auvinen P., Kaeaeriaeinen L.;
RT "Identification of a novel function of the alphavirus capping apparatus.
RT RNA 5'-triphosphatase activity of Nsp2.";
RL J. Biol. Chem. 275:17281-17287(2000).
RN [19]
RP ACTIVE SITE (PROTEASE NSP2), MUTAGENESIS OF CYS-1015 AND ASP-1824, FUNCTION
RP (PROTEASE NSP2), PROTEOLYTIC CLEAVAGE (POLYPROTEIN P1234), AND PROTEOLYTIC
RP CLEAVAGE (POLYPROTEIN P123).
RX PubMed=11257180; DOI=10.1099/0022-1317-82-4-765;
RA Merits A., Vasiljeva L., Ahola T., Kaeaeriaeinen L., Auvinen P.;
RT "Proteolytic processing of Semliki Forest virus-specific non-structural
RT polyprotein by nsP2 protease.";
RL J. Gen. Virol. 82:765-773(2001).
RN [20]
RP FUNCTION (PROTEASE NSP2), PROTEOLYTIC CLEAVAGE (POLYPROTEIN P1234), AND
RP ACTIVITY REGULATION (PROTEASE NSP2).
RX PubMed=11410598; DOI=10.1074/jbc.m104786200;
RA Vasiljeva L., Valmu L., Kaeaeriaeinen L., Merits A.;
RT "Site-specific protease activity of the carboxyl-terminal domain of Semliki
RT Forest virus replicase protein nsP2.";
RL J. Biol. Chem. 276:30786-30793(2001).
RN [21]
RP PHOSPHORYLATION AT THR-1680 AND THR-1681, AND MUTAGENESIS OF THR-1680 AND
RP THR-1681.
RX PubMed=11104756; DOI=10.1074/jbc.m006077200;
RA Vihinen H., Ahola T., Tuittila M., Merits A., Kaeaeriaeinen L.;
RT "Elimination of phosphorylation sites of Semliki Forest virus replicase
RT protein nsP3.";
RL J. Biol. Chem. 276:5745-5752(2001).
RN [22]
RP PROTEOLYTIC CLEAVAGE (POLYPROTEIN P1234), AND PROTEOLYTIC CLEAVAGE
RP (POLYPROTEIN P123).
RX PubMed=12917405; DOI=10.1074/jbc.m307481200;
RA Vasiljeva L., Merits A., Golubtsov A., Sizemskaja V., Kaeaeriaeinen L.,
RA Ahola T.;
RT "Regulation of the sequential processing of Semliki Forest virus replicase
RT polyprotein.";
RL J. Biol. Chem. 278:41636-41645(2003).
RN [23]
RP HOST TRANSLATION SHUTOFF.
RX PubMed=15930128; DOI=10.1091/mbc.e05-02-0124;
RA McInerney G.M., Kedersha N.L., Kaufman R.J., Anderson P., Liljestrom P.;
RT "Importance of eIF2alpha phosphorylation and stress granule assembly in
RT alphavirus translation regulation.";
RL Mol. Biol. Cell 16:3753-3763(2005).
RN [24]
RP HOST TRANSLATION SHUTOFF.
RX PubMed=16391235; DOI=10.1101/gad.357006;
RA Ventoso I., Sanz M.A., Molina S., Berlanga J.J., Carrasco L., Esteban M.;
RT "Translational resistance of late alphavirus mRNA to eIF2alpha
RT phosphorylation: a strategy to overcome the antiviral effect of protein
RT kinase PKR.";
RL Genes Dev. 20:87-100(2006).
RN [25]
RP FUNCTION (PROTEASE NSP2).
RX PubMed=16352561; DOI=10.1128/jvi.80.1.360-371.2006;
RA Sawicki D.L., Perri S., Polo J.M., Sawicki S.G.;
RT "Role for nsP2 proteins in the cessation of alphavirus minus-strand
RT synthesis by host cells.";
RL J. Virol. 80:360-371(2006).
RN [26]
RP SUBCELLULAR LOCATION (MRNA-CAPPING ENZYME NSP1), AND MUTAGENESIS OF ARG-253
RP AND TRP-259.
RX PubMed=17093195; DOI=10.1128/jvi.01785-06;
RA Spuul P., Salonen A., Merits A., Jokitalo E., Kaeaeriaeinen L., Ahola T.;
RT "Role of the amphipathic peptide of Semliki forest virus replicase protein
RT nsP1 in membrane association and virus replication.";
RL J. Virol. 81:872-883(2007).
RN [27]
RP SUBCELLULAR LOCATION (PROTEASE NSP2), AND NUCLEAR LOCALIZATION SIGNAL.
RC STRAIN=pV3000;
RX PubMed=17652399; DOI=10.1128/jvi.00371-07;
RA Montgomery S.A., Johnston R.E.;
RT "Nuclear import and export of Venezuelan equine encephalitis virus
RT nonstructural protein 2.";
RL J. Virol. 81:10268-10279(2007).
RN [28]
RP SUBCELLULAR LOCATION (MRNA-CAPPING ENZYME NSP1), AND PALMITOYLATION
RP (MRNA-CAPPING ENZYME NSP1).
RX PubMed=17554031; DOI=10.1099/vir.0.82865-0;
RA Zusinaite E., Tints K., Kiiver K., Spuul P., Karo-Astover L., Merits A.,
RA Sarand I.;
RT "Mutations at the palmitoylation site of non-structural protein nsP1 of
RT Semliki Forest virus attenuate virus replication and cause accumulation of
RT compensatory mutations.";
RL J. Gen. Virol. 88:1977-1985(2007).
RN [29]
RP FUNCTION (PROTEASE NSP2).
RX PubMed=17108023; DOI=10.1128/jvi.02073-06;
RA Garmashova N., Gorchakov R., Volkova E., Paessler S., Frolova E.,
RA Frolov I.;
RT "The Old World and New World alphaviruses use different virus-specific
RT proteins for induction of transcriptional shutoff.";
RL J. Virol. 81:2472-2484(2007).
RN [30]
RP FUNCTION (PROTEASE NSP2).
RX PubMed=22514352; DOI=10.1128/jvi.00541-12;
RA Akhrymuk I., Kulemzin S.V., Frolova E.I.;
RT "Evasion of the innate immune response: the Old World alphavirus nsP2
RT protein induces rapid degradation of Rpb1, a catalytic subunit of RNA
RT polymerase II.";
RL J. Virol. 86:7180-7191(2012).
RN [31]
RP FUNCTION (NON-STRUCTURAL PROTEIN 3), AND INTERACTION WITH HOST G3BP1
RP (NON-STRUCTURAL PROTEIN 3).
RX PubMed=23087212; DOI=10.1091/mbc.e12-08-0619;
RA Panas M.D., Varjak M., Lulla A., Eng K.E., Merits A.,
RA Karlsson Hedestam G.B., McInerney G.M.;
RT "Sequestration of G3BP coupled with efficient translation inhibits stress
RT granules in Semliki Forest virus infection.";
RL Mol. Biol. Cell 23:4701-4712(2012).
RN [32]
RP DOMAIN (NON-STRUCTURAL PROTEIN 3), AND INTERACTION WITH HOST G3BP1.
RX PubMed=24623412; DOI=10.1128/jvi.00439-14;
RA Panas M.D., Ahola T., McInerney G.M.;
RT "The C-terminal repeat domains of nsP3 from the Old World alphaviruses bind
RT directly to G3BP.";
RL J. Virol. 88:5888-5893(2014).
RN [33]
RP DOMAIN (NON-STRUCTURAL PROTEIN 3), INTERACTION WITH HOST G3BP1
RP (NON-STRUCTURAL PROTEIN 3), AND MUTAGENESIS OF PHE-1787; GLY-1788;
RP ASP-1789; PHE-1790; ASP-1791; THR-1803; PHE-1804; GLY-1805; ASP-1806;
RP PHE-1807 AND ASP-1808.
RX PubMed=25658430; DOI=10.1371/journal.ppat.1004659;
RA Panas M.D., Schulte T., Thaa B., Sandalova T., Kedersha N., Achour A.,
RA McInerney G.M.;
RT "Viral and cellular proteins containing FGDF motifs bind G3BP to block
RT stress granule formation.";
RL PLoS Pathog. 11:E1004659-E1004659(2015).
RN [34]
RP REVIEW.
RX PubMed=28104453; DOI=10.1016/j.virusres.2017.01.007;
RA Pietilae M.K., Hellstroem K., Ahola T.;
RT "Alphavirus polymerase and RNA replication.";
RL Virus Res. 234:44-57(2017).
RN [35]
RP PROTEOLYTIC CLEAVAGE (POLYPROTEIN P1234).
RX PubMed=29695431; DOI=10.1128/jvi.00151-18;
RA Lulla V., Karo-Astover L., Rausalu K., Saul S., Merits A., Lulla A.;
RT "Timeliness of proteolytic events is prerequisite for efficient functioning
RT of the alphaviral replicase.";
RL J. Virol. 92:0-0(2018).
RN [36]
RP STRUCTURE BY NMR OF 245-264.
RX PubMed=10984480; DOI=10.1074/jbc.m004865200;
RA Lampio A., Kilpelainen I., Pesonen S., Karhi K., Auvinen P., Somerharju P.,
RA Kaeaeriaeinen L.;
RT "Membrane binding mechanism of an RNA virus-capping enzyme.";
RL J. Biol. Chem. 275:37853-37859(2000).
RN [37] {ECO:0007744|PDB:5FW5}
RP X-RAY CRYSTALLOGRAPHY (1.92 ANGSTROMS) OF 1785-1809, INTERACTION WITH HOST
RP G3BP1 (NON-STRUCTURAL PROTEIN 3), AND DOMAIN (NON-STRUCTURAL PROTEIN 3).
RX PubMed=27383630; DOI=10.1098/rsob.160078;
RA Schulte T., Liu L., Panas M.D., Thaa B., Dickson N., Gotte B., Achour A.,
RA McInerney G.M.;
RT "Combined structural, biochemical and cellular evidence demonstrates that
RT both FGDF motifs in alphavirus nsP3 are required for efficient
RT replication.";
RL Open Biol. 6:0-0(2016).
CC -!- FUNCTION: [Polyprotein P1234]: Inactive precursor of the viral
CC replicase, which is activated by cleavages carried out by the viral
CC protease nsP2. {ECO:0000250|UniProtKB:Q8JUX6}.
CC -!- FUNCTION: [Polyprotein P123]: The early replication complex formed by
CC the polyprotein P123 and nsP4 synthesizes minus-strand RNAs (By
CC similarity). As soon P123 is cleaved into mature proteins, the plus-
CC strand RNAs synthesis begins (By similarity).
CC {ECO:0000250|UniProtKB:P03317}.
CC -!- FUNCTION: [Polyprotein P123']: The early replication complex formed by
CC the polyprotein P123' and nsP4 synthesizes minus-strand RNAs
CC (Probable). Polyprotein P123' is a short-lived polyprotein that
CC accumulates during early stage of infection (Probable). As soon P123'
CC is cleaved into mature proteins, the plus-strand RNAs synthesis begins
CC (Probable). {ECO:0000305}.
CC -!- FUNCTION: [mRNA-capping enzyme nsP1]: Cytoplasmic capping enzyme that
CC catalyzes two virus-specific reactions: methyltransferase and nsP1
CC guanylyltransferase (PubMed:7831320). mRNA-capping is necessary since
CC all viral RNAs are synthesized in the cytoplasm, and host capping
CC enzymes are restricted to the nucleus (Probable). The enzymatic
CC reaction involves a covalent link between 7-methyl-GMP and nsP1,
CC whereas eukaryotic capping enzymes form a covalent complex only with
CC GMP (Probable). nsP1 capping consists in the following reactions: GTP
CC is first methylated into 7-methyl-GMP and then is covalently linked to
CC nsP1 to form the m7GMp-nsP1 complex from which 7-methyl-GMP complex is
CC transferred to the mRNA to create the cap structure (Probable). NsP1 is
CC also needed for the initiation of the minus-strand RNAs synthesis (By
CC similarity). Probably serves as a membrane anchor for the replication
CC complex composed of nsP1-nsP4 (Probable). Palmitoylated nsP1 is
CC remodeling host cell cytoskeleton, and induces filopodium-like
CC structure formation at the surface of the host cell (By similarity).
CC {ECO:0000250|UniProtKB:P03317, ECO:0000250|UniProtKB:Q8JUX6,
CC ECO:0000269|PubMed:7831320, ECO:0000305, ECO:0000305|PubMed:17093195,
CC ECO:0000305|PubMed:7831320}.
CC -!- FUNCTION: [Protease nsP2]: Multifunctional protein whose N-terminus is
CC part of the RNA polymerase complex and displays NTPase, RNA
CC triphosphatase and helicase activities (PubMed:8057461,
CC PubMed:10217401, PubMed:10748213). NTPase and RNA triphosphatase are
CC involved in viral RNA capping and helicase keeps a check on the dsRNA
CC replication intermediates (Probable). The C-terminus harbors a protease
CC that specifically cleaves and releases the mature proteins
CC (PubMed:11257180). Required for the shutoff of minus-strand RNAs
CC synthesis (PubMed:16352561). Specifically inhibits the host IFN
CC response by promoting the nuclear export of host STAT1 (By similarity).
CC Also inhibits host transcription by inducing rapid proteasome-dependent
CC degradation of POLR2A, a catalytic subunit of the RNAPII complex
CC (PubMed:22514352, PubMed:17108023). The resulting inhibition of
CC cellular protein synthesis serves to ensure maximal viral gene
CC expression and to evade host immune response (Probable).
CC {ECO:0000250|UniProtKB:Q8JUX6, ECO:0000269|PubMed:10217401,
CC ECO:0000269|PubMed:10748213, ECO:0000269|PubMed:11257180,
CC ECO:0000269|PubMed:16352561, ECO:0000269|PubMed:17108023,
CC ECO:0000269|PubMed:22514352, ECO:0000269|PubMed:8057461,
CC ECO:0000305|PubMed:10748213, ECO:0000305|PubMed:22514352}.
CC -!- FUNCTION: [Non-structural protein 3']: Seems to be essential for minus-
CC strand RNAs and subgenomic 26S mRNAs synthesis (By similarity).
CC Displays mono-ADP-ribosylhydrolase activity (Probable). ADP-
CC ribosylation is a post-translational modification that controls various
CC processes of the host cell and the virus probably needs to revert it
CC for optimal viral replication (Probable). Binds proteins of FXR family
CC and sequesters them into the viral RNA replication complexes thereby
CC inhibiting the formation of host stress granules on viral mRNAs
CC (Probable). The nsp3'-FXR complexes bind viral RNAs and probably
CC orchestrate the assembly of viral replication complexes, thanks to the
CC ability of FXR family members to self-assemble and bind DNA (Probable).
CC {ECO:0000250|UniProtKB:P03317, ECO:0000305}.
CC -!- FUNCTION: [Non-structural protein 3]: Seems to be essential for minus-
CC strand RNAs and subgenomic 26S mRNAs synthesis (By similarity).
CC Displays mono-ADP-ribosylhydrolase activity (By similarity). ADP-
CC ribosylation is a post-translational modification that controls various
CC processes of the host cell and the virus probably needs to revert it
CC for optimal viral replication (By similarity). Binds proteins of G3BP
CC family and sequesters them into the viral RNA replication complexes
CC thereby inhibiting the formation of host stress granules on viral mRNAs
CC (PubMed:23087212). The nsp3-G3BP complexes bind viral RNAs and probably
CC orchestrate the assembly of viral replication complexes, thanks to the
CC ability of G3BP family members to self-assemble and bind DNA
CC (PubMed:27383630). {ECO:0000250|UniProtKB:P03317,
CC ECO:0000250|UniProtKB:Q8JUX6, ECO:0000269|PubMed:23087212,
CC ECO:0000269|PubMed:27383630}.
CC -!- FUNCTION: [RNA-directed RNA polymerase nsP4]: RNA dependent RNA
CC polymerase (By similarity). Replicates genomic and antigenomic RNA by
CC recognizing replications specific signals. The early replication
CC complex formed by the polyprotein P123 and nsP4 synthesizes minus-
CC strand RNAs (By similarity). The late replication complex composed of
CC fully processed nsP1-nsP4 is responsible for the production of genomic
CC and subgenomic plus-strand RNAs (By similarity).
CC {ECO:0000250|UniProtKB:P03317}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=GTP + S-adenosyl-L-methionine = N(7)-methyl-GTP + S-adenosyl-
CC L-homocysteine; Xref=Rhea:RHEA:46948, ChEBI:CHEBI:37565,
CC ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:87133;
CC Evidence={ECO:0000250|UniProtKB:P27282};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[nsP1 protein]-L-histidine + N(7)-methyl-GTP = [nsP1 protein]-
CC N(tele)-(N(7)-methylguanosine 5'-phospho)-L-histidine + diphosphate;
CC Xref=Rhea:RHEA:54792, Rhea:RHEA-COMP:13994, Rhea:RHEA-COMP:13995,
CC ChEBI:CHEBI:29979, ChEBI:CHEBI:33019, ChEBI:CHEBI:87133,
CC ChEBI:CHEBI:138334; Evidence={ECO:0000269|PubMed:7831320};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:54793;
CC Evidence={ECO:0000269|PubMed:7831320};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[nsP1 protein]-N(tele)-(N(7)-methylguanosine 5'-phospho)-L-
CC histidine + a 5'-end diphospho-(purine-ribonucleoside) in mRNA + H(+)
CC = [nsP1 protein]-L-histidine + a 5'-end (N(7)-methyl 5'-
CC triphosphoguanosine)-(purine-ribonucleoside) in mRNA;
CC Xref=Rhea:RHEA:54800, Rhea:RHEA-COMP:12925, Rhea:RHEA-COMP:13929,
CC Rhea:RHEA-COMP:13994, Rhea:RHEA-COMP:13995, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:29979, ChEBI:CHEBI:133968, ChEBI:CHEBI:138276,
CC ChEBI:CHEBI:138334; Evidence={ECO:0000250|UniProtKB:P27282};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 5'-end triphospho-(purine-ribonucleoside) in mRNA + H2O = a
CC 5'-end diphospho-(purine-ribonucleoside) in mRNA + H(+) + phosphate;
CC Xref=Rhea:RHEA:11008, Rhea:RHEA-COMP:13929, Rhea:RHEA-COMP:13942,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:138276, ChEBI:CHEBI:138288; EC=3.1.3.33;
CC Evidence={ECO:0000269|PubMed:10748213};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a ribonucleoside 5'-triphosphate + H2O = a ribonucleoside 5'-
CC diphosphate + H(+) + phosphate; Xref=Rhea:RHEA:23680,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:57930, ChEBI:CHEBI:61557; EC=3.6.1.15;
CC Evidence={ECO:0000269|PubMed:8057461};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=3.6.4.13;
CC Evidence={ECO:0000269|PubMed:10217401};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a ribonucleoside 5'-triphosphate + RNA(n) = diphosphate +
CC RNA(n+1); Xref=Rhea:RHEA:21248, Rhea:RHEA-COMP:14527, Rhea:RHEA-
CC COMP:17342, ChEBI:CHEBI:33019, ChEBI:CHEBI:61557, ChEBI:CHEBI:140395;
CC EC=2.7.7.48; Evidence={ECO:0000255|PROSITE-ProRule:PRU00539};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + RNA(n) = diphosphate + RNA(n)-3'-adenine ribonucleotide;
CC Xref=Rhea:RHEA:11332, Rhea:RHEA-COMP:14527, Rhea:RHEA-COMP:17347,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:140395,
CC ChEBI:CHEBI:173115; EC=2.7.7.19;
CC Evidence={ECO:0000250|UniProtKB:P03317};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=4-O-(ADP-D-ribosyl)-L-aspartyl-[protein] + H2O = ADP-D-ribose
CC + H(+) + L-aspartyl-[protein]; Xref=Rhea:RHEA:54428, Rhea:RHEA-
CC COMP:9867, Rhea:RHEA-COMP:13832, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:29961, ChEBI:CHEBI:57967,
CC ChEBI:CHEBI:138102; Evidence={ECO:0000250|UniProtKB:Q8JUX6};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:54429;
CC Evidence={ECO:0000250|UniProtKB:Q8JUX6};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=5-O-(ADP-D-ribosyl)-L-glutamyl-[protein] + H2O = ADP-D-ribose
CC + H(+) + L-glutamyl-[protein]; Xref=Rhea:RHEA:58248, Rhea:RHEA-
CC COMP:10208, Rhea:RHEA-COMP:15089, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:29973, ChEBI:CHEBI:57967,
CC ChEBI:CHEBI:142540; Evidence={ECO:0000250|UniProtKB:Q8JUX6};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:58249;
CC Evidence={ECO:0000250|UniProtKB:Q8JUX6};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ADP-beta-D-ribose 1''-phosphate + H2O = ADP-D-ribose +
CC phosphate; Xref=Rhea:RHEA:25029, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:57967, ChEBI:CHEBI:58753; EC=3.1.3.84;
CC Evidence={ECO:0000250|UniProtKB:Q8JUX6};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25030;
CC Evidence={ECO:0000250|UniProtKB:Q8JUX6};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:P03317};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000250|UniProtKB:P03317};
CC Note=For nsP4 adenylyltransferase activity; Mn(2+) supports catalysis
CC at 60% of the levels observed with Mg(2+).
CC {ECO:0000250|UniProtKB:P03317};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:P03317};
CC Note=For nsP4 RNA-directed RNA polymerase activity.
CC {ECO:0000250|UniProtKB:P03317};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:P27282};
CC Note=For nsP1 guanylylation. {ECO:0000250|UniProtKB:P27282};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Note=For nsP2 RNA triphosphatase activity.
CC {ECO:0000250|UniProtKB:Q8JUX6};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Note=For nsP2 NTPase activity. {ECO:0000250|UniProtKB:Q8JUX6};
CC -!- ACTIVITY REGULATION: [Protease nsP2]: Inhibited by N-ethylmaleimide,
CC Zn(2+), and Cu2(2+). {ECO:0000269|PubMed:11410598}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=2.99 mM for nsP2 RNA triphosphatase activity (at pH 8.0)
CC {ECO:0000269|PubMed:10748213};
CC KM=90 mM for nsP2 NTPase activity (at pH 7.5)
CC {ECO:0000269|PubMed:10748213};
CC -!- SUBUNIT: [mRNA-capping enzyme nsP1]: Interacts with non-structural
CC protein 3 (By similarity). Interacts with RNA-directed RNA polymerase
CC nsP4 (By similarity). Interacts with protease nsP2 (By similarity).
CC interacts with itself (By similarity). {ECO:0000250|UniProtKB:P03317,
CC ECO:0000250|UniProtKB:P27282}.
CC -!- SUBUNIT: [Non-structural protein 3]: Interacts with mRNA-capping enzyme
CC nsP1 (By similarity). Interacts with host DDX1 (By similarity).
CC Interacts with host DDX3 (By similarity). Interacts (via C-terminus)
CC with host G3BP1; this interaction inhibits the formation of host stress
CC granules on viral mRNAs and the nsp3-G3BP1 complexes bind viral RNAs
CC and probably orchestrate the assembly of viral replication complexes
CC (PubMed:24623412, PubMed:23087212, PubMed:25658430, PubMed:27383630).
CC Interacts (via C-terminus) with host G3BP2; this interaction inhibits
CC the formation of host stress granules on viral mRNAs and the nsp3-G3BP2
CC complexes bind viral RNAs and probably orchestrate the assembly of
CC viral replication complexes (By similarity).
CC {ECO:0000250|UniProtKB:P03317, ECO:0000250|UniProtKB:P27282,
CC ECO:0000269|PubMed:23087212, ECO:0000269|PubMed:24623412,
CC ECO:0000269|PubMed:25658430, ECO:0000269|PubMed:27383630}.
CC -!- SUBUNIT: [RNA-directed RNA polymerase nsP4]: Interacts with mRNA-
CC capping enzyme nsP1 (By similarity). Interacts with protease nsP2 (By
CC similarity). interacts with itself (By similarity).
CC {ECO:0000250|UniProtKB:P03317, ECO:0000250|UniProtKB:P27282}.
CC -!- SUBUNIT: [Protease nsP2]: Interacts with RNA-directed RNA polymerase
CC nsP4 (By similarity). Interacts with mRNA-capping enzyme nsP1 (By
CC similarity). Interacts with KPNA1/karyopherin-alpha1; this interaction
CC probably allows the active transport of protease nsP2 into the host
CC nucleus (By similarity). {ECO:0000250|UniProtKB:P03317,
CC ECO:0000250|UniProtKB:P27282}.
CC -!- SUBCELLULAR LOCATION: [Polyprotein P1234]: Host cytoplasmic vesicle
CC membrane {ECO:0000305}; Peripheral membrane protein {ECO:0000305}.
CC Note=Part of cytoplasmic vesicles, which are probably formed at the
CC plasma membrane and internalized leading to late endosomal/lysosomal
CC spherules containing the replication complex. {ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: [Polyprotein P123']: Host cytoplasmic vesicle
CC membrane {ECO:0000305}; Peripheral membrane protein {ECO:0000305}.
CC Note=Part of cytoplasmic vesicles, which are probably formed at the
CC plasma membrane and internalized leading to late endosomal/lysosomal
CC spherules containing the replication complex. {ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: [Polyprotein P123]: Host cytoplasmic vesicle
CC membrane {ECO:0000305}; Peripheral membrane protein {ECO:0000305}.
CC Note=Part of cytoplasmic vesicles, which are probably formed at the
CC plasma membrane and internalized leading to late endosomal/lysosomal
CC spherules containing the replication complex. {ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: [mRNA-capping enzyme nsP1]: Host cytoplasmic
CC vesicle membrane {ECO:0000305|PubMed:7747433}; Lipid-anchor
CC {ECO:0000305|PubMed:17093195, ECO:0000305|PubMed:8910486}. Host cell
CC membrane {ECO:0000269|PubMed:17554031, ECO:0000269|PubMed:7747433};
CC Lipid-anchor {ECO:0000305|PubMed:17093195, ECO:0000305|PubMed:8910486};
CC Cytoplasmic side {ECO:0000269|PubMed:7747433}. Host cell projection,
CC host filopodium {ECO:0000269|PubMed:17554031,
CC ECO:0000269|PubMed:8910486}. Note=In the late phase of infection, the
CC polyprotein is quickly cleaved before localization to cellular
CC membranes. Then a fraction of nsP1 localizes to the inner surface of
CC the plasma membrane and its filopodial extensions. Only the
CC palmitoylated nsP1 localizes to the host filopodia (PubMed:8910486,
CC PubMed:17554031). NsP1 is also part of cytoplasmic vesicles, which are
CC probably formed at the plasma membrane and internalized leading to late
CC endosomal/lysosomal spherules containing the replication complex
CC (PubMed:28104453). {ECO:0000269|PubMed:17554031,
CC ECO:0000269|PubMed:8910486, ECO:0000303|PubMed:28104453}.
CC -!- SUBCELLULAR LOCATION: [Protease nsP2]: Host cytoplasmic vesicle
CC membrane {ECO:0000305|PubMed:1386484}; Peripheral membrane protein
CC {ECO:0000305}. Host nucleus {ECO:0000269|PubMed:1386484,
CC ECO:0000269|PubMed:17652399, ECO:0000269|PubMed:8610462}. Host
CC cytoplasm {ECO:0000269|PubMed:8610462}. Note=In the late phase of
CC infection, the polyprotein is quickly cleaved before localization to
CC cellular membranes. Then approximately half of nsP2 is found in the
CC nucleus (PubMed:8610462). Shuttles between cytoplasm and nucleus (By
CC similarity). NsP2 is also part of cytoplasmic vesicles, which are
CC probably formed at the plasma membrane and internalized leading to late
CC endosomal/lysosomal spherules containing the replication complex
CC (PubMed:28104453). {ECO:0000250|UniProtKB:P27282,
CC ECO:0000269|PubMed:8610462, ECO:0000303|PubMed:28104453}.
CC -!- SUBCELLULAR LOCATION: [Non-structural protein 3]: Host cytoplasmic
CC vesicle membrane {ECO:0000250|UniProtKB:P03317}; Peripheral membrane
CC protein {ECO:0000305}. Note=In the late phase of infection, the
CC polyprotein is quickly cleaved before localization to cellular
CC membranes. Then nsP3 and nsP3' form aggregates in cytoplasm (By
CC similarity). NsP3 is also part of cytoplasmic vesicles, which are
CC probably formed at the plasma membrane and internalized leading to late
CC endosomal/lysosomal spherules containing the replication complex (By
CC similarity). {ECO:0000250|UniProtKB:P03317}.
CC -!- SUBCELLULAR LOCATION: [Non-structural protein 3']: Host cytoplasmic
CC vesicle membrane {ECO:0000250|UniProtKB:P03317}; Peripheral membrane
CC protein {ECO:0000305}. Note=In the late phase of infection, the
CC polyprotein is quickly cleaved before localization to cellular
CC membranes. Then nsP3 and nsP3' form aggregates in cytoplasm (By
CC similarity). NsP3 is also part of cytoplasmic vesicles, which are
CC probably formed at the plasma membrane and internalized leading to late
CC endosomal/lysosomal spherules containing the replication complex (By
CC similarity). {ECO:0000250|UniProtKB:P03317}.
CC -!- SUBCELLULAR LOCATION: [RNA-directed RNA polymerase nsP4]: Host
CC cytoplasmic vesicle membrane; Peripheral membrane protein
CC {ECO:0000269|PubMed:2904446}. Note=NsP4 is part of cytoplasmic
CC vesicles, which are probably formed at the plasma membrane and
CC internalized leading to late endosomal/lysosomal spherules containing
CC the replication complex. {ECO:0000303|PubMed:28104453}.
CC -!- DOMAIN: [Protease nsP2]: The N-terminus exhibits NTPase and RNA
CC triphosphatase activities and is proposed to have helicase activity,
CC whereas the C-terminus possesses protease activity (By similarity).
CC Contains a nuclear localization signal and a nuclear export signal,
CC these two motifs are probably involved in the shuttling between the
CC cytoplasm and the nucleus of nsP2 (By similarity). The C-terminus is
CC required for promoting the export of host STAT1 (By similarity).
CC {ECO:0000250|UniProtKB:P27282, ECO:0000250|UniProtKB:Q8JUX6}.
CC -!- DOMAIN: [Non-structural protein 3]: In the N-terminus, the macro domain
CC displays a mono-ADP-ribosylhydrolase activity (By similarity). The
CC central part has a zinc-binding function (By similarity). The C-
CC terminus contains two FGDF motifs necessary and sufficient for
CC formation of the nsP3/G3BP1 complex (PubMed:24623412, PubMed:25658430,
CC PubMed:27383630). {ECO:0000250|UniProtKB:P03317,
CC ECO:0000250|UniProtKB:Q8JUX6, ECO:0000269|PubMed:24623412,
CC ECO:0000269|PubMed:25658430, ECO:0000269|PubMed:27383630}.
CC -!- DOMAIN: [Non-structural protein 3']: In the N-terminus, the macro
CC domain displays a mono-ADP-ribosylhydrolase activity (By similarity).
CC The central part has a zinc-binding function (By similarity). The C-
CC terminus contains two FGDF motifs necessary and sufficient for
CC formation of the nsP3'/G3BP1 complex (Probable).
CC {ECO:0000250|UniProtKB:P03317, ECO:0000250|UniProtKB:Q8JUX6,
CC ECO:0000305|PubMed:24623412, ECO:0000305|PubMed:25658430,
CC ECO:0000305|PubMed:27383630}.
CC -!- PTM: [Polyprotein P1234]: Specific enzymatic cleavages in vivo yield
CC mature proteins (PubMed:11257180, PubMed:12917405, PubMed:29695431).
CC The processing of the polyprotein is temporally regulated
CC (PubMed:12917405, PubMed:29695431). In early stages (1.7 hpi), P1234 is
CC first cleaved in trans through its nsP2 protease activity, releasing
CC P123' and nsP4, which associate to form the early replication complex
CC (PubMed:12917405). At the same time, P1234 is also cut at the nsP1/nsP2
CC site early in infection but with lower efficiency (PubMed:12917405).
CC After replication of the viral minus-strand RNAs (4 hpi), the
CC polyproteins are cut at the nsP1/nsP2 and nsP2/nsP3 sites very
CC efficiently, preventing accumulation of P123' and P1234 and allowing
CC the formation of the late replication complex (PubMed:12917405).
CC NsP3'/nsP4 site is not cleaved anymore and P34 is produced rather than
CC nsP4 (By similarity). {ECO:0000250|UniProtKB:P03317,
CC ECO:0000269|PubMed:11257180, ECO:0000269|PubMed:12917405,
CC ECO:0000269|PubMed:29695431}.
CC -!- PTM: [Polyprotein P123']: Specific enzymatic cleavages in vivo yield
CC mature proteins (PubMed:11257180, PubMed:12917405, PubMed:29695431).
CC The processing of the polyprotein is temporally regulated
CC (PubMed:12917405, PubMed:29695431). In early stages (1.7 hpi), P123' is
CC cleaved at the nsP1/nsP2 site with low efficiency (PubMed:12917405).
CC After replication of the viral minus-strand RNAs (4 hpi), the
CC polyproteins are cut at the nsP1/nsP2 and nsP2/nsP3 sites very
CC efficiently, preventing accumulation of P123' and allowing the
CC formation of the late replication complex (PubMed:12917405).
CC {ECO:0000269|PubMed:11257180, ECO:0000269|PubMed:12917405,
CC ECO:0000269|PubMed:29695431}.
CC -!- PTM: [Polyprotein P123]: Specific enzymatic cleavages in vivo yield
CC mature proteins (PubMed:11257180, PubMed:12917405, PubMed:29695431).
CC The processing of the polyprotein is temporally regulated
CC (PubMed:12917405, PubMed:29695431). In early stages (1.7 hpi), P123 is
CC cleaved at the nsP1/nsP2 site with low efficiency (PubMed:12917405).
CC After replication of the viral minus-strand RNAs (4 hpi), the
CC polyproteins are cut at the nsP1/nsP2 and nsP2/nsP3 sites very
CC efficiently, preventing accumulation of P123 and allowing the formation
CC of the late replication complex (PubMed:12917405).
CC {ECO:0000269|PubMed:11257180, ECO:0000269|PubMed:12917405,
CC ECO:0000269|PubMed:29695431}.
CC -!- PTM: [mRNA-capping enzyme nsP1]: Palmitoylated by host
CC palmitoyltransferases ZDHHC2 and ZDHHC19.
CC {ECO:0000250|UniProtKB:Q8JUX6, ECO:0000269|PubMed:10888610,
CC ECO:0000269|PubMed:8910486}.
CC -!- PTM: [Non-structural protein 3]: Phosphorylated by host on serines and
CC threonines. {ECO:0000269|PubMed:11104756}.
CC -!- PTM: [Non-structural protein 3']: Phosphorylated by host on serines and
CC threonines. {ECO:0000269|PubMed:11104756}.
CC -!- PTM: [RNA-directed RNA polymerase nsP4]: Ubiquitinated; targets the
CC protein for rapid degradation via the ubiquitin system (By similarity).
CC Nsp4 is present in extremely low quantities due to low frequency of
CC translation through the amber stop-codon and the degradation by the
CC ubiquitin pathway (By similarity). {ECO:0000250|UniProtKB:P03317}.
CC -!- MISCELLANEOUS: Viral replication produces dsRNA in the late phase of
CC infection, resulting in a strong activation of host EIF2AK2/PKR,
CC leading to almost complete phosphorylation of EIF2A (PubMed:15930128,
CC PubMed:16391235). This inactivates completely cellular translation
CC initiation, resulting shutoff of host proteins synthesis
CC (PubMed:16391235). However, phosphorylation of EIF2A is probably not
CC the only mechanism responsible for the host translation shutoff (By
CC similarity). The viral translation can still occur normally because it
CC relies on a hairpin structure in the coding region of sgRNA and is
CC EIF2A-, EIF2D-, EIF4G- EIF4A-independent (By similarity).
CC {ECO:0000250|UniProtKB:P03317, ECO:0000269|PubMed:15930128,
CC ECO:0000269|PubMed:16391235}.
CC -!- CAUTION: There is no stop codon readthrough before nsP4 in the
CC prototype strain sequence. The opal termination codon may have been
CC mutated to a sense codon on passage in cell culture since the prototype
CC strain SFV4 is derived from the L10 strain, which is a laboratory
CC strain resulting from extensive passaging. Isolate Me Tri virus, which
CC has clearly been identified as a Semliki virus isolate, has an opal
CC codon instead of Arg-1812 further confirming the idea that the opal
CC codon may have muted in many SFV strains (PubMed:18753222). In the
CC isolates that have an opal codon, the genome codes for P123, but
CC readthrough of a terminator codon UGA occurs between the codons for
CC Leu-1811 and Leu-1813 giving rise to P1234. P1234 is cleaved quickly by
CC nsP2 into P123' and nsP4 (By similarity). Further processing of p123'
CC gives nsP1, nsP2 and nsP3' which is 6 amino acids longer than nsP3
CC since the cleavage site is after the readthrough (By similarity). The
CC presence of the opal codon may be a requirement for viral maintenance
CC in both vertebrate and invertebrate hosts and a selective advantage may
CC be conferred in cell culture for the sense codon (By similarity).
CC {ECO:0000250|UniProtKB:O90368, ECO:0000250|UniProtKB:Q8JUX6,
CC ECO:0000269|PubMed:18753222, ECO:0000305}.
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DR EMBL; X04129; CAA27741.1; -; Genomic_RNA.
DR EMBL; AJ251359; CAB62256.1; -; Genomic_RNA.
DR EMBL; AY112987; AAM64226.1; -; Genomic_RNA.
DR EMBL; DQ189079; ABA29023.1; -; Genomic_RNA.
DR EMBL; DQ189080; ABA29024.1; -; Genomic_RNA.
DR EMBL; DQ189081; ABA29025.1; -; Genomic_RNA.
DR EMBL; DQ189082; ABA29026.1; -; Genomic_RNA.
DR EMBL; DQ189083; ABA29028.1; -; Genomic_RNA.
DR EMBL; DQ189084; ABA29029.1; -; Genomic_RNA.
DR EMBL; DQ189085; ABA29031.1; -; Genomic_RNA.
DR EMBL; DQ189086; ABA29032.1; -; Genomic_RNA.
DR EMBL; EU350586; ACB12687.1; -; Genomic_RNA.
DR PIR; A23592; MNWVSF.
DR RefSeq; NP_463457.1; NC_003215.1.
DR PDB; 1FW5; NMR; -; A=245-264.
DR PDB; 5DRV; X-ray; 2.75 A; B=1785-1792.
DR PDB; 5FW5; X-ray; 1.92 A; C=1785-1809.
DR PDBsum; 1FW5; -.
DR PDBsum; 5DRV; -.
DR PDBsum; 5FW5; -.
DR SMR; P08411; -.
DR ELM; P08411; -.
DR IntAct; P08411; 2.
DR MEROPS; C09.001; -.
DR iPTMnet; P08411; -.
DR SwissPalm; P08411; -.
DR PRIDE; P08411; -.
DR GeneID; 922350; -.
DR KEGG; vg:922350; -.
DR BRENDA; 3.4.22.B79; 5671.
DR BRENDA; 3.6.1.74; 5671.
DR SABIO-RK; P08411; -.
DR EvolutionaryTrace; P08411; -.
DR Proteomes; UP000000570; Genome.
DR Proteomes; UP000100607; Genome.
DR Proteomes; UP000125835; Genome.
DR Proteomes; UP000136172; Genome.
DR Proteomes; UP000166518; Genome.
DR Proteomes; UP000174511; Genome.
DR GO; GO:0044162; C:host cell cytoplasmic vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0044176; C:host cell filopodium; IEA:UniProtKB-SubCell.
DR GO; GO:0042025; C:host cell nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-KW.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016887; F:ATP hydrolysis activity; IEA:RHEA.
DR GO; GO:0008234; F:cysteine-type peptidase activity; IEA:UniProtKB-KW.
DR GO; GO:0005525; F:GTP binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0008174; F:mRNA methyltransferase activity; IEA:InterPro.
DR GO; GO:0004651; F:polynucleotide 5'-phosphatase activity; IEA:UniProtKB-EC.
DR GO; GO:0004652; F:polynucleotide adenylyltransferase activity; IEA:UniProtKB-EC.
DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
DR GO; GO:0003724; F:RNA helicase activity; IEA:UniProtKB-EC.
DR GO; GO:0003968; F:RNA-directed 5'-3' RNA polymerase activity; IEA:UniProtKB-KW.
DR GO; GO:0006370; P:7-methylguanosine mRNA capping; IEA:UniProtKB-KW.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR GO; GO:0039563; P:suppression by virus of host JAK-STAT cascade via inhibition of STAT1 activity; IEA:UniProtKB-KW.
DR GO; GO:0039523; P:suppression by virus of host mRNA transcription via inhibition of RNA polymerase II activity; IEA:UniProtKB-KW.
DR GO; GO:0039502; P:suppression by virus of host type I interferon-mediated signaling pathway; IEA:UniProtKB-KW.
DR GO; GO:0006351; P:transcription, DNA-templated; IEA:InterPro.
DR GO; GO:0039694; P:viral RNA genome replication; IEA:InterPro.
DR CDD; cd21557; Macro_X_Nsp3-like; 1.
DR Gene3D; 3.40.220.10; -; 1.
DR Gene3D; 3.40.50.150; -; 1.
DR Gene3D; 3.40.50.300; -; 2.
DR Gene3D; 3.90.70.110; -; 1.
DR InterPro; IPR027351; (+)RNA_virus_helicase_core_dom.
DR InterPro; IPR002588; Alphavirus-like_MT_dom.
DR InterPro; IPR002620; Alphavirus_nsp2pro.
DR InterPro; IPR044936; Alphavirus_nsp2pro_sf.
DR InterPro; IPR043502; DNA/RNA_pol_sf.
DR InterPro; IPR002589; Macro_dom.
DR InterPro; IPR043472; Macro_dom-like.
DR InterPro; IPR044371; Macro_X_NSP3-like.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR007094; RNA-dir_pol_PSvirus.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR InterPro; IPR001788; Tymovirus_RNA-dep_RNA_pol.
DR Pfam; PF01661; Macro; 1.
DR Pfam; PF01707; Peptidase_C9; 1.
DR Pfam; PF00978; RdRP_2; 1.
DR Pfam; PF01443; Viral_helicase1; 1.
DR Pfam; PF01660; Vmethyltransf; 1.
DR SMART; SM00506; A1pp; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR SUPFAM; SSF52949; SSF52949; 1.
DR SUPFAM; SSF56672; SSF56672; 1.
DR PROSITE; PS51743; ALPHAVIRUS_MT; 1.
DR PROSITE; PS51154; MACRO; 1.
DR PROSITE; PS51520; NSP2PRO; 1.
DR PROSITE; PS51657; PSRV_HELICASE; 1.
DR PROSITE; PS50507; RDRP_SSRNA_POS; 1.
PE 1: Evidence at protein level;
KW 3D-structure; ATP-binding;
KW Eukaryotic host gene expression shutoff by virus;
KW Eukaryotic host transcription shutoff by virus; GTP-binding; Helicase;
KW Host cell membrane; Host cell projection; Host cytoplasm;
KW Host cytoplasmic vesicle; Host gene expression shutoff by virus;
KW Host membrane; Host nucleus; Host-virus interaction; Hydrolase;
KW Inhibition of host innate immune response by virus;
KW Inhibition of host interferon signaling pathway by virus;
KW Inhibition of host RNA polymerase II by virus;
KW Inhibition of host STAT1 by virus; Lipoprotein; Membrane; Metal-binding;
KW Methyltransferase; mRNA capping; mRNA processing; Multifunctional enzyme;
KW Nucleotide-binding; Nucleotidyltransferase; Palmitate; Phosphoprotein;
KW Protease; Reference proteome; RNA suppression of termination; RNA-binding;
KW RNA-directed RNA polymerase; S-adenosyl-L-methionine; Thiol protease;
KW Transferase; Ubl conjugation; Viral immunoevasion; Viral RNA replication;
KW Zinc.
FT CHAIN 1..2432
FT /note="Polyprotein P1234"
FT /id="PRO_0000308403"
FT CHAIN 1..1818
FT /note="Polyprotein P123'"
FT /id="PRO_0000227770"
FT CHAIN 1..1811
FT /note="Polyprotein P123"
FT /id="PRO_0000446657"
FT CHAIN 1..537
FT /note="mRNA-capping enzyme nsP1"
FT /id="PRO_0000041228"
FT CHAIN 538..1336
FT /note="Protease nsP2"
FT /id="PRO_0000041229"
FT CHAIN 1337..1818
FT /note="Non-structural protein 3'"
FT /id="PRO_0000041230"
FT CHAIN 1337..1811
FT /note="Non-structural protein 3"
FT /id="PRO_0000446658"
FT CHAIN 1819..2431
FT /note="RNA-directed RNA polymerase nsP4"
FT /id="PRO_0000041231"
FT DOMAIN 29..260
FT /note="Alphavirus-like MT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01079"
FT DOMAIN 692..844
FT /note="(+)RNA virus helicase ATP-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00990"
FT DOMAIN 845..993
FT /note="(+)RNA virus helicase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00990"
FT DOMAIN 1006..1329
FT /note="Peptidase C9"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00853"
FT DOMAIN 1337..1495
FT /note="Macro"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00490"
FT DOMAIN 2182..2297
FT /note="RdRp catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00539"
FT REGION 245..264
FT /note="NsP1 membrane-binding"
FT /evidence="ECO:0000269|PubMed:17093195"
FT REGION 1007..1026
FT /note="Nucleolus localization signal"
FT /evidence="ECO:0000269|PubMed:1386484"
FT REGION 1759..1779
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 1060..1069
FT /note="Nuclear export signal"
FT /evidence="ECO:0000250|UniProtKB:P27282"
FT MOTIF 1184..1188
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000269|PubMed:17652399,
FT ECO:0000269|PubMed:8610462"
FT MOTIF 1787..1790
FT /note="FGDF; binding to host G3BP1"
FT /evidence="ECO:0000269|PubMed:25658430,
FT ECO:0000305|PubMed:24623412"
FT MOTIF 1804..1807
FT /note="FGDF; binding to host G3BP1"
FT /evidence="ECO:0000269|PubMed:25658430,
FT ECO:0000305|PubMed:24623412"
FT ACT_SITE 1015
FT /note="For cysteine protease nsP2 activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00853"
FT ACT_SITE 1085
FT /note="For cysteine protease nsP2 activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00853"
FT BINDING 723..730
FT /ligand="a ribonucleoside 5'-triphosphate"
FT /ligand_id="ChEBI:CHEBI:61557"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00990"
FT BINDING 1346
FT /ligand="ADP-D-ribose"
FT /ligand_id="ChEBI:CHEBI:57967"
FT /evidence="ECO:0000250|UniProtKB:Q8JUX6"
FT BINDING 1360
FT /ligand="ADP-D-ribose"
FT /ligand_id="ChEBI:CHEBI:57967"
FT /evidence="ECO:0000250|UniProtKB:Q8JUX6"
FT BINDING 1368
FT /ligand="ADP-D-ribose"
FT /ligand_id="ChEBI:CHEBI:57967"
FT /evidence="ECO:0000250|UniProtKB:Q8JUX6"
FT BINDING 1448
FT /ligand="ADP-D-ribose"
FT /ligand_id="ChEBI:CHEBI:57967"
FT /evidence="ECO:0000250|UniProtKB:Q8JUX6"
FT BINDING 1449
FT /ligand="ADP-D-ribose"
FT /ligand_id="ChEBI:CHEBI:57967"
FT /evidence="ECO:0000250|UniProtKB:Q8JUX6"
FT BINDING 1450
FT /ligand="ADP-D-ribose"
FT /ligand_id="ChEBI:CHEBI:57967"
FT /evidence="ECO:0000250|UniProtKB:Q8JUX6"
FT BINDING 1598
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P03317"
FT BINDING 1600
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P03317"
FT BINDING 1623
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P03317"
FT BINDING 1641
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P03317"
FT SITE 38
FT /note="Involved in the phosphoramide link with 7-methyl-
FT GMP"
FT /evidence="ECO:0000250|UniProtKB:P27282"
FT SITE 537..538
FT /note="Cleavage; by protease nsP2"
FT /evidence="ECO:0000250|UniProtKB:P03317"
FT SITE 1336..1337
FT /note="Cleavage; by protease nsP2"
FT /evidence="ECO:0000250|UniProtKB:P03317"
FT SITE 1818..1819
FT /note="Cleavage; by protease nsP2"
FT /evidence="ECO:0000250|UniProtKB:Q8JUX6"
FT MOD_RES 1680
FT /note="Phosphothreonine; by host"
FT /evidence="ECO:0000269|PubMed:11104756"
FT MOD_RES 1681
FT /note="Phosphothreonine; by host"
FT /evidence="ECO:0000269|PubMed:11104756"
FT LIPID 418
FT /note="S-palmitoyl cysteine; by host"
FT /evidence="ECO:0000269|PubMed:10888610,
FT ECO:0000269|PubMed:8910486"
FT LIPID 420
FT /note="S-palmitoyl cysteine; by host"
FT /evidence="ECO:0000269|PubMed:10888610,
FT ECO:0000269|PubMed:8910486"
FT VARIANT 6
FT /note="H -> Y (in strain: Isolate L10)"
FT VARIANT 95..96
FT /note="VC -> DS (in strain: Isolate Garoff/Takkinen)"
FT VARIANT 119
FT /note="D -> N (in strain: Isolate Ts14)"
FT VARIANT 311
FT /note="E -> K (in strain: Isolate L10)"
FT VARIANT 427
FT /note="R -> K (in strain: Isolate Me Tri virus)"
FT /evidence="ECO:0000269|PubMed:18753222"
FT VARIANT 470
FT /note="K -> E (in strain: Isolate Me Tri virus)"
FT /evidence="ECO:0000269|PubMed:18753222"
FT VARIANT 482
FT /note="I -> M (in strain: Isolate Me Tri virus)"
FT /evidence="ECO:0000269|PubMed:18753222"
FT VARIANT 529
FT /note="E -> D (in strain: Isolate Ts10)"
FT VARIANT 596
FT /note="R -> G (in strain: Isolate Garoff/Takkinen)"
FT VARIANT 761
FT /note="H -> Y (in strain: Isolate Me Tri virus)"
FT /evidence="ECO:0000269|PubMed:18753222"
FT VARIANT 764..771
FT /note="LDIQAKTV -> KGTSRENS (in strain: Isolate Garoff/
FT Takkinen)"
FT VARIANT 764..771
FT /note="LDIQAKTV -> NWTSRKNS (in strain: Isolate L10)"
FT VARIANT 817
FT /note="D -> N (in strain: Isolate L10)"
FT VARIANT 826
FT /note="M -> T (in strain: Isolate L10)"
FT VARIANT 843
FT /note="H -> N (in strain: Isolate L10)"
FT VARIANT 845
FT /note="S -> N (in strain: Isolate Ts1)"
FT VARIANT 859
FT /note="S -> C (in strain: Isolate L10)"
FT VARIANT 869
FT /note="T -> S (in strain: Isolate Ts13)"
FT VARIANT 901
FT /note="V -> A (in strain: Isolate Garoff/Takkinen)"
FT VARIANT 981
FT /note="T -> M (in strain: Isolate Me Tri virus)"
FT /evidence="ECO:0000269|PubMed:18753222"
FT VARIANT 1052
FT /note="V -> E (in strain: Isolate Me Tri virus)"
FT /evidence="ECO:0000269|PubMed:18753222"
FT VARIANT 1114
FT /note="G -> R (in strain: Isolate Ts11)"
FT VARIANT 1199
FT /note="A -> T (in strain: Isolate Ts6)"
FT VARIANT 1258..1259
FT /note="SL -> I (in strain: Isolate Garoff/Takkinen and
FT Isolate L10)"
FT VARIANT 1384
FT /note="A -> E (in strain: Isolate L10 clone SFV4)"
FT VARIANT 1406
FT /note="A -> G (in strain: Isolate Me Tri virus)"
FT /evidence="ECO:0000269|PubMed:18753222"
FT VARIANT 1565
FT /note="Q -> R (in strain: Isolate Garoff/Takkinen)"
FT VARIANT 1579
FT /note="R -> G (in strain: Isolate Garoff/Takkinen)"
FT VARIANT 1644
FT /note="G -> V (in strain: Isolate Garoff/Takkinen, Isolate
FT L10 and Isolate L10 clone SFV4)"
FT VARIANT 1849
FT /note="E -> Q (in strain: Isolate Garoff/Takkinen)"
FT VARIANT 1921
FT /note="P -> R (in strain: Isolate L10)"
FT VARIANT 1938
FT /note="V -> A (in strain: Isolate L10)"
FT VARIANT 2060
FT /note="A -> V (in strain: Isolate Ts13)"
FT VARIANT 2088
FT /note="A -> D (in strain: Isolate L10)"
FT VARIANT 2405
FT /note="A -> T (in strain: Isolate Garoff/Takkinen)"
FT MUTAGEN 19
FT /note="L->E: Complete loss of guanylyltransferase and
FT guanine-7-methyl transferase activity in vitro."
FT /evidence="ECO:0000269|PubMed:8985362"
FT MUTAGEN 38
FT /note="H->A: Complete loss of guanylyltransferase and
FT guanine-7-methyl transferase activity in vitro."
FT /evidence="ECO:0000269|PubMed:8985362"
FT MUTAGEN 64
FT /note="D->A: 60% increase of guanine-7-methyl transferase
FT activity in vitro. Complete loss of guanylyltransferase
FT activity in vitro."
FT /evidence="ECO:0000269|PubMed:8985362"
FT MUTAGEN 81..83
FT /note="CVC->AVA: 60% loss of guanine-7-methyl transferase
FT activity and complete loss of guanylyltransferase activity
FT in vitro."
FT /evidence="ECO:0000269|PubMed:8985362"
FT MUTAGEN 90
FT /note="D->A: Complete loss of guanylyltransferase and
FT guanine-7-methyl transferase activity in vitro."
FT /evidence="ECO:0000269|PubMed:8985362"
FT MUTAGEN 93
FT /note="R->A: Complete loss of guanylyltransferase and
FT guanine-7-methyl transferase activity in vitro."
FT /evidence="ECO:0000269|PubMed:8985362"
FT MUTAGEN 135
FT /note="C->A: 90% loss of guanine-7-methyl transferase
FT activity and complete loss of guanylyltransferase activity
FT in vitro."
FT /evidence="ECO:0000269|PubMed:8985362"
FT MUTAGEN 142
FT /note="C->A: Complete loss of guanylyltransferase and
FT guanine-7-methyl transferase activity in vitro."
FT /evidence="ECO:0000269|PubMed:8985362"
FT MUTAGEN 153
FT /note="D->A: No effect on guanylyltransferase and guanine-
FT 7-methyl transferase activity in vitro."
FT /evidence="ECO:0000269|PubMed:8985362"
FT MUTAGEN 169
FT /note="K->A: 50% loss of guanine-7-methyl transferase
FT activity and no effect on guanylyltransferase activity in
FT vitro."
FT /evidence="ECO:0000269|PubMed:8985362"
FT MUTAGEN 180
FT /note="D->A: No effect on guanine-7-methyl transferase
FT activity in vitro."
FT /evidence="ECO:0000269|PubMed:8985362"
FT MUTAGEN 203
FT /note="E->A: No effect on guanylyltransferase and guanine-
FT 7-methyl transferase activity in vitro."
FT /evidence="ECO:0000269|PubMed:8985362"
FT MUTAGEN 214
FT /note="C->A: 90% loss of guanylyltransferase and guanine-7-
FT methyl transferase activity in vitro."
FT /evidence="ECO:0000269|PubMed:8985362"
FT MUTAGEN 249
FT /note="Y->A: 97% loss of guanine-7-methyl transferase
FT activity and complete loss of guanylyltransferase activity
FT in vitro."
FT /evidence="ECO:0000269|PubMed:8985362"
FT MUTAGEN 253
FT /note="R->A: Nsp1 accumulates in the cytoplasm and is
FT poorly palmitoylated."
FT /evidence="ECO:0000269|PubMed:17093195"
FT MUTAGEN 259
FT /note="W->A: Nsp1 accumulates in the cytoplasm and is
FT poorly palmitoylated."
FT /evidence="ECO:0000269|PubMed:17093195"
FT MUTAGEN 317
FT /note="K->A: 95% loss of guanine-7-methyl transferase
FT activity and 98% loss of guanylyltransferase activity in
FT vitro."
FT /evidence="ECO:0000269|PubMed:8985362"
FT MUTAGEN 418..420
FT /note="CCC->AAA: Complete loss of palmitoylation. Complete
FT loss of pathogenicity in mice."
FT /evidence="ECO:0000269|PubMed:10888610,
FT ECO:0000269|PubMed:8910486"
FT MUTAGEN 729
FT /note="K->N: Complete loss of NTPase and helicase
FT activity."
FT /evidence="ECO:0000269|PubMed:10217401,
FT ECO:0000269|PubMed:10748213, ECO:0000269|PubMed:8057461,
FT ECO:0000269|PubMed:8610462"
FT MUTAGEN 1015
FT /note="C->A: Complete loss of polyprotein processing."
FT /evidence="ECO:0000269|PubMed:11257180"
FT MUTAGEN 1186
FT /note="R->D: Complete loss of nuclear localization for
FT nsP2."
FT /evidence="ECO:0000269|PubMed:8610462"
FT MUTAGEN 1680
FT /note="T->A: Complete loss of threonine phosphorylation."
FT /evidence="ECO:0000269|PubMed:11104756"
FT MUTAGEN 1681
FT /note="T->A: Complete loss of threonine phosphorylation."
FT /evidence="ECO:0000269|PubMed:11104756"
FT MUTAGEN 1786
FT /note="T->A: Weak interaction with host G3BP1."
FT /evidence="ECO:0000269|PubMed:25658430"
FT MUTAGEN 1787
FT /note="F->A: Complete loss of interaction with host G3BP1."
FT /evidence="ECO:0000269|PubMed:25658430"
FT MUTAGEN 1788
FT /note="G->A: Complete loss of interaction with host G3BP1."
FT /evidence="ECO:0000269|PubMed:25658430"
FT MUTAGEN 1789
FT /note="D->A: Complete loss of interaction with host G3BP1."
FT /evidence="ECO:0000269|PubMed:25658430"
FT MUTAGEN 1790
FT /note="F->A: Complete loss of interaction with host G3BP1."
FT /evidence="ECO:0000269|PubMed:25658430"
FT MUTAGEN 1791
FT /note="D->A: No loss of interaction with host G3BP1."
FT /evidence="ECO:0000269|PubMed:25658430"
FT MUTAGEN 1803
FT /note="T->A: Weak interaction with host G3BP1."
FT /evidence="ECO:0000269|PubMed:25658430"
FT MUTAGEN 1804
FT /note="F->A: Complete loss of interaction with host G3BP1."
FT /evidence="ECO:0000269|PubMed:25658430"
FT MUTAGEN 1805
FT /note="G->A: Complete loss of interaction with host G3BP1."
FT /evidence="ECO:0000269|PubMed:25658430"
FT MUTAGEN 1806
FT /note="D->A: Complete loss of interaction with host G3BP1."
FT /evidence="ECO:0000269|PubMed:25658430"
FT MUTAGEN 1807
FT /note="F->A: Complete loss of interaction with host G3BP1."
FT /evidence="ECO:0000269|PubMed:25658430"
FT MUTAGEN 1808
FT /note="D->A: No loss of interaction with host G3BP1."
FT /evidence="ECO:0000269|PubMed:25658430"
FT MUTAGEN 1824
FT /note="D->A: No effect on polyprotein processing."
FT /evidence="ECO:0000269|PubMed:11257180"
FT CONFLICT 1537
FT /note="F -> L (in Ref. 5; ACB12687)"
FT /evidence="ECO:0000305"
FT CONFLICT 1591
FT /note="T -> S (in Ref. 5; ACB12687)"
FT /evidence="ECO:0000305"
FT CONFLICT 1644
FT /note="G -> V (in Ref. 5; ACB12687)"
FT /evidence="ECO:0000305"
FT HELIX 246..259
FT /evidence="ECO:0007829|PDB:1FW5"
FT STRAND 1786..1789
FT /evidence="ECO:0007829|PDB:5DRV"
FT HELIX 1794..1799
FT /evidence="ECO:0007829|PDB:5FW5"
SQ SEQUENCE 2432 AA; 269512 MW; BE7104A1EC3EF6EE CRC64;
MAAKVHVDIE ADSPFIKSLQ KAFPSFEVES LQVTPNDHAN ARAFSHLATK LIEQETDKDT
LILDIGSAPS RRMMSTHKYH CVCPMRSAED PERLVCYAKK LAAASGKVLD REIAGKITDL
QTVMATPDAE SPTFCLHTDV TCRTAAEVAV YQDVYAVHAP TSLYHQAMKG VRTAYWIGFD
TTPFMFDALA GAYPTYATNW ADEQVLQARN IGLCAASLTE GRLGKLSILR KKQLKPCDTV
MFSVGSTLYT ESRKLLRSWH LPSVFHLKGK QSFTCRCDTI VSCEGYVVKK ITMCPGLYGK
TVGYAVTYHA EGFLVCKTTD TVKGERVSFP VCTYVPSTIC DQMTGILATD VTPEDAQKLL
VGLNQRIVVN GRTQRNTNTM KNYLLPIVAV AFSKWAREYK ADLDDEKPLG VRERSLTCCC
LWAFKTRKMH TMYKKPDTQT IVKVPSEFNS FVIPSLWSTG LAIPVRSRIK MLLAKKTKRE
LIPVLDASSA RDAEQEEKER LEAELTREAL PPLVPIAPAE TGVVDVDVEE LEYHAGAGVV
ETPRSALKVT AQPNDVLLGN YVVLSPQTVL KSSKLAPVHP LAEQVKIITH NGRAGRYQVD
GYDGRVLLPC GSAIPVPEFQ ALSESATMVY NEREFVNRKL YHIAVHGPSL NTDEENYEKV
RAERTDAEYV FDVDKKCCVK REEASGLVLV GELTNPPFHE FAYEGLKIRP SAPYKTTVVG
VFGVPGSGKS AIIKSLVTKH DLVTSGKKEN CQEIVNDVKK HRGLDIQAKT VDSILLNGCR
RAVDILYVDE AFACHSGTLL ALIALVKPRS KVVLCGDPKQ CGFFNMMQLK VNFNHNICTE
VCHKSISRRC TRPVTAIVST LHYGGKMRTT NPCNKPIIID TTGQTKPKPG DIVLTCFRGW
VKQLQLDYRG HEVMTAAASQ GLTRKGVYAV RQKVNENPLY APASEHVNVL LTRTEDRLVW
KTLAGDPWIK VLSNIPQGNF TATLEEWQEE HDKIMKVIEG PAAPVDAFQN KANVCWAKSL
VPVLDTAGIR LTAEEWSTII TAFKEDRAYS PVVALNEICT KYYGVDLDSG LFSAPKVSLY
YENNHWDNRP GGRMYGFNAA TAARLEARHT FLKGQWHTGK QAVIAERKIQ PLSVLDNVIP
INRRLPHALV AEYKTVKGSR VEWLVNKVRG YHVLLVSEYN LALPRRRVTW LSPLNVTGAD
RCYDLSLGLP ADAGRFDLVF VNIHTEFRIH HYQQCVDHAM KLQMLGGDAL RLLKPGGSLL
MRAYGYADKI SEAVVSSLSR KFSSARVLRP DCVTSNTEVF LLFSNFDNGK RPSTLHQMNT
KLSAVYAGEA MHTAGCAPSY RVKRADIATC TEAAVVNAAN ARGTVGDGVC RAVAKKWPSA
FKGAATPVGT IKTVMCGSYP VIHAVAPNFS ATTEAEGDRE LAAVYRAVAA EVNRLSLSSV
AIPLLSTGVF SGGRDRLQQS LNHLFTAMDA TDADVTIYCR DKSWEKKIQE AIDMRTAVEL
LNDDVELTTD LVRVHPDSSL VGRKGYSTTD GSLYSYFEGT KFNQAAIDMA EILTLWPRLQ
EANEQICLYA LGETMDNIRS KCPVNDSDSS TPPRTVPCLC RYAMTAERIA RLRSHQVKSM
VVCSSFPLPK YHVDGVQKVK CEKGLLFDPT VPSVVSPRKY AASTTDHSDR SLRGFDLDWT
TDSSSTASDT MSLPSLQSCD IDSIYEPMAP IVVTADVHPE PAGIADLAAD VHPEPADHVD
LENPIPPPRP KRAAYLASRA AERPVPAPRK PTPAPRTAFR NKLPLTFGDF DEHEVDALAS
GITFGDFDDV LRLGRAGAYI FSSDTGSGHL QQKSVRQHNL QCAQLDAVEE EKMYPPKLDT
EREKLLLLKM QMHPSEANKS RYQSRKVENM KATVVDRLTS GARLYTGADV GRIPTYAVRY
PRPVYSPTVI ERFSSPDVAI AACNEYLSRN YPTVASYQIT DEYDAYLDMV DGSDSCLDRA
TFCPAKLRCY PKHHAYHQPT VRSAVPSPFQ NTLQNVLAAA TKRNCNVTQM RELPTMDSAV
FNVECFKRYA CSGEYWEEYA KQPIRITTEN ITTYVTKLKG PKAAALFAKT HNLVPLQEVP
MDRFTVDMKR DVKVTPGTKH TEERPKVQVI QAAEPLATAY LCGIHRELVR RLNAVLRPNV
HTLFDMSAED FDAIIASHFH PGDPVLETDI ASFDKSQDDS LALTGLMILE DLGVDQYLLD
LIEAAFGEIS SCHLPTGTRF KFGAMMKSGM FLTLFINTVL NITIASRVLE QRLTDSACAA
FIGDDNIVHG VISDKLMAER CASWVNMEVK IIDAVMGEKP PYFCGGFIVF DSVTQTACRV
SDPLKRLFKL GKPLTAEDKQ DEDRRRALSD EVSKWFRTGL GAELEVALTS RYEVEGCKSI
LIAMATLARD IKAFKKLRGP VIHLYGGPRL VR
