ID   POLN_CHIK3              Reviewed;        2474 AA.
AC   Q5XXP4;
DT   21-MAR-2006, integrated into UniProtKB/Swiss-Prot.
DT   23-NOV-2004, sequence version 1.
DT   18-JUN-2025, entry version 129.
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=3.4.22.- {ECO:0000250|UniProtKB:Q8JUX6};
DE              EC=3.6.1.15 {ECO:0000250|UniProtKB:Q8JUX6};
DE              EC=3.6.1.74 {ECO:0000250|UniProtKB:P08411};
DE              EC=3.6.4.13 {ECO:0000250|UniProtKB:Q8JUX6};
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:0000305};
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   Chikungunya virus (strain 37997) (CHIKV).
OC   Viruses; Riboviria; Orthornavirae; Kitrinoviricota; Alsuviricetes;
OC   Martellivirales; Togaviridae; Alphavirus; Chikungunya virus.
OX   NCBI_TaxID=371095;
OH   NCBI_TaxID=7159; Aedes aegypti (Yellowfever mosquito) (Culex aegypti).
OH   NCBI_TaxID=7160; Aedes albopictus (Asian tiger mosquito) (Stegomyia albopicta).
OH   NCBI_TaxID=299627; Aedes furcifer (Mosquito).
OH   NCBI_TaxID=188700; Aedes polynesiensis (Polynesian tiger mosquito).
OH   NCBI_TaxID=9533; Cercopithecus.
OH   NCBI_TaxID=9606; Homo sapiens (Human).
OH   NCBI_TaxID=9539; Macaca (macaques).
OH   NCBI_TaxID=9598; Pan troglodytes (Chimpanzee).
OH   NCBI_TaxID=9554; Papio (baboons).
OH   NCBI_TaxID=9573; Presbytis.
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX   PubMed=15891138; DOI=10.4269/ajtmh.2005.72.616;
RA   Vanlandingham D.L., Hong C., Klingler K., Tsetsarkin K., McElroy K.L.,
RA   Powers A.M., Lehane M.J., Higgs S.;
RT   "Differential infectivities of O'Nyong-Nyong and Chikungunya virus isolates
RT   in Anopheles gambiae and Aedes aegypti mosquitoes.";
RL   Am. J. Trop. Med. Hyg. 72:616-621(2005).
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
CC       guanylyltransferase (By similarity). 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 (By similarity). nsP1 capping consists in the following reactions:
CC       GTP is first methylated into 7-methyl-GMP and then is covalently linked
CC       to nsP1 to form the m7GMp-nsP1 complex from which 7-methyl-GMP complex
CC       is transferred to the mRNA to create the cap structure (By similarity).
CC       NsP1 is also needed for the initiation of the minus-strand RNAs
CC       synthesis (By similarity). At the initiation of virus replication,
CC       mediates the assembly of the viral replication complex made of the non-
CC       structural proteins, the association of this complex with the inner
CC       face of the plasma membrane and the formation of membranous spherules
CC       that serve as replication complex factories (By similarity). Forms the
CC       neck of these spherules with a central channel for mediating
CC       communication and the passage of RNA, nucleotides, and small proteins
CC       between the viral replication complex and the host cytoplasm (By
CC       similarity). Palmitoylated nsP1 is remodeling host cell cytoskeleton,
CC       and induces filopodium-like structure formation at the surface of the
CC       host cell (By similarity). {ECO:0000250|UniProtKB:P03317,
CC       ECO:0000250|UniProtKB:Q8JUX6}.
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 (By similarity). NTPase and RNA
CC       triphosphatase are involved in viral RNA capping and helicase keeps a
CC       check on the dsRNA replication intermediates (By similarity). The C-
CC       terminus harbors a protease that specifically cleaves the polyproteins
CC       and releases the mature proteins (By similarity). Required for the
CC       shutoff of minus-strand RNAs synthesis (By similarity). Specifically
CC       inhibits the host IFN response by promoting the nuclear export of host
CC       STAT1 (By similarity). Also inhibits host transcription by inducing the
CC       rapid proteasome-dependent degradation of POLR2A, a catalytic subunit
CC       of the RNAPII complex (By similarity). The resulting inhibition of
CC       cellular protein synthesis serves to ensure maximal viral gene
CC       expression and to evade host immune response (By similarity).
CC       {ECO:0000250|UniProtKB:P03317, ECO:0000250|UniProtKB:P08411,
CC       ECO:0000250|UniProtKB:Q8JUX6}.
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       (By similarity). 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 (By
CC       similarity). {ECO:0000250|UniProtKB:P03317,
CC       ECO:0000250|UniProtKB:Q8JUX6}.
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=N(7)-methyl-GTP + L-histidyl-[protein] = N(tele)-(N(7)-
CC         methylguanosine 5'-phospho)-L-histidyl-[protein] + diphosphate;
CC         Xref=Rhea:RHEA:54792, Rhea:RHEA-COMP:9745, Rhea:RHEA-COMP:13995,
CC         ChEBI:CHEBI:29979, ChEBI:CHEBI:33019, ChEBI:CHEBI:87133,
CC         ChEBI:CHEBI:138334; Evidence={ECO:0000250|UniProtKB:P27282};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:54793;
CC         Evidence={ECO:0000250|UniProtKB:P27282};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=N(tele)-(N(7)-methylguanosine 5'-phospho)-L-histidyl-[protein]
CC         + a 5'-end diphospho-(purine-ribonucleoside) in mRNA + H(+) = a 5'-
CC         end (N(7)-methyl 5'-triphosphoguanosine)-(purine-ribonucleoside) in
CC         mRNA + L-histidyl-[protein]; Xref=Rhea:RHEA:54800, Rhea:RHEA-
CC         COMP:9745, Rhea:RHEA-COMP:12925, Rhea:RHEA-COMP:13929, Rhea:RHEA-
CC         COMP:13995, ChEBI:CHEBI:15378, ChEBI:CHEBI:29979, ChEBI:CHEBI:133968,
CC         ChEBI:CHEBI:138276, ChEBI:CHEBI:138334;
CC         Evidence={ECO:0000250|UniProtKB:P27282};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=a 5'-end triphospho-ribonucleoside in mRNA + H2O = a 5'-end
CC         diphospho-ribonucleoside in mRNA + phosphate + H(+);
CC         Xref=Rhea:RHEA:67004, Rhea:RHEA-COMP:17164, Rhea:RHEA-COMP:17165,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:43474,
CC         ChEBI:CHEBI:167616, ChEBI:CHEBI:167618; EC=3.6.1.74;
CC         Evidence={ECO:0000250|UniProtKB:P08411};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:67005;
CC         Evidence={ECO:0000250|UniProtKB:P08411};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=a ribonucleoside 5'-triphosphate + H2O = a ribonucleoside 5'-
CC         diphosphate + phosphate + H(+); 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:0000250|UniProtKB:Q8JUX6};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=ATP + H2O = ADP + phosphate + H(+); 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:0000250|UniProtKB:Q8JUX6};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=RNA(n) + a ribonucleoside 5'-triphosphate = RNA(n+1) +
CC         diphosphate; 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=4-O-(ADP-D-ribosyl)-L-aspartyl-[protein] + H2O = L-aspartyl-
CC         [protein] + ADP-D-ribose + H(+); 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 = L-glutamyl-
CC         [protein] + ADP-D-ribose + H(+); 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=RNA(n) + ATP = RNA(n)-3'-adenine ribonucleotide + diphosphate;
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=ADP-alpha-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       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   -!- SUBUNIT: [mRNA-capping enzyme nsP1]: Homododecamer (By similarity). The
CC       enzyme forms a membrane-associated dodecameric ring with a central
CC       channel for the exchange of between the viral replication factories and
CC       the host cytoplasm (By similarity). 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). Interacts with host STING1; this
CC       interaction results in inhibition of cGAS-STING signaling and increased
CC       levels of palmitoylation and protein stabilization of nsP1 (By
CC       similarity). Interacts with host TMEM45B; this interaction leads to
CC       viral replication inhibition (By similarity).
CC       {ECO:0000250|UniProtKB:Q8JUX6}.
CC   -!- SUBUNIT: [Non-structural protein 3]: Interacts with mRNA-capping enzyme
CC       nsP1 (By similarity). Interacts (via C-terminus) with host G3BP1; this
CC       interaction inhibits the formation of host stress granules on viral
CC       mRNAs and the nsp3-G3BP1 complexes bind viral RNAs and probably
CC       orchestrate the assembly of viral replication complexes (By
CC       similarity). Interacts (via C-terminus) with host G3BP2; this
CC       interaction inhibits the formation of host stress granules on viral
CC       mRNAs and the nsp3-G3BP2 complexes bind viral RNAs and probably
CC       orchestrate the assembly of viral replication complexes (By
CC       similarity). Interacts (via C-terminus) with host NAP1L1 (By
CC       similarity). Interacts (via C-terminus) with host NAP1L4 (By
CC       similarity). Interacts (via C-terminus) with host DHX9; this
CC       interaction allows the recruitment of DHX9 to the plasma membrane,
CC       where it associates with viral replication complexes and may play a
CC       role in the translation-to-replication switch (By similarity).
CC       Interacts (via C-terminus) with host FHL1 (via LIM domain 1); this
CC       interaction is required for viral RNA replication (By similarity).
CC       Interacts (via C-terminus) with host CD2AP; this interaction plays a
CC       role in initiation of viral replication (By similarity). Interacts (via
CC       C-terminus) with host SH3KBP1; this interaction plays a role in
CC       initiation of viral replication (By similarity).
CC       {ECO:0000250|UniProtKB:Q8JUX6}.
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). Interacts with host
CC       TMEM45B; this interaction leads to viral replication inhibition (By
CC       similarity). {ECO:0000250|UniProtKB:P03317,
CC       ECO:0000250|UniProtKB:P27282, ECO:0000250|UniProtKB:Q8JUX6}.
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, ECO:0000250|UniProtKB:Q8JUX6}.
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:0000250|UniProtKB:P08411}; Lipid-anchor
CC       {ECO:0000250|UniProtKB:P08411}. Host cell membrane
CC       {ECO:0000250|UniProtKB:P08411}; Lipid-anchor
CC       {ECO:0000250|UniProtKB:P08411}; Cytoplasmic side
CC       {ECO:0000250|UniProtKB:P08411}. Host cell projection, host filopodium
CC       {ECO:0000250|UniProtKB:Q8JUX6}. Note=In the late phase of infection,
CC       the 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 (By similarity).
CC       NsP1 is also part of cytoplasmic vesicles, which are probably formed at
CC       the plasma membrane and internalized leading to late
CC       endosomal/lysosomal spherules containing the replication complex (By
CC       similarity). {ECO:0000250|UniProtKB:P08411,
CC       ECO:0000250|UniProtKB:Q8JUX6}.
CC   -!- SUBCELLULAR LOCATION: [Protease nsP2]: Host cytoplasmic vesicle
CC       membrane {ECO:0000250|UniProtKB:P08411}; Peripheral membrane protein
CC       {ECO:0000250|UniProtKB:P08411}. Host nucleus
CC       {ECO:0000250|UniProtKB:P27282}. Host cytoplasm
CC       {ECO:0000250|UniProtKB:P27282}. Note=In the late phase of infection,
CC       the polyprotein is quickly cleaved before localization to cellular
CC       membranes. Then approximately half of nsP2 is found in the nucleus (By
CC       similarity). Shuttles between cytoplasm and nucleus (By similarity).
CC       NsP2 is also part of cytoplasmic vesicles, which are probably formed at
CC       the plasma membrane and internalized leading to late
CC       endosomal/lysosomal spherules containing the replication complex (By
CC       similarity). {ECO:0000250|UniProtKB:P08411,
CC       ECO:0000250|UniProtKB:P27282}.
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:0000250|UniProtKB:P08411}. 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:0000250|UniProtKB:P08411}.
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: [mRNA-capping enzyme nsP1]: The N-terminus binds a zinc ion
CC       which stabilizes this region (By similarity). The C-terminus is
CC       disordered (By similarity). {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 called, the alphavirus unique domain (AUD) has a zinc-
CC       binding function (By similarity). The C-terminus region, also called
CC       hypervariable domain (HVD), is mainly disordered and binds several host
CC       proteins (By similarity). This intrinsically disordered domain contains
CC       2 SH3 domain-binding sites and 2 FGDF motifs necessary and sufficient
CC       for the formation of nsP3/G3BP complexes (By similarity).
CC       {ECO:0000250|UniProtKB:Q8JUX6}.
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 (By similarity).
CC       {ECO:0000250|UniProtKB:P03317, ECO:0000250|UniProtKB:Q8JUX6}.
CC   -!- PTM: [Polyprotein P1234]: Specific enzymatic cleavages in vivo yield
CC       mature proteins (By similarity). The processing of the polyprotein is
CC       temporally regulated (By similarity). In early stages (1.7 hpi), P1234
CC       is first cleaved in trans through its nsP2 protease activity, releasing
CC       P123' and nsP4, which associate to form the early replication complex
CC       (By similarity). At the same time, P1234 is also cut at the nsP1/nsP2
CC       site early in infection but with lower efficiency (By similarity).
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 (By similarity).
CC       NsP3'/nsP4 site is not cleaved anymore and P34 is produced rather than
CC       nsP4 (By similarity). {ECO:0000250|UniProtKB:P03317}.
CC   -!- PTM: [Polyprotein P123]: Specific enzymatic cleavages in vivo yield
CC       mature proteins (By similarity). The processing of the polyprotein is
CC       temporally regulated (By similarity). In early stages (1.7 hpi), P123
CC       is cleaved at the nsP1/nsP2 site with low efficiency (By similarity).
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 (By similarity).
CC       {ECO:0000250|UniProtKB:P03317}.
CC   -!- PTM: [Polyprotein P123']: Specific enzymatic cleavages in vivo yield
CC       mature proteins (By similarity). The processing of the polyprotein is
CC       temporally regulated (By similarity). In early stages (1.7 hpi), P123'
CC       is cleaved at the nsP1/nsP2 site with low efficiency (By similarity).
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 (By similarity).
CC       {ECO:0000250|UniProtKB:P03317}.
CC   -!- PTM: [mRNA-capping enzyme nsP1]: Palmitoylated by host
CC       palmitoyltransferases ZDHHC2 and ZDHHC19 (By similarity).
CC       Palmitoylation is increased by the interacton with host STING1 (By
CC       similarity). {ECO:0000250|UniProtKB:Q8JUX6}.
CC   -!- PTM: [Non-structural protein 3]: Phosphorylated by host on serines and
CC       threonines. {ECO:0000250|UniProtKB:P08411}.
CC   -!- PTM: [Non-structural protein 3']: Phosphorylated by host on serines and
CC       threonines. {ECO:0000250|UniProtKB:P08411}.
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 (By similarity).
CC       This inactivates completely cellular translation initiation, resulting
CC       shutoff of host proteins synthesis (By similarity). However,
CC       phosphorylation of EIF2A is probably not the only mechanism responsible
CC       for the host translation shutoff (By similarity). The viral translation
CC       can still occur normally because it relies on a hairpin structure in
CC       the coding region of sgRNA and is EIF2A-, EIF2D-, EIF4G- EIF4A-
CC       independent (By similarity). {ECO:0000250|UniProtKB:P03317}.
CC   -!- MISCELLANEOUS: The genome codes for P123, but readthrough of a
CC       terminator codon UGA occurs between the codons for Leu-1856 and Leu-
CC       1858 giving rise to P1234 (Probable). P1234 is cleaved quickly by nsP2
CC       into P123' and nsP4 (By similarity). Further processing of p123' gives
CC       nsP1, nsP2 and nsP3' which is 6 amino acids longer than nsP3 since the
CC       cleavage site is after the readthrough (By similarity). This unusual
CC       molecular mechanism ensures that few nsP4 are produced compared to
CC       other non-structural proteins (By similarity). Mutant viruses with no
CC       alternative termination site grow significantly slower than wild-type
CC       virus (By similarity). The opal termination codon is frequently mutated
CC       to a sense codon on passage in cell culture (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:P03317,
CC       ECO:0000305}.
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DR   EMBL; AY726732; AAU43880.1; -; Genomic_RNA.
DR   PDB; 6W0T; X-ray; 1.95 A; A/B/C/D=1334-1493.
DR   PDBsum; 6W0T; -.
DR   IntAct; Q5XXP4; 1.
DR   MEROPS; C09.001; -.
DR   Proteomes; UP000008450; 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:0140818; F:mRNA 5'-triphosphate monophosphatase activity; IEA:RHEA.
DR   GO; GO:0008174; F:mRNA methyltransferase activity; IEA:InterPro.
DR   GO; GO:1990817; F:poly(A) RNA polymerase activity; IEA:UniProtKB-EC.
DR   GO; GO:0004651; F:polynucleotide 5'-phosphatase 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 RNA polymerase activity; IEA:UniProtKB-KW.
DR   GO; GO:0006370; P:7-methylguanosine mRNA capping; IEA:UniProtKB-KW.
DR   GO; GO:0006351; P:DNA-templated transcription; IEA:InterPro.
DR   GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR   GO; GO:0016556; P:mRNA modification; IEA:InterPro.
DR   GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR   GO; GO:0039657; P:symbiont-mediated suppression of host gene expression; IEA:UniProtKB-KW.
DR   GO; GO:0039523; P:symbiont-mediated suppression of host mRNA transcription via inhibition of RNA polymerase II activity; IEA:UniProtKB-KW.
DR   GO; GO:0039694; P:viral RNA genome replication; IEA:InterPro.
DR   CDD; cd21557; Macro_X_Nsp3-like; 1.
DR   CDD; cd23250; Togaviridae_RdRp; 1.
DR   FunFam; 3.90.70.110:FF:000001; Non-structural polyprotein P1234; 1.
DR   FunFam; 3.40.220.10:FF:000015; Polyprotein P1234; 1.
DR   FunFam; 3.40.50.150:FF:000323; Polyprotein P1234; 1.
DR   FunFam; 3.40.50.300:FF:001403; Polyprotein P1234; 1.
DR   FunFam; 3.40.50.300:FF:001415; Polyprotein P1234; 1.
DR   Gene3D; 3.90.70.110; Alphavirus nsP2 protease domain; 1.
DR   Gene3D; 3.40.220.10; Leucine Aminopeptidase, subunit E, domain 1; 1.
DR   Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 2.
DR   Gene3D; 3.40.50.150; Vaccinia Virus protein VP39; 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; IPR048891; nsP3_ZBD.
DR   InterPro; IPR027417; P-loop_NTPase.
DR   InterPro; IPR001788; RNA-dep_RNA_pol_alsuvir.
DR   InterPro; IPR007094; RNA-dir_pol_PSvirus.
DR   InterPro; IPR029063; SAM-dependent_MTases_sf.
DR   InterPro; IPR047311; Togaviridae_RdRp.
DR   InterPro; IPR049329; ToMV_Hel_N.
DR   Pfam; PF01661; Macro; 1.
DR   Pfam; PF20852; nsP3_ZBD; 1.
DR   Pfam; PF01707; Peptidase_C9; 1.
DR   Pfam; PF00978; RdRP_2; 1.
DR   Pfam; PF20896; ToMV_Hel_N; 1.
DR   Pfam; PF01443; Viral_helicase1; 1.
DR   Pfam; PF01660; Vmethyltransf; 1.
DR   SMART; SM00506; A1pp; 1.
DR   SUPFAM; SSF56672; DNA/RNA polymerases; 1.
DR   SUPFAM; SSF52949; Macro domain-like; 1.
DR   SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 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 RNA polymerase II by virus; Lipoprotein; Membrane;
KW   Metal-binding; Methyltransferase; mRNA capping; mRNA processing;
KW   Multifunctional enzyme; Nucleotide-binding; Nucleotidyltransferase;
KW   Palmitate; Phosphoprotein; Protease; RNA suppression of termination;
KW   RNA-binding; RNA-directed RNA polymerase; S-adenosyl-L-methionine;
KW   Thiol protease; Transferase; Ubl conjugation; Viral RNA replication; Zinc.
FT   CHAIN           1..2474
FT                   /note="Polyprotein P1234"
FT                   /id="PRO_0000308396"
FT   CHAIN           1..1863
FT                   /note="Polyprotein P123'"
FT                   /id="PRO_0000227765"
FT   CHAIN           1..1856
FT                   /note="Polyprotein P123"
FT                   /id="PRO_0000446648"
FT   CHAIN           1..535
FT                   /note="mRNA-capping enzyme nsP1"
FT                   /id="PRO_0000227766"
FT   CHAIN           536..1333
FT                   /note="Protease nsP2"
FT                   /id="PRO_0000227767"
FT   CHAIN           1334..1863
FT                   /note="Non-structural protein 3'"
FT                   /id="PRO_0000227768"
FT   CHAIN           1334..1856
FT                   /note="Non-structural protein 3"
FT                   /id="PRO_0000446649"
FT   CHAIN           1864..2474
FT                   /note="RNA-directed RNA polymerase nsP4"
FT                   /id="PRO_0000227769"
FT   DOMAIN          28..259
FT                   /note="Alphavirus-like MT"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01079"
FT   DOMAIN          690..842
FT                   /note="(+)RNA virus helicase ATP-binding"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00990"
FT   DOMAIN          843..991
FT                   /note="(+)RNA virus helicase C-terminal"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00990"
FT   DOMAIN          1004..1327
FT                   /note="Peptidase C9"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00853"
FT   DOMAIN          1334..1493
FT                   /note="Macro"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00490"
FT   DOMAIN          2228..2343
FT                   /note="RdRp catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00539"
FT   REGION          295..450
FT                   /note="Membrane-binding and oligomerization"
FT                   /evidence="ECO:0000250|UniProtKB:Q8JUX6"
FT   REGION          1005..1024
FT                   /note="Nucleolus localization signal"
FT                   /evidence="ECO:0000250|UniProtKB:P08411"
FT   REGION          1651..1706
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1659..1857
FT                   /note="HVD"
FT                   /evidence="ECO:0000250|UniProtKB:Q8JUX6"
FT   REGION          1726..1739
FT                   /note="Interaction with host CD2AP"
FT                   /evidence="ECO:0000250|UniProtKB:Q8JUX6"
FT   REGION          1745..1793
FT                   /note="Interaction with host FHL1"
FT                   /evidence="ECO:0000250|UniProtKB:Q8JUX6"
FT   REGION          1756..1767
FT                   /note="Interaction with host CD2AP"
FT                   /evidence="ECO:0000250|UniProtKB:Q8JUX6"
FT   REGION          1820..1828
FT                   /note="Interaction with host CD2AP"
FT                   /evidence="ECO:0000250|UniProtKB:Q8JUX6"
FT   MOTIF           1058..1067
FT                   /note="Nuclear export signal"
FT                   /evidence="ECO:0000250|UniProtKB:P27282"
FT   MOTIF           1182..1186
FT                   /note="Nuclear localization signal"
FT                   /evidence="ECO:0000250|UniProtKB:P08411"
FT   MOTIF           1812..1815
FT                   /note="FGDF; binding to host G3BP1"
FT                   /evidence="ECO:0000250|UniProtKB:P08411"
FT   MOTIF           1830..1833
FT                   /note="FGDF; binding to host G3BP1"
FT                   /evidence="ECO:0000250|UniProtKB:P08411"
FT   COMPBIAS        1660..1679
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        37
FT                   /note="For mRNA-capping enzyme nsP1 activity"
FT                   /evidence="ECO:0000250|UniProtKB:Q8JUX6"
FT   ACT_SITE        1013
FT                   /note="For cysteine protease nsP2 activity"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00853"
FT   ACT_SITE        1083
FT                   /note="For cysteine protease nsP2 activity"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00853"
FT   BINDING         79
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000250|UniProtKB:Q8JUX6"
FT   BINDING         129
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000250|UniProtKB:Q8JUX6"
FT   BINDING         134
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000250|UniProtKB:Q8JUX6"
FT   BINDING         141
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000250|UniProtKB:Q8JUX6"
FT   BINDING         721..728
FT                   /ligand="a ribonucleoside 5'-triphosphate"
FT                   /ligand_id="ChEBI:CHEBI:61557"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00990"
FT   BINDING         1343
FT                   /ligand="ADP-D-ribose"
FT                   /ligand_id="ChEBI:CHEBI:57967"
FT                   /evidence="ECO:0000250|UniProtKB:P36328"
FT   BINDING         1357
FT                   /ligand="ADP-D-ribose"
FT                   /ligand_id="ChEBI:CHEBI:57967"
FT                   /evidence="ECO:0000250|UniProtKB:Q8JUX6"
FT   BINDING         1365
FT                   /ligand="ADP-D-ribose"
FT                   /ligand_id="ChEBI:CHEBI:57967"
FT                   /evidence="ECO:0000250|UniProtKB:Q8JUX6"
FT   BINDING         1445
FT                   /ligand="ADP-D-ribose"
FT                   /ligand_id="ChEBI:CHEBI:57967"
FT                   /evidence="ECO:0000250|UniProtKB:P36328"
FT   BINDING         1446
FT                   /ligand="ADP-D-ribose"
FT                   /ligand_id="ChEBI:CHEBI:57967"
FT                   /evidence="ECO:0000250|UniProtKB:Q8JUX6"
FT   BINDING         1447
FT                   /ligand="ADP-D-ribose"
FT                   /ligand_id="ChEBI:CHEBI:57967"
FT                   /evidence="ECO:0000250|UniProtKB:Q8JUX6"
FT   BINDING         1595
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000250|UniProtKB:P03317"
FT   BINDING         1597
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000250|UniProtKB:P03317"
FT   BINDING         1620
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000250|UniProtKB:P03317"
FT   BINDING         1638
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000250|UniProtKB:P03317"
FT   SITE            37
FT                   /note="Involved in the phosphoramide link with 7-methyl-
FT                   GMP"
FT                   /evidence="ECO:0000250|UniProtKB:P27282"
FT   SITE            535..536
FT                   /note="Cleavage; by protease nsP2"
FT                   /evidence="ECO:0000250|UniProtKB:P03317"
FT   SITE            1333..1334
FT                   /note="Cleavage; by protease nsP2"
FT                   /evidence="ECO:0000250|UniProtKB:P03317"
FT   SITE            1863..1864
FT                   /note="Cleavage; by protease nsP2"
FT                   /evidence="ECO:0000250|UniProtKB:Q8JUX6"
FT   LIPID           417
FT                   /note="S-palmitoyl cysteine; by host"
FT                   /evidence="ECO:0000250|UniProtKB:Q8JUX6"
FT   LIPID           419
FT                   /note="S-palmitoyl cysteine; by host"
FT                   /evidence="ECO:0000250|UniProtKB:Q8JUX6"
FT   STRAND          1337..1342
FT                   /evidence="ECO:0007829|PDB:6W0T"
FT   HELIX           1344..1346
FT                   /evidence="ECO:0007829|PDB:6W0T"
FT   STRAND          1352..1355
FT                   /evidence="ECO:0007829|PDB:6W0T"
FT   HELIX           1366..1373
FT                   /evidence="ECO:0007829|PDB:6W0T"
FT   HELIX           1375..1378
FT                   /evidence="ECO:0007829|PDB:6W0T"
FT   STRAND          1388..1393
FT                   /evidence="ECO:0007829|PDB:6W0T"
FT   STRAND          1396..1401
FT                   /evidence="ECO:0007829|PDB:6W0T"
FT   TURN            1406..1408
FT                   /evidence="ECO:0007829|PDB:6W0T"
FT   HELIX           1411..1432
FT                   /evidence="ECO:0007829|PDB:6W0T"
FT   STRAND          1435..1440
FT                   /evidence="ECO:0007829|PDB:6W0T"
FT   HELIX           1454..1465
FT                   /evidence="ECO:0007829|PDB:6W0T"
FT   STRAND          1470..1477
FT                   /evidence="ECO:0007829|PDB:6W0T"
FT   HELIX           1479..1490
FT                   /evidence="ECO:0007829|PDB:6W0T"
SQ   SEQUENCE   2474 AA;  275933 MW;  0699DB0485FB3097 CRC64;
     MDPVYVDIDA DSAFLKALQR AYPMFEVEPR QVTPNDHANA RAFSHLAIKL IEQEIDPDST
     ILDIGSAPAR RMMSDRKYHC VCPMRSAEDP ERLANYARKL ASAAGKVLDR NISEKIGDLQ
     AVMAVPDAET PTFCLHTDVS CRQRADVAIY QDVYAVHAPT SLYHQAIKGV RVAYWIGFDT
     TPFMYNAMAG AYPSYSTNWA DEQVLKAKNI GLCSTDLTEG RRGKLSIMRG KKMKPCDRVL
     FSVGSTLYPE SRKLLKSWHL PSVFHLKGKL SFTCRCDTVV SCEGYVVKRI TISPGLYGKT
     TGYAVTHHAD GFLMCKTTDT VDGERVSFSV CTYVPATICD QMTGILATEV TPEDAQKLLV
     GLNQRIVVNG RTQRNTNTMK NYLLPVVAQA FSKWAKECRK DMEDEKLLGI RERTLTCCCL
     WAFKKQKTHT VYKRPDTQSI QKVPAEFDSF VVPSLWSSGL SIPLRTRIKW LLSKVPKTDL
     IPYSGDAKEA RDAEKEAEEE REAELTREAL PPLQAAQDDV QVEIDVEQLE DRAGAGIIET
     PRGAIKVTAQ PTDHVVGEYL VLSPQTVLRS QKLSLIHALA EQVKTCTHSG RAGRYAVEAY
     DGRILVPSGY AISPEDFQSL SESATMVYNE REFVNRKLHH IALHGPALNT DEESYELVRA
     ERTEHEYVYD VDQRRCCKKE EAAGLVLVGD LTNPPYHEFA YEGLRIRPAC PYKTAVIGVF
     GVPGSGKSAI IKNLVTRQDL VTSGKKENCQ EISTDVMRQR NLEISARTVD SLLLNGCNRP
     VDVLYVDEAF ACHSGTLLAL IALVRPRQKV VLCGDPKQCG FFNMMQMKVN YNHNICTQVY
     HKSISRRCTL PVTAIVSSLH YEGKMRTTNE YNKPIVVDTT GSTKPDPGDL VLTCFRGWVK
     QLQIDYRGHE VMTAAASQGL TRKGVYAVRQ KVNENPLYAS TSEHVNVLLT RTEGKLVWKT
     LSGDPWIKTL QNPPKGNFKA TIKEWEVEHA SIMAGICNHQ VTFDTFQNKA NVCWAKSLVP
     ILETAGIKLN DRQWSQIIQA FKEDRAYSPE VALNEICTRM YGVDLDSGLF SKPLVSVHYA
     DNHWDNRPGG KMFGFNPEAA SILERKYPFT KGKWNTNKQI CVTTRRIEDF NPNTNIIPAN
     RRLPHSLVAE HRPVKGERME WLVNKINGHH VLLVSGYNLV LPTKRVTWVA PLGIRGADYT
     YNLELGLPAT LGRYDLVIIN IHTPFRIHHY QQCVDHAMKL QMLGGDSLRL LKPGGSLLIR
     AYGYADRTSE RVVCVLGRKF RSSRALKPPC VTSNTEMFFL FSNFDNGRRN FTTHVMNNQL
     NAAFVGQATR AGCAPSYRVK RMDIAKNDEE CVVNAANPRG LPGDGVCKAV YKKWPESFKN
     SATPVGTAKT VMCGTYPVIH AVGPNFSNYS ESEGDRELAA AYREVAKEVT RLGVNSVAIP
     LLSTGVYSGG KDRLTQSLNH LFTALDSTDA DVVIYCRDKE WEKKIAEAIQ MRTQVELLDE
     HISVDCDIIR VHPDSSLAGR KGYSTTEGSL YSYLEGTRFH QTAVDMAEVY TMWPKQTEAN
     EQVCLYALGE SIESIRQKCP VDDADASSPP KTVPCLCRYA MTPERVTRLR MNHVTSIIVC
     SSFPLPKYKI EGVQKVKCSK VMLFDHNVPS RVSPREYKSP QETAQEVSST TSLTHSQFDL
     SVDGEELPAP SDLEADAPIP EPTPDDRAVL TLPPTIDNFS AVSDWVMNTA PVAPPRRRRG
     KNLNVTCDER EGNVLPMASV RFFRADLHSI VQETAEIRDT AASLQAPLSV ATEPNQLPIS
     FGAPNETFPI TFGDFDEGEI ESLSSELLTF GDFSPGEVDD LTDSDWSTCS DTDDELXLDR
     AGGYIFSSDT GPGHLQQRSV RQTVLPVNTL EEVQEEKCYP PKLDEVKEQL LLKKLQESAS
     MANRSRYQSR KVENMKATIV QRLKGGCKLY LMSETPKVPT YRTTYPAPVY SPPINIRLSN
     PESAVAACNE FLARNYPTVA SYQITDEYDA YLDMVDGSES CLDRATFNPS KLRSYPKQHS
     YHAPTIRSAV PSPFQNTLQN VLAAATKRNC NVTQMRELPT LDSAVFNVEC FKKFACNQEY
     WKEFAASPIR ITTENLTTYV TKLKGPKAAA LFAKTHNLLP LQEVPMDRFT VDMKRDVKVT
     PGTKHTEERP KVQVIQAAEP LATAYLCGIH RELVRRLNAV LLPNVHTLFD MSAEDFDAII
     AAHFKPGDAV LETDIASFDK SQDDSLALTA LMLLEDLGVD HPLLDLIEAA FGEISSCHLP
     TGTRFKFGAM MKSGMFLTLF VNTLLNITIA SRVLEDRLTR SACAAFIGDD NIIHGVVSDE
     LMAARCATWM NMEVKIIDAV VSQKAPYFCG GFILYDTVAG TACRVADPLK RLFKLGKPLA
     AGDEQDDDRR RALADEVVRW QRTGLTDELE KAVHSRYEVQ GISVVVMSMA TFASSRSNFE
     KLRGPVVTLY GGPK
//