POLN_SLDV
ID POLN_SLDV Reviewed; 2593 AA.
AC Q8QL53;
DT 21-MAR-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2002, sequence version 1.
DT 03-AUG-2022, entry version 122.
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=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:0000250|UniProtKB:Q8JUX6};
DE EC=3.4.22.- {ECO:0000250|UniProtKB:Q8JUX6};
DE EC=3.6.1.15 {ECO:0000250|UniProtKB:Q8JUX6};
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: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 Sleeping disease virus (SDV).
OC Viruses; Riboviria; Orthornavirae; Kitrinoviricota; Alsuviricetes;
OC Martellivirales; Togaviridae; Alphavirus.
OX NCBI_TaxID=78540;
OH NCBI_TaxID=8022; Oncorhynchus mykiss (Rainbow trout) (Salmo gairdneri).
OH NCBI_TaxID=8030; Salmo salar (Atlantic salmon).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=12021349; DOI=10.1128/jvi.76.12.6155-6163.2002;
RA Weston J.H., Villoing S., Bremont M., Castric J., Pfeffer M., Jewhurst V.,
RA McLoughlin M., Rodseth O., Christie K.E., Koumans J., Todd D.;
RT "Comparison of two aquatic alphaviruses, Salmon pancreas disease virus and
RT Sleeping disease virus, by using genome sequence analysis, monoclonal
RT reactivity and cross-infection.";
RL J. Virol. 76:6155-6163(2002).
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 (Probable).
CC Polyprotein P123 is a short-lived polyprotein that accumulates during
CC early stage of infection (Probable). As soon P123 is cleaved into
CC mature proteins, the plus-strand RNAs synthesis begins (Probable).
CC {ECO:0000305}.
CC -!- FUNCTION: [mRNA-capping enzyme nsP1]: Cytoplasmic capping enzyme that
CC catalyzes two virus-specific reactions: methyltransferase and nsP1
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 (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 (By similarity).
CC NsP1 is also needed for the initiation of the minus-strand RNAs
CC synthesis (By similarity). Probably serves as a membrane anchor for the
CC replication complex composed of nsP1-nsP4 (By similarity).
CC Palmitoylated nsP1 is remodeling host cell cytoskeleton, and induces
CC filopodium-like structure formation at the surface of the host cell (By
CC similarity). {ECO:0000250|UniProtKB:P03317,
CC ECO:0000250|UniProtKB:P08411, ECO:0000250|UniProtKB:P27282,
CC ECO:0000250|UniProtKB:Q8JUX6, ECO:0000305}.
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 (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=[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:0000250|UniProtKB:P27282};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:54793;
CC Evidence={ECO:0000250|UniProtKB:P27282};
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:0000250|UniProtKB:Q8JUX6};
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:0000250|UniProtKB:Q8JUX6};
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:0000250|UniProtKB:Q8JUX6};
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=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=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=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 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]: 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:P27282,
CC ECO:0000250|UniProtKB:Q8JUX6}.
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).
CC {ECO:0000250|UniProtKB:P27282, 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).
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:P27282,
CC 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: [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 forms aggregates in cytoplasm (By similarity).
CC NsP3 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: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: [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).
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 the
CC formation of the late replication complex (By similarity). NsP3/nsP4
CC site is not cleaved anymore and P34 is produced rather than nsP4 (By
CC 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: [mRNA-capping enzyme nsP1]: Palmitoylated by host
CC palmitoyltransferases ZDHHC2 and ZDHHC19.
CC {ECO:0000250|UniProtKB:Q8JUX6}.
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 -!- CAUTION: There is no stop codon readthrough before nsP4
CC (PubMed:12021349). The opal termination codon has probably been 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:O90370, ECO:0000269|PubMed:12021349}.
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DR EMBL; AJ316246; CAC87660.1; -; Genomic_RNA.
DR RefSeq; NP_598184.1; NC_003433.1.
DR SMR; Q8QL53; -.
DR GeneID; 1729819; -.
DR KEGG; vg:1729819; -.
DR Proteomes; UP000006568; 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:0039523; P:suppression by virus of host mRNA transcription via inhibition of RNA polymerase II activity; 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; IPR002877; RNA_MeTrfase_FtsJ_dom.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR InterPro; IPR001788; Tymovirus_RNA-dep_RNA_pol.
DR Pfam; PF01728; FtsJ; 1.
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; SSF53335; SSF53335; 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 3: Inferred from homology;
KW ATP-binding; 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; Protease; RNA suppression of termination; RNA-binding;
KW RNA-directed RNA polymerase; S-adenosyl-L-methionine; Thiol protease;
KW Transferase; Ubl conjugation; Viral RNA replication; Zinc.
FT CHAIN 1..2593
FT /note="Polyprotein P1234"
FT /id="PRO_0000308406"
FT CHAIN 1..1984
FT /note="Polyprotein P123"
FT /id="PRO_0000228791"
FT CHAIN 1..561
FT /note="mRNA-capping enzyme nsP1"
FT /id="PRO_0000228792"
FT CHAIN 562..1420
FT /note="Protease nsP2"
FT /id="PRO_0000228793"
FT CHAIN 1421..1984
FT /note="Non-structural protein 3"
FT /id="PRO_0000228794"
FT CHAIN 1985..2593
FT /note="RNA-directed RNA polymerase nsP4"
FT /id="PRO_0000228795"
FT DOMAIN 39..275
FT /note="Alphavirus-like MT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01079"
FT DOMAIN 718..871
FT /note="(+)RNA virus helicase ATP-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00990"
FT DOMAIN 872..1020
FT /note="(+)RNA virus helicase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00990"
FT DOMAIN 1034..1392
FT /note="Peptidase C9"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00853"
FT DOMAIN 1421..1580
FT /note="Macro"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00490"
FT DOMAIN 2349..2464
FT /note="RdRp catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00539"
FT REGION 260..279
FT /note="nsP1 membrane-binding"
FT /evidence="ECO:0000250|UniProtKB:P08411"
FT REGION 1034..1054
FT /note="Nucleolus localization signal"
FT /evidence="ECO:0000250|UniProtKB:P08411"
FT REGION 1781..1832
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1860..1912
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1926..1985
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 1088..1097
FT /note="Nuclear export signal"
FT /evidence="ECO:0000250|UniProtKB:P27282"
FT MOTIF 1218..1222
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000250|UniProtKB:P08411"
FT COMPBIAS 1807..1825
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1890..1905
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1932..1959
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 1043
FT /note="For cysteine protease nsP2 activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00853"
FT ACT_SITE 1113
FT /note="For cysteine protease nsP2 activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00853"
FT BINDING 750..757
FT /ligand="a ribonucleoside 5'-triphosphate"
FT /ligand_id="ChEBI:CHEBI:61557"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00990"
FT BINDING 1444
FT /ligand="ADP-D-ribose"
FT /ligand_id="ChEBI:CHEBI:57967"
FT /evidence="ECO:0000250|UniProtKB:Q8JUX6"
FT BINDING 1452
FT /ligand="ADP-D-ribose"
FT /ligand_id="ChEBI:CHEBI:57967"
FT /evidence="ECO:0000250|UniProtKB:Q8JUX6"
FT BINDING 1533
FT /ligand="ADP-D-ribose"
FT /ligand_id="ChEBI:CHEBI:57967"
FT /evidence="ECO:0000250|UniProtKB:P36328"
FT BINDING 1534
FT /ligand="ADP-D-ribose"
FT /ligand_id="ChEBI:CHEBI:57967"
FT /evidence="ECO:0000250|UniProtKB:P36328"
FT BINDING 1701
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P03317"
FT BINDING 1703
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P03317"
FT BINDING 1726
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P03317"
FT BINDING 1744
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P03317"
FT SITE 48
FT /note="Involved in the phosphoramide link with 7-methyl-
FT GMP"
FT /evidence="ECO:0000250|UniProtKB:P27282"
FT SITE 561..562
FT /note="Cleavage; by protease nsP2"
FT /evidence="ECO:0000250|UniProtKB:P03317"
FT SITE 1420..1421
FT /note="Cleavage; by protease nsP2"
FT /evidence="ECO:0000250|UniProtKB:P03317"
FT SITE 1984..1985
FT /note="Cleavage; by protease nsP2"
FT /evidence="ECO:0000250|UniProtKB:Q8JUX6"
FT LIPID 437
FT /note="S-palmitoyl cysteine; by host"
FT /evidence="ECO:0000250|UniProtKB:Q8JUX6"
FT LIPID 439
FT /note="S-palmitoyl cysteine; by host"
FT /evidence="ECO:0000250|UniProtKB:Q8JUX6"
SQ SEQUENCE 2593 AA; 284853 MW; 2E2B4F651A45B8CF CRC64;
MMLNLTANPS AGTTVTVDLP ADHPALNQFK TAFPGFEVVA SNRSSNDHAA ARAFSHLATK
WIERDIDGRQ VIVADIGSAP ARRVGAPDNV TYHSVCPRKC AEDPERLASY ARKLVRAVEK
GDGHLVSDRI TDLKDVLENP DTSLETTSIC LNDDVSCKVK ADIAVYQDVY AVDAPSTIYA
QADKGTRVVY WIGFEPFVFH TDAMAGSFPL YDANWSDSAV LAAKNLPLCY SGLSEDSIKW
RFRFRDKPLV PSGEIHYSVG STHYVEDRDK LKSWHLPSTF HFVAPNKYTC RCDTVVSCGG
YVVKKITICE GIVGRPANEE LATSYHRDGV VVTKFSDTIN HEQVSFPVVT YIPAVICDQM
TAMTADPVKY PDVVKLLVGL NQRIVVNGTT VRNVNSMDNS LIPVFARALC SWADEARRDM
EDEQDMYGVT SVTTWICICR AYDKRQQHTF YRRPKQSSGI YVPAKFTGSL RASLSATYLN
LPLKQLLLNT LKRAIKPGDQ ALADETEARA HDAAEVHELT EEEGRQQAAN PSYIADVLGQ
DDEEEVDDGM SNVDLGEEDG VGSTIIDCQR GTVKVITAFG DNTMGEYLVL SPVTVLRTRK
LAVLLGPLAE EVMQYVHKGR TGRYAIEKNN LKVLIPTGVS LKTAHFQALT ESATLTYNDY
LFTCRTLDQL ATRGSAKNTD EVYYKLVDAA KAKDEYVYEL SSKQCVKKED ATGTVLQGDI
CNPPYHQFAF EALRKRPAHT HDVHTIGIYG VPGAGKTAII TTEVTTRDLV ASGKKENCED
IKRCVLERRG LKIAARTVDS LLYGAYRGAV DTLYVDEAYA CHSGTLLALI AAVRPTGKVV
LCGDPKQVGC VNQLQMRMHY NHEISDRVLR KNISRRCTHT LTAIVSNLNY EGRMKTTNPC
KKPVLIDTTG STKPDKEALV LTCFRGWVKD LKILYPHNEL MTAAASQGLT REKVYAVRCR
VTSNPLYEPT SEHITVLLTR TNDELVWKTL PNDPLIPILS KPPKGDYSAT MEDWEDEHNG
ILAALREACV PRMNFAHGKR NTCWAVTSSR VLHEAGVLIT PEDFNRIFPA FREDKPHSAL
AALDAVAALV WGLDTSSGIL SGKGSFMRLE NSHWSNSNRG YEYGLNLDAL EGYEIANPRM
IKALKQRRGR ECYDIETGKL VPMDPGRVQV PINRVVPHVL VDTSAAAKPG FLENRLSVDR
WDQVHSFKTR AAVKFAELTK RVSYNSVLDL GAARGGVTDY CVKKGKTVTC VSEQWDSKPR
GAVVITADIN GPLNNLGIFD LVFCDAAGPR RYHHYAQCED HARRSTSACK HGVERTAKGG
VFIVKAYGMA DRRTERAVEC TARYFKSVSV EKPVSSRITN VEVFFKFSGR CRPHARSIAH
LGPQLTDIYA RTRKAYKMLA RGSVADKVKV AEILNSMVGA APGYRVLNKN IITAEEEVLV
NAANSNGRPG DGVCGALYGA FGDAFPNGAI GAGNAVLVRG LEATIIHAAG ADFREVDEET
GARQLRAAYR AAATLVTANG ITSAAIPLLS THIFSNGRNR LEQSFGALVE AFDTTECDVT
IYCLANNMAA RIQQLIDDHA REEFDEEVVV EEEEEHEANA MCDTETLSSF GDETVWVPKH
STLAGRPGYS ATYGDRRSLF VGTKFHRAAV AMSSIEAAWP RTKEANAKLI EYIRGQHLVD
VLKSCPVNDI PVGRPPSSLP CGCIYAMTPE RVTVLKQRPQ EGFVVCSAFK LPLTNIQDVT
KVECTVRAPA EEPRPVRYLQ ERRPVQAAAR QPRPAIVAAS VAGTATSRRT PAPGSVQVRL
LPPRDGTVSR SSRTSSQSSV TSSAGPIMPV PRRAPVAPAA SLAGSVHSHS VRSAPAILRA
ASTGARSVRS VQSGLTGHRD DAVSVAGSVR QPSGPPSSVS TPAAPRGLTR EQFGAVRARA
RRDLELEGSE HGSQASFRSG SLVVGSTASS YSQRPDDQDT GSEPSGRGAA VRTRRRGQRD
GPGGYIFSSD QGTAHLSQHN TQTNNTTEVL MRTSVLPSND HGTPDLLAEM KKRLAYQMRP
TQKNKSRYLS AKVHNMKHKI VQCLQRGAGH YLREQHALPL WKNTFPKPRY SDACVVKFES
VNTAIVAANM FIGCNYPTLS SFGVTDKYDA YLDMVDGLNC NLDTVTFEPA KVRSLPKKSK
YNQPLIQSQV PGPMASTLQS ILMAATKRNC NVTQMRELPT MDSAAMNVEA FKKFACKDTD
LWTEFAEKPV RLSPGQIEEY VFHLQGAKAN VMHSRVEAAC PDLSEVAMDR FTLDMKRDVK
VTPGTKHVEE RPKVQVIQAA DPMATAYLCA IHRELVRRLK AVLKPSIHVL FDMSSEDFDA
IVGHGMKLGD KVLETDISSF DKSQDQAMAV TALMLLEDLG VEEDLLTLIE ASFGDITSVH
LPTGTRFQFG SMMKSGLFLT LFVNTLLNIT IAARVLREQL ADTRCAAFIG DDNVITGVVS
DDMMVARCAS WLNMEVKIME MEIGDRSPYF CGGFLLLDTV TGTVSRVSDP VKRLMKMGKP
ALNDPETDVD RCRALREEVE SWYRVGIQWP LQVAAATRYG VNHLPLATMA MATLAQDLRS
YLGARGEYVS LYA
