ID   POLN_WEEV               Reviewed;        2467 AA.
AC   P13896; Q9J1K2;
DT   01-JAN-1990, integrated into UniProtKB/Swiss-Prot.
DT   10-APR-2019, sequence version 3.
DT   02-SEP-2026, entry version 152.
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:P36328};
DE              EC=2.7.7.- {ECO:0000250|UniProtKB:P36328};
DE     AltName: Full=Non-structural protein 1;
DE   Contains:
DE     RecName: Full=Protease nsP2;
DE              EC=3.4.22.- {ECO:0000250|UniProtKB:P27282};
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=3.2.2.- {ECO:0000305};
DE   Contains:
DE     RecName: Full=Non-structural protein 3;
DE              Short=nsP3;
DE              EC=3.2.2.- {ECO:0000250|UniProtKB:P27282};
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   Western equine encephalitis virus (WEEV).
OC   Viruses; Riboviria; Orthornavirae; Kitrinoviricota; Alsuviricetes;
OC   Martellivirales; Togaviridae; Alphavirus; Alphavirus western.
OX   NCBI_TaxID=11039;
OH   NCBI_TaxID=7158; Aedes.
OH   NCBI_TaxID=7164; Anopheles.
OH   NCBI_TaxID=7177; Culex tarsalis (Encephalitis mosquito).
OH   NCBI_TaxID=30427; Haemorhous mexicanus (House finch) (Carpodacus mexicanus).
OH   NCBI_TaxID=9606; Homo sapiens (Human).
OH   NCBI_TaxID=48086; Lepus americanus (Snowshoe hare).
OH   NCBI_TaxID=8404; Lithobates pipiens (Northern leopard frog) (Rana pipiens).
OH   NCBI_TaxID=48849; Passer domesticus (House sparrow) (Fringilla domestica).
OH   NCBI_TaxID=34999; Thamnophis.
OH   NCBI_TaxID=37591; Urocitellus richardsonii (Richardson's ground squirrel) (Spermophilus richardsonii).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX   PubMed=10640553; DOI=10.1099/0022-1317-81-1-151;
RA   Netolitzky D.J., Schmaltz F.L., Parker M.D., Rayner G.A., Fisher G.R.,
RA   Trent D.W., Bader D.E., Nagata L.P.;
RT   "Complete genomic RNA sequence of western equine encephalitis virus and
RT   expression of the structural genes.";
RL   J. Gen. Virol. 81:151-159(2000).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 2431-2467.
RC   STRAIN=BFS1703;
RX   PubMed=3413072; DOI=10.1073/pnas.85.16.5997;
RA   Hahn C.S., Lustig S., Strauss E.G., Strauss J.H.;
RT   "Western equine encephalitis virus is a recombinant virus.";
RL   Proc. Natl. Acad. Sci. U.S.A. 85:5997-6001(1988).
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 the minus-strand RNAs
CC       (antigenome) (By similarity). Polyprotein P123 is a short-lived
CC       polyprotein that accumulates during early stage of infection
CC       (Probable). As soon P123 is cleaved into mature proteins, the plus-
CC       strand RNAs synthesis begins (By similarity).
CC       {ECO:0000250|UniProtKB:P03317, ECO:0000305}.
CC   -!- FUNCTION: [Polyprotein P123']: The early replication complex formed by
CC       the polyprotein P123' and nsP4 synthesizes minus-strand RNAs
CC       (antigenome) (Probable). Polyprotein P123' is a short-lived polyprotein
CC       that accumulates during early stage of infection (Probable). As soon
CC       P123' is cleaved into mature proteins, the plus-strand RNAs synthesis
CC       begins (Probable). {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). Nsp1 is
CC       needed for the initiation of the minus-strand RNAs synthesis (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: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). Inhibits host
CC       translation to ensure maximal viral gene expression and evade host
CC       immune response (By similarity). {ECO:0000250|UniProtKB:P03317,
CC       ECO:0000250|UniProtKB:P08411, ECO:0000250|UniProtKB:P27282,
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       Contains an ADP-ribose hydrolase activity that binds ADP-ribose and
CC       catalyzes the removal of mono-ADP-ribose (de-MARylation), usually bound
CC       to a glutamate or aspartate (By similarity). ADP-ribose hydrolase
CC       activity allows the virus to interfere with the host immune defenses
CC       involving poly-ADP-ribose polymerases (PARPs) (By similarity). Binds
CC       proteins of FXR and G3BP families and sequesters them into the viral
CC       RNA replication complexes thereby inhibiting the formation of host
CC       stress granules on viral mRNAs (By similarity). The nsp3-FXR and nsp3-
CC       G3BP complexes bind viral RNAs and probably orchestrate the assembly of
CC       viral replication complexes, thanks to the ability of G3BP and FXR
CC       family members to self-assemble and bind DNA (By similarity).
CC       {ECO:0000250|UniProtKB:P03317, ECO:0000250|UniProtKB:P27282,
CC       ECO:0000250|UniProtKB:Q4QXJ8}.
CC   -!- FUNCTION: [Non-structural protein 3]: Seems to be essential for minus-
CC       strand RNAs and subgenomic 26S mRNAs synthesis (By similarity).
CC       Contains an ADP-ribose hydrolase activity that binds ADP-ribose and
CC       catalyzes the removal of mono-ADP-ribose (de-MARylation), usually bound
CC       to a glutamate or aspartate (By similarity). ADP-ribose hydrolase
CC       activity allows the virus to interfere with the host immune defenses
CC       involving poly-ADP-ribose polymerases (PARPs) (By similarity). Binds
CC       proteins of FXR and G3BP families and sequesters them into the viral
CC       RNA replication complexes thereby inhibiting the formation of host
CC       stress granules on viral mRNAs (Probable). The nsp3'-FXR and nsp3-G3BP
CC       complexes bind viral RNAs and probably orchestrate the assembly of
CC       viral replication complexes, thanks to the ability of G3BP and FXR
CC       family members to self-assemble and bind DNA (Probable).
CC       {ECO:0000250|UniProtKB:P03317, ECO:0000250|UniProtKB:P27282,
CC       ECO:0000305}.
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:P27282};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:54429;
CC         Evidence={ECO:0000250|UniProtKB:P27282};
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:P27282};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:58249;
CC         Evidence={ECO:0000250|UniProtKB:P27282};
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   -!- 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: [mRNA-capping enzyme nsP1]: Inhibited by
CC       sinefungin. {ECO:0000250|UniProtKB:P27282}.
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:Q4QXJ8, ECO:0000250|UniProtKB:Q8JUX6}.
CC   -!- SUBUNIT: [Non-structural protein 3]: Assembles into tubular structures
CC       made by a helical arrangement of the alphavirus unique domain (AUD);
CC       further assembles into cytoplasmic granules organized into a network of
CC       tubular structures that contain viral genomic RNA, capsid and host
CC       factors required for productive infection (By similarity). Interacts
CC       with mRNA-capping enzyme nsP1 (By similarity). Interacts with host DDX1
CC       (By similarity). Interacts with host DDX3 (By similarity). Interacts
CC       (via C-terminus) with host FXR1; this interaction inhibits the
CC       formation of host stress granules on viral mRNAs and the nsp3-FXR1
CC       complexes bind viral RNAs and probably orchestrate the assembly of
CC       viral replication complexes (By similarity). Interacts (via C-terminus)
CC       with host FXR2; this interaction inhibits the formation of host stress
CC       granules on viral mRNAs and the nsp3-FXR2 complexes bind viral RNAs and
CC       probably orchestrate the assembly of viral replication complexes (By
CC       similarity). Interacts (via C-terminus) with host FMR1; this
CC       interaction inhibits the formation of host stress granules on viral
CC       mRNAs and the nsp3-FMR1 complexes bind viral RNAs and probably
CC       orchestrate the assembly of viral replication complexes (By
CC       similarity). {ECO:0000250|UniProtKB:P27282,
CC       ECO:0000250|UniProtKB:Q4QXJ8, 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:Q4QXJ8,
CC       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:Q4QXJ8, 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:P08411}. 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   -!- 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:0000305}; Peripheral membrane protein
CC       {ECO:0000305}. Note=In the late phase of infection, the polyprotein is
CC       quickly cleaved before localization to cellular membranes. Then nsP3
CC       and nsP3' form aggregates in cytoplasm (By similarity). NsP3' is also
CC       part of cytoplasmic vesicles, which are probably formed at the plasma
CC       membrane and internalized leading to late endosomal/lysosomal spherules
CC       containing the replication complex (Probable).
CC       {ECO:0000250|UniProtKB:P03317, ECO:0000305}.
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).
CC       {ECO:0000250|UniProtKB:P27282, 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 regions responsible for the formation of the
CC       nsP3/FXR complex (By similarity). {ECO:0000250|UniProtKB:P03317,
CC       ECO:0000250|UniProtKB:P27282, ECO:0000250|UniProtKB:Q4QXJ8}.
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 regions responsible for the formation of the
CC       nsP3'/FXR complex (By similarity). {ECO:0000250|UniProtKB:P03317,
CC       ECO:0000250|UniProtKB:P27282, ECO:0000250|UniProtKB:Q4QXJ8}.
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.
CC       {ECO:0000250|UniProtKB:P03317}.
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 Asn-1852 and Arg-
CC       1854 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; AF214040; AAF28339.1; -; Genomic_RNA.
DR   EMBL; J03854; AAA42998.1; -; Genomic_RNA.
DR   RefSeq; NP_640330.1; NC_003908.1.
DR   AlphaFoldDB; P13896; -.
DR   IntAct; P13896; 2.
DR   MEROPS; C09.002; -.
DR   GeneID; 944530; -.
DR   KEGG; vg:944530; -.
DR   Proteomes; UP000111743; Segment.
DR   GO; GO:0030430; C:host cell cytoplasm; ISS:UniProtKB.
DR   GO; GO:0044162; C:host cell cytoplasmic vesicle membrane; ISS:UniProtKB.
DR   GO; GO:0044176; C:host cell filopodium; IEA:UniProtKB-SubCell.
DR   GO; GO:0042025; C:host cell nucleus; ISS:UniProtKB.
DR   GO; GO:0020002; C:host cell plasma membrane; ISS:UniProtKB.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0016887; F:ATP hydrolysis activity; ISS:UniProtKB.
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; ISS:UniProtKB.
DR   GO; GO:0008174; F:mRNA methyltransferase activity; IEA:InterPro.
DR   GO; GO:1990817; F:poly(A) RNA polymerase activity; ISS:UniProtKB.
DR   GO; GO:0017111; F:ribonucleoside triphosphate phosphatase activity; ISS:UniProtKB.
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: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; 3.40.220.10:FF:000015; 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   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; Magnesium;
KW   Membrane; Metal-binding; Methyltransferase; mRNA capping; mRNA processing;
KW   Multifunctional enzyme; Nucleotide-binding; Nucleotidyltransferase;
KW   Palmitate; Protease; Reference proteome; 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..2467
FT                   /note="Polyprotein P1234"
FT                   /id="PRO_0000308408"
FT   CHAIN           1..1859
FT                   /note="Polyprotein P123'"
FT                   /id="PRO_0000228801"
FT   CHAIN           1..1852
FT                   /note="Polyprotein P123"
FT                   /id="PRO_0000228802"
FT   CHAIN           1..533
FT                   /note="mRNA-capping enzyme nsP1"
FT                   /id="PRO_0000228803"
FT   CHAIN           534..1327
FT                   /note="Protease nsP2"
FT                   /id="PRO_0000228804"
FT   CHAIN           1328..1852
FT                   /note="Non-structural protein 3'"
FT                   /id="PRO_0000228805"
FT   CHAIN           1348..1859
FT                   /note="Non-structural protein 3"
FT                   /id="PRO_0000228806"
FT   CHAIN           1860..2467
FT                   /note="RNA-directed RNA polymerase nsP4"
FT                   /id="PRO_0000228807"
FT   DOMAIN          28..257
FT                   /note="Alphavirus-like MT"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01079"
FT   DOMAIN          688..839
FT                   /note="(+)RNA virus helicase ATP-binding"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00990"
FT   DOMAIN          840..988
FT                   /note="(+)RNA virus helicase C-terminal"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00990"
FT   DOMAIN          1001..1320
FT                   /note="Peptidase C9"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00853"
FT   DOMAIN          1328..1486
FT                   /note="Macro"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00490"
FT   DOMAIN          2224..2339
FT                   /note="RdRp catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00539"
FT   REGION          242..261
FT                   /note="NsP1 membrane-binding"
FT                   /evidence="ECO:0000250|UniProtKB:P08411"
FT   REGION          1002..1021
FT                   /note="Nucleolus localization signal"
FT                   /evidence="ECO:0000250|UniProtKB:P08411"
FT   REGION          1487..1647
FT                   /note="AUD"
FT                   /evidence="ECO:0000250|UniProtKB:Q8JUX6"
FT   REGION          1798..1833
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1831..1847
FT                   /note="Binding to host FXR family members"
FT                   /evidence="ECO:0000250|UniProtKB:Q4QXJ8"
FT   MOTIF           1054..1063
FT                   /note="Nuclear export signal"
FT                   /evidence="ECO:0000250|UniProtKB:P27282"
FT   MOTIF           1177..1181
FT                   /note="Nuclear localization signal"
FT                   /evidence="ECO:0000250|UniProtKB:P27282"
FT   ACT_SITE        1010
FT                   /note="For cysteine protease nsP2 activity"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00853"
FT   ACT_SITE        1079
FT                   /note="For cysteine protease nsP2 activity"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00853"
FT   BINDING         719..726
FT                   /ligand="a ribonucleoside 5'-triphosphate"
FT                   /ligand_id="ChEBI:CHEBI:61557"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00990"
FT   BINDING         1337
FT                   /ligand="ADP-D-ribose"
FT                   /ligand_id="ChEBI:CHEBI:57967"
FT                   /evidence="ECO:0000250|UniProtKB:P36328"
FT   BINDING         1351
FT                   /ligand="ADP-D-ribose"
FT                   /ligand_id="ChEBI:CHEBI:57967"
FT                   /evidence="ECO:0000250|UniProtKB:Q8JUX6"
FT   BINDING         1359
FT                   /ligand="ADP-D-ribose"
FT                   /ligand_id="ChEBI:CHEBI:57967"
FT                   /evidence="ECO:0000250|UniProtKB:Q8JUX6"
FT   BINDING         1438
FT                   /ligand="ADP-D-ribose"
FT                   /ligand_id="ChEBI:CHEBI:57967"
FT                   /evidence="ECO:0000250|UniProtKB:P36328"
FT   BINDING         1439
FT                   /ligand="ADP-D-ribose"
FT                   /ligand_id="ChEBI:CHEBI:57967"
FT                   /evidence="ECO:0000250|UniProtKB:P36328"
FT   BINDING         1440
FT                   /ligand="ADP-D-ribose"
FT                   /ligand_id="ChEBI:CHEBI:57967"
FT                   /evidence="ECO:0000250|UniProtKB:Q8JUX6"
FT   BINDING         1588
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000250|UniProtKB:P03317"
FT   BINDING         1590
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000250|UniProtKB:P03317"
FT   BINDING         1613
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000250|UniProtKB:P03317"
FT   BINDING         1631
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000250|UniProtKB:P03317"
FT   BINDING         2252
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250|UniProtKB:P03317"
FT   BINDING         2326
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /ligand_label="2"
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            533..534
FT                   /note="Cleavage; by protease nsP2"
FT                   /evidence="ECO:0000250|UniProtKB:P03317"
FT   SITE            1327..1328
FT                   /note="Cleavage; by protease nsP2"
FT                   /evidence="ECO:0000250|UniProtKB:P03317"
FT   SITE            1859..1860
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   VARIANT         2461
FT                   /note="S -> N (in strain: BFS1703)"
SQ   SEQUENCE   2467 AA;  275102 MW;  EC5F7C1002D1F4AE CRC64;
     MERIHVDLDA DSPYVKSLQR TFPQFEIEAR QVTDNDHANA RAFSHVATKL IESEVDRDQV
     ILDIGSAPVR HAHSNHRYHC ICPMISAEDP DRLQRYAERL KKSDITDKNI ASKAADLLEV
     MSTPDAETPS LCMHTDATCR YFGSVAVYQD VYAVHAPTSI YHQALKGVRT IYWIGFDTTP
     FMYKNMAGSY PTYNTNWADE RVLEARNIGL GNSDLQESRL GKLSILRKKR LQPTNKIIFS
     VGSTIYTEDR SLLRSWHLPN VFHLKGKSNF TGRCGTIVSC EGYVIKKITI SPGLYGKVEN
     LASTMHREGF LSCKVTDTLR GERVSFAVCT YVPATLCDQM TGILATDVSV DDAQKLLVGL
     NQRIVVNGRT QRNTNTMQNY LLPVVAQAFS RWAREHRADL DDEKELGVRE RTLTMGCCWA
     FKTQKITSIY KKPGTQTIKK VPAVFDSFVI PRLTSHGLDM GFRRRLKLLL EPTVKPAPAI
     TMADVEHLRG LQQEAEEVAA AEEIREALPP LLPEIEKETV EAEVDLIMQE AGAGSVETPR
     GHIRVTSYPG EEKIGSYAIL SPQAVLNSEK LACIHPLAEQ VLVMTHKGRA GRYKVEPYHG
     KVIVPEGTAV PVQDFQALSE SATIVFNERE FVNRYLHHIA INGGALNTDE EYYKTVKTQD
     TDSEYVFDID ARKCVKREDA GPLCLTGDLV DPPFHEFAYE SLKTRPAAPH KVPTIGVYGV
     PGSGKSGIIK SAVTKKDLVV SAKKENCAEI IRDVRRMRRM DVAARTVDSV LLNGVKHPVN
     TLYIDEAFAC HAGTLLALIA IVKPKKVVLC GDPKQCGFFN MMCLKVHFNH DICTEVYHKS
     ISRRCTQTVT AIVSTLFYDK RMKTVNPCAD KIIIDTTGTT KPHKDDLILT CFRGWVKQLQ
     IDYKNHEIMT AAASQGLTRK GVYAVRYKVN ENPLYSQTSE HVNVLLTRTE KRIVWKTLAG
     DPWIKTLTAK YPGDFTASLD DWQREHDAIM ARVLDKPQTA DVFQNKVNVC WAKALEPVLA
     TANIVLTRQQ WETLHPFKHD RAYSPEMALN FFCTRFFGVD LDSGLFSAPT VALTYRDQHW
     DNSPGKNMYG LNREVAKELS RRYPCITKAV DTGRVADIRN NTIKDYSPTI NVVPLNRRLP
     HSLIVDHKGQ GTTDHSGFLS KMKGKSVLVI GDPISIPGKK VESMGPLPTN TIRCDLDLGI
     PSHVGKYDII FVNVRTPYRN HHYQQCEDHA IHHSMLTCKA VHHLNTGGTC VAIGYGLADR
     ATENIITAVA RSFRFTRVCQ PKNTAENTEV LFVFFGKDNG NHTHDQDRLG VVLDNIYQGS
     TRYEAGRAPA YRVIRGDISK SADQAIVNAA NSKGQPGSGV CGALYRKWPA AFDRQPIAVG
     TARLVKHEPL IIHAVGPNFS KMPEPEGDLK LAAAYMSIAS IVNAERITKI SVPLLSTGIY
     SGGKDRVMQS LHHLFTAFDT TDADVTIYCL DKQWETRIIE AIHRKESVEI LDDDKPVDID
     LVRVHPNSSL AGRPGYSVNE GKLYSYLEGT RFHQTAKDIA EIHAMWPNKS EANEQICLYI
     LGESMSSIRS KCPVEESEAS APPHTLPCLC NYAMTAERVY RLRSAKKEQF AVCSSFLLPK
     YRITGVQKLQ CSKPVLFSGV VPPAVHPRKY AEIILETPPP PATTTVICEP TVPERIPSPV
     ISRAPSAESL LSLGGVSFSS SATRSSTAWS DYDRRFVVTA DVHQANTSTW SIPSAPGLDV
     QLPSDVTDSH WSIPSASGFE VRTPSVQDLT AECAKPRGLA EIMQDFNTAP FQFLSDYRPV
     PAPRRRPIPS PRSTASAPPV PKPRRTKYQQ PPGVARAISE AELDEYIRQH SNXRYEAGAY
     IFSSETGQGH LQQKSVRQCK LQEPILDRAV HEKYYAPRLD LEREKMLQKK LQLCASEGNR
     SRYQSRKVEN MKAITAERLI SGLGTYLSSE VNPVECYRVN YPVPIYSSTV INRFTSAEVA
     VKTCNLVIQE NYPTVASYCI TDEYDAYLDM VDGASCCLDT ATFCPAKLRS YPKKHSYLQP
     EIRSAVPSPI QNTLQNVLAA ATKRNCNVTQ MRELPVLDSA AFNVDCFKKY ACNDEYWDTF
     RDNPIRLTTE NVTQYVTKLK GPKAAALFAN THNLKPLQEI PMDQFVMDLK RDVKVTPGTK
     HTEERPKVQV IQAADPLATA YLCGIHRELV RRLNAVLLPN IHTLFDMSAE DFDAIIAEHF
     HHGDPVLETD IASFDKSEDD AIAISALMIL EDLGVDQPLL DLIEAAFGNI TSVHLPTGTR
     FKFGAMMKSG MFLTLFVNTL VNIMIASRVL RERLTTSACA ASIGDDNIVH GVVSDTLMAE
     RCATWLNMEV KIIDAVIGIK APYFCGGFIL VDQITGTACR VADPLKRLFK LGKPLPVDDT
     QDCDRRRALH DEAMRWNRIG ITDELVKAVE SRYEIILAGL IITSLSTLAE SVKNFKSIRG
     SPITLYG
//