POLN_EEEVF
ID POLN_EEEVF Reviewed; 2494 AA.
AC Q4QXJ8; Q4QXK0; Q5XZF4;
DT 21-MAR-2006, integrated into UniProtKB/Swiss-Prot.
DT 10-APR-2019, sequence version 3.
DT 03-AUG-2022, entry version 111.
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=3.1.3.33 {ECO:0000250|UniProtKB:P08411};
DE EC=3.4.22.- {ECO:0000250|UniProtKB:P27282};
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:P27282};
DE Contains:
DE RecName: Full=Non-structural protein 3;
DE Short=nsP3;
DE EC=3.1.3.84 {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 Eastern equine encephalitis virus (strain Florida 91-469) (EEEV) (Eastern
OS equine encephalomyelitis virus).
OC Viruses; Riboviria; Orthornavirae; Kitrinoviricota; Alsuviricetes;
OC Martellivirales; Togaviridae; Alphavirus.
OX NCBI_TaxID=374598;
OH NCBI_TaxID=7158; Aedes.
OH NCBI_TaxID=9606; Homo sapiens (Human).
OH NCBI_TaxID=9126; Passeriformes.
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RC STRAIN=Florida91-469, Georgia 97, and PE6;
RX PubMed=16147892; DOI=10.1080/10425170500136889;
RA Platteborze P.L., Kondig J.P., Schoepp R.J., Wasieloski L.P.;
RT "Comparative sequence analysis of the eastern equine encephalitis virus
RT pathogenic strains FL91-4679 and GA97 to other North American strains.";
RL DNA Seq. 16:308-320(2005).
RN [2]
RP FUNCTION (NON-STRUCTURAL PROTEIN 3), DOMAIN (NON-STRUCTURAL PROTEIN 3),
RP INTERACTION WITH HOST FXR1 (NON-STRUCTURAL PROTEIN 3), INTERACTION WITH
RP HOST FXR2 (NON-STRUCTURAL PROTEIN 3), INTERACTION WITH HOST FMR1
RP (NON-STRUCTURAL PROTEIN 3), INTERACTION WITH HOST G3BP1 (NON-STRUCTURAL
RP PROTEIN 3), AND INTERACTION WITH HOST G3BP2 (NON-STRUCTURAL PROTEIN 3).
RC STRAIN=Florida93;
RX PubMed=28468889; DOI=10.1128/jvi.00371-17;
RA Frolov I., Kim D.Y., Akhrymuk M., Mobley J.A., Frolova E.I.;
RT "Hypervariable Domain of Eastern Equine Encephalitis Virus nsP3 Redundantly
RT Utilizes Multiple Cellular Proteins for Replication Complex Assembly.";
RL J. Virol. 91:0-0(2017).
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 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 FXR
CC and G3BP families and sequesters them into the viral RNA replication
CC complexes thereby inhibiting the formation of host stress granules on
CC viral mRNAs (PubMed:28468889). The nsp3-FXR and nsp3-G3BP complexes
CC bind viral RNAs and probably orchestrate the assembly of viral
CC replication complexes, thanks to the ability of G3BP and FXR family
CC members to self-assemble and bind DNA (Probable).
CC {ECO:0000250|UniProtKB:P03317, ECO:0000250|UniProtKB:P27282,
CC ECO:0000269|PubMed:28468889, ECO:0000305|PubMed:28468889}.
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: [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:P08411};
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: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 = 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:P27282};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:58249;
CC Evidence={ECO:0000250|UniProtKB:P27282};
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:P36328};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25030;
CC Evidence={ECO:0000250|UniProtKB:P36328};
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: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). Interacts (via C-terminus)
CC with host FXR1; this interaction inhibits the formation of host stress
CC granules on viral mRNAs and the nsp3-FXR1 complexes bind viral RNAs and
CC probably orchestrate the assembly of viral replication complexes
CC (PubMed:28468889). Interacts (via C-terminus) with host FXR2; this
CC interaction inhibits the formation of host stress granules on viral
CC mRNAs and the nsp3-FXR2 complexes bind viral RNAs and probably
CC orchestrate the assembly of viral replication complexes
CC (PubMed:28468889). 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
CC (PubMed:28468889). 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
CC (PubMed:28468889). 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
CC (PubMed:28468889). {ECO:0000250|UniProtKB:P27282,
CC ECO:0000250|UniProtKB:Q8JUX6, ECO:0000269|PubMed:28468889}.
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: [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 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 and nsp3/G3BP complexes (PubMed:28468889).
CC {ECO:0000250|UniProtKB:P03317, ECO:0000250|UniProtKB:P27282,
CC ECO:0000269|PubMed:28468889}.
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 and nsp3'/G3BP complexes (PubMed:28468889).
CC {ECO:0000250|UniProtKB:P03317, ECO:0000250|UniProtKB:P27282,
CC ECO:0000269|PubMed:28468889}.
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-1879 and Arg-
CC 1881 giving rise to P1234. P1234 is cleaved quickly by nsP2 into P123'
CC and nsP4 (By similarity). Further processing of p123' gives nsP1, nsP2
CC and nsP3' which is 6 amino acids longer than nsP3 since the cleavage
CC site is after the readthrough (By similarity). This unusual molecular
CC mechanism ensures that few nsP4 are produced compared to other non-
CC structural proteins (By similarity). Mutant viruses with no alternative
CC termination site grow significantly slower than wild-type virus (By
CC similarity). The opal termination codon is frequently mutated to a
CC sense codon on passage in cell culture (By similarity). The presence of
CC the opal codon may be a requirement for viral maintenance in both
CC vertebrate and invertebrate hosts and a selective advantage may be
CC conferred in cell culture for the sense codon (By similarity).
CC {ECO:0000250|UniProtKB:O90368, ECO:0000250|UniProtKB:P03317}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AY705241; AAT96379.1; -; Genomic_RNA.
DR EMBL; AY705240; AAT96377.1; -; Genomic_RNA.
DR EMBL; AY722102; AAU95734.1; -; Genomic_RNA.
DR MEROPS; C09.002; -.
DR PRIDE; Q4QXJ8; -.
DR Proteomes; UP000008298; Genome.
DR Proteomes; UP000110644; Genome.
DR Proteomes; UP000170335; 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; IPR029063; SAM-dependent_MTases_sf.
DR InterPro; IPR001788; Tymovirus_RNA-dep_RNA_pol.
DR Pfam; PF01661; Macro; 1.
DR Pfam; PF01707; Peptidase_C9; 1.
DR Pfam; PF00978; RdRP_2; 1.
DR Pfam; PF01443; Viral_helicase1; 1.
DR Pfam; PF01660; Vmethyltransf; 1.
DR SMART; SM00506; A1pp; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR SUPFAM; SSF52949; SSF52949; 1.
DR SUPFAM; SSF56672; SSF56672; 1.
DR PROSITE; PS51743; ALPHAVIRUS_MT; 1.
DR PROSITE; PS51154; MACRO; 1.
DR PROSITE; PS51520; NSP2PRO; 1.
DR PROSITE; PS51657; PSRV_HELICASE; 1.
DR PROSITE; PS50507; RDRP_SSRNA_POS; 1.
PE 1: Evidence at protein level;
KW 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; 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..2494
FT /note="Polyprotein P1234"
FT /id="PRO_0000308386"
FT CHAIN 1..1886
FT /note="Polyprotein P123'"
FT /id="PRO_0000228760"
FT CHAIN 1..1879
FT /note="Polyprotein P123"
FT /id="PRO_0000228761"
FT CHAIN 1..533
FT /note="mRNA-capping enzyme nsP1"
FT /id="PRO_0000228762"
FT CHAIN 534..1327
FT /note="Protease nsP2"
FT /id="PRO_0000228763"
FT CHAIN 1328..1886
FT /note="Non-structural protein 3'"
FT /id="PRO_0000228764"
FT CHAIN 1328..1879
FT /note="Non-structural protein 3"
FT /id="PRO_0000228765"
FT CHAIN 1887..2494
FT /note="RNA-directed RNA polymerase nsP4"
FT /id="PRO_0000228766"
FT DOMAIN 28..257
FT /note="Alphavirus-like MT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01079"
FT DOMAIN 674..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 2252..2367
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 1667..1711
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1761..1794
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1798..1810
FT /note="Binding to host G3BP family members"
FT /evidence="ECO:0000269|PubMed:28468889"
FT REGION 1858..1874
FT /note="Binding to host FXR family members"
FT /evidence="ECO:0000269|PubMed:28468889"
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 COMPBIAS 1667..1684
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1685..1711
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
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 1589
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P03317"
FT BINDING 1591
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P03317"
FT BINDING 1614
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P03317"
FT BINDING 1632
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 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 1886..1887
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 81
FT /note="I -> V (in strain: PE6)"
FT VARIANT 101
FT /note="R -> G (in strain: PE6)"
FT VARIANT 135
FT /note="T -> A (in strain: PE6)"
FT VARIANT 613
FT /note="L -> P (in strain: Georgia 97 and PE6)"
FT VARIANT 641
FT /note="V -> A (in strain: PE6)"
FT VARIANT 730
FT /note="K -> Q (in strain: PE6)"
FT VARIANT 1174
FT /note="M -> T (in strain: PE6)"
FT VARIANT 1358
FT /note="S -> G (in strain: Georgia 97 and PE6)"
FT VARIANT 1391
FT /note="V -> I (in strain: Georgia 97)"
FT VARIANT 1618
FT /note="Q -> H (in strain: Georgia 97)"
FT VARIANT 1774
FT /note="A -> V (in strain: PE6)"
FT VARIANT 1791
FT /note="G -> A (in strain: PE6)"
FT VARIANT 1864
FT /note="V -> A (in strain: Georgia 97 and PE6)"
SQ SEQUENCE 2494 AA; 277312 MW; B12F73524A899206 CRC64;
MEKVHVDLDA DSPFVKSLQR CFPHFEIEAT QVTDNDHANA RAFSHLATKL IEGEVDTDQV
ILDIGSAPVR HTHSKHKYHC ICPMKSAEDP DRLYRYADKL RKSDVTDKCI ASKAADLLTV
MSTPDAETPS LCMHTDSTCR YHGSVAVYQD VYAVHAPTSI YYQALKGVRT IYWIGFDTTP
FMYKNMAGAY PTYNTNWADE SVLEARNIGL GSSDLHEKSF GKVSIMRKKK LQPTNKVIFS
VGSTIYTEER ILLRSWHLPN VFHLKGKTSF TGRCNTIVSC EGYVVKKITL SPGIYGKVDN
LASTMHREGF LSCKVTDTLR GERVSFPVCT YVPATLCDQM TGILATDVSV DDAQKLLVGL
NQRIVVNGRT QRNTNTMQNY LLPVVAQAFS RWAREHRADL EDEKGLGVRE RSLVMGCCWA
FKTHKITSIY KRPGTQTIKK VPAVFNSFVI PQPTSYGLDI GLRRRIKMLF DAKKAPAPII
TEADVAHLKG LQDEAEAVAE AEAVRAALPP LLPEVDKETV EADIDLIMQE AGAGSVETPR
RHIKVTTYPG EEMIGSYAVL SPQAVLNSEK LACIHPLAEQ VLVMTHKGRA GRYKVEPYHG
RVIVPSGTAI PILDFQALSE SATIVFNERE FVNRYLHHIA VNGGALNTDE EYYKVVKSTE
TDSEYVFDID AKKCVKKGDA GPMCLVGELV DPPFHEFAYE SLKTRPAAPH KVPTIGVYGV
PGSGKSGIIK SAVTKRDLVV SAKKENCMEI IKDVKRMRGM DIAARTVDSV LLNGVKHSVD
TLYIDEAFAC HAGTLLALIA IVKPKKVVLC GDPKQCGFFN MMCLKVHFNH EICTEVYHKS
ISRRCTKTVT SIVSTLFYDK RMRTVNPCND KIIIDTTSTT KPLKDDIILT CFRGWVKQLQ
IDYKNHEIMT AAASQGLTRK GVYAVRYKVN ENPLYAQTSE HVNVLLTRTE KRIVWKTLAG
DPWIKTLTAS YPGNFTATLE EWQAEHDAIM AKILETPASS DVFQNKVNVC WAKALEPVLA
TANITLTRSQ WETIPAFKDD KAYSPEMALN FFCTRFFGVD IDSGLFSAPT VPLTYTNEHW
DNSPGPNMYG LCMRTAKELA RRYPCILKAV DTGRVADVRT DTIKDYNPLI NVVPLNRRLP
HSLVVTHRYT GNGDYSQLVT KMTGKTVLVV GTPMNIPGKR VETLGPSPQC TYKAELDLGI
PAALGKYDII FINVRTPYRH HHYQQCEDHA IHHSMLTRKA VDHLNKGGTC IALGYGTADR
ATENIISAVA RSFRFSRVCQ PKCAWENTEV AFVFFGKDNG NHLQDQDRLS VVLNNIYQGS
TQHEAGRAPA YRVVRGDITK SNDEVIVNAA NNKGQPGSGV CGALYRKWPG AFDKQPVATG
KAHLVKHSPN VIHAVGPNFS RLSENEGDQK LSEVYMDIAR IINNERFTKV SIPLLSTGIY
AGGKDRVMQS LNHLFTAMDT TDADITIYCL DKQWESRIKE AITRKESVEE LTEDDRPVDI
ELVRVHPLSS LAGRPGYSTT EGKVYSYLEG TRFHQTAKDI AEIYAMWPNK QEANEQICLY
VLGESMNSIR SKCPVEESEA SSPPHTIPCL CNYAMTAERV YRLRMAKNEQ FAVCSSFQLP
KYRITGVQKI QCSKPVIFSG TVPPAIHPRK FASVTVEDTP VVQPERLVPR RPAPPVPVPA
RIPSPPCTST NGSTTSIQSL GEDQSASASS GAEISVDQVS LWSIPSATGF DVRTSSSLSL
EQPTFPTMVV EAEIHASQGS LWSIPSITGS ETRAPSPPSQ DSRPSTPSAS GSHTSVDLIT
FDSVAEILED FSRSPFQFLS EIKPIPAPRT RVNNMSRSAD TIKPIPKPRK CQVKYTQPPG
VARVISAAEF DEFVRRHSNX RYEAGAYIFS SETGQGHLQQ KSTRQCKLQY PILERSVHEK
FYAPRLDLER EKLLQKKLQL CASEGNRSRY QSRKVENMKA ITVERLLQGI GSYLSAEPQP
VECYKVTYPA PMYSSTASNS FSSAEVAVKV CNLVLQENFP TVASYNITDE YDAYLDMVDG
ASCCLDTATF CPAKLRSFPK KHSYLRPEIR SAVPSPIQNT LQNVLAAATK RNCNVTQMRE
LPVLDSAAFN VECFKKYACN DEYWDFYKTN PIRLTAENVT QYVTKLKGPK AAALFAKTHN
LQPLHEIPMD RFVMDLKRDV KVTPGTKHTE ERPKVQVIQA ADPLATAYLC GIHRELVRRL
NAVLLPNIHT LFDMSAEDFD AIIAEHFQFG DAVLETDIAS FDKSEDDAIA MSALMILEDL
GVDQALLNLI EAAFGNITSV HLPTGTRFKF GAMMKSGMFL TLFINTVVNI MIASRVLRER
LTTSPCAAFI GDDNIVKGVT SDALMAERCA TWLNMEVKII DAVVGVKAPY FCGGFIVVDQ
ITGTACRVAD PLKRLFKLGK PLPLDDDQDV DRRRALHDEA ARWNRIGITE ELVKAVESRY
EVNYVSLIIT ALTTLASSVS NFKHIRGHPI TLYG
