POLN_WEEV
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 03-AUG-2022, entry version 135.
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 Western equine encephalitis virus (WEEV).
OC Viruses; Riboviria; Orthornavirae; Kitrinoviricota; Alsuviricetes;
OC Martellivirales; Togaviridae; Alphavirus.
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 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 (By similarity). The nsp3-FXR and nsp3-G3BP complexes bind
CC viral RNAs and probably orchestrate the assembly of viral replication
CC complexes, thanks to the ability of G3BP and FXR family members to
CC 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 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 and
CC G3BP families and sequesters them into the viral RNA replication
CC complexes thereby inhibiting the formation of host stress granules on
CC viral mRNAs (Probable). The nsp3'-FXR and nsp3-G3BP complexes bind
CC viral RNAs and probably orchestrate the assembly of viral replication
CC complexes, thanks to the ability of G3BP and FXR family members to
CC self-assemble and bind DNA (Probable). {ECO:0000250|UniProtKB:P03317,
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=[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:Q4QXJ8, 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 (By
CC similarity). 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 (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 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 -!- 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 MEROPS; C09.002; -.
DR PRIDE; P13896; -.
DR GeneID; 944530; -.
DR KEGG; vg:944530; -.
DR Proteomes; UP000007630; Genome.
DR Proteomes; UP000111743; 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 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..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 1798..1829
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 COMPBIAS 1802..1818
FT /note="Pro 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 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 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
