POLN_MAYAB
ID POLN_MAYAB Reviewed; 2437 AA.
AC Q8QZ73; Q8QHM4;
DT 04-APR-2006, integrated into UniProtKB/Swiss-Prot.
DT 10-APR-2019, sequence version 3.
DT 03-AUG-2022, entry version 123.
DE RecName: Full=Polyprotein P1234;
DE Short=P1234;
DE AltName: Full=Non-structural polyprotein;
DE Contains:
DE RecName: Full=Polyprotein P123';
DE Short=P123';
DE Contains:
DE RecName: Full=Polyprotein P123;
DE Short=P123;
DE Contains:
DE RecName: Full=mRNA-capping enzyme nsP1;
DE EC=2.1.1.- {ECO:0000250|UniProtKB:P27282};
DE EC=2.7.7.- {ECO:0000250|UniProtKB:P03317};
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:Q8JUX6};
DE EC=3.6.1.15 {ECO:0000250|UniProtKB:Q8JUX6};
DE EC=3.6.4.13 {ECO:0000250|UniProtKB:Q8JUX6};
DE AltName: Full=Non-structural protein 2;
DE Short=nsP2;
DE Contains:
DE RecName: Full=Non-structural protein 3';
DE Short=nsP3';
DE EC=3.1.3.84 {ECO:0000305};
DE Contains:
DE RecName: Full=Non-structural protein 3;
DE Short=nsP3;
DE EC=3.1.3.84 {ECO:0000250|UniProtKB:Q8JUX6};
DE Contains:
DE RecName: Full=RNA-directed RNA polymerase nsP4;
DE EC=2.7.7.19 {ECO:0000250|UniProtKB:P03317};
DE EC=2.7.7.48 {ECO:0000255|PROSITE-ProRule:PRU00539};
DE AltName: Full=Non-structural protein 4;
DE Short=nsP4;
OS Mayaro virus (strain Brazil) (MAYV).
OC Viruses; Riboviria; Orthornavirae; Kitrinoviricota; Alsuviricetes;
OC Martellivirales; Togaviridae; Alphavirus.
OX NCBI_TaxID=374990;
OH NCBI_TaxID=7159; Aedes aegypti (Yellowfever mosquito) (Culex aegypti).
OH NCBI_TaxID=7180; Haemagogus.
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RA Netto M.C.M.G., Shirako Y., Strauss E.G., Carvalho M.G.C., Strauss J.H.;
RL Submitted (FEB-2000) to the EMBL/GenBank/DDBJ databases.
RN [2] {ECO:0007744|PDB:5IQ5}
RP STRUCTURE BY NMR OF 1335-1493.
RX PubMed=25217003; DOI=10.1007/s12104-014-9572-0;
RA Melekis E., Tsika A.C., Lichiere J., Chasapis C.T., Margiolaki I.,
RA Papageorgiou N., Coutard B., Bentrop D., Spyroulias G.A.;
RT "NMR study of non-structural proteins--part I: (1)H, (13)C, (15)N backbone
RT and side-chain resonance assignment of macro domain from Mayaro virus
RT (MAYV).";
RL Biomol. NMR. Assign. 9:191-195(2015).
CC -!- FUNCTION: [Polyprotein P1234]: Inactive precursor of the viral
CC replicase, which is activated by cleavages carried out by the viral
CC protease nsP2. {ECO:0000250|UniProtKB:Q8JUX6}.
CC -!- FUNCTION: [Polyprotein P123]: The early replication complex formed by
CC the polyprotein P123 and nsP4 synthesizes minus-strand RNAs (By
CC similarity). As soon P123 is cleaved into mature proteins, the plus-
CC strand RNAs synthesis begins (By similarity).
CC {ECO:0000250|UniProtKB:P03317}.
CC -!- FUNCTION: [Polyprotein P123']: The early replication complex formed by
CC the polyprotein P123' and nsP4 synthesizes minus-strand RNAs
CC (Probable). Polyprotein P123' is a short-lived polyprotein that
CC accumulates during early stage of infection (Probable). As soon P123'
CC is cleaved into mature proteins, the plus-strand RNAs synthesis begins
CC (Probable). {ECO:0000305}.
CC -!- FUNCTION: [mRNA-capping enzyme nsP1]: Cytoplasmic capping enzyme that
CC catalyzes two virus-specific reactions: methyltransferase and 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 (By similarity). nsP1 capping consists in the following reactions:
CC GTP is first methylated into 7-methyl-GMP and then is covalently linked
CC to nsP1 to form the m7GMp-nsP1 complex from which 7-methyl-GMP complex
CC is transferred to the mRNA to create the cap structure (By similarity).
CC NsP1 is needed for the initiation of the minus-strand RNAs synthesis
CC (By similarity). Probably serves as a membrane anchor for the
CC replication complex composed of nsP1-nsP4 (By similarity).
CC Palmitoylated nsP1 is remodeling host cell cytoskeleton, and induces
CC filopodium-like structure formation at the surface of the host cell (By
CC similarity). {ECO:0000250|UniProtKB:P03317,
CC ECO:0000250|UniProtKB:P08411, ECO:0000250|UniProtKB:Q8JUX6,
CC ECO:0000305}.
CC -!- FUNCTION: [Protease nsP2]: Multifunctional protein whose N-terminus is
CC part of the RNA polymerase complex and displays NTPase, RNA
CC triphosphatase and helicase activities (By similarity). NTPase and RNA
CC triphosphatase are involved in viral RNA capping and helicase keeps a
CC check on the dsRNA replication intermediates (By similarity). The C-
CC terminus harbors a protease that specifically cleaves the polyproteins
CC and releases the mature proteins (By similarity). Required for the
CC shutoff of minus-strand RNAs synthesis (By similarity). Specifically
CC inhibits the host IFN response by promoting the nuclear export of host
CC STAT1 (By similarity). Also inhibits host transcription by inducing
CC rapid proteasome-dependent degradation of POLR2A, a catalytic subunit
CC of the RNAPII complex (By similarity). The resulting inhibition of
CC cellular protein synthesis serves to ensure maximal viral gene
CC expression and to evade host immune response (By similarity).
CC {ECO:0000250|UniProtKB:P03317, ECO:0000250|UniProtKB:P08411,
CC ECO:0000250|UniProtKB:Q8JUX6}.
CC -!- FUNCTION: [Non-structural protein 3']: Seems to be essential for minus-
CC strand RNAs and subgenomic 26S mRNAs synthesis (By similarity).
CC Displays mono-ADP-ribosylhydrolase activity (Probable). ADP-
CC ribosylation is a post-translational modification that controls various
CC processes of the host cell and the virus probably needs to revert it
CC for optimal viral replication (Probable). Binds proteins of FXR family
CC and sequesters them into the viral RNA replication complexes thereby
CC inhibiting the formation of host stress granules on viral mRNAs
CC (Probable). The nsp3'-FXR complexes bind viral RNAs and probably
CC orchestrate the assembly of viral replication complexes, thanks to the
CC ability of FXR family members to self-assemble and bind DNA (Probable).
CC {ECO:0000250|UniProtKB:P03317, ECO:0000305}.
CC -!- FUNCTION: [Non-structural protein 3]: Seems to be essential for minus-
CC strand RNAs and subgenomic 26S mRNAs synthesis (By similarity).
CC Displays mono-ADP-ribosylhydrolase activity (By similarity). ADP-
CC ribosylation is a post-translantional modification that controls
CC various processes of the host cell and the virus probably needs to
CC revert it for optimal viral replication (By similarity). Binds proteins
CC of G3BP family 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-G3BP complexes bind viral RNAs
CC and probably orchestrate the assembly of viral replication complexes,
CC thanks to the ability of G3BP family members to self-assemble and bind
CC DNA (By similarity). {ECO:0000250|UniProtKB:P03317,
CC ECO:0000250|UniProtKB:Q8JUX6}.
CC -!- FUNCTION: [RNA-directed RNA polymerase nsP4]: RNA dependent RNA
CC polymerase (By similarity). Replicates genomic and antigenomic RNA by
CC recognizing replications specific signals. The early replication
CC complex formed by the polyprotein P123 and nsP4 synthesizes minus-
CC strand RNAs (By similarity). The late replication complex composed of
CC fully processed nsP1-nsP4 is responsible for the production of genomic
CC and subgenomic plus-strand RNAs (By similarity). The core catalytic
CC domain of nsP4 also possesses terminal adenylyltransferase (TATase)
CC activity that is probably involved in maintenance and repair of the
CC poly(A) tail, an element required for replication of the viral genome
CC (By similarity). {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:P03317};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:54793;
CC Evidence={ECO:0000250|UniProtKB:P03317};
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=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=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:P03317};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:54429;
CC Evidence={ECO:0000250|UniProtKB:P03317};
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:P03317};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:58249;
CC Evidence={ECO:0000250|UniProtKB:P03317};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ADP-beta-D-ribose 1''-phosphate + H2O = ADP-D-ribose +
CC phosphate; Xref=Rhea:RHEA:25029, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:57967, ChEBI:CHEBI:58753; EC=3.1.3.84;
CC Evidence={ECO:0000250|UniProtKB:Q8JUX6};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25030;
CC Evidence={ECO:0000250|UniProtKB:Q8JUX6};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:P03317};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000250|UniProtKB:P03317};
CC Note=For nsP4 adenylyltransferase activity; Mn(2+) supports catalysis
CC at 60% of the levels observed with Mg(2+).
CC {ECO:0000250|UniProtKB:P03317};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC 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 -!- 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:P03317,
CC ECO:0000250|UniProtKB:P27282}.
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 G3BP1; this interaction inhibits the formation of host stress
CC granules on viral mRNAs and the nsp3-G3BP1 complexes bind viral RNAs
CC and probably orchestrate the assembly of viral replication complexes
CC (By similarity). Interacts (via C-terminus) with host G3BP2; this
CC interaction inhibits the formation of host stress granules on viral
CC mRNAs and the nsp3-G3BP2 complexes bind viral RNAs and probably
CC orchestrate the assembly of viral replication complexes (By
CC similarity). {ECO:0000250|UniProtKB:P03317,
CC ECO:0000250|UniProtKB:P27282}.
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:P03317, ECO:0000250|UniProtKB:P27282}.
CC -!- SUBUNIT: [Protease nsP2]: Interacts with RNA-directed RNA polymerase
CC nsP4 (By similarity). Interacts with mRNA-capping enzyme nsP1 (By
CC similarity). Interacts with KPNA1/karyopherin-alpha1; this interaction
CC probably allows the active transport of protease nsP2 into the host
CC nucleus (By similarity). {ECO:0000250|UniProtKB:P03317,
CC ECO:0000250|UniProtKB:P27282}.
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:0000250|UniProtKB:P03317}; Peripheral membrane
CC protein {ECO:0000305}. Note=In the late phase of infection, the
CC polyprotein is quickly cleaved before localization to cellular
CC membranes. Then nsP3 and nsP3' form aggregates in cytoplasm (By
CC similarity). NsP3' is also part of cytoplasmic vesicles, which are
CC probably formed at the plasma membrane and internalized leading to late
CC endosomal/lysosomal spherules containing the replication complex (By
CC similarity). {ECO:0000250|UniProtKB:P03317}.
CC -!- SUBCELLULAR LOCATION: [RNA-directed RNA polymerase nsP4]: Host
CC cytoplasmic vesicle membrane; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:P03317}. Note=NsP4 is part of cytoplasmic
CC vesicles, which are probably formed at the plasma membrane and
CC internalized leading to late endosomal/lysosomal spherules containing
CC the replication complex. {ECO:0000250|UniProtKB:P08411}.
CC -!- DOMAIN: [Protease nsP2]: The N-terminus exhibits NTPase and RNA
CC triphosphatase activities and is proposed to have helicase activity,
CC whereas the C-terminus possesses protease activity (By similarity).
CC Contains a nuclear localization signal and a nuclear export signal,
CC these two motifs are probably involved in the shuttling between the
CC cytoplasm and the nucleus of nsP2 (By similarity). The C-terminus is
CC required for promoting the export of host STAT1 (By similarity).
CC {ECO:0000250|UniProtKB:P27282, ECO:0000250|UniProtKB:Q8JUX6}.
CC -!- DOMAIN: [Non-structural protein 3]: In the N-terminus, the macro domain
CC displays a mono-ADP-ribosylhydrolase activity (By similarity). The
CC central part has a zinc-binding function (By similarity). The C-
CC terminus contains two FGDF motifs necessary and sufficient for
CC formation of the nsP3/G3BP1 complex (By similarity).
CC {ECO:0000250|UniProtKB:P03317, ECO:0000250|UniProtKB:P08411}.
CC -!- DOMAIN: [Non-structural protein 3']: In the N-terminus, the macro
CC domain displays a mono-ADP-ribosylhydrolase activity (By similarity).
CC The central part has a zinc-binding function (By similarity). The C-
CC terminus contains two FGDF motifs necessary and sufficient for
CC formation of the nsP3'/G3BP1 complex (By similarity).
CC {ECO:0000250|UniProtKB:P03317, ECO:0000250|UniProtKB:P08411}.
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:Q8JUX6}.
CC -!- PTM: [Non-structural protein 3]: Phosphorylated by host on serines and
CC threonines. {ECO:0000250|UniProtKB:P08411}.
CC -!- PTM: [Non-structural protein 3']: Phosphorylated by host on serines and
CC threonines. {ECO:0000250|UniProtKB:P08411}.
CC -!- PTM: [RNA-directed RNA polymerase nsP4]: Ubiquitinated; targets the
CC protein for rapid degradation via the ubiquitin system (By similarity).
CC Nsp4 is present in extremely low quantities due to low frequency of
CC translation through the amber stop-codon and the degradation by the
CC ubiquitin pathway (By similarity). {ECO:0000250|UniProtKB:P03317}.
CC -!- MISCELLANEOUS: Viral replication produces dsRNA in the late phase of
CC infection, resulting in a strong activation of host EIF2AK2/PKR,
CC leading to almost complete phosphorylation of EIF2A (By similarity).
CC This inactivates completely cellular translation initiation, resulting
CC shutoff of host proteins synthesis (By similarity). However,
CC phosphorylation of EIF2A is probably not the only mechanism responsible
CC for the host translation shutoff (By similarity). The viral translation
CC can still occur normally because it relies on a hairpin structure in
CC the coding region of sgRNA and is EIF2A-, EIF2D-, EIF4G- EIF4A-
CC independent (By similarity). {ECO:0000250|UniProtKB:P03317}.
CC -!- MISCELLANEOUS: The genome codes for P123, but readthrough of a
CC terminator codon UGA occurs between the codons for Ser-1819 and Leu-
CC 1821 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}.
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; AF237947; AAL79763.1; -; Genomic_RNA.
DR EMBL; AF237947; AAL79765.1; ALT_SEQ; Genomic_RNA.
DR RefSeq; NP_579968.1; NC_003417.1.
DR RefSeq; NP_579969.1; NC_003417.1.
DR PDB; 5IQ5; NMR; -; A=1335-1493.
DR PDBsum; 5IQ5; -.
DR SMR; Q8QZ73; -.
DR MEROPS; C09.001; -.
DR PRIDE; Q8QZ73; -.
DR GeneID; 935140; -.
DR GeneID; 935142; -.
DR KEGG; vg:935140; -.
DR KEGG; vg:935142; -.
DR Proteomes; UP000007774; 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; SSF53335; SSF53335; 1.
DR SUPFAM; SSF56672; SSF56672; 1.
DR PROSITE; PS51743; ALPHAVIRUS_MT; 1.
DR PROSITE; PS51154; MACRO; 1.
DR PROSITE; PS51520; NSP2PRO; 1.
DR PROSITE; PS51657; PSRV_HELICASE; 1.
DR PROSITE; PS50507; RDRP_SSRNA_POS; 1.
PE 1: Evidence at protein level;
KW 3D-structure; ATP-binding;
KW Eukaryotic host gene expression shutoff by virus;
KW Eukaryotic host transcription shutoff by virus; GTP-binding; Helicase;
KW Host cell membrane; Host cell projection; Host cytoplasm;
KW Host cytoplasmic vesicle; Host gene expression shutoff by virus;
KW Host membrane; Host nucleus; Host-virus interaction; Hydrolase;
KW Inhibition of host RNA polymerase II by virus; Lipoprotein; Membrane;
KW Metal-binding; Methyltransferase; mRNA capping; mRNA processing;
KW Multifunctional enzyme; Nucleotide-binding; Nucleotidyltransferase;
KW Palmitate; 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..2437
FT /note="Polyprotein P1234"
FT /id="PRO_0000308393"
FT CHAIN 1..1826
FT /note="Polyprotein P123'"
FT /id="PRO_0000229927"
FT CHAIN 1..1819
FT /note="Polyprotein P123"
FT /id="PRO_0000229926"
FT CHAIN 1..536
FT /note="mRNA-capping enzyme nsP1"
FT /id="PRO_0000229928"
FT CHAIN 537..1334
FT /note="Protease nsP2"
FT /id="PRO_0000229929"
FT CHAIN 1335..1826
FT /note="Non-structural protein 3'"
FT /id="PRO_0000229931"
FT CHAIN 1335..1819
FT /note="Non-structural protein 3"
FT /id="PRO_0000229930"
FT CHAIN 1827..2437
FT /note="RNA-directed RNA polymerase nsP4"
FT /id="PRO_0000229932"
FT DOMAIN 28..259
FT /note="Alphavirus-like MT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01079"
FT DOMAIN 691..843
FT /note="(+)RNA virus helicase ATP-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00990"
FT DOMAIN 844..992
FT /note="(+)RNA virus helicase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00990"
FT DOMAIN 1005..1327
FT /note="Peptidase C9"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00853"
FT DOMAIN 1335..1493
FT /note="Macro"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00490"
FT DOMAIN 2191..2306
FT /note="RdRp catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00539"
FT REGION 244..263
FT /note="NsP1 membrane-binding"
FT /evidence="ECO:0000250|UniProtKB:P08411"
FT REGION 1006..1025
FT /note="Nucleolus localization signal"
FT /evidence="ECO:0000250|UniProtKB:P08411"
FT REGION 1680..1735
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 1059..1068
FT /note="Nuclear export signal"
FT /evidence="ECO:0000250|UniProtKB:P27282"
FT MOTIF 1182..1186
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000250|UniProtKB:P08411"
FT MOTIF 1792..1795
FT /note="FGDF; binding to host G3BP1"
FT /evidence="ECO:0000250|UniProtKB:P08411"
FT MOTIF 1804..1807
FT /note="FGDF; binding to host G3BP1"
FT /evidence="ECO:0000250|UniProtKB:P08411"
FT COMPBIAS 1688..1703
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 1014
FT /note="For cysteine protease nsP2 activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00853"
FT ACT_SITE 1084
FT /note="For cysteine protease nsP2 activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00853"
FT BINDING 722..729
FT /ligand="a ribonucleoside 5'-triphosphate"
FT /ligand_id="ChEBI:CHEBI:61557"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00990"
FT BINDING 1344
FT /ligand="ADP-D-ribose"
FT /ligand_id="ChEBI:CHEBI:57967"
FT /evidence="ECO:0000250|UniProtKB:P36328"
FT BINDING 1358
FT /ligand="ADP-D-ribose"
FT /ligand_id="ChEBI:CHEBI:57967"
FT /evidence="ECO:0000250|UniProtKB:Q8JUX6"
FT BINDING 1366
FT /ligand="ADP-D-ribose"
FT /ligand_id="ChEBI:CHEBI:57967"
FT /evidence="ECO:0000250|UniProtKB:Q8JUX6"
FT BINDING 1446
FT /ligand="ADP-D-ribose"
FT /ligand_id="ChEBI:CHEBI:57967"
FT /evidence="ECO:0000250|UniProtKB:P36328"
FT BINDING 1447
FT /ligand="ADP-D-ribose"
FT /ligand_id="ChEBI:CHEBI:57967"
FT /evidence="ECO:0000250|UniProtKB:P36328"
FT BINDING 1448
FT /ligand="ADP-D-ribose"
FT /ligand_id="ChEBI:CHEBI:57967"
FT /evidence="ECO:0000250|UniProtKB:P36328"
FT BINDING 1596
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P03317"
FT BINDING 1598
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P03317"
FT BINDING 1621
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P03317"
FT BINDING 1639
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 536..537
FT /note="Cleavage; by protease nsP2"
FT /evidence="ECO:0000250|UniProtKB:P03317"
FT SITE 1334..1335
FT /note="Cleavage; by protease nsP2"
FT /evidence="ECO:0000250|UniProtKB:P03317"
FT SITE 1826..1827
FT /note="Cleavage; by protease nsP2"
FT /evidence="ECO:0000250|UniProtKB:Q8JUX6"
FT LIPID 417
FT /note="S-palmitoyl cysteine; by host"
FT /evidence="ECO:0000250|UniProtKB:Q8JUX6"
FT LIPID 419
FT /note="S-palmitoyl cysteine; by host"
FT /evidence="ECO:0000250|UniProtKB:Q8JUX6"
FT STRAND 1337..1344
FT /evidence="ECO:0007829|PDB:5IQ5"
FT STRAND 1350..1357
FT /evidence="ECO:0007829|PDB:5IQ5"
FT HELIX 1369..1374
FT /evidence="ECO:0007829|PDB:5IQ5"
FT HELIX 1376..1379
FT /evidence="ECO:0007829|PDB:5IQ5"
FT STRAND 1389..1403
FT /evidence="ECO:0007829|PDB:5IQ5"
FT HELIX 1407..1409
FT /evidence="ECO:0007829|PDB:5IQ5"
FT HELIX 1412..1433
FT /evidence="ECO:0007829|PDB:5IQ5"
FT STRAND 1436..1441
FT /evidence="ECO:0007829|PDB:5IQ5"
FT HELIX 1455..1466
FT /evidence="ECO:0007829|PDB:5IQ5"
FT STRAND 1471..1477
FT /evidence="ECO:0007829|PDB:5IQ5"
FT HELIX 1481..1492
FT /evidence="ECO:0007829|PDB:5IQ5"
SQ SEQUENCE 2437 AA; 271996 MW; B43A8C61A8B31829 CRC64;
MSKVFVDIEA ESPFLKSLQR AFPAFEVEAQ QVTPNDHANA RAFSHLATKL IEQETEKDTL
ILDIGSAPAR RMMSEHTYHC VCPMRSAEDP ERLLYYARKL AKASGEVVDR NIAAKIDDLQ
SVMATPDNES RTFCLHTDQT CRTQAEVAVY QDVYAVHAPT SLYFQAMKGV RTAYWIGFDT
TPFMFDTMAG AYPTYATNWA DEQVLKARNI GLCSASLTEG HLGKLSIMRK KKMTPSDQIM
FSVGSTLYIE SRRLLKSWHL PSVFHLKGRQ SYTCRCDTIV SCEGYVVKKI TMSPGVFGKT
SGYAVTHHAE GFLVCKTTDT IAGERVSFPI CTYVPSTICD QMTGILATEV TPEDAQKLLV
GLNQRIVVNG RTQRNTNTMK NYLLPVVSQA FSKWAKEYRL DQEDEKNMGM RERTLTCCCL
WAFKTHKNHT MYKKPDTQTI VKVPSEFNSF VIPSLWSAGL SIGIRHRIRL LLQSRRVEPL
VPSMDVGEAR AAEREAAEAK EAEDTLAALP PLIPTAPVLD DIPEVDVEEL EFRAGAGVVE
TPRNALKVTP QDRDTMVGSY LVLSPQTVLK SVKLQALHPL AESVKIITHK GRAGRYQVDA
YDGRVLLPTG AAIPVPDFQA LSESATMVYN EREFINRKLY HIAVHGAALN TDEEGYEKVR
AESTDAEYVY DVDRKQCVKR EEAEGLVMIG DLINPPFHEF AYEGLKRRPA APYKTTVVGV
FGVPGSGKSG IIKSLVTRGD LVASGKKENC QEIMLDVKRY RDLDMTAKTV DSVLLNGVKQ
TVDVLYVDEA FACHAGTLLA LIATVRPRKK VVLCGDPKQC GFFNLMQLQV NFNHNICTEV
DHKSISRRCT LPITAIVSTL HYEGRMRTTN PYNKPVIIDT TGQTKPNRED IVLTCFRGWV
KQLQLDYRGH EVMTAAASQG LTRKGVYAVR MKVNENPLYA QSSEHVNVLL TRTEGRLVWK
TLSGDPWIKT LSNIPKGNFT ATLEDWQREH DTIMRAITQE AAPLDVFQNK AKVCWAKCLV
PVLETAGIKL SATDWSAIIL AFKEDRAYSP EVALNEICTK IYGVDLDSGL FSAPRVSLHY
TTNHWDNSPG GRMYGFSVEA ANRLEQQHPF YRGRWASGQV LVAERKTQPI DVTCNLIPFN
RRLPHTLVTE YHPIKGERVE WLVNKIPGYH VLLVSEYNLI LPRRKVTWIA PPTVTGADLT
YDLDLGLPPN AGRYDLVFVN MHTPYRLHHY QQCVDHAMKL QMLGGDALYL LKPGGSLLLS
TYAYADRTSE AVVTALARRF SSFRAVTVRC VTSNTEVFLL FTNFDNGRRT VTLHQTNGKL
SSIYAGTVLQ AAGCAPAYAV KRADIATAIE DAVVNAANHR GQVGDGVCRA VARKWPQAFR
NAATPVGTAK TVKCDETYII HAVGPNFNNT SEAEGDRDLA AAYRAVAAEI NRLSISSVAI
PLLSTGIFSA GKDRVHQSLS HLLAAMDTTE ARVTIYCRDK TWEQKIKTVL QNRSATELVS
DELQFEVNLT RVHPDSSLVG RPGYSTTDGT LYSYMEGTKF HQAALDMAEI TTLWPRVQDA
NEHICLYALG ETMDNIRARC PVEDSDSSTP PKTVPCLCRY AMTPERVTRL RMHHTKDFVV
CSSFQLPKYR IPGVQRVKCE KVMLFDAAPP ASVSPVQYLT NQSETTISLS SFSITSDSSS
LSTFPDLESA EELDHDSQSV RPALNEPDDH QPTPTAELAT HPVPPPRPNR ARRLAAARVQ
VQVEVHQPPS NQPTKPIPAP RTSLRPVPAP RRYVPRPVVE LPWPLETIDV EFGAPTEEES
DITFGDFSAS EWETISNSSX LGRAGAYIFS SDVGPGHLQQ KSVRQHDLEV PIMDRVIEEK
VYPPKLDEAK EKQLLLKLQM HATDANRSRY QSRKVENMKA TIIDRLKQGS AYYVSAAADK
AVTYHVRYAK PRYSVPVMQR LSSATIAVAT CNEFLARNYP TVASYQITDE YDAYLDMVDG
SESCLDRANF CPAKLRCYPK HHAYHMPQIR SAVPSPFQNT LQNVLAAATK RNCNVTQMRE
LPTLDSAVYN VECFRKYACN NEYWEEFAKK PIRITTENLT TYVTKLKGGK AAALFAKTHN
LVPLQEVPMD RFIMDMKRDV KVTPGTKHTE ERPKVQVIQA AEPLATAYLC GIHRELVRRL
NAVLLPNIHT LFDMSAEDFD AIISEHFKPG DHVLETDIAS FDKSQDDSLA LTGLMILEDL
GVDNQLLDLI EAAFGQITSC HLPTGTRFKF GAMMKSGMFL TLFINTVLNI TIASRVLEAR
LTNSACAAFI GDDNVVHGVV SDKLMADRCA TWVNMEVKII DAVMCIKPPY FCGGFLVYDH
VTRTACRIAD PLKRLFKLGK PLPADDCQDE DRRRALYDEV KKWSRSGLGS EIEVALASRY
RLEGSYNLLL AMSTFAHSMK NFSALRGPVI HLYGGPK
