POLN_CHIK3
ID POLN_CHIK3 Reviewed; 2474 AA.
AC Q5XXP4;
DT 21-MAR-2006, integrated into UniProtKB/Swiss-Prot.
DT 23-NOV-2004, sequence version 1.
DT 03-AUG-2022, entry version 115.
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:P27282};
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 Chikungunya virus (strain 37997) (CHIKV).
OC Viruses; Riboviria; Orthornavirae; Kitrinoviricota; Alsuviricetes;
OC Martellivirales; Togaviridae; Alphavirus.
OX NCBI_TaxID=371095;
OH NCBI_TaxID=7159; Aedes aegypti (Yellowfever mosquito) (Culex aegypti).
OH NCBI_TaxID=7160; Aedes albopictus (Asian tiger mosquito) (Stegomyia albopicta).
OH NCBI_TaxID=299627; Aedes furcifer (Mosquito).
OH NCBI_TaxID=188700; Aedes polynesiensis (Polynesian tiger mosquito).
OH NCBI_TaxID=9533; Cercopithecus.
OH NCBI_TaxID=9606; Homo sapiens (Human).
OH NCBI_TaxID=9539; Macaca (macaques).
OH NCBI_TaxID=9598; Pan troglodytes (Chimpanzee).
OH NCBI_TaxID=9554; Papio (baboons).
OH NCBI_TaxID=9573; Presbytis.
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=15891138; DOI=10.4269/ajtmh.2005.72.616;
RA Vanlandingham D.L., Hong C., Klingler K., Tsetsarkin K., McElroy K.L.,
RA Powers A.M., Lehane M.J., Higgs S.;
RT "Differential infectivities of O'Nyong-Nyong and Chikungunya virus isolates
RT in Anopheles gambiae and Aedes aegypti mosquitoes.";
RL Am. J. Trop. Med. Hyg. 72:616-621(2005).
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
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 also needed for the initiation of the minus-strand RNAs
CC synthesis (By similarity). At the initiation of virus replication,
CC mediates the assembly of the viral replication complex made of the non-
CC structural proteins, the association of this complex with the inner
CC face of the plasma membrane and the formation of membranous spherules
CC that serve as replication complex factories (By similarity). Forms the
CC neck of these spherules with a central channel for mediating
CC communication and the passage of RNA, nucleotides, and small proteins
CC between the viral replication complex and the host cytoplasm (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:Q8JUX6}.
CC -!- FUNCTION: [Protease nsP2]: Multifunctional protein whose N-terminus is
CC part of the RNA polymerase complex and displays NTPase, RNA
CC triphosphatase and helicase activities (By similarity). NTPase and RNA
CC triphosphatase are involved in viral RNA capping and helicase keeps a
CC check on the dsRNA replication intermediates (By similarity). The C-
CC terminus harbors a protease that specifically cleaves the polyproteins
CC and releases the mature proteins (By similarity). Required for the
CC shutoff of minus-strand RNAs synthesis (By similarity). Specifically
CC inhibits the host IFN response by promoting the nuclear export of host
CC STAT1 (By similarity). Also inhibits host transcription by inducing the
CC rapid proteasome-dependent degradation of POLR2A, a catalytic subunit
CC of the RNAPII complex (By similarity). The resulting inhibition of
CC cellular protein synthesis serves to ensure maximal viral gene
CC expression and to evade host immune response (By similarity).
CC {ECO:0000250|UniProtKB:P03317, ECO:0000250|UniProtKB:P08411,
CC ECO:0000250|UniProtKB:Q8JUX6}.
CC -!- FUNCTION: [Non-structural protein 3']: Seems to be essential for minus-
CC strand RNAs and subgenomic 26S mRNAs synthesis (By similarity).
CC Displays mono-ADP-ribosylhydrolase activity (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-translational modification that controls various
CC processes of the host cell and the virus probably needs to revert it
CC for optimal viral replication (By similarity). Binds proteins of G3BP
CC family and sequesters them into the viral RNA replication complexes
CC thereby inhibiting the formation of host stress granules on viral mRNAs
CC (By similarity). The nsp3-G3BP complexes bind viral RNAs and probably
CC orchestrate the assembly of viral replication complexes, thanks to the
CC ability of G3BP family members to self-assemble and bind DNA (By
CC similarity). {ECO:0000250|UniProtKB:P03317,
CC ECO:0000250|UniProtKB:Q8JUX6}.
CC -!- FUNCTION: [RNA-directed RNA polymerase nsP4]: RNA dependent RNA
CC polymerase (By similarity). Replicates genomic and antigenomic RNA by
CC recognizing replications specific signals. The early replication
CC complex formed by the polyprotein P123 and nsP4 synthesizes minus-
CC strand RNAs (By similarity). The late replication complex composed of
CC fully processed nsP1-nsP4 is responsible for the production of genomic
CC and subgenomic plus-strand RNAs (By similarity).
CC {ECO:0000250|UniProtKB:P03317}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=GTP + S-adenosyl-L-methionine = N(7)-methyl-GTP + S-adenosyl-
CC L-homocysteine; Xref=Rhea:RHEA:46948, ChEBI:CHEBI:37565,
CC ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:87133;
CC Evidence={ECO:0000250|UniProtKB:P27282};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[nsP1 protein]-L-histidine + N(7)-methyl-GTP = [nsP1 protein]-
CC N(tele)-(N(7)-methylguanosine 5'-phospho)-L-histidine + diphosphate;
CC Xref=Rhea:RHEA:54792, Rhea:RHEA-COMP:13994, Rhea:RHEA-COMP:13995,
CC ChEBI:CHEBI:29979, ChEBI:CHEBI:33019, ChEBI:CHEBI:87133,
CC ChEBI:CHEBI:138334; Evidence={ECO:0000250|UniProtKB:P27282};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:54793;
CC Evidence={ECO:0000250|UniProtKB:P27282};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[nsP1 protein]-N(tele)-(N(7)-methylguanosine 5'-phospho)-L-
CC histidine + a 5'-end diphospho-(purine-ribonucleoside) in mRNA + H(+)
CC = [nsP1 protein]-L-histidine + a 5'-end (N(7)-methyl 5'-
CC triphosphoguanosine)-(purine-ribonucleoside) in mRNA;
CC Xref=Rhea:RHEA:54800, Rhea:RHEA-COMP:12925, Rhea:RHEA-COMP:13929,
CC Rhea:RHEA-COMP:13994, Rhea:RHEA-COMP:13995, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:29979, ChEBI:CHEBI:133968, ChEBI:CHEBI:138276,
CC ChEBI:CHEBI:138334; Evidence={ECO:0000250|UniProtKB:P27282};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 5'-end triphospho-(purine-ribonucleoside) in mRNA + H2O = a
CC 5'-end diphospho-(purine-ribonucleoside) in mRNA + H(+) + phosphate;
CC Xref=Rhea:RHEA:11008, Rhea:RHEA-COMP:13929, Rhea:RHEA-COMP:13942,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:138276, ChEBI:CHEBI:138288; EC=3.1.3.33;
CC Evidence={ECO:0000250|UniProtKB: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:Q8JUX6};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:54429;
CC Evidence={ECO:0000250|UniProtKB:Q8JUX6};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=5-O-(ADP-D-ribosyl)-L-glutamyl-[protein] + H2O = ADP-D-ribose
CC + H(+) + L-glutamyl-[protein]; Xref=Rhea:RHEA:58248, Rhea:RHEA-
CC COMP:10208, Rhea:RHEA-COMP:15089, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:29973, ChEBI:CHEBI:57967,
CC ChEBI:CHEBI:142540; Evidence={ECO:0000250|UniProtKB:Q8JUX6};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:58249;
CC Evidence={ECO:0000250|UniProtKB:Q8JUX6};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + RNA(n) = diphosphate + RNA(n)-3'-adenine ribonucleotide;
CC Xref=Rhea:RHEA:11332, Rhea:RHEA-COMP:14527, Rhea:RHEA-COMP:17347,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:140395,
CC ChEBI:CHEBI:173115; EC=2.7.7.19;
CC Evidence={ECO:0000250|UniProtKB:P03317};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ADP-beta-D-ribose 1''-phosphate + H2O = ADP-D-ribose +
CC phosphate; Xref=Rhea:RHEA:25029, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:57967, ChEBI:CHEBI:58753; EC=3.1.3.84;
CC Evidence={ECO:0000250|UniProtKB:Q8JUX6};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25030;
CC Evidence={ECO:0000250|UniProtKB:Q8JUX6};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:P03317};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000250|UniProtKB:P03317};
CC Note=For nsP4 adenylyltransferase activity; Mn(2+) supports catalysis
CC at 60% of the levels observed with Mg(2+).
CC {ECO:0000250|UniProtKB:P03317};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Note=For nsP4 RNA-directed RNA polymerase activity.
CC {ECO:0000250|UniProtKB:P03317};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:P27282};
CC Note=For nsP1 guanylylation. {ECO:0000250|UniProtKB:P27282};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Note=For nsP2 RNA triphosphatase activity.
CC {ECO:0000250|UniProtKB:Q8JUX6};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Note=For nsP2 NTPase activity. {ECO:0000250|UniProtKB:Q8JUX6};
CC -!- SUBUNIT: [mRNA-capping enzyme nsP1]: Homododecamer (By similarity). The
CC enzyme forms a membrane-associated dodecameric ring with a central
CC channel for the exchange of between the viral replication factories and
CC the host cytoplasm (By similarity). 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). Interacts with host STING1; this
CC interaction results in inhibition of cGAS-STING signaling and increased
CC levels of palmitoylation and protein stabilization of nsP1 (By
CC similarity). {ECO:0000250|UniProtKB:Q8JUX6}.
CC -!- SUBUNIT: [Non-structural protein 3]: Interacts with mRNA-capping enzyme
CC nsP1 (By similarity). 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 (By
CC 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). Interacts (via C-terminus) with host NAP1L1 (By
CC similarity). Interacts (via C-terminus) with host NAP1L4 (By
CC similarity). Interacts (via C-terminus) with host DHX9; this
CC interaction allows the recruitment of DHX9 to the plasma membrane,
CC where it associates with viral replication complexes and may play a
CC role in the translation-to-replication switch (By similarity).
CC Interacts (via C-terminus) with host FHL1 (via LIM domain 1); this
CC interaction is required for viral RNA replication (By similarity).
CC Interacts (via C-terminus) with host CD2AP; this interaction plays a
CC role in initiation of viral replication (By similarity). Interacts (via
CC C-terminus) with host SH3KBP1; this interaction plays a role in
CC initiation of viral replication (By similarity).
CC {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:P03317, ECO:0000250|UniProtKB:P27282,
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:P03317,
CC ECO:0000250|UniProtKB:P27282, 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:Q8JUX6}. Note=In the late phase of infection,
CC the polyprotein is quickly cleaved before localization to cellular
CC membranes. Then a fraction of nsP1 localizes to the inner surface of
CC the plasma membrane and its filopodial extensions. Only the
CC palmitoylated nsP1 localizes to the host filopodia (By similarity).
CC NsP1 is also part of cytoplasmic vesicles, which are probably formed at
CC the plasma membrane and internalized leading to late
CC endosomal/lysosomal spherules containing the replication complex (By
CC similarity). {ECO:0000250|UniProtKB:P08411,
CC ECO:0000250|UniProtKB:Q8JUX6}.
CC -!- SUBCELLULAR LOCATION: [Protease nsP2]: Host cytoplasmic vesicle
CC membrane {ECO:0000250|UniProtKB:P08411}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:P08411}. Host nucleus
CC {ECO:0000250|UniProtKB:P27282}. Host cytoplasm
CC {ECO:0000250|UniProtKB:P27282}. Note=In the late phase of infection,
CC the polyprotein is quickly cleaved before localization to cellular
CC membranes. Then approximately half of nsP2 is found in the nucleus (By
CC similarity). Shuttles between cytoplasm and nucleus (By similarity).
CC NsP2 is also part of cytoplasmic vesicles, which are probably formed at
CC the plasma membrane and internalized leading to late
CC endosomal/lysosomal spherules containing the replication complex (By
CC similarity). {ECO:0000250|UniProtKB:P08411,
CC ECO:0000250|UniProtKB:P27282}.
CC -!- SUBCELLULAR LOCATION: [Non-structural protein 3']: Host cytoplasmic
CC vesicle membrane {ECO:0000250|UniProtKB:P03317}; Peripheral membrane
CC protein {ECO:0000305}. Note=In the late phase of infection, the
CC polyprotein is quickly cleaved before localization to cellular
CC membranes. Then nsP3 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:P08411}. Note=NsP4 is part of cytoplasmic
CC vesicles, which are probably formed at the plasma membrane and
CC internalized leading to late endosomal/lysosomal spherules containing
CC the replication complex. {ECO:0000250|UniProtKB:P08411}.
CC -!- DOMAIN: [Protease nsP2]: The N-terminus exhibits NTPase and RNA
CC triphosphatase activities and is proposed to have helicase activity,
CC whereas the C-terminus possesses protease activity (By similarity).
CC Contains a nuclear localization signal and a nuclear export signal,
CC these two motifs are probably involved in the shuttling between the
CC cytoplasm and the nucleus of nsP2 (By similarity). The C-terminus is
CC required for promoting the export of host STAT1 (By similarity).
CC {ECO:0000250|UniProtKB:P27282, ECO:0000250|UniProtKB:Q8JUX6}.
CC -!- DOMAIN: [mRNA-capping enzyme nsP1]: The N-terminus binds a zinc ion
CC which stabilizes this region (By similarity). The C-terminus is
CC disordered (By similarity). {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 called, the alphavirus unique domain (AUD) has a zinc-
CC binding function (By similarity). The C-terminus region, also called
CC hypervariable domain (HVD), is mainly disordered and binds several host
CC proteins (By similarity). This intrinsically disordered domain contains
CC 2 SH3 domain-binding sites and 2 FGDF motifs necessary and sufficient
CC for the formation of nsP3/G3BP complexes (By similarity).
CC {ECO:0000250|UniProtKB:Q8JUX6}.
CC -!- DOMAIN: [Non-structural protein 3']: In the N-terminus, the macro
CC domain displays a mono-ADP-ribosylhydrolase activity (By similarity).
CC The central part has a zinc-binding function (By similarity). The C-
CC terminus contains two FGDF motifs necessary and sufficient for
CC formation of the nsP3'/G3BP1 complex (By similarity).
CC {ECO:0000250|UniProtKB:P03317, ECO:0000250|UniProtKB:Q8JUX6}.
CC -!- PTM: [Polyprotein P1234]: Specific enzymatic cleavages in vivo yield
CC mature proteins (By similarity). The processing of the polyprotein is
CC temporally regulated (By similarity). In early stages (1.7 hpi), P1234
CC is first cleaved in trans through its nsP2 protease activity, releasing
CC P123' and nsP4, which associate to form the early replication complex
CC (By similarity). At the same time, P1234 is also cut at the nsP1/nsP2
CC site early in infection but with lower efficiency (By similarity).
CC After replication of the viral minus-strand RNAs (4 hpi), the
CC polyproteins are cut at the nsP1/nsP2 and nsP2/nsP3 sites very
CC efficiently, preventing accumulation of P123' and P1234 and allowing
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 (By similarity).
CC Palmitoylation is increased by the interacton with host STING1 (By
CC similarity). {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 Leu-1856 and Leu-
CC 1858 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; AY726732; AAU43880.1; -; Genomic_RNA.
DR PDB; 6W0T; X-ray; 1.95 A; A/B/C/D=1334-1493.
DR PDBsum; 6W0T; -.
DR MEROPS; C09.001; -.
DR PRIDE; Q5XXP4; -.
DR Proteomes; UP000008450; 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 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; 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..2474
FT /note="Polyprotein P1234"
FT /id="PRO_0000308396"
FT CHAIN 1..1863
FT /note="Polyprotein P123'"
FT /id="PRO_0000227765"
FT CHAIN 1..1856
FT /note="Polyprotein P123"
FT /id="PRO_0000446648"
FT CHAIN 1..535
FT /note="mRNA-capping enzyme nsP1"
FT /id="PRO_0000227766"
FT CHAIN 536..1333
FT /note="Protease nsP2"
FT /id="PRO_0000227767"
FT CHAIN 1334..1863
FT /note="Non-structural protein 3'"
FT /id="PRO_0000227768"
FT CHAIN 1334..1856
FT /note="Non-structural protein 3"
FT /id="PRO_0000446649"
FT CHAIN 1864..2474
FT /note="RNA-directed RNA polymerase nsP4"
FT /id="PRO_0000227769"
FT DOMAIN 28..259
FT /note="Alphavirus-like MT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01079"
FT DOMAIN 690..842
FT /note="(+)RNA virus helicase ATP-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00990"
FT DOMAIN 843..991
FT /note="(+)RNA virus helicase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00990"
FT DOMAIN 1004..1327
FT /note="Peptidase C9"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00853"
FT DOMAIN 1334..1493
FT /note="Macro"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00490"
FT DOMAIN 2228..2343
FT /note="RdRp catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00539"
FT REGION 295..450
FT /note="Membrane-binding and oligomerization"
FT /evidence="ECO:0000250|UniProtKB:Q8JUX6"
FT REGION 1005..1024
FT /note="Nucleolus localization signal"
FT /evidence="ECO:0000250|UniProtKB:P08411"
FT REGION 1651..1711
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1659..1857
FT /note="HVD"
FT /evidence="ECO:0000250|UniProtKB:Q8JUX6"
FT REGION 1726..1739
FT /note="Interaction with host CD2AP"
FT /evidence="ECO:0000250|UniProtKB:Q8JUX6"
FT REGION 1745..1793
FT /note="Interaction with host FHL1"
FT /evidence="ECO:0000250|UniProtKB:Q8JUX6"
FT REGION 1756..1767
FT /note="Interaction with host CD2AP"
FT /evidence="ECO:0000250|UniProtKB:Q8JUX6"
FT REGION 1820..1828
FT /note="Interaction with host CD2AP"
FT /evidence="ECO:0000250|UniProtKB:Q8JUX6"
FT MOTIF 1058..1067
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 1812..1815
FT /note="FGDF; binding to host G3BP1"
FT /evidence="ECO:0000250|UniProtKB:P08411"
FT MOTIF 1830..1833
FT /note="FGDF; binding to host G3BP1"
FT /evidence="ECO:0000250|UniProtKB:P08411"
FT COMPBIAS 1654..1679
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 37
FT /note="For mRNA-capping enzyme nsP1 activity"
FT /evidence="ECO:0000250|UniProtKB:Q8JUX6"
FT ACT_SITE 1013
FT /note="For cysteine protease nsP2 activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00853"
FT ACT_SITE 1083
FT /note="For cysteine protease nsP2 activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00853"
FT BINDING 79
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q8JUX6"
FT BINDING 129
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q8JUX6"
FT BINDING 134
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q8JUX6"
FT BINDING 141
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q8JUX6"
FT BINDING 721..728
FT /ligand="a ribonucleoside 5'-triphosphate"
FT /ligand_id="ChEBI:CHEBI:61557"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00990"
FT BINDING 1343
FT /ligand="ADP-D-ribose"
FT /ligand_id="ChEBI:CHEBI:57967"
FT /evidence="ECO:0000250|UniProtKB:P36328"
FT BINDING 1357
FT /ligand="ADP-D-ribose"
FT /ligand_id="ChEBI:CHEBI:57967"
FT /evidence="ECO:0000250|UniProtKB:Q8JUX6"
FT BINDING 1365
FT /ligand="ADP-D-ribose"
FT /ligand_id="ChEBI:CHEBI:57967"
FT /evidence="ECO:0000250|UniProtKB:Q8JUX6"
FT BINDING 1445
FT /ligand="ADP-D-ribose"
FT /ligand_id="ChEBI:CHEBI:57967"
FT /evidence="ECO:0000250|UniProtKB:P36328"
FT BINDING 1446
FT /ligand="ADP-D-ribose"
FT /ligand_id="ChEBI:CHEBI:57967"
FT /evidence="ECO:0000250|UniProtKB:Q8JUX6"
FT BINDING 1447
FT /ligand="ADP-D-ribose"
FT /ligand_id="ChEBI:CHEBI:57967"
FT /evidence="ECO:0000250|UniProtKB:Q8JUX6"
FT BINDING 1595
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P03317"
FT BINDING 1597
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P03317"
FT BINDING 1620
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P03317"
FT BINDING 1638
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 535..536
FT /note="Cleavage; by protease nsP2"
FT /evidence="ECO:0000250|UniProtKB:P03317"
FT SITE 1333..1334
FT /note="Cleavage; by protease nsP2"
FT /evidence="ECO:0000250|UniProtKB:P03317"
FT SITE 1863..1864
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..1342
FT /evidence="ECO:0007829|PDB:6W0T"
FT HELIX 1344..1346
FT /evidence="ECO:0007829|PDB:6W0T"
FT STRAND 1352..1355
FT /evidence="ECO:0007829|PDB:6W0T"
FT HELIX 1366..1373
FT /evidence="ECO:0007829|PDB:6W0T"
FT HELIX 1375..1378
FT /evidence="ECO:0007829|PDB:6W0T"
FT STRAND 1388..1393
FT /evidence="ECO:0007829|PDB:6W0T"
FT STRAND 1396..1401
FT /evidence="ECO:0007829|PDB:6W0T"
FT TURN 1406..1408
FT /evidence="ECO:0007829|PDB:6W0T"
FT HELIX 1411..1432
FT /evidence="ECO:0007829|PDB:6W0T"
FT STRAND 1435..1440
FT /evidence="ECO:0007829|PDB:6W0T"
FT HELIX 1454..1465
FT /evidence="ECO:0007829|PDB:6W0T"
FT STRAND 1470..1477
FT /evidence="ECO:0007829|PDB:6W0T"
FT HELIX 1479..1490
FT /evidence="ECO:0007829|PDB:6W0T"
SQ SEQUENCE 2474 AA; 275933 MW; 0699DB0485FB3097 CRC64;
MDPVYVDIDA DSAFLKALQR AYPMFEVEPR QVTPNDHANA RAFSHLAIKL IEQEIDPDST
ILDIGSAPAR RMMSDRKYHC VCPMRSAEDP ERLANYARKL ASAAGKVLDR NISEKIGDLQ
AVMAVPDAET PTFCLHTDVS CRQRADVAIY QDVYAVHAPT SLYHQAIKGV RVAYWIGFDT
TPFMYNAMAG AYPSYSTNWA DEQVLKAKNI GLCSTDLTEG RRGKLSIMRG KKMKPCDRVL
FSVGSTLYPE SRKLLKSWHL PSVFHLKGKL SFTCRCDTVV SCEGYVVKRI TISPGLYGKT
TGYAVTHHAD GFLMCKTTDT VDGERVSFSV CTYVPATICD QMTGILATEV TPEDAQKLLV
GLNQRIVVNG RTQRNTNTMK NYLLPVVAQA FSKWAKECRK DMEDEKLLGI RERTLTCCCL
WAFKKQKTHT VYKRPDTQSI QKVPAEFDSF VVPSLWSSGL SIPLRTRIKW LLSKVPKTDL
IPYSGDAKEA RDAEKEAEEE REAELTREAL PPLQAAQDDV QVEIDVEQLE DRAGAGIIET
PRGAIKVTAQ PTDHVVGEYL VLSPQTVLRS QKLSLIHALA EQVKTCTHSG RAGRYAVEAY
DGRILVPSGY AISPEDFQSL SESATMVYNE REFVNRKLHH IALHGPALNT DEESYELVRA
ERTEHEYVYD VDQRRCCKKE EAAGLVLVGD LTNPPYHEFA YEGLRIRPAC PYKTAVIGVF
GVPGSGKSAI IKNLVTRQDL VTSGKKENCQ EISTDVMRQR NLEISARTVD SLLLNGCNRP
VDVLYVDEAF ACHSGTLLAL IALVRPRQKV VLCGDPKQCG FFNMMQMKVN YNHNICTQVY
HKSISRRCTL PVTAIVSSLH YEGKMRTTNE YNKPIVVDTT GSTKPDPGDL VLTCFRGWVK
QLQIDYRGHE VMTAAASQGL TRKGVYAVRQ KVNENPLYAS TSEHVNVLLT RTEGKLVWKT
LSGDPWIKTL QNPPKGNFKA TIKEWEVEHA SIMAGICNHQ VTFDTFQNKA NVCWAKSLVP
ILETAGIKLN DRQWSQIIQA FKEDRAYSPE VALNEICTRM YGVDLDSGLF SKPLVSVHYA
DNHWDNRPGG KMFGFNPEAA SILERKYPFT KGKWNTNKQI CVTTRRIEDF NPNTNIIPAN
RRLPHSLVAE HRPVKGERME WLVNKINGHH VLLVSGYNLV LPTKRVTWVA PLGIRGADYT
YNLELGLPAT LGRYDLVIIN IHTPFRIHHY QQCVDHAMKL QMLGGDSLRL LKPGGSLLIR
AYGYADRTSE RVVCVLGRKF RSSRALKPPC VTSNTEMFFL FSNFDNGRRN FTTHVMNNQL
NAAFVGQATR AGCAPSYRVK RMDIAKNDEE CVVNAANPRG LPGDGVCKAV YKKWPESFKN
SATPVGTAKT VMCGTYPVIH AVGPNFSNYS ESEGDRELAA AYREVAKEVT RLGVNSVAIP
LLSTGVYSGG KDRLTQSLNH LFTALDSTDA DVVIYCRDKE WEKKIAEAIQ MRTQVELLDE
HISVDCDIIR VHPDSSLAGR KGYSTTEGSL YSYLEGTRFH QTAVDMAEVY TMWPKQTEAN
EQVCLYALGE SIESIRQKCP VDDADASSPP KTVPCLCRYA MTPERVTRLR MNHVTSIIVC
SSFPLPKYKI EGVQKVKCSK VMLFDHNVPS RVSPREYKSP QETAQEVSST TSLTHSQFDL
SVDGEELPAP SDLEADAPIP EPTPDDRAVL TLPPTIDNFS AVSDWVMNTA PVAPPRRRRG
KNLNVTCDER EGNVLPMASV RFFRADLHSI VQETAEIRDT AASLQAPLSV ATEPNQLPIS
FGAPNETFPI TFGDFDEGEI ESLSSELLTF GDFSPGEVDD LTDSDWSTCS DTDDELXLDR
AGGYIFSSDT GPGHLQQRSV RQTVLPVNTL EEVQEEKCYP PKLDEVKEQL LLKKLQESAS
MANRSRYQSR KVENMKATIV QRLKGGCKLY LMSETPKVPT YRTTYPAPVY SPPINIRLSN
PESAVAACNE FLARNYPTVA SYQITDEYDA YLDMVDGSES CLDRATFNPS KLRSYPKQHS
YHAPTIRSAV PSPFQNTLQN VLAAATKRNC NVTQMRELPT LDSAVFNVEC FKKFACNQEY
WKEFAASPIR ITTENLTTYV TKLKGPKAAA LFAKTHNLLP LQEVPMDRFT VDMKRDVKVT
PGTKHTEERP KVQVIQAAEP LATAYLCGIH RELVRRLNAV LLPNVHTLFD MSAEDFDAII
AAHFKPGDAV LETDIASFDK SQDDSLALTA LMLLEDLGVD HPLLDLIEAA FGEISSCHLP
TGTRFKFGAM MKSGMFLTLF VNTLLNITIA SRVLEDRLTR SACAAFIGDD NIIHGVVSDE
LMAARCATWM NMEVKIIDAV VSQKAPYFCG GFILYDTVAG TACRVADPLK RLFKLGKPLA
AGDEQDDDRR RALADEVVRW QRTGLTDELE KAVHSRYEVQ GISVVVMSMA TFASSRSNFE
KLRGPVVTLY GGPK
