POLN_EEVVP
ID POLN_EEVVP Reviewed; 2493 AA.
AC P36328; Q52QW0; Q8JJT2; Q8QKW7; Q8UYL4; Q911J8; Q91KW9;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 10-APR-2019, sequence version 2.
DT 03-AUG-2022, entry version 159.
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:0000269|PubMed:26041283};
DE EC=2.7.7.- {ECO:0000269|PubMed:26041283};
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 Venezuelan equine encephalitis virus (strain P676) (VEEV).
OC Viruses; Riboviria; Orthornavirae; Kitrinoviricota; Alsuviricetes;
OC Martellivirales; Togaviridae; Alphavirus.
OX NCBI_TaxID=36385;
OH NCBI_TaxID=9913; Bos taurus (Bovine).
OH NCBI_TaxID=9268; Didelphis marsupialis (Southern opossum).
OH NCBI_TaxID=9793; Equus asinus (Donkey) (Equus africanus asinus).
OH NCBI_TaxID=9796; Equus caballus (Horse).
OH NCBI_TaxID=9606; Homo sapiens (Human).
OH NCBI_TaxID=53535; Melanoconion.
OH NCBI_TaxID=9272; Philander opossum (Gray four-eyed opossum).
OH NCBI_TaxID=10162; Proechimys.
OH NCBI_TaxID=42415; Sigmodon hispidus (Hispid cotton rat).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=1448915; DOI=10.1016/0042-6822(92)90232-e;
RA Kinney R.M., Tsuchiya K.R., Sneider J.M., Trent D.W.;
RT "Genetic evidence that epizootic Venezuelan equine encephalitis (VEE)
RT viruses may have evolved from enzootic VEE subtype I-D virus.";
RL Virology 191:569-580(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RC STRAIN=3908, 6119, PMCHo5, and V198;
RX PubMed=8709783; DOI=10.1016/s0140-6736(96)02275-1;
RA Weaver S.C., Salas R., Rico-Hesse R., Ludwig G.V., Oberste M.S.,
RA Boshell J., Tesh R.B.;
RT "Re-emergence of epidemic Venezuelan equine encephalomyelitis in South
RT America.";
RL Lancet 348:436-440(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RC STRAIN=P676;
RX PubMed=11390583; DOI=10.1128/jvi.75.13.5823-5832.2001;
RA Brault A.C., Powers A.M., Medina G., Wang E., Kang W., Salas R.A.,
RA De Siger J., Weaver S.C.;
RT "Potential sources of the 1995 Venezuelan equine encephalitis subtype IC
RT epidemic.";
RL J. Virol. 75:5823-5832(2001).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RC STRAIN=254934, and 255010;
RX PubMed=16485478; DOI=10.3201/eid1112.050533;
RA Navarro J.C., Medina G., Vasquez C., Coffey L.L., Wang E., Suarez A.,
RA Biord H., Salas M., Weaver S.C.;
RT "Postepizootic persistence of Venezuelan equine encephalitis virus,
RT Venezuela.";
RL Emerg. Infect. Dis. 11:1907-1915(2005).
RN [5]
RP FUNCTION (MRNA-CAPPING ENZYME NSP1).
RX PubMed=26041283; DOI=10.1128/jvi.00599-15;
RA Li C., Guillen J., Rabah N., Blanjoie A., Debart F., Vasseur J.J.,
RA Canard B., Decroly E., Coutard B.;
RT "mRNA capping by venezuelan equine encephalitis virus nsp1: functional
RT characterization and implications for antiviral research.";
RL J. Virol. 89:8292-8303(2015).
RN [6] {ECO:0007744|PDB:3GQE, ECO:0007744|PDB:3GQO}
RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 1330-1489 IN COMPLEX WITH
RP ADP-RIBOSE, AND CATALYTIC ACTIVITY.
RX PubMed=19386706; DOI=10.1128/jvi.00189-09;
RA Malet H., Coutard B., Jamal S., Dutartre H., Papageorgiou N., Neuvonen M.,
RA Ahola T., Forrester N., Gould E.A., Lafitte D., Ferron F., Lescar J.,
RA Gorbalenya A.E., de Lamballerie X., Canard B.;
RT "The crystal structures of Chikungunya and Venezuelan equine encephalitis
RT virus nsP3 macro domains define a conserved adenosine binding pocket.";
RL J. Virol. 83:6534-6545(2009).
RN [7] {ECO:0007744|PDB:5ISN, ECO:0007744|PDB:5MQX}
RP STRUCTURE BY NMR OF 1330-1489.
RX PubMed=25291978; DOI=10.1007/s12104-014-9584-9;
RA Makrynitsa G.I., Ntonti D., Marousis K.D., Tsika A.C., Lichiere J.,
RA Papageorgiou N., Coutard B., Bentrop D., Spyroulias G.A.;
RT "NMR study of non-structural proteins--part II: (1)H, (13)C, (15)N backbone
RT and side-chain resonance assignment of macro domain from Venezuelan equine
RT encephalitis virus (VEEV).";
RL Biomol. NMR. Assign. 9:247-251(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 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 (PubMed:26041283). 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 (PubMed:26041283).
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:Q8JUX6,
CC ECO:0000269|PubMed:26041283, 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 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-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 (By
CC similarity). {ECO:0000250|UniProtKB:P03317,
CC ECO:0000250|UniProtKB:P27282}.
CC -!- FUNCTION: [Non-structural protein 3']: Seems to be essential for minus-
CC strand RNAs and subgenomic 26S mRNAs synthesis (By similarity).
CC Displays mono-ADP-ribosylhydrolase activity (Probable). ADP-
CC ribosylation is a post-translational modification that controls various
CC processes of the host cell and the virus probably needs to revert it
CC for optimal viral replication (Probable). Binds proteins of FXR family
CC and sequesters them into the viral RNA replication complexes thereby
CC inhibiting the formation of host stress granules on viral mRNAs
CC (Probable). The nsp3'-FXR complexes bind viral RNAs and probably
CC orchestrate the assembly of viral replication complexes, thanks to the
CC ability of FXR family members to self-assemble and bind DNA (Probable).
CC {ECO:0000250|UniProtKB:P03317, ECO:0000305}.
CC -!- FUNCTION: [RNA-directed RNA polymerase nsP4]: RNA dependent RNA
CC polymerase (By similarity). Replicates genomic and antigenomic RNA by
CC recognizing replications specific signals. The early replication
CC complex formed by the polyprotein P123 and nsP4 synthesizes minus-
CC strand RNAs (By similarity). The late replication complex composed of
CC fully processed nsP1-nsP4 is responsible for the production of genomic
CC and subgenomic plus-strand RNAs (By similarity).
CC {ECO:0000250|UniProtKB:P03317}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=GTP + S-adenosyl-L-methionine = N(7)-methyl-GTP + S-adenosyl-
CC L-homocysteine; Xref=Rhea:RHEA:46948, ChEBI:CHEBI:37565,
CC ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:87133;
CC Evidence={ECO:0000269|PubMed:26041283};
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:0000269|PubMed:26041283};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:54793;
CC Evidence={ECO:0000269|PubMed:26041283};
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:0000269|PubMed:26041283};
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:0000269|PubMed:19386706};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25030;
CC Evidence={ECO:0000269|PubMed:19386706};
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:0000269|PubMed:26041283};
CC Note=For nsP1 guanylylation. {ECO:0000269|PubMed:26041283};
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:0000269|PubMed:26041283}.
CC -!- SUBUNIT: [mRNA-capping enzyme nsP1]: Interacts with non-structural
CC protein 3 (By similarity). Interacts with RNA-directed RNA polymerase
CC nsP4 (By similarity). Interacts with protease nsP2 (By similarity).
CC interacts with itself (By similarity). {ECO:0000250|UniProtKB:P27282,
CC ECO:0000250|UniProtKB:Q8JUX6}.
CC -!- SUBUNIT: [Non-structural protein 3]: Interacts with mRNA-capping enzyme
CC nsP1 (By similarity). Interacts with host DDX1 (By similarity).
CC Interacts with host DDX3 (By similarity). Interacts (via C-terminus)
CC with host FXR1; this interaction inhibits the formation of host stress
CC granules on viral mRNAs and the nsp3-FXR1 complexes bind viral RNAs and
CC probably orchestrate the assembly of viral replication complexes (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: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:Q8JUX6}.
CC -!- SUBUNIT: [Protease nsP2]: Interacts with RNA-directed RNA polymerase
CC nsP4 (By similarity). Interacts with mRNA-capping enzyme nsP1 (By
CC similarity). Interacts with KPNA1/karyopherin-alpha1; this interaction
CC probably allows the active transport of protease nsP2 into the host
CC nucleus (By similarity). {ECO:0000250|UniProtKB:P27282,
CC ECO:0000250|UniProtKB:Q8JUX6}.
CC -!- SUBCELLULAR LOCATION: [Polyprotein P1234]: Host cytoplasmic vesicle
CC membrane {ECO:0000305}; Peripheral membrane protein {ECO:0000305}.
CC Note=Part of cytoplasmic vesicles, which are probably formed at the
CC plasma membrane and internalized leading to late endosomal/lysosomal
CC spherules containing the replication complex. {ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: [Polyprotein P123']: Host cytoplasmic vesicle
CC membrane {ECO:0000305}; Peripheral membrane protein {ECO:0000305}.
CC Note=Part of cytoplasmic vesicles, which are probably formed at the
CC plasma membrane and internalized leading to late endosomal/lysosomal
CC spherules containing the replication complex. {ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: [Polyprotein P123]: Host cytoplasmic vesicle
CC membrane {ECO:0000305}; Peripheral membrane protein {ECO:0000305}.
CC Note=Part of cytoplasmic vesicles, which are probably formed at the
CC plasma membrane and internalized leading to late endosomal/lysosomal
CC spherules containing the replication complex. {ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: [mRNA-capping enzyme nsP1]: Host cytoplasmic
CC vesicle membrane {ECO:0000250|UniProtKB:P08411}; Lipid-anchor
CC {ECO:0000250|UniProtKB:P08411}. Host cell membrane
CC {ECO:0000250|UniProtKB:P08411}; Lipid-anchor
CC {ECO:0000250|UniProtKB:P08411}; Cytoplasmic side
CC {ECO:0000250|UniProtKB:P08411}. Host cell projection, host filopodium
CC {ECO:0000250|UniProtKB:P08411}. Note=In the late phase of infection,
CC the polyprotein is quickly cleaved before localization to cellular
CC membranes. Then a fraction of nsP1 localizes to the inner surface of
CC the plasma membrane and its filopodial extensions. Only the
CC palmitoylated nsP1 localizes to the host filopodia (By similarity).
CC NsP1 is also part of cytoplasmic vesicles, which are probably formed at
CC the plasma membrane and internalized leading to late
CC endosomal/lysosomal spherules containing the replication complex (By
CC similarity). {ECO:0000250|UniProtKB:P08411}.
CC -!- SUBCELLULAR LOCATION: [Protease nsP2]: Host cytoplasmic vesicle
CC membrane {ECO:0000250|UniProtKB:P08411}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:P08411}. Host nucleus
CC {ECO:0000250|UniProtKB:P27282}. Host cytoplasm
CC {ECO:0000250|UniProtKB:P27282}. Note=In the late phase of infection,
CC the polyprotein is quickly cleaved before localization to cellular
CC membranes. Then approximately half of nsP2 is found in the nucleus (By
CC similarity). Shuttles between cytoplasm and nucleus (By similarity).
CC NsP2 is also part of cytoplasmic vesicles, which are probably formed at
CC the plasma membrane and internalized leading to late
CC endosomal/lysosomal spherules containing the replication complex (By
CC similarity). {ECO:0000250|UniProtKB:P08411,
CC ECO:0000250|UniProtKB:P27282}.
CC -!- SUBCELLULAR LOCATION: [Non-structural protein 3]: Host cytoplasmic
CC vesicle membrane {ECO:0000250|UniProtKB:P03317}; Peripheral membrane
CC protein {ECO:0000305}. Note=In the late phase of infection, the
CC polyprotein is quickly cleaved before localization to cellular
CC membranes. Then nsP3 and nsP3' form aggregates in cytoplasm (By
CC similarity). NsP3 is also part of cytoplasmic vesicles, which are
CC probably formed at the plasma membrane and internalized leading to late
CC endosomal/lysosomal spherules containing the replication complex (By
CC similarity). {ECO:0000250|UniProtKB:P03317}.
CC -!- SUBCELLULAR LOCATION: [Non-structural protein 3']: Host cytoplasmic
CC vesicle membrane {ECO:0000305}; Peripheral membrane protein
CC {ECO:0000305}. Note=In the late phase of infection, the polyprotein is
CC quickly cleaved before localization to cellular membranes. Then nsP3
CC and nsP3' form aggregates in cytoplasm (By similarity). NsP3' is also
CC part of cytoplasmic vesicles, which are probably formed at the plasma
CC membrane and internalized leading to late endosomal/lysosomal spherules
CC containing the replication complex (Probable).
CC {ECO:0000250|UniProtKB:P03317, ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: [RNA-directed RNA polymerase nsP4]: Host
CC cytoplasmic vesicle membrane; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:P08411}. Note=NsP4 is part of cytoplasmic
CC vesicles, which are probably formed at the plasma membrane and
CC internalized leading to late endosomal/lysosomal spherules containing
CC the replication complex. {ECO:0000250|UniProtKB:P08411}.
CC -!- DOMAIN: [Protease nsP2]: The N-terminus exhibits NTPase and RNA
CC triphosphatase activities and is proposed to have helicase activity,
CC whereas the C-terminus possesses protease activity (By similarity).
CC Contains a nuclear localization signal and a nuclear export signal,
CC these two motifs are probably involved in the shuttling between the
CC cytoplasm and the nucleus of nsP2 (By similarity).
CC {ECO:0000250|UniProtKB:P27282, ECO:0000250|UniProtKB:Q8JUX6}.
CC -!- DOMAIN: [Non-structural protein 3']: In the N-terminus, the macro
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 approximate repeats necessary and sufficient for
CC formation of the nsP3'/FXR complex (By similarity).
CC {ECO:0000250|UniProtKB:P03317, ECO:0000250|UniProtKB:P27282}.
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 approximate repeats necessary and sufficient for
CC formation of the nsP3/FXR complex (By similarity).
CC {ECO:0000250|UniProtKB:P03317, ECO:0000250|UniProtKB:P27282}.
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: [Polyprotein P1234]: The genome codes for P123, but
CC readthrough of a terminator codon UGA occurs between the codons for
CC Gln-1879 and Arg-1881 giving rise to P1234 (By similarity). P1234 is
CC cleaved quickly by nsP2 into P123' and nsP4 (By similarity). Further
CC processing of p123' gives nsP1, nsP2 and nsP3' which is 6 amino acids
CC longer than nsP3 since the cleavage site is after the readthrough (By
CC similarity). This unusual molecular mechanism ensures that few nsP4 are
CC produced compared to other non-structural proteins (By similarity).
CC Mutant viruses with no alternative termination site grow significantly
CC slower than wild-type virus (By similarity). The opal termination codon
CC is frequently mutated to a sense codon on passage in cell culture (By
CC similarity). The presence of the opal codon may be a requirement for
CC viral maintenance in both vertebrate and invertebrate hosts and a
CC selective advantage may be conferred in cell culture for the sense
CC codon (By similarity). {ECO:0000250|UniProtKB:O90368,
CC ECO:0000250|UniProtKB:P03317}.
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DR EMBL; L04653; AAC19318.1; ALT_SEQ; Genomic_RNA.
DR EMBL; L04653; AAC19320.1; -; Genomic_RNA.
DR EMBL; U55347; AAM28637.1; -; Genomic_RNA.
DR EMBL; AF375051; AAK66989.1; -; Genomic_RNA.
DR EMBL; U55350; AAM28638.1; -; Genomic_RNA.
DR EMBL; AY986475; AAY16369.1; -; Genomic_RNA.
DR EMBL; AY973944; AAY16003.1; -; Genomic_RNA.
DR EMBL; U55345; AAM28636.1; -; Genomic_RNA.
DR EMBL; U55342; AAL61965.1; -; Genomic_RNA.
DR PIR; A44213; A44213.
DR RefSeq; NP_040822.1; NC_001449.1.
DR RefSeq; NP_040823.1; NC_001449.1.
DR PDB; 3GQE; X-ray; 2.30 A; A/B=1330-1489.
DR PDB; 3GQO; X-ray; 2.60 A; A/B/C/D=1330-1489.
DR PDB; 5ISN; NMR; -; A=1330-1489.
DR PDB; 5MQX; NMR; -; A=1330-1489.
DR PDBsum; 3GQE; -.
DR PDBsum; 3GQO; -.
DR PDBsum; 5ISN; -.
DR PDBsum; 5MQX; -.
DR SMR; P36328; -.
DR MEROPS; C09.002; -.
DR PRIDE; P36328; -.
DR GeneID; 2652923; -.
DR GeneID; 2652925; -.
DR KEGG; vg:2652923; -.
DR EvolutionaryTrace; P36328; -.
DR Proteomes; UP000008658; Genome.
DR Proteomes; UP000110878; Genome.
DR Proteomes; UP000125491; Genome.
DR Proteomes; UP000143596; Genome.
DR Proteomes; UP000166022; Genome.
DR Proteomes; UP000171441; Genome.
DR Proteomes; UP000173580; Genome.
DR Proteomes; UP000180662; 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; Repeat;
KW RNA suppression of termination; RNA-binding; RNA-directed RNA polymerase;
KW S-adenosyl-L-methionine; Thiol protease; Transferase; Ubl conjugation;
KW Viral RNA replication; Zinc.
FT CHAIN 1..2492
FT /note="Polyprotein P1234"
FT /id="PRO_0000308390"
FT CHAIN 1..1886
FT /note="Polyprotein P123'"
FT /id="PRO_0000228767"
FT CHAIN 1..1879
FT /note="Polyprotein P123"
FT /id="PRO_0000228768"
FT CHAIN 1..535
FT /note="mRNA-capping enzyme nsP1"
FT /id="PRO_0000041204"
FT CHAIN 536..1329
FT /note="Protease nsP2"
FT /id="PRO_0000041205"
FT CHAIN 1330..1886
FT /note="Non-structural protein 3'"
FT /id="PRO_0000228769"
FT CHAIN 1330..1879
FT /note="Non-structural protein 3"
FT /id="PRO_0000041206"
FT CHAIN 1887..2493
FT /note="RNA-directed RNA polymerase nsP4"
FT /id="PRO_0000041207"
FT DOMAIN 28..259
FT /note="Alphavirus-like MT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01079"
FT DOMAIN 690..841
FT /note="(+)RNA virus helicase ATP-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00990"
FT DOMAIN 842..990
FT /note="(+)RNA virus helicase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00990"
FT DOMAIN 1003..1322
FT /note="Peptidase C9"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00853"
FT DOMAIN 1330..1489
FT /note="Macro"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00490,
FT ECO:0000269|PubMed:25291978"
FT REPEAT 1818..1839
FT /note="1"
FT /evidence="ECO:0000250|UniProtKB:P27282"
FT REPEAT 1852..1873
FT /note="2"
FT /evidence="ECO:0000250|UniProtKB:P27282"
FT DOMAIN 2250..2365
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 1004..1023
FT /note="Nucleolus localization signal"
FT /evidence="ECO:0000250|UniProtKB:P08411"
FT REGION 1660..1684
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1790..1826
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1818..1873
FT /note="2 X 21 AA approximate repeats, binding to host FXR
FT family members"
FT /evidence="ECO:0000250|UniProtKB:P27282"
FT MOTIF 1056..1065
FT /note="Nuclear export signal"
FT /evidence="ECO:0000250|UniProtKB:P27282"
FT MOTIF 1179..1183
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000250|UniProtKB:P27282"
FT COMPBIAS 1669..1684
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1792..1806
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1810..1826
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 1012
FT /note="For cysteine protease nsP2 activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00853"
FT ACT_SITE 1081
FT /note="For cysteine protease nsP2 activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00853"
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 1339
FT /ligand="ADP-D-ribose"
FT /ligand_id="ChEBI:CHEBI:57967"
FT /evidence="ECO:0000269|PubMed:19386706"
FT BINDING 1353
FT /ligand="ADP-D-ribose"
FT /ligand_id="ChEBI:CHEBI:57967"
FT /evidence="ECO:0000250|UniProtKB:Q8JUX6"
FT BINDING 1361
FT /ligand="ADP-D-ribose"
FT /ligand_id="ChEBI:CHEBI:57967"
FT /evidence="ECO:0000250|UniProtKB:Q8JUX6"
FT BINDING 1441
FT /ligand="ADP-D-ribose"
FT /ligand_id="ChEBI:CHEBI:57967"
FT /evidence="ECO:0000269|PubMed:19386706"
FT BINDING 1442
FT /ligand="ADP-D-ribose"
FT /ligand_id="ChEBI:CHEBI:57967"
FT /evidence="ECO:0000269|PubMed:19386706"
FT BINDING 1443
FT /ligand="ADP-D-ribose"
FT /ligand_id="ChEBI:CHEBI:57967"
FT /evidence="ECO:0000269|PubMed:19386706"
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 535..536
FT /note="Cleavage; by protease nsP2"
FT /evidence="ECO:0000250|UniProtKB:P03317"
FT SITE 1329..1330
FT /note="Cleavage; by protease nsP2"
FT /evidence="ECO:0000250|UniProtKB:P03317"
FT SITE 1886..1887
FT /note="Cleavage; by protease nsP2"
FT /evidence="ECO:0000250|UniProtKB:Q8JUX6"
FT LIPID 419
FT /note="S-palmitoyl cysteine; by host"
FT /evidence="ECO:0000250|UniProtKB:Q8JUX6"
FT VARIANT 875
FT /note="V -> E (in strain: 3908, 6119, 254934, PMCHo5 and
FT V198)"
FT VARIANT 968
FT /note="I -> T (in strain: 3908, 6119, 254934, PMCHo5 and
FT V198)"
FT VARIANT 1390..1391
FT /note="AA -> VT (in strain: 3908, 6119, 254934, PMCHo5 and
FT V198)"
FT VARIANT 1767..1769
FT /note="GAV -> EAA (in strain: PMCHo5 and V198)"
FT VARIANT 1767
FT /note="G -> E (in strain: 3908, 6119 and 254934)"
FT VARIANT 1809
FT /note="P -> S (in strain: V198)"
FT VARIANT 2094
FT /note="V -> I (in strain: 254934)"
FT VARIANT 2207
FT /note="D -> Y (in strain: 3908, 6119, 254934, PMCHo5 and
FT V198)"
FT VARIANT 2423
FT /note="V -> A (in strain: V198)"
FT STRAND 1332..1338
FT /evidence="ECO:0007829|PDB:3GQE"
FT HELIX 1340..1342
FT /evidence="ECO:0007829|PDB:3GQE"
FT STRAND 1345..1352
FT /evidence="ECO:0007829|PDB:3GQE"
FT HELIX 1353..1355
FT /evidence="ECO:0007829|PDB:5ISN"
FT HELIX 1361..1363
FT /evidence="ECO:0007829|PDB:3GQE"
FT HELIX 1365..1369
FT /evidence="ECO:0007829|PDB:3GQE"
FT HELIX 1371..1373
FT /evidence="ECO:0007829|PDB:3GQE"
FT STRAND 1384..1387
FT /evidence="ECO:0007829|PDB:3GQE"
FT STRAND 1394..1398
FT /evidence="ECO:0007829|PDB:3GQE"
FT TURN 1402..1404
FT /evidence="ECO:0007829|PDB:3GQE"
FT HELIX 1407..1427
FT /evidence="ECO:0007829|PDB:3GQE"
FT STRAND 1431..1436
FT /evidence="ECO:0007829|PDB:3GQE"
FT STRAND 1439..1441
FT /evidence="ECO:0007829|PDB:5ISN"
FT TURN 1442..1444
FT /evidence="ECO:0007829|PDB:5ISN"
FT STRAND 1445..1447
FT /evidence="ECO:0007829|PDB:5ISN"
FT HELIX 1450..1461
FT /evidence="ECO:0007829|PDB:3GQE"
FT STRAND 1467..1473
FT /evidence="ECO:0007829|PDB:3GQE"
FT HELIX 1475..1487
FT /evidence="ECO:0007829|PDB:3GQE"
SQ SEQUENCE 2493 AA; 277950 MW; 0B7E85A996197E63 CRC64;
MEKVHVDIEE DSPFLRALQR SFPQFEVEAK QVTDNDHANA RAFSHLASKL IETEVDPSDT
ILDIGSAPAR RMYSKHKYHC ICPMRCAEDP DRLYKYATKL KKNCKEITDK ELDKKMKELA
AVMSDPDLET ETMCLHDDES CRYEGQVAVY QDVYAVDGPT SLYHQANKGV RVAYWIGFDT
TPFMFKNLAG AYPSYSTNWA DETVLTARNI GLCSSDVMER SRRGMSILRK KYLKPSNNVL
FSVGSTIYHE KRDLLRSWHL PSVFHLRGKQ NYTCRCETIV SCDGYVVKRI AISPGLYGKP
SGYAATMHRE GFLCCKVTDT LNGERVSFPV CTYVPATLCD QMTGILATDV SADDAQKLLV
GLNQRIVVNG RTQRNTNTMK NYLLPVVAQA FARWAKEYKE DQEDERPLGL RDRQLVMGCC
WAFRRHKITS IYKRPDTQTI IKVNSDFHSF VLPRIGSNTL EIGLRTRIRK MLEEHKEPSP
LITAEDIQEA KCAADEAKEV REAEELRAAL PPLAADFEEP TLEADVDLML QEAGAGSVET
PRGLIKVTSY AGEDKIGSYA VLSPQAVLKS EKLSCIHPLA EQVIVITHSG RKGRYAVEPY
HGKVVVPEGH AIPVQDFQAL SESATIVYNE REFVNRYLHH IATHGGALNT DEEYYKTVKP
SEHDGEYLYD IDRKQCVKKE LVTGLGLTGE LVDPPFHEFA YESLRTRPAA PYQVPTIGVY
GVPGSGKSGI IKSAVTKKDL VVSAKKENCA EIIRDVKKMK GLDVNARTVD SVLLNGCKHP
VETLYIDEAF ACHAGTLRAL IAIIRPKKAV LCGDPKQCGF FNMMCLKVHF NHEICTQVFH
KSISRRCTKS VTSVVSTLFY DKRMRTTNPK ETKIVIDTTG STKPKQDDLI LTCFRGWVKQ
LQIDYKGNEI MTAAASQGLT RKGVYAVRYK VNENPLYAPT SEHVNVLLTR TEDRIVWKTL
AGDPWIKILT AKYPGNFTAT IEEWQAEHDA IMRHILERPD PTDVFQNKAN VCWAKALVPV
LKTAGIDMTT EQWNTVDYFE TDKAHSAEIV LNQLCVRFFG LDLDSGLFSA PTVPLSIRNN
HWDNSPSPNM YGLNKEVVRQ LSRRYPQLPR AVATGRVYDM NTGTLRNYDP RINLVPVNRR
LPHALVLHHN EHPQSDFSSF VSKLKGRTVL VVGEKLSVPG KKVDWLSDQP EATFRARLDL
GIPGDVPKYD IVFINVRTPY KYHHYQQCED HAIKLSMLTK KACLHLNPGG TCVSIGYGYA
DRASESIIGA IARQFKFSRV CKPKSSHEET EVLFVFIGYD RKARTHNPYK LSSTLTNIYT
GSRLHEAGCA PSYHVVRGDI ATATEGVIIN AANSKGQPGG GVCGALYKKF PESFDLQPIE
VGKARLVKGA AKHIIHAVGP NFNKVSEVEG DKQLAEAYES IAKIVNDNNY KSVAIPLLST
GIFSGNKDRL TQSLNHLLTA LDTTDADVAI YCRDKKWEMT LKEAVARREA VEEICISDDS
SVTEPDAELV RVHPKSSLAG RKGYSTSDGK TFSYLEGTKF HQAAKDIAEI NAMWPVATEA
NEQVCMYILG ESMSSIRSKC PVEESEASTP PSTLPCLCIH AMTPERVQRL KASRPEQITV
CSSFPLPKYR ITGVQKIQCS QPILFSPKVP AYIHPRKYLV ETPPVEETPE SPAENQSTEG
TPEQPALVNV DATRTRMPEP IIIEEEEEDS ISLLSDGPTH QVLQVEADIH GSPSVSSSSW
SIPHASDFDV DSLSILDTLD GASVTSGAVS AETNSYFARS MEFRARPVPA PRTVFRNPPH
PAPRTRTPPL AHSRASSRTS LVSTPPGVNR VITREELEAL TPSRAPSRSA SRTSLVSNPP
GVNRVITREE FEAFVAQQQX RFDAGAYIFS SDTGQGHLQQ KSVRQTVLSE VVLERTELEI
SYAPRLDQEK EELLRKKLQL NPTPANRSRY QSRRVENMKA ITARRILQGL GHYLKAEGKV
ECYRTLHPVP LYSSSVNRAF SSPKVAVEAC NAMLKENFPT VASYCIIPEY DAYLDMVDGA
SCCLDTASFC PAKLRSFPKK HSYLEPTIRS AVPSAIQNTL QNVLAAATKR NCNVTQMREL
PVLDSAAFNV ECFKKYACNN EYWETFKENP IRLTEENVVN YITKLKGPKA AALFAKTHNL
NMLQDIPMDR FVMDLKRDVK VTPGTKHTEE RPKVQVIQAA DPLATADLCG IHRELVRRLN
AVLLPNIHTL FDMSAEDFDA IIAEHFQPGD CVLETDIASF DKSEDDAMAL TALMILEDLG
VDAELLTLIE AAFGEISSIH LPTKTKFKFG AMMKSGMFLT LFVNTVINIV IASRVLRERL
TGSPCAAFIG DDNIVKGVKS DKLMADRCAT WLNMEVKIID AVVGEKAPYF CGGFILCDSV
TGTACRVADP LKRLFKLGKP LAVDDEHDDD RRRALHEEST RWNRVGILPE LCKAVESRYE
TVGTSIIVMA MTTLASSVKS FSYLRGAPIT LYG
