L_HRSVA
ID L_HRSVA Reviewed; 2165 AA.
AC P28887; O41355; O41356; P90197; Q82021;
DT 01-DEC-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-1992, sequence version 1.
DT 03-AUG-2022, entry version 120.
DE RecName: Full=RNA-directed RNA polymerase L;
DE Short=Protein L;
DE AltName: Full=Large structural protein;
DE AltName: Full=Replicase;
DE AltName: Full=Transcriptase;
DE Includes:
DE RecName: Full=RNA-directed RNA polymerase;
DE EC=2.7.7.48 {ECO:0000269|PubMed:25010481, ECO:0000269|PubMed:31953395};
DE Includes:
DE RecName: Full=GTP phosphohydrolase {ECO:0000303|PubMed:28104450};
DE EC=3.6.1.- {ECO:0000303|PubMed:28104450};
DE Includes:
DE RecName: Full=GDP polyribonucleotidyltransferase {ECO:0000305};
DE EC=2.7.7.88 {ECO:0000269|PubMed:16189012, ECO:0000303|PubMed:28104450};
DE AltName: Full=PRNTase {ECO:0000305};
DE Includes:
DE RecName: Full=mRNA cap methyltransferase {ECO:0000305};
DE EC=2.1.1.375 {ECO:0000250|UniProtKB:P03523};
DE AltName: Full=mRNA (guanine-N(7)-)-methyltransferase {ECO:0000250|UniProtKB:P03523};
DE Short=G-N7-MTase {ECO:0000250|UniProtKB:P03523};
DE AltName: Full=mRNA (nucleoside-2'-O-)-methyltransferase {ECO:0000250|UniProtKB:P03523};
DE Short=N1-2'-O-MTase {ECO:0000250|UniProtKB:P03523};
GN Name=L;
OS Human respiratory syncytial virus A (strain A2).
OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Haploviricotina;
OC Monjiviricetes; Mononegavirales; Pneumoviridae; Orthopneumovirus.
OX NCBI_TaxID=11259;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=2053282; DOI=10.1016/0042-6822(91)90140-7;
RA Stec D.S., Hill M.G. III, Collins P.L.;
RT "Sequence analysis of the polymerase L gene of human respiratory syncytial
RT virus and predicted phylogeny of nonsegmented negative-strand viruses.";
RL Virology 183:273-287(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=7884888; DOI=10.1128/jvi.69.4.2412-2419.1995;
RA Yu Q., Hardy R.W., Wertz G.W.;
RT "Functional cDNA clones of the human respiratory syncytial (RS) virus N, P,
RT and L proteins support replication of RS virus genomic RNA analogs and
RT define minimal trans-acting requirements for RNA replication.";
RL J. Virol. 69:2412-2419(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RC STRAIN=Cold-passage attenuated;
RX PubMed=7747420; DOI=10.1006/viro.1995.1178;
RA Connors M., Crowe J.E. Jr., Firestone C.Y., Murphy B.R., Collins P.L.;
RT "A cold-passaged, attenuated strain of human respiratory syncytial virus
RT contains mutations in the F and L genes.";
RL Virology 208:478-484(1995).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RC STRAIN=Cold-passage attenuated;
RX PubMed=9035372; DOI=10.1007/bf00366988;
RA Crowe J.E. Jr., Firestone C.Y., Whitehead S.S., Collins P.L., Murphy B.R.;
RT "Acquisition of the ts phenotype by a chemically mutagenized cold-passaged
RT human respiratory syncytial virus vaccine candidate results from the
RT acquisition of a single mutation in the polymerase (L) gene.";
RL Virus Genes 13:269-273(1996).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RC STRAIN=Cold-passage attenuated;
RX PubMed=8918930; DOI=10.1006/viro.1996.0618;
RA Firestone C.Y., Whitehead S.S., Collins P.L., Murphy B.R., Crowe J.E. Jr.;
RT "Nucleotide sequence analysis of the respiratory syncytial virus subgroup A
RT cold-passaged (cp) temperature sensitive (ts) cpts-248/404 live attenuated
RT virus vaccine candidate.";
RL Virology 225:419-422(1996).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RC STRAIN=Cold-passage attenuated;
RX PubMed=9557743; DOI=10.1128/jvi.72.5.4467-4471.1998;
RA Whitehead S.S., Juhasz K., Firestone C.Y., Collins P.L., Murphy B.R.;
RT "Recombinant respiratory syncytial virus (RSV) bearing a set of mutations
RT from cold-passaged RSV is attenuated in chimpanzees.";
RL J. Virol. 72:4467-4471(1998).
RN [7]
RP FUNCTION.
RX PubMed=1404620; DOI=10.1128/jvi.66.11.6813-6818.1992;
RA Barik S.;
RT "Transcription of human respiratory syncytial virus genome RNA in vitro:
RT requirement of cellular factor(s).";
RL J. Virol. 66:6813-6818(1992).
RN [8]
RP FUNCTION.
RX PubMed=8445369; DOI=10.1099/0022-1317-74-3-485;
RA Barik S.;
RT "The structure of the 5' terminal cap of the respiratory syncytial virus
RT mRNA.";
RL J. Gen. Virol. 74:485-490(1993).
RN [9]
RP FUNCTION.
RX PubMed=8552680; DOI=10.1073/pnas.93.1.81;
RA Collins P.L., Hill M.G., Cristina J., Grosfeld H.;
RT "Transcription elongation factor of respiratory syncytial virus, a
RT nonsegmented negative-strand RNA virus.";
RL Proc. Natl. Acad. Sci. U.S.A. 93:81-85(1996).
RN [10]
RP FUNCTION.
RX PubMed=8794332; DOI=10.1128/jvi.70.10.6892-6901.1996;
RA Kuo L., Grosfeld H., Cristina J., Hill M.G., Collins P.L.;
RT "Effects of mutations in the gene-start and gene-end sequence motifs on
RT transcription of monocistronic and dicistronic minigenomes of respiratory
RT syncytial virus.";
RL J. Virol. 70:6892-6901(1996).
RN [11]
RP CATALYTIC ACTIVITY, AND FUNCTION.
RX PubMed=16189012; DOI=10.1128/jvi.79.20.13105-13115.2005;
RA Liuzzi M., Mason S.W., Cartier M., Lawetz C., McCollum R.S., Dansereau N.,
RA Bolger G., Lapeyre N., Gaudette Y., Lagace L., Massariol M.J., Do F.,
RA Whitehead P., Lamarre L., Scouten E., Bordeleau J., Landry S., Rancourt J.,
RA Fazal G., Simoneau B.;
RT "Inhibitors of respiratory syncytial virus replication target
RT cotranscriptional mRNA guanylylation by viral RNA-dependent RNA
RT polymerase.";
RL J. Virol. 79:13105-13115(2005).
RN [12]
RP FUNCTION.
RX PubMed=15681446; DOI=10.1128/jvi.79.4.2449-2460.2005;
RA McGivern D.R., Collins P.L., Fearns R.;
RT "Identification of internal sequences in the 3' leader region of human
RT respiratory syncytial virus that enhance transcription and confer
RT replication processivity.";
RL J. Virol. 79:2449-2460(2005).
RN [13]
RP REVIEW.
RX PubMed=16760383; DOI=10.1099/vir.0.81786-0;
RA Cowton V.M., McGivern D.R., Fearns R.;
RT "Unravelling the complexities of respiratory syncytial virus RNA
RT synthesis.";
RL J. Gen. Virol. 87:1805-1821(2006).
RN [14]
RP SUBCELLULAR LOCATION.
RX PubMed=17703289; DOI=10.1007/s00705-007-1048-4;
RA Carromeu C., Simabuco F.M., Tamura R.E., Farinha Arcieri L.E.,
RA Ventura A.M.;
RT "Intracellular localization of human respiratory syncytial virus L
RT protein.";
RL Arch. Virol. 152:2259-2263(2007).
RN [15]
RP CATALYTIC ACTIVITY, COFACTOR, MUTAGENESIS OF ASN-812, AND FUNCTION.
RX PubMed=25010481; DOI=10.1016/j.virol.2014.05.032;
RA Noton S.L., Aljabr W., Hiscox J.A., Matthews D.A., Fearns R.;
RT "Factors affecting de novo RNA synthesis and back-priming by the
RT respiratory syncytial virus polymerase.";
RL Virology 462:318-327(2014).
RN [16]
RP INTERACTION WITH THE PHOSHOPROTEIN.
RX PubMed=25653447; DOI=10.1128/jvi.03619-14;
RA Sourimant J., Rameix-Welti M.A., Gaillard A.L., Chevret D., Galloux M.,
RA Gault E., Eleouet J.F.;
RT "Fine mapping and characterization of the L-polymerase-binding domain of
RT the respiratory syncytial virus phosphoprotein.";
RL J. Virol. 89:4421-4433(2015).
RN [17]
RP REVIEW.
RX PubMed=28104450; DOI=10.1016/j.virusres.2017.01.008;
RA Fearns R., Plemper R.K.;
RT "Polymerases of paramyxoviruses and pneumoviruses.";
RL Virus Res. 234:87-102(2017).
RN [18]
RP FUNCTION.
RX PubMed=29873775; DOI=10.1093/nar/gky480;
RA Cressey T.N., Noton S.L., Nagendra K., Braun M.R., Fearns R.;
RT "Mechanism for de novo initiation at two sites in the respiratory syncytial
RT virus promoter.";
RL Nucleic Acids Res. 46:6785-6796(2018).
RN [19]
RP MUTAGENESIS OF PRO-1261; TRP-1262; PRO-1274 AND TYR-1276.
RX PubMed=31698413; DOI=10.1038/s41586-019-1759-1;
RA Pan J., Qian X., Lattmann S., El Sahili A., Yeo T.H., Jia H., Cressey T.,
RA Ludeke B., Noton S., Kalocsay M., Fearns R., Lescar J.;
RT "Structure of the human metapneumovirus polymerase phosphoprotein
RT complex.";
RL Nature 577:275-279(2020).
RN [20]
RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF ARG-1820; GLY-1855;
RP ASP-1936; GLU-1938; SER-1998 AND GLU-2004.
RX PubMed=33956914; DOI=10.1371/journal.ppat.1009562;
RA Sutto-Ortiz P., Tcherniuk S., Ysebaert N., Abeywickrema P., Noel M.,
RA Decombe A., Debart F., Vasseur J.J., Canard B., Roymans D., Rigaux P.,
RA Eleouet J.F., Decroly E.;
RT "The methyltransferase domain of the Respiratory Syncytial Virus L protein
RT catalyzes cap N7 and 2'-O-methylation.";
RL PLoS Pathog. 17:e1009562-e1009562(2021).
RN [21] {ECO:0007744|PDB:6PZK}
RP STRUCTURE BY ELECTRON MICROSCOPY (3.20 ANGSTROMS), INTERACTION WITH THE
RP PHOSHOPROTEIN, CATALYTIC ACTIVITY, FUNCTION, AND DOMAIN.
RX PubMed=31495574; DOI=10.1016/j.cell.2019.08.014;
RA Gilman M.S.A., Liu C., Fung A., Behera I., Jordan P., Rigaux P.,
RA Ysebaert N., Tcherniuk S., Sourimant J., Eleouet J.F., Sutto-Ortiz P.,
RA Decroly E., Roymans D., Jin Z., McLellan J.S.;
RT "Structure of the Respiratory Syncytial Virus Polymerase Complex.";
RL Cell 179:193-204.e14(2019).
RN [22] {ECO:0007744|PDB:6UEN}
RP STRUCTURE BY ELECTRON MICROSCOPY (3.67 ANGSTROMS) OF 1-1500, INTERACTION
RP WITH THE PHOSHOPROTEIN, MUTAGENESIS OF ASP-811, AND CATALYTIC ACTIVITY.
RX PubMed=31953395; DOI=10.1038/s41467-019-14246-3;
RA Cao D., Gao Y., Roesler C., Rice S., D'Cunha P., Zhuang L., Slack J.,
RA Domke M., Antonova A., Romanelli S., Keating S., Forero G., Juneja P.,
RA Liang B.;
RT "Cryo-EM structure of the respiratory syncytial virus RNA polymerase.";
RL Nat. Commun. 11:368-368(2020).
CC -!- FUNCTION: Responsible for RNA synthesis (replicase and transcriptase),
CC cap addition, and cap methylation (PubMed:25010481, PubMed:31495574).
CC Performs also the polyadenylation of subgenomic mRNAs by a stuttering
CC mechanism at a slipery stop site present at the end of viral genes
CC (PubMed:8794332). The template is composed of the viral RNA tightly
CC encapsidated by the nucleoprotein (N) (Probable). The viral polymerase
CC binds to the genomic RNA at two differents sites in the 3' leader
CC promoter thereby initiating either genome replication or mRNA
CC transcription (PubMed:29873775). In the transcription mode, the
CC polymerase performs the sequential transcription of all mRNAs using a
CC termination-reinitiation mechanism responding to gene start and gene
CC end signals (PubMed:8794332). Some polymerase disengage from the
CC template at each gene junction, resulting in a decreasing abundance of
CC transcripts from the 3' to the 5' end of the genome (Probable). The
CC first gene is the most transcribed, and the last the least transcribed
CC (Probable). Needs as cofactors the phosphoprotein for processivity and
CC the M2-1 anti-termination protein (PubMed:8552680, PubMed:31495574).
CC Polyribonucleotidyl transferase (PRNTase) adds the cap structure when
CC the nascent RNA chain length has reached few nucleotides
CC (PubMed:16189012, PubMed:8445369). Ribose 2'-O methylation of viral
CC mRNA cap precedes and facilitates subsequent guanine-N-7 methylation
CC (PubMed:33956914). In the replication mode, the polymerase replicates
CC the whole viral genome without recognizing the gene end transcriptional
CC signals (PubMed:15681446). The ability of the polymerase to override
CC the gene end signals as it is producing the antigenome is probably due
CC to replicative RNA becoming encapsidated with nucleoprotein as it is
CC synthesized (PubMed:15681446). {ECO:0000250|UniProtKB:P03523,
CC ECO:0000269|PubMed:15681446, ECO:0000269|PubMed:16189012,
CC ECO:0000269|PubMed:25010481, ECO:0000269|PubMed:29873775,
CC ECO:0000269|PubMed:31495574, ECO:0000269|PubMed:8445369,
CC ECO:0000269|PubMed:8552680, ECO:0000269|PubMed:8794332, ECO:0000305,
CC ECO:0000305|PubMed:1404620}.
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 ECO:0000269|PubMed:25010481};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=GTP + H2O = GDP + H(+) + phosphate; Xref=Rhea:RHEA:19669,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:37565,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:58189;
CC Evidence={ECO:0000303|PubMed:28104450};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 5'-end triphospho-adenylyl-adenylyl-cytidylyl-adenosine in
CC mRNA + GDP + H(+) = a 5'-end (5'-triphosphoguanosine)-adenylyl-
CC adenylyl-cytidylyl-adenosine in mRNA + diphosphate;
CC Xref=Rhea:RHEA:65436, Rhea:RHEA-COMP:16797, Rhea:RHEA-COMP:16799,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:33019, ChEBI:CHEBI:58189,
CC ChEBI:CHEBI:156484, ChEBI:CHEBI:156503; EC=2.7.7.88;
CC Evidence={ECO:0000269|PubMed:16189012};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 5'-end (5'-triphosphoguanosine)-adenylyl-adenylyl-cytidylyl-
CC adenosine in mRNA + 2 S-adenosyl-L-methionine = a 5'-end (N(7)-methyl
CC 5'-triphosphoguanosine)-(2'-O-methyladenylyl)-adenylyl-cytidylyl-
CC adenosine in mRNA + H(+) + 2 S-adenosyl-L-homocysteine;
CC Xref=Rhea:RHEA:65376, Rhea:RHEA-COMP:16797, Rhea:RHEA-COMP:16798,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789,
CC ChEBI:CHEBI:156483, ChEBI:CHEBI:156484; EC=2.1.1.375;
CC Evidence={ECO:0000269|PubMed:31495574, ECO:0000269|PubMed:33956914};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 5'-end (5'-triphosphoguanosine)-adenylyl-adenylyl-cytidylyl-
CC adenosine in mRNA + S-adenosyl-L-methionine = a 5'-end (5'-
CC triphosphoguanosine)-(2'-O-methyladenylyl)-adenylyl-cytidylyl-
CC adenosine in mRNA + H(+) + S-adenosyl-L-homocysteine;
CC Xref=Rhea:RHEA:65380, Rhea:RHEA-COMP:16797, Rhea:RHEA-COMP:16801,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789,
CC ChEBI:CHEBI:156482, ChEBI:CHEBI:156484;
CC Evidence={ECO:0000269|PubMed:33956914};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 5'-end (5'-triphosphoguanosine)-(2'-O-methyladenylyl)-
CC adenylyl-cytidylyl-adenosine in mRNA + S-adenosyl-L-methionine = a
CC 5'-end (N(7)-methyl 5'-triphosphoguanosine)-(2'-O-methyladenylyl)-
CC adenylyl-cytidylyl-adenosine in mRNA + S-adenosyl-L-homocysteine;
CC Xref=Rhea:RHEA:65440, Rhea:RHEA-COMP:16798, Rhea:RHEA-COMP:16801,
CC ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:156482,
CC ChEBI:CHEBI:156483; Evidence={ECO:0000269|PubMed:33956914};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:25010481};
CC Note=For RNA-directed RNA polymerase activity. Mn(2+) can stimulate de
CC novo initiation but it is inefficient at supporting elongation of de
CC novo initiated RNA. {ECO:0000269|PubMed:25010481};
CC -!- SUBUNIT: Interacts with the phosphoprotein (via C-terminus); the
CC association of P and L forms the polymerase complex.
CC {ECO:0000269|PubMed:25653447, ECO:0000269|PubMed:31495574,
CC ECO:0000269|PubMed:31953395}.
CC -!- SUBCELLULAR LOCATION: Virion {ECO:0000305}. Host cytoplasm
CC {ECO:0000269|PubMed:17703289}. Note=Localizes in cytoplasmic inclusion
CC bodies. {ECO:0000269|PubMed:17703289}.
CC -!- DOMAIN: Contains an RNA-dependent RNA polymerase (RdRp) domain, a
CC polyribonucleotidyl transferase (PRNTase or capping) domain and a
CC methyltransferase (MTase) domain. {ECO:0000269|PubMed:31495574}.
CC -!- SIMILARITY: Belongs to the paramyxovirus L protein family.
CC {ECO:0000305}.
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DR EMBL; M75730; AAA47418.1; -; Genomic_RNA.
DR EMBL; U27298; AAA84898.1; -; Genomic_RNA.
DR EMBL; U50362; AAB86667.1; -; Genomic_RNA.
DR EMBL; U50363; AAB86679.1; -; Genomic_RNA.
DR EMBL; U63644; AAC55973.1; -; Genomic_RNA.
DR EMBL; AF035006; AAC14905.1; -; Genomic_RNA.
DR PIR; A40317; RRNZA2.
DR PDB; 6PZK; EM; 3.20 A; A=1-2165.
DR PDB; 6UEN; EM; 3.67 A; A=1-1500.
DR PDBsum; 6PZK; -.
DR PDBsum; 6UEN; -.
DR SMR; P28887; -.
DR IntAct; P28887; 15.
DR ChEMBL; CHEMBL4630897; -.
DR BRENDA; 2.7.7.48; 17394.
DR Proteomes; UP000134464; Genome.
DR Proteomes; UP000181145; Genome.
DR Proteomes; UP000181262; Genome.
DR Proteomes; UP000181559; Genome.
DR GO; GO:0030430; C:host cell cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0003924; F:GTPase activity; IEA:RHEA.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004482; F:mRNA (guanine-N7-)-methyltransferase activity; IEA:InterPro.
DR GO; GO:0003968; F:RNA-directed 5'-3' RNA polymerase activity; IEA:UniProtKB-KW.
DR GO; GO:0039689; P:negative stranded viral RNA replication; IDA:UniProtKB.
DR InterPro; IPR039736; L_poly_C.
DR InterPro; IPR026890; Mononeg_mRNAcap.
DR InterPro; IPR014023; Mononeg_RNA_pol_cat.
DR InterPro; IPR025786; Mononega_L_MeTrfase.
DR InterPro; IPR016269; RNA-dir_pol_paramyxovirus.
DR Pfam; PF14318; Mononeg_mRNAcap; 1.
DR Pfam; PF00946; Mononeg_RNA_pol; 1.
DR PIRSF; PIRSF000830; RNA_pol_ParamyxoV; 1.
DR TIGRFAMs; TIGR04198; paramyx_RNAcap; 1.
DR PROSITE; PS50526; RDRP_SSRNA_NEG_NONSEG; 1.
DR PROSITE; PS51590; SAM_MT_MNV_L; 1.
PE 1: Evidence at protein level;
KW 3D-structure; ATP-binding; Host cytoplasm; Hydrolase; Magnesium;
KW Metal-binding; Methyltransferase; mRNA capping; mRNA processing;
KW Multifunctional enzyme; Nucleotide-binding; Nucleotidyltransferase;
KW Reference proteome; RNA-directed RNA polymerase; S-adenosyl-L-methionine;
KW Transferase; Viral RNA replication; Virion.
FT CHAIN 1..2165
FT /note="RNA-directed RNA polymerase L"
FT /id="PRO_0000142727"
FT DOMAIN 693..877
FT /note="RdRp catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00539"
FT DOMAIN 1820..2008
FT /note="Mononegavirus-type SAM-dependent 2'-O-MTase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00923"
FT REGION 968..1460
FT /note="GDP polyribonucleotidyltransferase"
FT /evidence="ECO:0000269|PubMed:31495574"
FT ACT_SITE 1338
FT /note="Nucleophile; for GDP polyribonucleotidyltransferase
FT activity"
FT /evidence="ECO:0000250|UniProtKB:P03523"
FT ACT_SITE 1831
FT /note="For mRNA (nucleoside-2'-O-)-methyltransferase
FT activity"
FT /evidence="ECO:0000250|UniProtKB:Q6WB93"
FT ACT_SITE 1936
FT /note="For mRNA (nucleoside-2'-O-)-methyltransferase
FT activity"
FT /evidence="ECO:0000250|UniProtKB:Q6WB93"
FT ACT_SITE 1973
FT /note="For mRNA (nucleoside-2'-O-)-methyltransferase
FT activity"
FT /evidence="ECO:0000250|UniProtKB:Q6WB93"
FT ACT_SITE 2004
FT /note="For mRNA (nucleoside-2'-O-)-methyltransferase
FT activity"
FT /evidence="ECO:0000250|UniProtKB:Q6WB93"
FT BINDING 700
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_note="catalytic; for RNA-directed RNA polymerase
FT activity"
FT /evidence="ECO:0000303|PubMed:31495574"
FT BINDING 811
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_note="catalytic; for RNA-directed RNA polymerase
FT activity"
FT /evidence="ECO:0000305|PubMed:31953395"
FT BINDING 1853..1857
FT /ligand="substrate"
FT /ligand_note="for mRNA (nucleoside-2'-O-)-methyltransferase
FT activity"
FT /evidence="ECO:0000250|UniProtKB:Q6WB93"
FT VARIANT 17
FT /note="S -> G"
FT VARIANT 319
FT /note="C -> Y (in strain: Cold-passage attenuated)"
FT VARIANT 831
FT /note="Q -> L"
FT VARIANT 1049
FT /note="N -> D"
FT VARIANT 1183
FT /note="D -> E"
FT VARIANT 1690
FT /note="H -> Y (in strain: Cold-passage attenuated)"
FT MUTAGEN 811
FT /note="D->A: Complete loss of RNA synthesis."
FT /evidence="ECO:0000269|PubMed:31953395"
FT MUTAGEN 812
FT /note="N->A: Complete loss of RNA synthesis."
FT /evidence="ECO:0000269|PubMed:25010481"
FT MUTAGEN 1261
FT /note="P->A: Inhibition of RNA synthesis."
FT /evidence="ECO:0000269|PubMed:31698413"
FT MUTAGEN 1262
FT /note="W->A: Inhibition of RNA synthesis."
FT /evidence="ECO:0000269|PubMed:31698413"
FT MUTAGEN 1274
FT /note="P->A: No effect on RNA synthesis."
FT MUTAGEN 1276
FT /note="Y->A: No effect on RNA synthesis."
FT MUTAGEN 1820
FT /note="R->A: Complete loss of methyltransferase activity."
FT /evidence="ECO:0000269|PubMed:33956914"
FT MUTAGEN 1855
FT /note="G->S: Complete loss of methyltransferase activity."
FT /evidence="ECO:0000269|PubMed:33956914"
FT MUTAGEN 1936
FT /note="D->A: About 90% loss of methyltransferase activity."
FT /evidence="ECO:0000269|PubMed:33956914"
FT MUTAGEN 1938
FT /note="E->A: Complete loss of methyltransferase activity."
FT /evidence="ECO:0000269|PubMed:33956914"
FT MUTAGEN 1998
FT /note="S->A: Complete loss of methyltransferase activity."
FT /evidence="ECO:0000269|PubMed:33956914"
FT MUTAGEN 2004
FT /note="E->A: Complete loss of methyltransferase activity."
FT /evidence="ECO:0000269|PubMed:33956914"
FT HELIX 25..36
FT /evidence="ECO:0007829|PDB:6PZK"
FT HELIX 46..52
FT /evidence="ECO:0007829|PDB:6PZK"
FT HELIX 56..62
FT /evidence="ECO:0007829|PDB:6PZK"
FT HELIX 67..75
FT /evidence="ECO:0007829|PDB:6PZK"
FT STRAND 78..81
FT /evidence="ECO:0007829|PDB:6PZK"
FT HELIX 84..92
FT /evidence="ECO:0007829|PDB:6PZK"
FT HELIX 99..130
FT /evidence="ECO:0007829|PDB:6PZK"
FT HELIX 188..196
FT /evidence="ECO:0007829|PDB:6PZK"
FT HELIX 202..227
FT /evidence="ECO:0007829|PDB:6PZK"
FT STRAND 233..247
FT /evidence="ECO:0007829|PDB:6PZK"
FT STRAND 250..255
FT /evidence="ECO:0007829|PDB:6PZK"
FT TURN 256..259
FT /evidence="ECO:0007829|PDB:6PZK"
FT STRAND 260..264
FT /evidence="ECO:0007829|PDB:6PZK"
FT HELIX 266..295
FT /evidence="ECO:0007829|PDB:6PZK"
FT TURN 297..299
FT /evidence="ECO:0007829|PDB:6PZK"
FT HELIX 307..324
FT /evidence="ECO:0007829|PDB:6PZK"
FT HELIX 325..328
FT /evidence="ECO:0007829|PDB:6PZK"
FT HELIX 329..332
FT /evidence="ECO:0007829|PDB:6PZK"
FT HELIX 335..347
FT /evidence="ECO:0007829|PDB:6PZK"
FT HELIX 350..378
FT /evidence="ECO:0007829|PDB:6PZK"
FT TURN 379..381
FT /evidence="ECO:0007829|PDB:6PZK"
FT TURN 383..386
FT /evidence="ECO:0007829|PDB:6PZK"
FT HELIX 390..393
FT /evidence="ECO:0007829|PDB:6PZK"
FT HELIX 397..412
FT /evidence="ECO:0007829|PDB:6PZK"
FT HELIX 416..421
FT /evidence="ECO:0007829|PDB:6PZK"
FT HELIX 422..426
FT /evidence="ECO:0007829|PDB:6PZK"
FT TURN 427..429
FT /evidence="ECO:0007829|PDB:6PZK"
FT HELIX 438..448
FT /evidence="ECO:0007829|PDB:6PZK"
FT STRAND 452..454
FT /evidence="ECO:0007829|PDB:6PZK"
FT HELIX 455..477
FT /evidence="ECO:0007829|PDB:6PZK"
FT HELIX 486..488
FT /evidence="ECO:0007829|PDB:6PZK"
FT HELIX 491..498
FT /evidence="ECO:0007829|PDB:6PZK"
FT TURN 505..507
FT /evidence="ECO:0007829|PDB:6PZK"
FT HELIX 512..515
FT /evidence="ECO:0007829|PDB:6PZK"
FT HELIX 516..518
FT /evidence="ECO:0007829|PDB:6PZK"
FT HELIX 533..536
FT /evidence="ECO:0007829|PDB:6PZK"
FT STRAND 539..541
FT /evidence="ECO:0007829|PDB:6PZK"
FT HELIX 546..552
FT /evidence="ECO:0007829|PDB:6PZK"
FT HELIX 555..557
FT /evidence="ECO:0007829|PDB:6PZK"
FT HELIX 560..569
FT /evidence="ECO:0007829|PDB:6PZK"
FT HELIX 570..572
FT /evidence="ECO:0007829|PDB:6PZK"
FT HELIX 577..579
FT /evidence="ECO:0007829|PDB:6PZK"
FT HELIX 582..587
FT /evidence="ECO:0007829|PDB:6PZK"
FT HELIX 594..596
FT /evidence="ECO:0007829|PDB:6PZK"
FT HELIX 598..601
FT /evidence="ECO:0007829|PDB:6PZK"
FT TURN 602..608
FT /evidence="ECO:0007829|PDB:6PZK"
FT STRAND 614..617
FT /evidence="ECO:0007829|PDB:6PZK"
FT STRAND 629..631
FT /evidence="ECO:0007829|PDB:6PZK"
FT HELIX 634..650
FT /evidence="ECO:0007829|PDB:6PZK"
FT HELIX 652..654
FT /evidence="ECO:0007829|PDB:6PZK"
FT STRAND 691..700
FT /evidence="ECO:0007829|PDB:6PZK"
FT HELIX 704..707
FT /evidence="ECO:0007829|PDB:6PZK"
FT HELIX 710..712
FT /evidence="ECO:0007829|PDB:6PZK"
FT HELIX 714..723
FT /evidence="ECO:0007829|PDB:6PZK"
FT HELIX 732..736
FT /evidence="ECO:0007829|PDB:6PZK"
FT HELIX 737..739
FT /evidence="ECO:0007829|PDB:6PZK"
FT STRAND 742..744
FT /evidence="ECO:0007829|PDB:6PZK"
FT HELIX 782..799
FT /evidence="ECO:0007829|PDB:6PZK"
FT STRAND 803..809
FT /evidence="ECO:0007829|PDB:6PZK"
FT STRAND 812..821
FT /evidence="ECO:0007829|PDB:6PZK"
FT HELIX 829..849
FT /evidence="ECO:0007829|PDB:6PZK"
FT TURN 850..852
FT /evidence="ECO:0007829|PDB:6PZK"
FT STRAND 859..865
FT /evidence="ECO:0007829|PDB:6PZK"
FT HELIX 869..871
FT /evidence="ECO:0007829|PDB:6PZK"
FT STRAND 873..875
FT /evidence="ECO:0007829|PDB:6PZK"
FT STRAND 878..880
FT /evidence="ECO:0007829|PDB:6PZK"
FT HELIX 883..887
FT /evidence="ECO:0007829|PDB:6PZK"
FT TURN 892..895
FT /evidence="ECO:0007829|PDB:6PZK"
FT HELIX 901..912
FT /evidence="ECO:0007829|PDB:6PZK"
FT HELIX 914..917
FT /evidence="ECO:0007829|PDB:6PZK"
FT HELIX 922..938
FT /evidence="ECO:0007829|PDB:6PZK"
FT HELIX 940..943
FT /evidence="ECO:0007829|PDB:6PZK"
FT TURN 945..947
FT /evidence="ECO:0007829|PDB:6PZK"
FT HELIX 950..965
FT /evidence="ECO:0007829|PDB:6PZK"
FT HELIX 971..978
FT /evidence="ECO:0007829|PDB:6PZK"
FT HELIX 983..985
FT /evidence="ECO:0007829|PDB:6PZK"
FT STRAND 988..991
FT /evidence="ECO:0007829|PDB:6PZK"
FT TURN 993..997
FT /evidence="ECO:0007829|PDB:6PZK"
FT HELIX 1004..1020
FT /evidence="ECO:0007829|PDB:6PZK"
FT STRAND 1024..1026
FT /evidence="ECO:0007829|PDB:6PZK"
FT HELIX 1035..1044
FT /evidence="ECO:0007829|PDB:6PZK"
FT HELIX 1055..1059
FT /evidence="ECO:0007829|PDB:6PZK"
FT HELIX 1073..1085
FT /evidence="ECO:0007829|PDB:6PZK"
FT HELIX 1091..1109
FT /evidence="ECO:0007829|PDB:6PZK"
FT TURN 1110..1113
FT /evidence="ECO:0007829|PDB:6PZK"
FT STRAND 1115..1117
FT /evidence="ECO:0007829|PDB:6PZK"
FT HELIX 1119..1128
FT /evidence="ECO:0007829|PDB:6PZK"
FT HELIX 1131..1141
FT /evidence="ECO:0007829|PDB:6PZK"
FT STRAND 1144..1146
FT /evidence="ECO:0007829|PDB:6PZK"
FT HELIX 1147..1152
FT /evidence="ECO:0007829|PDB:6PZK"
FT HELIX 1159..1179
FT /evidence="ECO:0007829|PDB:6PZK"
FT HELIX 1184..1187
FT /evidence="ECO:0007829|PDB:6PZK"
FT HELIX 1199..1209
FT /evidence="ECO:0007829|PDB:6PZK"
FT HELIX 1224..1227
FT /evidence="ECO:0007829|PDB:6PZK"
FT STRAND 1228..1233
FT /evidence="ECO:0007829|PDB:6PZK"
FT STRAND 1240..1245
FT /evidence="ECO:0007829|PDB:6PZK"
FT STRAND 1247..1250
FT /evidence="ECO:0007829|PDB:6PZK"
FT HELIX 1278..1280
FT /evidence="ECO:0007829|PDB:6PZK"
FT HELIX 1283..1298
FT /evidence="ECO:0007829|PDB:6PZK"
FT HELIX 1299..1301
FT /evidence="ECO:0007829|PDB:6PZK"
FT HELIX 1305..1315
FT /evidence="ECO:0007829|PDB:6PZK"
FT HELIX 1321..1324
FT /evidence="ECO:0007829|PDB:6PZK"
FT HELIX 1325..1327
FT /evidence="ECO:0007829|PDB:6PZK"
FT TURN 1336..1338
FT /evidence="ECO:0007829|PDB:6PZK"
FT STRAND 1351..1353
FT /evidence="ECO:0007829|PDB:6PZK"
FT HELIX 1355..1360
FT /evidence="ECO:0007829|PDB:6PZK"
FT STRAND 1361..1364
FT /evidence="ECO:0007829|PDB:6PZK"
FT HELIX 1366..1374
FT /evidence="ECO:0007829|PDB:6PZK"
FT TURN 1375..1378
FT /evidence="ECO:0007829|PDB:6PZK"
FT HELIX 1385..1403
FT /evidence="ECO:0007829|PDB:6PZK"
FT STRAND 1408..1414
FT /evidence="ECO:0007829|PDB:6PZK"
FT HELIX 1416..1418
FT /evidence="ECO:0007829|PDB:6PZK"
FT HELIX 1433..1442
FT /evidence="ECO:0007829|PDB:6PZK"
FT HELIX 1444..1446
FT /evidence="ECO:0007829|PDB:6PZK"
FT HELIX 1453..1459
FT /evidence="ECO:0007829|PDB:6PZK"
SQ SEQUENCE 2165 AA; 250386 MW; 5A3DCA0805305197 CRC64;
MDPIINGNSA NVYLTDSYLK GVISFSECNA LGSYIFNGPY LKNDYTNLIS RQNPLIEHMN
LKKLNITQSL ISKYHKGEIK LEEPTYFQSL LMTYKSMTSS EQIATTNLLK KIIRRAIEIS
DVKVYAILNK LGLKEKDKIK SNNGQDEDNS VITTIIKDDI LSAVKDNQSH LKADKNHSTK
QKDTIKTTLL KKLMCSMQHP PSWLIHWFNL YTKLNNILTQ YRSNEVKNHG FTLIDNQTLS
GFQFILNQYG CIVYHKELKR ITVTTYNQFL TWKDISLSRL NVCLITWISN CLNTLNKSLG
LRCGFNNVIL TQLFLYGDCI LKLFHNEGFY IIKEVEGFIM SLILNITEED QFRKRFYNSM
LNNITDAANK AQKNLLSRVC HTLLDKTVSD NIINGRWIIL LSKFLKLIKL AGDNNLNNLS
ELYFLFRIFG HPMVDERQAM DAVKINCNET KFYLLSSLSM LRGAFIYRII KGFVNNYNRW
PTLRNAIVLP LRWLTYYKLN TYPSLLELTE RDLIVLSGLR FYREFRLPKK VDLEMIINDK
AISPPKNLIW TSFPRNYMPS HIQNYIEHEK LKFSESDKSR RVLEYYLRDN KFNECDLYNC
VVNQSYLNNP NHVVSLTGKE RELSVGRMFA MQPGMFRQVQ ILAEKMIAEN ILQFFPESLT
RYGDLELQKI LELKAGISNK SNRYNDNYNN YISKCSIITD LSKFNQAFRY ETSCICSDVL
DELHGVQSLF SWLHLTIPHV TIICTYRHAP PYIGDHIVDL NNVDEQSGLY RYHMGGIEGW
CQKLWTIEAI SLLDLISLKG KFSITALING DNQSIDISKP IRLMEGQTHA QADYLLALNS
LKLLYKEYAG IGHKLKGTET YISRDMQFMS KTIQHNGVYY PASIKKVLRV GPWINTILDD
FKVSLESIGS LTQELEYRGE SLLCSLIFRN VWLYNQIALQ LKNHALCNNK LYLDILKVLK
HLKTFFNLDN IDTALTLYMN LPMLFGGGDP NLLYRSFYRR TPDFLTEAIV HSVFILSYYT
NHDLKDKLQD LSDDRLNKFL TCIITFDKNP NAEFVTLMRD PQALGSERQA KITSEINRLA
VTEVLSTAPN KIFSKSAQHY TTTEIDLNDI MQNIEPTYPH GLRVVYESLP FYKAEKIVNL
ISGTKSITNI LEKTSAIDLT DIDRATEMMR KNITLLIRIL PLDCNRDKRE ILSMENLSIT
ELSKYVRERS WSLSNIVGVT SPSIMYTMDI KYTTSTISSG IIIEKYNVNS LTRGERGPTK
PWVGSSTQEK KTMPVYNRQV LTKKQRDQID LLAKLDWVYA SIDNKDEFME ELSIGTLGLT
YEKAKKLFPQ YLSVNYLHRL TVSSRPCEFP ASIPAYRTTN YHFDTSPINR ILTEKYGDED
IDIVFQNCIS FGLSLMSVVE QFTNVCPNRI ILIPKLNEIH LMKPPIFTGD VDIHKLKQVI
QKQHMFLPDK ISLTQYVELF LSNKTLKSGS HVNSNLILAH KISDYFHNTY ILSTNLAGHW
ILIIQLMKDS KGIFEKDWGE GYITDHMFIN LKVFFNAYKT YLLCFHKGYG KAKLECDMNT
SDLLCVLELI DSSYWKSMSK VFLEQKVIKY ILSQDASLHR VKGCHSFKLW FLKRLNVAEF
TVCPWVVNID YHPTHMKAIL TYIDLVRMGL INIDRIHIKN KHKFNDEFYT SNLFYINYNF
SDNTHLLTKH IRIANSELEN NYNKLYHPTP ETLENILANP IKSNDKKTLN DYCIGKNVDS
IMLPLLSNKK LIKSSAMIRT NYSKQDLYNL FPMVVIDRII DHSGNTAKSN QLYTTTSHQI
SLVHNSTSLY CMLPWHHINR FNFVFSSTGC KISIEYILKD LKIKDPNCIA FIGEGAGNLL
LRTVVELHPD IRYIYRSLKD CNDHSLPIEF LRLYNGHINI DYGENLTIPA TDATNNIHWS
YLHIKFAEPI SLFVCDAELS VTVNWSKIII EWSKHVRKCK YCSSVNKCML IVKYHAQDDI
DFKLDNITIL KTYVCLGSKL KGSEVYLVLT IGPANIFPVF NVVQNAKLIL SRTKNFIMPK
KADKESIDAN IKSLIPFLCY PITKKGINTA LSKLKSVVSG DILSYSIAGR NEVFSNKLIN
HKHMNILKWF NHVLNFRSTE LNYNHLYMVE STYPYLSELL NSLTTNELKK LIKITGSLLY
NFHNE
