RDRP_TOML
ID RDRP_TOML Reviewed; 1616 AA.
AC P03587; O41352;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2000, sequence version 2.
DT 03-AUG-2022, entry version 108.
DE RecName: Full=Replicase large subunit;
DE EC=2.1.1.-;
DE EC=2.7.7.-;
DE EC=2.7.7.48 {ECO:0000255|PROSITE-ProRule:PRU00539};
DE EC=3.6.4.13;
DE AltName: Full=183 kDa protein;
DE AltName: Full=RNA-directed RNA polymerase {ECO:0000255|PROSITE-ProRule:PRU00539};
DE Contains:
DE RecName: Full=Replicase small subunit;
DE EC=2.1.1.-;
DE EC=2.7.7.-;
DE EC=3.6.4.13;
DE AltName: Full=126 kDa protein;
DE AltName: Full=Methyltransferase/RNA helicase;
DE Short=MT/HEL;
OS Tomato mosaic virus (strain L) (ToMV) (TMV strain tomato).
OC Viruses; Riboviria; Orthornavirae; Kitrinoviricota; Alsuviricetes;
OC Martellivirales; Virgaviridae; Tobamovirus.
OX NCBI_TaxID=12252;
OH NCBI_TaxID=4151; Antirrhinum majus (Garden snapdragon).
OH NCBI_TaxID=4071; Capsicum (peppers).
OH NCBI_TaxID=46246; Delphinium.
OH NCBI_TaxID=4101; Petunia.
OH NCBI_TaxID=4081; Solanum lycopersicum (Tomato) (Lycopersicon esculentum).
OH NCBI_TaxID=13707; Tagetes (marigolds).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=6549393; DOI=10.1093/oxfordjournals.jbchem.a135026;
RA Ohno T., Aoyagi M., Yamanashi Y., Saito H., Ikawa S., Meshi T., Okada Y.;
RT "Nucleotide sequence of the tobacco mosaic virus (tomato strain) genome and
RT comparison with the common strain genome.";
RL J. Biochem. 96:1915-1923(1984).
RN [2]
RP ACTIVITY REGULATION.
RX PubMed=3686829; DOI=10.1016/0042-6822(87)90147-4;
RA Watanabe Y., Kishibayashi N., Motoyoshi F., Okada Y.;
RT "Characterization of Tm-1 gene action on replication of common isolates and
RT a resistance-breaking isolate of TMV.";
RL Virology 161:527-532(1987).
RN [3]
RP MUTAGENESIS OF GLN-979.
RX PubMed=9018069; DOI=10.1099/0022-1317-78-2-461;
RA Hamamoto H., Watanabe Y., Kamada H., Okada Y.;
RT "Amino acid changes in the putative replicase of tomato mosaic tobamovirus
RT that overcome resistance in Tm-1 tomato.";
RL J. Gen. Virol. 78:461-464(1997).
RN [4]
RP FUNCTION, AND MUTAGENESIS OF CYS-349.
RX PubMed=14512550; DOI=10.1128/jvi.77.20.11016-11026.2003;
RA Kubota K., Tsuda S., Tamai A., Meshi T.;
RT "Tomato mosaic virus replication protein suppresses virus-targeted
RT posttranscriptional gene silencing.";
RL J. Virol. 77:11016-11026(2003).
RN [5]
RP MUTAGENESIS OF ASP-1097 AND ARG-1100.
RC STRAIN=cv. Craigella GCR237, and cv. Craigella GCR254;
RX PubMed=17238011; DOI=10.1007/s00705-006-0915-8;
RA Strasser M., Pfitzner A.J.P.;
RT "The double-resistance-breaking Tomato mosaic virus strain ToMV1-2 contains
RT two independent single resistance-breaking domains.";
RL Arch. Virol. 152:903-914(2007).
RN [6]
RP INTERACTION WITH HOST PROTEIN TM-1, AND ACTIVITY REGULATION.
RC STRAIN=cv. Craigella GCR237;
RX PubMed=17699618; DOI=10.1073/pnas.0703203104;
RA Ishibashi K., Masuda K., Naito S., Meshi T., Ishikawa M.;
RT "An inhibitor of viral RNA replication is encoded by a plant resistance
RT gene.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:13833-13838(2007).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 666-1111, AND INTERACTION WITH
RP HOST PROTEINS TOM1 AND ARL8.
RX PubMed=22573863; DOI=10.1128/jvi.00118-12;
RA Nishikiori M., Sugiyama S., Xiang H., Niiyama M., Ishibashi K., Inoue T.,
RA Ishikawa M., Matsumura H., Katoh E.;
RT "Crystal structure of the superfamily 1 helicase from Tomato mosaic
RT virus.";
RL J. Virol. 86:7565-7576(2012).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 666-1116 IN COMPLEX WITH ATP AND
RP TOMATO TM-1 PROTEIN, ACTIVITY REGULATION, AND INTERACTION WITH HOST PROTEIN
RP TM-1.
RX PubMed=25092327; DOI=10.1073/pnas.1407888111;
RA Ishibashi K., Kezuka Y., Kobayashi C., Kato M., Inoue T., Nonaka T.,
RA Ishikawa M., Matsumura H., Katoh E.;
RT "Structural basis for the recognition-evasion arms race between Tomato
RT mosaic virus and the resistance gene Tm-1.";
RL Proc. Natl. Acad. Sci. U.S.A. 111:E3486-E3495(2014).
CC -!- FUNCTION: [Replicase large subunit]: Is an RNA-dependent RNA polymerase
CC active in viral RNA replication. {ECO:0000269|PubMed:14512550}.
CC -!- FUNCTION: [Replicase small subunit]: Is a methyltransferase active in
CC RNA capping and an RNA helicase. Methyltransferase displays a
CC cytoplasmic capping enzyme activity. This function is necessary since
CC all viral RNAs are synthesized in the cytoplasm, and host capping
CC enzymes are restricted to the nucleus. Helicase region probably
CC exhibits NTPase and RNA unwinding activities (Potential). It also acts
CC as a suppressor of RNA-mediated gene silencing, also known as post-
CC transcriptional gene silencing (PTGS), a mechanism of plant viral
CC defense that limits the accumulation of viral RNAs. May mediate
CC silencing suppression through either inhibition of HEN1-mediated siRNA
CC or siRNA demethylation (By similarity). {ECO:0000250, ECO:0000305}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a ribonucleoside 5'-triphosphate + RNA(n) = diphosphate +
CC RNA(n+1); Xref=Rhea:RHEA:21248, Rhea:RHEA-COMP:14527, Rhea:RHEA-
CC COMP:17342, ChEBI:CHEBI:33019, ChEBI:CHEBI:61557, ChEBI:CHEBI:140395;
CC EC=2.7.7.48; Evidence={ECO:0000255|PROSITE-ProRule:PRU00539};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + 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 -!- ACTIVITY REGULATION: In resistant plants, is bound by host protein Tm-1
CC (e.g. tomato Tm-1 AC A7M6E7), thereby inhibiting replication complex
CC activity. {ECO:0000269|PubMed:17699618, ECO:0000269|PubMed:25092327,
CC ECO:0000269|PubMed:3686829}.
CC -!- SUBUNIT: Heterodimer of a large and a small subunit (By similarity).
CC May interact with the host proteins TOM1 and ARL8. Interacts via an ATP
CC bridge, with host protein Tm-1 (e.g. tomato Tm-1 AC A7M6E7)
CC (PubMed:17699618, PubMed:25092327). {ECO:0000250,
CC ECO:0000269|PubMed:17699618, ECO:0000269|PubMed:25092327}.
CC -!- MISCELLANEOUS: This protein is translated as a fusion protein by
CC episodic readthrough of a termination codon. When readthrough of the
CC terminator codon TGA occurs between the codons for Gln-1116 and Gln-
CC 1118, this results in the addition of the RdRp region to the replicase.
CC -!- SIMILARITY: Belongs to the ssRNA positive-strand viruses RNA-directed
CC RNA polymerase family. {ECO:0000305}.
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DR EMBL; X02144; CAA26085.1; -; Genomic_RNA.
DR EMBL; X02144; CAA26082.1; -; Genomic_RNA.
DR PIR; A04195; WMTM8T.
DR RefSeq; NP_078446.1; NC_002692.1.
DR RefSeq; NP_078447.1; NC_002692.1.
DR PDB; 3VKW; X-ray; 1.90 A; A=666-1111.
DR PDB; 3WRX; X-ray; 2.50 A; C/D=666-1116.
DR PDB; 3WRY; X-ray; 2.30 A; C/D=666-1116.
DR PDBsum; 3VKW; -.
DR PDBsum; 3WRX; -.
DR PDBsum; 3WRY; -.
DR SMR; P03587; -.
DR GeneID; 920838; -.
DR GeneID; 920841; -.
DR KEGG; vg:920838; -.
DR KEGG; vg:920841; -.
DR Proteomes; UP000001451; Genome.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016887; F:ATP hydrolysis activity; IEA:RHEA.
DR GO; GO:0008174; F:mRNA methyltransferase activity; IEA:InterPro.
DR GO; GO:0003723; F:RNA binding; IEA:InterPro.
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:0006396; P:RNA processing; IEA:InterPro.
DR GO; GO:0006351; P:transcription, DNA-templated; IEA:InterPro.
DR GO; GO:0039694; P:viral RNA genome replication; IEA:InterPro.
DR Gene3D; 3.40.50.300; -; 2.
DR InterPro; IPR027351; (+)RNA_virus_helicase_core_dom.
DR InterPro; IPR002588; Alphavirus-like_MT_dom.
DR InterPro; IPR043502; DNA/RNA_pol_sf.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR007094; RNA-dir_pol_PSvirus.
DR InterPro; IPR001788; Tymovirus_RNA-dep_RNA_pol.
DR Pfam; PF00978; RdRP_2; 1.
DR Pfam; PF01443; Viral_helicase1; 1.
DR Pfam; PF01660; Vmethyltransf; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR SUPFAM; SSF56672; SSF56672; 1.
DR PROSITE; PS51743; ALPHAVIRUS_MT; 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; Helicase; Host-virus interaction; Hydrolase;
KW Nucleotide-binding; Nucleotidyltransferase; Reference proteome;
KW RNA suppression of termination; RNA-directed RNA polymerase;
KW Suppressor of RNA silencing; Transferase; Viral RNA replication.
FT CHAIN 1..1616
FT /note="Replicase large subunit"
FT /id="PRO_0000041194"
FT CHAIN 1..1116
FT /note="Replicase small subunit"
FT /id="PRO_0000041195"
FT DOMAIN 72..281
FT /note="Alphavirus-like MT"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01079"
FT DOMAIN 801..963
FT /note="(+)RNA virus helicase ATP-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00990"
FT DOMAIN 964..1116
FT /note="(+)RNA virus helicase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00990"
FT DOMAIN 1380..1493
FT /note="RdRp catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00539"
FT REGION 50..458
FT /note="Methyltransferase"
FT REGION 830..1085
FT /note="Helicase"
FT BINDING 836..841
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00990,
FT ECO:0000269|PubMed:25092327, ECO:0007744|PDB:3WRX,
FT ECO:0007744|PDB:3WRY"
FT BINDING 868
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:25092327,
FT ECO:0007744|PDB:3WRX, ECO:0007744|PDB:3WRY"
FT BINDING 967..968
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:25092327,
FT ECO:0007744|PDB:3WRX, ECO:0007744|PDB:3WRY"
FT BINDING 1076
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:25092327,
FT ECO:0007744|PDB:3WRX, ECO:0007744|PDB:3WRY"
FT BINDING 1097..1100
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:25092327,
FT ECO:0007744|PDB:3WRX, ECO:0007744|PDB:3WRY"
FT MUTAGEN 349
FT /note="C->A: Loss of RNA silencing suppression activity."
FT /evidence="ECO:0000269|PubMed:14512550"
FT MUTAGEN 979
FT /note="Q->D,K: Overcome tomato Tm-1-mediated resistance (AC
FT A7M6E7) thus leading to increased infectivity in resistant
FT tomato plants."
FT /evidence="ECO:0000269|PubMed:9018069"
FT MUTAGEN 979
FT /note="Q->H: Normal tomato Tm-1-mediated resistance (AC
FT A7M6E7) leading to impaired infectivity in resistant tomato
FT plants."
FT /evidence="ECO:0000269|PubMed:9018069"
FT MUTAGEN 979
FT /note="Q->N,R: Overcome partially tomato Tm-1-mediated
FT resistance (AC A7M6E7) thus leading to increased
FT infectivity in resistant tomato plants."
FT /evidence="ECO:0000269|PubMed:9018069"
FT MUTAGEN 1097
FT /note="D->V: In ToMV1-2; overcome tomato Tm-1-mediated
FT resistance thus leading to increased infectivity in
FT resistant tomato plants; when associated with Q-1100."
FT /evidence="ECO:0000269|PubMed:17238011"
FT MUTAGEN 1100
FT /note="R->Q: In ToMV1-2; overcome tomato Tm-1-mediated
FT resistance thus leading to increased infectivity in
FT resistant tomato plants; when associated with V-1097."
FT /evidence="ECO:0000269|PubMed:17238011"
FT HELIX 672..675
FT /evidence="ECO:0007829|PDB:3WRY"
FT HELIX 676..679
FT /evidence="ECO:0007829|PDB:3VKW"
FT HELIX 684..687
FT /evidence="ECO:0007829|PDB:3VKW"
FT HELIX 701..729
FT /evidence="ECO:0007829|PDB:3VKW"
FT STRAND 730..732
FT /evidence="ECO:0007829|PDB:3VKW"
FT STRAND 740..746
FT /evidence="ECO:0007829|PDB:3VKW"
FT TURN 747..750
FT /evidence="ECO:0007829|PDB:3VKW"
FT STRAND 751..754
FT /evidence="ECO:0007829|PDB:3VKW"
FT STRAND 756..758
FT /evidence="ECO:0007829|PDB:3VKW"
FT STRAND 762..768
FT /evidence="ECO:0007829|PDB:3VKW"
FT STRAND 773..777
FT /evidence="ECO:0007829|PDB:3VKW"
FT STRAND 782..784
FT /evidence="ECO:0007829|PDB:3VKW"
FT STRAND 791..797
FT /evidence="ECO:0007829|PDB:3VKW"
FT HELIX 798..800
FT /evidence="ECO:0007829|PDB:3VKW"
FT HELIX 804..813
FT /evidence="ECO:0007829|PDB:3VKW"
FT STRAND 817..819
FT /evidence="ECO:0007829|PDB:3WRY"
FT STRAND 826..833
FT /evidence="ECO:0007829|PDB:3VKW"
FT HELIX 839..846
FT /evidence="ECO:0007829|PDB:3VKW"
FT TURN 849..851
FT /evidence="ECO:0007829|PDB:3VKW"
FT STRAND 853..857
FT /evidence="ECO:0007829|PDB:3VKW"
FT HELIX 859..869
FT /evidence="ECO:0007829|PDB:3VKW"
FT TURN 870..872
FT /evidence="ECO:0007829|PDB:3VKW"
FT TURN 879..881
FT /evidence="ECO:0007829|PDB:3VKW"
FT STRAND 882..884
FT /evidence="ECO:0007829|PDB:3VKW"
FT HELIX 885..890
FT /evidence="ECO:0007829|PDB:3VKW"
FT TURN 891..893
FT /evidence="ECO:0007829|PDB:3VKW"
FT STRAND 894..896
FT /evidence="ECO:0007829|PDB:3WRY"
FT STRAND 901..905
FT /evidence="ECO:0007829|PDB:3VKW"
FT HELIX 908..910
FT /evidence="ECO:0007829|PDB:3VKW"
FT HELIX 913..922
FT /evidence="ECO:0007829|PDB:3VKW"
FT STRAND 926..932
FT /evidence="ECO:0007829|PDB:3VKW"
FT HELIX 950..953
FT /evidence="ECO:0007829|PDB:3VKW"
FT STRAND 958..963
FT /evidence="ECO:0007829|PDB:3VKW"
FT STRAND 965..968
FT /evidence="ECO:0007829|PDB:3VKW"
FT HELIX 971..978
FT /evidence="ECO:0007829|PDB:3VKW"
FT STRAND 981..983
FT /evidence="ECO:0007829|PDB:3VKW"
FT STRAND 995..999
FT /evidence="ECO:0007829|PDB:3VKW"
FT HELIX 1003..1005
FT /evidence="ECO:0007829|PDB:3VKW"
FT TURN 1008..1010
FT /evidence="ECO:0007829|PDB:3VKW"
FT STRAND 1015..1021
FT /evidence="ECO:0007829|PDB:3VKW"
FT HELIX 1022..1029
FT /evidence="ECO:0007829|PDB:3VKW"
FT TURN 1030..1032
FT /evidence="ECO:0007829|PDB:3VKW"
FT STRAND 1034..1038
FT /evidence="ECO:0007829|PDB:3WRY"
FT HELIX 1040..1042
FT /evidence="ECO:0007829|PDB:3VKW"
FT STRAND 1047..1054
FT /evidence="ECO:0007829|PDB:3VKW"
FT HELIX 1068..1074
FT /evidence="ECO:0007829|PDB:3VKW"
FT STRAND 1075..1087
FT /evidence="ECO:0007829|PDB:3VKW"
FT HELIX 1090..1100
FT /evidence="ECO:0007829|PDB:3VKW"
FT HELIX 1103..1107
FT /evidence="ECO:0007829|PDB:3VKW"
SQ SEQUENCE 1616 AA; 183567 MW; A8EC8929B5CF7CAF CRC64;
MAYTQTATSS ALLETVRGNN TLVNDLAKRR LYDTAVDEFN ARDRRPKVNF SKVVSEEQTL
IATKAYPEFQ ITFYNTQNAV HSLAGGLRSL ELEYLMMQIP YGSLTYDIGG NFASHLFKGR
AYVHCCMPNL DVRDIMRHEG QKDSIELYLS RLERGNKHVP NFQKEAFDRY AEMPNEVVCH
DTFQTCRHSQ ECYTGRVYAI ALHSIYDIPA DEFGAALLRK NVHVCYAAFH FSENLLLEDS
HVNLDEINAC FQRDGDRLTF SFASESTLNY SHSYSNILKY VCKTYFPASN REVYMKEFLV
TRVNTWFCKF SRIDTFLLYK GVAHKGVDSE QFYKAMEDAW HYKKTLAMCN SERILLEDSS
SVNYWFPKMR DMVIVPLFDI SLETSKRTRK EVLVSKDFVY TVLNHIRTYQ AKALTYSNVL
SFVESIRSRV IINGVTARSE WDVDKSLLQS LSMTFFLHTK LAVLKDDLLI SKFALGPKTV
SQHVWDEISL AFGNAFPSIK ERLINRKLIK ITENALEIRV PDLYVTFHDR LVSEYKMSVD
MPVLDIRKKM EETEEMYNAL SELSVLKNSD KFDVDVFSQM CQSLEVDPMT AAKVIVAVMS
NESGLTLTFE QPTEANVALA LQDSEKASDG ALVVTSRDVE EPSIKGSMAR GELQLAGLSG
DVPESSYTRS EEIESLEQFH MATASSLIHK QMCSIVYTGP LKVQQMKNFI DSLVASLSAA
VSNLVKILKD TAAIDLETRQ KFGVLDVASK RWLVKPSAKN HAWGVVETHA RKYHVALLEH
DEFGIITCDN WRRVAVSSES VVYSDMAKLR TLRRLLKDGE PHVSSAKVVL VDGVPGCGKT
KEILSRVNFE EDLILVPGRQ AAEMIRRRAN ASGIIVATKD NVRTVDSFLM NYGKGARCQF
KRLFIDEGLM LHTGCVNFLV EMSLCDIAYV YGDTQQIPYI NRVTGFPYPA HFAKLEVDEV
ETRRTTLRCP ADVTHFLNQR YEGHVMCTSS EKKSVSQEMV SGAASINPVS KPLKGKILTF
TQSDKEALLS RGYADVHTVH EVQGETYADV SLVRLTPTPV SIIARDSPHV LVSLSRHTKS
LKYYTVVMDP LVSIIRDLER VSSYLLDMYK VDAGTQXQLQ VDSVFKNFNL FVAAPKTGDI
SDMQFYYDKC LPGNSTLLNN YDAVTMKLTD ISLNVKDCIL DMSKSVAAPK DVKPTLIPMV
RTAAEMPRQT GLLENLVAMI KRNFNSPELS GVVDIENTAS LVVDKFFDSY LLKEKRKPNK
NFSLFSRESL NRWIAKQEQV TIGQLADFDF VDLPAVDQYR HMIKAQPKQK LDLSIQTEYP
ALQTIVYHSK KINAIFGPLF SELTRQLLDS IDSSRFLFFT RKTPAQIEDF FGDLDSHVPM
DVLELDVSKY DKSQNEFHCA VEYEIWRRLG LEDFLAEVWK QGHRKTTLKD YTAGIKTCLW
YQRKSGDVTT FIGNTVIIAS CLASMLPMEK LIKGAFCGDD SLLYFPKGCE YPDIQQAANL
MWNFEAKLFK KQYGYFCGRY VIHHDRGCIV YYDPLKLISK LGAKHIKDWD HLEEFRRSLC
DVAESLNNCA YYTQLDDAVG EVHKTAPPGS FVYKSLVKYL SDKVLFRSLF LDGSSC
