L_RVFVZ
ID L_RVFVZ Reviewed; 2149 AA.
AC P27316;
DT 01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1992, sequence version 1.
DT 03-AUG-2022, entry version 81.
DE RecName: Full=RNA-directed RNA polymerase L;
DE Short=Protein L;
DE EC=2.7.7.48 {ECO:0000269|PubMed:34787453};
DE AltName: Full=Large structural protein;
DE AltName: Full=Replicase;
DE AltName: Full=Transcriptase;
DE Includes:
DE RecName: Full=cap-snatching endonuclease;
DE EC=3.1.-.- {ECO:0000250|UniProtKB:I0DF35};
GN Name=L;
OS Rift valley fever virus (strain ZH-548 M12) (RVFV).
OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina;
OC Ellioviricetes; Bunyavirales; Phenuiviridae; Phlebovirus.
OX NCBI_TaxID=11589;
OH NCBI_TaxID=7158; Aedes.
OH NCBI_TaxID=9913; Bos taurus (Bovine).
OH NCBI_TaxID=297284; Bos taurus x Bison bison (beefalo).
OH NCBI_TaxID=9837; Camelus bactrianus (Bactrian camel).
OH NCBI_TaxID=9925; Capra hircus (Goat).
OH NCBI_TaxID=9606; Homo sapiens (Human).
OH NCBI_TaxID=9940; Ovis aries (Sheep).
OH NCBI_TaxID=29031; Phlebotomus papatasi (Sandfly).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=1923828; DOI=10.1093/nar/19.19.5433;
RA Mueller R., Argentini C., Bouloy M., Prehaud C., Bishop D.H.L.;
RT "Completion of the genome sequence of Rift Valley fever phlebovirus
RT indicates that the L RNA is negative sense and codes for a putative
RT transcriptase-replicase.";
RL Nucleic Acids Res. 19:5433-5433(1991).
RN [2]
RP SUBUNIT.
RC STRAIN=MP12;
RX PubMed=19812169; DOI=10.1128/jvi.01310-09;
RA Zamoto-Niikura A., Terasaki K., Ikegami T., Peters C.J., Makino S.;
RT "Rift valley fever virus L protein forms a biologically active oligomer.";
RL J. Virol. 83:12779-12789(2009).
RN [3]
RP INTERACTION WITH GLYCOPROTEIN N.
RX PubMed=21445316; DOI=10.1371/journal.pone.0018070;
RA Piper M.E., Sorenson D.R., Gerrard S.R.;
RT "Efficient cellular release of Rift Valley fever virus requires genomic
RT RNA.";
RL PLoS ONE 6:E18070-E18070(2011).
RN [4]
RP FUNCTION.
RX PubMed=23824541; DOI=10.1101/gad.215384.113;
RA Hopkins K.C., McLane L.M., Maqbool T., Panda D., Gordesky-Gold B.,
RA Cherry S.;
RT "A genome-wide RNAi screen reveals that mRNA decapping restricts bunyaviral
RT replication by limiting the pools of Dcp2-accessible targets for cap-
RT snatching.";
RL Genes Dev. 27:1511-1525(2013).
RN [5]
RP FUNCTION, AND MUTAGENESIS OF ASP-111.
RX PubMed=23698297; DOI=10.1128/jvi.00371-13;
RA Klemm C., Reguera J., Cusack S., Zielecki F., Kochs G., Weber F.;
RT "Systems to establish bunyavirus genome replication in the absence of
RT transcription.";
RL J. Virol. 87:8205-8212(2013).
RN [6]
RP REVIEW.
RX PubMed=28418734; DOI=10.1080/1040841x.2017.1307805;
RA Amroun A., Priet S., de Lamballerie X., Querat G.;
RT "Bunyaviridae RdRps: structure, motifs, and RNA synthesis machinery.";
RL Crit. Rev. Microbiol. 43:753-778(2017).
RN [7]
RP REVIEW.
RX PubMed=31948728; DOI=10.1016/j.tim.2019.12.006;
RA Olschewski S., Cusack S., Rosenthal M.;
RT "The Cap-Snatching Mechanism of Bunyaviruses.";
RL Trends Microbiol. 28:293-303(2020).
RN [8]
RP INTERACTION WITH NUCLEOPROTEIN N.
RX PubMed=33952635; DOI=10.1128/jvi.00429-21;
RA Tercero B., Narayanan K., Terasaki K., Makino S.;
RT "Characterization of the Molecular Interactions That Govern the Packaging
RT of Viral RNA Segments into Rift Valley Fever Phlebovirus Particles.";
RL J. Virol. 95:e0042921-e0042921(2021).
RN [9]
RP STRUCTURE BY ELECTRON MICROSCOPY (3.60 ANGSTROMS) OF 216-, COFACTOR,
RP CATALYTIC ACTIVITY, AND MUTAGENESIS OF ASP-111.
RX PubMed=34787453; DOI=10.1128/jvi.01713-21;
RA Wang X., Hu C., Ye W., Wang J., Dong X., Xu J., Li X., Zhang M., Lu H.,
RA Zhang F., Wu W., Dai S., Wang H.W., Chen Z.;
RT "Structure of Rift Valley Fever Virus RNA-Dependent RNA Polymerase.";
RL J. Virol. 96:e0171321-e0171321(2022).
CC -!- FUNCTION: RNA-dependent RNA polymerase, which is responsible for the
CC replication and transcription of the viral RNA genome using antigenomic
CC RNA as an intermediate (PubMed:23698297). During transcription,
CC synthesizes subgenomic RNAs and assures their capping by a cap-
CC snatching mechanism, which involves the endonuclease activity cleaving
CC the host capped pre-mRNAs (PubMed:23824541). These short capped RNAs
CC are then used as primers for viral transcription. The 3'-end of
CC subgenomic mRNAs molecules are not polyadenylated. During replication,
CC the polymerase binds the 5' and 3' vRNA extremities at distinct sites
CC (By similarity). In turn, significant conformational changes occur in
CC the polymerase and in vRNA to initiate active RNA synthesis (By
CC similarity). As a consequence of the use of the same enzyme for both
CC transcription and replication, these mechanisms need to be well
CC coordinated (By similarity). {ECO:0000250|UniProtKB:A5HC98,
CC ECO:0000250|UniProtKB:I0DF35, ECO:0000269|PubMed:23698297,
CC ECO:0000269|PubMed:23824541}.
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:34787453};
CC -!- COFACTOR:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000269|PubMed:34787453};
CC Note=For endonuclease activity. Binds 2 Mn(2+) ions in the active site
CC (PubMed:34787453). The divalent metal ions are crucial for catalytic
CC activity (PubMed:31948728). {ECO:0000269|PubMed:31948728,
CC ECO:0000269|PubMed:34787453};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:34787453};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000269|PubMed:34787453};
CC Note=For polymerase activity. Initiation activity is stronger in the
CC presence of Mn(2+) than in the presence of Mg(2+).
CC {ECO:0000269|PubMed:34787453};
CC -!- SUBUNIT: Homomultimer (PubMed:19812169). Interacts with glycoprotein N;
CC this interaction allows efficient polymerase packaging into virus
CC particles (PubMed:21445316). Interacts with nucleoprotein N
CC (PubMed:33952635). {ECO:0000269|PubMed:19812169,
CC ECO:0000269|PubMed:21445316, ECO:0000269|PubMed:33952635}.
CC -!- SUBCELLULAR LOCATION: Host Golgi apparatus
CC {ECO:0000250|UniProtKB:I0DF35}. Host endoplasmic reticulum
CC {ECO:0000250|UniProtKB:I0DF35}. Host endoplasmic reticulum-Golgi
CC intermediate compartment {ECO:0000250|UniProtKB:I0DF35}. Virion
CC {ECO:0000250|UniProtKB:P20470}.
CC -!- DOMAIN: The N-terminus contains the endonuclease activity (endoN) (By
CC similarity). The central region contains the RdRp activity (By
CC similarity). The C-terminus contains the cap-binding region (By
CC similarity). {ECO:0000250|UniProtKB:A2SZS3,
CC ECO:0000250|UniProtKB:A5HC98, ECO:0000250|UniProtKB:I0DF35}.
CC -!- MISCELLANEOUS: Classified as His(+) endonuclease since it has a
CC histidine upstream of the active site that coordinates the first
CC cation. {ECO:0000303|PubMed:31948728}.
CC -!- SIMILARITY: Belongs to the Bunyavirales RNA polymerase family.
CC {ECO:0000305}.
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DR EMBL; X56464; CAA39836.1; -; Genomic_RNA.
DR PIR; S18676; S18676.
DR PDB; 7EEI; X-ray; 3.60 A; A=216-1990.
DR PDBsum; 7EEI; -.
DR SMR; P27316; -.
DR Proteomes; UP000002477; Genome.
DR GO; GO:0001882; F:nucleoside binding; IEA:InterPro.
DR GO; GO:0000166; F:nucleotide binding; IEA:UniProtKB-KW.
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; ISS:UniProtKB.
DR GO; GO:0039696; P:RNA-templated viral transcription; ISS:UniProtKB.
DR GO; GO:0006351; P:transcription, DNA-templated; IEA:InterPro.
DR InterPro; IPR022531; DUF3770.
DR InterPro; IPR029124; L_protein_N.
DR InterPro; IPR007099; RNA-dir_pol_NSvirus.
DR InterPro; IPR014385; RNA-dir_pol_phlebovirus.
DR InterPro; IPR007322; RNA_pol_bunyavir.
DR Pfam; PF04196; Bunya_RdRp; 1.
DR Pfam; PF12603; DUF3770; 1.
DR Pfam; PF15518; L_protein_N; 1.
DR PIRSF; PIRSF000826; L_PhleboV; 1.
DR PROSITE; PS50525; RDRP_SSRNA_NEG_SEG; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Host endoplasmic reticulum; Host Golgi apparatus; Hydrolase;
KW Magnesium; Manganese; Metal-binding; Nucleotide-binding;
KW Nucleotidyltransferase; Reference proteome; RNA-directed RNA polymerase;
KW Transferase; Viral RNA replication; Virion.
FT CHAIN 1..2149
FT /note="RNA-directed RNA polymerase L"
FT /id="PRO_0000222023"
FT DOMAIN 975..1166
FT /note="RdRp catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00539"
FT REGION 18..216
FT /note="Endonuclease"
FT /evidence="ECO:0000250|UniProtKB:A5HC98"
FT REGION 1706..1822
FT /note="Cap-binding"
FT /evidence="ECO:0000250|UniProtKB:A5HC98"
FT ACT_SITE 143
FT /note="For endonuclease activity"
FT /evidence="ECO:0000250|UniProtKB:I0DF35"
FT BINDING 79
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:A5HC98"
FT BINDING 111
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000305|PubMed:23698297"
FT BINDING 111
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000305|PubMed:23698297"
FT BINDING 125
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:A5HC98"
FT BINDING 1134
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_note="catalytic; for RdRp activity"
FT /evidence="ECO:0000250|UniProtKB:I0DF35"
FT MUTAGEN 111
FT /note="D->A: Loss of transcriptional activity but fully
FT active in replication."
FT /evidence="ECO:0000269|PubMed:23698297"
FT MUTAGEN 111
FT /note="D->A: RNA synthesis products are still produced."
FT /evidence="ECO:0000269|PubMed:34787453"
SQ SEQUENCE 2149 AA; 243591 MW; 8D5739C6079A88D7 CRC64;
MDSILSKQLV DKTGFVRVPI KHFDCTMLTL ALPTFDVSKM VDRITIDFNL DDIQGASEIG
STLLPSMSID VEDMANFVHD FTFGHLADKT DRLLMREFPM MNDGFDHLSP DMIIKTTSGV
YNIVEFTNFR GDERGAFQAA MIKLAKYEVP CENRSQGRTV VLYVVSAYRA WCMVYLELER
TLKQREMVYR YRLALSVMDE LRTLFPELSS TDEELGKTER ELPAMVSSIQ INWSVTESVF
PPFSREMFDR FRSSPPDSEY ITRIVSRCLI NSQEKLINSS FFAEGNDKAL RFSKNAEECS
LAVERALNQY RAEDNLRDLN DHKSTIQLPP WLSYHDVDGK DLCPLQGLDV RGDHPMCNLW
REVVTSANLE EIERMHDDAA AELEFAFGSK GQARERNRYH RVHLNMGSDV LVYIAALGVN
GKKHKADTLV QQMRDRSKQP FSPDHDVITY LNFSLHALVT CGQQMRTCTA LSLVIRDSVG
SPEDSSAILV RKGFHEIITE HYKFMGSRIG HGCQMVSLIG AELSASVKQH VKPNYFVIKR
LLGSGIFLLI KPTSSKSHIF VSFALSALAG PLISPLPGFS SPTKMLGILL VTDFVSYKLS
KLTNLCKCVS LMESSFSFWA EAFGIQAGTL VGDFVPRSSD SAAMDASYMG KLSLLTLLED
KAATEELQTI ARYIIMEGFV SPPEIPKPHK MTSKFPKVLR SELQVYLLNC LCRTIQRIAG
EPFILKKKDG SISWGGMFNP FSGRPLLDMQ PLISCCYNGY FKNKEEETEP SSLSGMYKKI
IELEHLRPQS DAFLGYKDPE LPRMHEFSVS YLKEACNHAK LVLRSLYGQN FMEQIDNQII
RELSGLTLER LATLKATSNF NENWYVYKDV ADKNYTRDKL LVKMSKYASE GKSLAIQKFE
DCMRQIESQG CMHICLFKKQ QHGGLREIYV MGAEERIVQS VVETIARSIG KFFASDTLCN
PPNKVKIPET HGIRARKQCK GPVWTCATSD DARKWNQGHF VTKFALMLCE FTSPKWWPLI
IRGCSMFTKK RMMMNLNYLK ILDGHRELDI RDDFVMDLFK AYHGEAEVPW AFKGKTYLET
TTGMMQGILH YTSSLLHTIH QEYIRSLSFK IFNLKVAPEM SKSLVCDMMQ GSDDSSMLIS
FPADDEKVLT RCKVAAAICF RMKKELGVYL AIYPSEKSTA NTDFVMEYNS EFYFHTQHVR
PTIRWIAACC SLPEVETLVA RQEEASNLMT SVTEGGGSFS LAAIIQQAQC TLHYMLMGMG
VSELFLEYKK AVLKWNDPGL GFFLLDNPYA CGLGGFRFNL FKAITRTDLQ KLYAFFMKKV
KGSAARDWAD EDVTIPETCS VSPGGALILS SSLKWGSRKK FQKLRDRLNI PENWIELINE
NPEVLYRAPR TGPEILLRIA EKVHSPGVVS SLSSGNAVCK VMASAVYFLS ATIFEDTGRP
EFNFLEDSKY SLLQKMAAYS GFHGFNDMEP EDILFLFPNI EELESLDSIV YNKGEIDIIP
RVNIRDATQT RVTIFNEQKN LRTSPEKLVS DKWFGTQKSR IGKTTFLAEW EKLKKIVKWL
EDAPEATLAH TPLNNHIQVR NFFARMESKP RTVRITGAPV KKRSGVSKIA MVIRDHFSRM
GHLRGVEDLA GFTRSVSAEI LKHFLFCILQ GPYSESYKLQ LIYRVLSSVS NVEIKESDGK
TKTNLIGILQ RFLDGDHVVP IIEEMGAGTV GGFIKRQQSK VVQNKVVYYG VGIWRGFMDG
YQVHLEIEND IGQPPRLRNV TTNCQSSPWD LSIPIRQWAE DMGVTNNQDY SSKSSRGARY
WMHSFRMQGP SKPFGCPVYI IKGDMSDVIR LRKEEVEMKV RGSTLNLYTK HHSHQDLHIL
SYTASDNDLS PGIFKSISDE GVAQALQLFE REPSNCWVRC ESVAPKFISA ILEICEGKRQ
IKGINRTRLS EIVRICSESS LRSKVGSMFS FVANVEEAHD VDYDALMDLM IEDAKNNAFS
HVVDCIELDV SGPYEMESFH GRSTLTCTPS TILIRTYTFY LTLHQTMISV QAFQVILDEG
VLLIALVNNY LRGSKANCWV RCESVAPKFI SAILEICEGK RQIKGINRTR LSEIVEFVLN
LPKIKSRIYV LICRQCHGAN FPPISVRRLM LEDIASVARR LIIVASFGS
