L_RVFV
ID L_RVFV Reviewed; 2092 AA.
AC A2SZS3; A2SZS6; F4ZDJ0;
DT 03-AUG-2022, integrated into UniProtKB/Swiss-Prot.
DT 06-MAR-2007, sequence version 1.
DT 03-AUG-2022, entry version 54.
DE RecName: Full=RNA-directed RNA polymerase L;
DE Short=Protein L;
DE EC=2.7.7.48 {ECO:0000250|UniProtKB:I0DF35};
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};
OS Rift valley fever virus (RVFV).
OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina;
OC Ellioviricetes; Bunyavirales; Phenuiviridae; Phlebovirus.
OX NCBI_TaxID=11588;
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].
RC STRAIN=T-46 {ECO:0000312|EMBL:ABD51509.1}, and
RC T1 {ECO:0000312|EMBL:ABD51511.1};
RA Bird B.H., Khristova M.L., Nichol S.T.;
RT "Rift Valley fever genomics.";
RL Submitted (JAN-2006) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RC STRAIN=ZH-501 {ECO:0000312|EMBL:ABD51510.1};
RX PubMed=17192303; DOI=10.1128/JVI.02095-06;
RA Bird B.H., Khristova M.L., Rollin P.E., Ksiazek T.G., Nichol S.T.;
RT "Complete genome analysis of 33 ecologically and biologically diverse Rift
RT Valley fever virus strains reveals widespread virus movement and low
RT genetic diversity due to recent common ancestry.";
RL J. Virol. 81:2805-2816(2007).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=20547879; DOI=10.1073/pnas.1001760107;
RA Raymond D.D., Piper M.E., Gerrard S.R., Smith J.L.;
RT "Structure of the Rift Valley fever virus nucleocapsid protein reveals
RT another architecture for RNA encapsidation.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:11769-11774(2010).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RC STRAIN=KEN/Bar-032/07 {ECO:0000312|EMBL:AEB20480.1};
RX PubMed=21282193; DOI=10.1093/infdis/jiq004;
RA Nderitu L., Lee J.S., Omolo J., Omulo S., O'Guinn M.L., Hightower A.,
RA Mosha F., Mohamed M., Munyua P., Nganga Z., Hiett K., Seal B., Feikin D.R.,
RA Breiman R.F., Njenga M.K.;
RT "Sequential Rift Valley fever outbreaks in eastern Africa caused by
RT multiple lineages of the virus.";
RL J. Infect. Dis. 203:655-665(2011).
RN [5]
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 [6]
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 [7] {ECO:0007744|PDB:6QHG}
RP X-RAY CRYSTALLOGRAPHY (1.48 ANGSTROMS) OF 1706-1822 IN COMPLEX WITH
RP 7N-METHYL-8-HYDROGUANOSINE-5'-TRIPHOSPHATE, AND DOMAIN.
RC STRAIN=ZH-501 {ECO:0000305};
RX PubMed=31136637; DOI=10.1371/journal.ppat.1007829;
RA Gogrefe N., Reindl S., Guenther S., Rosenthal M.;
RT "Structure of a functional cap-binding domain in Rift Valley fever virus L
RT protein.";
RL PLoS Pathog. 15:e1007829-e1007829(2019).
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 (Probable). During transcription, synthesizes
CC subgenomic RNAs and assures their capping by a cap-snatching mechanism,
CC which involves the endonuclease activity cleaving the host capped pre-
CC mRNAs (By similarity). These short capped RNAs are then used as primers
CC for viral transcription. The 3'-end of subgenomic mRNAs molecules are
CC not polyadenylated. During replication, the polymerase binds the 5' and
CC 3' vRNA extremities at distinct sites (By similarity). In turn,
CC significant conformational changes occur in the polymerase and in vRNA
CC to initiate active RNA synthesis (By similarity). As a consequence of
CC the use of the same enzyme for both transcription and replication,
CC these mechanisms need to be well coordinated (By similarity).
CC {ECO:0000250|UniProtKB:A5HC98, ECO:0000250|UniProtKB:I0DF35,
CC 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 -!- COFACTOR:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000250|UniProtKB:A5HC98};
CC Note=For endonuclease activity. Binds 2 Mn(2+) ions in the active site
CC (By similarity). The divalent metal ions are crucial for catalytic
CC activity (PubMed:31948728). {ECO:0000250|UniProtKB:A5HC98,
CC ECO:0000269|PubMed:31948728};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:I0DF35};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000250|UniProtKB:I0DF35};
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:0000250|UniProtKB:I0DF35};
CC -!- SUBUNIT: Homomultimer (By similarity). Interacts with glycoprotein N;
CC this interaction allows efficient polymerase packaging into virus
CC particles (By similarity). Interacts with nucleoprotein N (By
CC similarity). {ECO:0000250|UniProtKB:P27316}.
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
CC (PubMed:31136637). {ECO:0000250|UniProtKB:A5HC98,
CC ECO:0000250|UniProtKB:I0DF35, ECO:0000269|PubMed:31136637}.
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; DQ375405; ABD51509.1; -; Genomic_RNA.
DR EMBL; DQ375406; ABD51510.1; -; Genomic_RNA.
DR EMBL; DQ375407; ABD51511.1; -; Genomic_RNA.
DR EMBL; DQ375408; ABD51512.1; -; Genomic_RNA.
DR EMBL; HM586957; AEB20480.1; -; Genomic_RNA.
DR PDB; 6QHG; X-ray; 1.48 A; A/B=1706-1822.
DR PDBsum; 6QHG; -.
DR SMR; A2SZS3; -.
DR Proteomes; UP000105929; Genome.
DR Proteomes; UP000136639; Genome.
DR Proteomes; UP000150713; Genome.
DR GO; GO:0001882; F:nucleoside binding; IEA:InterPro.
DR GO; GO:0003968; F:RNA-directed 5'-3' RNA polymerase activity; IEA:UniProtKB-EC.
DR GO; GO:0006351; P:transcription, DNA-templated; IEA:InterPro.
DR GO; GO:0039694; P:viral RNA genome replication; 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; Transferase; Virion.
FT CHAIN 1..2092
FT /note="RNA-directed RNA polymerase L"
FT /id="PRO_0000456058"
FT DOMAIN 975..1166
FT /note="RdRp catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00539"
FT REGION 18..215
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:0000250|UniProtKB:A5HC98"
FT BINDING 111
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:A5HC98"
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 SITE 1713
FT /note="Interaction with the cap substrate"
FT /evidence="ECO:0000269|PubMed:31136637"
FT SITE 1716
FT /note="Interaction with the cap substrate"
FT /evidence="ECO:0000269|PubMed:31136637"
FT SITE 1717
FT /note="Interaction with the cap substrate"
FT /evidence="ECO:0000269|PubMed:31136637"
FT SITE 1728
FT /note="Interaction with the cap substrate"
FT /evidence="ECO:0000269|PubMed:31136637"
FT SITE 1782
FT /note="Interaction with the cap substrate"
FT /evidence="ECO:0000269|PubMed:31136637"
FT CONFLICT 23
FT /note="F -> Y (in Ref. 4; AEB20480)"
FT /evidence="ECO:0000305"
FT CONFLICT 59
FT /note="I -> V (in Ref. 3; ABD51512)"
FT /evidence="ECO:0000305"
FT CONFLICT 249
FT /note="R -> K (in Ref. 4; AEB20480)"
FT /evidence="ECO:0000305"
FT CONFLICT 278
FT /note="S -> N (in Ref. 4; AEB20480)"
FT /evidence="ECO:0000305"
FT CONFLICT 288
FT /note="A -> V (in Ref. 4; AEB20480)"
FT /evidence="ECO:0000305"
FT CONFLICT 300..302
FT /note="LAV -> SAI (in Ref. 4; AEB20480)"
FT /evidence="ECO:0000305"
FT CONFLICT 305
FT /note="A -> D (in Ref. 3; ABD51512)"
FT /evidence="ECO:0000305"
FT CONFLICT 349
FT /note="V -> I (in Ref. 4; AEB20480)"
FT /evidence="ECO:0000305"
FT CONFLICT 435
FT /note="D -> N (in Ref. 4; AEB20480)"
FT /evidence="ECO:0000305"
FT CONFLICT 440
FT /note="P -> L (in Ref. 4; AEB20480)"
FT /evidence="ECO:0000305"
FT CONFLICT 446
FT /note="D -> N (in Ref. 4; AEB20480)"
FT /evidence="ECO:0000305"
FT CONFLICT 493
FT /note="R -> K (in Ref. 4; AEB20480)"
FT /evidence="ECO:0000305"
FT CONFLICT 593
FT /note="T -> R (in Ref. 4; AEB20480)"
FT /evidence="ECO:0000305"
FT CONFLICT 663
FT /note="A -> T (in Ref. 4; AEB20480)"
FT /evidence="ECO:0000305"
FT CONFLICT 1123
FT /note="G -> S (in Ref. 4; AEB20480)"
FT /evidence="ECO:0000305"
FT CONFLICT 1333
FT /note="V -> I (in Ref. 4; AEB20480)"
FT /evidence="ECO:0000305"
FT CONFLICT 1922
FT /note="R -> K (in Ref. 4; AEB20480)"
FT /evidence="ECO:0000305"
FT CONFLICT 1984
FT /note="D -> N (in Ref. 4; AEB20480)"
FT /evidence="ECO:0000305"
FT CONFLICT 2001
FT /note="T -> A (in Ref. 4; AEB20480)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 2092 AA; 238002 MW; 08142F87D254DA82 CRC64;
MDSILSKQLV DKTGFVRVPI KHFDCTMLTL ALPTFDVSKM VDRITIDFNL DDIQGASEIG
STLLPSMSID VEDMANFVHD FTFGHLADKT DRLLMREFPM MNDGFDHLSP DMIIKTTSGM
YNIVEFTTFR GDERGAFQAA MTKLAKYEVP CENRSQGRTV VLYVVSAYRH GVWSNLELED
SEAEEMVYRY RLALSVMDEL RTLFPELSST DEELGKTERE LLAMVSSIQI NWSVTESVFP
PFSREMFDRF RSSPPDSEYI TRIVSRCLIN SQEKLINSSF FAEGNDKALR FSKNAEECSL
AVERALNQYR AEDNLRDLND HKSTIQLPPW LSYHDVDGKD LCPLQGLDVR GDHPMCNLWR
EVVTSANLEE IERMHDDAAA ELEFALSGVK DRPDERNRYH RVHLNMGSDD SVYIAALGVN
GKKHKADTLV QQMRDRSKQP FSPDHDVDHI SEFLSACSSD LWATDEDLYN PLSCDKELRL
AAQRIHQPSL SERGFNEIIT EHYKFMGSRI GSWCQMVSLI GAELSASVKQ HVKPNYFVIK
RLLGSGIFLL IKPTSSKSHI FVSFAIKRSC WAFDLSTSRV FKPYIDAGDL LVTDFVSYKL
SKLTNLCKCV SLMESSFSFW AEAFGIPSWN FVGDLFRSSD 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
IRGCSMFTRK RMMMNLNYLK ILDGHRELDI RDDFVMDLFK AYHGEAEVPW AFKGKTYLET
TTGMMQGILH YTSSLLHTIH QEYIRSLSFK IFNLKVAPEM SKGLVCDMMQ GSDDSSMLIS
FPADDEKVLT RCKVAAAICF RMKKELGVYL AIYPSEKSTA NTDFVMEYNS EFYFHTQHVR
PTIRWIAACC SLPEVETLVA RQEEASNLMT SVTEGGGSFS LAAMIQQAQC 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 RVTIFNEQKT LRTSPEKLVS DKWFGTQKSR IGKTTFLAEW EKLKKIVKWL
EDTPEATLAH TPLNNHIQVR NFFARMESKP RTVRITGAPV KKRSGVSKIA MVIRDNFSRM
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
IRGINRTRLS EIVRICSESS LRSKVGSMFS FVANVEEAHD VDYDALMDLM IEDAKNNAFS
HVVDCIELDV SGPYEMESFD TSDVNLFGPA HYKDISSLSM IAHPLMDKFV DYAISKMGRA
SVRKVLETGR CSSKDYDLSK VLFRTLQRPE ESIRIDDLEL YEETDVADDM LG
