L_GTOVV
ID L_GTOVV Reviewed; 2198 AA.
AC Q6UY70; Q6XQI7;
DT 10-FEB-2009, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 65.
DE RecName: Full=RNA-directed RNA polymerase L {ECO:0000255|HAMAP-Rule:MF_04086};
DE Short=Protein L {ECO:0000255|HAMAP-Rule:MF_04086};
DE EC=2.7.7.48 {ECO:0000255|HAMAP-Rule:MF_04086};
DE AltName: Full=Large structural protein {ECO:0000255|HAMAP-Rule:MF_04086};
DE AltName: Full=Replicase {ECO:0000255|HAMAP-Rule:MF_04086};
DE AltName: Full=Transcriptase {ECO:0000255|HAMAP-Rule:MF_04086};
DE Includes:
DE RecName: Full=cap-snatching endonuclease {ECO:0000255|HAMAP-Rule:MF_04086};
DE EC=3.1.-.- {ECO:0000255|HAMAP-Rule:MF_04086};
GN Name=L {ECO:0000255|HAMAP-Rule:MF_04086};
OS Guanarito mammarenavirus (isolate Human/Venezuela/NH-95551/1990) (GTOV).
OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina;
OC Ellioviricetes; Bunyavirales; Arenaviridae; Mammarenavirus.
OX NCBI_TaxID=45219;
OH NCBI_TaxID=9606; Homo sapiens (Human).
OH NCBI_TaxID=157541; Zygodontomys brevicauda.
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RA Bowen M.D., Thurman K., Minor E., Meyer R.F., Malfatti S.A., Do L.H.,
RA Smith K.L., McCready P.M., Chain P.S.G.;
RL Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=14698659; DOI=10.1016/j.virol.2003.08.016;
RA Charrel R.N., Lemasson J.J., Garbutt M., Khelifa R., De Micco P.,
RA Feldmann H., de Lamballerie X.;
RT "New insights into the evolutionary relationships between arenaviruses
RT provided by comparative analysis of small and large segment sequences.";
RL Virology 317:191-196(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=18602020; DOI=10.1016/j.mib.2008.06.001;
RA Charrel R.N., de Lamballerie X., Emonet S.;
RT "Phylogeny of the genus Arenavirus.";
RL Curr. Opin. Microbiol. 11:362-368(2008).
RN [4]
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 [5]
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).
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. During transcription, synthesizes subgenomic
CC RNAs and assures their capping by a cap-snatching mechanism, which
CC involves the endonuclease activity cleaving the host capped pre-mRNAs.
CC These short capped RNAs are then used as primers for viral
CC transcription. The 3'-end of subgenomic mRNAs molecules are
CC heterogeneous and not polyadenylated. The replicase function is to
CC direct synthesis of antigenomic and genomic RNA which are encapsidated
CC and non capped. As a consequence of the use of the same enzyme for both
CC transcription and replication, these mechanisms need to be well
CC coordinated. These processes may be regulated by proteins N and Z in a
CC dose-dependent manner. {ECO:0000255|HAMAP-Rule:MF_04086}.
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|HAMAP-Rule:MF_04086};
CC -!- COFACTOR:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_04086};
CC Note=For endonuclease activity. Binds 2 Mn(2+) ions in the active site.
CC The divalent metal ions are crucial for catalytic activity.
CC {ECO:0000255|HAMAP-Rule:MF_04086};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_04086};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_04086};
CC Note=For polymerase activity. {ECO:0000255|HAMAP-Rule:MF_04086};
CC -!- SUBUNIT: Homomultimer; the oligomeric structure is essential for the
CC polymerase activity. Interacts with nucleoprotein N. Interacts with
CC protein Z; this interaction inhibits viral transcription and
CC replication. {ECO:0000255|HAMAP-Rule:MF_04086}.
CC -!- SUBCELLULAR LOCATION: Virion {ECO:0000255|HAMAP-Rule:MF_04086}. Host
CC cytoplasm {ECO:0000255|HAMAP-Rule:MF_04086}.
CC -!- DOMAIN: The N-terminus contains the endonuclease activity (endoN). The
CC central region contains the RdRp activity. {ECO:0000255|HAMAP-
CC Rule:MF_04086}.
CC -!- MISCELLANEOUS: Classified as His(-) endonuclease since it does not have
CC a histidine upstream of the active site that coordinates the first
CC cation. His(-) endonucleases display very low activity in vitro,
CC although they are clearly active in vivo. {ECO:0000255|HAMAP-
CC Rule:MF_04086}.
CC -!- SIMILARITY: Belongs to the Bunyavirales RNA polymerase family.
CC {ECO:0000255|HAMAP-Rule:MF_04086}.
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DR EMBL; AY358024; AAQ55254.1; -; Genomic_RNA.
DR EMBL; AY216504; AAP44540.2; -; Genomic_RNA.
DR RefSeq; NP_899221.1; NC_005082.1.
DR SMR; Q6UY70; -.
DR PRIDE; Q6UY70; -.
DR GeneID; 2943171; -.
DR KEGG; vg:2943171; -.
DR Proteomes; UP000147629; Genome.
DR GO; GO:0030430; C:host cell cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0044423; C:virion component; IEA:UniProtKB-UniRule.
DR GO; GO:0016787; F:hydrolase activity; IEA:UniProtKB-KW.
DR GO; GO:0000166; F:nucleotide binding; IEA:UniProtKB-UniRule.
DR GO; GO:0003968; F:RNA-directed 5'-3' RNA polymerase activity; IEA:UniProtKB-UniRule.
DR GO; GO:0075526; P:cap snatching; IEA:UniProtKB-UniRule.
DR GO; GO:0039689; P:negative stranded viral RNA replication; ISS:UniProtKB.
DR GO; GO:0039696; P:RNA-templated viral transcription; ISS:UniProtKB.
DR HAMAP; MF_04086; ARENA_L; 1.
DR InterPro; IPR026382; CapSnatchArena.
DR InterPro; IPR007099; RNA-dir_pol_NSvirus.
DR InterPro; IPR010453; RNA_pol_arenavir.
DR Pfam; PF06317; Arena_RNA_pol; 1.
DR Pfam; PF17296; ArenaCapSnatch; 1.
DR PIRSF; PIRSF000836; L_ArenaV; 1.
DR PROSITE; PS50525; RDRP_SSRNA_NEG_SEG; 1.
PE 3: Inferred from homology;
KW Cap snatching; Host cytoplasm; Hydrolase; Magnesium; Manganese;
KW Metal-binding; Nucleotide-binding; Nucleotidyltransferase;
KW Reference proteome; RNA-directed RNA polymerase; Transferase;
KW Viral RNA replication; Virion.
FT CHAIN 1..2198
FT /note="RNA-directed RNA polymerase L"
FT /id="PRO_0000361636"
FT DOMAIN 1161..1359
FT /note="RdRp catalytic"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04086"
FT REGION 26..284
FT /note="Endonuclease"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04086"
FT ACT_SITE 115
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04086"
FT BINDING 51
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04086"
FT BINDING 89
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04086"
FT BINDING 89
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04086"
FT BINDING 102
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04086"
FT BINDING 1319
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_note="catalytic; for RdRp activity"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04086"
FT VARIANT 536
FT /note="V -> E"
FT VARIANT 1846
FT /note="S -> P"
SQ SEQUENCE 2198 AA; 250686 MW; 8ABCDA93A6EE54C4 CRC64;
MDEKVFVLKD FIRRQVPDIP ELSYQKEALL SQVEVPMVLT EGFKLLSCLV EIESCRKNSC
ECNFEQKFVD TILSENGVVA PTLPKVIPDG YRFFNKTLIL LETFVRVNPE EFEKKWKTDM
AKLLSLKEDI HRTGITLVPV VDGRGNYNTD LLPDWATERF RWLLIDLLRE SRGAPTMEIE
DQEYHRLIHS LSKTSNQSLG FENIECLKRV HLNYEERLNE QLLKDIVGEV RESKIREELI
KLKTWYREEI YRKGLGNFVQ TDRKSLLQTL VLSSAHSDSL APECPMCCSK ILDLCYQLSM
RIANQTSLEN NFDEPPLPTT QIEKVYLSLL SACNKIKGKK VFNTRRNTLL FLDLIILNFV
AHVYKTQPSE METLKKAGLI IGEMLLLPND RVLDILVARR LLLKKVESCC NWLDRCRHLL
RKEEPVLWDC VSEFTNVPDF ELLLSLAEEL CSEKPVMHYK PPSSLIGDCA HKDLMSMSDG
EFESLFKCLS HISLSLVNSM KTSFSSRLLV NEKDYKRYYG TVRLKECYVQ RFFLRVGLYG
LLFYQKTGEK SRCYSLYLSD KGNLVELGSF YSDPKRFFLP IFSEFVLLAT CAEMLSWLDF
DEKLVDAVTP LLKILVLSIL SSPTKRSQTF LQGLRYFIMA YVNQAHHIQL MSKLAVECKS
ASDVLIQRLS VKIVDMVLSD GSDPDMHMTR KFKFVLNVSY LCHLITKETP DRLTDQIKCF
EKFMEPKLEF GSLIVNPSLN GFLSKEQEDV MIEGVEKFFS KELLTVEDLK RPGVSRELLS
YCVSLFNKGR LRVNGTLGTD PYRPSFTSTA LDLSSNKSVV IPKLNEVGEI VSEYDKQKLV
STCITSMAER FKTKGRYNLD PDTIDFLIMR NLTNLLSARK LDSSKKEELS LLYEHLSEDV
MKAFEEIKYE VEITLSKMRL SRELECGHKK PCTLEGVWAP FNVLKVIRSE TSVHEIRDFD
PDLLGEDVYE KLCVAVYDSP LRPTFFLEKP LDICPLELLL KNLTTKSYED DEFFDCFKYI
LIQAGFDQRL GAYEHKNRSR LGLSEEAFRL KEDVRVSNRQ SNSEAIADRL DKSFFTSAAL
RNLCFYSEES PTEYTCISPN VGNLKFGLSY KEQVGSNREL YVGDLNTKMM TRLVEDFTEA
VANSMNYTCL NSEKEFERAI CDMKMAVNNG DLCCSLDHSK WGPFMSPALF HAFFGALKFK
ISKTGEQVDL GPVLNVLKWH LHKAVEVPIS VAEAYCTGML KRRLGLMSLS CQSVCEEFFH
QKLLLEEGVP SHIMSVLDMG QGILHNSSDL YGLITEQFIN YCLDFLFDVI PVSYTSSDDQ
ITTFKLPTMS SSEDGLDGFD WLELLCFHDF LSSKFNKFVS PKSVSGTFVA EFKSRFFVMG
EETPLLTKFV SAALHNVKCK TPTQLAETID TICDQCVANG VGIEIVTKIS ERVNRLIRYS
GYPQTPFLAV EKQDVKDWTD GSRGYRLQRN IEHYLQGSEQ LEFVRKCAKK VLLKIKKGQV
FEEYLVQLIG KDGDDALKGF LSYAGCESDE IKDVLKYRWL NLSANGDLRL VLRTKLMSTR
RVLEREQIPT LIKTLQSKLS KNFTKGVKKI LAESINKSAF QSSVASGFIG FCKSMGSKCV
RDGSGGFMYI REVLNKQRVC PCEICAQNPG IIFCSDALTL IPEFSRSILW DYFSLVLTNA
CELGEWVFSS VQPPKVPILL NNPNLFWAVK PRGTRLIEDQ LGLGHVLQSV RRSYPKVFEE
HLVPFMNDLQ VSRTTDFTRL RYLDVCVALD MMNENLGIVS HLLKAKDNSI YIVKQSECAV
AHIRQVEYVN QELGLSPQQI CSNFKIQLVF SSMINPLVIT TSVLKSFFWF NEVLNLEDES
QIDVGELTDF TILIKKYNLN RAMMLDDLTM GYVVSTISEP TIHLVSLKRN SNSIVGEQNS
EMLHGEQVED MYSIVLHIQL EHKRHSTKYH LSRTVVYSYT VECETNITDI EKEPSLATVK
NVVLRASGSI EGHQFLDGVN LVASQPIFTG KKVINLSELL ADSEITETYK EGDAVGSILL
NFGTFYEHID DRYAYEIVGP ECSDSPLVLD GGSILADGKK LSSIKVELTG DVILKALGAL
ESEKEVQSLL TGLWPFIRIN NLKVKMAQED FLLMYEMHRE SLLKSLEVFS EWCEFVDFSV
CYSKSLRDLV ISDSSGSLRL KGITCKPINL SNSVTEIE
