ID   L_OLVVA                 Reviewed;        2234 AA.
AC   Q6XQH7;
DT   20-JAN-2009, integrated into UniProtKB/Swiss-Prot.
DT   26-FEB-2008, sequence version 2.
DT   03-AUG-2022, entry version 71.
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   Oliveros mammarenavirus (isolate Mouse/Argentina/RIID 3229/1990) (OLVV).
OC   Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina;
OC   Ellioviricetes; Bunyavirales; Arenaviridae; Mammarenavirus.
OX   NCBI_TaxID=42764;
OH   NCBI_TaxID=10080; Bolomys.
RN   [1]
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   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RA   Emonet S., de Lamballerie X., de Micco P., Charrel R.N.;
RT   "Complete sequence determination and analysis of the large RNA segment of
RT   arenaviruses.";
RL   Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases.
RN   [3]
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   [4]
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; AY216514; AAP44550.2; -; Genomic_RNA.
DR   RefSeq; YP_001649214.1; NC_010250.1.
DR   SMR; Q6XQH7; -.
DR   GeneID; 5848321; -.
DR   KEGG; vg:5848321; -.
DR   Proteomes; UP000009264; 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   RNA-directed RNA polymerase; Transferase; Viral RNA replication; Virion.
FT   CHAIN           1..2234
FT                   /note="RNA-directed RNA polymerase L"
FT                   /id="PRO_0000361643"
FT   DOMAIN          1184..1383
FT                   /note="RdRp catalytic"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04086"
FT   REGION          26..283
FT                   /note="Endonuclease"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04086"
FT   REGION          879..898
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          927..949
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        879..893
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
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         1342
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"
SQ   SEQUENCE   2234 AA;  256250 MW;  4EC3FE652D19A594 CRC64;
     MDESVSSLFD LLRKHFPAKE EISRQITVVT SQTEMRMILT EGFKLLSLLI ELDSCEVNNC
     SHNKEDLTVE AILSKDNILT IALPRIVPDG YSLYGNVLIL LETFVRVNPS SFEQKYNQDM
     NKLLSLKNDL QLCGITLVPL VDGRTNYYNK FVDDWVIERF RWLLTQIMKV AKESGESIEE
     LEYQRLVTSL SKLENQSLGF ENIIKMPQTG IDYRDKLKAR MFANLSNKMK ESEINQSLLS
     LKLAFDEAYN DESHLKKFQK TNKEDLIFKL GQQINLSDEK LSCMSCSSKL FSIVSSITQN
     RDKLDSHVMS VSNAKLWHHE SGIANVNEYL RILSVCNKIK SAKILNTRRN TLLFLDMIVL
     NFIDDCWKND PTILFQFKKS GLLVGQLAYF VNDRFFDLLL LKELLSKKLK SSPDWIHRCL
     CNIRKQEFFD ISGVEFWIRQ PDYESVEELC CALEPVKPKL QYCRDEDNHE NHKLDLADKD
     NYFTCLSVLS SVCLGLVNSM KTSFTSKMVI NEKSPNNFYG EVELKECYCQ RFYVSDEITG
     LLFYQKTGEK SRCYSIGVTM HGSYKYIGSF YCDPKRFFLP IFSQVVLFQM TEEMMSWLPE
     EPSYKEPVVA NLRKLILMLL CNPSKRNQNF LQGMRYFIMA YVNQFHSVEL MSKLEVPCKS
     VSEECVQKLT YNLLVDVLTK GDVNEHMTRK FKFCLNVSYL CHLITKETPD RLTDQIKCFE
     KFLEPKLKFK SVIINPNLTG DLTEEQEEQL LNSIEKLLGK GLQDINDSSE PGISRELLSM
     CISAFNRDLL RVNGKLKNDP YKPNFTSTAL DLSSNKSVVI PKLDELGNPI SKYDYELLVS
     SCIASMAESF KTKGKYKLDP TSQEFLILKN LYSLMSKSKR DDHMKDSEDS KQNLSSDLEN
     LSEEQVLILE QVKRDVNLAL SKMRETKLKE KTEARQSSSG SSLKNQQKRQ AELQERLSEL
     WSEFMCMKII TVEVSLHEIK DFDPDLIDHT TLKSMLDKLY NSDLASEFFL EEILNPCPLE
     FLVKNMTTSS YLEGDLFECF KYTLISAGFD QKLGTYEHKN KTRLGFKYEA LKVREEGRMS
     LRESNSEAIA RRLDRSVFSN SALRNLCFYS DESPISYSHV SSDTGKLKFG LSYKEQVGSN
     RELYVGDLNT KLMTRLIEDF SESVVSNMNY SCLNSEKEFE RSVMEMKMSV NLGEMNFSLD
     HSKWGPYMSP VIFAAFLQGL KLEQGSMCTP VSVEPIITLL SWHIHKVVEV PYNVIHAYMT
     GMIKRQLGLM SPGESSKTEA FIHRLLVDER EPLSHVMSVL DMGQGILHNT SDLYGLVTEQ
     FINYAMRILY DVSMTSFTSS DDQITMVKLN EDLKDMDNPE VISNWERMIN FHTFISSKFN
     KFVSPKTVIG TFAAEFKSRF FVWGEEVPLL TKFVSAALHN IKCKTPIQLS ETIDTISDQC
     VANGVSVEIV SCISNRTNKL VRYSGFPDNP FLSVENMDVK DWVDGNRGYR LQRNIESHLE
     VDGCTRFVRQ AARKVFRNIK SGKIMEQTLV NLVQEDGDKA FQGFMKSVDV SDDDIKLLQN
     FRWINLSTHG DMRLVLRTKL MSSRRIIEQE EIPGLIKSIQ SKLSKNFVRG AKRILADSIN
     KSAFQSSIAS GFIGFCKSMG SKCVRLGGGG FGYIKDIKNK VKHDCLCDIC FRWRGCVYCP
     SSCADVFEFS RPLMWDYFTL VLTNACELGE WVFEDVEIPK DLYFLRNPNL FWLVKPRVTC
     QLEERLGLSH ILQSIRKNYP TLFETHLSPF MSDFMVGKTL GSLTVKFLDL CVALDLANEN
     LGITKHFLKE RRHEIYVVKQ DESSQSHIRN VKGIESSVEL NSMQVCNNFL TQLLMSSFIQ
     PLVLTSSVFK KFNWFAEVLC LKTEEEVCLK QLTDFVLQVK KFNVDRAMHI EDLSAGYISS
     TINVTSFSLS VPTFLECVDS DFINKEGNEP GDFKDLLSSE FTKDTLTLDF CIQVSHIKRS
     VKFNVKRTLV YTLAVRTQIE KKIILEAIGT DDQISLIVSE LDLFCSGHTG NHFVLDAAPL
     IYSEPLIAGS LKFDLLSMLR DQELSLTSSE KMPTFNFDFS SQKHHIVNKF AYKLVGPSVY
     DEPLVLNKGI VYSGERKLTS LGVDVSGERI VQAMGELDSI SEQELFLTNL WGYSKETDIK
     VRIIQDNLKI LTDNYFVQLK NSLKTFAEWL NLGNYMLCYS KTLDTIMISD VSGRIKLKGV
     ICRKLIEDEV MEVE