ID   L_TACVF                 Reviewed;        2210 AA.
AC   P20430;
DT   01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
DT   01-FEB-1991, sequence version 1.
DT   03-AUG-2022, entry version 91.
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   Tacaribe virus (strain Franze-Fernandez) (TCRV).
OC   Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina;
OC   Ellioviricetes; Bunyavirales; Arenaviridae; Mammarenavirus.
OX   NCBI_TaxID=928313;
OH   NCBI_TaxID=9416; Artibeus (neotropical fruit bats).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX   PubMed=2718387; DOI=10.1016/0042-6822(89)90349-8;
RA   Iapalucci S., Lopez R., Rey O., Lopez N., Franze-Fernandez M.T.,
RA   Cohen G.N., Lucero M., Ochoa A., Zakin M.M.;
RT   "Tacaribe virus L gene encodes a protein of 2210 amino acid residues.";
RL   Virology 170:40-47(1989).
RN   [2]
RP   INTERACTION WITH PROTEINS Z AND N.
RX   PubMed=12970423; DOI=10.1128/jvi.77.19.10383-10393.2003;
RA   Jacamo R., Lopez N., Wilda M., Franze-Fernandez M.T.;
RT   "Tacaribe virus Z protein interacts with the L polymerase protein to
RT   inhibit viral RNA synthesis.";
RL   J. Virol. 77:10383-10393(2003).
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; J04340; AAA47901.1; -; Genomic_RNA.
DR   PIR; A31468; RRXPTV.
DR   RefSeq; NP_694848.1; NC_004292.1.
DR   SMR; P20430; -.
DR   GeneID; 956595; -.
DR   KEGG; vg:956595; -.
DR   Proteomes; UP000008026; 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   1: Evidence at protein level;
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..2210
FT                   /note="RNA-directed RNA polymerase L"
FT                   /id="PRO_0000079200"
FT   DOMAIN          1172..1368
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         1330
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   2210 AA;  252232 MW;  EACF01C32761024F CRC64;
     MDETVSELKD LVRKHIPNRH EFAHQKDAFL SHCHSGSLLQ EGFKLLSNLV ELESCESHAC
     HLNTCQKYVD VILSDHGIPC PTLPKVIPDG FKLTGKTLIL LETFVRVNPE EFERKWKSDM
     TKLLNLKQDL LRSGITLVPV VDGRTNYSNR FTPEWVVERI RWLLIEILRK SRSSAEIDIE
     DQEYQRLIHS LSNVRNQSLG FENIECLKRN LLEYDDRLAK SLFVGVKGDV RESVIREELM
     KLRLWYKKEV FDKNLGKFRI TNRSELLNNL IRLGKHEDNT TSDCPFCVNK FMDIIYSLTF
     TALKRQDREK SNSELDQYVV CPHEKAYLGV LSICNKIKGL KVFNTRRNTL LFLDLIMVNF
     LDDLFTAKPE ALDSLRRSGL ILGQMVTLVN DRALDFLEAV KLIKKKIETN VKWVENCSKI
     LRRSQQDIWS QISVWARYPD LSKLISIAQT ISSDRPIMRY SAGGNFNTEC KHKTFHMMSD
     AEQVEAFKIL SSVSLSLINS MKTSFSSRLL INEKEYSRYF GNVRLRECYQ QRFFLTDGLI
     VILFYQKTGE RSGCYSIYTC EDGVLVEKGS FYCDPKRFFL PIFSQEVLVE MCDEMTTWLD
     FNSDLMVISK EKLRLLLLSI LCAPSKRNQV FLQGLRYFLM AYSNQFHHVD LLSKLKVECM
     SGSEVIVQRL AVDLFQCLLG EGVDSDPYFA RRFKYLLNVS YLCHLITKET PDRLTDQIKC
     FEKFIEPKID FNCVIVNPSL NGQLTEAQEG MMLDGLDKFY SKTLKDCSDT KLPGVSNELL
     SYCISLFNKG KLKVTGELKN DPFKPNITST ALDLSSNKSV VVPKLDELGN VLSVYDREKM
     ISSCVSSMAE RFKTKGRYNI DPSTLDYLIL KNLTGLVSIG SKTQRDCEEL SMMFEGLTEE
     QAEAFNDIKN SVQLAMVKMK DSKSGDVNLS PNQKEGRVKS STGTLEELWG PFGIMREIRT
     EVSLHEVKDF DPDVLASDLY KELCDVVYYS SSKPEYFLER PLEVCPLGLL LKNLTTSAYF
     DEEYFECFKY LLIQGHYDQK LGSYEHRSRS RLGFTNEALR VKDEVRLSMR ESNSEAIADK
     LDRSYFTNAA LRNLCFYSDD SPTEFTSISS NNGNLKFGLS YKEQVGSNRE LYVGDLNTKL
     ITRLVEDFAE AVGSSMRYTC LSSEKEFDRA ICDMKLAVNN GDLSCSLDHS KWGPTMSPAL
     FLTFLQFLEL RTPKERNIIN LEPVLNVLRW HLHKVIEVPV NVAEAYCTGN LKRSLGLMGC
     GSSSVGEEFF HQFMPVQGEI PSHIMSVLDM GQGILHNMSD LYGLITEQFL NYVLDLLYDV
     IPTSYTSSDD QVTLIKLPCA SDDNQVNDEW LEMLCFHEYL SSKLNKFVSP KSVAGTFVAE
     FKSRFFVMGE ETPLLTQFVA AALHNVKCKT PTQLSETIDT ICDQCVANGV SVQIVSKISQ
     RVNQLIKYSG FKETPFGAVE KQDVKDWVDG TRGYRLQRKI ESIFSDDEMT GFIRSCAKRV
     FNDIKRGKVF EENLISLIGR DGDDALVGFL RYSSCSEQDI MRALGFRWVN LSSFGDLRLV
     LRTKLMTSRR VLEREEVPTL IKTLQSRLSR NFTKGVKKIL AESINKSAFQ SSVASGFIGF
     CKSIGSKCVR DGEGGFLYIK DIYTKVKPCL CEVCNMKRGV IYCRPSLEKI EKFSKPILWD
     YFSLVLTNAC EIGEWVFSSV KEPQIPVVLS NRNLFWAVKP RIVRQLEDQL GMNHVLYSIR
     KNYPKLFDEH LSPFMSDLQV NRTLDGRKLK FLDVCIALDL MNENLGIVSH LLKARDNSVY
     IVKQSDCAMA HVRQSDYVDK EVGLSPQQVC YNFMVQIILS SMVNPLVMST SCLKSFFWFN
     EVLELEDDGQ IELGELTDFT FLVRDQKISR AMFIEDIAMG YVISNLEDVR LYIDKITIGE
     QPLAPGRHIN DLLDLLGNFD DHEDCDLRFL IQVEHSRTST KYRFKRKMTY SFSVTCVSKV
     IDLKEASVEL QVVDVTQSVS GSGGSHLLLD GVSMIAGLPI FTGQGTFNMA SLMMDADLVE
     TNDNLILTDV RFSFGGFLSE LSDKYAYTLN GPVDQGEPLV LRDGHFFMGT EKVSTYRVEL
     TGDIIVKAIG ALDDPEDVNA LLNQLWPYLK STAQVMLFQQ EDFVLVYDLH RSGLIRSLEL
     IGDWVEFVNF KVAYSKSLKD LVVSDNQGSL RLRGIMCRPL ARRNTVEDIE