ID   L_TAMVU                 Reviewed;        2221 AA.
AC   A9JR23; B2MW53;
DT   20-JAN-2009, integrated into UniProtKB/Swiss-Prot.
DT   05-FEB-2008, sequence version 1.
DT   03-AUG-2022, entry version 59.
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   Tamiami mammarenavirus (isolate Rat/United States/W 10777/1964) (TAMV).
OC   Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina;
OC   Ellioviricetes; Bunyavirales; Arenaviridae; Mammarenavirus.
OX   NCBI_TaxID=45223;
OH   NCBI_TaxID=42415; Sigmodon hispidus (Hispid cotton rat).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX   PubMed=17624390; DOI=10.1016/j.virol.2007.05.031;
RA   Cajimat M.N., Milazzo M.L., Hess B.D., Rood M.P., Fulhorst C.F.;
RT   "Principal host relationships and evolutionary history of the North
RT   American arenaviruses.";
RL   Virology 367:235-243(2007).
RN   [2]
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   [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; AY924393; AAX99349.1; -; Genomic_RNA.
DR   EMBL; EU627614; ACC94304.1; -; Genomic_RNA.
DR   RefSeq; YP_001911118.1; NC_010702.1.
DR   SMR; A9JR23; -.
DR   GeneID; 6301275; -.
DR   KEGG; vg:6301275; -.
DR   Proteomes; UP000008034; Genome.
DR   Proteomes; UP000172871; 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..2221
FT                   /note="RNA-directed RNA polymerase L"
FT                   /id="PRO_0000361647"
FT   DOMAIN          1171..1369
FT                   /note="RdRp catalytic"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04086"
FT   REGION          29..292
FT                   /note="Endonuclease"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04086"
FT   ACT_SITE        117
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04086"
FT   BINDING         54
FT                   /ligand="Mn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29035"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04086"
FT   BINDING         91
FT                   /ligand="Mn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29035"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04086"
FT   BINDING         91
FT                   /ligand="Mn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29035"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04086"
FT   BINDING         104
FT                   /ligand="Mn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29035"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04086"
FT   BINDING         1327
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         402
FT                   /note="K -> R"
FT   VARIANT         549
FT                   /note="R -> G"
FT   VARIANT         555..556
FT                   /note="LM -> KV"
SQ   SEQUENCE   2221 AA;  254530 MW;  DACEAA7C0EBF280F CRC64;
     MSECLTYFNE LKDLVRKWVP DEDTYVEQKT VLLSQVNFSS IVTEGLKLLS TLIEVDSCVK
     HGCIHNRSKT VNQILYDHRI VGPTLPDVVP DGYRVSGSTL ILLETFVRVN QESFECKYRH
     DFEKLMQLSK DLAKCGLTLV PVIDGRSSYY IERLPDWVIE RMRWLLLRIM SNLRDSGEKI
     EEMEYERLVH SLSNMENQNL GLESLASLRE EGLDYKTRLT KTLKEGIYSN MTTSECRVGI
     AKLYDHFCLL RDSGQYEDVY TTTSRSEMIT WLKTHELVQM SSSERETLIE AETCKFCQIH
     MYAVLKDLVL LRKGWKGSRC RDANEILAHK SLLSDCNKIK GLKVLNTRRN TLLCLDIIVL
     NSLINLIKLQ YTDLQYLINN HFKSVNDRLV SVDLIINKLD KKLTSDPNWL CKLRTKIGHK
     LKIYDLDHVI SWLRPIEVSH WYEFKLERDN SGECVKPTIK YKKSGVGDCQ GEDCNKDVIT
     DDSTFSDYLD ALSTLSMGLM NSMKTSSATK LVVNDERNYF GTVQCDECYF QDLDINYGTT
     LIYQKTGERT RCYGLMSKEG GGPDVYKVGK SFYADPKRYF LPIMSSEVIL KMCREMLSWL
     DWLSEKEMMD VRTKLYTLVI SILTVPSKRV QIYLQGFRYF IMAYVNEFHV KELVCKLKVK
     PLTRAELSVF TQMDDLVALL LTGTSEEHMT KSFKFILNLS YLCHLITKET PDRLTDQIKC
     FEKFLEPKLT FNSVILNLDS SPQLTEGTEE KIIGDLKKLF SKDLGVLDLK EPGVSKEVLS
     LCSSCFNNGM LSLPKVLSRD PQSPSFTSTA LDISSNKSVV VPKLNEVGET ITQYDYQSLL
     SSVVVEMAQS FKDKLRFKLD RRSLQYAIYK RLTNMVSKNE FRSKDDPNDS GILEDIEDLV
     DEGTHKLINE IEANVSDCLS KMSSGCNKSN QSSKGLKKFE KVDLLQKLWS REYMSLILSE
     TSFHEVKDFD PSLLPSESYQ EMCDAVYDSV YRNEFFTEKF LKLCPLELLI KNLATKHYEE
     GDYFECFKYL LIGAGCDNRV GRFDHRSRAR LGFKDTATLV KEESRISSRE SNSEAISKRL
     DKSFFTNSSL RNLCFYSEES PTYRSSVSSS VGKLKFGLSY KEQVGSNREL YIGDLNTKLT
     SRLIEDYFES LTSECRFSCL NNDSEFERAL LDMKSVVRLS GLAVSLDHSK WGPYMSPAIF
     NALFSNLDLQ LKDGGLIDKS PIENLLNWHL HKIVEVPYNV VEAYLKGYTK RSLGLMDRSS
     SSMTEDYFFR QFAKGVVPSH ITSVLDMGQG ILHNASDYYG LLTEQFITLC LELCFDVKMT
     AYTSSDDEIM LSNSYSLKRE SDDDLLDMEK CKEILEFHYY LSSKLNKFIS PKTVAGSFAS
     EFKSRFFIWS QEVPLLTKFV AAALHNVKAK SPHQLAETID TILDQCAANG VSIEIINELS
     KRTNRLISYS GHPVDPFLCV FTTDLKDWVD GSRGYRLQRS IESIINSEEI LSTIRDSCRQ
     LFYMIRSGRI QEEYLISALQ SSPDDCLRQM LKITGTNDSL IEEALTTRWL NLRAFGDLRL
     VLRTKIMTGT RILDKEEVPS LIKSVQSKLS KNFVRGAKKI ITDAINKSAF QSSICSGFIG
     LCKSMGSKCV RDGSGGFIYI KDLLKKIDRH TNCEVCCPLL SVFCEHSLRQ VAPYSRPLLW
     DYFSLTFSNA CELGNWVFSK VELPRPPLGS MNPNFFWPVK PGSHSELEDK VNMNHVLYSI
     KRNFPDLFDE HIAPFLSDLN SLKVSWVQRI KFLDLCVAMD MSSECLGIIS HIMRKRREEL
     YIVKQEELSV CHIRESCSLE KGLQLNSVEI CQNFLTQLLF ESMLNPVLLS TSQFKKYFWY
     GEVEFLPNDA DHDLGQLTQF IMDCKLLNIS RCMCLDDLDV GYVHSKIELS QVFINLSTFI
     NLVDWENRES YQSFDEVLIH SNADHIPLEI GIILSHTRKS FKFRYERKTN YYVKCGITIQ
     KSEISSFSTT LSDGFELHVE EIDCYVSGSE GDHISLDGVG LVPLHPLFSG KEALDLNKLL
     SDQDIEFKQI SLVFSKVKLD FKDHVKDLKN KFSYKLQGPE QGLEPLHLDK GQIMERNTVV
     SRLEVPVTSR SLFLALEALD PGNRPRFLSS LHEYMRKRPG KKDPCFVRMT QQDLCLLVEL
     YEAAFMQVLS AVSDWIEFGC FALCFSKTLN CIMIADDGGD YRLKGRPCKT LSAQKTLTDI
     E