ID   L_LASSJ                 Reviewed;        2218 AA.
AC   O09705;
DT   20-JAN-2009, integrated into UniProtKB/Swiss-Prot.
DT   01-JUL-1997, sequence version 1.
DT   03-AUG-2022, entry version 88.
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   Lassa virus (strain Mouse/Sierra Leone/Josiah/1976) (LASV).
OC   Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina;
OC   Ellioviricetes; Bunyavirales; Arenaviridae; Mammarenavirus.
OX   NCBI_TaxID=11622;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
OH   NCBI_TaxID=10112; Mastomys natalensis (African soft-furred rat) (Praomys natalensis).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX   PubMed=9049403; DOI=10.1099/0022-1317-78-3-547;
RA   Lukashevich I.S., Djavani M., Shapiro K., Sanchez A., Ravkov E.,
RA   Nichol S.T., Salvato M.S.;
RT   "The Lassa fever virus L gene: nucleotide sequence, comparison, and
RT   precipitation of a predicted 250 kDa protein with monospecific antiserum.";
RL   J. Gen. Virol. 78:547-551(1997).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX   PubMed=9281522; DOI=10.1006/viro.1997.8722;
RA   Djavani M., Lukashevich I.S., Sanchez A., Nichol S.T., Salvato M.S.;
RT   "Completion of the Lassa fever virus sequence and identification of a RING
RT   finger open reading frame at the L RNA 5' End.";
RL   Virology 235:414-418(1997).
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; U63094; AAB50401.1; -; Genomic_RNA.
DR   EMBL; U73034; AAC05817.1; -; Genomic_RNA.
DR   RefSeq; NP_694872.1; NC_004297.1.
DR   SMR; O09705; -.
DR   PRIDE; O09705; -.
DR   GeneID; 956587; -.
DR   KEGG; vg:956587; -.
DR   Proteomes; UP000002473; 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..2218
FT                   /note="RNA-directed RNA polymerase L"
FT                   /id="PRO_0000361639"
FT   DOMAIN          1174..1370
FT                   /note="RdRp catalytic"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04086"
FT   REGION          26..288
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         1332
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   2218 AA;  253432 MW;  F325C51F96ED2EA6 CRC64;
     MEEDIACVKD LVSKYLVDNE RLSRQKLAFL VQTEPRMLLM EGLKLLSLCI EVDSCNANGC
     EHNSEDKSVE RILHDHGILT PSLCLWYPDG YKLTGNVLIL LECFVRSSPA NFEQKYIEDF
     KKLEQLKEDL KSVDINLIPL IDGRTSFYNE QIPDWVNDKL RDTLFSLLKY AQESNSLFEE
     SEYSRLCESL FMTSGRLSGV ESLNVLMDNR SNHYEEVIAS CHQGINNKLT AHEVKLQIEE
     EYQVFRNRLR KGEIEGQFLK VDKSQLLNEL NNLYADKVVA EDNIEHLIYQ FKRASPILRF
     LYANVDEGNE KRGNQTIGEC QVQCWRSFLN KVKSLRILNT RRKLLLIFDA LILLASKHDL
     MKQKCLKGWL GSCFLRVKDR LVSLEATKRD LEKWGERGNR LRSRITQSSQ CLSKNQILNS
     IFQKTILKAT TALKDVGISV DHYKIDMEVI CLNSYDLIMD FDVSGVVPTI SYQRTEEETF
     PYVMGDVELL GTTDLERLSS LSLALVNSMK TSSTVKLRQN EFGPARYQVV RCKEAYCQEF
     SLGNTELQLI YQKTGECSKC YAINDNKVGE VCSFYADPKR YFPAIFSAEV LQTTISTMIS
     WIEDCNELEG QLNNIRSLTK MILVLILAHP SKRSQKLLQN LRYFVMAYLS DYHHKDLIDK
     IREELITDVE FLLYRLIRTL MNLVLSEDVK SMMTNRFKFI LNVSYMCHFI TKETPDRLTD
     QIKCFEKFLE PKVRFGHVST NPADTATEEE LDDMVYNAKK FLSKDGCTTI EGPDYKRPGV
     SKKYLSLLTS SFNNGSLFKE REVKREIKDP LITSGSAALD LASKKSVVVN KYTDGSRILN
     YDFNKLTALA VSQLTEVFSR KGKYLLNKQD YEYKVQQAMS NLVLGSGQLK SDADGADLDE
     ILLDGGASDY FDQLKETVEK IVDQYREPVK LGSGPNGDGQ PSINDLDEIV SNKFYIRLIK
     GELSNHMVEE FDHDILPGKF YEEFCNAVYE NSRLKQKYFY CGHMSQCPIG ELTKAVSTRT
     YFNHEYFQCF KSILLIMNAN TLMGRYTHYK SRNLNFKFDM GKLSDDVRIS ERESNSEALS
     KALSLTNCTT AMLKNLCFYS QESPQSYDSV GPDTGRLKFS LSYKEQVGGN RELYIGDLRT
     KMFTRLIEDY FEAISLQLSG SCLNNEKEFE NAILSMKLNV SLAHVSYSMD HSKWGPMMCP
     FLFLTVLQNL IFLSKDLQAD IKGRDYLSTL LMWHMHKMVE IPFNVVTAMM KSFIKAQLGL
     RKKTKQSITE DFFYSNFQAG VVPSHISSIL DMGQGILHNT SDFYALISER FINYAISCIC
     GGTIDAYTSS DDQISLFDQS LTELLQRDPE EFRTLIEFHY YMSDQLNKFV SPKSVIGRFV
     AEFKSRFFVW GDEVPLLTKF VAAALHNIKC KEPHQLAETI DTIIDQSVAN GVPVHLCNLI
     QKRTLNPLQY ARYPIDPFLL NCETDVRDWV DGNRSYRIMR QIEGLIPNAC SKIRSMLRKL
     YNRLKTGQLH EEFTTNYLSS EHLSSLRNLC ELLDVEPPSE SDLEYSWLNL AAHHPLRMVL
     RQKIIYSGAV NLDDEKIPTI VKTIQNKLSS TFTRGAQKLL SEAINKSAFQ SSIASGFVGL
     CRTLGSKCVR GPNKENLYIK SIQSLISDVK GIKLLTNSNG IQYWQVPLEL RNGSGGESVV
     SYFRPLLWDY MCISLSTAIE LGAWVLGEPK TVKVFDFFKH NPCDYFPLKP TASKLLEDRV
     GLNHIIHSLR RLYPSVFEKH ILPFMSDLAS TKMKWSPRIK FLDLCVALDV NCEALSLVSH
     IVKWKREEHY IVLSSELRLS HSRTHEPMVE ERVVSTSDAV DNFMRQIYFE SYVRPFVATT
     RTLGSFTWFP HKTSVPEGEG LHRMGPFSSF VEKVIHKGVE RPMFKHDLMM GYAWIDFDIE
     PARFNQNQLI ASGLVDPKFD SLEDFFDAVA SLPPGSAKLS QTVRFRVKSQ DASFKESFAI
     HLEYTGSMNQ QAKYLVHDVT VMYSGAVSPC VLSDCWRLVL SGPTFKGKSA WYVDTEIINE
     FLIDTNQLGH VTPVEIVVDM ERLQFTEYDF VLVGPCTEPT PLVVHRGGLW ECGKKLASFT
     PVIQDQDLEI FVREVGDTSS DLLIGALSDM MIDRLGLRMQ WSGVDIVSTL RAAAPSCEGI
     LSAVLEAVDN WVEFKGYALC YSKSRGKVMV QSSGGKLRLK GRTCEELTRK DECIEDIE