ID   L_SABVB                 Reviewed;        2212 AA.
AC   Q6UY61; Q6XQI5;
DT   20-JAN-2009, integrated into UniProtKB/Swiss-Prot.
DT   05-JUL-2004, sequence version 1.
DT   03-AUG-2022, entry version 70.
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   Sabia mammarenavirus (isolate Human/Brasil/SPH114202/1990) (SABV) (Sabi
OS   mammarenavirus).
OC   Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina;
OC   Ellioviricetes; Bunyavirales; Arenaviridae; Mammarenavirus.
OX   NCBI_TaxID=2169992;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
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; AY358026; AAQ55263.1; -; Genomic_RNA.
DR   EMBL; AY216506; AAP44542.2; -; Genomic_RNA.
DR   RefSeq; YP_089660.1; NC_006313.1.
DR   SMR; Q6UY61; -.
DR   PRIDE; Q6UY61; -.
DR   GeneID; 3077250; -.
DR   KEGG; vg:3077250; -.
DR   Proteomes; UP000009267; 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..2212
FT                   /note="RNA-directed RNA polymerase L"
FT                   /id="PRO_0000361646"
FT   DOMAIN          1175..1371
FT                   /note="RdRp catalytic"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04086"
FT   REGION          30..288
FT                   /note="Endonuclease"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04086"
FT   REGION          922..942
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        119
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04086"
FT   BINDING         55
FT                   /ligand="Mn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29035"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04086"
FT   BINDING         93
FT                   /ligand="Mn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29035"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04086"
FT   BINDING         93
FT                   /ligand="Mn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29035"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04086"
FT   BINDING         106
FT                   /ligand="Mn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29035"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04086"
FT   BINDING         1333
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         965
FT                   /note="T -> A"
SQ   SEQUENCE   2212 AA;  252797 MW;  CB68C2AC3F6A9256 CRC64;
     MQDPLLGTLS ELKDLVRKTI PDVIELAYQK DALLSQVHPR SVLIEGFKLL SLLVELESCK
     VNACHHNYEQ KFIDVILSDG GILCPTLPKV VPDGYNLMGK TLILLETFVR VNPDDFEKKW
     KADMSKLISL KTDLGKIGVT LVPVVDGRSN YNTSFVSDWT TERLRWLLIE VLKGMKTTSE
     LEIEEQEYHR LIHSLAKTNN QSLGFENLEC LKRNMLSYDQ LLDSSLLVGV KNDVKESKVM
     EELIRLKIWY KSEVYEKGLG KFVKTDKKVL LSQLITLGSH EENDSLDCAF CSSRILELCF
     KLSVKMHEDV LTRGLNLDGT KTLHSSVQSY LNVLSMCNKI KGSKIFNTRR NTLLFLDLIM
     LNFVVDEMVK DSTVIRNLKN AGLIVGQMIL LVNDRVLDIL TANKLIRQKL TTNEKWLSIC
     SSVLKRYDLE LWEKLCYLIR VPDFNELFQL AKELVSDRPM MRYSVHKAEE RQCCHKAMEN
     FTDDDFKIML KALSHLSLGL INSMKTSFSS RLLINERDYS RYFGNVRLRE CYIQRFPITN
     NIIGLLFYQK TGERSRCYSL YIAENGELTE IGSFYCDPKR YFVPIFSEAV ITSMCEEMIN
     WLNFDSELVR IVSTQLKTLM LLLLCSPSKR NQTFLQGLRY FIMAYVNQAH HIDLMSKLAV
     ECKSSSEIQL QRLCVRLFVS ILSGDNEIEY GFTRRFKFLL NISYLCHFIT KETPDRLTDQ
     IKCFEKFLEP KLKFNSVIVN PSLNGTLTES QEHQMISSID RFFSKELLDQ SDVKEPGVSR
     ELLGYCVSLF NRGKLRVSGD LKVDPFRPTF TSTALDISSN KSVVVPKLDE LGNIVDKYNK
     QLMVSSCVTS LVEMFKTKGR YNLDPDSIDF LVLKNLTNLV SANVPQEKSQ EELSTLYEAL
     TEDQISAFEQ VRDEVQLALH KMKSSDAREE RLQDPKRNEK NASKGKILES LWSPHQVNRA
     IKNETSIHEI KDFDPDILDS HLVEKLCHEV YNSSQKSLFF LDEPLKSVPL EMLLINLTTI
     AYEEEEFFEC FKYLLIQGDF DQKLGTYEHK SRSRLGLSSE ALKVQENARV STRESNAEAI
     AKKLDRTFFT SAALRNLCFY SEDSPTEFTS VSTNTGNLKF GLSYKEQVGS NRELYVGDLN
     TKLMTRLVED FSEVVTGSMR FSCLNSEKEF ERAICDMKMA VNNGDFSLSM DHSKWGPHMS
     PALFFTFLAN LNLTEPKSRT RLNLDPLLNI LKWHLHKTVE VPFNVAQAYC IGKLKRSLGL
     MECQCSSLTE EFYHSYLQIQ DEIPSHIMSV LDMGQGILHN LSDLYALITE QFLNYVIHKL
     FDIDVTSYTS SDDQISIMKL PLSTKENDED FDWLEIICFH EYLSSKLNKF VSPKSVVGNF
     VAEFKSRFFV MGEETPLLTK FVAAALHNVK CKTPTQLAET IDTICDQCVA NGVGVDIVSR
     ISERVNRLIS YSGYKETPFL TIVNQDVKDW TDGSRGYRLQ RNIENSFGNQ ELLRLIRRGA
     RKVFLEIKKG HVFEENLIGL IGRGGDEALR GFLLYAGFAE NDIVEALRHK WLNPSTFGDL
     RLVLRTKIMS SKRILERESV PSLIKTLQSR MSKNFIKGAK KILAESINKS AFQSSVASGF
     IGFCKSMGSK CVRDGKGGFM YLKELYNNVN KCGCCICLEW PGVVYCQDSL AKISQFARSI
     LWDYFTLVLT NACEIGEWVF SDVKSPSAPP ILSNPNLFWA VKPKIQKHIE DRLSLNHILH
     SIKRNYPYLF EEHLAPFMSD LQFNQMMNPS HVKFLDVCIA LDMMNENLGI IGHLLRGRNH
     FIYIVKQSEC ASAHIRQSDY VDHELGLSPQ QVCYNFKVQF LFSSMIDPLI VSTSTLKTFF
     WFNEVLSIEE EDQIDLGELT DFTLFIKTGH LNRAMTADDI TMGYVCSNLA EEIITLNSYG
     SFQEFRSNHP SKNDLSDILK TLTSESIKLT LDIQIVHMRN STKYNISRKI VYTLKALCAL
     PLEDCFTKDP VALVESLELF ASGVNGGHLQ LDGVTMVSVL PLLRGKKAVN LAQILMDNDL
     AATNDHNVME SVTLDFTKFH DELGDKFCYS LVGPEDQGNP IVLHNGMFMI DNQKLSYLKV
     EIFGDTIIKA LGALDSPREI GSLLHGLWPY LKATKQIINF DQTDFEMIYD LHRVVLLESI
     AQFGDWVEFA SFKVAFSKHY KDIVVADNLG NLRLKGVTCR LFRQQQSVED IE