ID   L_MACHU                 Reviewed;        2209 AA.
AC   Q6IUF8;
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   Machupo virus (MACV).
OC   Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina;
OC   Ellioviricetes; Bunyavirales; Arenaviridae; Mammarenavirus.
OX   NCBI_TaxID=11628;
OH   NCBI_TaxID=56210; Calomys callosus (Large vesper mouse).
OH   NCBI_TaxID=9534; Chlorocebus aethiops (Green monkey) (Cercopithecus aethiops).
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RC   STRAIN=Chicava;
RA   Hajjaj A., Chain P.S.G., Smith K.L., Imbro P.M., Malfatti S.A.;
RL   Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RC   STRAIN=Chicava;
RA   Jahrling P.B., Geisbert J., Ibrahim M.S.;
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).
RN   [5] {ECO:0007744|PDB:7VGQ, ECO:0007744|PDB:7VH1, ECO:0007744|PDB:7VH2, ECO:0007744|PDB:7VH3}
RP   STRUCTURE BY ELECTRON MICROSCOPY (3.60 ANGSTROMS), AND INTERACTION WITH
RP   PROTEIN Z.
RX   PubMed=34697302; DOI=10.1038/s41467-021-26432-3;
RA   Ma J., Zhang S., Zhang X.;
RT   "Structure of Machupo virus polymerase in complex with matrix protein Z.";
RL   Nat. Commun. 12:6163-6163(2021).
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 (By similarity). Interacts with nucleoprotein N (By
CC       similarity). Interacts with protein Z; this interaction inhibits viral
CC       transcription and replication (By similarity) (PubMed:34697302).
CC       {ECO:0000255|HAMAP-Rule:MF_04086, ECO:0000269|PubMed:34697302}.
CC   -!- INTERACTION:
CC       Q6IUF8; Q6UY77: Z; NbExp=3; IntAct=EBI-15954762, EBI-15954744;
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; AY624354; AAT45080.1; -; Genomic_RNA.
DR   PDB; 7VGQ; EM; 4.00 A; A=1-2209.
DR   PDB; 7VH1; EM; 4.20 A; A=1-2209.
DR   PDB; 7VH2; EM; 5.10 A; A=1-2209.
DR   PDB; 7VH3; EM; 3.60 A; A=1-2209.
DR   PDBsum; 7VGQ; -.
DR   PDBsum; 7VH1; -.
DR   PDBsum; 7VH2; -.
DR   PDBsum; 7VH3; -.
DR   SMR; Q6IUF8; -.
DR   DIP; DIP-59721N; -.
DR   IntAct; Q6IUF8; 1.
DR   PRIDE; Q6IUF8; -.
DR   Proteomes; UP000009263; 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   3D-structure; Cap snatching; Host cytoplasm; Hydrolase; Magnesium;
KW   Manganese; Metal-binding; Nucleotide-binding; Nucleotidyltransferase;
KW   RNA-directed RNA polymerase; Transferase; Viral RNA replication; Virion.
FT   CHAIN           1..2209
FT                   /note="RNA-directed RNA polymerase L"
FT                   /id="PRO_0000361641"
FT   DOMAIN          1172..1369
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   2209 AA;  250206 MW;  3A5E81BD278CBF72 CRC64;
     MDEYVQELKG LIRKHIPDRC EFAHQKVTFL SQVHPSPLLT EGFKLLSSLV ELESCEAHAC
     QANTDQRFVD VILSDNGILC PTLPKVIPDG FKLTGKTLIL LETFVRVNPD EFEKKWKADM
     SKLLNLKHDL QKSGVTLVPI VDGRSNYNNR FVADWVIERM RWLLIEILKA SKSMLEIDIE
     DQEYQRLIHS LSNVKNQSLG LENLEHLKRN SLDYDERLNE SLFIGLKGDI RESTVREELI
     KLKMWFKDEV FSKGLGKFKL TDRRELLESL SSLGAHLDSD VSSCPFCNNK LMEIVYNVTF
     SSVERTDGAA TVDQQFSTTH TNIEKHYLSV LSLCNKIKGL KVFNTRRNTL LFLDLIMVNL
     MVDISESCQD AIESLRKSGL IVGQMVMLVN DRVLDILEAI KLIRKKIGTN PNWVKNCSKI
     LERSHPEIWL QLNTLIRQPD FNSLISIAQY LVSDRPIMRY SVERGSDKIC RHKLFQEMSS
     FEQMRLFKTL SSISLSLINS MKTSFSSRLL VNEREFSKYF GNVRLRECYA QRFYLAESLV
     GFLFYQKTGE RSRCYSVYLS DNGVMSEQGS FYCDPKRFFL PVFSDEVLAG MCEEMTSWLD
     FDTGLMNDTG PILRLLVLAI LCSPSKRNQT FLQGLRYFLM AFANQIHHID LISKLVVECK
     SSSEVVVQRL AVGLFIRLLG GESDASSFFS RRFKYLLNVS YLCHLITKET PDRLTDQIKC
     FEKFIEPKVK FGCAVVNPSL NGKLTVDQED IMINGLKKFF SKSLRDTEDV QTPGVCKELL
     NYCVSLFNRG KLKVSGELKN NPFRPNITST ALDLSSNKSV VIPKLDELGN ILSTYDKEKL
     VSACVSSMAE RFKTKGRYNL DPESTDYLIL KNLTGLVSAG PKAKSSQEEL SLMYETLTEE
     QVESFNEIKY DVQVALAKMA DNSVNTRIKN LGRADNSVKN GNNPLDNLWS PFGVMKEIRA
     EVSLHEVKDF DPDVLPSDVY KELCDAVYKS SEKCNFFLEE VLDVCPLGLL LKNLTTSSYM
     EEEYFMCFKY LLIQGHFDQK LGSYEHKSRS RLGFTDETLR LKDEVRLSIR ESNSEAIADK
     LDKSYFTNAA LRNLCFYSED SPTEFTSISS NSGNLKFGLS YKEQVGSNRE LYVGDLNTKL
     MTRLVEDFSE AVGNSMKYTC LNSEKEFERA ICDMKMAVNN GDLSCSYDHS KWGPTMSPAL
     FLALLQMLEL RTPVDRSKID LDSVKSILKW HLHKVVEVPI NVAEAYCIGK LKRSLGLMGC
     GSTSLSEEFF HQTMQLSGQI PSHIMSVLDM GQGILHNTSD LYGLITEQFL CYALDLLYDV
     IPVSYTSSDD QITLVKTPSL DIEGGSDAAE WLEMICFHEF LSSKLNKFVS PKSVIGTFVA
     EFKSRFFVMG EETPLLTKFV SAALHNVKCK TPTQLSETID TICDQCIANG VSTKIVARIS
     KRVNQLIRYS GYGDTPFGAI EDQDVKDWVD GSRGYRLQRK IEAIFYDDKE TSFIRNCARK
     VFNDIKRGRI FEENLINLIG RGGDEALTGF LQYAGCSEQE VNRVLNYRWV NLSSFGDLRL
     VLRTKLMTSR RVLEREEVPT LIKTLQSKLS RNFTKGVKKI LAESINKSAF QSSVASGFIG
     FCKSMGSKCV RDGKGGFLYI KEVYSGINVC ICEICALKPK IIYCNDSLNK VSQFSKPILW
     DYFSLVLTNA CELGEWVFST VKEPQKPLVL NNQNFFWAVK PKVVRQIEDQ LGMNHVLQSI
     RRNYPVLFDE HLAPFMNDLQ VSRTMDSGRL KFLDVCIALD MMNENLGIIS HLLKTRDNSV
     YIVKQSDCAL AHIRQSSYTD WELGLSPQQI CTNFKTQLVL SSMVNPLVLS TSCLKSFFWF
     NEVLELEDDS QIELAELTDF ALMVKNQNVS RAMFVEDIAM GYVVSNFEGV RISLSNVMVD
     GVQLPPKEKA PDVGVLFGLK AENVIVGLVV QIDHVRMSTK FKLRRKMVYS FSLECTMDVG
     DIQNKEVILK VVAVDQSVSG SGGNHMLLDG VPVIASLPLF TGQASFDLAA MLIESNLAGS
     NDNFLMSNVT LDLGGFSPEL SDKYSYRLSG PENQEDPLVL KDGAFYVGGE RLSTYKVELT
     GDLVVKALGA LEDDEGVVSM LHQLWPYLKA TSQVILFQQE DFTIVHDLYK IQLTKSIESF
     GEWIEFTNFK VAYSKSLKEL VISDTQGSFR LKGVMCRPLA NTLQVEDIE