L_CPXVB
ID L_CPXVB Reviewed; 2208 AA.
AC Q6XQH2;
DT 20-JAN-2009, integrated into UniProtKB/Swiss-Prot.
DT 26-FEB-2008, sequence version 2.
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 Cupixi mammarenavirus (isolate Rat/Brasil/BeAn 119303/1970) (CPXV).
OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina;
OC Ellioviricetes; Bunyavirales; Arenaviridae; Mammarenavirus.
OX NCBI_TaxID=208899;
OH NCBI_TaxID=89099; Hylaeamys megacephalus (Large-headed rice rat) (Oryzomys megacephalus).
RN [1]
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 [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RA Emonet S., de Lamballerie X., de Micco P., Charrel R.N.;
RT "Complete sequence determination and analysis of the large RNA segment of
RT arenaviruses.";
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).
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; AY216519; AAP44555.2; -; Genomic_RNA.
DR RefSeq; YP_001649218.1; NC_010252.1.
DR SMR; Q6XQH2; -.
DR GeneID; 5848386; -.
DR KEGG; vg:5848386; -.
DR Proteomes; UP000008164; 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..2208
FT /note="RNA-directed RNA polymerase L"
FT /id="PRO_0000361635"
FT DOMAIN 1172..1370
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 2208 AA; 250981 MW; 637E5763AF088DFD CRC64;
MDEKISSLKD FVRKQIPDRP EFFYQKEALL SQVEVSLILT EGFKLMSCLV EVESCEKNSC
VHNSEQKFVD TILAENGIVG PTLPKVMPDG YRYFNKTLLL LEVFVRVRPD EFEKKWKSDM
GKLLSLKDDL LRCGISLVPI VDGRCSYNTS IIPEWATERF RWLLIELLKE SKEAMDFEIE
DQEYQRLIHS LSRTCNQSLG FENIEQLKKV HLNYEDRLNE VILAGLNSDL KESVIREELI
KLKAWYKKEV FEKGHGNFVR TNQTSLLKTL QEIGSHAGTT VPECPMCCSK VFDLCYQMML
KIEGKESLNS SVSSDNNNPQ ISLVGREYLY VLSVCNKIKG KKIFNTRRNT LLFLDLIILN
FVTEVFKKVP LGIQSLKVEG LIIGQMLLLT NDRALDILSA RRLLIKKIEC NESWVKKCGD
TLRRVEPSFW TSVCNYVKLP DFESLLLLAE VLCSDAPLLR YEPVQVEESH CTHKDFQLLN
INQQDCLFEC LSHISLSLIN SMKTSFSSRL LINEKDYKRY FGTVRLKECY VQRFLFTEGK
CGFLFYQKTG ERSRCFSIYL SENGQLTELG SFYADPKRYF LPIFSGCVLR SMCSEMITWL
DFDEELMHVV KPQLRSLVLS ILCSPTKRAQ NFLQGLRYFI MAFVNQAHHK QLMSKLIVEC
KSASDVLIQR LATKVFYTIL TFGEDPGIHM TRKFKFLLNV SYLCHLITKE TPDRLTDQIK
CFEKFLEPKL EFGSVVVNPS LNGILDPKQE DNMLNGLEKL FSKSLYDVED LKRPGISKDV
LNYCLSLFTR GKLKVTGVLK TDPFKPSFTS TALDLSSNKS VVVPKLDELG NIVSVYDKQK
LISSCVASMA ERFRTKGRFN LDPDTIDFLI MKNLTNLLSI SGESPKASEE LSLLYENLPE
EITQVYDEIK NDIQVTLGKI GAKGSYKQKN GKEGKAGSPS NAETLESIWA PFGVLREIKI
ETSTHEIKDF DPGLLSMDIY EKLCTTVFES SLKSSFFIDE VLSICPLELL LKNLTTKSFK
ENDFFECFKY ILIQAGYDQR LGTYEHRSRA RFGFREEVVR LRDDVRVSDR ESNSEAIAKR
LDRSFFTSAA LRNLCFYSEE SPTEYTCVSS NTGNMKFGLS YKEQVGSNRE LYVGDLNTKM
MTRLVEDFAE AVCNSMHYTC LNSESEFDRA ICDMKMAVNN GDLCLSMDHS KWGPFMSPAL
FHRFLSGAKL KTMRLGDSVD TKPVLNVLKW HIHKVVEVPY NVAEAYCTGM LKRRLGLMSL
QTQSISEAFF HQEIQTKKEV PSHIMSVLDM GQGILHNLSD LYGLISEQFL NYCLDFLYDA
IPTSYTSSDD QITMIRMPQQ SMETAEEGNA DWLELLCFHD FLSSKLNKFV SPKTVCGTFA
AEFKSRFFVM GEETPLLTKF VSAALHNVKC KTPSQLAETI DTICDQCVAN GVGVSIVSEI
SKRVNRLIKY SGYPLNPFLA VENQDVKDWV DGSRGYRLQR NIESCSIQES VLKQVRKFAK
DVFLKIKRGQ VFEEHLIQLI GADGDSAMEG FLSYVDCDKD KLREILEHRW LNLSANGDLR
LVLRTKLMSS KRVLEKEQIP TLVKTLQSKL SKSFTKGAKK ILAESINKSA FQASVASGFI
GFCESVGSKC VRDGSGGFLY IREVVSKIIS CQCTLCSANP GIIFCKNALS NVSNFSRPIL
WDYFSLVLTN ACELGEWVFS PTKRPQQPNL LQNPNLFWAV KPKSVRLIED QLGLGHVLQS
IRRSYPKIFE EHLIPFMSDL QVNRTIDFTR LKYLDVCVAI DMMNENLGIV SHLLKRKDNS
VYIVKQNECS VAHVREVQYV DHDIGLSPQQ VCTNFKLQLV LSSMISPLVI STSVLKSFFW
YNEVLKLEDN SLIDIGELTD FVILNKSYGV ERVMYLEDMA MGYVVSSVDE PEIHLINAWV
LTEHDVKKLE SGSKVGDKDG KALAITLNIQ FRHRRHSTKY HFTKGVVYSF TVEFQVPPSL
QGPNLNTVPV REMVLNASGM LGDHQSLDGV PLVASHPLMT GKKPIDLLTL LSESDIQISD
DTGQLMAVYL DFSEFQSLIE DKYSFKIVGP ERLDTPIILK GGVYMSEGKR LSTLMVELSG
NVIVKALGAI ETDKEVGSLL LGLWPYIKTT GQKIKMDQND FLLLYESHRE LLLKSLEGLG
GWLDFLDFSV CFSKSLSDLV ISDNTGSLRL KGVTCRPIHN PRIVEDID
