L_BCNVU
ID L_BCNVU Reviewed; 2216 AA.
AC A0PJ24;
DT 20-JAN-2009, integrated into UniProtKB/Swiss-Prot.
DT 09-JAN-2007, sequence version 1.
DT 03-AUG-2022, entry version 60.
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 Bear Canyon mammarenavirus (isolate Mouse/United States/AV A0070039/2000)
OS (BCNV).
OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina;
OC Ellioviricetes; Bunyavirales; Arenaviridae; Mammarenavirus.
OX NCBI_TaxID=192848;
OH NCBI_TaxID=42520; Peromyscus californicus (California mouse).
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 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 [3]
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; AY924390; AAX99344.1; -; Genomic_RNA.
DR RefSeq; YP_001649225.1; NC_010255.1.
DR SMR; A0PJ24; -.
DR PRIDE; A0PJ24; -.
DR GeneID; 5848382; -.
DR KEGG; vg:5848382; -.
DR Proteomes; UP000172257; 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..2216
FT /note="RNA-directed RNA polymerase L"
FT /id="PRO_0000361633"
FT DOMAIN 1167..1364
FT /note="RdRp catalytic"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04086"
FT REGION 26..289
FT /note="Endonuclease"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04086"
FT ACT_SITE 114
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 88
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04086"
FT BINDING 88
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04086"
FT BINDING 101
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04086"
FT BINDING 1323
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 2216 AA; 255780 MW; 50A106A262B03068 CRC64;
MSEYLDELKE LIRKWIPDEE MYIEQKTSFL SQVNLRSVVI EGLKLLSIII EIDSCKKHGC
VHNKNKTVNQ ILRDHRIVGP TLPDVVPDGY RVIGSTIILL EAFVRVSHES FEIKYKSDFE
KLMQLSKDLS RCGLTLIPVV DGRSNYYTEH FPDWTIERMR WLILKITNFL RDNGEEIEEL
EYSRLVYSLS NMENKNLGLE SLKILKEEGL DYKAKLMSVM RDGVNSNMSA SECRVEMAKI
YDQFSFLRKN GLYKDVYCKT SRTEIINWLK DHKLILLSGE TRTAMLDERQ CGYCRNHMFR
ILASLIKNKR HYQSLTNPKK CGSIQSHKKL LSDCNKIKGL KVLNTRRFTL LCLDVIILNS
LLELIDAGEI DNEFLVNNHF KSVNDRLVSI DLIIDRLNKK LMSKPNWIGS VKYKMKRTLE
IHGLYYVSKW LKQVDIDSWY EFKMMREHSD KCVKPTLKYK KDAARKCGQP EFGSSTILDD
EVFLEYLEAL STLSLGLVNS MKTSSAAKFL INDKSNYFGT VQCNECYFQD LDKSYNSLLI
YQKTGERSRC YGLMFKSEQF ENVYEVGESF YADPKRFFLP IMSSEVILKM CVEMLSWLDW
LSEQELKAFK SKLYTLIINI LTVPSKRVQV YLQGFRYLIM AFVNELHFKE LQNKLKVQPL
TISECYVFTL MDDLVHLLLT EAQEENMSKV FRFVLNLSYL CHLVTKETPD RLTDQIKCFE
KFLEPKVDFN SVFVNLDSSP HLSGEVEEKF IKDLNRLFSK DLGVEDLKDP GISKELISLC
ASCFNCGLLP MSKVLKHDPQ SPSFTSTALD ISSNKSVVVP KLDEVGETVT QYDYQSLLSS
TVVDMAQSFK DKLKYKLDRK SIQFAIFKRL TNMVLKRKTD HDVKDDLDDE LSEIVDDDTL
RVINDVEANV SECLSKMGKI SRAATVGGQN NLGRFEKIDT LKRLWDRESM NFILMETSLH
EVKDFDPSIF PIEKYKSMCE LVYDSKMKSE FFTDEVLKFC PLDLLVKNLA TKCYLEEDFF
ECFKYILISA GFDNRVGRYD HRSRSRLGFK DEAILIKENS RISSRESNSE AISRRLDKSF
FTNSSLRNLC FYSEESPTYR STVSSSVGKL KFGLSYKEQV GSNRELYVGD LNTKLTSRLI
EDYFESLTSE CKFSCLNNDA EFERALLDMK CVVRLSGLAV SMDHSKWGPY MSPAIFNILF
SNLNLELNDG VFIDKAPIEN LLNWHLHKIV EVPYNVIDAY LKGYTKRRLG LMDRSSTSIT
EDFIFNWFAK GVVPSHISSV LDMGQGILHN TSDYYGLLTE QFILQCLDFI FDIKSTAYTS
SDDEILLSNS PSLKKVDEDS LDINKCQEVL EFHNYLSSKF NKFVSPKTVA GSFASEFKSR
FFIWSQEVPL LTKFVAAALH NVKAKSPHQL AETVDTILDQ CIANGVSIEV VKAISRRTNK
LITYSGHPKN PFLCVENTDL KDWVDGSRGY RLQRSVESLF NDDDLPLTIR NSCRSLFHRI
RSGDIQEEFL INALQTSPDE CLAKMLRLSD VDESTIDKVL EFRWLNLRAH GDLRLVLRTK
VMSGTRILDR EEVPSLVKSV QSKLSKNFVR GAKKIITDAI NKSAFQSSIC SGFIGFCKSM
GSKCVRDGNG SFQYIKHFLK SIILHSHCEV CKPEMSVFCR AALEELKPFS RPIFWDYFSL
TFSNACELGN WVFSNVTIPK RTPTTVNPNF FWPVKPGSHT ELEDKVNMNH VLYSIKRNFP
DLFDEHIAPF LSDLNSLKIS WIQRIKFLDL CVAMDMSSEC LGIISHIMRR KREELYIVKQ
NELSVAHMRD SSPMEAGYQL NSSEICHNFL CQLVFESMLH PVLLTTGQFK KYFWFGEVEL
LPNEADHDLG QLTQFVMDCK TLNISRCMSL DDLDVGYVHS SILMGDIYVN FSSFLHLLDW
ENRRNYKTFD EIILCSREDT IPMEIDFTIS HSRKSFKFKY ERKTNYHIKS KVLVQKVDIE
EAQNQGFDIL ELEVHEIECF VSGSQGNHIS LDGVGLIPLH PLFSGKEFLD VNKLLIKQDE
NFESTHSVFS KVKLNFSNHT KDLKNKYSYK LQGPEYNMNP LHLYRGQIME NNFVISRLDV
QITSRSVFLA LEALESEDRI PFLISLHIYT RSNNKKENSC FIRMTQSDLC LLIDSYEKEF
TEVLKSLSDW MDFGDFALCF SNNLNCIMIA DPDGQFKLKG RQCRKVSSAS APLEID
