L_CHAVB
ID L_CHAVB Reviewed; 2208 AA.
AC B2C4J3;
DT 20-JAN-2009, integrated into UniProtKB/Swiss-Prot.
DT 20-MAY-2008, sequence version 1.
DT 03-AUG-2022, entry version 59.
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 Chapare mammarenavirus (isolate Human/Bolivia/810419/2003).
OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina;
OC Ellioviricetes; Bunyavirales; Arenaviridae; Mammarenavirus.
OX NCBI_TaxID=499556;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=18421377; DOI=10.1371/journal.ppat.1000047;
RA Delgado S., Erickson B.R., Agudo R., Blair P.J., Vallejo E., Albarino C.G.,
RA Vargas J., Comer J.A., Rollin P.E., Ksiazek T.G., Olson J.G., Nichol S.T.;
RT "Chapare virus, a newly discovered arenavirus isolated from a fatal
RT hemorrhagic fever case in Bolivia.";
RL PLoS Pathog. 4:E1000047-E1000047(2008).
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; EU260464; ABY87071.1; -; Genomic_RNA.
DR RefSeq; YP_001816785.1; NC_010563.1.
DR SMR; B2C4J3; -.
DR GeneID; 6216305; -.
DR KEGG; vg:6216305; -.
DR Proteomes; UP000008449; 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.
DR PROSITE; PS00501; SPASE_I_1; 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_0000361634"
FT DOMAIN 1171..1367
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 1329
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; 252825 MW; 01FBA91DEC3CA6B0 CRC64;
MDTFLLELKD LVRKYVPELV ELSFQKDALL SQVHPRLVLV EGFKLLSLLV ELESCKVNAC
RHNFEQKFVD VILSDHGVIC PTLPKVTPDG FNLMGKTLIL LETFVRVNPN DFERKWKADM
SKLMSLKDDL ARVGITMVPV VDGRGSYNTS YLPEWATERL RWLLIEILKG VKATSEIEIE
DQEYQRLIHS LAKANNQSMG FENLEFLKRR LLSYDQLLDT SLLVGIRNDV RESKIIEELI
KIKLWYKTEI FNKGLGKFKR TNKSNLLSDL LKIGLHQDSD TINCMFCSCK ILELCYTLSN
KLSIDHSKEE MKDDEVGGKQ PVCISYSSLL SICNKIKGSK IFNTRRNTLL FLDLIMLNFI
VDEMIQDDSV VDSLRGAGFI IGQMVVLVND RALDILAAMK LIRHKLGNSK DWLSVCGKVL
KRYDEEMWKE VKTYIKEPDF DMLFQLAKSL VSERPIMRYT VHKDNESRCL HQNSLNISDQ
SFKAMLKALS HVSLSLINSM KTSFSSRLLI NEKDYSRYYG NVRLKECYVQ RFPISSRVTG
YLFYQKTGER SRCYSLYISE NGELSELGSF YCDPKRFFLP VFSEDTIVSM CNEMVCWLDF
DEQLVELVKP KLRSLVLLLL CSPSKRNQTF IQGLRYFIMA YANQAHHVDL MSKLEIECKS
SSEIQLQRLA VTLFELVLST GDDKDFGFAR RFKFLLNISY LCHFVTKETP DRLTDQIKCF
EKFLEPKLNF NSVIVNPSLS GILTEAQEEI MTSSVNRFFQ KNLTNISDVK EPGVSKELIS
FCVSLFNRGK LRVSGDLKVD PFRPSFTSTA LDLSSNKSVV VPKLDELGNA LSKYDKQMMI
SSCVTTLTEM FKTKGRYNLD PDSLDFLVLK NLSNLVSVSV SKGQMKEELS LLYDTLSEEQ
LESFEQIKQD VQLTLSRMKE SKCNNVGLGN SRKVNKHLSK SELLETLWSP YQVLRAIKNE
VSIHEIKDFD PDIIEHETVK KLCDEVYQSS NKLEFFLEEP LKSVPLEFLL KNLTTIAYEE
TDYLECFKYL LIQGGFDQKL GSYEHKSRSR LGLSSEALRV QEDARVSTRE SNAEAIAKKL
DKTFFTSAAL RNLCFYSEDS PTEFTSVSTN TGNLKFGLSY KEQVGSNREL YVGDLNTKLM
TRLVEDFSEM ITSSMRYSCL NSEKEFERAI CDMKMAVNNG DISMSLDHSK WGPHMSPALF
YSFLANLNLT EPKSRAKLNL GPLLDILKWH LHKVVEVPFN VAQAYCVGKI KRSLGLMECQ
TSSVTEQFYH NFLQRENEIP SHIMSVLDMG QGILHNLSDL YALITEQFLN YAIYKLYDVD
VLSYTSSDDQ ISIMKLPAYE HIDEDSPDWL EIVCFHEYLS SKLNKFVSPK SVVGNFVAEF
KSRFFVMGEE TPLLTKFVAA ALHNVRCKTP TQLAETVDTI CDQCVANGVS VSIVSKISER
VNRLVKYSGF GETPFLSVVK QDVKDWSDGS RGYRLQRNIE NSLRDSKILE VMRKGARKVF
LGIKNGRIFE ENLIGLIGRG GDEALRGFLL YAEVDKDEIE NALRYRWVNT STFGDLRLVL
RTKIMSSKRV LERESIPSLV KTLQSRMSKN FTKGAKKILA ESINKSAFQS SVASGFIGFC
KSMGSKCVRD GSGGFIYLKD IYKKITTCEC KHCSVWRGVV YCEKSVEKIF QFTRSIMWDY
FTLVLTNACE LGEWVFSSVK LPTKATILDN PNLFWAIKPR THKHIEDRLG LNHILHSIKK
NYPQLFEEHL APFMSDLQSN QMINPSKIKF LDICVALDMV NENLGIIGHL LRGRNNTIYI
VKQSECAGAH VRQADYVDQD LGLSPQQICY NFKVQFLLSS MINPLIVSTS TLRSFFWFNE
VLSIEEDDQI ELGELTDFTL SIKTYNLERA MTLDDMTMGY VCSTLLDEVV SLESLDSCQD
LAALQFKRQD LSDFFRDLGE DFVKVGLNIQ IVHQRRSTKF DISRKVVYTF RILLLINLSE
HLREEVKIPV QSLSLYASGA GNNHLFLDGV SMIPTLPLFN GSKSVNLAKV LIEHELATSN
DFKLLECVIM DFSNFLDELR DKYSYVLVGP EEQENPIVFQ NGAFMADNQK LSYMRVEIFG
DTIVKALGAL ETDREIENLL CNLWPYLKSI KKTIDFNQAD FEMIYDLHRT ALLKSLCQMD
SWIEFTSFSV AYSKHLQDLV VSDNLGNLRL KGITCRPFRR DQCIQEIE
