L_WWAVU
ID L_WWAVU Reviewed; 2219 AA.
AC B2ZDY2;
DT 20-JAN-2009, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-2008, sequence version 1.
DT 03-AUG-2022, entry version 51.
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 Whitewater Arroyo mammarenavirus (isolate Rat/United States/AV
OS 9310135/1995) (WWAV).
OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina;
OC Ellioviricetes; Bunyavirales; Arenaviridae; Mammarenavirus.
OX NCBI_TaxID=46919;
OH NCBI_TaxID=42407; Neotoma (wood rats).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RC STRAIN=AV 9310135;
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 [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; EU646186; ACD03600.1; -; Genomic_RNA.
DR SMR; B2ZDY2; -.
DR Proteomes; UP000009268; 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..2219
FT /note="RNA-directed RNA polymerase L"
FT /id="PRO_0000361648"
FT DOMAIN 1170..1367
FT /note="RdRp catalytic"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04086"
FT REGION 29..292
FT /note="Endonuclease"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04086"
FT ACT_SITE 117
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04086"
FT BINDING 54
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04086"
FT BINDING 91
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04086"
FT BINDING 91
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04086"
FT BINDING 104
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_04086"
FT BINDING 1326
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 2219 AA; 255596 MW; 91D73267930FBB7D CRC64;
MVDCNDRINE LKDLIRKWVP DEEAYTEQKT TFLSQVNPSS IITEGLKLLS MLIEIDSCLK
HGCVFNRNKT VNQILKDHRI IGPTLPDVVP DGYRVSGSTI ILLETFVRVN QESFEQKYKH
DFEKLIQLSK DLSKCGLILV PVIDGRSNYY VDRFPDWVVE RIRWLLLKLM DNVKDTGERI
EELEYNRLIS SLSSMENQNL GLESLKALRE EGLDYKTKLM EAIRDGIRPN LTASECRIGI
AKVYDQFCLL RDSGQYQNVY CRTSRSEMIE WLKDHKLTSL INGSEGTFFN NERCGFCQNH
MLRVIAELVH SKRVSSNYTP TNDKEISRHK KLLSDCNKIK GLKVLNTRRH TLLCLDVIVL
NSLIEMIKLK INSSQFLINN HFKSVNDRLL SVDLIINKLE KKLLKQPDWL GNVKGKLSKR
IKPYNLDYVI TWLKELDYEF WYEFKFEREH SARYEKPTLR YKRQSERVCY QVEFGTDKIF
NEEVFLEYLD ALSSLSLGMM NSMKTSSATK LVINDEKSFY GTVQCEECYF QDLDSSYNSI
LLYQKTGEKS RCYGLMLNDD ELSDVYRVGQ SFYADPKRFF LPIMSSNVIL KTCEEMLSWL
DWLTNEETNM IRTKLFTLVI NVLTVPSKRV QIYLQGFRYF IMAFVNEFHF KRLNEKLSVQ
ALTSAEHHVF VLMDELVVCL LEEALEENMA KIFKFVLNLS YLCHFITKET PDRLTDQIKC
FEKFLEPKLQ FGSAFVNLDS SPSLPKEIED KFVKDINNLF SKDLHTNDLE SPGLSKEILS
LCTSCFNCGM LTVGKVLQND PQSPSFSSTA LDISSNKSVV VPKLDEVGEI ITHYDYQNLL
SSVVVEMAQS FKDKLRYKLD RKSVQYAIYR RLTNMVLTKN LNEKNHINEN CEDFEEFLDE
DTCRLISDIE SNVLECLSNM ATPPVRKVIK GQEITQRYEG PDLLGRLWSR ELMGPILAET
SLHEVKDFDP SIFSFETYQE LCELIFNSEL KEQFFLDDVL RFCPLELLVK NLTTKNFIEK
DFFECFKYIL ISAGFDNRVG RYDHRSRSRL GFKDAAYHVK EKSRISLRES NSEAVSKRLD
KSFFTNSSLR NLCFYSEESP TFQSTVSSST GKLKFGLSYK EQVGSNRELY VGDLNTKLTS
RLIEDYFESI TSESKFSCLN NDSEFEKAIL DMKSVVRLSG LAVSLDHSKW GPYMSPAIFN
SLFTSLDLQL RDGSLIDKSP IENLLNWHLH KLVEVPYNVI EAYLKGYTKR GLGLMDKMSS
TVCEDFIFNW FAKGQVPSHI SSVLDMGQGI LHNTSDYYGL VTEQFIMLCL ELCFDVRMTA
YTSSDDEIML SNSHSLKDKS DESLDIQKCG ELLEFHYYLS SKLNKFVSPK TVAGSFASEF
KSRFFIWSQE VPLLTKFVAA ALHNVKAKSP HQLAETVDTI LDQCVANGVS IKIIKEISKR
TNRLISYSGH PIDPFLCVVE TDLKDWVDGS RGYRLQRSIE SIIADDKQLS IIRNSCKKLF
YKIRSGDIQE EYLVNALQSS PDDCLRQMLR ITEVDDQTIE KLIEIRWLNL RAFGDLRLVL
RTKIMSGTRI LDREEVPSLI RSVQSKLSKN FVRGAKKIVT DAINKSAFQS SVCSGFIGVC
KSMGSKCVRD GSGGFVYIKS LLSEVVCHHT CETCKPRFSV YCKSALERIS KYSRSLLWDY
FSLVFTNACE LGNWVFSCVE TPKKIPSVVN PNFFWCVKPG SHTELEDKVN MNHVLYSIKR
NFPDLFDEHI APFLSDLSSL KISWVQRIRF LDLCVAMDMS SECLGVISHI MRRKREESYI
VKQNELSLAH MRDSTPLEGG FQLNSLEICR NFLYQIVFES MLHPVLLTTS QFKKYFWYGE
VELLPNDADH DLGQLTQFIM DCKTLNVSRC MSLDDLDVGY VHSKITLSDV FINLSSFIHL
LDWGNLCDYE SFDKIILESG LEQVPIEIGI VVSHVRRSFK FKYDRKTNYH IKCKIIIRKS
ELIMSKVNGV DILEIEVSEI ECFVSGSQGH HISLDGVGLI PLHPLFSGKE LIDFNKLLAD
QSIEFKQVSS VFQKVKLDFK QHVKELRNKF SYKFQGPEQG LSPLHLYRGQ IIERDTIVSR
LDVPVTSKSV FLALEALDAA DHTPFLKSLH TYMKTRMSKS NPCFIRMTQE DLCLLIESYE
VAFANILKSE SDWVEFGDFA LCFSNSLNCI MIADDGGQFK LKGRKCRSAS TNPRPLEIE
