L_DOBV
ID L_DOBV Reviewed; 2151 AA.
AC Q806Y6;
DT 25-MAY-2022, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2003, sequence version 1.
DT 03-AUG-2022, entry version 73.
DE RecName: Full=RNA-directed RNA polymerase L;
DE Short=Protein L;
DE EC=2.7.7.48 {ECO:0000255|PROSITE-ProRule:PRU00539};
DE AltName: Full=Large structural protein;
DE AltName: Full=RdRp {ECO:0000305};
DE AltName: Full=Replicase;
DE AltName: Full=Transcriptase;
DE Includes:
DE RecName: Full=cap-snatching endonuclease;
DE EC=3.1.-.- {ECO:0000250|UniProtKB:P23456};
GN Name=L {ECO:0000312|EMBL:CAC85167.1};
OS Dobrava-Belgrade orthohantavirus (DOBV) (Dobrava virus).
OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina;
OC Ellioviricetes; Bunyavirales; Hantaviridae; Mammantavirinae;
OC Orthohantavirus.
OX NCBI_TaxID=1980467;
OH NCBI_TaxID=39030; Apodemus agrarius (Eurasian field mouse).
OH NCBI_TaxID=54292; Apodemus flavicollis (Yellow-necked field mouse).
OH NCBI_TaxID=134909; Apodemus ponticus (Caucasus field mouse).
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RC STRAIN=DOBV/Ano-Poroia/Afl9/1999;
RX PubMed=12457975; DOI=10.1016/s0168-1702(02)00179-x;
RA Nemirov K., Hentonnen H., Vaheri A., Plyusnin A.;
RT "Phylogenetic evidence for host switching in the evolution of hantaviruses
RT carried by Apodemus mice.";
RL Virus Res. 90:207-215(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RC STRAIN=DOBV/Ano-Poroia/Afl9/1999;
RX PubMed=12526053; DOI=10.1002/jmv.10304;
RA Nemirov K., Vapalahti O., Papa A., Plyusnina A., Lundkvist A.,
RA Antoniadis A., Plyusnin A.;
RT "Genetic characterization of new Dobrava hantavirus isolate from Greece.";
RL J. Med. Virol. 69:408-416(2003).
RN [3]
RP REVIEW.
RX PubMed=15503219; DOI=10.1007/s00705-004-0414-8;
RA Kukkonen S.K., Vaheri A., Plyusnin A.;
RT "L protein, the RNA-dependent RNA polymerase of hantaviruses.";
RL Arch. Virol. 150:533-556(2005).
RN [4]
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 [5]
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 (By similarity). During transcription,
CC synthesizes subgenomic RNAs and assures their capping by a cap-
CC snatching mechanism, which involves the endonuclease activity cleaving
CC the host capped pre-mRNAs. These short capped RNAs are then used as
CC primers for viral transcription. Cleaves ssRNA substrates but not DNA
CC (By similarity). Seems to downregulate the expression of its own and
CC heterologous mRNAs through its endonuclease activity (By similarity).
CC {ECO:0000250|UniProtKB:Q9E005}.
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|PROSITE-ProRule:PRU00539};
CC -!- COFACTOR:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000250|UniProtKB:P23456};
CC Note=For endonuclease activity. Binds 2 Mn2+ ions in the active site.
CC The divalent metal ions are crucial for catalytic activity
CC (PubMed:31948728). {ECO:0000250|UniProtKB:P23456,
CC ECO:0000269|PubMed:31948728};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:A2SZS3};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000250|UniProtKB:A2SZS3};
CC Note=For polymerase activity. {ECO:0000250|UniProtKB:A2SZS3};
CC -!- SUBUNIT: Interacts with the viral nucleoprotein.
CC {ECO:0000250|UniProtKB:Q89709}.
CC -!- SUBCELLULAR LOCATION: Host cytoplasm, host perinuclear region
CC {ECO:0000250|UniProtKB:Q9YQR5}.
CC -!- DOMAIN: The N-terminus contains the endonuclease activity (endoN) (By
CC similarity). The central region contains the RdRp activity (By
CC similarity). The C-terminus contains the cap-binding region (By
CC similarity). {ECO:0000250|UniProtKB:A2SZS3,
CC ECO:0000250|UniProtKB:I0DF35, ECO:0000250|UniProtKB:Q9E005}.
CC -!- MISCELLANEOUS: Classified as His(+) endonuclease since it has a
CC histidine upstream of the active site that coordinates the first
CC cation. {ECO:0000303|PubMed:31948728}.
CC -!- SIMILARITY: Belongs to the Bunyavirales RNA polymerase family.
CC {ECO:0000305}.
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DR EMBL; AJ410617; CAC85167.1; -; Genomic_RNA.
DR RefSeq; NP_942555.1; NC_005235.1.
DR GeneID; 2656265; -.
DR KEGG; vg:2656265; -.
DR Proteomes; UP000202548; Genome.
DR GO; GO:0044220; C:host cell perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0004519; F:endonuclease activity; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0000166; F:nucleotide binding; IEA:UniProtKB-KW.
DR GO; GO:0003968; F:RNA-directed 5'-3' RNA polymerase activity; IEA:UniProtKB-KW.
DR GO; GO:0075526; P:cap snatching; IEA:UniProtKB-KW.
DR GO; GO:0006351; P:transcription, DNA-templated; IEA:InterPro.
DR GO; GO:0039694; P:viral RNA genome replication; IEA:InterPro.
DR InterPro; IPR016268; RNA-dir_pol_hantavirus.
DR InterPro; IPR024378; RNA-dir_pol_N_hantavirus.
DR InterPro; IPR007099; RNA-dir_pol_NSvirus.
DR InterPro; IPR007322; RNA_pol_bunyavir.
DR Pfam; PF04196; Bunya_RdRp; 1.
DR Pfam; PF12426; DUF3674; 1.
DR PIRSF; PIRSF000825; L_HantaV; 1.
DR PROSITE; PS50525; RDRP_SSRNA_NEG_SEG; 1.
PE 3: Inferred from homology;
KW Cap snatching; Endonuclease; Host cytoplasm; Hydrolase; Magnesium;
KW Manganese; Metal-binding; Nuclease; Nucleotide-binding;
KW Nucleotidyltransferase; RNA-directed RNA polymerase; Transferase;
KW Viral RNA replication.
FT CHAIN 1..2151
FT /note="RNA-directed RNA polymerase L"
FT /id="PRO_0000455191"
FT DOMAIN 956..1142
FT /note="RdRp catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00539"
FT ACT_SITE 124
FT /note="For endonuclease activity"
FT /evidence="ECO:0000250|UniProtKB:P23456"
FT BINDING 36
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q9E005"
FT BINDING 54
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P23456"
FT BINDING 97
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q9E005"
FT BINDING 97
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q9E005"
FT BINDING 110
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q9E005"
FT BINDING 111
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q9E005"
FT BINDING 1099
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_note="catalytic; for RdRp activity"
FT /evidence="ECO:0000250|UniProtKB:I0DF35"
SQ SEQUENCE 2151 AA; 246532 MW; 61231C9463B71742 CRC64;
MEKYREIHRD LQSFPVGSLT AVECIDYLDR LYAIRHDIVD QMIKHDWSDN KDSEESIGKV
LLFAGVPNNV ITAMEKKIIP DHPSGKTLRS FFKMTPDNYK ITGSTIEFVE VTVTVDVDKG
IREKRLKYEA GLKYIEQELH NHFLRGDIPQ PYKITFQVVS VRTDGSNIST QWPSRRNDGV
VQYMRLVQAE ISYVREHLIR QEERAALEAM FNLKFNISNI KNQPYYIPDY RGIPLIHPNI
NDLVVYMRDW LSKSHKFSFH EGKVPAVFDC FNENELEHAV KYPISRHPRN FLLIQCSLLS
SYNPATILSD QVDSRRACNS VLNLIPETPT SFLIHDMAYR YINLTREDMV SFYAPKTQFI
PTQNVKEPGT FKLTANSMRP ESKAMLDMLG SHEPGEKKGA LIESLNLSSH IVQSECVSLI
TKILSDLELN ISEPTSHGSF TTKHTYVDNV LEKFFQNEIQ RYLLDVLKKT TAWHIGHLIR
DITESLIAHS GLKRSKYWSV HAYNNGNVIL FILPSKSLEV AGSYIRFVTV FRMGPGLVDK
DNLDTILTDQ DVTWGVSKVM SIDLNRLLAL NIAFEKALIA TATWFQYYTE DQGQFPLQHA
IRSVFAYHLL LAVCQKMKLC AIFDNLRYLI PAVTSLYSGF PSLINKLFER PFKSALEVYV
YYNIKSLLVA LAQNNKARFY SKVKLLGLTV DQSTVGASGI YPSFMSRVIY KHYRSLISEV
TTCFFLFEKG LHGNMNEEAK IHLETVEWAL KFRQKEDQYG ESMVENGYTI GELNDNQDLV
EQQLYCQDAV ELAAVELNKI LSTKSQVVAN SILNKYWEVP YFSQTRNISL KGMSGQVQED
GHLAASVTII EAIRYLSSSQ NNPSVLQLYE ETRKVKAQAR IVRKYQRTEA DRGFFITTLP
TRCRLEIIED YYDAISKNVA EEYISYGGER KILCIQSALE KALRWASGES FIELSNGKFI
RMKRKLMYVS ADATKWSPGD NSAKFRRFTA ALHNGLPDDR LKNCVIDALR NVYKTDFYMS
RKLRAYIDNM NGHEPAVKNF LEFFPDGHCG EVRGNWLQGN LNKCSSLFGV GMSLLFKQLW
NELFPELDCF FEFAHHSDDA LFIYGYLEPI DDGTDWFLYV SQQIQAGHLH WFSVNTEMWK
SMFNLHEHVL LLGSIKISPK KTTLSPTNAE FLSTFFESCA VSIPFIKILL GSLSDLPGLG
YFDDLAAAQS RCVKAMDLGA SPQVAQLAVA LCTNKVERLY GTAVGMIKHP STYLQVKHGD
TPIPLGGSGA MSIMELATAG IGMSDKNLLK RALLGYIHKR QKNMAYILGL FKFLMNLSKD
TFQHERLGEF SFIGKVQWKI FIPKSEFEFF DMYTPKFLKL WSEQHVTYDY IIPKGRDNLL
IYLVRKINDP SIVTAMTMQS PLQLRFRMQA KQHMKVCKLD DDWVTFREIL AAANSFAQLY
EVTQEDLDLF QTLTSCTFSK EYAWKDFLNG VQCDVIPTKQ IQRAKVARTF TVREKDQIIQ
NSIPAVIGYK FAVTVDEMSD VLDSAKFPDS LAVDLKTMKD GVYRELGLDI SQAEVMKKVA
PMLYKSSKSR VVIVQGNVEG TAEAICGYWL RTMSLVKTIR VKPHKEVLKA VSIFNRKEDI
GQQKDLAALR LCIEVWRWCK ANNAPYQEWF HALWFEDKTF SEWLDRFIRV GVPPVDPEIQ
CAALMIADIR GDLSVLQVQA NRRAYSGKQY DAYCVQTYNE ETKLYEGDLR VTFNFGLDCA
RLEIFWDKQT YILETSITQK HVLKIMMDEV TKELLRCGMR FKTEQVSNVK HLVLFKTEAG
FEWGKPNIPC IVYKNCALRT GLRANQTVNH KFMISIKDNG LRAIAQYDDE SPRFLLAHAF
HTIRDIRYQA VDAVSNVWFI HKGIKLFLNP IISSGLLENF MKNLPAAIPP AAYSLIMNRA
KISVDLFMFN DLLRLINPSN TLDLSGLQPT EDGFSTVSSM SSRLWSEEVS FVDEDEEIDD
EFTIDLQDVD FENIDVEADI EHFLQDESSY TGDLLIMSEE TEVKKMRGII KLLEPVRLIK
SWVSKGLCIE KVYSPTNIIL MTRYLSKNFN FSGRQVSLLD PYDLTEFESI VKGWGECVVD
QFSTFDQETQ LLVSQKGICP EDVVPDSLFS FRHTIVLLRR LFPQDSVSTF Y
