L_PUUMS
ID L_PUUMS Reviewed; 2156 AA.
AC P0C760; I4EPA5;
DT 28-JUL-2009, integrated into UniProtKB/Swiss-Prot.
DT 28-JUL-2009, sequence version 1.
DT 03-AUG-2022, entry version 49.
DE RecName: Full=RNA-directed RNA polymerase L;
DE Short=Protein L;
DE EC=2.7.7.48;
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;
OS Puumala virus (strain Sotkamo/V-2969/81).
OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina;
OC Ellioviricetes; Bunyavirales; Hantaviridae; Mammantavirinae;
OC Orthohantavirus.
OX NCBI_TaxID=39002;
OH NCBI_TaxID=9606; Homo sapiens (Human).
OH NCBI_TaxID=447135; Myodes glareolus (Bank vole) (Clethrionomys glareolus).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=9381791; DOI=10.1016/s0168-1702(97)00073-7;
RA Piiparinen H., Vapalahti O., Plyusnin A., Vaheri A., Lankinen H.;
RT "Sequence analysis of the Puumala hantavirus Sotkamo strain L segment.";
RL Virus Res. 51:1-7(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RC STRAIN=Isolate Sotkamo 2009/WHO Arbovirus collection;
RX PubMed=22798055; DOI=10.1007/s11262-012-0780-3;
RA Kurolt I.C., Paessler S., Markotic A.;
RT "Resequencing of the Puumala virus strain Sotkamo from the WHO Arbovirus
RT collection.";
RL Virus Genes 45:389-392(2012).
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 Mn(2+) 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; Z66548; -; NOT_ANNOTATED_CDS; Genomic_RNA.
DR EMBL; HE801635; CCH22849.1; -; Genomic_RNA.
DR SMR; P0C760; -.
DR Proteomes; UP000008482; Genome.
DR Proteomes; UP000110237; 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:0039689; P:negative stranded viral RNA replication; ISS:UniProtKB.
DR GO; GO:0039696; P:RNA-templated viral transcription; ISS:UniProtKB.
DR GO; GO:0006351; P:transcription, DNA-templated; 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; Reference proteome; RNA-directed RNA polymerase;
KW Transferase; Viral RNA replication.
FT CHAIN 1..2156
FT /note="RNA-directed RNA polymerase L"
FT /id="PRO_0000379782"
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"
FT VARIANT 157
FT /note="N -> D (in strain: isolate Sotkamo 2009/WHO
FT Arbovirus collection)"
FT VARIANT 1477
FT /note="T -> I (in strain: isolate Sotkamo 2009/WHO
FT Arbovirus collection)"
FT VARIANT 1776
FT /note="R -> H (in strain: isolate Sotkamo 2009/WHO
FT Arbovirus collection)"
FT VARIANT 2133
FT /note="F -> L (in strain: isolate Sotkamo 2009/WHO
FT Arbovirus collection)"
SQ SEQUENCE 2156 AA; 246999 MW; 3DA19810F1A067F8 CRC64;
MEKYRDIHER VKEAVPGETS AVECLDLLDR LYAVRHDVVD QMIKHDWSDN KDREQPIGLV
LLMAGVPNDV IQSMEKRVIP GSPSGQILRS FFKMTPDNYK ITGNLIEFIE VTVTADVARG
VREKILKYQG GLEFIEQLLQ IEAQKGNCQS GFKIKFNVVA VRTDGSNIST QWPSRRNEGV
VQAMRLIQAD INFVREHLIK NDERGALEAM FNLKFHVTGP KVRTFDIPNY RPQPLCQPIL
ENLVDYCKNW LGTDHAFAFK EVTGQRVFNV FREEEEIHAS KYGHSRKPRN FLLCQISLQS
PYLPSTIASD QYDTRLACSE ILKNYPETPL QLLARDMAYK YITLDHDDII NYYNPRVYFK
PTQNIKEPGT FKLNLSNMDP KSKALIDVIS KDSKKGVFGE LIDSVDVASQ VQHNECSKTI
EKILSDLEVN LGDVANGLDQ PKKTTGVDDI LRKFYDNELV KYLISVIRKT TAWHLGHLLR
DITESLIAHA GLKRSKYWSA HGYACGSVLL CILPSKSLEV AGSFIRFFTV FKEGLGLIDT
DNLDSKAEID GVSWCFSKII SLDLNRLLAL NIAFEKSLLA TATWFQYYTE DQGHFPLQHA
LRSVFAFHFL LSVSQKMKLC AIFDNLRYLI PAVTSTYSGF EPLIRKFFER PFKSALEVYL
YGIIKVLLVS LAQNNKIRFY SRVRLLGLTV DQSTIGASGV YPSLMSRVVY KHYRSLISEA
TTCFFLFEKG LHGNLTEEAK IHLETVEWAR KFREKERELG SYIMEEGYHI QDVLNNQVAV
EQQLFCQEVV ELAAQELNTY LHAKSQVMAS NIMNKHWDKP YFSQTRNISL KGMSGALQED
GHLAASVTLI EAIRFLNHSQ NNPTVLELYE QTKKQRAQAR IVRKYQRTEA DRGFFITTLP
TRVRLEIIED YYDAIAKVVP EEYISYGGER KILNIQQALE KALRWASGES EIQSSLGHSI
KLKRKLMYVS ADATKWSPGD NSAKFRRFTQ SLYDGLRDDK LKNCVVDALR NIYETDFFIS
RKLHRYIDNM GELSDEVLDF LSFFPNKVSA SIKGNWLQGN LNKCSSLFGA AISLLFKRVW
AKLYPELECF FEFAHHSDDA LFIYGYLEPI DDGTEWFQYV TQQIQAGNFH WHAVNQEMWK
SMFNLHEHIL LMGSIKISPK KTTVSPTNAE FLSTFFEGCA VSIPFIKILL GSLSDLPGLG
YFDDLAAAQS RCVKALDMGA CPQLAQLGIV LCTSKVERLY GTAPGMVNNP TAYLKVDRNL
IPIPLGGDGS MSIMELATAG IGMADKNILK NAFITYKHAK KDNDRYVLGL FKFLMSLSDD
IFQHDRLGEF SFVGKVQWKV FTPKSEFEFY DQYSRKYLEL WSEQHPVYDY IIPRGRDNLL
VYLVRKLNDP SIVTAMTMQS PLQLRFRMQA KQHMKVCKLG GEWVTFREVL AAADAFASEY
RPTLQDMELF QTLVNCTFSK EYAWRDFLNE VQCDVLTTRQ IHRPKVARTF TVKERDQTIQ
NPITAVIGYK YASKVDEISD VLDSALHPDS LSTDLQLMRE GVYRELGLDI SQPNVLKKVA
PLLYKSGKSR IVIVQGNVEG TAESICSYWL KTMSLVKTIK VKPKKEVLKA VSLYGKKEKV
GDLTHLAAMR LCIEVWRWCK ANEQDSVTWL KYLVFENKTL EQWVDLFCSR GVLPIDPEIQ
CLGLLVYDLK GQKGLLQIQA NRRAYSGKQY DAYCVQTYNE ETKLYEGDLR VTFNFGIDCA
RLEIFWDKKE YILETSITQR NVLKILMEEV TKELLRCGMR FKTEQVNSSR SVVLFKTESG
FEWGKPNVPC IVYRNCTLRT GLRVRHPTNK AFSITIQANG FRAMAQLDEE NPRFLLAHAY
HNLKDVRYQA LQAVGNVWFK MTQHKLFINP IISAGLLENF MKGLPAAIPP AAYSLIMNKA
KISVDLFMFN ELLALINPQN VLNLDGIEET SEGFTTVSTI SSTQWSEEVS LTLDDSDDDD
DASNLDYTID LDDIDFETID LKEDIEHFLQ DESAYTGDLL IQTEETEVRK LRGMIKILEP
VKLIKSWVSK GLSIDKIYNP VNIILMTRYM SKHYNFQAKQ LSLMDPYDLT EFESVVKGWG
ECVKDRFIEL DQEAQRKVTE ERVLPEDVLP DSFFSFRHAD ILLKRLFPRD SASSFY
