ID   L_PUUMG                 Reviewed;        2156 AA.
AC   P27176;
DT   01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
DT   01-AUG-1992, sequence version 1.
DT   03-AUG-2022, entry version 76.
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 Bank vole/Russia/CG1820/1984).
OC   Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina;
OC   Ellioviricetes; Bunyavirales; Hantaviridae; Mammantavirinae;
OC   Orthohantavirus.
OX   NCBI_TaxID=1337063;
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=2053288; DOI=10.1016/0042-6822(91)90152-2;
RA   Stohwasser R., Raab K., Darai G., Bautz E.K.F.;
RT   "Primary structure of the large (L) RNA segment of nephropathia epidemica
RT   virus strain Hallnas B1 coding for the viral RNA polymerase.";
RL   Virology 183:386-391(1991).
RN   [2]
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   [3]
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   [4]
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}.
CC   -!- CAUTION: The sequence was wrongly described as Hallnas B1 strain.
CC       {ECO:0000305|PubMed:2053288}.
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DR   EMBL; M63194; -; NOT_ANNOTATED_CDS; Genomic_RNA.
DR   PIR; A40319; RRVUNE.
DR   SMR; P27176; -.
DR   PRIDE; P27176; -.
DR   Proteomes; UP000008481; 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; RNA-directed RNA polymerase; Transferase;
KW   Viral RNA replication.
FT   CHAIN           1..2156
FT                   /note="RNA-directed RNA polymerase L"
FT                   /id="PRO_0000222022"
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   2156 AA;  247050 MW;  1D3C0A34C0DF99A6 CRC64;
     MEKYREIHER VKEAVPGETS AVECLDLLDR LYAVRHDVVD QMIKHDWSDN KDKEQPIGLV
     LLMAGVPNDV IQSMEKRIIP GSPSGQILRS FFKMTPDNYK ITGNLIEFIE VTVTADVARG
     VREKILKYQG GLEFIEQLLQ IEAQKGNCQS GFRIKFDVVA IRTDGSNIST QWPSRRNEGV
     VQAMRLIQAD INFVREHLIK NDERGALEAM FNLKFHVTGP KVRTFDIPNY RPQQLCQPVL
     ENLVEYCKNW LGTDHAFAFK EVTGQRVFNV FRDEEELHAS KYGHSRKPRN FLLCQISLQV
     PYLPSTIASD QYDTRLACSE ILKNYPETPL QLLARDMAYK YITLDNEDII NYYNPRVYFK
     PTQNIKEPGT FKLNLSNMDP KSKALIDVIS KDSKKGVFGE LIDSIDVASQ VQQNECAKTI
     EKILSDLEVN LGDSTAGLDQ PKRTTGVDDI LRKFYDNELV KYLISVIRKT TARHLGHLLR
     DITESLIAHA GLKRSKYWSA HGYAYGSVLL CILPSKSLEV AGSFIRFFTV FKEGLGLIDA
     DNLDSKVEID GVTWCFSKII SLDLNRLLAL NIAFEKSLLA TATWFQYYTE DQGHFPLQHA
     LRSVFAFHFL LATSQKMKLC AIFDNLRYLI PAVTSTYSGF EPLIRKFFER PFKSALEVYL
     YNIIKTLLVS LAQNNKIRFY SRVRLLGLTV DQSSIGASGV YPSLMSRVVY KHYRSLISEA
     TTCFFLFEKG LHGNLTEEAK IHLETVEWAR KFREKERKLG SYIMEEGYHI QDVLNNQVVV
     EQQLFCQEVV ELAAQELNTY LHAKSQVMAS NIMNKHWDKP YFSQTRNISL KGMSGALQED
     GHLAASVTLI EAIRFLNHSQ NNPTVLELYE QTKKQKAQAR IVRKYQRTEA DRGFFITTLP
     TRVRLEIIED YYDAIARVVP EEYISYGGET KILNIQQALE KALRWASGES EIQSSIGHSI
     KLKRKLMYVS ADATKWSPGD NSAKFRRFTQ SLYDGLRDDK LKNCVVDALR NIYETDFFIS
     RKLHRYIDNM GELSDEVLDF LSFFPNKVSA SIKGNWLQGN LNKCSSLFGA AVSLLFKRVW
     AKLYPELECF FEFAHHSDDA LFIYGYLEPV DDGTEWFQYV TQQIQAGNFH WHAVNQEMWK
     SMFNLHEHIL LMGSIKISPK KTTVSPTNAE FLSTFFEGCA VSIPFIKILL GSLSDLPGLG
     YFDDLAAAQS RCVKALDMGA CPQLAQLGIV LCTSKVERLY GTAPGMVNNP TAYLKVDRSL
     IPIPLGGDGS MSIMELATAG IGMADKNILK NAFITYKHAK KDNDRYVLGL FKFLMSLSDD
     IFQHDRLGEF SFVGKVQWKV FTPKSEFEFY DQYSRKYLEL WSEQHPVYDY IIPRGRDNLL
     VYLVRKLNDP SIVTAMTMQS PLQLRFRMQA KQHMKVCKLD GEWVTFREVL AAADAFASEY
     RPTLQDMELF QTLVNCTFSK EYAWRDFLNE VQCDVLTTRQ IHRPKVARTF TVKEKDQTIQ
     NPITAVIGYK YASKVDEISD VLDSAIHPDS LSTDLQLMRE GVYRELGLDI SQPNVLKKVA
     PLLYKSGKSR IVIVQGNVEG TAESICSYWL KTMSLVKTIK VKPKKEVLKA VSLYGKKEKA
     GDLTHLAAMR LCIEVWRWCK ANEQDSVSWL KYLMFENKTL EQWIDSFCSR GVLPVDPEIQ
     CLGLLVYDLK GQKGLLQIQA NRRAYSGKQY DAYCVQTYNE ETKLYEGDLR VTFNFGIDCA
     RLEIFWDKRE YILETSITQR NVLKILMEEV TKELLRCGMR FKTEQVNSSR SVVLFKTESG
     FEWGKPNVPC IVYRNCTLRT GLRVRQPTNK AFSITIQANG FRAMAQLDEE NPRFLLAHAY
     HNLKDVRYQA LQAVGNVWFK MTQHKLFINP IISAGLLENF MKGLPAAIPP AAYSLIMNKA
     KISVDLFMFN ELLALINPQN VLNLDGIEET SEGYTTVSTI SSTQWSEEVS LTMDDSDDDG
     DASQLDYTID LDDIDFETID LKEDIEHFLQ DESAYTGDLL IQTEETEIRK LRGMIKILEP
     VKLIKSWVSK GLSIDKIYNP VNIILMTRYM SKHYNFHAKQ LSLMDPYDLT EFESIVKGWG
     ECVKDRFIEL DQEAQRKVTE ERVLPEDVLP DSLFSFRHAD ILLKRLFPRD SASSFY