ID   L_SEOU8                 Reviewed;        2151 AA.
AC   P27314;
DT   01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
DT   01-AUG-1992, sequence version 1.
DT   03-AUG-2022, entry version 82.
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   Seoul virus (strain 80-39).
OC   Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina;
OC   Ellioviricetes; Bunyavirales; Hantaviridae; Mammantavirinae;
OC   Orthohantavirus.
OX   NCBI_TaxID=12557;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
OH   NCBI_TaxID=10116; Rattus norvegicus (Rat).
OH   NCBI_TaxID=10117; Rattus rattus (Black rat).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX   PubMed=1840713; DOI=10.1016/0168-1702(91)90094-c;
RA   Antic D., Lim B.U., Yong Kang C.;
RT   "Nucleotide sequence and coding capacity of the large (L) genomic RNA
RT   segment of Seoul 80-39 virus, a member of the hantavirus genus.";
RL   Virus Res. 19:59-66(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}.
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DR   EMBL; X56492; CAA39847.1; -; Genomic_RNA.
DR   PIR; S16449; S16449.
DR   SMR; P27314; -.
DR   PRIDE; P27314; -.
DR   Proteomes; UP000207620; 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..2151
FT                   /note="RNA-directed RNA polymerase L"
FT                   /id="PRO_0000222024"
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;  246664 MW;  AA567FF1DBBEE543 CRC64;
     MEKYREIHRD LKEFTINSLT AVECMDYLDR LYAVRHDIVD QMIKHEWSDN KDSEEPISKV
     LLFAGIPNNV ITALEKKVIP DHPSGKTLRS FFKMTPDNYR ITGSLIEFVE VTVTADVDKG
     IREKKMKYEL GLKYLEQELM TFFHRGELQN PYKITFKVVA VRTDGSNIST QWPSARNDGV
     VQYMRLVQAE ISYVREHLVK TEERAALEAM FNLKFNISSL KTQPYFIPEY KGIDLIRPDI
     DGLVNYAQSW MSKTQEFSFF EVKGSAVFDC FNENEQGHIV KYPMSRHPRN FLLIQCTVLT
     AYKPATILSD QLDSRRACIQ FLNLIPETPA SILAHDMAHR YINLTRDDLL AYYAPRIQFN
     PTQNIKEPGT FKLTSNMMRP ESKIMLDMLS QHEPRENLGK SIESLNISSH IVQSDCVSLI
     TKILSDLELN ISEPSSHEQI TAKHTHVDTV LDKFFQNETQ KYLIDILKKT TAWHIGHLVR
     DITESLIAHS GLRRSKYWSI HAYNNGSVIL FILPSKSLEV AGSFVRFMTA FKLGPGLVDK
     DNLDSILADG DILWGVSKIM SLDLNRLLAL NIAFEKALLA TATWFQYYTE DQSQFPLQHS
     IRSVFAYHFL LAICQKMKLC AIFDNLRYLI PAVTSLYSGF PSLVEKLFER PFKSALEVYV
     YYNIKSLLVA LAQNNKARFY SKVKLLGLTV DQSTVGASGI YPSFMSRVVY KHYKSLISEV
     TTCFFLFEKG LHGNVNEEAK IHLETVEWAT KFKEKEDKYG EMLVEHGYTI GELVESSELA
     VQQLYCQDAV ELAANELNRV LIAKSQVVAN SILNKYWEEP YFSQTRNISL KGMSGQVQED
     GHLSSSTTII EAIRYLSNSR NNPNVLQLYE ETRHQKAQAR IVRKFQRTEA DRGFFITTLP
     TRCRLEIIED YYDAISKNVA EEYISYGGER KILCIQAALE KALRWASGES FIELSNGKFI
     RMKRKLMYVS ADATKWSPGD NSAKFRRFTA ALHNGLPDDR LKNCVIDALR HVYKTDFYMS
     RKLRHYIDSM DTYEPHVRDF LNFFPDGHHG EVRGNWLQGN LNKCSSLFGV AMSLLFKEIW
     TRLFPELDCF FEFAHHSDDA LFIYGYLEPA DDGTDWFLFV SQQIQAGKLH WFNVNTEMWK
     SMFNLHEHIL LLGSIKISPK KTTLSPTNAE FLSTFFEGCA VSIPFIKILL GSLSDLPGLG
     YFDDLAAAQT RCVKAMDLGA SPQISQLAVS LSTSKVERLY GTSIGMVNYP GTYLRTKHSE
     TPIPLGGSGA MSIMELSTAG IGMSDKNLLK QALIGYMHKH QKQMSYILGL FKFLMDLSGE
     TFQHERLGQF SFIGKVQWKI FTPKSEFEFS DMYSQKFLKV WSEQHPTYDY IIPKGRDNLL
     IYLVRKLNDP SIITAMTMQS PLQLRFRMQA KQHMKVCRLD GDWVTFREVL AAANSFAESY
     EPSQNDIDLF QTLTSCTFSK EYAWKDFLNN VHCDVIPTKQ VQRAKVARTF TVREKDRIIQ
     NSIPAVIGYK FAVTVDEMSD VLDTAKFPDS LAVDLKTMKD GVYRELGLDI SSPDVMKKVA
     PMLYKSAKSR VVIVQGNVEG TAEAICAYWL RNMSLIKTIK VKPHKEVLQA VSIFNRKEDI
     GQQKDLSALK LCIEVWRWAK ANNAPYRDWF HALWFEDKTF SEWLDRFIRV GVPPIDPEIQ
     CAALMIADVK GDRSVLQLQA NRRAYSGKQY DAYCVQTYNE ETKLYEGDLR VTFNFGLDCA
     RLEIFWDKKT YILETSITQK HVLKIMMEEV SKELVRCGMR FNTEQVNGVK HLVLFKTDSG
     FEWGKPNIPC IVYKNCALRT GLRTNQAINH KFMITIKDDG LRAIAQYDED SPRFLLAHAF
     HTIRDVRYQA VDAVSNVWFT HKGIKLYLNP IISSGLLEYF MKNIPAAIPP AAYSLIMNRA
     KISVDLFMFN DLLRLINPGN TLDLSGLEIT GEGYSTVNSL SSRLWSEEMS LVDDEEEMDD
     EFTIDLQDVD FENIDIEADV EHFLQDESAY TGDLLIMSEE TEVKKMRGII KLLEPVKLIK
     SWVSRGLSIE KVYNPVNIIL MTRYISKNFN FSGKQVSLLD PYDLTELESI VKGWGESVVD
     QFDSLDLEAQ NLVQKQGIVP EDVIPDSLFS FRHTMVLLRR LFGQDSVSTF Y