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 08-NOV-2023, entry version 87. 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; Orthohantavirus seoulense. 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; X56492; CAA39847.1; -; Genomic_RNA. DR PIR; S16449; S16449. DR SMR; 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-dependent RNA polymerase activity; IEA:UniProtKB-KW. DR GO; GO:0075526; P:cap snatching; IEA:UniProtKB-KW. DR GO; GO:0006351; P:DNA-templated transcription; IEA:InterPro. DR GO; GO:0039689; P:negative stranded viral RNA replication; ISS:UniProtKB. DR GO; GO:0039696; P:RNA-templated viral transcription; ISS:UniProtKB. DR InterPro; IPR048006; CapSnatch_bunyavir. 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 NCBIfam; TIGR04202; capSnatchArena; 1. 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 //