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 08-NOV-2023, entry version 55. 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; Orthohantavirus puumalaense. 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}. 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; 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-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..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/WHOArbovirus FT collection)" FT VARIANT 1477 FT /note="T -> I (in strain: isolate Sotkamo 2009/WHOArbovirus FT collection)" FT VARIANT 1776 FT /note="R -> H (in strain: isolate Sotkamo 2009/WHOArbovirus FT collection)" FT VARIANT 2133 FT /note="F -> L (in strain: isolate Sotkamo 2009/WHOArbovirus FT 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 //