ID   L_IPPYV                 Reviewed;        2208 AA.
AC   Q27YE1;
DT   20-JAN-2009, integrated into UniProtKB/Swiss-Prot.
DT   04-APR-2006, sequence version 1.
DT   03-AUG-2022, entry version 68.
DE   RecName: Full=RNA-directed RNA polymerase L {ECO:0000255|HAMAP-Rule:MF_04086};
DE            Short=Protein L {ECO:0000255|HAMAP-Rule:MF_04086};
DE            EC=2.7.7.48 {ECO:0000255|HAMAP-Rule:MF_04086};
DE   AltName: Full=Large structural protein {ECO:0000255|HAMAP-Rule:MF_04086};
DE   AltName: Full=Replicase {ECO:0000255|HAMAP-Rule:MF_04086};
DE   AltName: Full=Transcriptase {ECO:0000255|HAMAP-Rule:MF_04086};
DE   Includes:
DE     RecName: Full=cap-snatching endonuclease {ECO:0000255|HAMAP-Rule:MF_04086};
DE              EC=3.1.-.- {ECO:0000255|HAMAP-Rule:MF_04086};
GN   Name=L {ECO:0000255|HAMAP-Rule:MF_04086};
OS   Ippy mammarenavirus (isolate Rat/Central African Republic/Dak An B 188
OS   d/1970) (IPPYV).
OC   Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina;
OC   Ellioviricetes; Bunyavirales; Arenaviridae; Mammarenavirus.
OX   NCBI_TaxID=55096;
OH   NCBI_TaxID=10111; Praomys (African soft-furred rats).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX   PubMed=16494913; DOI=10.1016/j.virol.2006.01.026;
RA   Emonet S., Lemasson J.J., Gonzalez J.P., de Lamballerie X., Charrel R.N.;
RT   "Phylogeny and evolution of old world arenaviruses.";
RL   Virology 350:251-257(2006).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX   PubMed=18602020; DOI=10.1016/j.mib.2008.06.001;
RA   Charrel R.N., de Lamballerie X., Emonet S.;
RT   "Phylogeny of the genus Arenavirus.";
RL   Curr. Opin. Microbiol. 11:362-368(2008).
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. During transcription, synthesizes subgenomic
CC       RNAs and assures their capping by a cap-snatching mechanism, which
CC       involves the endonuclease activity cleaving the host capped pre-mRNAs.
CC       These short capped RNAs are then used as primers for viral
CC       transcription. The 3'-end of subgenomic mRNAs molecules are
CC       heterogeneous and not polyadenylated. The replicase function is to
CC       direct synthesis of antigenomic and genomic RNA which are encapsidated
CC       and non capped. As a consequence of the use of the same enzyme for both
CC       transcription and replication, these mechanisms need to be well
CC       coordinated. These processes may be regulated by proteins N and Z in a
CC       dose-dependent manner. {ECO:0000255|HAMAP-Rule:MF_04086}.
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|HAMAP-Rule:MF_04086};
CC   -!- COFACTOR:
CC       Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC         Evidence={ECO:0000255|HAMAP-Rule:MF_04086};
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       {ECO:0000255|HAMAP-Rule:MF_04086};
CC   -!- COFACTOR:
CC       Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC         Evidence={ECO:0000255|HAMAP-Rule:MF_04086};
CC       Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC         Evidence={ECO:0000255|HAMAP-Rule:MF_04086};
CC       Note=For polymerase activity. {ECO:0000255|HAMAP-Rule:MF_04086};
CC   -!- SUBUNIT: Homomultimer; the oligomeric structure is essential for the
CC       polymerase activity. Interacts with nucleoprotein N. Interacts with
CC       protein Z; this interaction inhibits viral transcription and
CC       replication. {ECO:0000255|HAMAP-Rule:MF_04086}.
CC   -!- SUBCELLULAR LOCATION: Virion {ECO:0000255|HAMAP-Rule:MF_04086}. Host
CC       cytoplasm {ECO:0000255|HAMAP-Rule:MF_04086}.
CC   -!- DOMAIN: The N-terminus contains the endonuclease activity (endoN). The
CC       central region contains the RdRp activity. {ECO:0000255|HAMAP-
CC       Rule:MF_04086}.
CC   -!- MISCELLANEOUS: Classified as His(-) endonuclease since it does not have
CC       a histidine upstream of the active site that coordinates the first
CC       cation. His(-) endonucleases display very low activity in vitro,
CC       although they are clearly active in vivo. {ECO:0000255|HAMAP-
CC       Rule:MF_04086}.
CC   -!- SIMILARITY: Belongs to the Bunyavirales RNA polymerase family.
CC       {ECO:0000255|HAMAP-Rule:MF_04086}.
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DR   EMBL; DQ328878; ABC71143.1; -; Genomic_RNA.
DR   RefSeq; YP_516233.1; NC_007906.1.
DR   SMR; Q27YE1; -.
DR   PRIDE; Q27YE1; -.
DR   GeneID; 3953120; -.
DR   KEGG; vg:3953120; -.
DR   Proteomes; UP000009261; Genome.
DR   GO; GO:0030430; C:host cell cytoplasm; IEA:UniProtKB-SubCell.
DR   GO; GO:0044423; C:virion component; IEA:UniProtKB-UniRule.
DR   GO; GO:0016787; F:hydrolase activity; IEA:UniProtKB-KW.
DR   GO; GO:0000166; F:nucleotide binding; IEA:UniProtKB-UniRule.
DR   GO; GO:0003968; F:RNA-directed 5'-3' RNA polymerase activity; IEA:UniProtKB-UniRule.
DR   GO; GO:0075526; P:cap snatching; IEA:UniProtKB-UniRule.
DR   GO; GO:0039689; P:negative stranded viral RNA replication; ISS:UniProtKB.
DR   GO; GO:0039696; P:RNA-templated viral transcription; ISS:UniProtKB.
DR   HAMAP; MF_04086; ARENA_L; 1.
DR   InterPro; IPR026382; CapSnatchArena.
DR   InterPro; IPR007099; RNA-dir_pol_NSvirus.
DR   InterPro; IPR010453; RNA_pol_arenavir.
DR   Pfam; PF06317; Arena_RNA_pol; 1.
DR   Pfam; PF17296; ArenaCapSnatch; 1.
DR   PIRSF; PIRSF000836; L_ArenaV; 1.
DR   PROSITE; PS50525; RDRP_SSRNA_NEG_SEG; 1.
PE   3: Inferred from homology;
KW   Cap snatching; Host cytoplasm; Hydrolase; Magnesium; Manganese;
KW   Metal-binding; Nucleotide-binding; Nucleotidyltransferase;
KW   Reference proteome; RNA-directed RNA polymerase; Transferase;
KW   Viral RNA replication; Virion.
FT   CHAIN           1..2208
FT                   /note="RNA-directed RNA polymerase L"
FT                   /id="PRO_0000361637"
FT   DOMAIN          1160..1356
FT                   /note="RdRp catalytic"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04086"
FT   REGION          26..291
FT                   /note="Endonuclease"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04086"
FT   ACT_SITE        115
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04086"
FT   BINDING         51
FT                   /ligand="Mn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29035"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04086"
FT   BINDING         89
FT                   /ligand="Mn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29035"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04086"
FT   BINDING         89
FT                   /ligand="Mn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29035"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04086"
FT   BINDING         102
FT                   /ligand="Mn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29035"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04086"
FT   BINDING         1318
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /ligand_note="catalytic; for RdRp activity"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_04086"
SQ   SEQUENCE   2208 AA;  253006 MW;  1DFF7E36C03D7E13 CRC64;
     MEESLRETKL LISRYLRQDE RIARQKLAFL GQSEPRSLLI EGLKLLSLCI EIDSCDTNCC
     THNTEGQSVE NFLFQNHILC PSLPLVVPDG MKLNGNILII LECFVRSNPT NFQQKYQEDS
     VKLDSLKGDL ERAGISLIPI IDGRTSYYNS LMEEWVCDQF RHNLFKLLEF EQENNALFEE
     SEYLRLCESL NVSGGRASGA QGLHSLLDCR GEHYNEILKA CHIGIDPSIG GVELKGQIEN
     LYQVFRQKLK KGVIKHQFRK VDQKSLLKEY CEMYKGIGIC GVEETTVDAL AAELPNISPI
     LRYIHLRIDS ESNAEVNEIS NLPTGLRSAF NKVKSLKVLN TRRKLLLLID TIILMSHCYV
     RELFPTLCER DWLGSSFFSV GDRLVSVGAI QHDLSKWLKR RLKANGGVGQ KSTELHKMIN
     TMIQKSSKAL GDVGLSFESY GVSFDFLNKV GLEEIMRFKI VGVTPTISYI KTNQQPPIPL
     REFSAEDDSD LKMLSSLSLS LVNSMKTSST VKTRQNAMGR ERYRVVQCKE CYYQELGNEY
     RDLVLLYQKT GEGSKCYSVN SKRVGEICSF YADPKRYFCP IFSENVITKV IDTMMTWLMG
     IVELEDSLRD IKKLTKMILL VILCQPSKRS QKLLQNLRYF IMAFVSDYHH VELFDKLREE
     LITDAEFFLF KLLGKILTIL LNDEVSTMLN NRFKFILNIS YFCHFITKET PDRLTDQIKC
     FEKYLEPKIQ FGSLTVNPKE TPTDEEKDDI LHGVNMFLSK KTCDEVDDPP SKKPGVSKKV
     FSLMLSAFNS GLLFKESELK KGMKDPLEDS GSATALDLAS NKSVVINKYT KDGRVLDYNY
     DKLVSVAVCQ LSEIFSRKGK YLLNKEDYDY KIQEVLSSLV IGSSKSEQPE EILDVDSDYM
     DQLKASVERV LDQYKPNRGV RSQNNDKSVN DLKIIVEDEL SRRLILGELS YHLVEDFDKG
     LLSENFYKEV CEKAFNNKDF RTKYFYDSEA GLCPIEKMTQ ALATRTYMSG EYFHCFKSLL
     LQMDANKLSG KYSHYKSQNL NFRFDHGRLM DDSRISERES NSEALSKALS LVNCLTSALK
     NLCFYSQESP SSYTETGPDT GRMKFSLSYK EQVGGNRELY IGDLRTKMFT RFVEDYFESY
     TKQLEGSCLN NEKEFEKAIL GMKLGVSLAH ASYSLDHSKW GPMMCPFLFL MLYRNLSPKL
     KGTEVELKGC DNISTILSWH IHKLVEVPFN VVTAMMRSYI KRKLGIMKDT SQTITESLFF
     SEFERGVIPS HFSSVLDMGQ GILHNTSDFY GLISERFINY ALRLVSGNPI EAYTSSDDQI
     SLFSHKFTEL MDTDPEEFLI YLEFHNYLSS LLNKFISPKS VVGRFVAEFK SRFYVWGDEV
     PLLSKFVAAS LHNIKCKEPH QLAETVDTII DQAVANGVPV SVCNEVQKRT LRLLEFSKYP
     IDPFLLHSDS DVKDWVDGNR GYRIMRVIEQ TLPEGTASVR SLLRILYNKL KSNELHEEFA
     SAYLSQNRSE TLVGLAELMG VKPPSTEDLM ICWLNLTACH PLRMVLRQKV IYPSALNLEE
     EKVPTLIRTL QNKLSSGFTR GAQKLLSEAV NKSAFQSSIA SGFVGLCKTL GSKCVRDPER
     ESHYIKSIIQ YLQTHCNVKP LNKGHLNLWV YESKTDDTQS ASVKPWQIEL LRPLLWDYLC
     IALSTSLEIG PWVLGEPVFK VKSDFWKPRP CDYFPLRPAH NRILEDRIGM NHIIHAVRRL
     YPEMFEKHLL PYMSDLAAMK LKWSPRIKFL DLCVTLDVNC EALSLISHVV KWKREEHYIV
     LSDDLLVSHD RKHTTLMDET VVSTSDVADN FLKQIYFESF VKPFVATSRT LGSFSWFPHR
     SSLPQGEGIE RLGPFSTFIE KVVFKGIERP MYRYDLFMGY SWLDYEIELA HLNQSQLIAS
     GLTEESCFED VDQFWHYLST LKVGSVKLSK TVRLTQKTQG KLQGQKFSVH LNFTGFITNS
     CTFVPKQLEV LYSGPVDEHF VIDCWSLLKS DREFKAGASE WFVHSDVVDA YISTASPSSE
     AYPLDVWLEP DLLELSVSDI SKVGPEVNIV PLVVEDGHLL ELKEKVAIIN PVILDQDIEV
     FINELKEDHW DLLVCKFADI LKHRQCCNLY LINVDILTIA LRILNDKAEE FISKSMQEID
     QWFDFKGYSL CFSKSRRQVM RHSSTGTMRL KGRLCQPAFY VEVVEEID