ID   L_BUNL8                 Reviewed;        2263 AA.
AC   Q8JPR2;
DT   10-AUG-2010, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-2002, sequence version 1.
DT   24-JAN-2024, entry version 83.
DE   RecName: Full=RNA-directed RNA polymerase L;
DE            Short=Protein L;
DE            EC=2.7.7.48 {ECO:0000250|UniProtKB:I0DF35};
DE   AltName: Full=Large structural protein;
DE   AltName: Full=Replicase;
DE   AltName: Full=Transcriptase;
DE   Includes:
DE     RecName: Full=cap-snatching endonuclease;
DE              EC=3.1.-.- {ECO:0000250|UniProtKB:A5HC98};
GN   Name=L;
OS   Bunyavirus La Crosse (isolate Human/United States/L78/1978).
OC   Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina;
OC   Ellioviricetes; Bunyavirales; Peribunyaviridae; Orthobunyavirus;
OC   Orthobunyavirus lacrosseense.
OX   NCBI_TaxID=796210;
OH   NCBI_TaxID=9850; Cervidae (Deer).
OH   NCBI_TaxID=9606; Homo sapiens (Human).
OH   NCBI_TaxID=7162; Ochlerotatus triseriatus (Eastern treehole mosquito) (Aedes triseriatus).
OH   NCBI_TaxID=13712; Tamias.
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RA   Hughes M.T., Kempf B.J., Blair C.D., Beaty B.J.;
RT   "Complete sequence of the Bunyavirus, La Crosse virus, Human/78 strain.";
RL   Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX   PubMed=17488515; DOI=10.1186/1743-422x-4-41;
RA   Bennett R.S., Ton D.R., Hanson C.T., Murphy B.R., Whitehead S.S.;
RT   "Genome sequence analysis of La Crosse virus and in vitro and in vivo
RT   phenotypes.";
RL   Virol. J. 4:41-41(2007).
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 (By similarity). These short capped RNAs are
CC       then used as primers for viral transcription. The 3'-end of subgenomic
CC       mRNAs molecules are not polyadenylated. During replication, the
CC       polymerase binds the 5' and 3' vRNA extremities at distinct sites (By
CC       similarity). In turn, significant conformational changes occur in the
CC       polymerase and in vRNA to initiate active RNA synthesis (By
CC       similarity). As a consequence of the use of the same enzyme for both
CC       transcription and replication, these mechanisms need to be well
CC       coordinated (By similarity). {ECO:0000250|UniProtKB:A5HC98,
CC       ECO:0000250|UniProtKB:I0DF35, ECO:0000250|UniProtKB:P20470}.
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:0000250|UniProtKB:P20470};
CC   -!- COFACTOR:
CC       Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC         Evidence={ECO:0000250|UniProtKB:A5HC98};
CC       Note=For endonuclease activity. Binds 2 Mn(2+) ions in the active site
CC       (By similarity). The divalent metal ions are crucial for catalytic
CC       activity (PubMed:31948728). {ECO:0000250|UniProtKB:A5HC98,
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. Initiation activity is stronger in the
CC       presence of Mn(2+) than in the presence of Mg(2+).
CC       {ECO:0000250|UniProtKB:A2SZS3};
CC   -!- SUBUNIT: Homomultimer (By similarity). Interacts with the glycoprotein
CC       N; this interaction allows efficient polymerase packaging into virus
CC       particles (By similarity). Interacts with nucleoprotein N (By
CC       similarity). {ECO:0000250|UniProtKB:P27316}.
CC   -!- SUBCELLULAR LOCATION: Host Golgi apparatus
CC       {ECO:0000250|UniProtKB:I0DF35}. Host endoplasmic reticulum
CC       {ECO:0000250|UniProtKB:I0DF35}. Host endoplasmic reticulum-Golgi
CC       intermediate compartment {ECO:0000250|UniProtKB:I0DF35}. Virion
CC       {ECO:0000250|UniProtKB:P20470}.
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:A5HC98, ECO:0000250|UniProtKB:I0DF35}.
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; AF528165; AAM94387.1; -; Genomic_RNA.
DR   EMBL; EF485035; ABQ12635.1; -; Viral_cRNA.
DR   RefSeq; NP_671968.1; NC_004108.1.
DR   SMR; Q8JPR2; -.
DR   GeneID; 956554; -.
DR   KEGG; vg:956554; -.
DR   Proteomes; UP000008768; Genome.
DR   Proteomes; UP000121242; Genome.
DR   GO; GO:0044165; C:host cell endoplasmic reticulum; IEA:UniProtKB-SubCell.
DR   GO; GO:0044172; C:host cell endoplasmic reticulum-Golgi intermediate compartment; IEA:UniProtKB-SubCell.
DR   GO; GO:0044177; C:host cell Golgi apparatus; IEA:UniProtKB-SubCell.
DR   GO; GO:0044423; C:virion component; IEA:UniProtKB-KW.
DR   GO; GO:0016787; F:hydrolase 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:0006351; P:DNA-templated transcription; IEA:InterPro.
DR   GO; GO:0039689; P:negative stranded viral RNA replication; IDA:UniProtKB.
DR   GO; GO:0039696; P:RNA-templated viral transcription; IDA:UniProtKB.
DR   CDD; cd22349; PDDEXK_RNA_polymerase-like; 1.
DR   Gene3D; 3.40.91.60; -; 1.
DR   InterPro; IPR048006; CapSnatch_bunyavir.
DR   InterPro; IPR029124; L_protein_N.
DR   InterPro; IPR048547; L_thumb_ring_bunyavir.
DR   InterPro; IPR007099; RNA-dir_pol_NSvirus.
DR   InterPro; IPR014384; RNA-dir_pol_orthobunyavirus.
DR   InterPro; IPR007322; RNA_pol_bunyavir.
DR   NCBIfam; TIGR04202; capSnatchArena; 1.
DR   Pfam; PF04196; Bunya_RdRp; 1.
DR   Pfam; PF15518; L_protein_N; 1.
DR   Pfam; PF21561; L_thumb_ring_vir; 1.
DR   PIRSF; PIRSF000824; L_OrthobunV; 1.
DR   PROSITE; PS50525; RDRP_SSRNA_NEG_SEG; 1.
PE   3: Inferred from homology;
KW   Coiled coil; Host endoplasmic reticulum; Host Golgi apparatus; Hydrolase;
KW   Magnesium; Manganese; Metal-binding; Nucleotide-binding;
KW   Nucleotidyltransferase; Reference proteome; RNA-directed RNA polymerase;
KW   Transferase; Viral RNA replication; Virion; Zinc.
FT   CHAIN           1..2263
FT                   /note="RNA-directed RNA polymerase L"
FT                   /id="PRO_0000397189"
FT   DOMAIN          1042..1230
FT                   /note="RdRp catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00539"
FT   REGION          1..185
FT                   /note="Endonuclease"
FT                   /evidence="ECO:0000250|UniProtKB:A5HC98"
FT   REGION          1841..1977
FT                   /note="Cap-binding"
FT                   /evidence="ECO:0000250|UniProtKB:A5HC98"
FT   COILED          1003..1033
FT                   /evidence="ECO:0000255"
FT   BINDING         34
FT                   /ligand="Mn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29035"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250|UniProtKB:A5HC98"
FT   BINDING         52
FT                   /ligand="Mn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29035"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250|UniProtKB:A5HC98"
FT   BINDING         79
FT                   /ligand="Mn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29035"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250|UniProtKB:A5HC98"
FT   BINDING         79
FT                   /ligand="Mn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29035"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000250|UniProtKB:A5HC98"
FT   BINDING         92
FT                   /ligand="Mn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29035"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250|UniProtKB:A5HC98"
FT   BINDING         93
FT                   /ligand="Mn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29035"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000250|UniProtKB:A5HC98"
FT   BINDING         1188
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /ligand_note="catalytic; for RdRp activity"
FT                   /evidence="ECO:0000250|UniProtKB:I0DF35"
FT   BINDING         2064
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000250|UniProtKB:A5HC98"
FT   BINDING         2169
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000250|UniProtKB:A5HC98"
FT   BINDING         2178
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000250|UniProtKB:A5HC98"
FT   BINDING         2182
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000250|UniProtKB:A5HC98"
SQ   SEQUENCE   2263 AA;  263013 MW;  A612682C8495E627 CRC64;
     MDYQEYQQFL ARINTARDAC VAKDIDVDLL MARHDYFGRE LCKSLNIEYR NDVPFVDIIL
     DIRPEVDPLT IDAPHITPDN YLYINNVLYI IDYKVSVSNE SSVITYDKYY ELTRDISDRL
     SIPIEIVIVR IDPVSKDLHI NSDRFKELYP TIVVDINFNQ FFDLKQLLYE KFGDDEEFLL
     KVAHGDFTLT APWCKTGCPE FWKHPIYKEF KMSMPVPERR LFEESVKFNA YESERWNTNL
     VKIREYTKKD YSEHISKSAK NIFLASGFYK QPNKNEISEG WTLMVERVQD QREISKSLHD
     QKPSIHFIWG AHNPGNSNNA TFKLILLSKS LQSIKGISTY TEAFKSLGKM MDIGDKAIEY
     EEFCMSLKSK ARSSWKQIMN KKLEPKQINN ALVLWEQQFM VNNDLIDKSE KLKLFKNFCG
     IGKHKQFKNK MLEDLEVSKP KILDFDDANM YLASLTMMEQ SKKILSKSNG LKPDNFILNE
     FGSKIKDANK ETYDNMHKIF ETRYWQCISD FSTLMKNILS VSQYNRHNTF RIAMCANNNV
     FAIVFPSADI KTKKATVVYS IIVLHKEEEN IFNPGCLHGT FKCMNGYISI SRAIRLDKER
     CQRIVSSPGL FLTTCLLFKH DNPTLVMSDI MNFSIYTSLS ITKSVLSLTE PARYMIMNSL
     AISSNVKDYI AEKFSPYTKT LFSVYMTRLI KNACFDAYDQ RQRVQLRDIY LSDYDITQKG
     IKDNRELTSI WFPGSVTLKE YLTQIYLPFY FNAKGLHEKH HVMVDLAKTI LEIECEQREN
     IKEIWSTNCT KQTVNLKILI HSLCKNLLAD TSRHNHLRNR IENRNNFRRS ITTISTFTSS
     KSCLKIGDFR KEKELQSVKQ KKILEVQSRK MRLANPMFVT DEQVCLEVGH CNYEMLRNAM
     PNYTDYISTK VFDRLYELLD KGVLTDKPVI EQIMDMMVDH KKFYFTFFNK GQKTSKDREI
     FVGEYEAKMC MYAVERIAKE RCKLNPDEMI SEPGDGKLKV LEQKSEQEIR FLVETTRQKN
     REIDEAIEAL AAEGYESNLE KIEKLSLGKA KGLKMEINAD MSKWSAQDVF YKYFWLIALD
     PILYPQEKER ILYFMCNYMD KELILPDELL FNLLDQKVAY QNDIIATMTN QLNSNTVLIK
     RNWLQGNFNY TSSYVHSCAM SVYKEILKEA ITLLDGSILV NSLVHSDDNQ TSITIVQDKM
     ENDKIIDFAM KEFERACLTF GCQANMKKTY VTNCIKEFVS LFNLYGEPFS IYGRFLLTSV
     GDCAYIGPYE DLASRISSAQ TAIKHGCPPS LAWVSIAISH WMTSLTYNML PGQSNDPIDY
     FPAENRKDIP IELNGVLDAP LSMISTVGLE SGNLYFLIKL LSKYTPVMQK RESVVNQIAE
     VKNWKVEDLT DNEIFRLKIL RYLVLDAEMD PSDIMGETSD MRGRSILTPR KFTTAGSLRK
     LYSFSKYQDR LSSPGGMVEL FTYLLEKPEL LVTKGEDMKD YMESVIFRYN SKRFKESLSI
     QNPAQLFIEQ ILFSHKPIID FSGIRDKYIN LHDSRALEKE PDILGKVTFT EAYRLLMRDL
     SSLELTNDDI QVIYSYIILN DPMMITIANT HILSIYGSPQ RRMGMSCSTM PEFRNLKLIH
     HSPALVLRAY SKNNPDIQGA DPTEMARDLV HLKEFVENTN LEEKMKVRIA INEAEKGQRD
     IVFELKEMTR FYQVCYEYVK STEHKIKVFI LPTKSYTTTD FCSLMQGNLI KDKEWYTVHY
     LKQILSGGHK AIMQHNATSE QNIAFECFKL ITHFADSFID SLSRSAFLQL IIDEFSYKDV
     KVSKLYDIIK NGYNRTDFIP LLFRTGDLRQ ADLDKYDAMK SHERVTWNDW QTSRHLDMGS
     INLTITGYNR SITIIGEDNK LTYAELCLTR KTPENITISG RKLLGARHGL KFENMSKIQT
     YPGNYYITYR KKDRHQFVYQ IHSHESITRR NEEHMAIRTR IYNEITPVCV VNVAEVDGDQ
     RILIRSLDYL NNDIFSLSRI KVGLDEFATI KKAHFSKMVS FEGPPIKTGL LDLTELMKSQ
     DLLNLNYDNI RNSNLISFSK LICCEGSDNI NDGLEFLSDD PMNFTEGEAI HSTPIFNIYY
     SKRGERHMTY RNAIKLLIER ETKIFEEAFT FSENGFISPE NLGCLEAVVS LIKLLKTNEW
     STVIDKCIHI CLIKNGMDHM YHSFDVPKCF MGNPITRDMN WMMFREFINS LPGTDIPPWN
     VMTENFKKKC IALINSKLET QRDFSEFTKL MKKEGGRSNI EFD
//