L_BUNL8
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 03-AUG-2022, entry version 76.
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 La Crosse orthobunyavirus.
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 PRIDE; Q8JPR2; -.
DR GeneID; 956554; -.
DR KEGG; vg:956554; -.
DR Proteomes; UP000008768; Genome.
DR Proteomes; UP000121242; Genome.
DR GO; GO:0030430; C:host cell cytoplasm; IEA:UniProtKB-SubCell.
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-directed 5'-3' RNA polymerase activity; IEA:UniProtKB-KW.
DR GO; GO:0039689; P:negative stranded viral RNA replication; IDA:UniProtKB.
DR GO; GO:0039696; P:RNA-templated viral transcription; IDA:UniProtKB.
DR GO; GO:0006351; P:transcription, DNA-templated; IEA:InterPro.
DR InterPro; IPR029124; L_protein_N.
DR InterPro; IPR007099; RNA-dir_pol_NSvirus.
DR InterPro; IPR014384; RNA-dir_pol_orthobunyavirus.
DR InterPro; IPR007322; RNA_pol_bunyavir.
DR Pfam; PF04196; Bunya_RdRp; 1.
DR Pfam; PF15518; L_protein_N; 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
