L_BUNYW
ID L_BUNYW Reviewed; 2238 AA.
AC P20470;
DT 01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1991, sequence version 1.
DT 03-AUG-2022, entry version 89.
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 Bunyamwera virus (BUNV).
OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina;
OC Ellioviricetes; Bunyavirales; Peribunyaviridae; Orthobunyavirus.
OX NCBI_TaxID=35304;
OH NCBI_TaxID=7159; Aedes aegypti (Yellowfever mosquito) (Culex aegypti).
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=2596023; DOI=10.1016/0042-6822(89)90555-2;
RA Elliott R.M.;
RT "Nucleotide sequence analysis of the large (L) genomic RNA segment of
RT Bunyamwera virus, the prototype of the family Bunyaviridae.";
RL Virology 173:426-436(1989).
RN [2]
RP FUNCTION.
RX PubMed=12642095; DOI=10.1016/s0042-6822(02)00070-3;
RA Flick K., Hooper J.W., Schmaljohn C.S., Pettersson R.F., Feldmann H.,
RA Flick R.;
RT "Rescue of Hantaan virus minigenomes.";
RL Virology 306:219-224(2003).
RN [3]
RP FUNCTION, INTERACTION WITH N, AND SUBCELLULAR LOCATION.
RX PubMed=19141438; DOI=10.1099/vir.0.007567-0;
RA Shi X., Elliott R.M.;
RT "Generation and analysis of recombinant Bunyamwera orthobunyaviruses
RT expressing V5 epitope-tagged L proteins.";
RL J. Gen. Virol. 90:297-306(2009).
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 (Probable). During transcription, synthesizes
CC subgenomic RNAs and assures their capping by a cap-snatching mechanism,
CC which involves the endonuclease activity cleaving the host capped pre-
CC mRNAs (By similarity). These short capped RNAs are then used as primers
CC for viral transcription. The 3'-end of subgenomic mRNAs molecules are
CC not polyadenylated. During replication, the polymerase binds the 5' and
CC 3' vRNA extremities at distinct sites (By similarity). In turn,
CC significant conformational changes occur in the polymerase and in vRNA
CC to initiate active RNA synthesis (By similarity). As a consequence of
CC the use of the same enzyme for both transcription and replication,
CC these mechanisms need to be well coordinated (By similarity).
CC {ECO:0000250|UniProtKB:A5HC98, ECO:0000250|UniProtKB:I0DF35,
CC ECO:0000269|PubMed:12642095, ECO:0000269|PubMed:19141438, ECO:0000305}.
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: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 (By similarity). {ECO:0000250|UniProtKB:A5HC98};
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
CC (PubMed:19141438). {ECO:0000250|UniProtKB:P27316,
CC ECO:0000269|PubMed:19141438}.
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:0000305}. Host cytoplasm {ECO:0000269|PubMed:19141438}.
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:0000305}.
CC -!- SIMILARITY: Belongs to the Bunyavirales RNA polymerase family.
CC {ECO:0000305}.
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DR EMBL; X14383; CAA32553.1; -; Genomic_RNA.
DR PIR; A33744; RRVUBY.
DR RefSeq; NP_047211.1; NC_001925.1.
DR SMR; P20470; -.
DR PRIDE; P20470; -.
DR GeneID; 2648215; -.
DR KEGG; vg:2648215; -.
DR Proteomes; UP000002476; Genome.
DR GO; GO:0030430; C:host cell cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0008234; F:cysteine-type peptidase 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; ISS:UniProtKB.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR GO; GO:0039696; P:RNA-templated viral transcription; ISS: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 1: Evidence at protein level;
KW Host cytoplasm; Host endoplasmic reticulum; Host Golgi apparatus;
KW Hydrolase; Magnesium; Manganese; Metal-binding; Nucleotide-binding;
KW Nucleotidyltransferase; Protease; Reference proteome;
KW RNA-directed RNA polymerase; Thiol protease; Transferase;
KW Ubl conjugation pathway; Viral RNA replication; Virion.
FT CHAIN 1..2238
FT /note="RNA-directed RNA polymerase L"
FT /id="PRO_0000222020"
FT DOMAIN 1016..1207
FT /note="RdRp catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00539"
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 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"
SQ SEQUENCE 2238 AA; 258670 MW; 1ED00AB156BAC8DA CRC64;
MEDQAYDQYL HRIQAARTAT VAKDISADIL EARHDYFGRE LCNSLGIEYK NNVLLDEIIL
DVVPGVNLLN YNIPNVTPDN YIWDGHFLII LDYKVSVGND SSEITYKKYT SLILPVMSEL
GIDTEIAIIR ANPVTYQISI IGEEFKQRFP NIPIQLDFGR FFELRKMLLD KFADDEEFLM
MIAHGDFTLT APWCTSDTPE LEEHEIFQEF INSMPPRFVS LFKEAVNFSA YSSERWNTFL
YRARAETEVD YNQFLSDKAH KIFMLEGDYM RPTQAEIDKG WELMSQRVYT EREIITDVTK
QKPSIHFIWV KNADRKLIGS TAKLIYLSNS LQSITEQSTW TDALKAIGKS MDIDGKVGQY
ETLCAERKMI ARSTGKKVDN KRLEAVKIGN ALVLWEQQFI LANDLFKNQE RQKFMKNFFG
IGKHKSFKDK TSSDIETDKP KILDFNNTIV LMAARTMVNK NKALLAKDNT LQDLHPIIMQ
YASEIKEASK DTFDALLKIS KTCFWQCIVD VSTIMRNILA VSQYNRHNTF RVAMCANDSV
YALVFPSSDI KTKRATVVFS IVCMHKEKND LMDAGALFTT LECKNKEYIS ISKAIRLDKE
RCQRIVSSPG LFILSSMLLY NNNPEVNLVD VLNFTFYTSL SITKSMLSLT EPSRYMIMNS
LAISSHVRDY IAEKFSPYTK TLFSVYMVNL IKRGCASANE QSSKIQLRNI YLSDYDITQK
GVNDGRNLDS IWFPGKVNLK EYINQIYLPF YFNAKGLHEK HHVMIDLAKT VLEIEMNQRS
DNLGIWSKAE KKQHVNLPIL IHSIAKSLIL DTSRHNHLRN RVESRNNFRR SITTISTFTS
SKSCIKIGDF REIKDKETEK SKKSTEKFDK KFRLSNPLFL EDEEANLEVQ HCNYRALIQK
IPNYKDYISV KVFDRLYELL KNGVLTDKPF IELAMEMMKN HKEFSFTFFN KGQKTAKDRE
IFVGEFEAKM CMYVVERISK ERCKLNTDEM ISEPGDSKLK ILEKKAEEEI RYIVERTKDS
IIKGDPSKAL KLEINADMSK WSAQDVFYKY FWLIAMDPIL YPAEKTRILY FMCNYMQKLL
ILPDDLIANI LDQKRPYNDD LILEMTNGLN YNYVQIKRNW LQGNFNYISS YVHSCAMLVY
KDILKECMKL LDGDCLINSM VHSDDNQTSL AIIQNKVSDQ IVIQYAANTF ESVCLTFGCQ
ANMKKTYITH TCKEFVSLFN LHGEPLSVFG RFLLPSVGDC AYIGPYEDLA SRLSAAQQSL
KHGCPPSLVW LAISCSHWIT FFTYNMLDDQ INAPQQHLPF NNRKEIPVEL NGYLNAPLYL
IALVGLEAGN LWFLINILKK LVPLDKQKET IQSQCLHLCN SIDKLTESEK FKLKILRYLT
LDTEMSVDNN MGETSDMRSR SLLTPRKFTT LGSLNKLVSY NDFRSSLDDQ RFTDNLNFML
NNPELLVTKG ENKEQFMQSV LFRYNSKRFK ESLSIQNPAQ LFIEQILFSH KPIIDYSSIF
DKLTSLAEAD IIEELPEIIG RVTFPQAYQM INRDIGQLPL DIDDIKLIFR YCILNDPLMI
TAANTSLLCV KGTPQDRTGL SASQMPEFRN MKLIHHSPAL VLKAFSKGTS DIPGADPIEL
EKDLHHLNEF VETTAIKEKI LHNIDNPPKH LIGNEILIYR IREMTKLYQV CYDYVKSTEH
KVKIFILPMK SYTAIDFCTL IQGNTISDNK WYTMHYLKQI ASGSIKGNIV TTSTSEQIIA
NECFRVLCHF ADSFVEEASR LSFINEVLDN FTYKNISVNS LFNTLLASTT RLDFIPLLFR
LKVLTQTDLN RFDALKTNER VSWNNWQTNR SLNSGLIDLT ISGYLRSIRV VGEDNKLKIA
ELTIPNFYPN TVFHAGNKLL NSRHGLKFEY MEEIVLDEKY NYYITYQKKR AHIYTYQVST
IEHILRRNNE GLQSRGPRYN KMVPVCPVVL SVRDELFRMS LENVFSLNMT NFSMSRLFVS
PDEVATVKKA HMSKMMFFSG PTIKAGIINL TSLMRTQELL TLNYDNLCKS SIVPFCRILE
CNGDEQGELI FLSDEVMDFT ISEEIESMPL FTIRYQKRGT EIMTYKNAIM KLVSAGVDEI
KEVFDFSKQG FYSKKNLGII NTICSIINIL ETNEWSTILY NSFHIAMLLE SMDREFHMFT
LPEAFFINVA GGVVNWTKLL KFIKSLPVIE QEPWSMMMSR FVEKTVYLIE REMNKDVDFT
DFLDELEFSS GKSLFTFF
