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   24-JAN-2024, entry version 96.
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;
OC   Orthobunyavirus bunyamweraense.
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   GeneID; 2648215; -.
DR   KEGG; vg:2648215; -.
DR   Proteomes; UP000002476; 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: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-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; ISS:UniProtKB.
DR   GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR   GO; GO:0039696; P:RNA-templated viral transcription; ISS: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   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
//