ID   L_SBVBH                 Reviewed;        2254 AA.
AC   H2AM11;
DT   29-MAY-2013, integrated into UniProtKB/Swiss-Prot.
DT   21-MAR-2012, sequence version 1.
DT   03-AUG-2022, entry version 36.
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   Bovine Schmallenberg virus (isolate Bovine/BH80/Germany/2011) (SBV).
OC   Viruses; Riboviria; Orthornavirae; Negarnaviricota; Polyploviricotina;
OC   Ellioviricetes; Bunyavirales; Peribunyaviridae; Orthobunyavirus;
OC   Schmallenberg orthobunyavirus.
OX   NCBI_TaxID=1318464;
OH   NCBI_TaxID=9913; Bos taurus (Bovine).
OH   NCBI_TaxID=9940; Ovis aries (Sheep).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX   PubMed=22376991; DOI=10.3201/eid1803.111905;
RA   Hoffmann B., Scheuch M., Hoper D., Jungblut R., Holsteg M., Schirrmeier H.,
RA   Eschbaumer M., Goller K.V., Wernike K., Fischer M., Breithaupt A.,
RA   Mettenleiter T.C., Beer M.;
RT   "Novel orthobunyavirus in cattle, europe, 2011.";
RL   Emerg. Infect. Dis. 18:469-472(2012).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RA   Hoeper D.;
RL   Submitted (JAN-2012) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RC   STRAIN=Germany;
RX   PubMed=23326235; DOI=10.1371/journal.ppat.1003133;
RA   Varela M., Schnettler E., Caporale M., Murgia C., Barry G., McFarlane M.,
RA   McGregor E., Piras I.M., Shaw A., Lamm C., Janowicz A., Beer M., Glass M.,
RA   Herder V., Hahn K., Baumgartner W., Kohl A., Palmarini M.;
RT   "Schmallenberg virus pathogenesis, tropism and interaction with the innate
RT   immune system of the host.";
RL   PLoS Pathog. 9:E1003133-E1003133(2013).
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 (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: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 (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; JX853179; AGC84160.1; -; Viral_cRNA.
DR   EMBL; HE649912; CCF55029.1; -; Genomic_RNA.
DR   SMR; H2AM11; -.
DR   GO; GO:0008234; F:cysteine-type peptidase activity; 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; IPR007322; RNA_pol_bunyavir.
DR   Pfam; PF04196; Bunya_RdRp; 1.
DR   Pfam; PF15518; L_protein_N; 1.
DR   PROSITE; PS50525; RDRP_SSRNA_NEG_SEG; 1.
PE   3: Inferred from homology;
KW   Host endoplasmic reticulum; Host Golgi apparatus; Hydrolase; Magnesium;
KW   Nucleotide-binding; Nucleotidyltransferase; Protease;
KW   RNA-directed RNA polymerase; Thiol protease; Transferase;
KW   Ubl conjugation pathway; Viral RNA replication; Virion.
FT   CHAIN           1..2254
FT                   /note="RNA-directed RNA polymerase L"
FT                   /id="PRO_0000422476"
FT   DOMAIN          1023..1214
FT                   /note="RdRp catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00539"
SQ   SEQUENCE   2254 AA;  261027 MW;  4FE8F8FCEC43B644 CRC64;
     METYKINIFR DRINQCRSAE EAKDIVADLL MARHDYFGRE VCYYLDIEFR QDVPAYDILL
     EFLPAGTAFN IRNCTPDNFI IHNGKLYIID YKVSTDHAYG QKTYEKYTQI FGDALSELPF
     DFEVVIIRAD PLRDTIHVNS NQFLEIFGPL NINLDFTWFF NLRSLIYEKY KDDDRFLEIV
     NQGEFTMTGP WIDEDTPELY SHPVFLEFYD SLDEMAKLTF HESMTFDATR GEKWNQNLQK
     VINRYGNDYN IFVKEAAAGI FRCEGNYPKP NHDEITIGWN QMVQRVSTER NLTQDVSKQK
     PSIHFIWGQP DETSNATTPK LIKIAKALQN ISGESTYISA FRALGMLMDF SENTALYEAH
     TSKLKSMARQ TSKRIDTKLE PIKIGTATIY WEQQFKLDTE IMNTKDKSHL LKDFLGIGGH
     VQFSKKTIDD LDTDKPTILD FNKKEVIDFC KFQYENVKKI LSGDNNLERI GCYLEEYGAN
     IASCSKDTWD QINQIGKSNY WACIKDFSVL MKNMLAVSQY NRHNTFRVVC CANNNLFGFV
     MPSSDIKAKR STLVYFLAVL HSTPQNVMHH GALHATFKTG SKYLSISKGM RLDKERCQRI
     VSSPGLFMLT TLMFAGDNPT LNLTDVMNFT FHTSLSITKA MLSLTEPSRY MIMNSLAISS
     HVRDYIAEKF GPYTKTSFSV VMANLIKRGC YMAYNQRDKV DMRNICLTDY EITQKGVRDN
     RDLSSIWFEG YVSLKEYINQ IYLPFYFNSK GLHEKHHVMI DLAKTILDIE RDQRLNIPGI
     WSTTPRKQTA NLNITIYAVA KNLIMDTARH NYIRSRIENT NNLNRSICTI STFTSSKSCI
     KVGDFEKEKS SATKKAADCM SKEIKKYTIA NPEFVDEELL NATIRHSRYE DLKKAIPNYI
     DIMSTKVFDS LYQKIKRKEI DDKPTVYHIL SAMKNHTDFK FTFFNKGQKT AKDREIFVGE
     FEAKMCLYLV ERISKERCKL NPDEMISEPG DSKLKKLEEL AESEIRFTAA TMKQIKERYL
     AEMGEASHMI AYKPHSVKIE INADMSKWSA QDVLFKYFWL FALDPALYLQ EKERILYFLC
     NYMQKKLILP DEMLCSILDQ RIKHEDDIIY EMTNGLSQNW VNIKRNWLQG NLNYTSSYLH
     SCSMNVYKDI LKRAATLLEG EVLVNSMVHS DDNHTSIVMI QDKLDDDIVI EFSAKLFEKI
     CLTFGNQANM KKTYITNFIK EFVSLFNIYG EPFSVYGRFI LTSVGDCAFL GPYEDVASRL
     SATQTAIKHG APPSLAWTAI ALTQWITHST YNMLPGQIND PTSSLPSHDR FELPIELCGL
     INSELPTIAI AGLEADNLSY LVRLSKRMSP IHLCREPIQH QYENIHTWDI SKLTQCDIFR
     LKLLRYMTLD STMSSDDGMG ETSEMRSRSL LTPRKFTTAS SLSRLHSYAD YQKTIQDQQK
     IEELFEYFIA NPQLLVTKGE TCEEFCMSVL FRYNSRKFKE SLSIQNPAQL FIEQVLFANK
     PMIDYTSIHD RLFGIQDDPN INDATCIIGK KTFVETYQQI KIDVEKFTLD VEDIKTIYSF
     CIMNDPILVA CANNLLISIQ GVEMQRLGMT CCYMPEIKSL KVIYHSPALV LRAYVTDNYE
     QKGMEPDEMR RDIYHLEEFI EKTKLRTNMQ GRIANNEIKL MKRDLKFEVQ ELTKFYQICY
     EYVKSTEHKI KIFILPKKAY TPIDFCSLVT GNLISDNKWM VVHYLKQITV PAKKAQIATS
     IDLEIQIAYE CFRLIAHFAD MFLNDDSKKA YINAIINTYT YKDVQVSSLY KKIKNSRLRS
     KIIPLLYHLG DLQQIDVDRF DAEKAEEQIT WNNWQTSREF TTGPIDLSIK GYGRSIRIVG
     EDNKLTAAEM QLSRVRSDIV SRHGQALLNK PHGLKLEKME PVTDLNPKLW YIAYQLREKK
     RYHYGVFSTS YIEEHNSRIE ASRIRKTNKW IPVCPIAISK QSSDGKPSLA KIPMLNIGEI
     KFTKLQIAVD DHAMIRKAPF SKMVFFDGPP IQSGGIDIGK LMKNQNILNL RLDNIQSITL
     LDLCRIFSCR GSKVDQDAFE FLSDEPLDED VIDELDSSPA LVVSYTKKST KSNSFKNVIV
     RALIRECDIF EDIMDITDDG FTSDSNLEVL ENLTWILNML ATNQWSTELL ACIHMCLYRN
     EMDHIYHNFQ VPEIFVDNPI SLNVKWDEVI MFLNILRDRD YKFEPWVSIL NHSLTKAIEY
     AYKKMEEERK QKSTGINKFL KGKKMGGRSK FDFQ