ID   L_BRSVA                 Reviewed;        2162 AA.
AC   O91940; Q77KZ5;
DT   03-MAR-2009, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1998, sequence version 1.
DT   03-AUG-2022, entry version 105.
DE   RecName: Full=RNA-directed RNA polymerase L;
DE            Short=Protein L;
DE   AltName: Full=Large structural protein;
DE   AltName: Full=Replicase;
DE   AltName: Full=Transcriptase;
DE   Includes:
DE     RecName: Full=RNA-directed RNA polymerase;
DE              EC=2.7.7.48 {ECO:0000250|UniProtKB:P28887};
DE   Includes:
DE     RecName: Full=GTP phosphohydrolase {ECO:0000250|UniProtKB:P28887};
DE              EC=3.6.1.- {ECO:0000250|UniProtKB:P28887};
DE   Includes:
DE     RecName: Full=GDP polyribonucleotidyltransferase {ECO:0000305};
DE              EC=2.7.7.88 {ECO:0000250|UniProtKB:P28887};
DE     AltName: Full=PRNTase {ECO:0000305};
DE   Includes:
DE     RecName: Full=mRNA cap methyltransferase {ECO:0000305};
DE              EC=2.1.1.375 {ECO:0000250|UniProtKB:P03523};
DE     AltName: Full=mRNA (guanine-N(7)-)-methyltransferase {ECO:0000250|UniProtKB:P03523};
DE              Short=G-N7-MTase {ECO:0000250|UniProtKB:P03523};
DE     AltName: Full=mRNA (nucleoside-2'-O-)-methyltransferase {ECO:0000250|UniProtKB:P03523};
DE              Short=N1-2'-O-MTase {ECO:0000250|UniProtKB:P03523};
GN   Name=L;
OS   Bovine respiratory syncytial virus (strain A51908) (BRS).
OC   Viruses; Riboviria; Orthornavirae; Negarnaviricota; Haploviricotina;
OC   Monjiviricetes; Mononegavirales; Pneumoviridae; Orthopneumovirus.
OX   NCBI_TaxID=11247;
OH   NCBI_TaxID=9913; Bos taurus (Bovine).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX   PubMed=9747733; DOI=10.1099/0022-1317-79-9-2231;
RA   Yunus A.S., Collins P.L., Samal S.K.;
RT   "Sequence analysis of a functional polymerase (L) gene of bovine
RT   respiratory syncytial virus: determination of minimal trans-acting
RT   requirements for RNA replication.";
RL   J. Gen. Virol. 79:2231-2238(1998).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RC   STRAIN=ATCC51908;
RX   PubMed=11724268; DOI=10.1023/a:1011888019966;
RA   Yunus A.S., Khattar S.K., Collins P.L., Samal S.K.;
RT   "Rescue of bovine respiratory syncytial virus from cloned cDNA: entire
RT   genome sequence of BRSV strain A51908.";
RL   Virus Genes 23:157-164(2001).
CC   -!- FUNCTION: Responsible for RNA synthesis (replicase and transcriptase),
CC       cap addition, and cap methylation. Performs also the polyadenylation of
CC       subgenomic mRNAs by a stuttering mechanism at a slipery stop site
CC       present at the end of viral genes. The template is composed of the
CC       viral RNA tightly encapsidated by the nucleoprotein (N). The viral
CC       polymerase binds to the genomic RNA at two differents sites in the 3'
CC       leader promoter thereby initiating either genome replication or mRNA
CC       transcription. In the transcription mode, the polymerase performs the
CC       sequential transcription of all mRNAs using a termination-reinitiation
CC       mechanism responding to gene start and gene end signals. Some
CC       polymerase disengage from the template at each gene junction, resulting
CC       in a decreasing abundance of transcripts from the 3' to the 5' end of
CC       the genome. The first gene is the most transcribed, and the last the
CC       least transcribed. Needs as cofactors the phosphoprotein for
CC       processivity and the M2-1 anti-termination protein. Polyribonucleotidyl
CC       transferase (PRNTase) adds the cap structure when the nascent RNA chain
CC       length has reached few nucleotides (By similarity). Ribose 2'-O
CC       methylation of viral mRNA cap precedes and facilitates subsequent
CC       guanine-N-7 methylation (By similarity). In the replication mode, the
CC       polymerase replicates the whole viral genome without recognizing the
CC       gene end transcriptional signals. The ability of the polymerase to
CC       override the gene end signals as it is producing the antigenome is
CC       probably due to replicative RNA becoming encapsidated with
CC       nucleoprotein as it is synthesized (By similarity).
CC       {ECO:0000250|UniProtKB:P03523, ECO:0000250|UniProtKB:P28887}.
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   -!- CATALYTIC ACTIVITY:
CC       Reaction=GTP + H2O = GDP + H(+) + phosphate; Xref=Rhea:RHEA:19669,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:37565,
CC         ChEBI:CHEBI:43474, ChEBI:CHEBI:58189;
CC         Evidence={ECO:0000250|UniProtKB:P28887};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=a 5'-end triphospho-adenylyl-adenylyl-cytidylyl-adenosine in
CC         mRNA + GDP + H(+) = a 5'-end (5'-triphosphoguanosine)-adenylyl-
CC         adenylyl-cytidylyl-adenosine in mRNA + diphosphate;
CC         Xref=Rhea:RHEA:65436, Rhea:RHEA-COMP:16797, Rhea:RHEA-COMP:16799,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:33019, ChEBI:CHEBI:58189,
CC         ChEBI:CHEBI:156484, ChEBI:CHEBI:156503; EC=2.7.7.88;
CC         Evidence={ECO:0000250|UniProtKB:P28887};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=a 5'-end (5'-triphosphoguanosine)-adenylyl-adenylyl-cytidylyl-
CC         adenosine in mRNA + 2 S-adenosyl-L-methionine = a 5'-end (N(7)-methyl
CC         5'-triphosphoguanosine)-(2'-O-methyladenylyl)-adenylyl-cytidylyl-
CC         adenosine in mRNA + H(+) + 2 S-adenosyl-L-homocysteine;
CC         Xref=Rhea:RHEA:65376, Rhea:RHEA-COMP:16797, Rhea:RHEA-COMP:16798,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789,
CC         ChEBI:CHEBI:156483, ChEBI:CHEBI:156484; EC=2.1.1.375;
CC         Evidence={ECO:0000250|UniProtKB:P03523};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=a 5'-end (5'-triphosphoguanosine)-adenylyl-adenylyl-cytidylyl-
CC         adenosine in mRNA + S-adenosyl-L-methionine = a 5'-end (5'-
CC         triphosphoguanosine)-(2'-O-methyladenylyl)-adenylyl-cytidylyl-
CC         adenosine in mRNA + H(+) + S-adenosyl-L-homocysteine;
CC         Xref=Rhea:RHEA:65380, Rhea:RHEA-COMP:16797, Rhea:RHEA-COMP:16801,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789,
CC         ChEBI:CHEBI:156482, ChEBI:CHEBI:156484;
CC         Evidence={ECO:0000250|UniProtKB:P03523};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=a 5'-end (5'-triphosphoguanosine)-(2'-O-methyladenylyl)-
CC         adenylyl-cytidylyl-adenosine in mRNA + S-adenosyl-L-methionine = a
CC         5'-end (N(7)-methyl 5'-triphosphoguanosine)-(2'-O-methyladenylyl)-
CC         adenylyl-cytidylyl-adenosine in mRNA + S-adenosyl-L-homocysteine;
CC         Xref=Rhea:RHEA:65440, Rhea:RHEA-COMP:16798, Rhea:RHEA-COMP:16801,
CC         ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:156482,
CC         ChEBI:CHEBI:156483; Evidence={ECO:0000250|UniProtKB:P03523};
CC   -!- COFACTOR:
CC       Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC         Evidence={ECO:0000250|UniProtKB:P28887};
CC       Note=For RNA-directed RNA polymerase activity. Mn(2+) can stimulate de
CC       novo initiation but it is inefficient at supporting elongation of de
CC       novo initiated RNA. {ECO:0000250|UniProtKB:P28887};
CC   -!- SUBUNIT: Interacts with the phosphoprotein (via C-terminus); the
CC       association of P and L forms the polymerase complex.
CC       {ECO:0000250|UniProtKB:P28887}.
CC   -!- SUBCELLULAR LOCATION: Virion {ECO:0000250|UniProtKB:P28887}. Host
CC       cytoplasm {ECO:0000250|UniProtKB:P28887}. Note=Localizes in cytoplasmic
CC       inclusion bodies. {ECO:0000250|UniProtKB:P28887}.
CC   -!- DOMAIN: Contains an RNA-dependent RNA polymerase (RdRp) domain, a
CC       polyribonucleotidyl transferase (PRNTase or capping) domain and a
CC       methyltransferase (MTase) domain. {ECO:0000250|UniProtKB:P28887}.
CC   -!- SIMILARITY: Belongs to the paramyxovirus L protein family.
CC       {ECO:0000305}.
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DR   EMBL; AF065167; AAC36684.1; -; Genomic_RNA.
DR   EMBL; AF295543; AAL49402.1; -; Genomic_RNA.
DR   SMR; O91940; -.
DR   IntAct; O91940; 1.
DR   PRIDE; O91940; -.
DR   Proteomes; UP000007616; Genome.
DR   GO; GO:0030430; C:host cell cytoplasm; IEA:UniProtKB-SubCell.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0003924; F:GTPase activity; IEA:RHEA.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0004482; F:mRNA (guanine-N7-)-methyltransferase activity; IEA:InterPro.
DR   GO; GO:0003968; F:RNA-directed 5'-3' RNA polymerase activity; IEA:UniProtKB-KW.
DR   InterPro; IPR039736; L_poly_C.
DR   InterPro; IPR026890; Mononeg_mRNAcap.
DR   InterPro; IPR014023; Mononeg_RNA_pol_cat.
DR   InterPro; IPR025786; Mononega_L_MeTrfase.
DR   InterPro; IPR016269; RNA-dir_pol_paramyxovirus.
DR   Pfam; PF14318; Mononeg_mRNAcap; 1.
DR   Pfam; PF00946; Mononeg_RNA_pol; 1.
DR   PIRSF; PIRSF000830; RNA_pol_ParamyxoV; 1.
DR   TIGRFAMs; TIGR04198; paramyx_RNAcap; 1.
DR   PROSITE; PS50526; RDRP_SSRNA_NEG_NONSEG; 1.
DR   PROSITE; PS51590; SAM_MT_MNV_L; 1.
PE   3: Inferred from homology;
KW   ATP-binding; Host cytoplasm; Hydrolase; Magnesium; Metal-binding;
KW   Methyltransferase; mRNA capping; mRNA processing; Multifunctional enzyme;
KW   Nucleotide-binding; Nucleotidyltransferase; Reference proteome;
KW   RNA-directed RNA polymerase; S-adenosyl-L-methionine; Transferase;
KW   Viral RNA replication; Virion.
FT   CHAIN           1..2162
FT                   /note="RNA-directed RNA polymerase L"
FT                   /id="PRO_0000365785"
FT   DOMAIN          690..874
FT                   /note="RdRp catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00539"
FT   DOMAIN          1816..2004
FT                   /note="Mononegavirus-type SAM-dependent 2'-O-MTase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00923"
FT   REGION          965..1457
FT                   /note="GDP polyribonucleotidyltransferase"
FT                   /evidence="ECO:0000250|UniProtKB:P28887"
FT   ACT_SITE        1335
FT                   /note="Nucleophile; for GDP polyribonucleotidyltransferase
FT                   activity"
FT                   /evidence="ECO:0000250|UniProtKB:P03523"
FT   ACT_SITE        1827
FT                   /note="For mRNA (nucleoside-2'-O-)-methyltransferase
FT                   activity"
FT                   /evidence="ECO:0000250|UniProtKB:Q6WB93"
FT   ACT_SITE        1932
FT                   /note="For mRNA (nucleoside-2'-O-)-methyltransferase
FT                   activity"
FT                   /evidence="ECO:0000250|UniProtKB:Q6WB93"
FT   ACT_SITE        1969
FT                   /note="For mRNA (nucleoside-2'-O-)-methyltransferase
FT                   activity"
FT                   /evidence="ECO:0000250|UniProtKB:Q6WB93"
FT   ACT_SITE        2000
FT                   /note="For mRNA (nucleoside-2'-O-)-methyltransferase
FT                   activity"
FT                   /evidence="ECO:0000250|UniProtKB:Q6WB93"
FT   BINDING         697
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /ligand_note="catalytic; for RNA-directed RNA polymerase
FT                   activity"
FT                   /evidence="ECO:0000250|UniProtKB:P28887"
FT   BINDING         808
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /ligand_note="catalytic; for RNA-directed RNA polymerase
FT                   activity"
FT                   /evidence="ECO:0000250|UniProtKB:P28887"
FT   BINDING         1849..1853
FT                   /ligand="substrate"
FT                   /ligand_note="for mRNA (nucleoside-2'-O-)-methyltransferase
FT                   activity"
FT                   /evidence="ECO:0000250|UniProtKB:Q6WB93"
FT   VARIANT         459
FT                   /note="S -> R"
FT   VARIANT         788
FT                   /note="T -> S"
SQ   SEQUENCE   2162 AA;  249439 MW;  09EC484329C83B29 CRC64;
     MDTLIHENST NVYLTDSYLK GVISFSECNA LGSYLLDGPY LKNDYTNIIS RQKPLIEHIN
     LKKLSIIQSF VTKYNKGELG LEEPTYFQSL LMTYKSLSTS ELITTTTLFK KIIRRAIEIS
     DVKVYAILNK LGLKEKGKVD RCDDTNTTLS NIVRDNILSV ISDNTPSTKK PNNSSCKPDQ
     PIKTTILCKL LSSMSHPPTW LIHWFNLYTK LNDILTQYRT NEARNHGYIL IDTRTLGEFQ
     FILNQYGCIV YHKKLKKITI TTYNQFLTWK DISLSRLNVC MITWISNCLN TLNKSLGLRC
     EFNNVTLSQL FLHGDCILKL FHNEGYYIIK EVEGFIMSLI LNLTEEDQFR KRFFNSMLNN
     ITDAAARAQQ DLLSRARHTI LDKTISDNIL NGKWLILLGK FLKLIKLAGA NNLNNLSELY
     FLFRIFGHPM VDERQAMDAV RLNCNETKFY LLSSLSMLSG AFIYRIIKGF VNTYNRWPTL
     RNAIVLPLRW INYYKLNTYP SLLELTEADL IILSGLRFYR EFHLPKKVDL EVIINDKAIS
     PPKNLIWTSF PKNYMPSHIQ IYIEHERLKF TESDRSRRVL EYYLRNNRFS ESDLYNCIVN
     QEYLNNPNHV ISLTGKEREL SVGRMFAMQP GMFRQVQIMA EKLIAENILQ FFPESLTRYG
     DLELQKILEL KAGISNKANR CNDNYNNYIS KCSIITDLSK FNQAFRYETS CICSDVLDEL
     HGVQSLFSWL HLTIPFATVI CTYRHAPPYI RNHITDLNKV DEQSGLYRYH MGGIEGWCQK
     LWTIEAITLL DLISIKGKFS ITALINGDNQ SIDISKPIKL NEGQTHAQAD YLLALKSLKL
     LYKEYASIGH KLKGTETYIS RDMQFMSKTI QHNGVYYPAS IKKVLRVGPW INTILDDFKV
     SMESIGSLTQ ELEYRGESLL CSLIFRNVWL YNQIALQLKN HALCHNKLYL DILKVLAHLK
     MFFNLDNIDT ALTLYMNLPM LFGGGDPNLL YRSFYRRTPD FLTEAIAHSV FVLSYYTGHD
     LQDKLQDLPD DKLNKFLTCI ITFDKNPNAE FVTLMRDPQA LGSERQAKVT SEINRLAVTE
     VLSNAPNKIF AKSAQHYTTT EVDLNDVMQK IEPTYPHGLR VVYESLPFYK AEKIVNLISG
     TKSITNILEK TSAIDYTDIE RAIDMMRKNI TLLIRILPLD YNKAKLGLLS LNNLSITDIS
     KYVRERSWSL SNIVGITSPS ILYTMDIKYT TSTITSGIII EKYNSNFLTR GERGPTKPWV
     GSSTQEKKTM PVYNRQVLTK KQKDQIDLLA KLDWVYASID NKDEFMEVLC LGTLGLSYEK
     AKKLFPQYLS VNYLHRLTVS SRPCEFPASI PAYRTTNYHF DTSPINRILT EKYGDEDIDI
     VFQNCISFGL SLMSVVEQFT NVCPNRIILI PKLNEIHLMK PPIFTGDVDI CKLNQVIQKQ
     HMFLPDKISL SQYVELFLSN KTLKNSPHIS SNLVLVHKMS DYFLHKYVLS TNLAGHWIMI
     IQLMKDSKGI FEKDWGEGYI TDHMFLDLNV FFDAYKTYLL CFHKGYGKAK LECDMNTSDL
     FCTLELIDIS YWKSMSKVFL EQKVVKHIIN QDSSLHRVRG CHSFKLWFLK RLNTSKFIVC
     PWVVNIDYHP THMKAILTYM ELTTMGLVHV DKLYTDQKHK LNDGFYTSNL FYINYNFSDN
     THLLTKQIRV ANSELIDNYN TLYHPSPESL ESILKRSNQS NNVIELKDYP IDKFQSPKGR
     GVSDITCISS NQKIKQGYNN QDLYNLFPAV IIDKIVDHSG NIANINQMYT ITPNQLTLIS
     NGTSLYCMLP WHHINRFNFV FSSTGCKIST KLILKDLKIK DPHCIAFIGE GAGNLLLRTV
     VELHPDIKYI YRSLKDCNDH SLPIEFLRLY NGHISIDYGE NLTIPATDAT NAIHWSYLHI
     RYAEPINLFV CDAELPDLTN WSRIVSEWYK HVRCCKYCST IDRSKLIVKY HAQDITDFKL
     NNISIVKTYV CLGSKLKGSE VYLVLTVGPS NIFPSFNVVQ NAKLILSRTQ NFPMPKKIDK
     DSVDANIKSL IPFLCYPITK KGIKAALSKL KDVVDGNILS YSIAGRNEVY SNKLINYKLL
     NILKWLDHIL NFRSLEFSYN HLYMIESTYP FLSELLNSLT TNELKKLIKV TGSVLYSLQH
     EL