ID   L_HRSVB                 Reviewed;        2166 AA.
AC   O36635; O36637;
DT   03-MAR-2009, integrated into UniProtKB/Swiss-Prot.
DT   01-JAN-1998, sequence version 1.
DT   03-AUG-2022, entry version 103.
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   Human respiratory syncytial virus B (strain B1).
OC   Viruses; Riboviria; Orthornavirae; Negarnaviricota; Haploviricotina;
OC   Monjiviricetes; Mononegavirales; Pneumoviridae; Orthopneumovirus.
OX   NCBI_TaxID=79692;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX   PubMed=9391135; DOI=10.1073/pnas.94.25.13961;
RA   Karron R.A., Buonagurio D.A., Georgiu A.F., Whitehead S.S., Adamus J.E.,
RA   Clements-Mann M.L., Harris D.O., Randolph V.B., Udem S.A., Murphy B.R.,
RA   Sidhu M.S.;
RT   "Respiratory syncytial virus (RSV) SH and G proteins are not essential for
RT   viral replication in vitro: clinical evaluation and molecular
RT   characterization of a cold-passaged, attenuated RSV subgroup B mutant.";
RL   Proc. Natl. Acad. Sci. U.S.A. 94:13961-13966(1997).
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; AF013254; AAB82439.1; -; Genomic_RNA.
DR   EMBL; AF013255; AAB82445.1; -; Genomic_RNA.
DR   RefSeq; NP_056866.1; NC_001781.1.
DR   SMR; O36635; -.
DR   PRIDE; O36635; -.
DR   GeneID; 1489827; -.
DR   KEGG; vg:1489827; -.
DR   Proteomes; UP000002472; Genome.
DR   Proteomes; UP000180717; 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; IPR003006; Ig/MHC_CS.
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   Pfam; PF14318; Mononeg_mRNAcap; 1.
DR   Pfam; PF00946; Mononeg_RNA_pol; 1.
DR   TIGRFAMs; TIGR04198; paramyx_RNAcap; 1.
DR   PROSITE; PS00290; IG_MHC; 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..2166
FT                   /note="RNA-directed RNA polymerase L"
FT                   /id="PRO_0000365786"
FT   DOMAIN          693..877
FT                   /note="RdRp catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00539"
FT   DOMAIN          1820..2008
FT                   /note="Mononegavirus-type SAM-dependent 2'-O-MTase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00923"
FT   REGION          968..1460
FT                   /note="GDP polyribonucleotidyltransferase"
FT                   /evidence="ECO:0000250|UniProtKB:P28887"
FT   ACT_SITE        1338
FT                   /note="Nucleophile; for GDP polyribonucleotidyltransferase
FT                   activity"
FT                   /evidence="ECO:0000250|UniProtKB:P03523"
FT   ACT_SITE        1831
FT                   /note="For mRNA (nucleoside-2'-O-)-methyltransferase
FT                   activity"
FT                   /evidence="ECO:0000250|UniProtKB:Q6WB93"
FT   ACT_SITE        1936
FT                   /note="For mRNA (nucleoside-2'-O-)-methyltransferase
FT                   activity"
FT                   /evidence="ECO:0000250|UniProtKB:Q6WB93"
FT   ACT_SITE        1973
FT                   /note="For mRNA (nucleoside-2'-O-)-methyltransferase
FT                   activity"
FT                   /evidence="ECO:0000250|UniProtKB:Q6WB93"
FT   ACT_SITE        2004
FT                   /note="For mRNA (nucleoside-2'-O-)-methyltransferase
FT                   activity"
FT                   /evidence="ECO:0000250|UniProtKB:Q6WB93"
FT   BINDING         700
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         811
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         1853..1857
FT                   /ligand="substrate"
FT                   /ligand_note="for mRNA (nucleoside-2'-O-)-methyltransferase
FT                   activity"
FT                   /evidence="ECO:0000250|UniProtKB:Q6WB93"
FT   VARIANT         822
FT                   /note="R -> K"
FT   VARIANT         1662
FT                   /note="N -> H"
FT   VARIANT         1886
FT                   /note="L -> I"
FT   VARIANT         2030
FT                   /note="F -> L"
SQ   SEQUENCE   2166 AA;  249767 MW;  B2D8925C7935EFFD CRC64;
     MDPIINGNSA NVYLTDSYLK GVISFSECNA LGSYLFNGPY LKNDYTNLIS RQSPLLEHMN
     LKKLTITQSL ISRYHKGELK LEEPTYFQSL LMTYKSMSSS EQIATTNLLK KIIRRAIEIS
     DVKVYAILNK LGLKEKDRVK PNNNSGDENS VLTTIIKDDI LSAVESNQSY TNSDKNHSVN
     QNITIKTTLL KKLMCSMQHP PSWLIHWFNL YTKLNNILTQ YRSNEVKSHG FILIDNQTLS
     GFQFILNQYG CIVYHKGLKK ITTTTYNQFL TWKDISLSRL NVCLITWISN CLNTLNKSLG
     LRCGFNNVVL SQLFLYGDCI LKLFHNEGFY IIKEVEGFIM SLILNITEED QFRKRFYNSM
     LNNITDAAIK AQKNLLSRVC HTLLDKTVSD NIINGKWIIL LSKFLKLIKL AGDNNLNNLS
     ELYFLFRIFG HPMVDERQAM DAVRINCNET KFYLLSSLST LRGAFIYRII KGFVNTYNRW
     PTLRNAIVLP LRWLNYYKLN TYPSLLEITE NDLIILSGLR FYREFHLPKK VDLEMIINDK
     AISPPKDLIW TSFPRNYMPS HIQNYIEHEK LKFSESDRSR RVLEYYLRDN KFNECDLYNC
     VVNQSYLNNS NHVVSLTGKE RELSVGRMFA MQPGMFRQIQ ILAEKMIAEN ILQFFPESLT
     RYGDLELQKI LELKAGISNK SNRYNDNYNN YISKCSIITD LSKFNQAFRY ETSCICSDVL
     DELHGVQSLF SWLHLTIPLV TIICTYRHAP PFIKDHVVNL NEVDEQSGLY RYHMGGIEGW
     CQKLWTIEAI SLLDLISLKG KFSITALING DNQSIDISKP VRLIEGQTHA QADYLLALNS
     LKLLYKEYAG IGHKLKGTET YISRDMQFMS KTIQHNGVYY PASIKKVLRV GPWINTILDD
     FKVSLESIGS LTQELEYRGE SLLCSLIFRN IWLYNQIALQ LRNHALCNNK LYLDILKVLK
     HLKTFFNLDS IDMALSLYMN LPMLFGGGDP NLLYRSFYRR TPDFLTEAIV HSVFVLSYYT
     GHDLQDKLQD LPDDRLNKFL TCVITFDKNP NAEFVTLMRD PQALGSERQA KITSEINRLA
     VTEVLSIAPN KIFSKSAQHY TTTEIDLNDI MQNIEPTYPH GLRVVYESLP FYKAEKIVNL
     ISGTKSITNI LEKTSAIDTT DINRATDMMR KNITLLIRIL PLDCNKDKRE LLSLENLSIT
     ELSKYVRERS WSLSNIVGVT SPSIMFTMDI KYTTSTIASG IIIEKYNVNS LTRGERGPTK
     PWVGSSTQEK KTMPVYNRQV LTKKQRDQID LLAKLDWVYA SIDNKDEFME ELSTGTLGLS
     YEKAKKLFPQ YLSVNYLHRL TVSSRPCEFP ASIPAYRTTN YHFDTSPINH VLTEKYGDED
     IDIVFQNCIS FGLSLMSVVE QFTNICPNRI ILIPKLNEIH LMKPPIFTGD VDIIKLKQVI
     QKQHMFLPDK ISLTQYVELF LSNKALKSGS NINSNLILVH KMSDYFHNAY ILSTNLAGHW
     ILIIQLMKDS KGIFEKDWGE GYITDHMFIN LNVFFNAYKT YLLCFHKGYG KAKLECDMNT
     SDLLCVLELI DSSYWKSMSK VFLEQKVIKY IVNQDTSLHR IKGCHSFKLW FLKRLNNAKF
     TVCPWVVNID YHPTHMKAIL SYIDLVRMGL INVDKLTIKN KNKFNDEFYT SNLFYISYNF
     SDNTHLLTKQ IRIANSELED NYNKLYHPTP ETLENISLIP VKSNNSNKPK FCISGNTESI
     MMSTFSNKMH IKSSTVTTRF NYSKQDLYNL FPNVVIDRII DHSGNTAKSN QLYITTSHQT
     SLVRNSASLY CMLPWHHVNR FNFVFSSTGC KISIEYILKD LKIKDPSCIA FIGEGAGNLL
     LRTVVELHPD IRYIYRSLKD CNDHSLPIEF LRLYNGHINI DYGENLTIPA TDATNNIHWS
     YLHIKFAEPI SIFVCDAELP VTANWSKIII EWSKHVRKCK YCSSVNRCIL IAKYHAQDDI
     DFKLDNITIL KTYVCLGSKL KGSEVYLVLT IGPANILPVF DVVQNAKLIF SRTKNFIMPK
     KTDKESIDAN IKSLIPFLCY PITKKGIKTS LSKLKSVVNG DILSYSIAGR NEVFSNKLIN
     HKHMNILKWL DHVLNFRSAE LNYNHLYMIE STYPYLSELL NSLTTNELKK LIKITGSVLY
     NLPNEQ