L_HRSVL
ID L_HRSVL Reviewed; 2165 AA.
AC Q9IWW8;
DT 03-MAR-2009, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 95.
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 A (strain Long).
OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Haploviricotina;
OC Monjiviricetes; Mononegavirales; Pneumoviridae; Orthopneumovirus.
OX NCBI_TaxID=11260;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RA Martinez L., Delgado T., Melero J., Garcia-Barreno B.;
RT "Human repiratory syncytial virus phosphoprotein plays a central role in
RT the interaction of ribonucleoprotein components and modulates the
RT phosphorylated state of the 22k transcriptional anti-terminator.";
RL Submitted (APR-2000) to the EMBL/GenBank/DDBJ databases.
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; AF254574; AAF71286.1; -; Genomic_RNA.
DR SMR; Q9IWW8; -.
DR PRIDE; Q9IWW8; -.
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; RNA-directed RNA polymerase;
KW S-adenosyl-L-methionine; Transferase; Viral RNA replication; Virion.
FT CHAIN 1..2165
FT /note="RNA-directed RNA polymerase L"
FT /id="PRO_0000365787"
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"
SQ SEQUENCE 2165 AA; 250591 MW; 14F8E66A75EBD9B2 CRC64;
MDPIINGNSA NVYLTDSYLK GVISFSECNA LGSYIFNGPY LKNDYTNLIS RQNPLIEHMN
LKKLNITQSL ISKYHKGEIK LEEPTYFQSL LMTYKSMTSL EQIATTNLLK KIIRRAIEIS
DVKVYAILNK LGLKEKDKIK SNNGQDEDNS VITTIIKDDI LSAVKDNQSH LKADKNHSTK
QKDTIKTTLL KKLMCSMQHP PSWLIHWFNL YTKLNNILTQ YRSNEVKNHG FILIDNQTLS
GFQFILNQYG CIVYHKELKR ITVTTYNQFL TWKDISLSRL NVCLITWISN CLNTLNKSLG
LRCGFNNVIL TQLFLYGDCI LKLFHNEGFY IIKEVEGFIM SLILNITEED QFRKRFYNSM
LNNITDAANK AQKNLLSRVC HTLLDKTVSD NIINGRWIIL LSKFLKLIKL AGDNNLNNLS
ELYFLFRIFG HPMVDERQAM DAVKVNCNET KFYLLSSLSM LRGAFIYRII KGFVNNYNRW
PTLRNAIVLP LRWLTYYKLN TYPSLLELTE RDLIVLSGLR FYREFRLPKK VDLEMIINDK
AISPPKNLIW TSFPRNYMPS HIQNYIEHEK LKFSESDKSR RVLEYYLRDN KFNECDLYNC
VVNQSYLNNP NHVVSLTGKE RELSVGRMFA MQPGMFRQVQ ILAEKMIAEN ILQFFPESLT
RYGDLELQKI LELKAGISNK SNRYNDNYNN YISKCSIITD LSKFNQAFRY ETSCICSDVL
DELHGVQSLF SWLHLTIPHV TIICTYRHAP PYIRDHNVDL NNVDEQSGLY RYHMGGIEGW
CQKLWTIEAI SLLDLISLKG KFSITALING DNQSIDISKP VRLMEGQTHA QADYLLALNS
LKLLYKEYAG IGHKLKGTET YISRDMQFMS KTIQHNGVYY PASIKKVLRV GPWINTILDD
FKVSLESIGS LTQELEYRGE SLLCSLIFRN VWLYNQIALQ LKNHALCNNK LYLDILKVLK
HLKTFFNLDN IDTALTLYMN LPMLFGGGDP NLLYRSFYRR TPDFLTEAIV HSVFILSYYT
NHDLKDKLQD LSDDRLNKFL TCIITFDKNP NAEFVTLMRD PQALGSERQA KITSEINRLA
VTEVLSTAPN KIFSKSAQHY TTTEIDLNDI MQNIEPTYPH GLRVVYESLP FYKAEKIVNL
ISGTKSITNI LEKTSAIDLT DIDRATEMMR KNITLLIRIL PLDCNRDKRE ILSMENLSIT
ELSKYVRERS WSLSNIVGVT SPSIMYTMDI KYTTSTIASG IIIEKYNVNS LTRGERGPTK
PWVGSSTQEK KTMPVYNRQV LTKKQRDQID LLAKLDWVYA SIDNKDEFME ELSIGTLGLT
YEKAKKLFPQ YLSVNYLHRL TVSSRPCEFP ASIPAYRTTN YHFDTSPINR ILTEKYGDED
IDIVFQNCIS FGLSLMSVVE QFTNVCPNRI ILIPKLNEIH LMKPPIFTGD VDIHKLKQVI
QKQHMFLPDK ISLTQYVELF LSNKTLKSGS HVNSNLILAH KISDYFHNTY ILSTNLAGHW
ILIIQLMKDS KGIFEKDWGE GYITDHMFIN LKVFFNAYKT YLLCFHKGYG KAKLECDMNT
SDLLCVLELI DSSYWKSMSK VFLEQKVIKY ILSQDASLHR VKGCHSFKLW FLKRLNVAEF
TVCPWVVNID YHPTHMKAIL TYIDLVRMRL INIDRIHIKN KHKFNDEFYT SNLFYINYNF
SDNTHLLTKH IRIANSELEN NYNKLYHPTP ETLENILANP IKSNDKKTLN DYCIGKNVDS
IMLPLLSNKK LVKSSAMIRT NYSKQDLYNL FPTVVIDRII DHSGNTAKYN QLYTTTSHQI
SLVHNSTSLY CMLPWHHINR FNFVFSSTGC KISIEYILKD LKIKDPNCIA FIGEGAGNLL
LRTVVELHPD IRYIYRSLKD CNDHSLPIEF LRLYNGHINI DYGENLTIPA TDATNNIHWS
YLHIKFAEPI SLFVCDAELP VTVNWSKIII EWSKHVRKCK YCSSVNKCTL IVKYHAQDDI
DFKLDNITIL KTYVCLGSKL KGSEVYLVLT IGPANIFPVF NVVQNAKLIL SRTKNFIMPK
KADKESIDAN IKSLIPFLCY PITKKGINTA LSKLKSVVSG DILSYSIAGR NEVFSNKLIN
HKHMNILKWF NHVLNFRSTE LNYNHLYMVE STYPYLSELL NSLTTNELKK LIKITGSLLY
NFHNE
