L_MPV15
ID L_MPV15 Reviewed; 2040 AA.
AC Q50EW2; Q5MKL9;
DT 03-MAR-2009, integrated into UniProtKB/Swiss-Prot.
DT 07-JUN-2005, sequence version 1.
DT 03-AUG-2022, entry version 77.
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 Murine pneumonia virus (strain 15) (MPV).
OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Haploviricotina;
OC Monjiviricetes; Mononegavirales; Pneumoviridae; Orthopneumovirus.
OX NCBI_TaxID=296738;
OH NCBI_TaxID=10090; Mus musculus (Mouse).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RC STRAIN=15;
RX PubMed=15744580; DOI=10.1007/s11262-004-5631-4;
RA Krempl C.D., Lamirande E.W., Collins P.L.;
RT "Complete sequence of the RNA genome of pneumonia virus of mice (PVM).";
RL Virus Genes 30:237-249(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RC STRAIN=15;
RX PubMed=15604443; DOI=10.1099/vir.0.80315-0;
RA Thorpe L.C., Easton A.J.;
RT "Genome sequence of the non-pathogenic strain 15 of pneumonia virus of mice
RT and comparison with the genome of the pathogenic strain J3666.";
RL J. Gen. Virol. 86:159-169(2005).
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; AY729016; AAW79184.1; -; Genomic_RNA.
DR EMBL; AY743910; AAW02843.1; -; Genomic_RNA.
DR SMR; Q50EW2; -.
DR Proteomes; UP000133604; Genome.
DR Proteomes; UP000147186; 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 Pfam; PF14318; Mononeg_mRNAcap; 1.
DR Pfam; PF00946; Mononeg_RNA_pol; 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..2040
FT /note="RNA-directed RNA polymerase L"
FT /id="PRO_0000365788"
FT DOMAIN 640..822
FT /note="RdRp catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00539"
FT DOMAIN 1694..1884
FT /note="Mononegavirus-type SAM-dependent 2'-O-MTase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00923"
FT REGION 913..1395
FT /note="GDP polyribonucleotidyltransferase"
FT /evidence="ECO:0000250|UniProtKB:P28887"
FT ACT_SITE 1273
FT /note="Nucleophile; for GDP polyribonucleotidyltransferase
FT activity"
FT /evidence="ECO:0000250|UniProtKB:P03523"
FT ACT_SITE 1705
FT /note="For mRNA (nucleoside-2'-O-)-methyltransferase
FT activity"
FT /evidence="ECO:0000250|UniProtKB:Q6WB93"
FT ACT_SITE 1811
FT /note="For mRNA (nucleoside-2'-O-)-methyltransferase
FT activity"
FT /evidence="ECO:0000250|UniProtKB:Q6WB93"
FT ACT_SITE 1849
FT /note="For mRNA (nucleoside-2'-O-)-methyltransferase
FT activity"
FT /evidence="ECO:0000250|UniProtKB:Q6WB93"
FT ACT_SITE 1880
FT /note="For mRNA (nucleoside-2'-O-)-methyltransferase
FT activity"
FT /evidence="ECO:0000250|UniProtKB:Q6WB93"
FT BINDING 647
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 757
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 1728..1732
FT /ligand="substrate"
FT /ligand_note="for mRNA (nucleoside-2'-O-)-methyltransferase
FT activity"
FT /evidence="ECO:0000250|UniProtKB:Q6WB93"
FT VARIANT 1931
FT /note="I -> L"
SQ SEQUENCE 2040 AA; 234515 MW; 26D5109CBDD22D07 CRC64;
MDPIDEQEVN VYLPDSYLKG VISFSETNAL GSCIIGRPFL KDDFTATTSI RNPLIEHKRI
RDTKLVKNIV SNPQYRLVEP LQMQHELLSV LSPNFILHTA NLRKIIQRSV DITDKKLNPI
LHILNLNSPN QEGKVSERLT RLIKKHLSHI PNWVSSWYNI WVNLNNLLQE YRSKEVIDHN
CVLTRQLSGS FIHVVMSQYG VVIISKKSKR YTMCTYNQFL TWKDLALSRF NANYVVWLSN
VLNTLNEGLG LRCRLKGHLL SKLYISTDIF LSSTSNEFYN VVKEFEGFIM SLILKQTEEA
LFSTRFYNNM LNNLIDAIDR ARLEYLARCA NSAARINLPS TDVMIASLGD ILSLINVLGE
SNLNNLSELY FIFRIFGHPM VDERKAMDAV RDNCCETKFL TAKNLASLRG AYVYRIIKGF
VANYNRWPYI KTRVCLTPTW INYLDTNSCP SLLEMTEDDF IVLAGVHFIR EFHIPKLTDL
EIILNDKAIS PPKSLIWSCF PKNYIPQVIQ DEYARRYCRA KAPLKTRRVL EFYLQDKDFK
LDQLHRVVVN QDYLNDKEHI ISLTGKEREL GVGRMFAMQP GKQRQVQILA EKLLADNILQ
FFPETLTRYG DLELQKILEL KAGLSNKNDR SKDSYNNYIS RCSLITDLSK FNQAFRYESS
CVCSDLLDEL HGTQSLFSWL HLTVPLTTIM CTYRHAPPDT GNNYNVDDIA EQSGLYRYHM
GGIEGWCQKL WTTEAIALLD TVAVKGRFQL TSLINGDNQS IDISKPTRLG TRTQSEADYD
LAINSLRLIS AAYKGIGHKL KEGETYLSRD MQFMSKTIQH EGVYYPASIK KILRVGPWIN
TILDDIKTST ESIGSLTQEL EYKGESLMSS LLLRNFWLYR LYSVDLKDHS LCGKQLYRSL
IKVLKHLKRC FNLENLGECL ELFLNVPMQF GGADPNVIYR SFYRRTPDFL TESITHLILI
LKHFRRDLEF NKDNVSKAVL SLLEFTKNDS AEFVTLMRDP QAIGSERQAK ITSDINRTAV
TSVLSNAPNE IFRTSALHYS STENELNGIA SGVSPVYPHG LRVLYESLPF YKAEKIVNMV
SGTKSITNIL EKTSAISYTD IIRATNMMVE NLTLLTRIMK PGADTSLDPD TIVITILSKI
IRDKSWDVGD IIGVTSPSPV SCFKVVYTST LQNNSVVIER YTTDTYTRGK RGPTKPWVGS
STQEKKSMPV YNRQVLTRGQ RDQIENIAKL EWVFSSVANI DSLLNELSTM TLGLSLRKCR
QLFPTYLSLN FLHRLSVSSR PREYPSSLPA YRTTNFHFDT GPINKVLTER FGDEDINLVF
QNAISYGLST MSLVEQFTGV CPNKVLLVPK LQEIQLMKVP IFQGGFNLQS IIPIIRQQHM
FLPNHITPAQ YIELFLSSKQ FHSRINLKHN NRFKLVLQKD YFNGENMIET LSTCLAGHWI
IILMLMKESQ GIFDKEWYDG FVTDHMFLDL QLFLSSFKTF LTVFNFAYLK VGSNIEEITG
NQANLLELLD LGYWKNMYKV FSETKVRLAL LKQDLSFNSV KNSSSFRHWF INSLQEVQCT
SVPWVVNVTR NPTHLKGVLQ YMKMIESGMI QGYSANISSV LSIPYNYPDM AHMMTKIIRN
RGHMSYDYPK MKKSLTFSMT DMSDSYMLNL FPKVECSYMS GYLDKLDDTL QLLKKPPVGR
KVPSVALPWH HCNRYNFVFS STGCKVSVID MLPKHFRRSN LKVICFIGEG AGNLMLRAVL
EVGGNIKLIY RSLKDPDDHH VPVEFLRLKP CYPYIDTGGS LSLASTDATN KAHWDYLHLH
WTDPLNLIVC DAEISGVKHW LKILHRWYEH MTSCKHCLKS EHDKYLIIKY HAQDDLIDLP
HGVRLLKCNI CLGSKLSGSE SYLLIGLGLS NKLPVYSEVL HSKLLLAECH QFHHPKYLDV
SGINTNIKSL IPMLDYPITY NKITTLLESV RELSSNKNKN TMWIGRNPVY HNKWLKRKYF
NILKWLKYCI ELPAFRMDYN SFERIEMLYP NLRDLVDSVS TSELKKVIKV TGILFRSNTM
