ID L_PI3H4 Reviewed; 2233 AA.
AC P12577;
DT 01-OCT-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1989, sequence version 1.
DT 24-JAN-2024, entry version 114.
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:P03523};
DE EC=3.6.1.- {ECO:0000250|UniProtKB:P03523};
DE Includes:
DE RecName: Full=GDP polyribonucleotidyltransferase {ECO:0000305};
DE EC=2.7.7.88 {ECO:0000250|UniProtKB:P03523};
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 parainfluenza 3 virus (strain Wash/47885/57) (HPIV-3) (Human
OS parainfluenza 3 virus (strain NIH 47885)).
OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Haploviricotina;
OC Monjiviricetes; Mononegavirales; Paramyxoviridae; Orthoparamyxovirinae;
OC Respirovirus; Respirovirus pneumoniae.
OX NCBI_TaxID=11217;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE.
RX PubMed=2841798; DOI=10.1016/0042-6822(88)90594-6;
RA Galinski M.S., Mink M.A., Pons M.W.;
RT "Molecular cloning and sequence analysis of the human parainfluenza 3 virus
RT gene encoding the L protein.";
RL Virology 165:499-510(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-26.
RX PubMed=2822598; DOI=10.1159/000149722;
RA Storey D.G., Cote M.-J., Dimock K., Kang C.Y.;
RT "Nucleotide sequence of the coding and flanking regions of the human
RT parainfluenza virus 3 hemagglutinin-neuraminidase gene: comparison with
RT other paramyxoviruses.";
RL Intervirology 27:69-80(1987).
CC -!- FUNCTION: RNA-directed RNA polymerase that catalyzes the transcription
CC of viral mRNAs, their capping and polyadenylation. The template is
CC composed of the viral RNA tightly encapsidated by the nucleoprotein
CC (N). The viral polymerase binds to the genomic RNA at the 3' leader
CC promoter, and transcribes subsequently all viral mRNAs with a
CC decreasing efficiency. The first gene is the most transcribed, and the
CC last the least transcribed. The viral phosphoprotein acts as a
CC processivity factor. Capping is concommitant with initiation of mRNA
CC transcription. Indeed, a GDP polyribonucleotidyl transferase (PRNTase)
CC adds the cap structure when the nascent RNA chain length has reached
CC few nucleotides. Ribose 2'-O methylation of viral mRNA cap precedes and
CC facilitates subsequent guanine-N-7 methylation, both activities being
CC carried by the viral polymerase. Polyadenylation of mRNAs occur by a
CC stuttering mechanism at a slipery stop site present at the end viral
CC genes. After finishing transcription of a mRNA, the polymerase can
CC resume transcription of the downstream gene.
CC {ECO:0000250|UniProtKB:P03523}.
CC -!- FUNCTION: RNA-directed RNA polymerase that catalyzes the replication of
CC viral genomic RNA. The template is composed of the viral RNA tightly
CC encapsidated by the nucleoprotein (N). The replicase mode is dependent
CC on intracellular N protein concentration. In this mode, the polymerase
CC replicates the whole viral genome without recognizing transcriptional
CC signals, and the replicated genome is not caped or polyadenylated.
CC {ECO:0000250|UniProtKB:P03523}.
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=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 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)-(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 -!- 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 -!- SUBUNIT: Interacts with the P protein. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Virion {ECO:0000305}. Host cytoplasm
CC {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the paramyxovirus L protein family.
CC {ECO:0000305}.
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DR EMBL; M21649; AAA46854.1; -; Genomic_RNA.
DR EMBL; M20402; AAA46857.1; -; mRNA.
DR PIR; B46451; B46451.
DR SMR; P12577; -.
DR GO; GO:0030430; C:host cell cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0044423; C:virion component; IEA:UniProtKB-KW.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0003924; F:GTPase activity; IEA:RHEA.
DR GO; GO:0004482; F:mRNA 5'-cap (guanine-N7-)-methyltransferase activity; IEA:InterPro.
DR GO; GO:0003968; F:RNA-dependent 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 NCBIfam; TIGR04198; paramyx_RNAcap; 1.
DR Pfam; PF14318; Mononeg_mRNAcap; 1.
DR Pfam; PF00946; Mononeg_RNA_pol; 1.
DR PIRSF; PIRSF000830; RNA_pol_ParamyxoV; 1.
DR PROSITE; PS50526; RDRP_SSRNA_NEG_NONSEG; 1.
DR PROSITE; PS51590; SAM_MT_MNV_L; 1.
PE 2: Evidence at transcript level;
KW ATP-binding; Host cytoplasm; Hydrolase; Methyltransferase; mRNA capping;
KW mRNA processing; Multifunctional enzyme; Nucleotide-binding;
KW Nucleotidyltransferase; RNA-directed RNA polymerase;
KW S-adenosyl-L-methionine; Transferase; Viral RNA replication; Virion.
FT CHAIN 1..2233
FT /note="RNA-directed RNA polymerase L"
FT /id="PRO_0000142733"
FT DOMAIN 656..840
FT /note="RdRp catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00539"
FT DOMAIN 1775..1982
FT /note="Mononegavirus-type SAM-dependent 2'-O-MTase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00923"
FT BINDING 1805..1814
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255"
FT CONFLICT 26
FT /note="K -> R (in Ref. 2; AAA46857)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 2233 AA; 255806 MW; DBBB8B5DE74B4638 CRC64;
MDTESNNGTV SDILYPECHL NSPIVKGKIA QLHTIMSLPQ PYDMDDDSIL VITRQKIKLN
KLDKRQRSIR RLKLILTEKV NDLGKYTFIR YPEMSKEMFK LHIPGINSKV TELLLKADRT
YSQMTDGLRD LWINVLSKLA SKNDGSNYDL NEEINNISKV HTTYKSDKWY NPFKTWFTIK
YDMRRLQKAR NEVTFNMGKD YNLLEDQKNF LLIHPELVLI LDKQNYNGYL ITPELVLPYC
DVVEGRWNIS ACAKLDPKLQ SMYQKGNNLW EVIDKLFPIM GEKTFDVISL LEPLALSLIQ
THDPVKQLRG AFLNHVLSEM ELIFESRESI KEFLSVDYID KILDIFNKST IDEIAEIFSF
FRTFGHPPLE ASIAAEKVRK YMYIGKQLKF DTINKCHAIF CTIIINGYRE RHGGQWPPVT
LPDHAHEFII NAYGSNSAIS YENAVDYYQS FIGIKFNKFI EPQLDEDLTI YMKDKALSPK
KSNWDTVSPA SNLLYRTNAS NESRRLVEKF IADSKFDPNQ ILDYVESGDW LDDPEFNISY
SLKEKEIKQE GRLFAKMTYK MRATQVLSET LLANNIGKFF QENGMVKGEI ELLKRLTTIS
ISGVPRYNEV YNNSKSHTDD LKTYNKISNL NLSSNQKSKK FEFKSTDIYN DGYETVSCFL
TTDLKKYCLN WRYESTALFG ETCNQIFGLN KLFNWLHPRL EGSTIYVGDP YCPPSDKEHI
SLEDHPDSGF YVHNPRGGIE GFCQKLWTLI SISAIHLAAV RIGVRVTAMV QGDNQAIAVT
TRVPNNYDYR VKKEIVYKDV VRFFDSLREV MDDLGHELKL NETIISSKMF IYSKRIYYDG
RILPQALKAL SRCVFWSETV IDETRSASSN LATSFAKAIE NGYSPVLGYA CSIFKNIQQL
YIALGMNINP TITQNIKDLY FRNPNWMQYA SLIPASVGGF NYMAMSRCFV RNIGDPSVAA
LADIKRFIKA NLLDRSVLYR IMNQEPGESS FLDWASDPYS CNLPQSQNIT TMIKNITARN
VLQDSPNPLL SGLFTNTMIE EDEELAEFLM DRKVILPRVA HDILDNSLTG IRNAIAGMLD
TTKSLIRVGI NRGGLTYSLL RKISNYDLVQ YETLSRTLRL IVSDKIRYED MCSVDLAIAL
RQKMWIHLSG GRMISGLETP DPLELLSGVI ITGSEHCKIC YSSDGTNPYT WMYLPGNIKI
GSAETGISSL RVPYFGSVTD ERSEAQLGYI KNLSKPAKAA IRIAMIYTWA FGNDEISWME
ASQIAQTRAN FTLDSLKILT PVATSTNLSH RLKDTATQMK FSSTSLIRVS RFITMSNDNM
SIKEANETKD TNLIYQQIML TGLSVFEYLF RLEETTGHNP IVMHLHIEDE CCIKESFNDE
HINPESTLEL IRYPESNEFI YDKDPLKDVD LSKLMVIKDH SYTIDMNYWD DTDIIHAISI
CTAITIADTM SQLDRDNLKE IIVIANDDDI NSLITEFLTL DILVFLKTFG GLLVNQFAYT
LYSLKTEGRD LIWDYIMRTL RDTSHSILKV LSNALSHPKV FKRFWDCGVL NPIYGPNTAS
QDQIKLALSI CEYSLDLFMR EWLNGVSLEI YICDSDMEVA NDRKQAFISR HLSFVCCLAE
IASFGPNLLN LTYLERLDLL KQYLELNIKD DPTLKYVQIS GLLIKSFPST VTYVRKTAIK
YLRIRGISPP EVIDDWDPIE DENMLDNIVK TINDNCNKDN KGNKINNFWG LALKNYQVLK
IRSITSDSDN NDRSDASTGG LTLPQGGNYL SHQLRLFGIN STSCLKALEL SQILMKEVNK
DQDRLFLGEG AGAMLACYDA TLGPAVNYYN SGLNITDVIG QRELKIFPSE VSLVGKKLGN
VTQILNRVKV LFNGNPNSTW IGNMECETLI WSELNDKSIG LVHCDMEGAI GKSEETVLHE
HYSVIRITYL IGDDDVVLIS KIIPTITPNW SRILYLYKLY WKDVSIISLK TSNPASTELY
LISKDAYCTI MEPSEVVLSK LKRLSLLEEN NLLKWIILSK KKNNEWLHHE IKEGERDYGV
MRPYHMALQI FGFQINLNHL AKEFLSTPDL TNINNIIQSF QRTIKDVLFE WINITHDGKR
HKLGGRYNIF PLKNKGKLRL LSRRLVLSWI SLSLSTRLLT GRFPDEKFEH RAQTGYVSLP
DTDLESLKLL SKNTIKNYRE CIGSISYWFL TKEVKILMKL IGGAKLLGIP RQYKEPEEQL
LEDYNQHDEF DID
//
