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   03-AUG-2022, entry version 110.
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.
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   PRIDE; P12577; -.
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: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; IPR024352; L_methyltrans_paramyxo.
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; PF12803; G-7-MTase; 1.
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   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