ID   L_NDVB                  Reviewed;        2204 AA.
AC   P11205;
DT   01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT   01-JUL-1989, sequence version 1.
DT   03-AUG-2022, entry version 113.
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   Newcastle disease virus (strain Beaudette C/45) (NDV).
OC   Viruses; Riboviria; Orthornavirae; Negarnaviricota; Haploviricotina;
OC   Monjiviricetes; Mononegavirales; Paramyxoviridae; Avulavirinae;
OC   Orthoavulavirus; Avian orthoavulavirus 1.
OX   NCBI_TaxID=11178;
OH   NCBI_TaxID=9031; Gallus gallus (Chicken).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX   PubMed=3035486; DOI=10.1093/nar/15.10.3961;
RA   Yusoff K., Millar N.S., Chambers P., Emmerson P.T.;
RT   "Nucleotide sequence analysis of the L gene of Newcastle disease virus:
RT   homologies with Sendai and vesicular stomatitis viruses.";
RL   Nucleic Acids Res. 15:3961-3976(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; X05399; CAA28985.1; -; Genomic_RNA.
DR   PIR; A26747; RRNZNV.
DR   SMR; P11205; -.
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   GO; GO:0039697; P:negative stranded viral RNA transcription; IDA:UniProtKB.
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   3: Inferred from homology;
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..2204
FT                   /note="RNA-directed RNA polymerase L"
FT                   /id="PRO_0000142731"
FT   DOMAIN          634..818
FT                   /note="RdRp catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00539"
FT   DOMAIN          1745..1958
FT                   /note="Mononegavirus-type SAM-dependent 2'-O-MTase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00923"
FT   BINDING         1775..1784
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255"
SQ   SEQUENCE   2204 AA;  248824 MW;  C67B8674D904802C CRC64;
     MASSGPERAE HQIILPESHL SSPLVKHKLL YYWKLTGLPL PDECDFDHLI LSRQWKKILE
     SASPDTERMI KLGRAVHQTL NHNSRITGVL HPRCLEELAS IEVPDSTNKF RKIEKKIQIH
     NTRYGELFTR LCTHIEKKLL GSSWSNNVPR SEEFNSIRTD PAFWFHSKWS TAKFAWLHIK
     QIQRHLIVAA RTRSAANKLV MLTHKVGQVF VTPELVIVTH TNENKFTCLT QELVLMYADM
     MEGRDMVNII STTAVHLRSL SEKIDDILQL IDALAKDLGN QVYDVVSLME GFAYGAVQLL
     EPSGRFAGHF FAFNLQELKD ILIGLLPNDI AESVTHAIAT VFSGLEQNQA AEMLCLLRLW
     GHPLLESRIA AKAVRSQMCA PKMVDFDMIL QVLSFFKGTI INGYRKKNAG VWPRVKVDTI
     YGKIIGQLHA DSAEISHDIM LREYKSLSAL EFEPCIEYDP VTNLSMFLKD KAIAHPNDNW
     LASFRRNLLS EDQKKHVKEA TSTNRLLIEF LESNDFDPYK EMEYLTTLEY LRDDDVAVSY
     SLKEKEVKVN GRIFAKLTKK LRNCQVMAEG ILADQIAPFF QGNGVIQDSI SLTKSTLAMS
     QLSFNSNKKR ITDCKERVSS NRNHDPKSKN RRRVATFITT DLQKYCLNWR YQTIKLFAHA
     INQLMGLPHF FEWIHLRLMD TTMFVGDPFN PPSDPTDCDL SRVPNDDIYI VSARGGIEGL
     CQKLWTMISI AAIQLAAARS HCRVACMVQG DNQVIAVTRE VRSDDSPEMV LTQLHQASDN
     FFKELIHVNH LIGHNLKDRE TIRSDTFFIY SKRIFKDGAI LSQVLKNSSK LVMVSGDLSE
     NTVMSCANIA STVARLCENG LPKDFCYYLN YIMSCVQTYF DSEFSYNNNS HPDLNQSWIE
     DISFVHSYVL TPAQLGGLSN LQYSRLYTRN IGDPGTTAFA EIKRLEAVGL LSPNIMTNIL
     TRPPGNGDWA SLCNDPYSFN FETVASPNIV LKKHTQRVLF ETCSNPLLSG VHTEDNEAEE
     KALAEFLLNQ EVIHPRVAHA IMEASSVGRR KQIQGLVDTT NTVIKIALTR RPLGIKRLMR
     IVNYSSMHAM LFRDDVFSSN RSNHPLVSSN MCSLTLADYA RNRSWSPLTG GRKILGVSNP
     DTIELVEGEI LSVSGGCTRC DSGDEQFTWF HLPSNIELTD DTSKNPPMRV PYLGSKTQER
     RAASLAKIAH MSPHVKAALR ASSVLIWAYG DNEVNWTAAL TIAKSRCNIN LEYLRLLSPL
     PTAGNLQHRL DDGITQMTFT PASLYRCHLT FTYPMILKGY SLKKESKRGM WFINRVMLLG
     LSLIESIFPM TTTRTYDEIT LHLHSKFSCC IREAPVAVPF ELLGVAPELR TVTSNKFMYD
     PSPVSEGDFA RLDLAIFKSY ELNLESYPTI ELMNILSISS GKLIGQSVVS YDEDTSIKND
     AIIVYDNTRN WISEAQNSDV VRLFEYAALE VLLDCSYQLY YLRVRGLDNI VLYMGDLYKN
     MPGILLSNIA ATISHPVIHS RLHAVGLVNH NGSHQLADTD FIEMSAKLLV SCTRRVISGL
     YSGNKYDLLF PSVLDDNLNE KMLQLISRLC CLYTVLFATT REIPKIRGLS AEEKCSVLTE
     YLLSDAVKPL LSPDQVSSIM SPNIITFPAN LYYMSRKSLN LIREREDKDS ILALLFPQEP
     LLEFPSVQDI GARVKDPFTR QPAAFLQELD LSAPARYDAF TLSQIHPELT SPNPEEDYLV
     RYLFRGIGTA SSSWYKASHL LSVPEVRCAR HGNSLYLAEG SGAIMSLLEL HVPHETIYYN
     TLFSNEMNPP QRHFGPTPTQ FLNSVVYRNL QAEVTCKDGF VQEFRPLWRE NTEESDLTSD
     KAVGYITSAV PYRSVSLLHC DIEIPPGSNQ SLLDQLAINL SLIAMHSVRE GGVVIIKVLY
     AMGYYFHLLM NLFAPCSTKG YILSNGYACR GDMECYLVFV MGYLGGPTFV HEVVRMAKTL
     VQRHGTLLSK SDEITLTRLF TSQRQRVTDI LSSPLPRLIK YLRKNIDTAL IEAGGQPVRP
     FCAESLVSTL ADITQITQII ASHIDTVIRS VIYMEAEGDL ADTVFLFTPY NLSTDGKKRT
     SLKQCTRQIL EVTILGLRVE DLNKIGDVIS LVLKGMISME DLIPLRTYLK HSTCPKYLKA
     VLGITKLKEM FTDTSVLYLT RAQQKFYMKT IGNAVKGYYS NCDS