ID   L_PI2HT                 Reviewed;        2262 AA.
AC   P26676;
DT   01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
DT   01-AUG-1992, sequence version 1.
DT   03-AUG-2022, entry version 128.
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 2 virus (strain Toshiba) (HPIV-2).
OC   Viruses; Riboviria; Orthornavirae; Negarnaviricota; Haploviricotina;
OC   Monjiviricetes; Mononegavirales; Paramyxoviridae; Rubulavirinae;
OC   Orthorubulavirus; Human parainfluenza 2 virus.
OX   NCBI_TaxID=11214;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX   PubMed=1645865; DOI=10.1093/nar/19.10.2739;
RA   Kawano M., Okamoto K., Bando H., Kondo K., Tsurudome M., Komada H.,
RA   Nishio M., Ito Y.;
RT   "Characterizations of the human parainfluenza type 2 virus gene encoding
RT   the L protein and the intergenic sequences.";
RL   Nucleic Acids Res. 19:2739-2746(1991).
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}.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; X57559; CAA40788.1; -; Genomic_RNA.
DR   PIR; S16664; S16664.
DR   SMR; P26676; -.
DR   DrugBank; DB00811; Ribavirin.
DR   DrugBank; DB06408; Taribavirin.
DR   PRIDE; P26676; -.
DR   Proteomes; UP000000472; 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: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   InterPro; IPR002877; RNA_MeTrfase_FtsJ_dom.
DR   Pfam; PF01728; FtsJ; 1.
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; Reference proteome; RNA-directed RNA polymerase;
KW   S-adenosyl-L-methionine; Transferase; Viral RNA replication; Virion.
FT   CHAIN           1..2262
FT                   /note="RNA-directed RNA polymerase L"
FT                   /id="PRO_0000142734"
FT   DOMAIN          661..844
FT                   /note="RdRp catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00539"
FT   DOMAIN          1780..1993
FT                   /note="Mononegavirus-type SAM-dependent 2'-O-MTase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00923"
FT   BINDING         1810..1819
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255"
SQ   SEQUENCE   2262 AA;  256383 MW;  82468303F4453B48 CRC64;
     MAASSEILLP EVHLNSPIVK HKLIYYLLLG HFPHDLDISE ISPLHNNDWD QIAREESNLA
     ERLGVAKSEL IKRVPAFRAT RWRSHAAVLI WPSCIPFLVK FLPHSKLQPV EQWYKLINAS
     CNTISDSIDR CMENISIKLT GKNNLFSRSR GTAGAGKNSK ITLNDIQSIW ESNKWQPNVS
     LWLTIKYQMR QLIMHQSSRQ PTDLVHIVDT RSGLIVITPE LVICFDRLNS VLMYFTFEMT
     LMVSDMFEGR MNVTALCTIS HYLSPLGPRI DRLFSIVDEL AQLLGDTVYK VIASLESLVY
     GCLQLKDPVV ELAGSFHSFI TQEIIDILIG SKALDKDESI TVTTQLLDIF SNLSPDLIAE
     MLCLMRLWGH PTLTAAQVGK VRESMCAGKL LDFPTIMKTL AFFHTILING YRRKKNGMWP
     PLILPKNASK SLIEFQHDNA EISYEYTLKH WKEISLIEFR KCFDFDPGEE LSIFMKDKAI
     SAPRSDWMSV FRRSLIKQRH QRHHIPMPNP FNRRLLLNFL EDDSFDPVAE LRYVTGGEYL
     QDDTFCASYS LKEKEIKPDG RIFAKLTNRM RSCQVIAEAI LANHAGTLMK ENGVVLNQLS
     LTKSLLTMSQ IGIISEKAKR YTRDNISSQG FHTIKTDSKN KRKSKTASSY LTDPDDTFEL
     SACFITTDLA KYCLQWRYQT IIHFARTLNR MYGVPHLFEW IHLRLIRSTL YVGDPFNPPA
     ATDAFDLDKV LNGDIFIVSK GGIEGLCQKM WTMISISVII LSSAESKTRV MSMVQGDNQA
     IAVTTRVPRS LPSIQKKELA YAASKLFFER LRANNYGLGH QLKAQETIIS STFFIYSKRV
     FYQGRILTQA LKNASKLCLT ADVLGECTQA SCSNSATTIM RLTENGVEKD TCYKLNIYQS
     IRQLTYDLIF PQYSIPGETI SEIFLQHPRL ISRIVLLPSQ LGGLNYLACS RLFNRNIGDP
     LGTAVADLKR LIKCGALESW ILYNLLARKP GKGSWATLAA DPYSLNQEYL YPPTTILKRH
     TQNTLMEICR NPMLKGVFTD NAKEEENLLA KFLLDRDIVL PRVAHIIIDQ SSIGRKKQIQ
     GFFDTTRTIM RRSFEIKPLS TKKTLSVIEY NTNYLSYNYP VILNPLPIPG YLNYITDQTC
     SIDISRSLRK LSWSSLLNGR TLEGLETPDP IEVVNGFLIV GTGDCDFCMQ GDDKFTWFFL
     PMGIIIDGNP ETNPPIRVPY IGSRTEERRV ASMAYIKGAT HSLKAALRGA GVYIWAFGDT
     VVNWNDALDI ANTRVKISLE QLQTLTPLPT SANITHRLDD GATTLKFTPA SSYAFSSYTH
     ISNDQQYLEI DQRVVDSNII YQQLMITGLG IIETYHNPPI RTSTQEITLH LHTSSSCCVR
     SVDGCLICES NGEVPQITVP YTNTFVYDPD PLADYEIAHL DYLSYQAKIG STDYYSLTDK
     IDLLAHLTAK QMINSIIGLD ETVSIVNDAV ILSDYTNNWI SECSYTKIDL VFKLMAWNFL
     LELAFQMYYL RISSWTNIFD YTYMTLRRIP GTALNNIAAT ISHPKLLRRA MNLDIITPIH
     APYLASLDYV KLSIDAIQWG VKQVLADLSN GIDLEILILS EDSMEISDRA MNLIARKLTL
     LALVKGENYT FPKIKGMPPE EKCLVLTEYL AMCYQNTHHL DPDLQKYLYN LTNPKLTAFP
     SNNFYLTRKI LNQIRESDEG QYIITSYYES FEQLETDIIL HSTLTAPYDN SENSNKVRFI
     PFDIFPHPES LEKYPLPVDH DSQSAISTLI PGPPSHHVLR PLGVSSTAWY KGISYCRYLE
     TQKIQTGDHL YLAEGSGASM SLLELLFPGD TVYYNSLFSS GENPPQRNYA PLPTQFVQSV
     PYKLWQADLA DDSNLIKDFV PLWNGNGAVT DLSTKDAVAF IIHKVGAEKA SLVHIDLEST
     ANINQQTLSR SQIHSLIIAT TVLKRGGILI YKTSWLPFSR FSQLAGLLWC FFDRIHLIRS
     SYSDPHSHEV YLVCRLAADF RTIGFSAALV TATTLHNDGF TTIHPDVVCS YWQHHLENVG
     RVGKVIDEIL DGLATNFFAG DNGLILRCGG TPSSRKWLEI DQLASFDLVQ DALVTLITIH
     LKEIIEVQSS HTEDYTSLLF TPYNIGAAGK VRTIIKLILE RSLMYTVRNW LVLPSSIRDS
     VRQDLELGSF RLMSILSEQT FLKKTPTKKY LLDQLTRTYI STFFNSHSVL PLHRPYQKQI
     WKALGSVIYC SETVDIPLIK DIQIEDINDF EDIERGIDGE EL