ID   L_EBORR                 Reviewed;        2212 AA.
AC   Q8JPX5; Q5UAK4;
DT   11-JUL-2006, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-2002, sequence version 1.
DT   03-AUG-2022, entry version 96.
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   Reston ebolavirus (strain Reston-89) (REBOV) (Reston Ebola virus).
OC   Viruses; Riboviria; Orthornavirae; Negarnaviricota; Haploviricotina;
OC   Monjiviricetes; Mononegavirales; Filoviridae; Ebolavirus.
OX   NCBI_TaxID=386032;
OH   NCBI_TaxID=77231; Epomops franqueti (Franquet's epauleted fruit bat).
OH   NCBI_TaxID=9606; Homo sapiens (Human).
OH   NCBI_TaxID=77243; Myonycteris torquata (Little collared fruit bat).
OH   NCBI_TaxID=9823; Sus scrofa (Pig).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX   PubMed=12191779; DOI=10.1016/s0168-1702(02)00087-4;
RA   Groseth A., Stroeher U., Theriault S., Feldmann H.;
RT   "Molecular characterization of an isolate from the 1989/90 epizootic of
RT   Ebola virus Reston among macaques imported into the United States.";
RL   Virus Res. 87:155-163(2002).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RC   STRAIN=Isolate Pennsylvania-89;
RX   PubMed=15661171; DOI=10.1016/j.virol.2004.11.018;
RA   Boehmann Y., Enterlein S., Randolf A., Muehlberger E.I.;
RT   "A reconstituted replication and transcription system for Ebola virus
RT   Reston and comparison with Ebola virus Zaire.";
RL   Virology 332:406-417(2005).
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   -!- SUBCELLULAR LOCATION: Host cytoplasm. Virion {ECO:0000250}.
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DR   EMBL; AF522874; AAN04454.1; -; Genomic_RNA.
DR   EMBL; AY769362; AAV48581.1; -; Genomic_RNA.
DR   RefSeq; NP_690587.1; NC_004161.1.
DR   SMR; Q8JPX5; -.
DR   PRIDE; Q8JPX5; -.
DR   GeneID; 955191; -.
DR   KEGG; vg:955191; -.
DR   Proteomes; UP000007207; Genome.
DR   Proteomes; UP000138664; 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   GO; GO:0039689; P:negative stranded viral RNA replication; ISS:UniProtKB.
DR   GO; GO:0039697; P:negative stranded viral RNA transcription; ISS:UniProtKB.
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; IPR017235; RNA-dir_pol_L_filovirus.
DR   Pfam; PF14318; Mononeg_mRNAcap; 1.
DR   Pfam; PF00946; Mononeg_RNA_pol; 1.
DR   PIRSF; PIRSF037548; RNA_pol_Filoviridae; 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..2212
FT                   /note="RNA-directed RNA polymerase L"
FT                   /id="PRO_0000245048"
FT   DOMAIN          625..809
FT                   /note="RdRp catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00539"
FT   DOMAIN          1803..2001
FT                   /note="Mononegavirus-type SAM-dependent 2'-O-MTase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00923"
FT   REGION          1651..1697
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        1667..1683
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   VARIANT         192
FT                   /note="K -> R (in strain: Isolate Pennsylvania-89)"
FT   VARIANT         324
FT                   /note="H -> R (in strain: Isolate Pennsylvania-89)"
FT   VARIANT         442
FT                   /note="F -> V (in strain: Isolate Pennsylvania-89)"
FT   VARIANT         600
FT                   /note="E -> G (in strain: Isolate Pennsylvania-89)"
FT   VARIANT         755
FT                   /note="K -> E (in strain: Isolate Pennsylvania-89)"
FT   VARIANT         1374
FT                   /note="D -> G (in strain: Isolate Pennsylvania-89)"
FT   VARIANT         1487
FT                   /note="E -> D (in strain: Isolate Pennsylvania-89)"
FT   VARIANT         1679
FT                   /note="E -> A (in strain: Isolate Pennsylvania-89)"
FT   VARIANT         1896..1898
FT                   /note="ASQ -> SSH (in strain: Isolate Pennsylvania-89)"
FT   VARIANT         1909
FT                   /note="S -> SS (in strain: Isolate Pennsylvania-89)"
SQ   SEQUENCE   2212 AA;  252549 MW;  C28CE580881136E3 CRC64;
     MATQHTQYPD ARLSSPIVLD QCDLVTRACG LYSSYSLNPQ LRQCKLPKHI YRLKFDTIVS
     KFLSDTPVAT LPIDYLVPIL LRSLTGHGDR PLTPTCNQFL DEIINYTLHD AAFLDYYLKA
     TGAQDHLTNI ATREKLKNEI LNNDYVHQLF FWHDLSILAR RGRLNRGNNR STWFVHDEFI
     DILGYGDYIF WKIPLSLLPV TIDGVPHAAT DWYQPTLFKE SILGHSQILS VSTAEILIMC
     KDIITCRFNT SLIASIAKLE DVDVSDYPDP SDILKIYNAG DYVISILGSE GYKIIKYLEP
     LCLAKIQLCS KFTERKGRFL TQMHLSVIND LRELISNRRL KDYQQEKIRD FHKILLQLQL
     SPQQFCELFS VQKHWGHPIL HSEKAIQKVK RHATILKALR PNVIFETYCV FKYNIAKHYF
     DSQGTWYSVI SDRNLTPGLN SFIKRNHFPS LPMIKDLLWE FYHLNHPPLF STKVISDLSI
     FIKDRATAVE QTCWDAVFEP NVLGYNPPNK FSTKRVPEQF LEQEDFSIES VLNYAQELHY
     LLPQNRNFSF SLKEKELNIG RTFGKLPYLT RNVQTLCEAL LADGLAKAFP SNMMVVTERE
     QKESLLHQAS WHHTSDDFGE NATVRGSSFV TDLEKYNLAF RYEFTAPFIE YCNHCYGVRN
     VFNWMHYLIP QCYMHVSDYY NPPHNVNLSN REYPPEGPSS YRGHLGGIEG LQQKLWTSIS
     CAQISLVEIK TGFKLRSAVM GDNQCITVLS VFPLKTDPEE QEQSAEDNAA RVAASLAKVT
     SACGIFLKPD ETFVHSGFIY FGKKQYLNGV QLPQSLKTAA RMAPLSDAIF DDLQGTLASI
     GTAFERAISE TRHILPCRIV AAFHTYFAVR ILQYHHLGFN KGIDLGQLSL SKPLDYGTIT
     LTLAVPQVLG GLSFLNPEKC FYRNFGDPVT SGLFQLRVYL EMVNMKDLFC PLISKNPGNC
     SAIDFVLNPS GLNVPGSQDL TSFLRQIVRR SITLTARNKL INTLFHASAD LEDEMVCKWL
     LSSNPVMSRF AADIFSRTPS GKRLQILGYL EGTRTLLASK IINNNSETPV LDKLRKITLQ
     RWNLWFSYLD HCDQLLADAL QKISCTVDLA QILREYTWSH ILEGRSLIGA TLPCMVEQFK
     VKWLGQYEPC PECLNKKGSN AYVSVAVKDQ VVSAWPNTSR ISWTIGSGVP YIGSRTEDKI
     GQPAIKPRCP SSALKEAIEL ASRLTWVTQG GSNSEQLIRP FLEARVNLSV SEVLQMTPSH
     YSGNIVHRYN DQYSPHSFMA NRMSNTATRL IVSTNTLGEF SGGGQAARDS NIIFQNVINL
     AVALYDIRFR NTNTSDIRHN RAHLHLTECC TKEVPAQYLT YTSALNLDLS RYRDNELIYD
     SNPLKGGLNC NLTIDSPLVK GPRLNMIEDD LLRFPHLSGW ELAKTVVQSI ISDNSNSSTD
     PISSGETRSF TTHFLTYPQI GLLYSFGAVL CFYLGNTILW TKKLDYEQFL YYLHNQLHNL
     PHRALRVFKP TFKHASVMSR LMEIDSNFSI YIGGTSGDRG LSDAARLFLR TAIASFLQFL
     KSWIIDRQKT IPLWIVYPLE GQQPESINEF LHKILGLLKQ GPKSIPKEVS IQNDGHLDLA
     ENNYVYNSKS TASNFFHASL AYWRSRKSRK TQDHNDFSRG DGTLTEPVRK FSSNHQSDEK
     YYNVTCGKSP KPQERKDFSQ YRLSNNGQTM SNHRKKGKFH KWNPCKMLME SQRGTVLTEG
     DYFQNNTPPT DDVSSPHRLI LPFFKLGNHN HAHDQDAQEL MNQNIKQYLH QLRSMLDTTI
     YCRFTGIVSS MHYKLDEVLL EYNSFDSAIT LAEGEGSGAL LLLQKYSTRL LFLNTLATEH
     SIESEVVSGF STPRMLLPIM QKVHEGQVTV ILNNSASQIT DITSSMWLSN QKYNLPCQVE
     IIMMDAETTE NLNRSQLYRA VYNLILDHID PQYLKVVVLK VFLSDIEGIL WINDYLAPLF
     GAGYLIKPIT SSARSSEWYL CLSNLISTNR RSAHQTHKAC LGVIRDALQA QVQRGVYWLS
     HIAQYATKNL HCEYIGLGFP SLEKVLYHRY NLVDTGLGPL SSVIRHLTNL QAEIRDLVLD
     YNLMRESRTQ TYHFIKTAKG RITKLVNDFL KFSLIVQALK NNSSWYTELK KLPEVINVCN
     RFYHTHNCEC QEKFFVQTLY LQRLRDAEIK LIERLTGLMR FYPEGLIYSN HT