ID   L_MABVM                 Reviewed;        2331 AA.
AC   P31352; Q38L39; Q6T6T7; Q6T6U4;
DT   01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
DT   01-FEB-1996, sequence version 2.
DT   23-FEB-2022, 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   Lake Victoria marburgvirus (strain Musoke-80) (MARV) (Marburg virus (strain
OS   Kenya/Musoke/1980)).
OC   Viruses; Riboviria; Orthornavirae; Negarnaviricota; Haploviricotina;
OC   Monjiviricetes; Mononegavirales; Filoviridae; Marburgvirus.
OX   NCBI_TaxID=33727;
OH   NCBI_TaxID=9534; Chlorocebus aethiops (Green monkey) (Cercopithecus aethiops).
OH   NCBI_TaxID=9606; Homo sapiens (Human).
OH   NCBI_TaxID=9407; Rousettus aegyptiacus (Egyptian rousette) (Egyptian fruit bat).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX   PubMed=1546452; DOI=10.1016/0042-6822(92)90456-y;
RA   Muehlberger E., Sanchez A., Randolf A., Will C., Kiley M.P., Klenk H.-D.,
RA   Feldmann H.;
RT   "The nucleotide sequence of the L gene of Marburg virus, a filovirus:
RT   homologies with paramyxoviruses and rhabdoviruses.";
RL   Virology 187:534-547(1992).
RN   [2]
RP   SEQUENCE REVISION.
RA   Feldmann H.;
RL   Submitted (SEP-1994) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RC   STRAIN=pp3/guinea pig lethal, and pp4/guinea pig nonlethal;
RA   Chain P.S.G., Malfatti S.A., Hajjaj A., Vergez L.M., Do L.H., Smith K.L.,
RA   McCready P.M.;
RL   Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RC   STRAIN=pp3/guinea pig lethal, and pp4/guinea pig nonlethal;
RA   Ichou M.A., Paragas J., Jahrling P.B., Ibrahim M.S., Lofts L., Hevey M.,
RA   Schmaljohn A.;
RL   Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RC   STRAIN=Isolate Enterlein;
RX   PubMed=16379005; DOI=10.1128/jvi.80.2.1038-1043.2006;
RA   Enterlein S., Volchkov V., Weik M., Kolesnikova L., Volchkova V.,
RA   Klenk H.-D., Muehlberger E.;
RT   "Rescue of recombinant Marburg virus from cDNA is dependent on nucleocapsid
RT   protein VP30.";
RL   J. Virol. 80:1038-1043(2006).
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; M92834; AAA46562.1; ALT_SEQ; Genomic_RNA.
DR   EMBL; Z12132; CAA78120.1; -; Genomic_DNA.
DR   EMBL; AY430365; AAR85466.1; -; Genomic_RNA.
DR   EMBL; AY430366; AAR85459.1; -; Genomic_RNA.
DR   EMBL; DQ217792; ABA87130.1; -; Genomic_RNA.
DR   PIR; A42450; RRIWMV.
DR   RefSeq; YP_001531159.1; NC_001608.3.
DR   SMR; P31352; -.
DR   ChEMBL; CHEMBL4523583; -.
DR   GeneID; 920946; -.
DR   KEGG; vg:920946; -.
DR   Proteomes; UP000007771; Genome.
DR   Proteomes; UP000137266; Genome.
DR   Proteomes; UP000160614; Genome.
DR   Proteomes; UP000180448; Genome.
DR   GO; GO:0030430; C:host cell cytoplasm; IEA:UniProtKB-SubCell.
DR   GO; GO:0019013; C:viral nucleocapsid; IDA:CACAO.
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; IDA:UniProtKB.
DR   GO; GO:0039697; P:negative stranded viral RNA transcription; IDA: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; Reference proteome; RNA-directed RNA polymerase;
KW   S-adenosyl-L-methionine; Transferase; Viral RNA replication; Virion.
FT   CHAIN           1..2331
FT                   /note="RNA-directed RNA polymerase L"
FT                   /id="PRO_0000222169"
FT   DOMAIN          628..812
FT                   /note="RdRp catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00539"
FT   DOMAIN          1921..2118
FT                   /note="Mononegavirus-type SAM-dependent 2'-O-MTase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00923"
FT   VARIANT         489
FT                   /note="L -> A (in strain: pp3/guinea pig lethal, pp4/guinea
FT                   pig nonlethal and Isolate Enterlein)"
FT   VARIANT         741
FT                   /note="S -> C (in strain: pp3/guinea pig lethal)"
FT   VARIANT         979
FT                   /note="R -> G (in strain: pp3/guinea pig lethal, pp4/guinea
FT                   pig nonlethal and Isolate Enterlein)"
FT   VARIANT         1428
FT                   /note="S -> T (in strain: Isolate Enterlein)"
SQ   SEQUENCE   2331 AA;  267093 MW;  1D54C60DA1BED3CF CRC64;
     MQHPTQYPDA RLSSPIILDQ CDLLARSLGL YSHYSHNPKL RNCRIPHHIY RLRNSTALKT
     FLQNCSILTV PFHSIWDHIL TSIQYDAINH VDDFKYLLPS ELVKYANWDN EFLKAYLNKI
     LGLDHVFSAS ARSQCEDFSP KENPYYWGML LLVHLSQLAR RIKGQRGSLR SNWKFIGTDL
     ELFGIADFVI FKVPVKTIIR NAVSLQASKP GLRIWYRDQN LTPYLCDDEF IVSVASYECF
     IMIKDVFIER YNTWEICARA WLEDSDGADY PPLDVLGELY NQGDQIIAMY LEDGFKLIKH
     LEPLCVSCIQ THGIFTPRKY WFQSQMIKSY YDELHDLNLK LQISDNKAEC AQNFIKTIVQ
     AKLTPQQYCE LFSLQKHWGH PVLYNDVALD KVKKHAQSTK ILKPKVMFET FCVFKFIVAK
     NHYHSQGSWY KTTHDLHLTP YLRQHIVSNS FPSQAEIYQH LWEWYFVEHE PLFSTKIISD
     LSIFIKDRLT AVNQECWDSV FDRSVLGYNP PVRFQSKRVP EQFLGQADFS LNQILEFAEK
     LEYLAPSYRN FSFSLKEKEL NIGRTFGKLP YRVRNVQTLA EALLADGLAK AFPSNMMVVT
     EREQKEALLH QASWHHNSAS IGENAIVRGA SFVTDLEKYN LAFRYEFTRH FIDYCNRCYG
     VKNLFDWMHF LIPLCYMHVS DFYSPPHCVT EDNRNNPPDC ANAYHYHLGG IEGLQQKLWT
     CISCAQITLV ELKTKLKLKS SVMGDNQCIT TLSLFPIDAP NDYQENEAEL NAARVAVELA
     ITTGYSGIFL KPEETFVHSG FIYFGKKQYL NGVQLPQSLK TMARCGPLSD SIFDDLQGSL
     ASIGTSFERG TSETRHIFPS RWIASFHSML AINLLNQNHL GFPLGFNIDI SCFKKPLTFS
     EKLIALITPQ VLGGLSFLNP EKLFYRNISD PLTSGLFQLK NALEFLEKEE LFYILISKKP
     GLADASDFVM NPLGLNVPRS KEIITFLRQT VRENITITSQ NRIINSLFHI GSDLEDQRVC
     EWLLSSNPVM SRFAADIFSR TPSGKRLQVL GYLEGTRTLL ASRTISLTTE GTMLMKLREL
     TRNRWKSWFS YIDALDDDLS ESLEKFTCTV DVANFLRAYS WSDVLKGKRL IGATLPCLLE
     QFEVKWINLS EDLREQFNLS SDSKSTINLL PYDCKELRLE GSNDTELNYV SCALDRKVVQ
     KHPSVNRLAW TIGNRAPYIG SRTEDKIGYP PLRVNCPSAA LKEAIEMVSR LLWVTQGTAD
     REKLLIPLLN SRVNLDYQTV LNFLPTHYSG NIVHRYNDQY GQHSFMANRM SNTSTRAIIS
     TNTLGKYAGG GQAAIDSNII FQNTINLGVA VLDIALSLAK LSSASNVTFR LMLNKCCTRH
     VPSEYLYFDK PLDVDLNKYM DNELVYDNDP LCSGIKGRLG RVSRSTLSLS LNVSDIGSYD
     FPTIAAWTLG ETIVGSIFSD ESSQSTDPIS SGCTKTFVTH FLVYPVESIF YAFGANLIVE
     SLSLSRIKSI KNLSDLTFLI SSTIRNLSHR SLRILQSTFR HELVLTRLAH HIPLISLMLG
     GSAGEKSSSD AVRLFLTASY QNFINNFSCL MKKGQSSLPV WLYFPSEGQQ LKPILKILQR
     LSDLLSPDKI QKRKILADTC CPIGSFWVYP SKSTRTNHYY ASLNYWRDKA NKVKNTPFSH
     LINCSFPEFS SHTSSVSSNQ QVTNSKYIVY PENITEINAR TRLINYGSTA LQGMDTKMPL
     SEQNLVENCR PSEGIRFKDN QKITKHDQRC EREESSPQQM FPEDNMQTPA HIHSSSPFQI
     LIKSLDAHED FDASKIILNS EINNLNLTEY TLNTKLLTTP TRTEILDTSP LQSSRYSSTS
     RERSLLSREQ ASYLYVDCSN IPSISLDPGF RSMSDQNQVQ MLINTYKRDL HACFDSNQFC
     RFTGVVSSMH YKLYDLLPPG KLKKAICLAE GEGSGARLLL KWKETDYLFF NTLATDSQQE
     AEILSGRVIP RMLYNIDRLS ALLESRRLIL NNLTIQITDI TNPLWLDSVI QYLPEDSDIL
     TMDAETTKDE TREQLYKTIV NIWTRTSPNI PKISIIKVFL LDYEGTLFLM KNAIQYYGQV
     QLKKPYSSNA KNSEWYLCCG KRRIQRLQID FSDQVGIFLI CKAMSRQRQA IPYWLKHIEK
     NYPASLHEFF LTLGFPSLES SFCHRYTIPF SEGKALFHKV QSYVRQGKQH LHSLMLDYEN
     NSPLLDLRNH FICSLRGKIT KYYNDILKLN LVIKAVEKGK NWSQLVEILP NMHSVCIVHV
     DHECSGCEKR LLLKLDFIRN TKIAEQKLLN RVIGYILFFP FGLFKSGSLR A