ID   L_EBOSU                 Reviewed;        2210 AA.
AC   Q5XX01;
DT   11-JUL-2006, integrated into UniProtKB/Swiss-Prot.
DT   23-NOV-2004, sequence version 1.
DT   24-JAN-2024, entry version 93.
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   Sudan ebolavirus (strain Human/Uganda/Gulu/2000) (SEBOV) (Sudan Ebola
OS   virus).
OC   Viruses; Riboviria; Orthornavirae; Negarnaviricota; Haploviricotina;
OC   Monjiviricetes; Mononegavirales; Filoviridae; Orthoebolavirus;
OC   Orthoebolavirus sudanense; Sudan ebolavirus.
OX   NCBI_TaxID=386033;
OH   NCBI_TaxID=77231; Epomops franqueti (Franquet's epauletted fruit bat) (Epomophorus franqueti).
OH   NCBI_TaxID=9606; Homo sapiens (Human).
OH   NCBI_TaxID=77243; Myonycteris torquata (Little collared fruit bat).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX   PubMed=16139097; DOI=10.1016/j.virusres.2005.03.028;
RA   Sanchez A., Rollin P.E.;
RT   "Complete genome sequence of an Ebola virus (Sudan species) responsible for
RT   a 2000 outbreak of human disease in Uganda.";
RL   Virus Res. 113:16-25(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; AY729654; AAU43890.1; -; Genomic_RNA.
DR   RefSeq; YP_138527.1; NC_006432.1.
DR   PDB; 6YU8; X-ray; 1.84 A; A=1741-2046.
DR   PDBsum; 6YU8; -.
DR   SMR; Q5XX01; -.
DR   IntAct; Q5XX01; 1.
DR   ABCD; Q5XX01; 1 sequenced antibody.
DR   GeneID; 3160771; -.
DR   KEGG; vg:3160771; -.
DR   Proteomes; UP000000277; Segment.
DR   GO; GO:0030430; C:host cell cytoplasm; IEA:UniProtKB-SubCell.
DR   GO; GO:0044423; C:virion component; IEA:UniProtKB-KW.
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 5'-cap (guanine-N7-)-methyltransferase activity; IEA:InterPro.
DR   GO; GO:0003968; F:RNA-dependent 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; IPR039530; L_methyltransferase_rhabdo.
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   NCBIfam; TIGR04198; paramyx_RNAcap; 1.
DR   Pfam; PF14314; Methyltrans_Mon_2nd; 1.
DR   Pfam; PF14318; Mononeg_mRNAcap; 1.
DR   Pfam; PF00946; Mononeg_RNA_pol; 1.
DR   PIRSF; PIRSF037548; RNA_pol_Filoviridae; 1.
DR   PROSITE; PS50526; RDRP_SSRNA_NEG_NONSEG; 1.
DR   PROSITE; PS51590; SAM_MT_MNV_L; 1.
PE   1: Evidence at protein level;
KW   3D-structure; ATP-binding; Host cytoplasm; Hydrolase; Methyltransferase;
KW   mRNA capping; 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..2210
FT                   /note="RNA-directed RNA polymerase L"
FT                   /id="PRO_0000245049"
FT   DOMAIN          626..810
FT                   /note="RdRp catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00539"
FT   DOMAIN          1802..2000
FT                   /note="Mononegavirus-type SAM-dependent 2'-O-MTase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00923"
FT   REGION          1694..1736
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   STRAND          1757..1762
FT                   /evidence="ECO:0007829|PDB:6YU8"
FT   HELIX           1777..1793
FT                   /evidence="ECO:0007829|PDB:6YU8"
FT   HELIX           1812..1817
FT                   /evidence="ECO:0007829|PDB:6YU8"
FT   TURN            1818..1820
FT                   /evidence="ECO:0007829|PDB:6YU8"
FT   STRAND          1825..1831
FT                   /evidence="ECO:0007829|PDB:6YU8"
FT   HELIX           1836..1843
FT                   /evidence="ECO:0007829|PDB:6YU8"
FT   STRAND          1848..1853
FT                   /evidence="ECO:0007829|PDB:6YU8"
FT   HELIX           1873..1878
FT                   /evidence="ECO:0007829|PDB:6YU8"
FT   HELIX           1879..1883
FT                   /evidence="ECO:0007829|PDB:6YU8"
FT   STRAND          1888..1892
FT                   /evidence="ECO:0007829|PDB:6YU8"
FT   HELIX           1906..1910
FT                   /evidence="ECO:0007829|PDB:6YU8"
FT   HELIX           1911..1913
FT                   /evidence="ECO:0007829|PDB:6YU8"
FT   STRAND          1919..1923
FT                   /evidence="ECO:0007829|PDB:6YU8"
FT   HELIX           1934..1946
FT                   /evidence="ECO:0007829|PDB:6YU8"
FT   TURN            1950..1952
FT                   /evidence="ECO:0007829|PDB:6YU8"
FT   STRAND          1955..1961
FT                   /evidence="ECO:0007829|PDB:6YU8"
FT   HELIX           1965..1974
FT                   /evidence="ECO:0007829|PDB:6YU8"
FT   HELIX           1976..1978
FT                   /evidence="ECO:0007829|PDB:6YU8"
FT   STRAND          1979..1986
FT                   /evidence="ECO:0007829|PDB:6YU8"
FT   STRAND          1996..2004
FT                   /evidence="ECO:0007829|PDB:6YU8"
FT   HELIX           2016..2036
FT                   /evidence="ECO:0007829|PDB:6YU8"
SQ   SEQUENCE   2210 AA;  251294 MW;  9FCCAF21F7AA0078 CRC64;
     MMATQHTQYP DARLSSPIVL DQCDLVTRAC GLYSEYSLNP KLKTCRLPKH IYRLKYDTIV
     LRFISDVPVA TIPIDYIAPM LINVLADSKN VPLEPPCLSF LDEIVNYTVQ DAAFLNYYMN
     QIKTQEGVIT DQLKQNIRRV IHKNRYLSAL FFWHDLAILT RRGRMNRGNV RSTWFVTNEV
     VDILGYGDYI FWKIPIALLP MNTANVPHAS TDWYQPNIFK EAIQGHTHII SVSTAEVLIM
     CKDLVTSRFN TLLIAELARL EDPVSADYPL VDNIQSLYNA GDYLLSILGS EGYKIIKYLE
     PLCLAKIQLC SQYTERKGRF LTQMHLAVIQ TLRELLLNRG LKKSQLSKIR EFHQLLLRLR
     STPQQLCELF SIQKHWGHPV LHSEKAIQKV KNHATVLKAL RPIIIFETYC VFKYSVAKHF
     FDSQGTWYSV ISDRCLTPGL NSYIRRNQFP PLPMIKDLLW EFYHLDHPPL FSTKIISDLS
     IFIKDRATAV EQTCWDAVFE PNVLGYSPPY RFNTKRVPEQ FLEQEDFSIE SVLQYAQELR
     YLLPQNRNFS FSLKEKELNV GRTFGKLPYL TRNVQTLCEA LLADGLAKAF PSNMMVVTER
     EQKESLLHQA SWHHTSDDFG EHATVRGSSF VTDLEKYNLA FRYEFTAPFI KYCNQCYGVR
     NVFDWMHFLI PQCYMHVSDY YNPPHNVTLE NREYPPEGPS AYRGHLGGIE GLQQKLWTSI
     SCAQISLVEI KTGFKLRSAV MGDNQCITVL SVFPLESSPN EQERCAEDNA ARVAASLAKV
     TSACGIFLKP DETFVHSGFI YFGKKQYLNG IQLPQSLKTA ARMAPLSDAI FDDLQGTLAS
     IGTAFERSIS ETRHILPCRV AAAFHTYFSV RILQHHHLGF HKGSDLGQLA INKPLDFGTI
     ALSLAVPQVL GGLSFLNPEK CLYRNLGDPV TSGLFQLKHY LSMVGMSDIF HALIAKSPGN
     CSAIDFVLNP GGLNVPGSQD LTSFLRQIVR RSITLSARNK LINTLFHASA DLEDELVCKW
     LLSSTPVMSR FAADIFSRTP SGKRLQILGY LEGTRTLLAS KMISNNAETP ILERLRKITL
     QRWNLWFSYL DHCDPALMEA IQPIKCTVDI AQILREYSWA HILDGRQLIG ATLPCIPEQF
     QTTWLKPYEQ CVECSSTNNS SPYVSVALKR NVVSAWPDAS RLGWTIGDGI PYIGSRTEDK
     IGQPAIKPRC PSAALREAIE LTSRLTWVTQ GSANSDQLIR PFLEARVNLS VQEILQMTPS
     HYSGNIVHRY NDQYSPHSFM ANRMSNTATR LMVSTNTLGE FSGGGQAARD SNIIFQNVIN
     FAVALYDIRF RNTCTSSIQY HRAHIHLTNC CTREVPAQYL TYTTTLNLDL SKYRNNELIY
     DSDPLRGGLN CNLSIDSPLM KGPRLNIIED DLIRLPHLSG WELAKTVLQS IISDSSNSST
     DPISSGETRS FTTHFLTYPK IGLLYSFGAL ISFYLGNTIL CTKKIGLTEF LYYLQNQIHN
     LSHRSLRIFK PTFRHSSVMS RLMDIDPNFS IYIGGTAGDR GLSDAARLFL RIAISTFLSF
     VEEWVIFRKA NIPLWVIYPL EGQRSDPPGE FLNRVKSLIV GTEDDKNKGS ILSRSGEKCS
     SNLVYNCKST ASNFFHASLA YWRGRHRPKK TIGATNATTA PHIILPLGNS DRPPGLDLNR
     NNDTFIPTRI KQIVQGDSRN DRTTTTRFPP KSRSTPTSAT EPPTKMYEGS TTHQGKLTDT
     HLDEDHNAKE FPSNPHRLVV PFFKLTKDGE YSIEPSPEES RSNIKGLLQH LRTMVDTTIY
     CRFTGIVSSM HYKLDEVLWE YNKFESAVTL AEGEGSGALL LIQKYGVKKL FLNTLATEHS
     IESEVISGYT TPRMLLPIMP KTHRGELEVI LNNSASQITD ITHRDWFSNQ KNRIPNDADI
     ITMDAETTEN LDRSRLYEAV YTIICNHINP KTLKVVILKV FLSDLDGMCW INNYLAPMFG
     SGYLIKPITS SAKSSEWYLC LSNLLSTLRT TQHQTQANCL HVVQCALQQQ VQRGSYWLSH
     LTKYTTSRLH NSYIAFGFPS LEKVLYHRYN LVDSRNGPLV SITRHLALLQ TEIRELVTDY
     NQLRQSRTQT YHFIKTSKGR ITKLVNDYLR FELVIRALKN NSTWHHELYL LPELIGVCHR
     FNHTRNCTCS ERFLVQTLYL HRMSDAEIKL MDRLTSLVNM FPEGFRSSSV
//