L_EBOZM
ID L_EBOZM Reviewed; 2212 AA.
AC Q05318; O39794; Q773N0; Q8JS59; Q9DQD1;
DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT 30-MAY-2000, sequence version 2.
DT 03-AUG-2022, entry version 120.
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 Zaire ebolavirus (strain Mayinga-76) (ZEBOV) (Zaire Ebola virus).
OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Haploviricotina;
OC Monjiviricetes; Mononegavirales; Filoviridae; Ebolavirus.
OX NCBI_TaxID=128952;
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).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=10073695; DOI=10.1099/0022-1317-80-2-355;
RA Volchkov V.E., Volchkova V.A., Chepurnov A.A., Blinov V.M., Netesov S.V.,
RA Feldmann H.;
RT "Characterization of the L gene and 5' trailer region of Ebola virus.";
RL J. Gen. Virol. 80:355-362(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 1-54.
RX PubMed=8237108; DOI=10.1016/0168-1702(93)90063-s;
RA Sanchez A., Kiley M.P., Holloway B.P., Auperin D.D.;
RT "Sequence analysis of the Ebola virus genome: organization, genetic
RT elements, and comparison with the genome of Marburg virus.";
RL Virus Res. 29:215-240(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RA Wilson J.A., Kondig J.P., Kuehne A.I., Hart M.K.;
RL Submitted (AUG-2002) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH VP35, AND REGION.
RX PubMed=23582637; DOI=10.1016/j.virol.2013.03.013;
RA Trunschke M., Conrad D., Enterlein S., Olejnik J., Brauburger K.,
RA Muehlberger E.;
RT "The L-VP35 and L-L interaction domains reside in the amino terminus of the
RT Ebola virus L protein and are potential targets for antivirals.";
RL Virology 441:135-145(2013).
RN [5]
RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF 742-ASP--GLN-744.
RX PubMed=28991917; DOI=10.1371/journal.pntd.0005996;
RA Schmidt M.L., Hoenen T.;
RT "Characterization of the catalytic center of the Ebola virus L
RT polymerase.";
RL PLoS Negl. Trop. Dis. 11:E0005996-E0005996(2017).
RN [6]
RP FUNCTION, MUTAGENESIS OF ASP-742, AND COFACTOR.
RX PubMed=29507309; DOI=10.1038/s41598-018-22328-3;
RA Tchesnokov E.P., Raeisimakiani P., Ngure M., Marchant D., Goette M.;
RT "Recombinant RNA-Dependent RNA Polymerase Complex of Ebola Virus.";
RL Sci. Rep. 8:3970-3970(2018).
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, ECO:0000269|PubMed:23582637,
CC ECO:0000269|PubMed:28991917, ECO:0000269|PubMed:29507309}.
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, ECO:0000269|PubMed:23582637,
CC ECO:0000269|PubMed:28991917, ECO:0000269|PubMed:29507309}.
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 -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:29507309};
CC -!- SUBUNIT: Forms homooligomers. Interacts with VP35; this complex
CC constitutes a functional polymerase complex.
CC {ECO:0000269|PubMed:23582637}.
CC -!- SUBCELLULAR LOCATION: Virion. Host cytoplasm
CC {ECO:0000269|PubMed:23582637, ECO:0000269|PubMed:28991917}. Note=Found
CC in cytoplasmic inclusion bodies present in infected cells.
CC {ECO:0000269|PubMed:23582637, ECO:0000269|PubMed:28991917}.
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; X67110; CAA47483.1; -; Genomic_RNA.
DR EMBL; AF272001; AAG40171.1; -; Genomic_RNA.
DR EMBL; AF086833; AAD14589.1; -; Genomic_RNA.
DR EMBL; L11365; AAB81007.1; -; Genomic_RNA.
DR EMBL; AY142960; AAN37511.1; -; Genomic_RNA.
DR EMBL; AF499101; AAM76038.1; -; Genomic_RNA.
DR RefSeq; NP_066251.1; NC_002549.1.
DR SMR; Q05318; -.
DR IntAct; Q05318; 1.
DR ChEMBL; CHEMBL4303062; -.
DR DrugBank; DB11676; Galidesivir.
DR DrugBank; DB15686; GS-441524.
DR DrugBank; DB14761; Remdesivir.
DR PRIDE; Q05318; -.
DR GeneID; 911824; -.
DR KEGG; vg:911824; -.
DR Proteomes; UP000007209; Genome.
DR Proteomes; UP000109874; Genome.
DR Proteomes; UP000149419; Genome.
DR Proteomes; UP000150973; 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; IDA:UniProtKB.
DR GO; GO:0039697; P:negative stranded viral RNA transcription; IDA:UniProtKB.
DR Gene3D; 3.40.50.150; -; 1.
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 InterPro; IPR029063; SAM-dependent_MTases_sf.
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; 2.
DR PROSITE; PS50526; RDRP_SSRNA_NEG_NONSEG; 1.
DR PROSITE; PS51590; SAM_MT_MNV_L; 1.
PE 1: Evidence at protein level;
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..2212
FT /note="RNA-directed RNA polymerase L"
FT /id="PRO_0000222167"
FT DOMAIN 625..809
FT /note="RdRp catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00539"
FT DOMAIN 1805..2003
FT /note="Mononegavirus-type SAM-dependent 2'-O-MTase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00923"
FT REGION 1..450
FT /note="Homooligomerization"
FT /evidence="ECO:0000269|PubMed:23582637"
FT REGION 1..380
FT /note="Interaction with VP35"
FT /evidence="ECO:0000269|PubMed:23582637"
FT REGION 1653..1689
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 741..744
FT /note="Essential for both viral transcription and
FT replication"
FT /evidence="ECO:0000269|PubMed:28991917"
FT COMPBIAS 1655..1673
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1674..1688
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VARIANT 820
FT /note="T -> A"
FT VARIANT 934
FT /note="F -> L"
FT VARIANT 1532
FT /note="I -> V"
FT MUTAGEN 742..744
FT /note="DNQ->AAA: Complete loss of replication and
FT transcription."
FT /evidence="ECO:0000269|PubMed:28991917"
FT MUTAGEN 742
FT /note="D->A: Complete loss OF RNA synthesis."
FT /evidence="ECO:0000269|PubMed:29507309"
SQ SEQUENCE 2212 AA; 252724 MW; 5B07EDDC370E2934 CRC64;
MATQHTQYPD ARLSSPIVLD QCDLVTRACG LYSSYSLNPQ LRNCKLPKHI YRLKYDVTVT
KFLSDVPVAT LPIDFIVPVL LKALSGNGFC PVEPRCQQFL DEIIKYTMQD ALFLKYYLKN
VGAQEDCVDE HFQEKILSSI QGNEFLHQMF FWYDLAILTR RGRLNRGNSR STWFVHDDLI
DILGYGDYVF WKIPISMLPL NTQGIPHAAM DWYQASVFKE AVQGHTHIVS VSTADVLIMC
KDLITCRFNT TLISKIAEIE DPVCSDYPNF KIVSMLYQSG DYLLSILGSD GYKIIKFLEP
LCLAKIQLCS KYTERKGRFL TQMHLAVNHT LEEITEMRAL KPSQAQKIRE FHRTLIRLEM
TPQQLCELFS IQKHWGHPVL HSETAIQKVK KHATVLKALR PIVIFETYCV FKYSIAKHYF
DSQGSWYSVT SDRNLTPGLN SYIKRNQFPP LPMIKELLWE FYHLDHPPLF STKIISDLSI
FIKDRATAVE RTCWDAVFEP NVLGYNPPHK FSTKRVPEQF LEQENFSIEN VLSYAQKLEY
LLPQYRNFSF SLKEKELNVG RTFGKLPYPT RNVQTLCEAL LADGLAKAFP SNMMVVTERE
QKESLLHQAS WHHTSDDFGE HATVRGSSFV TDLEKYNLAF RYEFTAPFIE YCNRCYGVKN
VFNWMHYTIP QCYMHVSDYY NPPHNLTLEN RDNPPEGPSS YRGHMGGIEG LQQKLWTSIS
CAQISLVEIK TGFKLRSAVM GDNQCITVLS VFPLETDADE QEQSAEDNAA RVAASLAKVT
SACGIFLKPD ETFVHSGFIY FGKKQYLNGV QLPQSLKTAT RMAPLSDAIF DDLQGTLASI
GTAFERSISE TRHIFPCRIT AAFHTFFSVR ILQYHHLGFN KGFDLGQLTL GKPLDFGTIS
LALAVPQVLG GLSFLNPEKC FYRNLGDPVT SGLFQLKTYL RMIEMDDLFL PLIAKNPGNC
TAIDFVLNPS GLNVPGSQDL TSFLRQIVRR TITLSAKNKL INTLFHASAD FEDEMVCKWL
LSSTPVMSRF AADIFSRTPS GKRLQILGYL EGTRTLLASK IINNNTETPV LDRLRKITLQ
RWSLWFSYLD HCDNILAEAL TQITCTVDLA QILREYSWAH ILEGRPLIGA TLPCMIEQFK
VFWLKPYEQC PQCSNAKQPG GKPFVSVAVK KHIVSAWPNA SRISWTIGDG IPYIGSRTED
KIGQPAIKPK CPSAALREAI ELASRLTWVT QGSSNSDLLI KPFLEARVNL SVQEILQMTP
SHYSGNIVHR YNDQYSPHSF MANRMSNSAT RLIVSTNTLG EFSGGGQSAR DSNIIFQNVI
NYAVALFDIK FRNTEATDIQ YNRAHLHLTK CCTREVPAQY LTYTSTLDLD LTRYRENELI
YDSNPLKGGL NCNISFDNPF FQGKRLNIIE DDLIRLPHLS GWELAKTIMQ SIISDSNNSS
TDPISSGETR SFTTHFLTYP KIGLLYSFGA FVSYYLGNTI LRTKKLTLDN FLYYLTTQIH
NLPHRSLRIL KPTFKHASVM SRLMSIDPHF SIYIGGAAGD RGLSDAARLF LRTSISSFLT
FVKEWIINRG TIVPLWIVYP LEGQNPTPVN NFLYQIVELL VHDSSRQQAF KTTISDHVHP
HDNLVYTCKS TASNFFHASL AYWRSRHRNS NRKYLARDSS TGSSTNNSDG HIERSQEQTT
RDPHDGTERN LVLQMSHEIK RTTIPQENTH QGPSFQSFLS DSACGTANPK LNFDRSRHNV
KFQDHNSASK REGHQIISHR LVLPFFTLSQ GTRQLTSSNE SQTQDEISKY LRQLRSVIDT
TVYCRFTGIV SSMHYKLDEV LWEIESFKSA VTLAEGEGAG ALLLIQKYQV KTLFFNTLAT
ESSIESEIVS GMTTPRMLLP VMSKFHNDQI EIILNNSASQ ITDITNPTWF KDQRARLPKQ
VEVITMDAET TENINRSKLY EAVYKLILHH IDPSVLKAVV LKVFLSDTEG MLWLNDNLAP
FFATGYLIKP ITSSARSSEW YLCLTNFLST TRKMPHQNHL SCKQVILTAL QLQIQRSPYW
LSHLTQYADC ELHLSYIRLG FPSLEKVLYH RYNLVDSKRG PLVSITQHLA HLRAEIRELT
NDYNQQRQSR TQTYHFIRTA KGRITKLVND YLKFFLIVQA LKHNGTWQAE FKKLPELISV
CNRFYHIRDC NCEERFLVQT LYLHRMQDSE VKLIERLTGL LSLFPDGLYR FD
