L_RABVP
ID L_RABVP Reviewed; 2142 AA.
AC P11213;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1990, sequence version 2.
DT 03-AUG-2022, entry version 123.
DE RecName: Full=Large structural protein;
DE Short=Protein L;
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 Rabies virus (strain Pasteur vaccins / PV) (RABV).
OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Haploviricotina;
OC Monjiviricetes; Mononegavirales; Rhabdoviridae; Alpharhabdovirinae;
OC Lyssavirus.
OX NCBI_TaxID=103929;
OH NCBI_TaxID=9606; Homo sapiens (Human).
OH NCBI_TaxID=40674; Mammalia.
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=3407152; DOI=10.1016/0042-6822(88)90600-9;
RA Tordo N., Poch O., Ermine A., Keith G., Rougeon F.;
RT "Completion of the rabies virus genome sequence determination: highly
RT conserved domains among the L (polymerase) proteins of unsegmented
RT negative-strand RNA viruses.";
RL Virology 165:565-576(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 1-28.
RX PubMed=3459163; DOI=10.1073/pnas.83.11.3914;
RA Tordo N., Poch O., Ermine A., Keith G., Rougeon F.;
RT "Walking along the rabies genome: is the large G-L intergenic region a
RT remnant gene?";
RL Proc. Natl. Acad. Sci. U.S.A. 83:3914-3918(1986).
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: May form homodimer. Interacts with the P protein.
CC {ECO:0000250|UniProtKB:P03523}.
CC -!- SUBCELLULAR LOCATION: Virion {ECO:0000250|UniProtKB:P03523}. Host
CC cytoplasm {ECO:0000250|UniProtKB:P03523}. Note=L and P are packaged
CC asymmetrically towards the blunt end of the virus.
CC {ECO:0000250|UniProtKB:P03523}.
CC -!- SIMILARITY: Belongs to the rhabdoviruses protein L family.
CC {ECO:0000305}.
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DR EMBL; M13215; AAA47219.1; -; Genomic_RNA.
DR PIR; A29248; ZLVNPV.
DR RefSeq; NP_056797.1; NC_001542.1.
DR SMR; P11213; -.
DR DrugBank; DB11603; Rabies immune globulin, human.
DR GeneID; 1489857; -.
DR KEGG; vg:1489857; -.
DR BRENDA; 2.7.7.88; 14818.
DR Proteomes; UP000008649; 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 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; IPR017234; RNA-dir_pol_rhabdovirus.
DR Pfam; PF14314; Methyltrans_Mon; 1.
DR Pfam; PF14318; Mononeg_mRNAcap; 1.
DR Pfam; PF00946; Mononeg_RNA_pol; 1.
DR PIRSF; PIRSF037546; RNA_pol_RhabdoV_sub; 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..2142
FT /note="Large structural protein"
FT /id="PRO_0000222840"
FT DOMAIN 611..799
FT /note="RdRp catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00539"
FT DOMAIN 1674..1871
FT /note="Mononegavirus-type SAM-dependent 2'-O-MTase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00923"
FT REGION 1..24
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1562..2127
FT /note="Interaction with P protein"
FT /evidence="ECO:0000250"
FT BINDING 1701..1710
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255"
SQ SEQUENCE 2142 AA; 244487 MW; 56ABB69E922EDD1C CRC64;
MLDPGEVYDD PIDPIELEAE PRGTPTVPNI LRNSDYNLNS PLIEDPARLM LEWLKTGNRP
YRMTLTDNCS RSFRVLKDYF KKVDLGSLKV GGMAAQSMIS LWLYGAHSES NRSRRCITDL
AHFYSKSSPI EKLLNLTLGN RGLRIPPEGV LSCLERVDYD NAFGRYLANT YSSYLFFHVI
TLYMNALDWD EEKTILALWK DLTSVDIGKD LVKFKDQIWG LLIVTKDFVY SQSSNCLFDR
NYTLMLKDLF LSRFNSLMVL LSPPEPRYSD DLISQLCQLY IAGDQVLSMC GNSGYEVIKI
LEPYVVNSLV QRAEKFRPLI HSLGDFPVFI KDKVSQLEET FGSCARRFFR ALDQFDNIHD
LVFVYGCYRH WGHPYIDYRK GLSKLYDQVH IKKVIDKSYQ ECLASDLARR ILRWGFDKYS
KWYLDSRFLA RDHPLTPYIK TQTWPPKHIV DLVGDTWHKL PITQIFEIPE SMDPSEILDD
KSHSFTRTRL ASWLSENRGG PVPSEKVIIT ALSKPPVNPR EFLKSIDLGG LPDEDLIIGL
KPKERELKIE GRFFALMSWN LRLYFVITEK LLANYILPLF DALTMTDNLN KVFKKLIDRV
TGQGLLDYSR VTYAFHLDYE KWNNHQRLES TEDVFSVLDQ VFGLKRVFSR THEFFQKSWI
YYSDRSDLIG LREDQIYCLD ASNGPTCWNG QDGGLEGLRQ KGWSLVSLLM IDRESQIRNT
RTKVLAQGDN QVLCPTYMLS PGLSQEGLLY ELESISRNAF SIYRAVEEGA SKLGLIIKKE
ETMCSYDFLI YGKTPLFRGN ILVPESKRWA RVSCVSNDQI VNLANIMSTV STNALTVAQH
SQSLIKPMRD FLLMSVQAVF HYLLFSPILK GRVYKILSAE GESFLLAMSR IIYLDPSLGG
VSGMSLGRFH IRQFSDPVSE GLSFWREIWL SSHESWIHAL CQEAGNPDLG ERTLESFTRL
LEDPTTLNIR GGASPTILLK DAIRKALYDE VDKVENSEFR EAILLSKTHR DNFILFLTSV
EPLFPRFLSE LFSSSFLGIP ESIIGLIQNS RTIRRQFRKS LSKTLEESFY NSEIHGISRM
TQTPQRVGGV WPCSSERADL LREISWGRKV VGTTVPHPSE MLGLLPKSSI SCTCGATGGG
NPRVSVSVLP SFDQSFFCTG PLKGYLGSST SMSTQLFHAW EKVTNVHVVK RALSLKESIN
WFITRDSNLA QTLIRNIVSL TGPDFPLEEA PVFKRTGSAL HRFKSARYSE GGYSSVCPNL
LSHISVSTDT MSDLTQDGKN YDFMFQPLML YAQTWTSELV QRDTRLRDST FHWHLQCNRC
VRPIDDVTLE TSQIFEFPDV SKRISRMVSG AVPHFQRLPD IRLRPGDFES LSGREKSHHI
GSAQGLLYSI LVAIHDSGYN DGTIFPVNIY GKVSPRDYLR GLARGVLIGS SICFLTRMTN
ININRPLELI SGVISYILLR LDNHPSLYIM LREPSFREEI FSIPQKIPAA YPTTMKEGNR
SILCYLQHVL RYEREVITAS PENDWLWIFS DFRSAKMTYL TLITYQSHLL LQRVERNLSK
SMRDNLRQLS SLMRQVLGGH GEDTLESDDN IQRLLKDSLR RTRWVDQEVR HAARTMTGDY
SPNKKVSRKV GCSEWVCSAQ QVAVSTSANP APVSELDIRA LSKRFQNPLI SGLRVVQWAT
GAHYKLKPIL DDLNVFPSLC LVVGDGSGGI SRAVLNMFPD AKLVFNSLLE VNDLMASGTH
PLPPSAIMRG GNDIVSRVID FDSIWEKPSD LRNLATWKYF QSVQKQVNMS YDLIICDAEV
TDIASINRIT LLMSDFALSI DGPLYLVFKT YGTMLVNPNY KAIQHLSRAF PSVTGFITQV
TSSFSSELYL RFSKRGKFFR DAEYLTSSTL REMSLVLFNC SSPKSEMQRA RSLNYQDLVR
GFPEEIISNP YNEMIITLID SDVESFLVHK MVDDLELQRG TLSKVAIIIA IMIVFSNRVF
NVSKPLTDPL FYPPSDPKIL RHFNICCSTM MYLSTALGDV PSFARLHDLY NRPITYYFRK
QVILGNVYLS WSWSNDTSVF KRVACNSSLS LSSHWIRLIY KIVKTTRLVG SIKDLSGEVE
RHLHRYNRWI TLENIRSRSS LLDYSCLCIG YSWKPAHAKT LV
