L_RABVB
ID L_RABVB Reviewed; 2128 AA.
AC Q66T60;
DT 10-JUL-2007, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2004, sequence version 1.
DT 25-MAY-2022, entry version 72.
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 silver-haired bat-associated) (RABV) (SHBRV).
OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Haploviricotina;
OC Monjiviricetes; Mononegavirales; Rhabdoviridae; Alpharhabdovirinae;
OC Lyssavirus.
OX NCBI_TaxID=445793;
OH NCBI_TaxID=9606; Homo sapiens (Human).
OH NCBI_TaxID=40674; Mammalia.
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=15520387; DOI=10.1073/pnas.0407289101;
RA Faber M., Pulmanausahakul R., Nagao K., Prosniak M., Rice A.B.,
RA Koprowski H., Schnell M.J., Dietzschold B.;
RT "Identification of viral genomic elements responsible for rabies virus
RT neuroinvasiveness.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:16328-16332(2004).
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; AY705373; AAU11519.1; -; Genomic_RNA.
DR SMR; Q66T60; -.
DR PRIDE; Q66T60; -.
DR Proteomes; UP000006845; 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 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; RNA-directed RNA polymerase;
KW S-adenosyl-L-methionine; Transferase; Viral RNA replication; Virion.
FT CHAIN 1..2128
FT /note="Large structural protein"
FT /id="PRO_0000294418"
FT DOMAIN 612..800
FT /note="RdRp catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00539"
FT DOMAIN 1675..1872
FT /note="Mononegavirus-type SAM-dependent 2'-O-MTase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00923"
FT REGION 1563..2128
FT /note="Interaction with P protein"
FT /evidence="ECO:0000250"
SQ SEQUENCE 2128 AA; 243090 MW; A039BB2078B76EFD CRC64;
MMIDPGEVYD DPIDLIESEA EPKGNPTIPN ILRNSDYNLN SPLIEDPARL MLEWLKTGNR
PLRMTLTDNC SRSHKVLKDY FKRVDLGSLK VGGAAAQSMI SLWLYGAHSE SNRSRKCIND
LAQFYYKSSP IEKLLNCTLG NRGLKTPPEG VLSCLARVDY DKAFGRYLAN IYSSYLFFHV
ITLYMNALDW DEEKTILALW RDITSIDTGK DLVKFKDQIW GLLIVTKDFV YSQSTGCLFD
RNYTLMLKDL FLSRFNSLMI LLSPPEPRYS DDLISQLCQL YIAGDQVLSM CGNSGYEVIK
ILEPYVVNSL VQRAEKFRPL IHSLGDFPTF IRDKVGQLEG TFGPSAKRFF KVLDQFDNIH
DLVFVYGCYR HWGHPYIDYR KGLSKLYDQV HLKKVIDKSY QECLASDLAR RILRWGFDKY
SKWYLDSRLL SRDHPLIPYI KTQTWPPRHI VDLVGDTWHK LPITQIFEIP ESMDPSEILD
DKSHSFTRTR LASWLSENRG GPVPSEKVII TALSKPPVNP REFLKSIDLG GLPDEDLIIG
LKPKERELKI EGRFFALMSW NLRLYFVITE KLLANYILPL FDALTMTDNL NKVFKKLIDR
VTGQGLLDYS RVTYAFRLDY EKWNNHQRLE STEDVFSVLD QVFGLKRVFS RTHEFFQRSW
IYYSDRSDLI GLWEDQIYCL DMSDGPTCWN GQDGGLEGLR QKGWSLVSLL MIDRESQTRN
TRTKILAQGD NQVLCPTYML SPGLSREGLL YELESISRNA LSIYRAIEEG ASKLGLIIKK
EETMCSYDFL IYGKTPLFRG NILVPESKRW ARVSCISNDQ IVNLANTMST VSTNALTVAQ
HSQSLIKPMR DFLLMSVQAV FHYLLFSPIL KGRVYKILSA EGDNFLLAMS RIIYLDPSLG
GVSGMSLGRF HIRQFSDPVS EGLSFWREIW LSSNESWIHA LCQEAGNPDL GERTLESFTR
LLEDPTTLNI KGGASPTILL KDAIRKALYD EVDEVENSEF REAILLSKTH RDNFILFLKS
IEPLFPRFLS ELFSSSFLGI PESIIGLIQN SRTIRRQFRR SLSRTLEESF YNSETHGINR
MTQTPQRVGR VWPCSSERAD LLREISWGRK VVGTTVPHPS EMLGLIPKSS ISCTCGAAGG
GNPRISVSVL PSFDQSFFSR GPLKGYLGSS TSMSTQLFHA WEKVTNVHVV KRALSLKESI
NWFITRNSNR AQTLIRNIMS LTGPDFPLEE APVFKRTGSA LHRFKSARYS EGGYSSVCPN
LLSHISVSTD TMSDLTQDGR NYDFMFQPLM LYAQTWTSEL VQKDTRLKDS TFHWHLRCNK
CIRPIDDMTL DTSQVFEFPD VSRRISRMVS GAVPHFRKLP DIRLRPGDFE SLSGKEKSRH
IGSAQGLLYS ILVAIHDSGY NDGTIFPVNI YSKVSPRDYL RGLARGVLIG SSICFLTRMT
NININRPLEL ISGVISYILL RLDNHPSLYI MLREPSLRGE IFSIPQKVPA AYPTTMKEGN
RSILCYLQHV LRYEREAITA SPENDWLWIF SDFRSSKMTY LTLITYQSHL LLQRVDKNLS
KSMRANLRQM SSLMRQVLGG HGEDTLESDE DIQRLLKDSL RRTRWVDQEV RHAARTMTGS
YSPHRRVSRK AGCSEWVCSA QQVAVSTSAN PAPASELDIR TLSRRLQNPL ISGLRVVQWA
TGAHYKLKPI LDDLNVFPSL CLVVGDGSGG ISRAVLNMFP DARLVFNSLL EVNDLMASGT
HPLPPSAIMS GGDDIISRVI DFDSIWEKPS DLRNLTTWRY FQSVQEQVNM SYDLIICDAE
VTDIASINRI TLLMSDFALS IDGPLYLVFK TYGTMLVNPD YRAIQHLSRA FPAVTGFITQ
MTSSFSSELY LRFSKRGKFF RDAEYLTSST LREMSLVLFN CSSPKSEMQR ARSLNYQDLV
RGFPDEVISN PYNEMIITLI DSDVESFLVH KMVDDLELQR GTLSKVSIII AIMIVFSNRV
FNVSKPLTDP LFYPPFDPKI LRHFNICCST MMYLSTALGD VPSFARLHDL YNRPITYYFR
KQVIRGNIYL SWSWSDDTSV FKRVACNSSL SLSSHWIRLI YKIVKTTRLV GSIEDLSGEI
EKHLRGYNRW ITLDDIRSRS SLLDYSCL
