L_RABVH
ID L_RABVH Reviewed; 2127 AA.
AC Q8B6J5;
DT 10-JUL-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 25-MAY-2022, entry version 82.
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 HEP-Flury) (RABV).
OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Haploviricotina;
OC Monjiviricetes; Mononegavirales; Rhabdoviridae; Alpharhabdovirinae;
OC Lyssavirus.
OX NCBI_TaxID=11296;
OH NCBI_TaxID=9606; Homo sapiens (Human).
OH NCBI_TaxID=40674; Mammalia.
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=12505638; DOI=10.1016/s0166-0934(02)00249-5;
RA Inoue K., Shoji Y., Kurane I., Iijima T., Sakai T., Morimoto K.;
RT "An improved method for recovering rabies virus from cloned cDNA.";
RL J. Virol. Methods 107:229-236(2003).
RN [2]
RP INTERACTION WITH PROTEIN P.
RC STRAIN=CVS;
RX PubMed=9499045; DOI=10.1128/jvi.72.3.1925-1930.1998;
RA Chenik M., Schnell M., Conzelmann K.K., Blondel D.;
RT "Mapping the interacting domains between the rabies virus polymerase and
RT phosphoprotein.";
RL J. Virol. 72:1925-1930(1998).
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; AB085828; BAC53869.1; -; Genomic_RNA.
DR SMR; Q8B6J5; -.
DR Proteomes; UP000006846; 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 1: Evidence at protein level;
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..2127
FT /note="Large structural protein"
FT /id="PRO_0000294421"
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..27
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1562..2127
FT /note="Interaction with P protein"
SQ SEQUENCE 2127 AA; 242955 MW; E9B31C8642375518 CRC64;
MLDPGEVYDD PIDPIESEAE PRGTPTVPNI LRNSDYNLNS PLIEDSAKLM LEWLKTGNRP
YRMTLTDNCS RSYKDLKDYF KKVDLGSLKV GGTAAQSMIS LWLYGAHSES NRSRRCITDL
AHFYSKSSPI EKLLNCTLGN RGLRIPPEGV LSCLERVDYD KAFGRYLANT YSSYLFFHVI
TLYMNALDWE EEKTILALWK DLTSVDTGKD LVKFKDQIWG LLIVTKDFVY SQSSNCLFDR
NYTLMLKDLF LSRFNSLMIL LSPPEPRYSD DLISQLCQLY IAGDQVLSLC GNSGYEVIKI
LEPYVVNSLV QRAEKFRPLI HSLGDFPMFI KDKVNQLEGT FGPSAKRFFR VLDQFDNIHD
LVFVYGCYRH WGHPYIDYRK GLLKLYDQVH IKKVIDKSYQ ECLASDLARR ILRWGFDKYS
KWYLDSRFLA RDHPLAPYIK TQTWPPKHIV DLVGDTWHKL PITQIFEIPE SMDPSEILDD
KSHSFTRTRL ASWLSENRGG PVPSEKVIIT ALSQPPVNPR EFLKSIDLGG LPDDDLIIGL
RPKERELKIE GRFFALMSWN LRLYFVITEK LLANYILPLF DALTMTDNLN KVFKKLIDRV
TGQGLLDYSR VTYAFHLDYE KWNNHQRLES TEDVFSVLDQ VFGLKRVFSR THEFFQKSWI
YYSDRSDLIG LREDQIYCLD MSNGPTCWNG QDGGLEGLRQ KGWSLVSLLM IDRESQTRNT
RTKILAQGDN QVLCPTYMLS PGLSQEGLLY ELESISRNAL SIYRAIEEGA SKLGLIIKKE
ETMCSYDFLI YGKTPLFRGN ILVPESKRWA RVSCISNDQI VNLANIMSTV STNALTVAQH
SQSLIKPMRD FLLMSVQAVF HYLLFSPILK GRVYKILSAE GESFLLAMSR IIYLDPSLGG
VSGMSLGRFH IRQFSDPVSE GLSFWREIWL SSHESWIHAL CQEAGNPDLG ERTLESFTRL
LEDPTTLNIK GGASPTILLK DAIRKALYDE VDKVENSEFR EAILLSKTHR DNFILFLKSV
EPLFPRFLSE LFSSSFLGIP ESIIGLIQNS RTIRRQFRKS LSRTLEESFY NSEIHGINRM
TQTPQRVGRV WPCSSERADL LREISWGRKV VGTTVPHPSE MLGLLPKSSI SCTCGATGGG
NPRVSVSVLP SFDQSFFSRG PLKGYLGSST SMSTQLFHAW EKVTNVHVVK RAISLKESIN
WFINRNSNLA QTLIRNIMSL TGPDFSLEEA PVFKRTGSAL HRFKSARYSE GGYSSVCPNL
LSHISVSTDT MSDLTQDGKN YDFMFQPLML YAQTWTSELV QRDTRLRDST FHWHLRCNRC
VRPIEDITLE TSQIFEFPDV SKRISRMVSG AVPHFQKLPD IRLRPGDFES LSGREKSRHI
GSAQGLLYSI LVAIHDSGYN DGTIFPVNIY GKVSPRDYLR GLARGILIGS SICFLTRMTN
INIKRPLELI SGVISYILLR LDNHPSLYIM LREPSLRGEI FSIPQKIPAA YPTTMKEGNR
SILCYLQHVL RYEREVITAS PENDWLWIFS DFRSAKMTYL TLITYQSHLL LQRVERNLSK
SMRATLQQMG SLMRQVLGGH GEDTLESDDD IQRLLKDSLR RTRWVDQEVR HAARTMSGDY
SPNKRVSRKA GCSEWVCSAQ QVAVSTSANP APVSELDIRA LSKRFQNPLI SGLRVVQWAT
GAHYKLKPIL DDLNVFPSLC LVVGDGSGGI SRAVLNMFPD SKLVFNSLLE VNDLMASGTR
PLPPSAIMSG GDDIISRVID FDSIWEKPSD LRNLATWRYF QSVQKQVNMS YDLIICDAEV
TDIASINRIT LLMSDFALSI DGPLYLVFKT YGTMLVNPDY KAIQHLSRAF PSVTGFITQV
TSSFSSELYL RFSKRGKFFR DAEYLTSSTL REMSLVLFNC SSPKSEMQRA RSLNYQDLVR
GFPEEIISNP YNEMIITLID SDVESFLVHK MVDDLELQRG TLSKVAIIIS IMIVFSNRVF
NISKPLTDPL FYPPSDPKIL RHFNICCSTM MYLSTALGDV PSFARLHDLY NRPITYYFRK
QVIRGNIYLS WSWSDDTPVF KRVACNSSLS LSSHWIRLIY KIVKTTRLVG RIEDLSGEVE
RHLHGYNRWI TLEDIRSRSS LLDYSCL
