ID   L_RABVN                 Reviewed;        2127 AA.
AC   Q9IPJ5; Q75T08; Q9JH63;
DT   10-JUL-2007, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-2000, sequence version 1.
DT   03-AUG-2022, entry version 92.
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 Nishigahara RCEH) (RABV).
OC   Viruses; Riboviria; Orthornavirae; Negarnaviricota; Haploviricotina;
OC   Monjiviricetes; Mononegavirales; Rhabdoviridae; Alpharhabdovirinae;
OC   Lyssavirus.
OX   NCBI_TaxID=11298;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
OH   NCBI_TaxID=40674; Mammalia.
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX   PubMed=1588319; DOI=10.1099/0022-1317-73-5-1149;
RA   Sacramento D., Badrane H., Bourhy H., Tordo N.;
RT   "Molecular epidemiology of rabies virus in France: comparison with vaccine
RT   strains.";
RL   J. Gen. Virol. 73:1149-1158(1992).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RC   STRAIN=Isolate RC-HL;
RX   PubMed=11270607; DOI=10.1111/j.1348-0421.2001.tb01274.x;
RA   Ito N., Kakemizu M., Ito K.A., Yamamoto A., Yoshida Y., Sugiyama M.,
RA   Minamoto N.;
RT   "A comparison of complete genome sequences of the attenuated RC-HL strain
RT   of rabies virus used for production of animal vaccine in Japan, and the
RT   parental Nishigahara strain.";
RL   Microbiol. Immunol. 45:51-58(2001).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RC   STRAIN=Isolate Ni-CE, and Nishigahara RCEH;
RX   PubMed=17010466; DOI=10.1016/j.virusres.2006.08.011;
RA   Shimizu K., Ito N., Mita T., Yamada K., Hosokawa-Muto J., Sugiyama M.,
RA   Minamoto N.;
RT   "Involvement of nucleoprotein, phosphoprotein, and matrix protein genes of
RT   rabies virus in virulence for adult mice.";
RL   Virus Res. 123:154-160(2007).
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; AB009663; BAA24087.2; -; Genomic_RNA.
DR   EMBL; AB044824; BAA96806.1; -; Genomic_RNA.
DR   EMBL; AB128149; BAD04914.1; -; Genomic_RNA.
DR   PIR; PQ0341; PQ0341.
DR   PIR; PQ0363; PQ0363.
DR   SMR; Q9IPJ5; -.
DR   PRIDE; Q9IPJ5; -.
DR   BRENDA; 2.7.7.88; 14818.
DR   Proteomes; UP000006366; Genome.
DR   Proteomes; UP000007309; Genome.
DR   Proteomes; UP000007310; 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..2127
FT                   /note="Large structural protein"
FT                   /id="PRO_0000294423"
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"
FT                   /evidence="ECO:0000250"
FT   VARIANT         26
FT                   /note="T -> S (in strain: Isolate RC-HL)"
FT   VARIANT         47
FT                   /note="A -> V (in strain: Isolate RC-HL)"
FT   VARIANT         61
FT                   /note="C -> R (in strain: Isolate Ni-CE)"
FT   VARIANT         86
FT                   /note="G -> D (in strain: Isolate RC-HL)"
FT   VARIANT         121
FT                   /note="A -> V (in strain: Isolate Ni-CE)"
FT   VARIANT         144
FT                   /note="R -> K (in strain: Isolate RC-HL)"
FT   VARIANT         194
FT                   /note="T -> A (in strain: Isolate RC-HL)"
FT   VARIANT         274
FT                   /note="S -> A (in strain: Isolate RC-HL)"
FT   VARIANT         933
FT                   /note="Q -> H (in strain: Isolate RC-HL)"
FT   VARIANT         942
FT                   /note="Q -> H (in strain: Isolate RC-HL)"
FT   VARIANT         1079
FT                   /note="R -> Q (in strain: Isolate Ni-CE)"
FT   VARIANT         1157
FT                   /note="F -> S (in strain: Isolate RC-HL)"
FT   VARIANT         1226..1227
FT                   /note="PL -> SI (in strain: Isolate RC-HL)"
FT   VARIANT         1372..1374
FT                   /note="SGR -> NGI (in strain: Isolate RC-HL)"
FT   VARIANT         1394
FT                   /note="T -> I (in strain: Isolate RC-HL)"
FT   VARIANT         1592
FT                   /note="Q -> R (in strain: Isolate RC-HL)"
FT   VARIANT         1860
FT                   /note="A -> V (in strain: Isolate RC-HL)"
FT   VARIANT         1990
FT                   /note="L -> M (in strain: Isolate RC-HL)"
FT   VARIANT         2029
FT                   /note="L -> M (in strain: Isolate RC-HL)"
SQ   SEQUENCE   2127 AA;  242338 MW;  261C047600FAEADA CRC64;
     MLDPGEVYDD PIDPVESDAE PRGAPTVPNI LRNSDYNLNS PLIEDPARLM LEWLKTGNRP
     CRMTLTDNCS RSYKVLKDYF KKVDLGSLKV GGTAAQSMIS LWLYGAHSES NRSRRCITDL
     AHFYSKSSPI EKLLNCTLGN RGLRIPPEGV LSCLEKVDYD KAFGRYLANT YSSYLFFHVI
     ILYMNALDRD EEKTILALWK DLTSVDIGKD LVKFKDQIWG LLIVTKDFVY SQSSNCLFDR
     NYTLMLKDLF LSRFNSLMIL LSPPEPLYSD DLISQLCQLY IAGDQVLSMC GNSGYEVIKI
     LEPYVVNSLV RRAEKFRPLI HSLGDFPVFI KDKVSQLEGT FGPSAKRFFK VLDQFDNIHD
     LVFVYGCYRH WGHPYIDYRK GLSKLYDQVH MKKVIDKSYQ ECLASDLARR ILRWGFDKYS
     KWYLDSRFLA QDHPLTPYVK TQTWPPRHIA DLVGDTWHKL PITQIFEIPE SMDPSEILDD
     KSHSLTRTRL ASWLSENRGG PVPSEKVIIT ALSKPPINPR EFLKSIDLGG LPDEDLIIGL
     KPKERELKIE GRFFALMSWN LRLYFVITEK LLANYILPLF DALTMTDNLN KVFKKLIDRV
     TGQGLLDYSR VTYAFHLDYE KWNNHQRLES TEDVFSVLDQ VFGLKRVFSR THEFFQKSWI
     YYSDRSDLIG LWEDQIYCLD ISNGPTCWNG QDGGLEGLRQ KGWSLVSLLM IDRESQTRNT
     RTKILAQGDN QVLCPTYMLS PGLSLEGLLY ELESISRNAL SIYRAIEEGA SKLGLIIKKE
     ETMCSYDFLI YGKTPLFRGN ILVPESKRWA RVSCISNDQI VNLANIMSTV STNALTVAQH
     SQSLIKPMRD FLLMSVQAVF HYLLFSPILK GRVYKILSAE GESFLLAMSR IIYLDPSLGG
     VSGMSLGRFH IRQFSDPVSE GLSFWREIWL SSQESWIHAL 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 RALSLKESIN
     WFITRNSNLA QTLIRNIISL TGPDFPLEEA PVFKRTGSAL HRFKSARYSE GGYSSVCPNL
     LSHISVSTDT MSDLTQDGKN YDFMFQPLML YAQTWTSELV QRDTRLRDST FHWHLRCNRC
     VRPIDDITLE TSQIFEFPDV SKRISRMVSG AVPHFRKLPD IRLRPGDFES LSGREKSRHI
     GSAQGLLYSI LVATHDSGYN DGTIFPVNIY GKVSPRDYLR GLARGVLIGS SICFLTRMTN
     ININRPLELI SGVISYILLR LDNHPSLYVM LREPSLRGEI FSIPQKIPAA YPTTMKEGNR
     SILCYLQHVL RYEREVITAS PENDWLWIFS DFRSAKMTYL TLITYQSHLL LQRVERNLSK
     GMRANLQQLS SLMRQVLGGH GEDTLESDDD IQRLLKDSLR RTRWVDQEVR HAAKTMTGDY
     SPNKKVSRKA GCSEWVCSAQ QVAVSTSANP APVSELDIRA LSKRFQNPLI SGLRVVQWAT
     GAHYKLKPIL DDLKVFPSLC LVVGDGSGGI SRAVLNMFPD AKLVFNSLLE VNDLMASGTH
     PLPPSAIMSG GDDIVSRVID FDSIWEKPSD LRNLTTWGYF QSVQKQVNMS FDLIICDAEV
     TDIASINQIT LLMSDFALSI DGPLYLVFKT YGTMLVNPDY KAIQHLSRAF PSVTGFVTQA
     TSSFSSELYL RFSKRGKFFR DAEYLTSSTL REMSLVLFNC SSPKSEMQRA RSLNYQDLVR
     GFPEEIISNP YNEMIITLID NDVESFLVHK MVDDLELQRG TLSKVAIIIA IVIVFSNRVF
     NISKPLADPL FYPPSDPKIL RHFNICCSTL MYLSTALGDV PSFTRLHDLY NRPITYYFRK
     QVIRGNIYLS WSWSGDTLVF KRVACNSSLS LSSHWIRLIY KIVKTTRLVG NIEDLSREVE
     RHLHGYNRWI TLKDIRSRSS LLDYSCL