ID   L_RABVI                 Reviewed;        2127 AA.
AC   A3RM23; Q58FH0;
DT   10-JUL-2007, integrated into UniProtKB/Swiss-Prot.
DT   03-APR-2007, sequence version 1.
DT   25-MAY-2022, entry version 65.
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 India) (RABV).
OC   Viruses; Riboviria; Orthornavirae; Negarnaviricota; Haploviricotina;
OC   Monjiviricetes; Mononegavirales; Rhabdoviridae; Alpharhabdovirinae;
OC   Lyssavirus.
OX   NCBI_TaxID=445790;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
OH   NCBI_TaxID=40674; Mammalia.
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RC   STRAIN=Isolate Germany;
RA   Pfefferle S., Panning M., Drosten C.;
RT   "Virological characterization of cases of transplantation-associated Rabies
RT   in Germany.";
RL   Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RA   Desai A., Nagaraja T., Muhamuda K., Madhusudana S., Ravi V.;
RT   "Complete nucleotide sequencing of an Indian isolate of Rabies virus.";
RL   Submitted (FEB-2007) to the EMBL/GenBank/DDBJ databases.
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; AY956319; AAX56085.1; -; Genomic_RNA.
DR   EMBL; EF437215; ABO15580.1; -; Genomic_RNA.
DR   SMR; A3RM23; -.
DR   Proteomes; UP000008620; Genome.
DR   Proteomes; UP000008996; 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_0000294422"
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         93
FT                   /note="T -> A (in strain: Isolate Germany)"
FT   VARIANT         232
FT                   /note="H -> Q (in strain: Isolate Germany)"
FT   VARIANT         361
FT                   /note="L -> V (in strain: Isolate Germany)"
FT   VARIANT         471
FT                   /note="P -> S (in strain: Isolate Germany)"
FT   VARIANT         488
FT                   /note="A -> T (in strain: Isolate Germany)"
FT   VARIANT         502
FT                   /note="A -> V (in strain: Isolate Germany)"
FT   VARIANT         525
FT                   /note="T -> S (in strain: Isolate Germany)"
FT   VARIANT         966
FT                   /note="T -> A (in strain: Isolate Germany)"
FT   VARIANT         1373
FT                   /note="G -> D (in strain: Isolate Germany)"
FT   VARIANT         1825
FT                   /note="Y -> C (in strain: Isolate Germany)"
FT   VARIANT         1841
FT                   /note="K -> N (in strain: Isolate Germany)"
FT   VARIANT         1845
FT                   /note="H -> Q (in strain: Isolate Germany)"
FT   VARIANT         1872
FT                   /note="F -> C (in strain: Isolate Germany)"
FT   VARIANT         1904
FT                   /note="R -> K (in strain: Isolate Germany)"
FT   VARIANT         1960
FT                   /note="R -> G (in strain: Isolate Germany)"
FT   VARIANT         2091
FT                   /note="S -> N (in strain: Isolate Germany)"
SQ   SEQUENCE   2127 AA;  242770 MW;  55202B0E620305C8 CRC64;
     MLDPGEVYDD PVDPIESDAE PRGAPTVPNI LRNSDYNLNS PLIEDPARLM LEWLTTGNRP
     YRMTLTDNCS RSYKVLKDYF KKVDLGSLKV GGTAAQSMIS LWLYGAHSES NRSRKCITEL
     AHFYSKSSPI EKLLNCTLGN RGLRIPPEGV LSCLERVDYD KAFGRYLANT YSSYLFFHVI
     TLYMNALDWD EEKTILALWK ELTSVDIGKD LVKFKDQIWG LLIVTKDFVY SHSSNCLFDR
     NYTLMLKDLF LSRFNSLMIL LSPPEPRYSD DLISQLCQLY IAGDQVLSMC GNSGYEVIKI
     LEPYVVNSLV QRAERFRPLI HSLGDFPVFI KDKVSQLEGT FGPSAKRFFG VLDQFDNIHD
     LVFVYGCYRH WGHPYIDYRK GLSKLYDQVH IKKVIDKSYQ ECLASDLARR ILRWGFDKYS
     KWYLDSRLLT RDHPLTPYIK TQTWPPKHIV DLVGDTWHKL PITQIFEIPE PMDPSEILDD
     KSHSFTRARL ASWLSENRGG PAPSEKVIIT ALSKPPVNPR EFLKTIDLGG LPDEDLIIGL
     KPKERELKIE GRFFALMSWN LRLYFVITEK LLANYILPLF DALTMTDNLN KVFKKLIDRV
     TGQGLLDYSR VTYAFHLDYE KWNNHQRLES TEDVFSVLDH VFGLKRVFSR THEFFQKSWI
     YYSDRSDLIG LWEDQIYCLD MSNGPTCWNG QDGGLEGLRQ KGWSLVSLLM IDRESQTRNT
     RTKILAQGDN QVLCPTYMLS PGLSREGLLY 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 RTIRRQFRRS LSRTLEESFY NSEIHGINRM
     TQTPQRVGRV WPCSSERADL LREISWGRKV VGTTVPHPSE MLGLLPKSSI SCPCGATGGG
     NPRVSVSVLP SFDQSFFSRG PLKGYLGSST SMSTQLFHAW EKVTNVHVVK RALSLKESIN
     WFITRNSNLA QTLIRNIMSL TGPDFPLEEA PVFKRTGSAL HRFKSARYSE GGYSSVCPNL
     LSHISVSTDT MSDLTQDGKN YDFMFQPLML YAQTWTSELV QKDTRLRDST FHWHLRCNRC
     VRPIDDITLE TSQIFEFPDV SKRISRMVSG AVPHFQKLPD IRLKPGDFES LSGREKSRHI
     GSAQGLLYSI LVAIHDSGYN DGTIFPVNIY GKVSPRDYLR GLARGVLIGS SICFLTRMTN
     ININRPLELI SGVISYILLR LDNHPSLYIM LREPSLRGEI FSIPQKIPAA YPTTMKEGNR
     SILCYLQHVL RYEREVITAS PENDWLWIFS DFRSAKMTYL TLITYQSHLL LQRVERNLSK
     SMRANLRQMS SLMRQVLGGH GEDTLESDDD VQRLLKDSLR RTRWVDQEVR HAARTMTGDY
     SPNKKLSRKA GGSEWVCSAQ QVAVSTSANP APVLELDIRA LSKRFQNPLI SGLRVVQWAT
     GAHYKLKPIL DDLNVFPSLC LVVGDGSGGI SRAVLNMFPD AKLVFNSLLE VNDLMASGTH
     PLPPSAIMSG GDDIVSRVID FDSIWEKPSD LRNLTTWKYF QSVQKQVNMS YDLIICDAEV
     TDIASINRIT LLMSDFALSI DGPLYLVFKT YGTMLVNPDY KAIQHLSRAF PSVTGFITQV
     TSSFSSELYL RFSKRGKFFR DAEYLTSSTL REMSLVLFNC SSPRSEMQRA RSLNYQDLVR
     GFPEEIISNP YNEMIITLID SDVESFLVHK MVDDLELQRR TLSKVAIIIA IMIVFSNRVF
     NVSKPLTDPL FYPPSDPKIL RHFNICCSTM MYLSTALGDV PSFARLHDLY NRPITYYFRK
     QVIRGNIYLS WSWSDDTAVF KRVACNSSLS LSSHWIRLIY KIVKTTRLVG SIEDLSGEIE
     RHLRGYNRWI TLEDIRCRSS LLDYSCL