ID   L_MUMPM                 Reviewed;        2261 AA.
AC   P30929; Q783V6;
DT   01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
DT   01-JUL-1993, sequence version 1.
DT   02-SEP-2026, entry version 128.
DE   RecName: Full=RNA-directed RNA polymerase L;
DE            Short=Protein L;
DE   AltName: Full=Large structural protein;
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     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   Mumps virus genotype B (strain Miyahara vaccine) (MuV).
OC   Viruses; Riboviria; Orthornavirae; Negarnaviricota; Haploviricotina;
OC   Monjiviricetes; Mononegavirales; Paramyxoviridae; Rubulavirinae;
OC   Orthorubulavirus; Orthorubulavirus parotitidis; Mumps orthorubulavirus.
OX   NCBI_TaxID=11171;
OH   NCBI_TaxID=9606; Homo sapiens (Human).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX   PubMed=1585659; DOI=10.1016/0042-6822(92)90555-4;
RA   Okazaki K., Tanabayashi K., Takeuchi K., Hishiyama M., Okazaki K.,
RA   Yamada A.;
RT   "Molecular cloning and sequence analysis of the mumps virus gene encoding
RT   the L protein and the trailer sequence.";
RL   Virology 188:926-930(1992).
RN   [2]
RP   INTERACTION WITH THE HOST RUVBL1, AND INTERACTION WITH THE HOST RUVBL2.
RX   PubMed=31121004; DOI=10.1371/journal.ppat.1007749;
RA   Katoh H., Sekizuka T., Nakatsu Y., Nakagawa R., Nao N., Sakata M., Kato F.,
RA   Kuroda M., Kidokoro M., Takeda M.;
RT   "The R2TP complex regulates paramyxovirus RNA synthesis.";
RL   PLoS Pathog. 15:e1007749-e1007749(2019).
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 concomitant 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=RNA(n) + a ribonucleoside 5'-triphosphate = RNA(n+1) +
CC         diphosphate; 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 + S-adenosyl-L-methionine = a 5'-end (5'-
CC         triphosphoguanosine)-(2'-O-methyladenylyl)-adenylyl-cytidylyl-
CC         adenosine in mRNA + S-adenosyl-L-homocysteine + H(+);
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 + phosphate + H(+); 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: Interacts with the P protein (By similarity). Interacts with
CC       host RUVBL1 and RUVBL2 (R2TP complex); this interaction regulates the
CC       viral transcription (PubMed:31121004). {ECO:0000250|UniProtKB:C0JJA4,
CC       ECO:0000269|PubMed:31121004}.
CC   -!- SUBCELLULAR LOCATION: Virion {ECO:0000250|UniProtKB:C0JJA4}.
CC   -!- SIMILARITY: Belongs to the paramyxovirus L protein family.
CC       {ECO:0000305}.
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DR   EMBL; D10575; BAA01432.1; -; Genomic_RNA.
DR   EMBL; AB040874; BAA94391.1; -; Genomic_RNA.
DR   PIR; A42548; A42548.
DR   AlphaFoldDB; P30929; -.
DR   SMR; P30929; -.
DR   KEGG; vg:1489763; -.
DR   Proteomes; UP000002331; Segment.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0003924; F:GTPase activity; ISS:UniProtKB.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0004482; F:mRNA 5'-cap (guanine-N7-)-methyltransferase activity; IEA:InterPro.
DR   GO; GO:0062105; F:RNA 2'-O-methyltransferase activity; IEA:RHEA.
DR   GO; GO:0003968; F:RNA-directed RNA polymerase activity; IEA:UniProtKB-KW.
DR   Gene3D; 3.40.50.12760; -; 1.
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; IPR016269; RNA-dir_pol_paramyxovirus.
DR   NCBIfam; TIGR04198; paramyx_RNAcap; 1.
DR   Pfam; PF14318; Mononeg_mRNAcap; 1.
DR   Pfam; PF00946; Mononeg_RNA_pol; 1.
DR   PIRSF; PIRSF000830; RNA_pol_ParamyxoV; 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; Hydrolase; Magnesium; Metal-binding; Methyltransferase;
KW   mRNA capping; mRNA processing; Multifunctional enzyme; Nucleotide-binding;
KW   Nucleotidyltransferase; Reference proteome; RNA-directed RNA polymerase;
KW   S-adenosyl-L-methionine; Transferase; Viral RNA replication; Virion; Zinc.
FT   CHAIN           1..2261
FT                   /note="RNA-directed RNA polymerase L"
FT                   /id="PRO_0000142730"
FT   DOMAIN          662..846
FT                   /note="RdRp catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00539"
FT   DOMAIN          1781..1994
FT                   /note="Mononegavirus-type SAM-dependent 2'-O-MTase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00923"
FT   REGION          630..651
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          919..1405
FT                   /note="PRNTase"
FT                   /evidence="ECO:0000250|UniProtKB:C0JJA4"
FT   REGION          1222..1258
FT                   /note="priming-capping loop"
FT                   /evidence="ECO:0000250|UniProtKB:P03523"
FT   ACT_SITE        1298
FT                   /note="Nucleophile; for GDP polyribonucleotidyltransferase"
FT                   /evidence="ECO:0000250|UniProtKB:P03523"
FT   ACT_SITE        1792
FT                   /note="For mRNA (guanine-N(7)-)-methyltransferase and mRNA
FT                   (nucleoside-2'-O-)-methyltransferase"
FT                   /evidence="ECO:0000250|UniProtKB:Q06996"
FT   ACT_SITE        1917
FT                   /note="For mRNA (guanine-N(7)-)-methyltransferase and mRNA
FT                   (nucleoside-2'-O-)-methyltransferase"
FT                   /evidence="ECO:0000250|UniProtKB:Q06996"
FT   ACT_SITE        1953
FT                   /note="For mRNA (guanine-N(7)-)-methyltransferase and mRNA
FT                   (nucleoside-2'-O-)-methyltransferase"
FT                   /evidence="ECO:0000250|UniProtKB:P03523"
FT   ACT_SITE        1990
FT                   /note="For mRNA (guanine-N(7)-)-methyltransferase and mRNA
FT                   (nucleoside-2'-O-)-methyltransferase"
FT                   /evidence="ECO:0000250|UniProtKB:Q06996"
FT   BINDING         669
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /ligand_note="catalytic; for RNA-directed RNA polymerase
FT                   activity"
FT                   /evidence="ECO:0000250|UniProtKB:P28887"
FT   BINDING         779
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /ligand_note="catalytic; for RNA-directed RNA polymerase
FT                   activity"
FT                   /evidence="ECO:0000250|UniProtKB:P28887"
FT   BINDING         1142
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /ligand_note="structural"
FT                   /evidence="ECO:0000250|UniProtKB:C0JJA4"
FT   BINDING         1174
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /ligand_note="structural"
FT                   /evidence="ECO:0000250|UniProtKB:C0JJA4"
FT   BINDING         1187
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /ligand_note="structural"
FT                   /evidence="ECO:0000250|UniProtKB:C0JJA4"
FT   BINDING         1190
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /ligand_note="structural"
FT                   /evidence="ECO:0000250|UniProtKB:C0JJA4"
FT   BINDING         1372
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /ligand_note="structural"
FT                   /evidence="ECO:0000250|UniProtKB:C0JJA4"
FT   BINDING         1374
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /ligand_note="structural"
FT                   /evidence="ECO:0000250|UniProtKB:C0JJA4"
FT   BINDING         1379
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /ligand_note="structural"
FT                   /evidence="ECO:0000250|UniProtKB:C0JJA4"
FT   BINDING         1380
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /ligand_note="structural"
FT                   /evidence="ECO:0000250|UniProtKB:C0JJA4"
FT   BINDING         1811..1820
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255"
SQ   SEQUENCE   2261 AA;  256575 MW;  A789F54BFC1EB5EB CRC64;
     MAGLNEILLP EVHLNSPIVR YKLFYYILHG QLPNDLEPDD LGPLANQNWK AIRAEESQVH
     ARLKQIRVEL IARIPSLRWT RSQREIAILI WPRILPILQA YDLRQSMQLP TVWEKLTQST
     VNLISDGLER VVLHISNQLT GKPNLFTRSR AGQDVKDYSI PSTRELSQIW FNNEWSGSVK
     TWLMIKYRMR QLITNQKTGE LTDLVTIVDT RSTLCIIAPE LVALYSNEHK ALTYLTFEMV
     LMVTDMLEGR LNVSSLCTAS HYLSPLKKRI EILLTLVDDL ALLMGDKVYG VVSSLESFVY
     AQLQYGDPVV DIKGTFYGFI CNEILDLLTE DNIFTEEEAN KVLLDLTSQF DNLSPDLTAE
     LLCIMRLWGH PTLTASQAAS KVRESMCAPK VLDFQTIMKT LAFFHAILIN GYRRSHNGIW
     PPTTLHGNAP KSLIEMRHDN SELKYEYVLK NWKSISMLRI HKCFDASPDE DLSIFMKDKA
     ISCPKQDWMG VFRRSLIKQR YRDANRPLPQ PFNRRLLLNF LEDDRFDPIK ELEYVTSGEY
     LRDPEFCASY SLKEKEIKAT GRIFAKMTKR MRSCQVIAES LLANHAGKLM RENGVVLDQL
     KLTKSLLTMN QIGIISEHSR RSTADNMTLA HSGSNKHRIN NSQFKKNKDS KHEMPDDGFE
     IAACFLTTDL TKYCLNWRYQ VIIPFARTLN SMYGIPHLFE WIHLRLMRST LYVGDPFNPP
     SDPTQLDLDT ALNDDIFIVS PRGGIEGLCQ KLWTMISIST IILSATEANT RVMSMVQGDN
     QAIAITTRVV RSLSHSEKKE QAYKASKLFF ERLRANNHGI GHHLKEQETI LSSDFFIYSK
     RVFYKGRILT QALKNVSKMC LTADILGDCS QASCSNLATT VMRLTENGVE KDLCYFLNAF
     MTIRQLCYDL VFPQTKSLSQ DITNAYLNHP ILISRLCLLP SQLGGLNFLS CSRLFNRNIG
     DPLVSAIADV KRLIKAGCLD IWVLYNILGR RPGKGKWSTL AADPYTLNID YLVPSKTFLK
     KHAQYTLMER SVNPMLRGVF SENAAEEEEE LAQYLLDREV VMPRVAHVIL AQSSCGRRKQ
     IQGYLDSTRT IIRYSLEVRP LSAKKLNTVI EYNLLYLSYN LEIIEKPNIV QPFLNAINVD
     TCSIDIARSL RKLSWATLLN GRPIEGLETP DPIELVHGCL IIGSDECEHC SSGDDKFTWF
     FLPKGIRLDN DPASNPPIRV PYIGSKTDER RVASMAYIKG ASVSLKSALR LAGVYIWAFG
     DTEESWQDAY ELASTRVNLT LEQLQSLTPL PTSANLVHRL DDGTTQLKFT PASSYAFSSF
     VHISNDCQVL EIDDQVTDSN LIYQQVMITG LALIETWNNP PINFSVYETT LHLHTGSSCC
     IRPVESCVVN PPLLPVPFIN VPQMNKFVYD PEPLSLLEME KIEDIAYQTR IGGLDQIPLL
     EKIPLLAHLT AKQMVNSITG LDEATSIVND AVVQADYTSN WISECCYTYI DSVFVYSGWA
     LLLELSYQMY YLRIQGIQGI LDYVYMTLRR IPGMAITGIS STISHPRILR RCINLDVIAP
     INSPHIASLD YTKLSIDAVM WGTKQVLTNI SQGIDYEIVV PSESQLTLSD RVLNLVARKL
     SLLAIIWANY NYPPKVKGMS PEDKCQALTT HLLQTVEYVE HIQIEKTNIR RMIIEPKLTA
     YPSNLFYLSR KLLNAIRDSE EGQFLIASYY NSFGYLEPIL MESKIFNLSS SESASLTEFD
     FILNLELSEA SLEKYSLPSL LMTAENMDNP FPQPPLHHVL RPLGLSSTSW YKTISVLNYI
     SHMKISDGAH LYLAEGSGAS MSLIETFLPG EIIWYNSLFN SGENPPQRNF APLPTQFIES
     VPYRLIQAGI AAGSGVVQSF YPLWNGNSDI TDLSTKTSVE YIIHKVGADT CALVHVDLEG
     VPGSMNSMLE RAQVHALLIT VTVLKPGGLL ILKASWEPFN RFSFLLTILW QFSSTIRILR
     SSYSDPNNHE VYIIATLAVD PTTSSFTTAL NRARTLNEQG FSLIPPELVS EYWRRRVEQG
     QIIQDCIDKV ISECVRDQYL ADNNIILQAG GTPSTRKWLD LPDYLSFNEL QSEMARLITI
     HLKEVIEILK GQSSDHDTLL FTSYNVGPLG KINTILRLIV ERILMYTVRN WCILPTQTRL
     TLRQSIELGE FRLRDVITPM EILKLSPNRK YLKSALNQST FNHLMGETSD ILLNRSYQKR
     IWKAIGCVIY CFGLLTPDVE DSERIDIDND IPDYDIHGDI I
//