L_MEASE
ID L_MEASE Reviewed; 2183 AA.
AC P12576;
DT 01-OCT-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1989, sequence version 1.
DT 03-AUG-2022, entry version 116.
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 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 Measles virus (strain Edmonston) (MeV) (Subacute sclerose panencephalitis
OS virus).
OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Haploviricotina;
OC Monjiviricetes; Mononegavirales; Paramyxoviridae; Orthoparamyxovirinae;
OC Morbillivirus.
OX NCBI_TaxID=11235;
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2835864; DOI=10.1016/0042-6822(88)90563-6;
RA Blumberg B.M., Crowley J.C., Silverman J.I., Menonna J., Cook S.D.,
RA Dowling P.C.;
RT "Measles virus L protein evidences elements of ancestral RNA polymerase.";
RL Virology 164:487-497(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE.
RX PubMed=2596022; DOI=10.1016/0042-6822(89)90554-0;
RA Cattaneo R., Schmid A., Spielhofer P., Kaelin K., Baczko K., Meulen V.,
RA Pardowitz J., Flanagan S., Rima B.K., Udem S.A.;
RT "Mutated and hypermutated genes of persistent measles viruses which caused
RT lethal human brain diseases.";
RL Virology 173:415-425(1989).
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: Interacts with the P protein. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Virion {ECO:0000305}. Host cytoplasm
CC {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the paramyxovirus L protein family.
CC {ECO:0000305}.
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DR EMBL; M20865; AAA46430.1; -; mRNA.
DR EMBL; K01711; AAA75501.1; -; Genomic_RNA.
DR PIR; A28919; ZLNZMV.
DR SMR; P12576; -.
DR PRIDE; P12576; -.
DR Proteomes; UP000000833; Genome.
DR GO; GO:0030430; C:host cell cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0019013; C:viral nucleocapsid; IDA:CACAO.
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 Gene3D; 3.40.50.150; -; 1.
DR InterPro; IPR024352; L_methyltrans_paramyxo.
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 InterPro; IPR029063; SAM-dependent_MTases_sf.
DR Pfam; PF12803; G-7-MTase; 1.
DR Pfam; PF14318; Mononeg_mRNAcap; 1.
DR Pfam; PF00946; Mononeg_RNA_pol; 1.
DR PIRSF; PIRSF000830; RNA_pol_ParamyxoV; 1.
DR TIGRFAMs; TIGR04198; paramyx_RNAcap; 1.
DR PROSITE; PS50526; RDRP_SSRNA_NEG_NONSEG; 1.
DR PROSITE; PS51590; SAM_MT_MNV_L; 1.
PE 2: Evidence at transcript level;
KW ATP-binding; Host cytoplasm; Hydrolase; Methyltransferase; mRNA capping;
KW mRNA processing; Multifunctional enzyme; Nucleotide-binding;
KW Nucleotidyltransferase; Reference proteome; RNA-directed RNA polymerase;
KW S-adenosyl-L-methionine; Transferase; Viral RNA replication; Virion.
FT CHAIN 1..2183
FT /note="RNA-directed RNA polymerase L"
FT /id="PRO_0000142729"
FT DOMAIN 656..840
FT /note="RdRp catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00539"
FT DOMAIN 1755..1958
FT /note="Mononegavirus-type SAM-dependent 2'-O-MTase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00923"
FT BINDING 1785..1794
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255"
SQ SEQUENCE 2183 AA; 247648 MW; 1B0B03CA2E2B6EA5 CRC64;
MDSLSVNQIL YPEVHLDSPI VTNKIVAILE YARVPHAYSL EDPTLCQNIK HRLKNGFSNQ
MIINNVEVGN VIKSKLRSYP AHSHIPYPNC NQDLFNIEDK ESTRKIRELL KKGNSLYSKV
SDKVFQCLRD TNSRLGLGSE LREDIKEKVI NLGVYMHSSQ WFEPFLFWFT VKTEMRSVIK
SQTHTCHRRR HTPVFFTGSS VELLISRDLV AIISKESQHV YYLTFELVLM YCDVIEGRLM
TETAMTIDAR YTELLGRVRY MWKLIDGFFP ALGNPTYQIV AMLEPLSLAY LQLRDITVEL
RGAFLNHCFT EIHDVLDQNG FSDEGTYHEL IEALDYIFIT DDIHLTGEIF SFFRSFGHPR
LEAVTAAENV RKYMNQPKVI VYETLMKGHA IFCGIIINGY RDRHGGSWPP LTLPLHAADT
IRNAQASGEG LTHEQCVDNW KSFAGVKFGC FMPLSLDSDL TMYLKDKALA ALQREWDSVY
PKEFLRYDPP KGTGSRRLVD VFLNDSSFDP YDVIMYVVSG AYLHDPEFNL SYSLQEKEIK
ETGRLFAKMT YKMRACQVIA ENLISNGIGK YFKDNGMAKD EQDLTKALHT LAVSGVPKDL
KESHRGGPVL KTYSRSPVHT STRNVRAAKG FIGFPQVIRQ DQDTDHPENM EAYETVSAFI
TTDLKKYCLN WRYETISLFA QRLNEIYGLP SFFQWLHKRL ETSVLYVSDP HCPPDLDAHI
PLYKVPNDQI FIKYPMGGIE GYCQKLWTIS TIPYLYLAAY ESGVRIASLV QGDNQTIAVT
KRVPSTWPYN LKKREAARVT RDYFVILRQR LHDIGHHLKA NETIVSSHFF VYSKGIYYDG
LLVSQSLKSI ARCVFWSETI VDETRAACSN IATTMAKSIE RGYDRYLAYS LNFLKVIQQI
LISLGFTINS TMTRDVVIPL LTNNDLLIRM ALLPAPIGGM NYLNMSRLFV RNIGDPVTSS
IADLKRMILA SLMPEETLHQ VMTQQPGDSS FLDWASDPYS ANLVCVQSIT RLLKNITARF
VLIHSPNPML KGLFHDDSKE EDEGLAAFLM DRHIIVPRAA HEILDHSVTG ARESIAGMLD
TTKGLIRASM RKGGLTSRVI TRLSNYDYEQ FRAGMVLLTG RKRNVLIDKE SCSVQLARAL
RSHMWARLAR GRPIYGLEVP DVLESMRGHL IRRHETCVIC ECGSVNYGWF FVPSGCQLDD
IDKETSSLRV PYIGSTTDER TDMKLAFVRA PSRSLRSAVR IATVYSWAYG DDDSSWNEAW
LLARQRANVS LEELRVITPI STSTNLAHRL RDRSTQVKYS GTSLVRVARY TTISNDNLSF
VISDKKVDTN FIYQQGMLLG LGVLETLFRL EKDTGSSNTV LHLHVETDCC VIPMIDHPRI
PSSRKLELRA ELCTNPLIYD NAPLIDRDAT RLYTQSHRRH LVEFVTWSTP QLYHILAKST
ALSMIDLVTK FEKDHMNEIS ALIGDDDINS FITEFLLIEP RLFTIYLGQC AAINWAFDVH
YHRPSGKYQM GELLSSFLSR MSKGVFKVLV NALSHPKIYK KFWHCGIIEP IHGPSLDAQN
LHTTVCNMVY TCYMTYLDLL LNEELEEFTF LLCESDEDVV PDRFDNIQAK HLCVLADLYC
QPGTCPPIQG LRPVEKCAVL TDHIKAEAML SPAGSSWNIN PIIVDHYSCS LTYLRRGSIK
QIRLRVDPGF IFDALAEVNV SQPKIGSNNI SNMSIKAFRP PHDDVAKLLK DINTSKHNLP
ISGGNLANYE IHAFRRIGLN SSACYKAVEI STLIRRCLEP GEDGLFLGEG SGSMLITYKE
ILKLSKCFYN SGVSANSRSG QRELAPYPSE VGLVEHRMGV GNIVKVLFNG RPEVTWVGSV
DCFNFIVSNI PTSSVGFIHS DIETLPDKDT IEKLEELAAI LSMALLLGKI GSILVIKLMP
FSGDFVQGFI SYVGSHYREV NLVYPRYSNF ISTESYLVMT DLKANRLMNP EKIKQQIIES
SVRTSPGLIG HILSIKQLSC IQAIVGDAVS RGDINPTLKK LTPIEQVLIN CGLAINGPKL
CKELIHHDVA SGQDGLLNSI LILYRELARF KDNQRSQQGM FHAYPVLVSS RQRELISRIT
RKFWGHILLY SGNRKLINKF IQNLKSGYLI LDLHQNIFVK NLSKSEKQII MTGGLKREWV
FKVTVKETKE WYKLVGYSAL IKD
