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Information on EC 2.7.7.48 - RNA-directed RNA polymerase and Organism(s) West Nile virus and UniProt Accession P06935
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2.7.7.48 RNA-directed RNA polymeraseIUBMB Comments
Catalyses RNA-template-directed extension of the 3'- end of an RNA strand by one nucleotide at a time. Can initiate a chain de novo. See also EC 2.7.7.6 DNA-directed RNA polymerase.
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Word Map
- 2.7.7.48
- viruses
- strand
-
rnaps
-
single-stranded
- bacteriophage
- chromatin
- vaccine
- infectious
-
holoenzyme
- rrna
- helicase
- dsrnas
- ribonucleoproteins
- virion
- coronavirus
-
dna-dependent
-
outbreak
- replicons
- covid-19
- polyproteins
-
footprint
-
polyadenylation
- fever
- dengue
- pandemic
- polya
- nucleocapsids
-
serotype
- ribavirin
-
sequence-specific
- pre-mrnas
-
virological
-
non-structural
- duplex
-
stem-loops
- nucleoprotein
-
virus-infected
-
supercoiled
- rifampicin
-
unwind
-
virus-like
-
nucleolar
-
non-nucleoside
- gastroenteritis
- encephalitis
-
stall
-
anti-hcv
- dicer
-
virus-specific
- rotavirus
- synthesis
- drug development
- pharmacology
- medicine
- analysis
- molecular biology
The taxonomic range for the selected organisms is: West Nile virus
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Synonyms
rna polymerase, rna-binding protein, rna-dependent rna polymerase, rdrp, nonstructural protein, transcriptase, vp1 protein, pol iv, rna-dependent rna polymerases, ns5b polymerase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
111 kDa protein
-
-
-
-
180 kDa protein
-
-
-
-
182 kDa protein
-
-
-
-
183 kDa protein
-
-
-
-
186 kDa protein
-
-
-
-
216.5 kDa protein
-
-
-
-
2A protein
-
-
-
-
3D pol
-
-
-
-
3D polymerase
-
-
-
-
69.6 kDa protein
-
-
-
-
core protein
-
-
-
-
core protein VP1
-
-
-
-
inner layer protein VP1
-
-
-
-
L protein
-
-
-
-
large structural protein
-
-
-
-
M1 phosphoprotein
-
-
-
-
NIB
-
-
-
-
nonstructural phosphoprotein
-
-
-
-
nonstructural protein
-
-
-
-
nonstructural protein 5B
-
-
-
-
NS5
NS5B
-
-
-
-
NS5B protein
-
-
-
-
nucleocapsid phosphoprotein
-
-
-
-
nucleotidyltransferase, ribonucleate, RNA-dependent
-
-
-
-
ORF1
-
-
-
-
ORF1A
-
-
-
-
ORF1B
-
-
-
-
P protein
-
-
-
-
P180
-
-
-
-
P3D
-
-
-
-
P66
-
-
-
-
P70
-
-
-
-
P88 protein
-
-
-
-
PB1
-
-
-
-
PB1 proteins
-
-
-
-
PB2
-
-
-
-
PB2 proteins
-
-
-
-
Phage f2 replicase
-
-
-
-
Pol
-
-
-
-
polymerase acidic protein
-
-
-
-
polymerase basic 1 protein
-
-
-
-
polymerase L
-
-
-
-
proteins PB1
-
-
-
-
proteins, PB 2
-
-
-
-
proteins, specific or class, lambda3, of reovirus
-
-
-
-
proteins, specific or class, PB 1
-
-
-
-
proteins, specific or class, PB 2
-
-
-
-
Q-beta replicase
-
-
-
-
Qbeta replicase
-
-
-
-
Qbeta-replicase
-
-
-
-
RDRP
replicase, phage f2
-
-
-
-
replicase, Qbeta
-
-
-
-
ribonucleic acid replicase
-
-
-
-
ribonucleic acid-dependent ribonucleate nucleotidyltransferase
-
-
-
-
ribonucleic acid-dependent ribonucleic acid polymerase
-
-
-
-
ribonucleic replicase
-
-
-
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ribonucleic synthetase
-
-
-
-
RNA nucleotidyltransferase (RNA-directed)
-
-
-
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RNA replicase
-
-
-
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RNA synthetase
-
-
-
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RNA transcriptase
-
-
-
-
RNA-binding protein
-
-
-
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RNA-dependent ribonucleate nucleotidyltransferase
-
-
-
-
RNA-dependent RNA polymerase
RNA-dependent RNA replicase
-
-
-
-
RNA-directed RNA polymerase
-
-
-
-
sigma NS protein
-
-
-
-
transcriptase
-
-
-
-
VP1
-
-
-
-
VP1 protein
-
-
-
-
NS5
-
consists of a C-terminal RNA-dependent RNA polymerase domain and an N-terminal methyltransferase domain
RDRP
-
-
-
-
RNA-dependent RNA polymerase
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
nucleotidyl group transfer
-
-
-
-
SYSTEMATIC NAME
IUBMB Comments
nucleoside-triphosphate:RNA nucleotidyltransferase (RNA-directed)
Catalyses RNA-template-directed extension of the 3'- end of an RNA strand by one nucleotide at a time. Can initiate a chain de novo. See also EC 2.7.7.6 DNA-directed RNA polymerase.
CAS REGISTRY NUMBER
COMMENTARY
9026-28-2
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
nucleoside triphosphate + RNAn
diphosphate + RNAn+1
-
both 5'- and 3'-terminal regions of the (+)-strand RNA template including the wild type cyclization motifs are important for RNA synthesis. However, the 3'-terminal region of the (-)-strand RNA template alone is sufficient for RNA synthesis. The (+)-strand 5'-cyclization motif is critical for (-)-strand RNA synthesis but neither the (-)-strand 5'- nor 3'-cyclization motif is important for the (+)-strand RNA synthesis. Cyclization of the viral RNA play a role for (-)-strand RNA synthesis but not for (+)-strand RNA synthesis
-
-
?
additional information
?
-
NS5 is the largest and the most conserved of the flavivirus proteins. It contains an N-terminal methyl transferase domain and a C-terminal RdRp domain. The main enzymatic activity observed in extracts of infected cells with endogenous templates is the elongation of already initiated RNA synthesis
-
-
?
additional information
?
-
formation of an RNA-RNA complex between the 5' and 3' terminal nucleotides of the viral genome is necessary for polymerase activity, template specificity for a flavivirus RdRp, analysis and mechanism, overview. Viral protein NS5 has the ability to bind RNA with high affinity
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
additional information
?
-
NS5 is the largest and the most conserved of the flavivirus proteins. It contains an N-terminal methyl transferase domain and a C-terminal RdRp domain. The main enzymatic activity observed in extracts of infected cells with endogenous templates is the elongation of already initiated RNA synthesis
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Mn2+
-
0.05 mM, 40% of the activity compared to reaction with 3 mM Mg2+. 5.0 mM, 70% of the activity compared to the reaction with 3 mM Mg2+, Mn2+ is present as the sole divalent cation
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Mn2+
-
concentrations of 1.0 mM, 0.5 mM and 0.05 mM in the presence of Mg2+ inhibit activity by 75%, 50% and 25%, respectively
remdesivir triphosphate
-
remdesivir or its derivatives have the potential to become broad-spectrum antiviral agent effective against many RNA viruses
additional information
-
the 5'-cap inhibits the (-)-strand RNA synthesis from the 3'-fold-back structure of (+)-strand RNA template without affecting the de novo synthesis of RNA
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00166
remdesivir triphosphate
West Nile virus
-
pH and temperature not specified in the publication
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.6 - 8.4
-
pH 7.6: about 80% of maximal activity, pH 8.4: about 65% of maximal activity, in Tris hydrochloride buffer
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
additional information
RdRp activity is associated with heavy cytoplasmic membrane fractions in the host cell
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
physiological function
-
Flavivirus replication occurs on the ER and is regulated by many mechanisms and factors. NS5, which consists of a C-terminal RNA-dependent RNA polymerase (RdRp) domain and an N-terminal methyltransferase domain, plays a pivotal role in genome replication and capping. The C-terminal RdRp domain acts as the polymerase for RNA synthesis and cooperates with diverse viral proteins to facilitate productive RNA proliferation within the replication complex. RdRp recognizes the initiation site of the genome via an RdRp-UTR interaction, the interaction between RdRp and NS3 promotes NTPase and helicase activity, and the interaction between the RdRp and the MTase is involved in new RNA synthesis. The RdRp is indispensable for flavivirus replication because of not only its own polymerase activity, but also its interactions with other viral proteins and RNAs, which leads to efficient genomic RNA replication
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). POLG_WNV
3430
20
380110
Swiss-Prot
other Location (Reliability: 5)
PDB
SCOP
CATH
UNIPROT
ORGANISM
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
A365N
mutation selected to stabilize the secondary structural elements near the rNTP binding pocket of the enzyme. Mutant viruses were tested in vitro on Vero, C6/36, Culex tarsalis and DF-1 cell types and in vivo in one day old chickens and Culex pipiens mosquitoes. Mutation affects plaque morphology and particularly alters growth and RNA replication kinetics
T363N
mutation selected to stabilize the secondary structural elements near the rNTP binding pocket of the enzyme. Mutant viruses were tested in vitro on Vero, C6/36, Culex tarsalis and DF-1 cell types and in vivo in one day old chickens and Culex pipiens mosquitoes. Mutation affects plaque morphology and alters growth and RNA replication kinetics
T537I
mutation selected to stabilize the secondary structural elements near the rNTP binding pocket of the enzyme. Mutant viruses were tested in vitro on Vero, C6/36, Culex tarsalis and DF-1 cell types and in vivo in one day old chickens and Culex pipiens mosquitoes. Mutation affects plaque morphology and alters growth and RNA replication kinetics
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Grun, J.B.; Brinton, M.A.
Characterization of West Nile virus RNA-dependent RNA polymerase and cellular terminal adenylyl and uridylyl transferases in cell-free extracts
J. Virol.
60
1113-1124
1986
West Nile virus
Nomaguchi, M.; Teramoto, T.; Yu, L.; Markoff, L.; Padmanabhan, R.
Requirements for West Nile virus (-)- and (+)-strand subgenomic RNA synthesis in vitro by the viral RNA-dependent RNA polymerase expressed in Escherichia coli
J. Biol. Chem.
279
12141-12151
2004
West Nile virus
Villordo, S.M.; Gamarnik, A.V.
Genome cyclization as strategy for flavivirus RNA replication
Virus Res.
139
230-239
2009
Dengue virus, Japanese encephalitis virus, Yellow fever virus, Saint Louis encephalitis virus, West Nile virus (P06935), Japanese encephalitis virus JEV, Saint Louis encephalitis virus SLEV, Dengue virus DENV, West Nile virus WNV (P06935)
Van Slyke, G.A.; Ciota, A.T.; Willsey, G.G.; Jaeger, J.; Shi, P.Y.; Kramer, L.D.
Point mutations in the West Nile virus (Flaviviridae; Flavivirus) RNA-dependent RNA polymerase alter viral fitness in a host-dependent manner in vitro and in vivo
Virology
427
18-24
2012
West Nile virus (Q8JU43), West Nile virus, West Nile virus 3356 (Q8JU43)
Konkolova, E.; Dejmek, M.; Hrebabecky, H.; Sala, M.; Boeserle, J.; Nencka, R.; Boura, E.
Remdesivir triphosphate can efficiently inhibit the RNA-dependent RNA polymerase from various flaviviruses
Antiviral Res.
182
104899
2020
Japanese encephalitis virus, West Nile virus, Yellow fever virus, Dengue virus type 3, Tick-borne encephalitis virus (Q01299), Zika virus (Q32ZE1)
Duan, Y.; Zeng, M.; Jiang, B.; Zhang, W.; Wang, M.; Jia, R.; Zhu, D.; Liu, M.; Zhao, X.; Yang, Q.; Wu, Y.; Zhang, S.; Liu, Y.; Zhang, L.; Yu, Y.; Pan, L.; Chen, S.; Cheng, A.
Flavivirus RNA-dependent RNA polymerase interacts with genome UTRs and viral proteins to facilitate flavivirus RNA replication
Viruses
11
929
2019
Japanese encephalitis virus, West Nile virus, Yellow fever virus, Dengue virus type 2, Dengue virus type 4, dengue virus type I, Zika virus, Dengue virus type 3
EXTERNAL LINKS (specific for EC-Number 2.7.7.48)
Transporter Classification Database (TCDB): 1.G.3.1.7, 1.A.53.1.5, 1.A.85.1.6, 1.A.122.1.2, 1.A.53.1.7, 1.A.85.1.7, 1.G.3.1.2, 1.G.3.1.1, 1.A.85.1.4, 1.A.85.1.8, 1.A.53.1.11, 1.A.53.1.6, 1.A.85.1.1
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