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Information on EC 2.7.7.48 - RNA-directed RNA polymerase and Organism(s) Dengue virus type 2 and UniProt Accession P29991

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EC Tree
IUBMB 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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This record set is specific for:
Dengue virus type 2
UNIPROT: P29991
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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
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
111 kDa protein
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-
-
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180 kDa protein
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-
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182 kDa protein
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-
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183 kDa protein
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-
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186 kDa protein
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-
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216.5 kDa protein
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-
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2A protein
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-
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3D pol
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-
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3D polymerase
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-
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69.6 kDa protein
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-
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core protein
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-
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core protein VP1
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inner layer protein VP1
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L protein
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-
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large structural protein
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-
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M1 phosphoprotein
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-
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NIB
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-
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nonstructural phosphoprotein
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nonstructural protein
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nonstructural protein 5B
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NS5
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consists of a C-terminal RNA-dependent RNA polymerase domain and an N-terminal methyltransferase domain
NS5B
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NS5B protein
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nucleocapsid phosphoprotein
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nucleotidyltransferase, ribonucleate, RNA-dependent
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ORF1
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ORF1A
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ORF1B
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P protein
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-
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P180
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-
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P3D
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-
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P66
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-
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P70
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-
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P88 protein
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-
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PB1
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-
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PB1 proteins
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-
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PB2
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PB2 proteins
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Phage f2 replicase
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Pol
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polymerase acidic protein
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polymerase basic 1 protein
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polymerase L
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proteins PB1
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proteins, PB 2
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proteins, specific or class, lambda3, of reovirus
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proteins, specific or class, PB 1
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proteins, specific or class, PB 2
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Q-beta replicase
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Qbeta replicase
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Qbeta-replicase
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replicase, phage f2
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replicase, Qbeta
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ribonucleic acid replicase
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ribonucleic acid-dependent ribonucleate nucleotidyltransferase
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ribonucleic acid-dependent ribonucleic acid polymerase
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ribonucleic replicase
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ribonucleic synthetase
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RNA nucleotidyltransferase (RNA-directed)
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RNA replicase
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RNA synthetase
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RNA transcriptase
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RNA-binding protein
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RNA-dependent ribonucleate nucleotidyltransferase
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RNA-dependent RNA polymerase
RNA-dependent RNA replicase
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RNA-directed RNA polymerase
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sigma NS protein
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transcriptase
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VP1
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VP1 protein
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
nucleotidyl group transfer
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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 hide
9026-28-2
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SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
nucleoside triphosphate + RNAn
diphosphate + RNAn+1
show the reaction diagram
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-
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
nucleoside triphosphate + RNAn
diphosphate + RNAn+1
show the reaction diagram
-
-
-
-
?
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
2'-C-ethynyl-2'-fluoro-uridine triphosphate
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2'-C-ethynyl-4'-fluoro-uridine triphosphate
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2'-C-ethynyl-uridine triphosphate
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2'-C-methyl-4'-fluoro-uridine triphosphate
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2'-C-methyl-uridine triphosphate
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2'-C-propynyl-4'-fluoro-uridine triphosphate
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2'-C-propynyl-uridine triphosphate
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propan-2-yl (2S)-2-([([(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-3,4-dihydroxy-4-(prop-1-yn-1-yl)oxolan-2-yl]methoxy)(phenoxy)phosphoryl]amino)propanoate
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propan-2-yl (2S)-2-([([(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-3,4-dihydroxy-4-methyloxolan-2-yl]methoxy)(phenoxy)phosphoryl]amino)propanoate
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propan-2-yl (2S)-2-([([(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-4-ethynyl-3,4-dihydroxyoxolan-2-yl]methoxy)(phenoxy)phosphoryl]amino)propanoate
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propan-2-yl (2S)-2-([([(2S,3S,4R,5R)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-fluoro-3,4-dihydroxy-4-(prop-1-yn-1-yl)oxolan-2-yl]methoxy)(phenoxy)phosphoryl]amino)propanoate
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propan-2-yl (2S)-2-([([(2S,3S,4R,5R)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-fluoro-3,4-dihydroxy-4-methyloxolan-2-yl]methoxy)(phenoxy)phosphoryl]amino)propanoate
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propan-2-yl (2S)-2-([([(2S,3S,4R,5R)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-4-ethynyl-2-fluoro-3,4-dihydroxyoxolan-2-yl]methoxy)(phenoxy)phosphoryl]amino)propanoate
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the prodrug displays potent anti-dengue virus activity in the primary human peripheral blood mononuclear cell-based assay with no significant cytotoxicity in human hepatocellular liver carcinoma cell lines and no mitochondrial toxicity in the cell-based assay using human prostate cancer cell lines
sofosbuvir
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sofosbuvir triphosphate
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IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0159
2'-C-ethynyl-2'-fluoro-uridine triphosphate
Dengue virus type 2
-
pH and temperature not specified in the publication
0.00065
2'-C-ethynyl-4'-fluoro-uridine triphosphate
Dengue virus type 2
-
pH and temperature not specified in the publication
0.0016
2'-C-ethynyl-uridine triphosphate
Dengue virus type 2
-
pH and temperature not specified in the publication
0.0066
2'-C-methyl-4'-fluoro-uridine triphosphate
Dengue virus type 2
-
pH and temperature not specified in the publication
0.005
2'-C-methyl-uridine triphosphate
Dengue virus type 2
-
pH and temperature not specified in the publication
0.0028
2'-C-propynyl-4'-fluoro-uridine triphosphate
Dengue virus type 2
-
pH and temperature not specified in the publication
0.002
2'-C-propynyl-uridine triphosphate
Dengue virus type 2
-
pH and temperature not specified in the publication
0.0019
propan-2-yl (2S)-2-([([(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-3,4-dihydroxy-4-(prop-1-yn-1-yl)oxolan-2-yl]methoxy)(phenoxy)phosphoryl]amino)propanoate
Dengue virus type 2
-
pH and temperature not specified in the publication
0.00019
propan-2-yl (2S)-2-([([(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-3,4-dihydroxy-4-methyloxolan-2-yl]methoxy)(phenoxy)phosphoryl]amino)propanoate
Dengue virus type 2
-
pH and temperature not specified in the publication
0.00045
propan-2-yl (2S)-2-([([(2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-4-ethynyl-3,4-dihydroxyoxolan-2-yl]methoxy)(phenoxy)phosphoryl]amino)propanoate
Dengue virus type 2
-
pH and temperature not specified in the publication
0.009
propan-2-yl (2S)-2-([([(2S,3S,4R,5R)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-fluoro-3,4-dihydroxy-4-(prop-1-yn-1-yl)oxolan-2-yl]methoxy)(phenoxy)phosphoryl]amino)propanoate
Dengue virus type 2
-
pH and temperature not specified in the publication
0.0011
propan-2-yl (2S)-2-([([(2S,3S,4R,5R)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-fluoro-3,4-dihydroxy-4-methyloxolan-2-yl]methoxy)(phenoxy)phosphoryl]amino)propanoate
Dengue virus type 2
-
pH and temperature not specified in the publication
0.00057
propan-2-yl (2S)-2-([([(2S,3S,4R,5R)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-4-ethynyl-2-fluoro-3,4-dihydroxyoxolan-2-yl]methoxy)(phenoxy)phosphoryl]amino)propanoate
Dengue virus type 2
-
pH and temperature not specified in the publication
0.0012
sofosbuvir
Dengue virus type 2
-
pH and temperature not specified in the publication
0.018
sofosbuvir triphosphate
Dengue virus type 2
-
pH and temperature not specified in the publication
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
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
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Wang, G.; Lim, S.P.; Chen, Y.L.; Hunziker, J.; Rao, R.; Gu, F.; Seh, C.C.; Ghafar, N.A.; Xu, H.; Chan, K.; Lin, X.; Saunders, O.L.; Fenaux, M.; Zhong, W.; Shi, P.Y.; Yokokawa, F.
Structure-activity relationship of uridine-based nucleoside phosphoramidate prodrugs for inhibition of dengue virus RNA-dependent RNA polymerase
Bioorg. Med. Chem. Lett.
28
2324-2327
2018
Dengue virus type 2
Manually annotated by BRENDA team
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
Manually annotated by BRENDA team