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Protein

Genome polyprotein

Gene
N/A
Organism
Dengue virus type 2 (strain Thailand/NGS-C/1944) (DENV-2)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Capsid protein C: Plays a role in virus budding by binding to the cell membrane and gathering the viral RNA into a nucleocapsid that forms the core of a mature virus particle. During virus entry, may induce genome penetration into the host cytoplasm after hemifusion induced by the surface proteins. Can migrate to the cell nucleus where it modulates host functions. Overcomes the anti-viral effects of host EXOC1 by sequestering and degrading the latter through the proteasome degradation pathway.By similarity
Capsid protein C: Inhibits RNA silencing by interfering with host Dicer.By similarity
Peptide pr: Prevents premature fusion activity of envelope proteins in trans-Golgi by binding to envelope protein E at pH6.0. After virion release in extracellular space, gets dissociated from E dimers.By similarity
Protein prM: Acts as a chaperone for envelope protein E during intracellular virion assembly by masking and inactivating envelope protein E fusion peptide. prM is the only viral peptide matured by host furin in the trans-Golgi network probably to avoid catastrophic activation of the viral fusion activity in acidic Golgi compartment prior to virion release. prM-E cleavage is inefficient, and many virions are only partially matured. These uncleaved prM would play a role in immune evasion.By similarity
Small envelope protein M: May play a role in virus budding. Exerts cytotoxic effects by activating a mitochondrial apoptotic pathway through M ectodomain. May display a viroporin activity.By similarity
Envelope protein E: Binds to host cell surface receptor and mediates fusion between viral and cellular membranes. Envelope protein is synthesized in the endoplasmic reticulum in the form of heterodimer with protein prM. They play a role in virion budding in the ER, and the newly formed immature particle is covered with 60 spikes composed of heterodimer between precursor prM and envelope protein E. The virion is transported to the Golgi apparatus where the low pH causes dissociation of PrM-E heterodimers and formation of E homodimers. prM-E cleavage is inefficient, and many virions are only partially matured. These uncleaved prM would play a role in immune evasion.By similarity
Non-structural protein 1: Involved in immune evasion, pathogenesis and viral replication. Once cleaved off the polyprotein, is targeted to three destinations: the viral replication cycle, the plasma membrane and the extracellular compartment. Essential for viral replication. Required for formation of the replication complex and recruitment of other non-structural proteins to the ER-derived membrane structures. Excreted as a hexameric lipoparticle that plays a role against host immune response. Antagonizing the complement function. Binds to the host macrophages and dendritic cells. Inhibits signal transduction originating from Toll-like receptor 3 (TLR3).By similarity
Non-structural protein 1: Disrupts the host endothelial glycocalyx layer of host pulmonary microvascular endothelial cells, inducing degradation of sialic acid and shedding of heparan sulfate proteoglycans. NS1 induces expression of sialidases, heparanase, and activates cathepsin L, which activates heparanase via enzymatic cleavage. These effects are probably linked to the endothelial hyperpermeability observed in severe dengue disease.By similarity
Non-structural protein 2A: Component of the viral RNA replication complex that functions in virion assembly and antagonizes the host immune response.By similarity
Serine protease subunit NS2B: Required cofactor for the serine protease function of NS3. May have membrane-destabilizing activity and form viroporins (By similarity).PROSITE-ProRule annotationBy similarity
Serine protease NS3: Displays three enzymatic activities: serine protease, NTPase and RNA helicase. NS3 serine protease, in association with NS2B, performs its autocleavage and cleaves the polyprotein at dibasic sites in the cytoplasm: C-prM, NS2A-NS2B, NS2B-NS3, NS3-NS4A, NS4A-2K and NS4B-NS5. NS3 RNA helicase binds RNA and unwinds dsRNA in the 3' to 5' direction.PROSITE-ProRule annotation
Non-structural protein 4A: Regulates the ATPase activity of the NS3 helicase activity. NS4A allows NS3 helicase to conserve energy during unwinding. Plays a role in the inhibition of the host innate immune response. Interacts with host MAVS and thereby prevents the interaction between DDX58 and MAVS. In turn, IFN-beta production is impaired.By similarity1 Publication
Peptide 2k: Functions as a signal peptide for NS4B and is required for the interferon antagonism activity of the latter.By similarity
Non-structural protein 4B: Induces the formation of ER-derived membrane vesicles where the viral replication takes place. Inhibits interferon (IFN)-induced host STAT1 phosphorylation and nuclear translocation, thereby preventing the establishment of cellular antiviral state by blocking the IFN-alpha/beta pathway.By similarity
RNA-directed RNA polymerase NS5: Replicates the viral (+) and (-) RNA genome, and performs the capping of genomes in the cytoplasm. NS5 methylates viral RNA cap at guanine N-7 and ribose 2'-O positions. Besides its role in RNA genome replication, also prevents the establishment of cellular antiviral state by blocking the interferon-alpha/beta (IFN-alpha/beta) signaling pathway. Inhibits host TYK2 and STAT2 phosphorylation, thereby preventing activation of JAK-STAT signaling pathway.By similarity

Catalytic activityi

Selective hydrolysis of -Xaa-Xaa-|-Yaa- bonds in which each of the Xaa can be either Arg or Lys and Yaa can be either Ser or Ala.
Nucleoside triphosphate + RNA(n) = diphosphate + RNA(n+1).PROSITE-ProRule annotation
NTP + H2O = NDP + phosphate.1 Publication
ATP + H2O = ADP + phosphate.1 Publication
S-adenosyl-L-methionine + G(5')pppR-RNA = S-adenosyl-L-homocysteine + m7G(5')pppR-RNA.PROSITE-ProRule annotation
S-adenosyl-L-methionine + a 5'-(N7-methyl 5'-triphosphoguanosine)-(purine-ribonucleotide)-[mRNA] = S-adenosyl-L-homocysteine + a 5'-(N7-methyl 5'-triphosphoguanosine)-(2'-O-methyl-purine-ribonucleotide)-[mRNA].PROSITE-ProRule annotation

Kineticsi

Vmax with 0.65 nmol/s/µg enzyme for RTPase activity with triphosphorylated RNA as substrate.1 Publication
  1. KM=29.3 µM for triphosphorylated RNA1 Publication

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Active sitei1526Charge relay system; for serine protease NS3 activityPROSITE-ProRule annotation1
    Active sitei1550Charge relay system; for serine protease NS3 activityPROSITE-ProRule annotation1
    Active sitei1610Charge relay system; for serine protease NS3 activityPROSITE-ProRule annotation1
    Sitei1932Involved in NS3 ATPase and RTPase activitiesBy similarity1
    Sitei1935Involved in NS3 ATPase and RTPase activitiesBy similarity1
    Binding sitei2505mRNA capPROSITE-ProRule annotation1
    Binding sitei2508mRNA cap; via carbonyl oxygenPROSITE-ProRule annotation1
    Binding sitei2509mRNA capPROSITE-ProRule annotation1
    Binding sitei2511mRNA cap; via carbonyl oxygenPROSITE-ProRule annotation1
    Sitei2516mRNA cap bindingPROSITE-ProRule annotation1
    Binding sitei2520mRNA capPROSITE-ProRule annotation1
    Binding sitei2547S-adenosyl-L-methioninePROSITE-ProRule annotation1
    Active sitei2552For 2'-O-MTase activityBy similarity1
    Sitei2552Essential for 2'-O-methyltransferase activityPROSITE-ProRule annotation1
    Binding sitei2577S-adenosyl-L-methionine; via carbonyl oxygenPROSITE-ProRule annotation1
    Binding sitei2578S-adenosyl-L-methionine; via carbonyl oxygenPROSITE-ProRule annotation1
    Binding sitei2595S-adenosyl-L-methioninePROSITE-ProRule annotation1
    Binding sitei2596S-adenosyl-L-methionine; via carbonyl oxygenPROSITE-ProRule annotation1
    Binding sitei2622S-adenosyl-L-methioninePROSITE-ProRule annotation1
    Binding sitei2623S-adenosyl-L-methionine; via carbonyl oxygenPROSITE-ProRule annotation1
    Active sitei2637For 2'-O-MTase activityBy similarity1
    Sitei2637Essential for 2'-O-methyltransferase and N-7 methyltransferase activityPROSITE-ProRule annotation1
    Sitei2638S-adenosyl-L-methionine bindingPROSITE-ProRule annotation1
    Binding sitei2641mRNA capPROSITE-ProRule annotation1
    Active sitei2672For 2'-O-MTase activityBy similarity1
    Sitei2672Essential for 2'-O-methyltransferase activityPROSITE-ProRule annotation1
    Binding sitei2703mRNA capPROSITE-ProRule annotation1
    Binding sitei2705mRNA capPROSITE-ProRule annotation1
    Active sitei2708For 2'-O-MTase activityBy similarity1
    Sitei2708Essential for 2'-O-methyltransferase activityPROSITE-ProRule annotation1
    Binding sitei2710S-adenosyl-L-methioninePROSITE-ProRule annotation1
    Metal bindingi2929Zinc 1By similarity1
    Metal bindingi2933Zinc 1; via tele nitrogenBy similarity1
    Metal bindingi2938Zinc 1By similarity1
    Metal bindingi2941Zinc 1By similarity1
    Metal bindingi3203Zinc 2; via tele nitrogenBy similarity1
    Metal bindingi3219Zinc 2By similarity1
    Metal bindingi3338Zinc 2By similarity1

    Regions

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Nucleotide bindingi1668 – 1675ATPPROSITE-ProRule annotation8

    GO - Molecular functioni

    GO - Biological processi

    Keywordsi

    Molecular functionHelicase, Hydrolase, Ion channel, Methyltransferase, Multifunctional enzyme, Nucleotidyltransferase, Protease, RNA-binding, RNA-directed RNA polymerase, Serine protease, Suppressor of RNA silencing, Transferase, Viral ion channel
    Biological processActivation of host autophagy by virus, Clathrin-mediated endocytosis of virus by host, Fusion of virus membrane with host endosomal membrane, Fusion of virus membrane with host membrane, Host-virus interaction, Inhibition of host innate immune response by virus, Inhibition of host interferon signaling pathway by virus, Inhibition of host MAVS by virus, Inhibition of host RLR pathway by virus, Inhibition of host STAT2 by virus, Inhibition of host TYK2 by virus, Ion transport, mRNA capping, mRNA processing, Transcription, Transcription regulation, Transport, Viral attachment to host cell, Viral immunoevasion, Viral penetration into host cytoplasm, Viral RNA replication, Virus endocytosis by host, Virus entry into host cell
    LigandATP-binding, Metal-binding, Nucleotide-binding, S-adenosyl-L-methionine, Zinc

    Protein family/group databases

    TCDBi1.G.3.1.2 the viral pore-forming membrane fusion protein-3 (vmfp3) family

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Genome polyprotein
    Cleaved into the following 13 chains:
    Alternative name(s):
    Core protein
    Alternative name(s):
    Matrix protein
    Alternative name(s):
    Flavivirin protease NS2B regulatory subunit
    Non-structural protein 2B
    Serine protease NS3 (EC:3.4.21.91, EC:3.6.1.15By similarity, EC:3.6.4.13By similarity)
    Alternative name(s):
    Flavivirin protease NS3 catalytic subunit
    Non-structural protein 3
    RNA-directed RNA polymerase NS5 (EC:2.1.1.56PROSITE-ProRule annotation, EC:2.1.1.57PROSITE-ProRule annotation, EC:2.7.7.48PROSITE-ProRule annotation)
    Alternative name(s):
    Non-structural protein 5
    OrganismiDengue virus type 2 (strain Thailand/NGS-C/1944) (DENV-2)
    Taxonomic identifieri11065 [NCBI]
    Taxonomic lineageiVirusesssRNA virusesssRNA positive-strand viruses, no DNA stageFlaviviridaeFlavivirusDengue virus group
    Virus hostiAedimorphus [TaxID: 53540]
    Diceromyia [TaxID: 53539]
    Erythrocebus patas (Red guenon) (Cercopithecus patas) [TaxID: 9538]
    Homo sapiens (Human) [TaxID: 9606]
    Stegomyia [TaxID: 53541]
    Proteomesi
    • UP000007196 Componenti: Genome

    Subcellular locationi

    Capsid protein C :
    • Virion By similarity
    • Host nucleus By similarity
    • Host cytoplasm By similarity
    • host perinuclear region By similarity
    Peptide pr :
    • Secreted By similarity
    Small envelope protein M :
    Envelope protein E :
    Non-structural protein 1 :
    • Secreted By similarity
    • Host endoplasmic reticulum membrane ; Peripheral membrane protein ; Lumenal side By similarity
    • Note: Located in RE-derived vesicles hosting the replication complex.By similarity
    Non-structural protein 2A :
    Serine protease subunit NS2B :
    Serine protease NS3 :
    • Host endoplasmic reticulum membrane PROSITE-ProRule annotation; Peripheral membrane protein PROSITE-ProRule annotation; Cytoplasmic side PROSITE-ProRule annotation
    • Note: Remains non-covalently associated to serine protease subunit NS2B.PROSITE-ProRule annotation
    Non-structural protein 4A :
    • Host endoplasmic reticulum membrane 1 Publication; Multi-pass membrane protein 1 Publication
    • Host mitochondrion By similarity
    • Note: Located in RE-associated vesicles hosting the replication complex. Interacts with host MAVS in the mitochondrion-associated endoplasmic reticulum membranes.By similarity
    Non-structural protein 4B :
    • Host endoplasmic reticulum membrane 1 Publication; Multi-pass membrane protein 1 Publication
    • Note: Located in RE-derived vesicles hosting the replication complex.By similarity
    RNA-directed RNA polymerase NS5 :
    • Host endoplasmic reticulum membrane ; Peripheral membrane protein ; Cytoplasmic side
    • Host nucleus By similarity
    • Note: Located in RE-associated vesicles hosting the replication complex. NS5 protein is mainly localized in the nucleus rather than in ER vesicles, especially in the DENV 2, 3, 4 serotypes.By similarity

    Topology

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Topological domaini1 – 101CytoplasmicSequence analysisAdd BLAST101
    Transmembranei102 – 122HelicalSequence analysisAdd BLAST21
    Topological domaini123 – 238ExtracellularSequence analysisAdd BLAST116
    Transmembranei239 – 259HelicalSequence analysisAdd BLAST21
    Topological domaini260 – 265CytoplasmicSequence analysis6
    Transmembranei266 – 280HelicalSequence analysisAdd BLAST15
    Topological domaini281 – 725ExtracellularSequence analysisAdd BLAST445
    Transmembranei726 – 746HelicalSequence analysisAdd BLAST21
    Topological domaini747 – 752CytoplasmicSequence analysis6
    Transmembranei753 – 773HelicalSequence analysisAdd BLAST21
    Topological domaini774 – 1195ExtracellularSequence analysisAdd BLAST422
    Transmembranei1196 – 1220Helical1 PublicationAdd BLAST25
    Topological domaini1221 – 1226Cytoplasmic1 Publication6
    Transmembranei1227 – 1245Helical1 PublicationSequence analysisAdd BLAST19
    Topological domaini1246 – 1269Lumenal1 PublicationAdd BLAST24
    Transmembranei1270 – 1290Helical1 PublicationSequence analysisAdd BLAST21
    Topological domaini1291Cytoplasmic1 Publication1
    Transmembranei1292 – 1310Helical1 PublicationSequence analysisAdd BLAST19
    Topological domaini1311 – 1317Lumenal1 Publication7
    Transmembranei1318 – 1338Helical1 PublicationSequence analysisAdd BLAST21
    Topological domaini1339 – 1346CytoplasmicSequence analysis8
    Transmembranei1347 – 1367HelicalSequence analysisAdd BLAST21
    Topological domaini1368 – 1370LumenalSequence analysis3
    Transmembranei1371 – 1391HelicalSequence analysisAdd BLAST21
    Topological domaini1392 – 1447CytoplasmicSequence analysisAdd BLAST56
    Intramembranei1448 – 1468HelicalSequence analysisAdd BLAST21
    Topological domaini1469 – 2147CytoplasmicSequence analysisAdd BLAST679
    Transmembranei2148 – 2168Helical1 PublicationAdd BLAST21
    Topological domaini2169 – 2170Lumenal1 Publication2
    Intramembranei2171 – 2191Helical1 PublicationAdd BLAST21
    Topological domaini2192Lumenal1 Publication1
    Transmembranei2193 – 2213Helical1 PublicationAdd BLAST21
    Topological domaini2214 – 2228CytoplasmicSequence analysisAdd BLAST15
    Transmembranei2229 – 2249Helical; Note=Signal for NS4BSequence analysisAdd BLAST21
    Topological domaini2250 – 2274LumenalSequence analysisAdd BLAST25
    Intramembranei2275 – 2295HelicalSequence analysisAdd BLAST21
    Topological domaini2296 – 2316LumenalSequence analysisAdd BLAST21
    Intramembranei2317 – 2337HelicalSequence analysisAdd BLAST21
    Topological domaini2338 – 2347LumenalSequence analysis10
    Transmembranei2348 – 2368HelicalSequence analysisAdd BLAST21
    Topological domaini2369 – 2413CytoplasmicSequence analysisAdd BLAST45
    Transmembranei2414 – 2434HelicalSequence analysisAdd BLAST21
    Topological domaini2435 – 2459LumenalSequence analysisAdd BLAST25
    Transmembranei2460 – 2480HelicalSequence analysisAdd BLAST21
    Topological domaini2481 – 3391CytoplasmicSequence analysisAdd BLAST911

    GO - Cellular componenti

    Keywords - Cellular componenti

    Capsid protein, Host cytoplasm, Host endoplasmic reticulum, Host membrane, Host mitochondrion, Host nucleus, Membrane, Secreted, Viral envelope protein, Virion

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi1659 – 1662RKRK → QNGN: Complete loss of RNA-stimulated NTPase activity. 1 Publication4

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00004052161 – 3391Genome polyproteinAdd BLAST3391
    ChainiPRO_00000379581 – 100Capsid protein CBy similarityAdd BLAST100
    PropeptideiPRO_0000261388101 – 114ER anchor for the capsid protein C, removed in mature form by serine protease NS3By similarityAdd BLAST14
    ChainiPRO_0000261389115 – 280Protein prMBy similarityAdd BLAST166
    ChainiPRO_0000037959115 – 205Peptide prBy similarityAdd BLAST91
    ChainiPRO_0000037960206 – 280Small envelope protein MBy similarityAdd BLAST75
    ChainiPRO_0000037961281 – 775Envelope protein E1 PublicationAdd BLAST495
    ChainiPRO_0000037962776 – 1127Non-structural protein 1By similarityAdd BLAST352
    ChainiPRO_00000379631128 – 1345Non-structural protein 2ABy similarityAdd BLAST218
    ChainiPRO_00000379641346 – 1475Serine protease subunit NS2BBy similarityAdd BLAST130
    ChainiPRO_00000379651476 – 2093Serine protease NS3By similarityAdd BLAST618
    ChainiPRO_00000379662094 – 2220Non-structural protein 4ABy similarityAdd BLAST127
    PeptideiPRO_00002613912221 – 2243Peptide 2kBy similarityAdd BLAST23
    ChainiPRO_00000379672244 – 2491Non-structural protein 4BBy similarityAdd BLAST248
    ChainiPRO_00000379682492 – 3391RNA-directed RNA polymerase NS5By similarityAdd BLAST900

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Glycosylationi183N-linked (GlcNAc...) asparagine; by hostPROSITE-ProRule annotation1
    Disulfide bondi283 ↔ 310By similarity
    Disulfide bondi340 ↔ 401By similarity
    Glycosylationi347N-linked (GlcNAc...) asparagine; by hostPROSITE-ProRule annotation1
    Disulfide bondi354 ↔ 385By similarity
    Disulfide bondi372 ↔ 396By similarity
    Glycosylationi433N-linked (GlcNAc...) asparagine; by hostPROSITE-ProRule annotation1
    Disulfide bondi465 ↔ 565By similarity
    Disulfide bondi582 ↔ 613By similarity
    Disulfide bondi779 ↔ 790By similarity
    Disulfide bondi830 ↔ 918By similarity
    Glycosylationi905N-linked (GlcNAc...) asparagine; by hostPROSITE-ProRule annotation1
    Disulfide bondi954 ↔ 998By similarity
    Glycosylationi982N-linked (GlcNAc...) asparagine; by host1
    Disulfide bondi1055 ↔ 1104By similarity
    Disulfide bondi1066 ↔ 1088By similarity
    Disulfide bondi1087 ↔ 1091By similarity
    Glycosylationi2301N-linked (GlcNAc...) asparagine; by hostPROSITE-ProRule annotation1
    Glycosylationi2305N-linked (GlcNAc...) asparagine; by hostPROSITE-ProRule annotation1
    Glycosylationi2457N-linked (GlcNAc...) asparagine; by hostPROSITE-ProRule annotation1
    Modified residuei2547PhosphoserineBy similarity1

    Post-translational modificationi

    Genome polyprotein: Specific enzymatic cleavages in vivo yield mature proteins. Cleavages in the lumen of endoplasmic reticulum are performed by host signal peptidase, whereas cleavages in the cytoplasmic side are performed by serine protease NS3. Signal cleavage at the 2K-4B site requires a prior NS3 protease-mediated cleavage at the 4A-2K site.By similarity1 Publication
    Protein prM: Cleaved in post-Golgi vesicles by a host furin, releasing the mature small envelope protein M, and peptide pr. This cleavage is incomplete as up to 30% of viral particles still carry uncleaved prM.By similarity
    Envelope protein E: N-glycosylated.By similarity
    Non-structural protein 1: N-glycosylated. The excreted form is glycosylated and this is required for efficient secretion of the protein from infected cells.By similarity
    RNA-directed RNA polymerase NS5: Sumoylation of RNA-directed RNA polymerase NS5 increases NS5 protein stability allowing proper viral RNA replication.By similarity
    RNA-directed RNA polymerase NS5: Phosphorylated on serines residues (PubMed:7642575). This phosphorylation may trigger NS5 nuclear localization.By similarity1 Publication

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sitei100 – 101Cleavage; by viral protease NS3By similarity2
    Sitei114 – 115Cleavage; by host signal peptidaseBy similarity2
    Sitei205 – 206Cleavage; by host furinSequence analysisBy similarity2
    Sitei280 – 281Cleavage; by host signal peptidase1 Publication2
    Sitei775 – 776Cleavage; by host signal peptidase1 Publication2
    Sitei1127 – 1128Cleavage; by hostBy similarity2
    Sitei1345 – 1346Cleavage; by viral protease NS3By similarity2
    Sitei1475 – 1476Cleavage; by autolysis1 Publication2
    Sitei2093 – 2094Cleavage; by autolysisBy similarity2
    Sitei2220 – 2221Cleavage; by viral protease NS3By similarity2
    Sitei2243 – 2244Cleavage; by host signal peptidaseBy similarity2
    Sitei2491 – 2492Cleavage; by viral protease NS31 Publication2

    Keywords - PTMi

    Cleavage on pair of basic residues, Disulfide bond, Glycoprotein, Phosphoprotein, Ubl conjugation

    Proteomic databases

    PRIDEiP14340

    PTM databases

    iPTMnetiP14340

    Interactioni

    Subunit structurei

    Capsid protein C: Homodimer (By similarity). Interacts (via N-terminus) with host EXOC1 (via C-terminus); this interaction results in EXOC1 degradation through the proteasome degradation pathway (By similarity). Protein prM: Forms heterodimers with envelope protein E in the endoplasmic reticulum and Golgi (By similarity). Envelope protein E: Homodimer; in the endoplasmic reticulum and Golgi (By similarity). Interacts with protein prM (By similarity). Interacts with non-structural protein 1. Non-structural protein 1: Homodimer; Homohexamer when secreted (By similarity). Interacts with envelope protein E. Non-structural protein 2A: Interacts (via N-terminus) with serine protease NS3 (By similarity). Non-structural protein 2B: Forms a heterodimer with serine protease NS3 (By similarity). May form homooligomers (By similarity). Serine protease NS3: Forms a heterodimer with NS2B (By similarity). Interacts with NS4B (By similarity). Interacts with unphosphorylated RNA-directed RNA polymerase NS5; this interaction stimulates RNA-directed RNA polymerase NS5 guanylyltransferase activity (PubMed:15917225). Non-structural protein 4A: Interacts with host MAVS; this interaction inhibits the synthesis of IFN-beta (By similarity). Non-structural protein 4A: Interacts with host MAVS; this interaction inhibits the synthesis of IFN-beta. Non-structural protein 4B: Interacts with serine protease NS (By similarity). RNA-directed RNA polymerase NS5: Homodimer (By similarity). Interacts with host STAT2; this interaction inhibits the phosphorylation of the latter, and, when all viral proteins are present (polyprotein), targets STAT2 for degradation (By similarity). Interacts with serine protease NS3 (PubMed:15917225).By similarity1 Publication

    Binary interactionsi

    Show more details

    GO - Molecular functioni

    Protein-protein interaction databases

    IntActiP14340, 13 interactors

    Chemistry databases

    BindingDBiP14340

    Structurei

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    3IYAelectron microscopy22.00A/B/C281-675[»]
    D/E/F115-195[»]
    3J27electron microscopy3.60A/C/E281-775[»]
    B/D/F206-280[»]
    3J2Pelectron microscopy3.60A/C281-775[»]
    B/D206-280[»]
    4CBFelectron microscopy4.10A/C/E288-721[»]
    4UIHelectron microscopy20.00A/B/C281-775[»]
    DisProtiDP00876
    ProteinModelPortaliP14340
    SMRiP14340
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Domaini1476 – 1653Peptidase S7PROSITE-ProRule annotationAdd BLAST178
    Domaini1655 – 1811Helicase ATP-bindingPROSITE-ProRule annotationAdd BLAST157
    Domaini1821 – 1988Helicase C-terminalPROSITE-ProRule annotationAdd BLAST168
    Domaini2493 – 2755mRNA cap 0-1 NS5-type MTPROSITE-ProRule annotationAdd BLAST263
    Domaini3019 – 3168RdRp catalyticPROSITE-ProRule annotationAdd BLAST150

    Region

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Regioni1 – 15Interaction with host EXOC1By similarityAdd BLAST15
    Regioni37 – 72Hydrophobic; homodimerization of capsid protein CBy similarityAdd BLAST36
    Regioni378 – 391Fusion peptideBy similarityAdd BLAST14
    Regioni1398 – 1437Interacts with and activates NS3 proteasePROSITE-ProRule annotationAdd BLAST40
    Regioni1659 – 1662Important for RNA-binding1 Publication4

    Motif

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Motifi1759 – 1762DEAH boxPROSITE-ProRule annotation4
    Motifi2568 – 2571SUMO-interacting motifBy similarity4

    Compositional bias

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Compositional biasi97 – 100Poly-Arg4
    Compositional biasi1434 – 1437Poly-Glu4
    Compositional biasi2148 – 2154Poly-Leu7
    Compositional biasi3383 – 3386Poly-Glu4

    Domaini

    The transmembrane domains of the small envelope protein M and envelope protein E contain an endoplasmic reticulum retention signal.By similarity

    Sequence similaritiesi

    In the N-terminal section; belongs to the class I-like SAM-binding methyltransferase superfamily. mRNA cap 0-1 NS5-type methyltransferase family.PROSITE-ProRule annotation

    Keywords - Domaini

    Transmembrane, Transmembrane helix

    Phylogenomic databases

    OrthoDBiVOG09000016

    Family and domain databases

    CDDicd12149 Flavi_E_C, 1 hit
    Gene3Di1.10.10.930, 1 hit
    1.10.8.970, 1 hit
    1.20.1280.260, 1 hit
    2.60.260.50, 1 hit
    2.60.40.350, 1 hit
    2.60.98.10, 3 hits
    3.30.387.10, 2 hits
    3.30.67.10, 4 hits
    InterProiView protein in InterPro
    IPR011492 DEAD_Flavivir
    IPR000069 Env_glycoprot_M_flavivir
    IPR038302 Env_glycoprot_M_sf_flavivir
    IPR013755 Flav_gly_cen_dom_subdom1
    IPR001122 Flavi_capsidC
    IPR037172 Flavi_capsidC_sf
    IPR027287 Flavi_E_Ig-like
    IPR026470 Flavi_E_Stem/Anchor_dom
    IPR038345 Flavi_E_Stem/Anchor_dom_sf
    IPR001157 Flavi_NS1
    IPR000752 Flavi_NS2A
    IPR000487 Flavi_NS2B
    IPR000404 Flavi_NS4A
    IPR001528 Flavi_NS4B
    IPR002535 Flavi_propep
    IPR038688 Flavi_propep_sf
    IPR000336 Flavivir/Alphavir_Ig-like_sf
    IPR001850 Flavivirus_NS3_S7
    IPR014412 Gen_Poly_FLV
    IPR011998 Glycoprot_cen/dimer
    IPR036253 Glycoprot_cen/dimer_sf
    IPR038055 Glycoprot_E_dimer_dom
    IPR013756 GlyE_cen_dom_subdom2
    IPR014001 Helicase_ATP-bd
    IPR001650 Helicase_C
    IPR014756 Ig_E-set
    IPR026490 mRNA_cap_0/1_MeTrfase
    IPR027417 P-loop_NTPase
    IPR009003 Peptidase_S1_PA
    IPR000208 RNA-dir_pol_flavivirus
    IPR007094 RNA-dir_pol_PSvirus
    IPR002877 rRNA_MeTrfase_FtsJ_dom
    IPR029063 SAM-dependent_MTases
    PfamiView protein in Pfam
    PF01003 Flavi_capsid, 1 hit
    PF07652 Flavi_DEAD, 1 hit
    PF02832 Flavi_glycop_C, 1 hit
    PF00869 Flavi_glycoprot, 1 hit
    PF01004 Flavi_M, 1 hit
    PF00948 Flavi_NS1, 1 hit
    PF01005 Flavi_NS2A, 1 hit
    PF01002 Flavi_NS2B, 1 hit
    PF01350 Flavi_NS4A, 1 hit
    PF01349 Flavi_NS4B, 1 hit
    PF00972 Flavi_NS5, 1 hit
    PF01570 Flavi_propep, 1 hit
    PF01728 FtsJ, 1 hit
    PF00949 Peptidase_S7, 1 hit
    PIRSFiPIRSF003817 Gen_Poly_FLV, 1 hit
    SMARTiView protein in SMART
    SM00487 DEXDc, 1 hit
    SM00490 HELICc, 1 hit
    SUPFAMiSSF101257 SSF101257, 1 hit
    SSF50494 SSF50494, 1 hit
    SSF52540 SSF52540, 2 hits
    SSF53335 SSF53335, 1 hit
    SSF56983 SSF56983, 1 hit
    SSF81296 SSF81296, 1 hit
    TIGRFAMsiTIGR04240 flavi_E_stem, 1 hit
    PROSITEiView protein in PROSITE
    PS51527 FLAVIVIRUS_NS2B, 1 hit
    PS51528 FLAVIVIRUS_NS3PRO, 1 hit
    PS51192 HELICASE_ATP_BIND_1, 1 hit
    PS51194 HELICASE_CTER, 1 hit
    PS50507 RDRP_SSRNA_POS, 1 hit
    PS51591 RNA_CAP01_NS5_MT, 1 hit

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    P14340-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MNNQRKKARN TPFNMLKRER NRVSTVQQLT KRFSLGMLQG RGPLKLFMAL
    60 70 80 90 100
    VAFLRFLTIP PTAGILKRWG TIKKSKAINV LRGFRKEIGR MLNILNRRRR
    110 120 130 140 150
    TAGMIIMLIP TVMAFHLTTR NGEPHMIVSR QEKGKSLLFK TEDGVNMCTL
    160 170 180 190 200
    MAMDLGELCE DTITYKCPFL KQNEPEDIDC WCNSTSTWVT YGTCTTTGEH
    210 220 230 240 250
    RREKRSVALV PHVGMGLETR TETWMSSEGA WKHAQRIETW ILRHPGFTIM
    260 270 280 290 300
    AAILAYTIGT THFQRALIFI LLTAVAPSMT MRCIGISNRD FVEGVSGGSW
    310 320 330 340 350
    VDIVLEHGSC VTTMAKNKPT LDFELIETEA KQPATLRKYC IEAKLTNTTT
    360 370 380 390 400
    DSRCPTQGEP SLNEEQDKRF VCKHSMVDRG WGNGCGLFGK GGIVTCAMFT
    410 420 430 440 450
    CKKNMKGKVV QPENLEYTIV ITPHSGEEHA VGNDTGKHGK EIKITPQSSI
    460 470 480 490 500
    TEAELTGYGT VTMECSPRTG LDFNEMVLLQ MENKAWLVHR QWFLDLPLPW
    510 520 530 540 550
    LPGADTQGSN WIQKETLVTF KNPHAKKQDV VVLGSQEGAM HTALTGATEI
    560 570 580 590 600
    QMSSGNLLFT GHLKCRLRMD KLQLKGMSYS MCTGKFKVVK EIAETQHGTI
    610 620 630 640 650
    VIRVQYEGDG SPCKIPFEIM DLEKRHVLGR LITVNPIVTE KDSPVNIEAE
    660 670 680 690 700
    PPFGDSYIII GVEPGQLKLN WFKKGSSIGQ MIETTMRGAK RMAILGDTAW
    710 720 730 740 750
    DFGSLGGVFT SIGKALHQVF GAIYGAAFSG VSWIMKILIG VIITWIGMNS
    760 770 780 790 800
    RSTSLSVSLV LVGVVTLYLG VMVQADSGCV VSWKNKELKC GSGIFITDNV
    810 820 830 840 850
    HTWTEQYKFQ PESPSKLASA IQKAHEEGIC GIRSVTRLEN LMWKQITPEL
    860 870 880 890 900
    NHILSENEVK LTIMTGDIKG IMQAGKRSLQ PQPTELKYSW KTWGKAKMLS
    910 920 930 940 950
    TESHNQTFLI DGPETAECPN TNRAWNSLEV EDYGFGVFTT NIWLKLREKQ
    960 970 980 990 1000
    DVFCDSKLMS AAIKDNRAVH ADMGYWIESA LNDTWKIEKA SFIEVKSCHW
    1010 1020 1030 1040 1050
    PKSHTLWSNG VLESEMIIPK NFAGPVSQHN YRPGYHTQTA GPWHLGKLEM
    1060 1070 1080 1090 1100
    DFDFCEGTTV VVTEDCGNRG PSLRTTTASG KLITEWCCRS CTLPPLRYRG
    1110 1120 1130 1140 1150
    EDGCWYGMEI RPLKEKEENL VNSLVTAGHG QIDNFSLGVL GMALFLEEML
    1160 1170 1180 1190 1200
    RTRVGTKHAI LLVAVSFVTL ITGNMSFRDL GRVMVMVGAT MTDDIGMGVT
    1210 1220 1230 1240 1250
    YLALLAAFKV RPTFAAGLLL RKLTSKELMM TTIGIVLLSQ STIPETILEL
    1260 1270 1280 1290 1300
    TDALALGMMV LKMVRKMEKY QLAVTIMAIL CVPNAVILQN AWKVSCTILA
    1310 1320 1330 1340 1350
    VVSVSPLFLT SSQQKADWIP LALTIKGLNP TAIFLTTLSR TNKKRSWPLN
    1360 1370 1380 1390 1400
    EAIMAVGMVS ILASSLLKND IPMTGPLVAG GLLTVCYVLT GRSADLELER
    1410 1420 1430 1440 1450
    AADVKWEDQA EISGSSPILS ITISEDGSMS IKNEEEEQTL TILIRTGLLV
    1460 1470 1480 1490 1500
    ISGLFPVSIP ITAAAWYLWE VKKQRAGVLW DVPSPPPVGK AELEDGAYRI
    1510 1520 1530 1540 1550
    KQKGILGYSQ IGAGVYKEGT FHTMWHVTRG AVLMHKGKRI EPSWADVKKD
    1560 1570 1580 1590 1600
    LISYGGGWKL EGEWKEGEEV QVLALEPGKN PRAVQTKPGL FKTNAGTIGA
    1610 1620 1630 1640 1650
    VSLDFSPGTS GSPIIDKKGK VVGLYGNGVV TRSGAYVSAI AQTEKSIEDN
    1660 1670 1680 1690 1700
    PEIEDDIFRK RKLTIMDLHP GAGKTKRYLP AIVREAIKRG LRTLILAPTR
    1710 1720 1730 1740 1750
    VVAAEMEEAL RGLPIRYQTP AIRAEHTGRE IVDLMCHATF TMRLLSPVRV
    1760 1770 1780 1790 1800
    PNYNLIIMDE AHFTDPASIA ARGYISTRVE MGEAAGIFMT ATPPGSRDPF
    1810 1820 1830 1840 1850
    PQSNAPIMDE EREIPERSWS SGHEWVTDFK GKTVWFVPSI KAGNDIAACL
    1860 1870 1880 1890 1900
    RKNGKKVIQL SRKTFDSEYV KTRTNDWDFV VTTDISEMGA NFKAERVIDP
    1910 1920 1930 1940 1950
    RRCMKPVILT DGEERVILAG PMPVTHSSAA QRRGRIGRNP KNENDQYIYM
    1960 1970 1980 1990 2000
    GEPLENDEDC AHWKEAKMLL DNINTPEGII PSMFEPEREK VDAIDGEYRL
    2010 2020 2030 2040 2050
    RGEARKTFVD LMRRGDLPVW LAYRVAAEGI NYADRRWCFD GIKNNQILEE
    2060 2070 2080 2090 2100
    NVEVEIWTKE GERKKLKPRW LDAKIYSDPL ALKEFKEFAA GRKSLTLNLI
    2110 2120 2130 2140 2150
    TEMGRLPTFM TQKARDALDN LAVLHTAEAG GRAYNHALSE LPETLETLLL
    2160 2170 2180 2190 2200
    LTLLATVTGG IFLFLMSGRG IGKMTLGMCC IITASILLWY AQIQPHWIAA
    2210 2220 2230 2240 2250
    SIILEFFLIV LLIPEPEKQR TPQDNQLTYV VIAILTVVAA TMANEMGFLE
    2260 2270 2280 2290 2300
    KTKKDLGLGS ITTQQPESNI LDIDLRPASA WTLYAVATTF VTPMLRHSIE
    2310 2320 2330 2340 2350
    NSSVNVSLTA IANQATVLMG LGKGWPLSKM DIGVPLLAIG CYSQVNPITL
    2360 2370 2380 2390 2400
    TAALFLLVAH YAIIGPGLQA KATREAQKRA AAGIMKNPTV DGITVIDLDP
    2410 2420 2430 2440 2450
    IPYDPKFEKQ LGQVMLLVLC VTQVLMMRTT WALCEALTLA TGPISTLWEG
    2460 2470 2480 2490 2500
    NPGRFWNTTI AVSMANIFRG SYLAGAGLLF SIMKNTTNTR RGTGNIGETL
    2510 2520 2530 2540 2550
    GEKWKSRLNA LGKSEFQIYK KSGIQEVDRT LAKEGIKRGE TDHHAVSRGS
    2560 2570 2580 2590 2600
    AKLRWFVERN MVTPEGKVVD LGCGRGGWSY YCGGLKNVRE VKGLTKGGPG
    2610 2620 2630 2640 2650
    HEEPIPMSTY GWNLVRLQSG VDVFFTPPEK CDTLLCDIGE SSPNPTVEAG
    2660 2670 2680 2690 2700
    RTLRVLNLVE NWLNNNTQFC IKVLNPYMPS VIEKMEALQR KYGGALVRNP
    2710 2720 2730 2740 2750
    LSRNSTHEMY WLSNASGNIV SSVNMISRML INRFTMRHKK ATYEPDVDLG
    2760 2770 2780 2790 2800
    SGTRNIGIES EIPNLDIIGK RIEKIKQEHE TSWHYDQDHP YKTWAYHGSY
    2810 2820 2830 2840 2850
    ETKQTGSASS MGNGVVRLLT KPWDVVPMVT QMAMTDTTPF GQQRVFKEKV
    2860 2870 2880 2890 2900
    DTRTQEPKEG TKKLMKITAE WLWKELGKKK TPRMCTREEF TRKVRSNAAL
    2910 2920 2930 2940 2950
    GAIFTDENKW KSAREAVEDS RFWELVDKER NLHLEGKCET CVYNMMGKRE
    2960 2970 2980 2990 3000
    KKLGEFGKAK GSRAIWYMWL GARFLEFEAL GFLNEDHWFS RENSLSGVEG
    3010 3020 3030 3040 3050
    EGLHKLGYIL RDVSKKEGGA MYADDTAGWD TRITLEDLKN EEMVTNHMEG
    3060 3070 3080 3090 3100
    EHKKLAEAIF KLTYQNKVVR VQRPTPRGTV MDIISRRDQR GSGQVGTYGL
    3110 3120 3130 3140 3150
    NTFTNMEAQL IRQMEGEGVF KSIQHLTVTE EIAVQNWLAR VGRERLSRMA
    3160 3170 3180 3190 3200
    ISGDDCVVKP LDDRFASALT ALNDMGKVRK DIQQWEPSRG WNDWTQVPFC
    3210 3220 3230 3240 3250
    SHHFHELIMK DGRVLVVPCR NQDELIGRAR ISQGAGWSLR ETACLGKSYA
    3260 3270 3280 3290 3300
    QMWSLMYFHR RDLRLAANAI CSAVPSHWVP TSRTTWSIHA KHEWMTTEDM
    3310 3320 3330 3340 3350
    LTVWNRVWIQ ENPWMEDKTP VESWEEIPYL GKREDQWCGS LIGLTSRATW
    3360 3370 3380 3390
    AKNIQTAINQ VRSLIGNEEY TDYMPSMKRF RKEEEEAGVL W
    Length:3,391
    Mass (Da):379,501
    Last modified:October 1, 1996 - v2
    Checksum:iFFF98B4FF5B4BC57
    GO

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    M29095 Genomic RNA Translation: AAA42941.1

    Similar proteinsi

    Entry informationi

    Entry nameiPOLG_DEN2N
    AccessioniPrimary (citable) accession number: P14340
    Secondary accession number(s): Q66347
    , Q66348, Q66349, Q66350, Q66351, Q66352, Q66353, Q66354, Q66355, Q66356, Q89579
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 1, 1990
    Last sequence update: October 1, 1996
    Last modified: May 23, 2018
    This is version 173 of the entry and version 2 of the sequence. See complete history.
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programViral Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome

    Documents

    1. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    2. SIMILARITY comments
      Index of protein domains and families

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