UniProtKB - Q9WDA6 (POLG_DEN2Q)
Genome polyprotein
Functioni
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 similarityInhibits RNA silencing by interfering with host Dicer.
By similarityPrevents 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 similarityActs 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 similarityMay play a role in virus budding. Exerts cytotoxic effects by activating a mitochondrial apoptotic pathway through M ectodomain. May display a viroporin activity.
By similarityBinds 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 similarityInvolved 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 similarityDisrupts 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 similarityComponent of the viral RNA replication complex that functions in virion assembly and antagonizes the host immune response.
By similarityRequired cofactor for the serine protease function of NS3. May have membrane-destabilizing activity and form viroporins (By similarity).
PROSITE-ProRule annotationBy similarityDisplays 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 annotationRegulates 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. Interacts with host AUP1 which mediates induction of lipophagy in host cells and facilitates production of virus progeny particles (By similarity).
By similarityFunctions as a signal peptide for NS4B and is required for the interferon antagonism activity of the latter.
By similarityInduces 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 similarityReplicates 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).
May reduce immune responses by preventing the recruitment of the host PAF1 complex to interferon-responsive genes (By similarity).
By similarityCatalytic activityi
- EC:2.7.7.48PROSITE-ProRule annotation
- EC:3.6.1.15
- EC:3.6.4.13
- a 5'-end (5'-triphosphoguanosine)-(ribonucleoside) in mRNA + S-adenosyl-L-methionine = a 5'-end (N7-methyl 5'-triphosphoguanosine)-ribonucleoside in mRNA + S-adenosyl-L-homocysteinePROSITE-ProRule annotationEC:2.1.1.56PROSITE-ProRule annotation
- a 5'-end (N7-methyl 5'-triphosphoguanosine)-ribonucleoside in mRNA + S-adenosyl-L-methionine = a 5'-end (N7-methyl 5'-triphosphoguanosine)-(2'-O-methyl-ribonucleoside) in mRNA + H+ + S-adenosyl-L-homocysteinePROSITE-ProRule annotationEC:2.1.1.57PROSITE-ProRule annotation
- 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. EC:3.4.21.91
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Active sitei | 1526 | Charge relay system; for serine protease NS3 activityPROSITE-ProRule annotation | 1 | |
Active sitei | 1550 | Charge relay system; for serine protease NS3 activityPROSITE-ProRule annotation | 1 | |
Active sitei | 1610 | Charge relay system; for serine protease NS3 activityPROSITE-ProRule annotation | 1 | |
Sitei | 1932 | Involved in NS3 ATPase and RTPase activitiesBy similarity | 1 | |
Sitei | 1935 | Involved in NS3 ATPase and RTPase activitiesBy similarity | 1 | |
Sitei | 2505 | mRNA cap bindingPROSITE-ProRule annotation | 1 | |
Sitei | 2508 | mRNA cap binding; via carbonyl oxygenPROSITE-ProRule annotation | 1 | |
Sitei | 2509 | mRNA cap bindingPROSITE-ProRule annotation | 1 | |
Sitei | 2511 | mRNA cap binding; via carbonyl oxygenPROSITE-ProRule annotation | 1 | |
Sitei | 2516 | mRNA cap bindingPROSITE-ProRule annotation | 1 | |
Sitei | 2520 | mRNA cap bindingPROSITE-ProRule annotation | 1 | |
Binding sitei | 2547 | S-adenosyl-L-methioninePROSITE-ProRule annotation | 1 | |
Active sitei | 2552 | For 2'-O-MTase activityBy similarity | 1 | |
Sitei | 2552 | Essential for 2'-O-methyltransferase activityPROSITE-ProRule annotation | 1 | |
Binding sitei | 2577 | S-adenosyl-L-methionine; via carbonyl oxygenPROSITE-ProRule annotation | 1 | |
Binding sitei | 2578 | S-adenosyl-L-methionine; via carbonyl oxygenPROSITE-ProRule annotation | 1 | |
Binding sitei | 2595 | S-adenosyl-L-methioninePROSITE-ProRule annotation | 1 | |
Binding sitei | 2596 | S-adenosyl-L-methionine; via carbonyl oxygenPROSITE-ProRule annotation | 1 | |
Binding sitei | 2622 | S-adenosyl-L-methioninePROSITE-ProRule annotation | 1 | |
Binding sitei | 2623 | S-adenosyl-L-methionine; via carbonyl oxygenPROSITE-ProRule annotation | 1 | |
Active sitei | 2637 | For 2'-O-MTase activityBy similarity | 1 | |
Sitei | 2637 | Essential for 2'-O-methyltransferase and N-7 methyltransferase activityPROSITE-ProRule annotation | 1 | |
Binding sitei | 2638 | S-adenosyl-L-methioninePROSITE-ProRule annotation | 1 | |
Sitei | 2641 | mRNA cap bindingPROSITE-ProRule annotation | 1 | |
Active sitei | 2672 | For 2'-O-MTase activityBy similarity | 1 | |
Sitei | 2672 | Essential for 2'-O-methyltransferase activityPROSITE-ProRule annotation | 1 | |
Sitei | 2703 | mRNA cap bindingPROSITE-ProRule annotation | 1 | |
Sitei | 2705 | mRNA cap bindingPROSITE-ProRule annotation | 1 | |
Active sitei | 2708 | For 2'-O-MTase activityBy similarity | 1 | |
Sitei | 2708 | Essential for 2'-O-methyltransferase activityPROSITE-ProRule annotation | 1 | |
Binding sitei | 2710 | S-adenosyl-L-methioninePROSITE-ProRule annotation | 1 | |
Metal bindingi | 2929 | Zinc 1By similarity | 1 | |
Metal bindingi | 2933 | Zinc 1; via tele nitrogenBy similarity | 1 | |
Metal bindingi | 2938 | Zinc 1By similarity | 1 | |
Metal bindingi | 2941 | Zinc 1By similarity | 1 | |
Metal bindingi | 3203 | Zinc 2; via tele nitrogenBy similarity | 1 | |
Metal bindingi | 3219 | Zinc 2By similarity | 1 | |
Metal bindingi | 3338 | Zinc 2By similarity | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 1668 – 1675 | ATPPROSITE-ProRule annotation | 8 |
GO - Molecular functioni
- ATP binding Source: UniProtKB-KW
- ATP hydrolysis activity Source: RHEA
- double-stranded RNA binding Source: InterPro
- ion channel activity Source: UniProtKB-KW
- metal ion binding Source: UniProtKB-KW
- mRNA (guanine-N7-)-methyltransferase activity Source: UniProtKB-EC
- mRNA (nucleoside-2'-O-)-methyltransferase activity Source: UniProtKB-EC
- protein dimerization activity Source: InterPro
- RNA-directed 5'-3' RNA polymerase activity Source: UniProtKB-KW
- RNA helicase activity Source: UniProtKB-EC
- serine-type endopeptidase activity Source: InterPro
- structural molecule activity Source: InterPro
GO - Biological processi
- clathrin-dependent endocytosis of virus by host cell Source: UniProtKB-KW
- fusion of virus membrane with host endosome membrane Source: UniProtKB-KW
- induction by virus of host autophagy Source: UniProtKB
- pore formation by virus in membrane of host cell Source: UniProtKB-KW
- protein complex oligomerization Source: UniProtKB-KW
- suppression by virus of host JAK-STAT cascade via inhibition of host TYK2 activity Source: UniProtKB-KW
- suppression by virus of host JAK-STAT cascade via inhibition of STAT2 activity Source: UniProtKB-KW
- suppression by virus of host type I interferon-mediated signaling pathway Source: UniProtKB-KW
- suppression by virus of host viral-induced cytoplasmic pattern recognition receptor signaling pathway via inhibition of MAVS activity Source: UniProtKB-KW
- viral RNA genome replication Source: InterPro
- virion attachment to host cell Source: UniProtKB-KW
Keywordsi
Protein family/group databases
MEROPSi | S07.001 |
Names & Taxonomyi
Protein namesi | Recommended name: Genome polyproteinCleaved 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 |
Organismi | Dengue virus type 2 (strain Peru/IQT2913/1996) (DENV-2) |
Taxonomic identifieri | 408694 [NCBI] |
Taxonomic lineagei | Viruses › Riboviria › Orthornavirae › Kitrinoviricota › Flasuviricetes › Amarillovirales › Flaviviridae › Flavivirus › |
Virus hosti | Aedimorphus [TaxID: 53540] Diceromyia [TaxID: 53539] Erythrocebus patas (Red guenon) (Cercopithecus patas) [TaxID: 9538] Homo sapiens (Human) [TaxID: 9606] Stegomyia [TaxID: 53541] |
Proteomesi |
|
Subcellular locationi
- Virion By similarity
- Host nucleus By similarity
- Host cytoplasm By similarity
- host perinuclear region By similarity
- Secreted By similarity
- Virion membrane By similarity; Multi-pass membrane protein Sequence analysis
- Host endoplasmic reticulum membrane By similarity; Multi-pass membrane protein Sequence analysis
- Virion membrane By similarity; Multi-pass membrane protein Sequence analysis
- Host endoplasmic reticulum membrane By similarity; Multi-pass membrane protein Sequence analysis
- 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
- Host endoplasmic reticulum membrane By similarity; Multi-pass membrane protein By similarity
- Host endoplasmic reticulum membrane ; Multi-pass membrane protein By similarity
- 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
- Host endoplasmic reticulum membrane By similarity; Multi-pass membrane protein By similarity
- 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
- Host endoplasmic reticulum membrane By similarity; Multi-pass membrane protein By similarity Note: Located in RE-derived vesicles hosting the replication complex.By similarity
- 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 key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 1 – 101 | CytoplasmicSequence analysisAdd BLAST | 101 | |
Transmembranei | 102 – 122 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 123 – 238 | ExtracellularSequence analysisAdd BLAST | 116 | |
Transmembranei | 239 – 259 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 260 – 265 | CytoplasmicSequence analysis | 6 | |
Transmembranei | 266 – 280 | HelicalSequence analysisAdd BLAST | 15 | |
Topological domaini | 281 – 725 | ExtracellularSequence analysisAdd BLAST | 445 | |
Transmembranei | 726 – 746 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 747 – 752 | CytoplasmicSequence analysis | 6 | |
Transmembranei | 753 – 773 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 774 – 1195 | ExtracellularSequence analysisAdd BLAST | 422 | |
Transmembranei | 1196 – 1220 | HelicalSequence analysisAdd BLAST | 25 | |
Topological domaini | 1221 – 1226 | CytoplasmicSequence analysis | 6 | |
Transmembranei | 1227 – 1245 | HelicalSequence analysisAdd BLAST | 19 | |
Topological domaini | 1246 – 1269 | LumenalSequence analysisAdd BLAST | 24 | |
Transmembranei | 1270 – 1290 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 1291 | CytoplasmicSequence analysis | 1 | |
Transmembranei | 1292 – 1312 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 1313 – 1317 | LumenalSequence analysis | 5 | |
Transmembranei | 1318 – 1338 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 1339 – 1346 | CytoplasmicSequence analysis | 8 | |
Transmembranei | 1347 – 1367 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 1368 – 1370 | LumenalSequence analysis | 3 | |
Transmembranei | 1371 – 1391 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 1392 – 1447 | CytoplasmicSequence analysisAdd BLAST | 56 | |
Intramembranei | 1448 – 1468 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 1469 – 2147 | CytoplasmicSequence analysisAdd BLAST | 679 | |
Transmembranei | 2148 – 2168 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 2169 – 2170 | LumenalSequence analysis | 2 | |
Intramembranei | 2171 – 2191 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 2192 | LumenalSequence analysis | 1 | |
Transmembranei | 2193 – 2213 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 2214 – 2228 | CytoplasmicSequence analysisAdd BLAST | 15 | |
Transmembranei | 2229 – 2249 | Helical; Note=Signal for NS4BSequence analysisAdd BLAST | 21 | |
Topological domaini | 2250 – 2274 | LumenalSequence analysisAdd BLAST | 25 | |
Intramembranei | 2275 – 2295 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 2296 – 2316 | LumenalSequence analysisAdd BLAST | 21 | |
Intramembranei | 2317 – 2337 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 2338 – 2347 | LumenalSequence analysis | 10 | |
Transmembranei | 2348 – 2368 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 2369 – 2413 | CytoplasmicSequence analysisAdd BLAST | 45 | |
Transmembranei | 2414 – 2434 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 2435 – 2459 | LumenalSequence analysisAdd BLAST | 25 | |
Transmembranei | 2460 – 2480 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 2481 – 3391 | CytoplasmicSequence analysisAdd BLAST | 911 |
Keywords - Cellular componenti
Capsid protein, Host cytoplasm, Host endoplasmic reticulum, Host membrane, Host mitochondrion, Host nucleus, Membrane, Secreted, Viral envelope protein, VirionPTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000405218 | 1 – 3391 | Genome polyproteinAdd BLAST | 3391 | |
ChainiPRO_0000268028 | 1 – 100 | Capsid protein CBy similarityAdd BLAST | 100 | |
PropeptideiPRO_0000268029 | 101 – 114 | ER anchor for the capsid protein C, removed in mature form by serine protease NS3By similarityAdd BLAST | 14 | |
ChainiPRO_0000268030 | 115 – 280 | Protein prMBy similarityAdd BLAST | 166 | |
ChainiPRO_0000268031 | 115 – 205 | Peptide prBy similarityAdd BLAST | 91 | |
ChainiPRO_0000268032 | 206 – 280 | Small envelope protein MBy similarityAdd BLAST | 75 | |
ChainiPRO_0000268033 | 281 – 775 | Envelope protein EBy similarityAdd BLAST | 495 | |
ChainiPRO_0000268034 | 776 – 1127 | Non-structural protein 1By similarityAdd BLAST | 352 | |
ChainiPRO_0000268036 | 1128 – 1345 | Non-structural protein 2ABy similarityAdd BLAST | 218 | |
ChainiPRO_0000268037 | 1346 – 1475 | Serine protease subunit NS2BBy similarityAdd BLAST | 130 | |
ChainiPRO_0000268038 | 1476 – 2093 | Serine protease NS3By similarityAdd BLAST | 618 | |
ChainiPRO_0000268039 | 2094 – 2220 | Non-structural protein 4ABy similarityAdd BLAST | 127 | |
PeptideiPRO_0000268040 | 2221 – 2243 | Peptide 2kBy similarityAdd BLAST | 23 | |
ChainiPRO_0000268041 | 2244 – 2491 | Non-structural protein 4BBy similarityAdd BLAST | 248 | |
ChainiPRO_0000268042 | 2492 – 3391 | RNA-directed RNA polymerase NS5By similarityAdd BLAST | 900 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Glycosylationi | 183 | N-linked (GlcNAc...) asparagine; by hostPROSITE-ProRule annotation | 1 | |
Disulfide bondi | 283 ↔ 310 | By similarity | ||
Disulfide bondi | 340 ↔ 401 | By similarity | ||
Glycosylationi | 347 | N-linked (GlcNAc...) asparagine; by hostPROSITE-ProRule annotation | 1 | |
Disulfide bondi | 354 ↔ 385 | By similarity | ||
Disulfide bondi | 372 ↔ 396 | By similarity | ||
Glycosylationi | 433 | N-linked (GlcNAc...) asparagine; by hostPROSITE-ProRule annotation | 1 | |
Disulfide bondi | 465 ↔ 565 | By similarity | ||
Disulfide bondi | 582 ↔ 613 | By similarity | ||
Disulfide bondi | 779 ↔ 790 | By similarity | ||
Disulfide bondi | 830 ↔ 918 | By similarity | ||
Glycosylationi | 905 | N-linked (GlcNAc...) asparagine; by hostPROSITE-ProRule annotation | 1 | |
Disulfide bondi | 954 ↔ 998 | By similarity | ||
Glycosylationi | 982 | N-linked (GlcNAc...) asparagine; by hostPROSITE-ProRule annotation | 1 | |
Disulfide bondi | 1055 ↔ 1104 | By similarity | ||
Disulfide bondi | 1066 ↔ 1088 | By similarity | ||
Disulfide bondi | 1087 ↔ 1091 | By similarity | ||
Glycosylationi | 1134 | N-linked (GlcNAc...) asparagine; by hostPROSITE-ProRule annotation | 1 | |
Glycosylationi | 2301 | N-linked (GlcNAc...) asparagine; by hostPROSITE-ProRule annotation | 1 | |
Glycosylationi | 2305 | N-linked (GlcNAc...) asparagine; by hostPROSITE-ProRule annotation | 1 | |
Glycosylationi | 2457 | N-linked (GlcNAc...) asparagine; by hostPROSITE-ProRule annotation | 1 | |
Modified residuei | 2547 | PhosphoserineBy similarity | 1 |
Post-translational modificationi
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sitei | 100 – 101 | Cleavage; by viral protease NS3By similarity | 2 | |
Sitei | 114 – 115 | Cleavage; by host signal peptidaseBy similarity | 2 | |
Sitei | 205 – 206 | Cleavage; by host furinSequence analysisBy similarity | 2 | |
Sitei | 280 – 281 | Cleavage; by host signal peptidaseBy similarity | 2 | |
Sitei | 775 – 776 | Cleavage; by host signal peptidaseBy similarity | 2 | |
Sitei | 1127 – 1128 | Cleavage; by hostBy similarity | 2 | |
Sitei | 1345 – 1346 | Cleavage; by viral protease NS3By similarity | 2 | |
Sitei | 1475 – 1476 | Cleavage; by autolysisBy similarity | 2 | |
Sitei | 2093 – 2094 | Cleavage; by autolysisBy similarity | 2 | |
Sitei | 2220 – 2221 | Cleavage; by viral protease NS3By similarity | 2 | |
Sitei | 2243 – 2244 | Cleavage; by host signal peptidaseBy similarity | 2 | |
Sitei | 2491 – 2492 | Cleavage; by viral protease NS3By similarity | 2 |
Keywords - PTMi
Cleavage on pair of basic residues, Disulfide bond, Glycoprotein, Phosphoprotein, Ubl conjugationInteractioni
Subunit structurei
Homodimer.
Interacts (via N-terminus) with host EXOC1 (via C-terminus); this interaction results in EXOC1 degradation through the proteasome degradation pathway.
By similarityForms heterodimers with envelope protein E in the endoplasmic reticulum and Golgi.
By similarityHomodimer; in the endoplasmic reticulum and Golgi.
Interacts with protein prM.
Interacts with non-structural protein 1.
By similarityHomodimer; Homohexamer when secreted.
Interacts with envelope protein E.
By similarityForms a heterodimer with serine protease NS3. May form homooligomers.
By similarityForms a heterodimer with NS2B.
Interacts with NS4B.
Interacts with unphosphorylated RNA-directed RNA polymerase NS5; this interaction stimulates RNA-directed RNA polymerase NS5 guanylyltransferase activity.
Interacts with host SHFL.
By similarityInteracts with host MAVS; this interaction inhibits the synthesis of IFN-beta.
Interacts with host SHFL (By similarity).
Interacts with host AUP1; the interaction occurs in the presence of Dengue virus NS4B and induces lipophagy which facilitates production of virus progeny particles (By similarity). May interact with host SRPRA and SEC61G (By similarity).
By similarityHomodimer (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 (By similarity).
Interacts with host PAF1 complex; the interaction may prevent the recruitment of the PAF1 complex to interferon-responsive genes, and thus reduces the immune response (By similarity).
By similarityGO - Molecular functioni
- protein dimerization activity Source: InterPro
Structurei
3D structure databases
BMRBi | Q9WDA6 |
SMRi | Q9WDA6 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | Q9WDA6 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 1476 – 1653 | Peptidase S7PROSITE-ProRule annotationAdd BLAST | 178 | |
Domaini | 1655 – 1811 | Helicase ATP-bindingPROSITE-ProRule annotationAdd BLAST | 157 | |
Domaini | 1821 – 1988 | Helicase C-terminalPROSITE-ProRule annotationAdd BLAST | 168 | |
Domaini | 2493 – 2755 | mRNA cap 0-1 NS5-type MTPROSITE-ProRule annotationAdd BLAST | 263 | |
Domaini | 3020 – 3169 | RdRp catalyticPROSITE-ProRule annotationAdd BLAST | 150 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 1 – 15 | Interaction with host EXOC1By similarityAdd BLAST | 15 | |
Regioni | 37 – 72 | Hydrophobic; homodimerization of capsid protein CBy similarityAdd BLAST | 36 | |
Regioni | 378 – 391 | Fusion peptideBy similarityAdd BLAST | 14 | |
Regioni | 1398 – 1437 | Interacts with and activates NS3 proteasePROSITE-ProRule annotationAdd BLAST | 40 | |
Regioni | 1659 – 1662 | Important for RNA-bindingBy similarity | 4 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 1759 – 1762 | DEAH boxPROSITE-ProRule annotation | 4 | |
Motifi | 2568 – 2571 | SUMO-interacting motifBy similarity | 4 |
Domaini
Sequence similaritiesi
Keywords - Domaini
Transmembrane, Transmembrane helixFamily and domain databases
CDDi | cd20761, capping_2-OMTase_Flaviviridae, 1 hit cd12149, Flavi_E_C, 1 hit |
Gene3Di | 1.10.10.930, 1 hit 1.10.8.970, 1 hit 1.20.1280.260, 1 hit 2.40.10.10, 1 hit 2.60.260.50, 1 hit 2.60.40.350, 1 hit 2.60.98.10, 1 hit 3.30.387.10, 1 hit 3.30.67.10, 1 hit 3.40.50.150, 1 hit 3.40.50.300, 2 hits |
InterProi | View protein in InterPro IPR011492, DEAD_Flavivir IPR043502, DNA/RNA_pol_sf 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 IPR043504, Peptidase_S1_PA_chymotrypsin IPR000208, RNA-dir_pol_flavivirus IPR007094, RNA-dir_pol_PSvirus IPR002877, rRNA_MeTrfase_FtsJ_dom IPR029063, SAM-dependent_MTases |
Pfami | View 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 |
PIRSFi | PIRSF003817, Gen_Poly_FLV, 1 hit |
SMARTi | View protein in SMART SM00487, DEXDc, 1 hit SM00490, HELICc, 1 hit |
SUPFAMi | SSF101257, SSF101257, 1 hit SSF50494, SSF50494, 1 hit SSF52540, SSF52540, 2 hits SSF53335, SSF53335, 1 hit SSF56672, SSF56672, 1 hit SSF56983, SSF56983, 1 hit SSF81296, SSF81296, 1 hit |
TIGRFAMsi | TIGR04240, flavi_E_stem, 1 hit |
PROSITEi | View 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 |
i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
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 TKDGTNMCTL
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 THFQRVLIFI LLTAIAPSMT MRCIGISNRD FVEGVSGGSW
310 320 330 340 350
VDIVLEHGSC VTTMAKNKPT LDFELIKTEA KQPATLRKYC IEAKLTNTTT
360 370 380 390 400
DSRCPTQGEP TLNEEQDKRF VCKHSMVDRG WGNGCGLFGK GGIVTCAMFT
410 420 430 440 450
CKKNMEGKIV QPENLEYTVV ITPHSGEEHA VGNDTGKHGK EVKITPQSSI
460 470 480 490 500
TEAELTGYGT VTMECSPRTG LDFNEMVLLQ MEDKAWLVHR QWFLDLPLPW
510 520 530 540 550
LPGADTQGSN WIQKETLVTF KNPHAKKQDV VVLGSQEGAM HTALTGATEI
560 570 580 590 600
QMSSGNLLFT GHLKCRLRMD KLQLKGMSYS MCTGKFKIVK EIAETQHGTI
610 620 630 640 650
VIRVQYEGDG SPCKIPFEIM DLEKRHVLGR LITVNPIVTE KDSPVNIEAE
660 670 680 690 700
PPFGDSYIII GAEPGQLKLD WFKKGSSIGQ MFETTMRGAK RMAILGDTAW
710 720 730 740 750
DFGSLGGVFT SIGKALHQVF GAIYGAAFSG VSWTMKILIG VIITWIGMNS
760 770 780 790 800
RSTSLSVSLV LVGIVTLYLG VMVQADSGCV VSWKNKELKC GSGIFVTDNV
810 820 830 840 850
HTWTEQYKFQ PESPSKLASA IQKAHEEGIC GIRSVTRLEN LMWKQITSEL
860 870 880 890 900
NHILSENEVK LTIMTGDIKG IMQVGKRSLR PQPTELRYSW KTWGKAKMLS
910 920 930 940 950
TELHNQTFLI DGPETAECPN TNRAWNSLEV EDYGFGVFTT NIWLRLREKQ
960 970 980 990 1000
DAFCDSKLMS AAIKDNRAVH ADMGYWIESA LNDTWKIEKA SFIEVKSCHW
1010 1020 1030 1040 1050
PKSHTLWSNG VLESEMVIPK NIAGPVSQHN NRPGYHTQTA GPWHLGKLEM
1060 1070 1080 1090 1100
DFDFCEGTTV VVTEECGNRG PSLRTTTASG KLITEWCCRS CTLPPLRYRG
1110 1120 1130 1140 1150
EDGCWYGMEI RPLKEKEENL VSSLVTAGHG QIDNFSLGIL GMALFLEEML
1160 1170 1180 1190 1200
RTRVGTKHAI LLVAVSFLTL ITGNMSFRDL GRVMVMVGAT MTDDIGMGVT
1210 1220 1230 1240 1250
YLALLAAFKV RPTFAAGLLL RKLTSKELMM TTIGIVLLSQ SSIPETILEL
1260 1270 1280 1290 1300
TDALALGMMV LKMVRNMEKY QLAVTIMAIL CVPNAVILQN AWKVSCTTLA
1310 1320 1330 1340 1350
VVSVSPLLLT SSQQKADWIP LALTIKGLNP TAIFLTTLTR TSKKRSWPLN
1360 1370 1380 1390 1400
EAIMAVGMVS ILASSLLKND IPMTGPLVAG GLLTVCYVLT GRSADLELER
1410 1420 1430 1440 1450
ATDVKWDDQA EISGSSPILS ITISEDGSMS IKNEEEEQTL TILIRTGLLV
1460 1470 1480 1490 1500
ISGLFPVSIP ITAAAWYLWE VKKQRAGVLW DVPSPPPVGR AELEDGAYRI
1510 1520 1530 1540 1550
KQKGILGYSQ IGAGVYKEGT FHTMWHVTRG AVLMHKGKRI EPSWADVKKD
1560 1570 1580 1590 1600
LISYGGGWKL EGEWKEGEEV QVLALEPGKN PRAVQTKPGL FRTNTGTIGA
1610 1620 1630 1640 1650
VSLDFSPGTS GSPIVDKKGK VVGLYGNGVV TRGGAYVSAI AQTEKGIEDN
1660 1670 1680 1690 1700
PEIEDDIFRK RRLTIMDLHP GAGKTKRYLP AIVREAIKRG LRTLILAPTR
1710 1720 1730 1740 1750
VVAAEMEEAL RGLPIRYQTP AIRAEHTGRE IVDLMCHATF TMRLLSPIRV
1760 1770 1780 1790 1800
PNYNLIIMDE AHFTDPASIA ARGYISTRVE MGEAAGIFMT ATPPGSRDPF
1810 1820 1830 1840 1850
PQSNAPIMDE EREIPERSWN SGHEWVTDFK GKTVWFVPSI KTGNDIAACL
1860 1870 1880 1890 1900
RKNGKRVIQL SRKTFDSEYV KTRTNDWDFV VTTDISEMGA NFKAERVIDP
1910 1920 1930 1940 1950
RRCMKPVILT DGEERVILAG PMPVTHSSAA QRRGRIGRNP RNENDQYIYM
1960 1970 1980 1990 2000
GEPLENDEDC AHWKEAKMLL DNINTPEGII PSMFEPEREK VDAIDGEYRL
2010 2020 2030 2040 2050
RGEARKTFVD LMRRGDLPVW LAYKVAAEGI NYADRRWCFD GTRNNQILEE
2060 2070 2080 2090 2100
NVEVEIWTKE GERKKLKPRW LDARIYSDPL ALKEFKEFAA GRKSLTLNLI
2110 2120 2130 2140 2150
TEMGRLPTFM TQKARDALDN LAVLHTAEAG GKAYNHALSE LPETLETLLL
2160 2170 2180 2190 2200
LTLLATVTGG IFLFLMSGRG IGKMTLGMCC IITASILLWY AQIQPHWIAA
2210 2220 2230 2240 2250
SIILEFFLIV LLIPEPEKQR TPQDNQLTYV IIAILTVVAA TMANEMGFLE
2260 2270 2280 2290 2300
KTKKDLGLGH IATQQPESNI LDIDLRPASA WTLYAVATTF ITPMLRHSIE
2310 2320 2330 2340 2350
NSSVNVSLTA IANQATVLMG LGKGWPLSKM DIGVPLLAIG CYSQVNPITL
2360 2370 2380 2390 2400
TAALLMLVAH YAIIGPGLQA KATREAQKRA AAGIMKNPTV DGITVIDLDP
2410 2420 2430 2440 2450
IPYDPKFEKQ LGQVMLLVLC VTQVLMMRTT WALCEALTLA TGPVSTLWEG
2460 2470 2480 2490 2500
NPGRFWNTTI AVSMANIFRG SYLAGAGLLF SIMKNTTSTR RGTGNMGETL
2510 2520 2530 2540 2550
GEKWKNRLNA LGKSEFQIYK KSGIQEVDRT LAKEGIKRGE TDHHAVSRGS
2560 2570 2580 2590 2600
AKLRWFVERN LVTPEGKVVD LGCGRGGWSY YCGGLKNVRE VKGLTKGGPG
2610 2620 2630 2640 2650
HEEPIPMSTY GWNLVRLQSG VDVFFVPPEK CDTLLCDIGE SSPNPTVEAG
2660 2670 2680 2690 2700
RTLRVLNLVE NWLNNNTQFC VKVLNPYMPS VIERMETLQR KYGGALVRNP
2710 2720 2730 2740 2750
LSRNSTHEMY WVSNASGNIV SSVNMISRML INRFTMRHKK ATYEPDVDLG
2760 2770 2780 2790 2800
SGTRNIGIES ETPNLDIIGK RIEKIKQEHE TSWHYDQDHP YKTWAYHGSY
2810 2820 2830 2840 2850
ETKQTGSASS MVNGVVRLLT KPWDVIPMVT QMAMTDTTPF GQQRVFKEKV
2860 2870 2880 2890 2900
DTRTQEPKEG TKKLMKITAE WLWKELGKKK TPRMCTREEF TKKVRSNAAL
2910 2920 2930 2940 2950
GAIFTDENKW KSAREAVEDN RFWELVDKER NLHLEGKCET CVYNMMGKRE
2960 2970 2980 2990 3000
KKLGEFGKAK GSRAIWYMWL GARFLEFEAL GFLNEDHWFS RENSLSGVEG
3010 3020 3030 3040 3050
EGLHKLGYIL REVSKKEGGA MYADDTAGWD TRITIEDLKN EEMITNHMAG
3060 3070 3080 3090 3100
EHKKLAEAIF KLTYQNKVVR VQRPTPRGTV MDIISRRDQR GSGQVVTYGL
3110 3120 3130 3140 3150
NTFTNMEAQL IRQMEGEGVF KSIQHLTASE EIAVQDWLVR VGRERLSRMA
3160 3170 3180 3190 3200
ISGDDCVVKP LDDRFAKALT ALNDMGKVRK DIQQWEPSRG WNDWTQVPFC
3210 3220 3230 3240 3250
SHHFHELIMK DGRTLVVPCR NQDELIGRAR ISQGAGWSLR ETACLGKSYA
3260 3270 3280 3290 3300
QMWSLMYFHR RDLRLAANAI CSAVPSHWVP TSRTTWSIHA SHEWMTTEDM
3310 3320 3330 3340 3350
LTVWNRVWIL ENPWMEDKTP VESWEEIPYL GKREDQWCGS LIGLTSRATW
3360 3370 3380 3390
AKNIQTAINQ VRSLIGNEEY TDYMPSMKRF RREEEEVGVL W
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF100468 Genomic RNA Translation: AAD32963.1 |
PIRi | B25817 JS0219 |
Similar proteinsi
Cross-referencesi
Web resourcesi
Virus Pathogen Resource |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF100468 Genomic RNA Translation: AAD32963.1 |
PIRi | B25817 JS0219 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
3IXY | electron microscopy | - | A/B/C | 281-675 | [»] | |
BMRBi | Q9WDA6 | |||||
SMRi | Q9WDA6 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein family/group databases
MEROPSi | S07.001 |
Protocols and materials databases
ABCDi | Q9WDA6, 2 sequenced antibodies |
Miscellaneous databases
EvolutionaryTracei | Q9WDA6 |
PROi | PR:Q9WDA6 |
Family and domain databases
CDDi | cd20761, capping_2-OMTase_Flaviviridae, 1 hit cd12149, Flavi_E_C, 1 hit |
Gene3Di | 1.10.10.930, 1 hit 1.10.8.970, 1 hit 1.20.1280.260, 1 hit 2.40.10.10, 1 hit 2.60.260.50, 1 hit 2.60.40.350, 1 hit 2.60.98.10, 1 hit 3.30.387.10, 1 hit 3.30.67.10, 1 hit 3.40.50.150, 1 hit 3.40.50.300, 2 hits |
InterProi | View protein in InterPro IPR011492, DEAD_Flavivir IPR043502, DNA/RNA_pol_sf 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 IPR043504, Peptidase_S1_PA_chymotrypsin IPR000208, RNA-dir_pol_flavivirus IPR007094, RNA-dir_pol_PSvirus IPR002877, rRNA_MeTrfase_FtsJ_dom IPR029063, SAM-dependent_MTases |
Pfami | View 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 |
PIRSFi | PIRSF003817, Gen_Poly_FLV, 1 hit |
SMARTi | View protein in SMART SM00487, DEXDc, 1 hit SM00490, HELICc, 1 hit |
SUPFAMi | SSF101257, SSF101257, 1 hit SSF50494, SSF50494, 1 hit SSF52540, SSF52540, 2 hits SSF53335, SSF53335, 1 hit SSF56672, SSF56672, 1 hit SSF56983, SSF56983, 1 hit SSF81296, SSF81296, 1 hit |
TIGRFAMsi | TIGR04240, flavi_E_stem, 1 hit |
PROSITEi | View 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 |
MobiDBi | Search... |
Entry informationi
Entry namei | POLG_DEN2Q | |
Accessioni | Q9WDA6Primary (citable) accession number: Q9WDA6 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | December 12, 2006 |
Last sequence update: | November 1, 1999 | |
Last modified: | May 25, 2022 | |
This is version 144 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Viral Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
3D-structureDocuments
- PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families