P33478 (POLG_DEN1S) Reviewed, UniProtKB/Swiss-Prot
Last modified
May 29, 2013.
Version 126.
History...
Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order
Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize orderNames and origin
Protein attributes
| Sequence length | 3396 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is further processed into a mature form. |
| Protein existence | Inferred from homology |
General annotation (Comments)
| Function | Capsid protein C self-assembles to form an icosahedral capsid about 30 nm in diameter. The capsid encapsulates the genomic RNA By similarity. prM acts as a chaperone for envelope protein E during intracellular virion assembly by masking and inactivating envelope protein E fusion peptide. prM is matured in the last step of virion assembly, presumably to avoid catastrophic activation of the viral fusion peptide induced by the acidic pH of the trans-Golgi network. After cleavage by host furin, the pr peptide is released in the extracellular medium and small envelope protein M and envelope protein E homodimers are dissociated By similarity. Envelope protein E binding to host cell surface receptor is followed by virus internalization through clathrin-mediated endocytosis. Envelope protein E is subsequently involved in membrane fusion between virion and host late endosomes. Synthesized as a homodimer with prM which acts as a chaperone for envelope protein E. After cleavage of prM, envelope protein E dissociate from small envelope protein M and homodimerizes By similarity. Non-structural protein 1 is involved in virus replication and regulation of the innate immune response. Soluble and membrane-associated NS1 may activate human complement and induce host vascular leakage. This effect might explain the clinical manifestations of dengue hemorrhagic fever and dengue shock syndrome By similarity. Non-structural protein 2A may be involved viral RNA replication and capsid assembly Potential. Non-structural protein 2B is a required cofactor for the serine protease function of NS3 By 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 By similarity. Non-structural protein 4A induces host endoplasmic reticulum membrane rearrangements leading to the formation of virus-induced membranous vesicles hosting the dsRNA and polymerase, functioning as a replication complex. NS4A might also regulate the ATPase activity of the NS3 helicase By similarity. 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 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 (-) 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 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 activity | 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). NTP + H2O = NDP + phosphate. ATP + H2O = ADP + phosphate. S-adenosyl-L-methionine + G(5')pppR-RNA = S-adenosyl-L-homocysteine + m7G(5')pppR-RNA. S-adenosyl-L-methionine + m7G(5')pppR-RNA = S-adenosyl-L-homocysteine + m7G(5')pppRm-RNA. |
| Subunit structure | Capsid protein C forms homodimers. prM and envelope protein E form heterodimers in the endoplasmic reticulum and Golgi. In immature particles, there are 60 icosaedrally organized trimeric spikes on the surface. Each spike consists of three heterodimers of envelope protein M precursor (prM) and envelope protein E. NS1 forms homodimers as well as homohexamers when secreted. NS1 may interact with NS4A. NS3 and NS2B form a heterodimer. NS3 is the catalytic subunit, whereas NS2B strongly stimulates the latter, acting as a cofactor. In the absence of the NS2B, NS3 protease is unfolded and inactive. NS3 interacts with unphosphorylated NS5; this interaction stimulates NS5 guanylyltransferase activity. NS5 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. |
| Subcellular location | Capsid protein C: Virion Potential. Peptide pr: Secreted By similarity. Small envelope protein M: Virion membrane; Multi-pass membrane protein By similarity. Host endoplasmic reticulum membrane; Multi-pass membrane protein By similarity. Envelope protein E: Virion membrane; Multi-pass membrane protein By similarity. Host endoplasmic reticulum membrane; Multi-pass membrane protein By similarity. Non-structural protein 1: Secreted. Host endoplasmic reticulum membrane; Peripheral membrane protein; Lumenal side By similarity. Non-structural protein 2A-alpha: Host endoplasmic reticulum membrane; Multi-pass membrane protein Potential. Non-structural protein 2A: Host endoplasmic reticulum membrane; Multi-pass membrane protein Potential. Serine protease subunit NS2B: Host endoplasmic reticulum membrane; Peripheral membrane protein; Cytoplasmic side By similarity. Serine protease NS3: Host endoplasmic reticulum membrane; Peripheral membrane protein; Cytoplasmic side By similarity. Note: Remains non-covalently associated to NS3 protease By similarity. Non-structural protein 4A: Host endoplasmic reticulum membrane; Multi-pass membrane protein By similarity. Note: Located in RE-associated vesicles hosting the replication complex. Non-structural protein 4B: Host endoplasmic reticulum membrane; Multi-pass membrane protein By similarity. RNA-directed RNA polymerase NS5: Host endoplasmic reticulum membrane; Peripheral membrane protein; Cytoplasmic side By similarity. Host nucleus By similarity. Note: Located in RE-associated vesicles hosting the replication complex. |
| Domain | Transmembrane domains of the small envelope protein M and envelope protein E contains an endoplasmic reticulum retention signals By similarity. |
| Post-translational modification | Specific enzymatic cleavages in vivo yield mature proteins. The nascent protein C contains a C-terminal hydrophobic domain that act as a signal sequence for translocation of prM into the lumen of the ER. Mature protein C is cleaved at a site upstream of this hydrophobic domain by NS3. prM is cleaved in post-Golgi vesicles by a host furin, releasing the mature small envelope protein M, and peptide pr. Non-structural protein 2A-alpha, a C-terminally truncated form of non-structural protein 2A, results from partial cleavage by NS3. Peptide 2K acts as a signal sequence and is removed from the N-terminus of NS4B by the host signal peptidase in the ER lumen. Signal cleavage at the 2K-4B site requires a prior NS3 protease-mediated cleavage at the 4A-2K site By similarity. RNA-directed RNA polymerase NS5 is phosphorylated on serines residues. This phosphorylation may trigger NS5 nuclear localization By similarity. Envelope protein E and non-structural protein 1 are N-glycosylated By similarity. |
| Sequence similarities | In the N-terminal section; belongs to the class I-like SAM-binding methyltransferase superfamily. mRNA cap 0-1 NS5-type methyltransferase family. Contains 1 helicase ATP-binding domain. Contains 1 helicase C-terminal domain. Contains 1 mRNA cap 0-1 NS5-type MT domain. Contains 1 peptidase S7 domain. Contains 1 RdRp catalytic domain. |
Ontologies
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||||
Molecule processing | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 3396 | 3396 | Genome polyprotein | PRO_0000405206 | |||||||
| Chain | 1 – 100 | 100 | Capsid protein C By similarity | PRO_0000037894 | |||||||
| Propeptide | 101 – 114 | 14 | ER anchor for the protein C, removed in mature form by serine protease NS3 | PRO_0000037895 | |||||||
| Chain | 115 – 280 | 166 | prM By similarity | PRO_0000264654 | |||||||
| Chain | 115 – 205 | 91 | Peptide pr By similarity | PRO_0000264655 | |||||||
| Chain | 206 – 280 | 75 | Small envelope protein M By similarity | PRO_0000037896 | |||||||
| Chain | 281 – 774 | 494 | Envelope protein E By similarity | PRO_0000037897 | |||||||
| Chain | 775 – 1126 | 352 | Non-structural protein 1 By similarity | PRO_0000037898 | |||||||
| Chain | 1127 – 1344 | 218 | Non-structural protein 2A By similarity | PRO_0000037899 | |||||||
| Chain | 1127 – 1315 | 189 | Non-structural protein 2A-alpha By similarity | PRO_0000264656 | |||||||
| Chain | 1345 – 1474 | 130 | Serine protease subunit NS2B By similarity | PRO_0000037900 | |||||||
| Chain | 1475 – 2093 | 619 | Serine protease NS3 By similarity | PRO_0000037901 | |||||||
| Chain | 2094 – 2220 | 127 | Non-structural protein 4A By similarity | PRO_0000037902 | |||||||
| Peptide | 2221 – 2243 | 23 | Peptide 2k | PRO_0000264657 | |||||||
| Chain | 2244 – 2492 | 249 | Non-structural protein 4B By similarity | PRO_0000037903 | |||||||
| Chain | 2493 – 3396 | 904 | RNA-directed RNA polymerase NS5 By similarity | PRO_0000037904 | |||||||
Regions | |||||||||||
| Topological domain | 1 – 101 | 101 | Cytoplasmic Potential | ||||||||
| Transmembrane | 102 – 119 | 18 | Helical; Potential | ||||||||
| Topological domain | 120 – 242 | 123 | Extracellular Potential | ||||||||
| Transmembrane | 243 – 260 | 18 | Helical; Potential | ||||||||
| Topological domain | 261 | 1 | Cytoplasmic Potential | ||||||||
| Transmembrane | 262 – 280 | 19 | Helical; Potential | ||||||||
| Topological domain | 281 – 725 | 445 | Extracellular Potential | ||||||||
| Intramembrane | 726 – 746 | 21 | Helical; Potential | ||||||||
| Topological domain | 747 – 752 | 6 | Extracellular Potential | ||||||||
| Intramembrane | 753 – 775 | 23 | Helical; Potential | ||||||||
| Topological domain | 776 – 1124 | 349 | Extracellular Potential | ||||||||
| Transmembrane | 1125 – 1145 | 21 | Helical; Potential | ||||||||
| Topological domain | 1146 – 1156 | 11 | Cytoplasmic Potential | ||||||||
| Transmembrane | 1157 – 1177 | 21 | Helical; Potential | ||||||||
| Topological domain | 1178 – 1198 | 21 | Lumenal Potential | ||||||||
| Transmembrane | 1199 – 1219 | 21 | Helical; Potential | ||||||||
| Topological domain | 1220 – 1288 | 69 | Cytoplasmic Potential | ||||||||
| Transmembrane | 1289 – 1309 | 21 | Helical; Potential | ||||||||
| Topological domain | 1310 – 1314 | 5 | Lumenal Potential | ||||||||
| Transmembrane | 1315 – 1335 | 21 | Helical; Potential | ||||||||
| Topological domain | 1336 – 1345 | 10 | Cytoplasmic Potential | ||||||||
| Transmembrane | 1346 – 1366 | 21 | Helical; Potential | ||||||||
| Topological domain | 1367 – 1369 | 3 | Lumenal Potential | ||||||||
| Transmembrane | 1370 – 1390 | 21 | Helical; Potential | ||||||||
| Topological domain | 1391 – 1446 | 56 | Cytoplasmic Potential | ||||||||
| Intramembrane | 1447 – 1467 | 21 | Helical; Potential | ||||||||
| Topological domain | 1468 – 2147 | 680 | Cytoplasmic Potential | ||||||||
| Transmembrane | 2148 – 2168 | 21 | Helical; Potential | ||||||||
| Topological domain | 2169 – 2170 | 2 | Lumenal Potential | ||||||||
| Intramembrane | 2171 – 2191 | 21 | Helical; Potential | ||||||||
| Topological domain | 2192 | 1 | Lumenal Potential | ||||||||
| Transmembrane | 2193 – 2213 | 21 | Helical; Potential | ||||||||
| Topological domain | 2214 – 2228 | 15 | Cytoplasmic Potential | ||||||||
| Transmembrane | 2229 – 2249 | 21 | Helical; Note=Signal for NS4B; Potential | ||||||||
| Topological domain | 2250 – 2275 | 26 | Lumenal Potential | ||||||||
| Intramembrane | 2276 – 2296 | 21 | Helical; Potential | ||||||||
| Topological domain | 2297 – 2348 | 52 | Lumenal Potential | ||||||||
| Transmembrane | 2349 – 2369 | 21 | Helical; Potential | ||||||||
| Topological domain | 2370 – 2414 | 45 | Cytoplasmic Potential | ||||||||
| Transmembrane | 2415 – 2435 | 21 | Helical; Potential | ||||||||
| Topological domain | 2436 – 2460 | 25 | Lumenal Potential | ||||||||
| Transmembrane | 2461 – 2481 | 21 | Helical; Potential | ||||||||
| Topological domain | 2482 – 3396 | 915 | Cytoplasmic Potential | ||||||||
| Domain | 1475 – 1652 | 178 | Peptidase S7 | ||||||||
| Domain | 1655 – 1811 | 157 | Helicase ATP-binding | ||||||||
| Domain | 1821 – 1988 | 168 | Helicase C-terminal | ||||||||
| Domain | 2494 – 2755 | 262 | mRNA cap 0-1 NS5-type MT | ||||||||
| Domain | 3019 – 3168 | 150 | RdRp catalytic | ||||||||
| Nucleotide binding | 1668 – 1675 | 8 | ATP By similarity | ||||||||
| Region | 33 – 74 | 42 | Hydrophobic; homodimerization of capsid protein C By similarity | ||||||||
| Region | 1397 – 1436 | 40 | Interacts with and activates NS3 protease By similarity | ||||||||
| Motif | 1759 – 1762 | 4 | DEAH box | ||||||||
Sites | |||||||||||
| Active site | 1525 | 1 | Charge relay system; for serine protease NS3 activity By similarity | ||||||||
| Active site | 1549 | 1 | Charge relay system; for serine protease NS3 activity By similarity | ||||||||
| Active site | 1609 | 1 | Charge relay system; for serine protease NS3 activity By similarity | ||||||||
| Binding site | 2506 | 1 | mRNA cap By similarity | ||||||||
| Binding site | 2509 | 1 | mRNA cap; via carbonyl oxygen By similarity | ||||||||
| Binding site | 2510 | 1 | mRNA cap By similarity | ||||||||
| Binding site | 2512 | 1 | mRNA cap; via carbonyl oxygen By similarity | ||||||||
| Binding site | 2521 | 1 | mRNA cap By similarity | ||||||||
| Binding site | 2548 | 1 | S-adenosyl-L-methionine By similarity | ||||||||
| Binding site | 2578 | 1 | S-adenosyl-L-methionine; via carbonyl oxygen By similarity | ||||||||
| Binding site | 2579 | 1 | S-adenosyl-L-methionine; via carbonyl oxygen By similarity | ||||||||
| Binding site | 2596 | 1 | S-adenosyl-L-methionine By similarity | ||||||||
| Binding site | 2597 | 1 | S-adenosyl-L-methionine; via carbonyl oxygen By similarity | ||||||||
| Binding site | 2623 | 1 | S-adenosyl-L-methionine By similarity | ||||||||
| Binding site | 2624 | 1 | S-adenosyl-L-methionine; via carbonyl oxygen By similarity | ||||||||
| Binding site | 2642 | 1 | mRNA cap By similarity | ||||||||
| Binding site | 2703 | 1 | mRNA cap By similarity | ||||||||
| Binding site | 2705 | 1 | mRNA cap By similarity | ||||||||
| Binding site | 2710 | 1 | S-adenosyl-L-methionine By similarity | ||||||||
| Site | 100 – 101 | 2 | Cleavage; by viral protease NS3 Potential | ||||||||
| Site | 114 – 115 | 2 | Cleavage; by host signal peptidase By similarity | ||||||||
| Site | 205 – 206 | 2 | Cleavage; by host furin Potential | ||||||||
| Site | 280 – 281 | 2 | Cleavage; by host signal peptidase Potential | ||||||||
| Site | 774 – 775 | 2 | Cleavage; by host signal peptidase Potential | ||||||||
| Site | 1126 – 1127 | 2 | Cleavage; by host By similarity | ||||||||
| Site | 1344 – 1345 | 2 | Cleavage; by viral protease NS3 Potential | ||||||||
| Site | 1474 – 1475 | 2 | Cleavage; by autolysis Potential | ||||||||
| Site | 2093 – 2094 | 2 | Cleavage; by autolysis Potential | ||||||||
| Site | 2220 – 2221 | 2 | Cleavage; by viral protease NS3 Potential | ||||||||
| Site | 2243 – 2244 | 2 | Cleavage; by host signal peptidase Potential | ||||||||
| Site | 2492 – 2493 | 2 | Cleavage; by viral protease NS3 Potential | ||||||||
| Site | 2517 | 1 | mRNA cap binding By similarity | ||||||||
| Site | 2553 | 1 | Essential for 2'-O-methyltransferase activity By similarity | ||||||||
| Site | 2638 | 1 | Essential for 2'-O-methyltransferase and N-7 methyltransferase activity By similarity | ||||||||
| Site | 2639 | 1 | S-adenosyl-L-methionine binding By similarity | ||||||||
| Site | 2672 | 1 | Essential for 2'-O-methyltransferase activity By similarity | ||||||||
| Site | 2708 | 1 | Essential for 2'-O-methyltransferase activity By similarity | ||||||||
Amino acid modifications | |||||||||||
| Glycosylation | 183 | 1 | N-linked (GlcNAc...); by host Potential | ||||||||
| Glycosylation | 347 | 1 | N-linked (GlcNAc...); by host Potential | ||||||||
| Glycosylation | 433 | 1 | N-linked (GlcNAc...); by host Potential | ||||||||
| Glycosylation | 981 | 1 | N-linked (GlcNAc...); by host Potential | ||||||||
| Glycosylation | 2302 | 1 | N-linked (GlcNAc...); by host Potential | ||||||||
| Glycosylation | 2306 | 1 | N-linked (GlcNAc...); by host Potential | ||||||||
| Glycosylation | 2458 | 1 | N-linked (GlcNAc...); by host Potential | ||||||||
| Disulfide bond | 283 ↔ 310 | By similarity | |||||||||
| Disulfide bond | 340 ↔ 401 | By similarity | |||||||||
| Disulfide bond | 354 ↔ 385 | By similarity | |||||||||
| Disulfide bond | 372 ↔ 396 | By similarity | |||||||||
| Disulfide bond | 465 ↔ 565 | By similarity | |||||||||
| Disulfide bond | 582 ↔ 613 | By similarity | |||||||||
Sequences
| ||||||||||||||||||
References
| [1] | "Full-length cDNA sequence of dengue type 1 virus (Singapore strain S275/90)." Fu J., Tan B.H., Yap E.H., Chan Y.C., Tan Y.H. Virology 188:953-958(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA]. |
Web resources
Cross-references
Sequence databases | |
|---|---|
| EMBL GenBank DDBJ | M87512 Genomic RNA. No translation available. |
| PIR | A42551. |
3D structure databases | |
| ProteinModelPortal | P33478. |
| SMR | P33478. Positions 21-100, 115-195, 281-673, 1494-2093, 2498-2759, 2765-3374. |
| ModBase | Search... |
Protein family/group databases | |
| MEROPS | S07.001. |
Protocols and materials databases | |
| StructuralBiologyKnowledgebase | Search... |
Family and domain databases | |
| Gene3D | 2.60.40.350. 1 hit. 2.60.98.10. 2 hits. 3.30.387.10. 1 hit. |
| InterPro | IPR011492. DEAD_Flavivir. IPR000069. Env_glycoprot_M_flavivir. IPR013755. Flav_gly_cen_dom_subdom1. IPR001122. Flavi_capsidC. IPR026470. Flavi_E_Stem/Anchor_dom. IPR001157. Flavi_NS1. IPR000752. Flavi_NS2A. IPR000487. Flavi_NS2B. IPR000404. Flavi_NS4A. IPR001528. Flavi_NS4B. IPR002535. Flavi_propep. IPR000336. Flavivir/Alphavir_Ig-like. IPR001850. Flavivirus_NS3_S7. IPR027287. Flavovir_Ig-like. IPR014412. Gen_Poly_FLV. IPR011998. Glycoprot_cen/dimer. IPR013754. GlyE_dim. IPR014001. Helicase_ATP-bd. IPR001650. Helicase_C. IPR014756. Ig_E-set. IPR026490. mRNA_cap_0/1_MeTrfase. IPR027417. P-loop_NTPase. IPR000208. RNA-dir_pol_flavivirus. IPR007094. RNA-dir_pol_PSvirus. IPR002877. rRNA_MeTrfase_FtsJ_dom. IPR009003. Trypsin-like_Pept_dom. [Graphical view] |
| 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. PF00271. Helicase_C. 1 hit. PF00949. Peptidase_S7. 1 hit. [Graphical view] |
| PIRSF | PIRSF003817. Gen_Poly_FLV. 1 hit. |
| SMART | SM00487. DEXDc. 1 hit. SM00490. HELICc. 1 hit. [Graphical view] |
| SUPFAM | SSF56983. Flavi_glycoprotE. 1 hit. SSF81296. Ig_E-set. 1 hit. SSF50494. Pept_Ser_Cys. 1 hit. SSF52540. SSF52540. 2 hits. |
| TIGRFAMs | TIGR04240. flavi_E_stem. 1 hit. |
| PROSITE | PS00690. DEAH_ATP_HELICASE. False negative. 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. [Graphical view] |
| ProtoNet | Search... |
Entry information
| Entry name | POLG_DEN1S | ||||||||
| Accession | Primary (citable) accession number: P33478 | ||||||||
| Entry history |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation program | Viral Protein Annotation Program | ||||||||
Relevant documents
| Peptidase families Classification of peptidase families and list of entries |
| SIMILARITY comments Index of protein domains and families |

Clusters with
