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UniProtKB/Swiss-Prot entry P29990


[Entry info] [Name and origin] [References] [Comments] [Cross-references] [Keywords] [Features] [Sequence] [Tools]

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Entry information
Entry name POLG_DEN26
Primary accession number P29990
Secondary accession numbers None
Integrated into Swiss-Prot on April 1, 1993
Sequence was last modified on April 1, 1993 (Sequence version 1)
Annotations were last modified on    November 25, 2008 (Entry version 87)
Name and origin of the protein
Protein name Genome polyprotein
Synonyms None
Contains Protein C
     (Core protein)
     (Capsid protein)
prM
Peptide pr
Small envelope protein M
     (Matrix protein)
Envelope protein E
Non-structural protein 1
     (NS1)
Non-structural protein 2A
     (NS2A)
Non-structural protein 2A-alpha
     (NS2A-alpha)
Serine protease subunit NS2B
     (Non-structural protein 2B)
Serine protease subunit NS3
     (EC 3.4.21.91)
     (Non-structural protein 3)
Non-structural protein 4A
     (NS4A)
Peptide 2k
Non-structural protein 4B
     (NS4B)
RNA-directed RNA polymerase NS5
     (EC 2.7.7.48)
     (EC 2.1.1.56)
     (Non-structural protein 5)
Gene name None
From
Dengue virus type 2 (strain Thailand/16681/1984) (DENV-2) [TaxID: 31634] 
Taxonomy Viruses; ssRNA positive-strand viruses, no DNA stage; Flaviviridae; Flavivirus; Dengue virus group.
Virus hosts Aedes aegypti (Yellowfever mosquito) [TaxID: 7159]
Aedes furcifer [TaxID: 299627]
Aedes taylori [TaxID: 299628]
Erythrocebus patas (Red guenon) (Cercopithecus patas) [TaxID: 9538]
Homo sapiens (Human) [TaxID: 9606]
Protein existence 1: Evidence at protein level;
References
[1]
NUCLEOTIDE SEQUENCE [GENOMIC RNA].
DOI=10.1016/0042-6822(92)90460-7; PubMed=1312269 [NCBI, ExPASy, EBI, Israel, Japan]
Blok J., McWilliam S.M., Butler H.C., Gibbs A.J., Weiller G., Herring B.L., Hemsley A.C., Aaskov J.G., Yoksan S., Bhamarapravati N.;
"Comparison of a dengue-2 virus and its candidate vaccine derivative: sequence relationships with the flaviviruses and other viruses.";
Virology 187:573-590(1992).
[2]
PROTEOLYTIC PROCESSING OF POLYPROTEIN.
DOI=10.1128/JVI.78.5.2367-2381.2004; PubMed=14963133 [NCBI, ExPASy, EBI, Israel, Japan]
Keelapang P., Sriburi R., Supasa S., Panyadee N., Songjaeng A., Jairungsri A., Puttikhunt C., Kasinrerk W., Malasit P., Sittisombut N.;
"Alterations of pr-M cleavage and virus export in pr-M junction chimeric dengue viruses.";
J. Virol. 78:2367-2381(2004).
[3]
FUNCTION OF NON-STRUCTURAL PROTEIN 4B.
DOI=10.1128/JVI.79.13.8004-8013.2005; PubMed=15956546 [NCBI, ExPASy, EBI, Israel, Japan]
Munoz-Jordan J.L., Laurent-Rolle M., Ashour J., Martinez-Sobrido L., Ashok M., Lipkin W.I., Garcia-Sastre A.;
"Inhibition of alpha/beta interferon signaling by the NS4B protein of flaviviruses.";
J. Virol. 79:8004-8013(2005).
[4]
FUNCTION OF NS1.
DOI=10.1086/500949; PubMed=16544248 [NCBI, ExPASy, EBI, Israel, Japan]
Avirutnan P., Punyadee N., Noisakran S., Komoltri C., Thiemmeca S., Auethavornanan K., Jairungsri A., Kanlaya R., Tangthawornchaikul N., Puttikhunt C., Pattanakitsakul S.N., Yenchitsomanus P.T., Mongkolsapaya J., Kasinrerk W., Sittisombut N., Husmann M., Blettner M., Vasanawathana S., Bhakdi S., Malasit P.;
"Vascular leakage in severe dengue virus infections: a potential role for the nonstructural viral protein NS1 and complement.";
J. Infect. Dis. 193:1078-1088(2006).
[5]
POLYPROTEIN CLEAVAGE.
DOI=10.1042/BJ20061136; PubMed=17067286 [NCBI, ExPASy, EBI, Israel, Japan]
Shiryaev S.A., Kozlov I.A., Ratnikov B.I., Smith J.W., Lebl M., Strongin A.Y.;
"Cleavage preference distinguishes the two-component NS2B-NS3 serine proteinases of Dengue and West Nile viruses.";
Biochem. J. 401:743-752(2007).
[6]
CHARACTERIZATION OF NS1.
DOI=10.1016/j.jviromet.2007.01.008; PubMed=17331594 [NCBI, ExPASy, EBI, Israel, Japan]
Noisakran S., Dechtawewat T., Rinkaewkan P., Puttikhunt C., Kanjanahaluethai A., Kasinrerk W., Sittisombut N., Malasit P.;
"Characterization of dengue virus NS1 stably expressed in 293T cell lines.";
J. Virol. Methods 142:67-80(2007).
Comments
  • FUNCTION: Protein C packages viral RNA to form a viral nucleocapsid, and promotes virion budding (By similarity).
  • FUNCTION: 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).
  • FUNCTION: Envelope protein E binds cell surface receptor and is involved in membrane fusion between virion and target cell. Synthesized as an 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).
  • FUNCTION: Non-structural protein 1 is slowly secreted from mammalian cells, but not from mosquito cells. Secreted form elicits protective immune response and plays an essential role in RNA replication (By similarity). 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.
  • FUNCTION: Non-structural protein 2B is a required cofactor for the serine protease function of NS3 (By similarity).
  • FUNCTION: Serine protease NS3 displays three enzymatic activities: serine protease, NTPase and RNA helicase. NS3 serine protease, in association with NS2B, 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).
  • FUNCTION: Non-structural protein 4A plays a role in RNA replication. Enhances inhibition of cell antiviral response by non-structural protein 4B (By similarity).
  • FUNCTION: Non-structural protein 4B prevent the establishment of cellular antiviral state by blocking the interferon-alpha/beta (IFN-alpha/beta) and IFN-gamma signaling pathways (By similarity).
  • FUNCTION: RNA-directed RNA polymerase NS5 replicates the viral (+) and (-) genome, and assure the capping of genomes in the cytoplasm. May be involved in methylation of 5'RNA cap structure (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.
  • CATALYTIC ACTIVITY: Nucleoside triphosphate + RNA(n) = diphosphate + RNA(n+1).
  • CATALYTIC ACTIVITY: S-adenosyl-L-methionine + G(5')pppR-RNA = S-adenosyl-L-homocysteine + m7G(5')pppR-RNA.
  • SUBUNIT: prM and envelope protein E form heterodimers in the endoplasmic reticulum and Golgi. Envelope protein E forms homodimers. NS1 forms homodimers as well as homohexamers when secreted. NS1 may interact with NS4A. NS3 and NS2B form an heterodimer. NS3 interacts with unphosphorylated NS5 (By similarity).
  • SUBCELLULAR LOCATION: Protein C: Virion (By similarity).
  • SUBCELLULAR LOCATION: Peptide pr: Secreted (By similarity).
  • SUBCELLULAR LOCATION: Small envelope protein M: Virion membrane; Single-pass type I membrane protein (By similarity).
  • SUBCELLULAR LOCATION: Envelope protein E: Virion membrane; Single-pass type I membrane protein (By similarity).
  • SUBCELLULAR LOCATION: Non-structural protein 1: Secreted. Endoplasmic reticulum membrane; Peripheral membrane protein; Lumenal side (By similarity).
  • SUBCELLULAR LOCATION: Non-structural protein 2A-alpha: Endoplasmic reticulum membrane (By similarity).
  • SUBCELLULAR LOCATION: Non-structural protein 2A: Endoplasmic reticulum membrane (By similarity).
  • SUBCELLULAR LOCATION: Serine protease subunit NS2B: Endoplasmic reticulum membrane; Peripheral membrane protein; Cytoplasmic side (By similarity).
  • SUBCELLULAR LOCATION: Serine protease subunit NS3: Endoplasmic reticulum membrane; Peripheral membrane protein; Cytoplasmic side (By similarity).
  • SUBCELLULAR LOCATION: Non-structural protein 4A: Endoplasmic reticulum membrane; Peripheral membrane protein; Cytoplasmic side (By similarity).
  • SUBCELLULAR LOCATION: Non-structural protein 4B: Endoplasmic reticulum membrane; Multi-pass membrane protein (By similarity). Note=The C-terminal transmembrane domain of non-structural protein 4B is presumably reoriented after cleavage on the lumenal side (By similarity).
  • SUBCELLULAR LOCATION: RNA-directed RNA polymerase NS5: Endoplasmic reticulum membrane; Peripheral membrane protein; Cytoplasmic side. Nucleus (By similarity).
  • DOMAIN: Transmembrane domains of the small envelope protein M and envelope protein E contains an endoplasmic reticulum retention signals (By similarity).
  • PTM: 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 (By similarity).
  • PTM: RNA-directed RNA polymerase NS5 is phosphorylated on serines residues. This phosphorylation may trigger NS5 nuclear localization (By similarity).
  • PTM: Envelope protein E and non-structural protein 1 are N-glycosylated (By similarity).
  • MISCELLANEOUS: The virion is assembled in the endoplasmic reticulum lumen, transported by vesicles to the Golgi, then transported again to the cell membrane where it is released outside the cell.
  • SIMILARITY: Contains 1 helicase ATP-binding domain.
  • SIMILARITY: Contains 1 helicase C-terminal domain.
  • SIMILARITY: Contains 1 peptidase S7 domain [view classification].
  • SIMILARITY: Contains 1 RdRp catalytic domain.
Copyright
Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.
Cross-references
Sequence databases
EMBL
M84727; AAA73185.1; -; Genomic_RNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
PIR A42451; GNWV16.
3D structure databases
HSSP Q88653; 1OKE. [HSSP ENTRY / PDB]
ModBase P29990.
Ontologies
GO
GO:0005789; Cellular component: endoplasmic reticulum membrane (inferred from electronic annotation from UniProtKB-SubCell).
GO:0005576; Cellular component: extracellular region (inferred from electronic annotation from UniProtKB-KW).
GO:0016021; Cellular component: integral to membrane (inferred from electronic annotation from InterPro).
GO:0005634; Cellular component: nucleus (inferred from electronic annotation from UniProtKB-KW).
GO:0030529; Cellular component: ribonucleoprotein complex (inferred from electronic annotation from UniProtKB-KW).
GO:0019028; Cellular component: viral capsid (inferred from electronic annotation from InterPro).
GO:0019031; Cellular component: viral envelope (inferred from electronic annotation from InterPro).
GO:0005524; Molecular function: ATP binding (inferred from electronic annotation from InterPro).
GO:0008026; Molecular function: ATP-dependent helicase activity (inferred from electronic annotation from InterPro).
GO:0003725; Molecular function: double-stranded RNA binding (inferred from electronic annotation from InterPro).
GO:0046872; Molecular function: metal ion binding (inferred from electronic annotation from UniProtKB-KW).
GO:0004482; Molecular function: mRNA (guanine-N7-)-methyltransferase activity (inferred from electronic annotation from EC).
GO:0003724; Molecular function: RNA helicase activity (inferred from electronic annotation from InterPro).
GO:0003968; Molecular function: RNA-directed RNA polymerase activity (inferred from electronic annotation from InterPro).
GO:0004252; Molecular function: serine-type endopeptidase activity (inferred from electronic annotation from InterPro).
GO:0005198; Molecular function: structural molecule activity (inferred from electronic annotation from InterPro).
GO:0006355; Biological process: regulation of transcription, DNA-dependent (inferred from electronic annotation from UniProtKB-KW).
GO:0006410; Biological process: transcription, RNA-dependent (inferred from electronic annotation from UniProtKB-KW).
GO:0019079; Biological process: viral genome replication (inferred from electronic annotation from InterPro).
QuickGo view.
Family and domain databases
InterPro IPR014001; DEAD-like_N.
IPR011492; DEAD_Flavivir.
IPR001650; DNA/RNA_helicase_C.
IPR002464; DNA/RNA_helicase_DEAH_CS.
IPR011999; Flav_glyE_cen_dm.
IPR013754; Flav_glyE_dim.
IPR001122; Flavi_capsidC.
IPR000069; Flavi_M.
IPR001157; Flavi_NS1.
IPR000752; Flavi_NS2A.
IPR000487; Flavi_NS2B.
IPR000404; Flavi_NS4A.
IPR001528; Flavi_NS4B.
IPR002535; Flavi_propep.
IPR000336; Flv_glyE_Ig-like.
IPR014412; Gen_Poly_FLV.
IPR014021; Helicase_SF1/SF2_ATP-bd.
IPR001850; Peptidase_S7.
IPR000208; RNA_pol_flaviviral.
IPR007094; RNA_pol_PSvir.
IPR002877; RrmJFtsJ_MeTrfase.
Graphical view of domain structure.
Gene3D G3DSA:2.60.98.10; Flav_glyE_dim; 1.
G3DSA:2.60.40.350; Flv_glyE_Ig-like; 1.
Pfam PF01003; Flavi_capsid; 1.
PF07652; Flavi_DEAD; 1.
PF02832; Flavi_glycop_C; 1.
PF00869; Flavi_glycoprot; 1.
PF01004; Flavi_M; 1.
PF00948; Flavi_NS1; 1.
PF01005; Flavi_NS2A; 1.
PF01002; Flavi_NS2B; 1.
PF01350; Flavi_NS4A; 1.
PF01349; Flavi_NS4B; 1.
PF00972; Flavi_NS5; 1.
PF01570; Flavi_propep; 1.
PF01728; FtsJ; 1.
PF00949; Peptidase_S7; 1.
Pfam graphical view of domain structure.
PIRSF PIRSF003817; Gen_Poly_FLV; 1.
ProDom PD001496; Flavi_NS1; 1.
[Domain structure / List of seq. sharing at least 1 domain]
SMART SM00487; DEXDc; 1.
SM00490; HELICc; 1.
SMART graphical view of domain structure.
PROSITE PS00690; DEAH_ATP_HELICASE; FALSE_NEG.
PS51192; HELICASE_ATP_BIND_1; 1.
PS51194; HELICASE_CTER; FALSE_NEG.
PS50507; RDRP_SSRNA_POS; 1.
PROSITE graphical view of domain structure (profiles).
BLOCKS P29990.
ProtoNet P29990.
Other
UniRef View cluster of proteins with at least 50% / 90% / 100% identity.
Keywords
ATP-binding; Capsid protein; Cleavage on pair of basic residues; Complete proteome; Endoplasmic reticulum; Envelope protein; Glycoprotein; Helicase; Hydrolase; Membrane; Metal-binding; Multifunctional enzyme; Nucleotide-binding; Nucleotidyltransferase; Nucleus; Phosphoprotein; Protease; Ribonucleoprotein; RNA replication; RNA-binding; RNA-directed RNA polymerase; Secreted; Serine protease; Transcription; Transcription regulation; Transferase; Transmembrane; Viral nucleoprotein; Virion.
Features
SEVIEWER logo Feature table viewer FT aligner logo Feature aligner
KeyFrom    To Length Description FTId
CHAIN   1    100  100     Protein C. PRO_0000037925
PROPEP   101    114  14     ER anchor for the protein C, removed in mature form by serine protease NS3. PRO_0000037926
CHAIN   115    280  166     prM. PRO_0000264673
CHAIN   115    205  91     Peptide pr. PRO_0000264674
CHAIN   206    280  75     Small envelope protein M. PRO_0000037927
CHAIN   281    775  495     Envelope protein E. PRO_0000037928
CHAIN   776   1127  352     Non-structural protein 1. PRO_0000037929
CHAIN   1128   1345  218     Non-structural protein 2A. PRO_0000037930
CHAIN   1128   1315  188     Non-structural protein 2A-alpha. PRO_0000264675
CHAIN   1346   1475  130     Serine protease subunit NS2B. PRO_0000037931
CHAIN   1476   2093  618     Serine protease subunit NS3. PRO_0000037932
CHAIN   2094   2220  127     Non-structural protein 4A. PRO_0000037933
PEPTIDE   2221   2243  23     Peptide 2k. PRO_0000264676
CHAIN   2244   2491  248     Non-structural protein 4B. PRO_0000037934
CHAIN   2492   3391  900     RNA-directed RNA polymerase NS5. PRO_0000037935
TOPO_DOM   1    101  101     Cytoplasmic (Potential). 
TRANSMEM   102    122  21     Potential. 
TOPO_DOM   123    238  116     Extracellular (Potential). 
TRANSMEM   239    259  21     Potential. 
TOPO_DOM   260    265  6     Cytoplasmic (Potential). 
TRANSMEM   266    286  21     Potential. 
TOPO_DOM   287    725  439     Extracellular (Potential). 
TRANSMEM   726    746  21     Potential. 
TOPO_DOM   747    752  6     Cytoplasmic (Potential). 
TRANSMEM   753    773  21     Potential. 
TOPO_DOM   774   1156  383     Extracellular (Potential). 
TRANSMEM   1157   1177  21     Potential. 
TOPO_DOM   1178   1447  270     Cytoplasmic (Potential). 
TRANSMEM   1448   1468  21     Potential. 
TOPO_DOM   1469   2192  724     Lumenal (Potential). 
TRANSMEM   2193   2213  21     Potential. 
TOPO_DOM   2214   2220  7     Cytoplasmic (Potential). 
TRANSMEM   2221   2240  20     Potential. 
TOPO_DOM   2241   2347  107     Lumenal (Potential). 
TRANSMEM   2348   2368  21     Potential. 
TOPO_DOM   2369   2413  45     Cytoplasmic (Potential). 
TRANSMEM   2414   2434  21     Potential. 
TOPO_DOM   2435   2459  25     Lumenal (Potential). 
TRANSMEM   2460   2480  21     Potential. 
TOPO_DOM   2481   3391  911     Cytoplasmic (Potential). 
DOMAIN   1655   1811  157     Helicase ATP-binding. 
DOMAIN   1821   1988  168     Helicase C-terminal. 
DOMAIN   3020   3169  150     RdRp catalytic. 
NP_BIND   1668   1675  8     ATP (Potential). 
MOTIF   1759   1762  4     DEAH box (By similarity). 
ACT_SITE   1526   1526        Charge relay system; for serine protease NS3 activity (By similarity). 
ACT_SITE   1550   1550        Charge relay system; for serine protease NS3 activity (By similarity). 
ACT_SITE   1610   1610        Charge relay system; for serine protease NS3 activity (By similarity). 
SITE   100    101  2     Cleavage; by serine protease NS3 (By similarity). 
SITE   114    115  2     Cleavage; by host signal peptidase (By similarity). 
SITE   205    206  2     Cleavage; by host furin (By similarity). 
SITE   280    281  2     Cleavage; by host signal peptidase (By similarity). 
SITE   775    776  2     Cleavage; by host signal peptidase (By similarity). 
SITE   1127   1128  2     Cleavage; by host (By similarity). 
SITE   1315   1316  2     Cleavage; by serine protease NS3 (By similarity). 
SITE   1345   1346  2     Cleavage; by serine protease NS3 (By similarity). 
SITE   1475   1476  2     Cleavage; by serine protease NS3 (By similarity). 
SITE   2093   2094  2     Cleavage; by serine protease NS3 (By similarity). 
SITE   2220   2221  2     Cleavage; by host signal peptidase (By similarity). 
SITE   2243   2244  2     Cleavage; by serine protease NS3 (By similarity). 
SITE   2491   2492  2     Cleavage; by serine protease NS3 (By similarity). 
CARBOHYD   183    183        N-linked (GlcNAc...) (Potential). 
CARBOHYD   347    347        N-linked (GlcNAc...) (Potential). 
CARBOHYD   433    433        N-linked (GlcNAc...) (Potential). 
CARBOHYD   982    982        N-linked (GlcNAc...) (Potential). 
CARBOHYD   2301   2301        N-linked (GlcNAc...) (Potential). 
CARBOHYD   2305   2305        N-linked (GlcNAc...) (Potential). 
CARBOHYD   2457   2457        N-linked (GlcNAc...) (Potential). 
DISULFID   283    310        By similarity. 
DISULFID   340    401  &