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UniProtKB/Swiss-Prot entry P09866


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

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Entry information
Entry name POLG_DEN4D
Primary accession number P09866
Secondary accession numbers Q88661 Q88662 Q88663 Q88664 Q88665 Q88666 Q88667 Q88668 Q88669 Q88670 Q88671 Q99BK4 Q9DKQ5 Q9DKQ6 Q9DKQ7
Integrated into Swiss-Prot on July 1, 1989
Sequence was last modified on January 16, 2004 (Sequence version 2)
Annotations were last modified on    November 25, 2008 (Entry version 95)
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 4 (strain Dominica/814669/1981) (DENV-4) [TaxID: 408871] 
Taxonomy Viruses; ssRNA positive-strand viruses, no DNA stage; Flaviviridae; Flavivirus; Dengue virus group.
Virus hosts Aedes aegypti (Yellowfever mosquito) [TaxID: 7159]
Aedes albopictus (Forest day mosquito) [TaxID: 7160]
Aedes polynesiensis [TaxID: 188700]
Homo sapiens (Human) [TaxID: 9606]
Protein existence 1: Evidence at protein level;
References
[1]
NUCLEOTIDE SEQUENCE [GENOMIC RNA], AND SEQUENCE REVISION.
Yamashiro T., Shameem G., Lai C.-J.;
Submitted (FEB-2000) to the EMBL/GenBank/DDBJ databases.
[2]
NUCLEOTIDE SEQUENCE [GENOMIC RNA].
Durbin A.P., Karron R.A., Sun W., Vaughn D.W., Reynolds M.J., Perreault J.R., Men R.H., Lai C.-J., Elkins W.R., Chanock R.M., Murphy B.R., Whitehead S.S.;
"A live attenuated dengue virus type 4 vaccine candidate with a 30 nucleotide deletion in the 3' untranslated region is highly attenuated and immunogenic in humans.";
Submitted (DEC-2000) to the EMBL/GenBank/DDBJ databases.
[3]
NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 1-777.
DOI=10.1016/0042-6822(86)90169-8; PubMed=3022479 [NCBI, ExPASy, EBI, Israel, Japan]
Zhao B., Mackow E., Buckler-White A., Markoff L., Chancock R.M., Lai C.-J., Makino Y.;
"Cloning full-length dengue type 4 viral DNA sequences: analysis of genes coding for structural proteins.";
Virology 155:77-88(1986).
[4]
NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 775-3387.
DOI=10.1016/0042-6822(87)90458-2; PubMed=3039728 [NCBI, ExPASy, EBI, Israel, Japan]
Mackow E., Makino Y., Zhao B., Zhang Y.M., Markoff L., Buckler-White A., Guiler M., Chanock R., Lai C.-J.;
"The nucleotide sequence of dengue type 4 virus: analysis of genes coding for nonstructural proteins.";
Virology 159:217-228(1987).
[5]
PROTEOLYTIC PROCESSING OF THE M PROTEIN.
STRAIN=814669;
PubMed=2501515 [NCBI, ExPASy, EBI, Israel, Japan]
Markoff L.;
"In vitro processing of dengue virus structural proteins: cleavage of the pre-membrane protein.";
J. Virol. 63:3345-3352(1989).
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. 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).
  • 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
M14931; AAA42964.2; -; Genomic_RNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF326825; AAG45435.1; -; Genomic_RNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF326826; AAG45436.1; -; Genomic_RNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF326827; AAG45437.1; -; Genomic_RNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF326573; AAK01233.1; -; Genomic_RNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
3D structure databases
PDB
2H0P; NMR; -; A=568-679.[ExPASy / RCSB / EBI]
PDBsum 2H0P; -.
SMR P09866; 1647-2092, 2494-2755, 2761-3371.
ModBase P09866.
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.
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.
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).
Other
ProtoNet P09866.
UniRef View cluster of proteins with at least 50% / 90% / 100% identity.
Keywords
3D-structure; 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     99  99     Protein C (By similarity). PRO_0000038000
PROPEP   100    113  14     ER anchor for the protein C, removed in mature form by serine protease NS3 (By similarity). PRO_0000038001
CHAIN   114    279  166     prM (By similarity). PRO_0000308297
CHAIN   114    204  91     Peptide pr (By similarity). PRO_0000308298
CHAIN   205    279  75     Small envelope protein M (By similarity). PRO_0000038002
CHAIN   280    774  495     Envelope protein E (By similarity). PRO_0000038003
CHAIN   775   1126  352     Non-structural protein 1 (By similarity). PRO_0000038004
CHAIN   1127   1344  218     Non-structural protein 2A (By similarity). PRO_0000038005
CHAIN   1127      ?        Non-structural protein 2A-alpha (By similarity). PRO_0000308299
CHAIN   1345   1474  130     Serine protease subunit NS2B (By similarity). PRO_0000038006
CHAIN   1475   2092  618     Serine protease subunit NS3 (By similarity). PRO_0000038007
CHAIN   2093   2219  127     Non-structural protein 4A (By similarity). PRO_0000038008
PEPTIDE   2220   2242  23     Peptide 2k (By similarity). PRO_0000308300
CHAIN   2243   2487  245     Non-structural protein 4B (By similarity). PRO_0000038009
CHAIN   2488   3387  900     RNA-directed RNA polymerase NS5 (By similarity). PRO_0000038010
TOPO_DOM   1    100  100     Cytoplasmic (Potential). 
TRANSMEM   101    121  21     Potential. 
TOPO_DOM   122    237  116     Extracellular (Potential). 
TRANSMEM   238    258  21     Potential. 
TOPO_DOM   259    264  6     Cytoplasmic (Potential). 
TRANSMEM   265    285  21     Potential. 
TOPO_DOM   286    724  439     Extracellular (Potential). 
TRANSMEM   725    745  21     Potential. 
TOPO_DOM   746    751  6     Cytoplasmic (Potential). 
TRANSMEM   752    772  21     Potential. 
TOPO_DOM   773   1155  383     Extracellular (Potential). 
TRANSMEM   1156   1176  21     Potential. 
TOPO_DOM   1177   1446  270     Cytoplasmic (Potential). 
TRANSMEM   1447   1467  21     Potential. 
TOPO_DOM   1468   2191  724     Lumenal (Potential). 
TRANSMEM   2192   2212  21     Potential. 
TOPO_DOM   2213   2219  7     Cytoplasmic (Potential). 
TRANSMEM   2220   2239  20     Potential. 
TOPO_DOM   2240   2343  104     Lumenal (Potential). 
TRANSMEM   2344   2364  21     Potential. 
TOPO_DOM   2365   2409  45     Cytoplasmic (Potential). 
TRANSMEM   2410   2430  21     Potential. 
TOPO_DOM   2431   2455  25     Lumenal (Potential). 
TRANSMEM   2456   2476  21     Potential. 
TOPO_DOM   2477   3387  911     Cytoplasmic (Potential). 
DOMAIN   1654   1810  157     Helicase ATP-binding. 
DOMAIN   1820   1987  168     Helicase C-terminal. 
DOMAIN   3016   3166  151     RdRp catalytic. 
NP_BIND   1667   1674  8     ATP (Potential). 
MOTIF   1758   1761  4     DEAH box (By similarity). 
ACT_SITE   1525   1525        Charge relay system; for serine protease NS3 activity (By similarity). 
ACT_SITE   1549   1549        Charge relay system; for serine protease NS3 activity (By similarity). 
ACT_SITE   1609   1609        Charge relay system; for serine protease NS3 activity (By similarity). 
SITE   99    100  2     Cleavage; by serine protease NS3 (By similarity). 
SITE   113    114  2     Cleavage; by host signal peptidase (By similarity). 
SITE   204    205  2     Cleavage; by host furin (By similarity). 
SITE   279    280  2     Cleavage; by host signal peptidase (By similarity). 
SITE   774    775  2     Cleavage; by host signal peptidase (By similarity). 
SITE   1126   1127  2     Cleavage; by host (By similarity). 
SITE   1344   1345  2     Cleavage; by serine protease NS3 (By similarity). 
SITE   1474   1475  2     Cleavage; by serine protease NS3 (By similarity). 
SITE   2092   2093  2     Cleavage; by serine protease NS3 (By similarity). 
SITE   2219   2220  2     Cleavage; by host signal peptidase (By similarity). 
SITE   2242   2243  2     Cleavage; by serine protease NS3 (By similarity). 
SITE   2487   2488  2     Cleavage; by serine protease NS3 (By similarity). 
CARBOHYD   182    182        N-linked (GlcNAc...). 
CARBOHYD   346    346        N-linked (GlcNAc...) (Potential). 
CARBOHYD   432    432        N-linked (GlcNAc...) (Potential). 
CARBOHYD   904    904        N-linked (GlcNAc...) (Potential). 
CARBOHYD   981    981        N-linked (GlcNAc...) (Potential). 
CARBOHYD   2297   2297        N-linked (GlcNAc...) (Potential).