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Reviewed, UniProtKB/Swiss-Prot P33478 (POLG_DEN1S)

Last modified September 2, 2008. Version 82. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

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Names and origin

Protein namesRecommended name:
    Genome polyprotein
Cleaved into the following 14 chains:
    1- Recommended name:
            Protein C
        Alternative name(s):
            Core protein
            Capsid protein
    2- Recommended name:
            prM
    3- Recommended name:
            Peptide pr
    4- Recommended name:
            Small envelope protein M
        Alternative name(s):
            Matrix protein
    5- Recommended name:
            Envelope protein E
    6- Recommended name:
            Non-structural protein 1
                Short name=NS1
    7- Recommended name:
            Non-structural protein 2A
                Short name=NS2A
    8- Recommended name:
            Non-structural protein 2A-alpha
                Short name=NS2A-alpha
    9- Recommended name:
            Serine protease subunit NS2B
        Alternative name(s):
            Non-structural protein 2B
    10- Recommended name:
            Serine protease subunit NS3
              EC=3.4.21.91
        Alternative name(s):
            Non-structural protein 3
    11- Recommended name:
            Non-structural protein 4A
                Short name=NS4A
    12- Recommended name:
            Peptide 2k
    13- Recommended name:
            Non-structural protein 4B
                Short name=NS4B
    14- Recommended name:
            RNA-directed RNA polymerase NS5
              EC=2.7.7.48
              EC=2.1.1.56
        Alternative name(s):
            Non-structural protein 5
OrganismDengue virus type 1 (strain Singapore/S275/1990) (DENV-1) [Complete proteome]
Taxonomic identifier33741 [NCBI]
Taxonomic lineageViruses › ssRNA positive-strand viruses, no DNA stage › Flaviviridae › Flavivirus › Dengue virus group
Virus hostAedes aegypti (Yellowfever mosquito) [TaxID: 7159]
Homo sapiens (Human) [TaxID: 9606]

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Protein attributes

Sequence length3396 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
Protein existenceInferred from homology.

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General annotation (Comments)

Function

Protein C packages viral RNA to form a viral nucleocapsid, and promotes virion budding 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 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.

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.

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, 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 plays a role in RNA replication. Enhances inhibition of cell antiviral response by non-structural protein 4B By similarity.

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.

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.

Nucleoside triphosphate + RNA(n) = diphosphate + RNA(n+1).

S-adenosyl-L-methionine + G(5')pppR-RNA = S-adenosyl-L-homocysteine + m(7)G(5')pppR-RNA.

Subunit structure

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

Note= 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.

Protein C: VirionBy similarity.

Peptide pr: SecretedBy similarity.

Small envelope protein M: Virion membrane; Single-pass type I membrane proteinBy similarity.

Envelope protein E: Virion membrane; Single-pass type I membrane proteinBy similarity.

Non-structural protein 1: Secreted. Endoplasmic reticulum membrane; Peripheral membrane protein; Lumenal sideBy similarity.

Non-structural protein 2A-alpha: Endoplasmic reticulum membraneBy similarity.

Non-structural protein 2A: Endoplasmic reticulum membraneBy similarity.

Serine protease subunit NS2B: Endoplasmic reticulum membrane; Peripheral membrane protein; Cytoplasmic sideBy similarity.

Serine protease subunit NS3: Endoplasmic reticulum membrane; Peripheral membrane protein; Cytoplasmic sideBy similarity.

Non-structural protein 4A: Endoplasmic reticulum membrane; Peripheral membrane protein; Cytoplasmic sideBy similarity.

Non-structural protein 4B: Endoplasmic reticulum membrane; Multi-pass membrane proteinBy similarity. Note= The C-terminal transmembrane domain of non-structural protein 4B is presumably reoriented after cleavage on the lumenal side By similarity.

RNA-directed RNA polymerase NS5: Endoplasmic reticulum membrane; Peripheral membrane protein; Cytoplasmic side. NucleusBy similarity.

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 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

Contains 1 helicase ATP-binding domain.

Contains 1 helicase C-terminal domain.

Contains 1 peptidase S7 domain.

Contains 1 RdRp catalytic domain.

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Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical view

Molecule processing

Chain1 – 100100Protein C
Propeptide101 – 11414ER anchor for the protein C, removed in mature form by serine protease NS3
Chain115 – 280166prM
Chain115 – 20591Peptide pr
Chain206 – 28075Small envelope protein M
Chain281 – 774494Envelope protein E
Chain775 – 1126352Non-structural protein 1
Chain1127 – 1344218Non-structural protein 2A
Chain1127 – 1315189Non-structural protein 2A-alpha
Chain1345 – 1474130Serine protease subunit NS2B
Chain1475 – 2093619Serine protease subunit NS3
Chain2094 – 2220127Non-structural protein 4A
Peptide2221 – 224323Peptide 2k
Chain2244 – 2492249Non-structural protein 4B
Chain2493 – 3396904RNA-directed RNA polymerase NS5

Regions

Topological domain1 – 101101Cytoplasmic Potential
Transmembrane102 – 12221 Potential
Topological domain123 – 238116Extracellular Potential
Transmembrane239 – 25921 Potential
Topological domain260 – 2656Cytoplasmic Potential
Transmembrane266 – 28621 Potential
Topological domain287 – 724438Extracellular Potential
Transmembrane725 – 74521 Potential
Topological domain746 – 7516Cytoplasmic Potential
Transmembrane752 – 77221 Potential
Topological domain773 – 1155383Extracellular Potential
Transmembrane1156 – 117621 Potential
Topological domain1177 – 1446270Cytoplasmic Potential
Transmembrane1447 – 146721 Potential
Topological domain1468 – 2192725Lumenal Potential
Transmembrane2193 – 221321 Potential
Topological domain2214 – 22207Cytoplasmic Potential
Transmembrane2221 – 224020 Potential
Topological domain2241 – 2348108Lumenal Potential
Transmembrane2349 – 236921 Potential
Topological domain2370 – 241445Cytoplasmic Potential
Transmembrane2415 – 243521 Potential
Topological domain2436 – 246025Lumenal Potential
Transmembrane2461 – 248121 Potential
Topological domain2482 – 3391910Cytoplasmic Potential
Domain1655 – 1811157Helicase ATP-binding
Domain1821 – 1988168Helicase C-terminal
Domain3019 – 3168150RdRp catalytic
Nucleotide binding1668 – 16758ATP Potential
Motif1759 – 17624DEAH box By similarity

Sites

Active site15251Charge relay system; for serine protease NS3 activity By similarity
Active site15491Charge relay system; for serine protease NS3 activity By similarity
Active site16091Charge relay system; for serine protease NS3 activity By similarity
Site100 – 1012Cleavage; by serine protease NS3 By similarity
Site114 – 1152Cleavage; by host signal peptidase By similarity
Site205 – 2062Cleavage; by host furin By similarity
Site280 – 2812Cleavage; by host signal peptidase By similarity
Site774 – 7752Cleavage; by host signal peptidase By similarity
Site1126 – 11272Cleavage; by host By similarity
Site1314 – 13152Cleavage; by serine protease NS3 By similarity
Site1474 – 14752Cleavage; by serine protease NS3 By similarity
Site2220 – 22212Cleavage; by host signal peptidase By similarity
Site2243 – 22442Cleavage; by serine protease NS3 By similarity
Site2492 – 24932Cleavage; by serine protease NS3 By similarity

Amino acid modifications

Glycosylation1831N-linked (GlcNAc...) Potential
Glycosylation3471N-linked (GlcNAc...) Potential
Glycosylation4331N-linked (GlcNAc...) Potential
Glycosylation9811N-linked (GlcNAc...) Potential
Glycosylation23021N-linked (GlcNAc...) Potential
Glycosylation23061N-linked (GlcNAc...) Potential
Glycosylation24581N-linked (GlcNAc...) Potential
Disulfide bond283 ↔ 310 By similarity
Disulfide bond340 ↔ 401 By similarity
Disulfide bond354 ↔ 385 By similarity
Disulfide bond372 ↔ 396 By similarity
Disulfide bond465 ↔ 565 By similarity
Disulfide bond582 ↔ 613 By similarity

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Sequences

Sequence Length<