Genome Polyprotein (NS1) Dengue Virus Type 2 Recombinant Protein

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.