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Showing Protein Genome polyprotein (HMDBP14240)

IdentificationBiological propertiesGene propertiesProtein propertiesExternal linksReferencesXMLShow 0 metabolites
Identification
HMDB Protein ID HMDBP14240
Secondary Accession Numbers None
Name Genome polyprotein
Synonyms Not Available
Gene Name (REFSEQ) DENGUE VIRUS 1; POLYPROTEIN
Protein Type Unknown
Biological Properties
General Function Not Available
Specific Function Plays a role in virus budding by binding to the cell membrane and gathering the viral RNA into a nucleocapsid that forms the core of a mature virus particle (PubMed:11893341). During virus entry, may induce genome penetration into the host cytoplasm after hemifusion induced by the surface proteins. Can migrate to the cell nucleus where it modulates host functions (PubMed:18420804, PubMed:21909430). Overcomes the anti-viral effects of host EXOC1 by sequestering and degrading the latter through the proteasome degradation pathway (PubMed:23522008).Inhibits RNA silencing by interfering with host Dicer.Prevents premature fusion activity of envelope proteins in trans-Golgi by binding to envelope protein E at pH6.0. After virion release in extracellular space, gets dissociated from E dimers.Acts as a chaperone for envelope protein E during intracellular virion assembly by masking and inactivating envelope protein E fusion peptide. prM is the only viral peptide matured by host furin in the trans-Golgi network probably to avoid catastrophic activation of the viral fusion activity in acidic Golgi compartment prior to virion release (PubMed:9971841). prM-E cleavage is inefficient, and many virions are only partially matured. These uncleaved prM would play a role in immune evasion (PubMed:21388812).May play a role in virus budding (PubMed:25326389). Exerts cytotoxic effects by activating a mitochondrial apoptotic pathway through M extodomain (PubMed:13679613). May display a viroporin activity (PubMed:16007501).Binds to host cell surface receptor and mediates fusion between viral and cellular membranes. Envelope protein is synthesized in the endoplasmic reticulum in the form of heterodimer with protein prM. They play a role in virion budding in the ER, and the newly formed immature particle is covered with 60 spikes composed of heterodimer between precursor prM and envelope protein E. The virion is transported to the Golgi apparatus where the low pH causes dissociation of PrM-E heterodimers and formation of E homodimers (PubMed:18369148). prM-E cleavage is ineficient, and many virions are only partially matured. These uncleaved prM would play a role in immune evasion (PubMed:11893341).Involved in immune evasion, pathogenesis and viral replication. Once cleaved off the polyprotein, is targeted to three destinations: the viral replication cycle, the plasma membrane and the extracellular compartment. Essential for viral replication. Required for formation of the replication complex and recruitment of other non-structural proteins to the ER-derived membrane structures. Excreted as a hexameric lipoparticle that plays a role against host immune response. Antagonizing the complement function. Binds to the host macrophages and dendritic cells. Inhibits signal transduction originating from Toll-like receptor 3 (TLR3).Disrupts the host endothelial glycocalyx layer of host pulmonary microvascular endothelial cells, inducing degradation of sialic acid and shedding of heparan sulfate proteoglycans. NS1 induces expression of sialidases, heparanase, and activates cathepsin L, which activates heparanase via enzymatic cleavage. These effects are probably linked to the endothelial hyperpermeability observed in severe dengue disease.Component of the viral RNA replication complex that functions in virion assembly and antagonizes the host immune response.Required cofactor for the serine protease function of NS3. May have membrane-destabilizing activity and form viroporins (PubMed:26728778).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.Regulates the ATPase activity of the NS3 helicase activity. NS4A allows NS3 helicase to conserve energy during unwinding. Plays a role in the inhibition of the host innate immune response. Interacts with host MAVS and thereby prevents the interaction between DDX58 and MAVS. In turn, IFN-beta production is impaired. Interacts with host AUP1 which mediates induction of lipophagy in host cells and facilitates production of virus progeny particles (By similarity).Functions as a signal peptide for NS4B and is required for the interferon antagonism activity of the latter.Induces the formation of ER-derived membrane vesicles where the viral replication takes place (By similarity). Inhibits interferon (IFN)-induced host STAT1 phosphorylation and nuclear translocation, thereby preventing the establishment of a cellular antiviral state by blocking the IFN-alpha/beta pathway (PubMed:15956546).Replicates the viral (+) and (-) RNA 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 RNA 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.
Pathways Not Available
Reactions Not Available
GO Classification
Biological Process
induction by virus of host autophagy
viral RNA genome replication
suppression by virus of host type I interferon-mediated signaling pathway
fusion of virus membrane with host endosome membrane
clathrin-dependent endocytosis of virus by host cell
pore formation by virus in membrane of host cell
suppression by virus of host MAVS activity
suppression by virus of host STAT2 activity
suppression by virus of host TYK2 activity
protein oligomerization
virion attachment to host cell
viral budding from endoplasmic reticulum membrane
Cellular Component
host cell nucleus
integral to membrane of host cell
host cell perinuclear region of cytoplasm
host cell mitochondrion
virion membrane
host cell endoplasmic reticulum membrane
cytoplasmic viral factory
integral to membrane
viral capsid
viral envelope
extracellular region
Molecular Function
serine-type endopeptidase activity
ion channel activity
RNA-directed RNA polymerase activity
structural molecule activity
mRNA (nucleoside-2'-O-)-methyltransferase activity
mRNA (guanine-N7-)-methyltransferase activity
protein dimerization activity
nucleoside-triphosphatase activity
double-stranded RNA binding
RNA helicase activity
ATP binding
metal ion binding
Cellular Location Not Available
Gene Properties
Chromosome Location Not Available
Locus Not Available
SNPs Not Available
Gene Sequence Not Available
Protein Properties
Number of Residues 3392
Molecular Weight 378699.135
Theoretical pI 8.424
Pfam Domain Function
Signals Not Available
Transmembrane Regions
  • 102-119;243-260;262-280;726-746;753-773;1196-1220;1227-1245;1270-1290;1292-1310;1316-1336;1352-1370;1372-1391;2149-2169;2194-2214;2230-2244;2350-2370;2416-2436;2462-2482;
Protein Sequence Not Available
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID P17763
UniProtKB/Swiss-Prot Entry Name POLG_DEN1W
PDB IDs
GenBank Gene ID Not Available
GeneCard ID Not Available
GenAtlas ID Not Available
HGNC ID Not Available
References
General References
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