Query author contributions in Reactome
Reactome depends on collaboration between our curation team and outside experts to assemble and peer-review its pathway modules. The integration of ORCID within Reactome enables us to meet a key challenge with authoring, curating and reviewing biological information by incentivizing and crediting the external experts that contribute their expertise and time to the Reactome curation process. More information is available at ORCID and Reactome.
If you have an ORCID ID that is not listed on this page, please forward this information to us and we will update your Reactome pathway records.
Details on Person UniProt:P29990 Unknown
| Class:Id | ReferenceGeneProduct:3244616 |
|---|---|
| _chainChangeLog | chain:1-3391 added on Sat February 7 2015;chain:1-100 added on Sat February 7 2015;propeptide:101-114 added on Sat February 7 2015;chain:115-280 added on Sat February 7 2015;chain:115-205 added on Sat February 7 2015;chain:206-280 added on Sat February 7 2015;chain:281-775 added on Sat February 7 2015;chain:776-1127 added on Sat February 7 2015;chain:1128-1345 added on Sat February 7 2015;chain:1128-1315 added on Sat February 7 2015;chain:1346-1475 added on Sat February 7 2015;chain:1476-2093 added on Sat February 7 2015;chain:2094-2220 added on Sat February 7 2015;peptide:2221-2243 added on Sat February 7 2015;chain:2244-2491 added on Sat February 7 2015;chain:2492-3391 added on Sat February 7 2015 |
| _displayName | UniProt:P29990 Unknown |
| _timestamp | 2026-02-20 22:47:38 |
| chain | chain:1-3391 chain:1-100 propeptide:101-114 chain:115-280 chain:115-205 chain:206-280 chain:281-775 chain:776-1127 chain:1128-1345 chain:1346-1475 chain:1476-2093 chain:2094-2220 peptide:2221-2243 chain:2244-2491 chain:2492-3391 |
| checksum | 2E20AD0D6C978ECC |
| comment | FUNCTION Capsid protein C self-assembles to form an icosahedral capsid about 30 nm in diameter. The capsid encapsulates the genomic RNA (Probable). 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. 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. Overcomes the anti-viral effects of host EXOC1 by sequestering and degrading the latter through the proteasome degradation pathway (PubMed:23522008).FUNCTION 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.FUNCTION Acts as a chaperone for envelope protein E during intracellular virion assembly by masking and inactivating envelope protein E fusion loop. 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. prM-E cleavage is inefficient, and many virions are only partially matured. These uncleaved prM would play a role in immune evasion.FUNCTION May play a role in virus budding. Exerts cytotoxic effects by activating a mitochondrial apoptotic pathway through M ectodomain. May display a viroporin activity.FUNCTION Type II fusion protein that binds to host cell surface receptor and mediates fusion between viral and cellular membranes (Probable). The envelope protein E shifts from dimeric state to trimeric state to perform fusion with the host membrane (By similarity). The fusion loops of the three subunits come together to form a membrane-insertable tip containing aromatic residues (By similarity). 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 heterodimers of precursor prM and envelope protein E (By similarity). Envelope protein exposes a positively-charged pr-binding pocket at the E dimer interface, inducing (prM/E)2 dimer formation to generate smooth particles in the Golgi (By similarity). The virion is transported to the Golgi apparatus where the low pH causes dissociation of PrM-E heterodimers and formation of E homodimers (By similarity). prM-E cleavage is inefficient, and many virions are only partially matured. These uncleaved prM would play a role in immune evasion (By similarity). Pr is shed from the particle upon subsequent secretion into the extracellular environment, leaving an activated particle, prone to mediate acidic pH-triggered membrane fusion upon entry into a target cell (By similarity).FUNCTION 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).FUNCTION 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) (By similarity). Mediates complement activation, which may contribute to the pathogenesis of the vascular leakage that occurs in severe dengue disease (PubMed:16544248). Activates autophagy through the AMPK/ERK/mTOR signaling pathway. Mechanistically, acts as the assembly platform for STK11-AMPK interactions and promotes STK11-AMPK interactions. In turn, promotes phosphorylation of the AMPK kinase structural domain and activates AMPK, thereby positively regulating the AMPK/ERK/mTOR signaling pathway and inducing autophagy (PubMed:37821951).FUNCTION Component of the viral RNA replication complex that functions in virion assembly and antagonizes the host immune response.FUNCTION Required cofactor for the serine protease function of NS3. May have membrane-destabilizing activity and form viroporins (By similarity).FUNCTION 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.FUNCTION 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 RIGI 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).FUNCTION Functions as a signal peptide for NS4B and is required for the interferon antagonism activity of the latter.FUNCTION Induces the formation of ER-derived membrane vesicles where the viral replication takes place. 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 (PubMed:15956546).FUNCTION Replicates the viral (+) and (-) RNA genome, and performs the capping of genomes in the cytoplasm (By similarity). NS5 methylates viral RNA cap at guanine N-7 and ribose 2'-O positions (PubMed:19850911). 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 (PubMed:15944325). Inhibits host TYK2 and STAT2 phosphorylation, thereby preventing activation of JAK-STAT signaling pathway (PubMed:19754307). May reduce immune responses by preventing the recruitment of the host PAF1 complex to interferon-responsive genes (PubMed:30550790).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 RNA(n) + a ribonucleoside 5'-triphosphate = RNA(n+1) + diphosphateCATALYTIC ACTIVITY a ribonucleoside 5'-triphosphate + H2O = a ribonucleoside 5'-diphosphate + phosphate + H(+)CATALYTIC ACTIVITY ATP + H2O = ADP + phosphate + H(+)CATALYTIC ACTIVITY a 5'-end (5'-triphosphoguanosine)-ribonucleoside in mRNA + S-adenosyl-L-methionine = a 5'-end (N(7)-methyl 5'-triphosphoguanosine)-ribonucleoside in mRNA + S-adenosyl-L-homocysteineCATALYTIC ACTIVITY a 5'-end (N(7)-methyl 5'-triphosphoguanosine)-ribonucleoside in mRNA + S-adenosyl-L-methionine = a 5'-end (N(7)-methyl 5'-triphosphoguanosine)-(2'-O-methyl-ribonucleoside) in mRNA + S-adenosyl-L-homocysteine + H(+)SUBUNIT Homodimer (PubMed:12768036, PubMed:15269372). Interacts (via N-terminus) with host EXOC1 (via C-terminus); this interaction results in EXOC1 degradation through the proteasome degradation pathway (PubMed:19889084, PubMed:23522008). Interacts (via the NLS) with host KPNA2/Importin alpha-1; this interaction allows the nuclear import of the capsid protein (By similarity).SUBUNIT Heterodimer with envelope protein E; each spike of the immature virion in the ER/Golgi consists of three prM-E heterodimers.SUBUNIT Heterotetramer with envelope protein E, made up of two M-E dimers; in mature virion, prefusion state.SUBUNIT Homodimer; in mature virion, prefusion state (By similarity). Homotrimer; in mature virion, postfusion state (By similarity). Heterotetramer with the small membrane protein, made up of two M-E dimers; in mature virion, prefusion state (By similarity). Heterodimer with protein prM; each spike of the immature virion in the ER/Golgi consists of three prM-E heterodimers (By similarity). Interacts with the peptide pr; this interaction allows the stabilization of the E dimer at acidic pH (By similarity). Pr remains bound to the particle as long as the pH is acidic because of electrostatic complementarity, dissociation of pr occurs at neutral pH upon virus release from the infected cell (By similarity). Interacts with non-structural protein 1 (By similarity).SUBUNIT Homodimer; Homohexamer when secreted. Interacts with envelope protein E (By similarity). Interacts with host PRKAA1 (PubMed:37821951).SUBUNIT Interacts (via N-terminus) with serine protease NS3 (By similarity).SUBUNIT Forms a heterodimer with serine protease NS3. May form homooligomers (By similarity).SUBUNIT Forms a heterodimer with NS2B (By similarity). Interacts with NS4B (By similarity). Interacts with unphosphorylated RNA-directed RNA polymerase NS5; this interaction stimulates RNA-directed RNA polymerase NS5 guanylyltransferase activity (PubMed:19850911). Interacts with host SHFL (By similarity).SUBUNIT Interacts with host MAVS; this interaction inhibits the synthesis of IFN-beta (By similarity). Interacts with host SHFL (By similarity). Interacts with host AUP1; the interaction occurs in the presence of Dengue virus NS4B and induces lipophagy which facilitates production of virus progeny particles (By similarity). May interact with host SRPRA and SEC61G (PubMed:30550790).SUBUNIT Interacts with serine protease NS3.SUBUNIT Homodimer (By similarity). Interacts with host STAT2; this interaction inhibits the phosphorylation of the latter, and, when all viral proteins are present (polyprotein), targets STAT2 for degradation (PubMed:19754307, PubMed:30550790). Interacts with serine protease NS3 (PubMed:19850911). Interacts (via C-terminus) with host SCRIB (via PDZ3); this interaction targets NS5 to the cell membrane periphery and nucleus, thereby allowing efficient host nuclear STAT1 inhibition (By similarity). Interacts with host PAF1 complex; the interaction may prevent the recruitment of the PAF1 complex to interferon-responsive genes, and thus reduces the immune response (PubMed:30550790). Interacts with host KPNA2/importin-alpha; this interaction allows the nuclear localization of NS5 (By similarity).SUBCELLULAR LOCATION Pr remains bound to the immature particle as long as the pH is acidic because of electrostatic complementarity, dissociation of pr occurs at neutral pH upon virus release from the infected cell.SUBCELLULAR LOCATION Located in RE-derived vesicles hosting the replication complex.SUBCELLULAR LOCATION Remains non-covalently associated to serine protease subunit NS2B.SUBCELLULAR LOCATION Located in RE-associated vesicles hosting the replication complex. Interacts with host MAVS in the mitochondrion-associated endoplasmic reticulum membranes.SUBCELLULAR LOCATION Located in RE-derived vesicles hosting the replication complex.SUBCELLULAR LOCATION Located in RE-associated vesicles hosting the replication complex. NS5 protein is mainly localized in the nucleus rather than in ER vesicles, especially in the DENV 2, 3, 4 serotypes.DOMAIN The transmembrane domains contain an endoplasmic reticulum retention signal.DOMAIN The transmembrane domains contain an endoplasmic reticulum retention signal.DOMAIN The pr domain has a critical role in holding the spikes made of three prM-E heterodimers in a metastable conformation.DOMAIN The C-terminal 18 amino acids are important for the subcellular location of NS5.PTM Specific enzymatic cleavages in vivo yield mature proteins. Cleavages in the lumen of endoplasmic reticulum are performed by host signal peptidase, whereas cleavages in the cytoplasmic side are performed by serine protease NS3. Signal cleavage at the 2K-4B site requires a prior NS3 protease-mediated cleavage at the 4A-2K site.PTM Cleaved in post-Golgi vesicles by a host furin, releasing the mature small envelope protein M, and peptide pr. This cleavage is incomplete as up to 30% of viral particles still carry uncleaved prM.PTM N-glycosylated.PTM N-glycosylated. The excreted form is glycosylated and this is required for efficient secretion of the protein from infected cells.PTM Acetylated by host KAT5. Acetylation modulates NS3 RNA-binding and unwinding activities and plays an important positive role for viral replication.PTM Sumoylation of RNA-directed RNA polymerase NS5 increases NS5 protein stability allowing proper viral RNA replication.PTM Phosphorylated on serines residues. This phosphorylation may trigger NS5 nuclear localization.SIMILARITY In the N-terminal section; belongs to the class I-like SAM-binding methyltransferase superfamily. mRNA cap 0-1 NS5-type methyltransferase family. |
| created | [InstanceEdit:3244632] Shamovsky, V, 2013-03-28 |
| description | recommendedName: Genome polyprotein component recommendedName: Capsid protein C alternativeName: Core protein /component component recommendedName: Protein prM /component component recommendedName: Peptide pr /component component recommendedName: Small envelope protein M alternativeName: Matrix protein /component component recommendedName: Envelope protein E /component component recommendedName: Non-structural protein 1 shortName: NS1 /component component recommendedName: Non-structural protein 2A shortName: NS2A /component component recommendedName: Serine protease subunit NS2B alternativeName: Flavivirin protease NS2B regulatory subunit alternativeName: Non-structural protein 2B /component component recommendedName: Serine protease NS3 ecNumber: 3.4.21.91 ecNumber evidence="11"3.6.1.15 ecNumber evidence="11"3.6.4.13 alternativeName: Flavivirin protease NS3 catalytic subunit alternativeName: Non-structural protein 3 /component component recommendedName: Non-structural protein 4A shortName: NS4A /component component recommendedName: Peptide 2k /component component recommendedName: Non-structural protein 4B shortName: NS4B /component component recommendedName: RNA-directed RNA polymerase/Methyltransferase NS5 ecNumber evidence="18"2.1.1.56 ecNumber evidence="18"2.1.1.57 ecNumber evidence="14"2.7.7.48 alternativeName: Non-structural protein 5 /component |
| identifier | P29990 |
| isSequenceChanged | FALSE |
| keyword | 3D-structure Acetylation Activation of host autophagy by virus ATP-binding Capsid protein Clathrin-mediated endocytosis of virus by host Cleavage on pair of basic residues Disulfide bond Fusion of virus membrane with host endosomal membrane Fusion of virus membrane with host membrane Glycoprotein Helicase Host cytoplasm Host endoplasmic reticulum Host membrane Host mitochondrion Host nucleus Host-virus interaction Hydrolase Inhibition of host innate immune response by virus Inhibition of host interferon signaling pathway by virus Inhibition of host MAVS by virus Inhibition of host RLR pathway by virus Inhibition of host STAT2 by virus Inhibition of host TYK2 by virus Interferon antiviral system evasion Ion channel Ion transport Membrane Metal-binding Methyltransferase mRNA capping mRNA processing Multifunctional enzyme Nucleotide-binding Nucleotidyltransferase Phosphoprotein Protease RNA-binding RNA-directed RNA polymerase S-adenosyl-L-methionine Secreted Serine protease Transcription Transcription regulation Transferase Transmembrane Transmembrane helix Transport Ubl conjugation Viral attachment to host cell Viral envelope protein Viral immunoevasion Viral ion channel Viral penetration into host cytoplasm Viral RNA replication Virion Virus endocytosis by host Virus entry into host cell Zinc |
| modified | [InstanceEdit:3445779] Weiser, JD [InstanceEdit:5433710] Weiser, JD [InstanceEdit:5634237] Weiser, JD [InstanceEdit:5673015] Weiser, JD [InstanceEdit:5691543] Weiser, JD [InstanceEdit:6791590] Weiser, JD [InstanceEdit:6807888] Weiser, JD [InstanceEdit:8856987] Weiser, JD [InstanceEdit:8869714] Weiser, JD [InstanceEdit:8934940] Weiser, JD [InstanceEdit:8944791] Weiser, JD [InstanceEdit:8964659] Weiser, JD [InstanceEdit:9027688] Weiser, JD [InstanceEdit:9037114] Weiser, JD [InstanceEdit:9637257] Weiser, JD [InstanceEdit:9657908] Weiser, JD [InstanceEdit:9666080] Weiser, JD [InstanceEdit:9676415] Weiser, JD [InstanceEdit:9688885] Weiser, JD [InstanceEdit:9706439] Weiser, JD [InstanceEdit:9730071] Weiser, JD [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9862192] Weiser, Joel, 2024-02-26 [InstanceEdit:9909836] Weiser, Joel, 2024-05-14 [InstanceEdit:9917590] Weiser, Joel, 2024-08-09 [InstanceEdit:9939033] Weiser, Joel, 2025-02-21 [InstanceEdit:9983091] Weiser, Joel, 2026-02-20 |
| name | Genome polyprotein |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| secondaryIdentifier | POLG_DEN26 |
| sequenceLength | 3391 |
| species | [Species:3244621] Dengue virus type 2 |
| (referenceEntity) | [EntityWithAccessionedSequence:3244620] NS2B [cytosol] [Dengue virus type 2] [EntityWithAccessionedSequence:3244645] K27polyUb-NS3 [endoplasmic reticulum membrane] [Dengue virus type 2] [EntityWithAccessionedSequence:9918767] NS12A [endoplasmic reticulum membrane] [Dengue virus type 2] [EntityWithAccessionedSequence:9918774] NS2B [endoplasmic reticulum membrane] [Dengue virus type 2] [EntityWithAccessionedSequence:9918777] unfolded HyPro-Polyprotein [endoplasmic reticulum membrane] [Dengue virus type 2] [EntityWithAccessionedSequence:9918783] NS4B [endoplasmic reticulum membrane] [Dengue virus type 2] [EntityWithAccessionedSequence:9918789] NS2A [endoplasmic reticulum membrane] [Dengue virus type 2] [EntityWithAccessionedSequence:9918790] Nascent polyprotein [endoplasmic reticulum membrane] [Dengue virus type 2] [EntityWithAccessionedSequence:9918791] C-prM-E-NS12A [endoplasmic reticulum membrane] [Dengue virus type 2] [EntityWithAccessionedSequence:9918796] pre-prM [endoplasmic reticulum membrane] [Dengue virus type 2] |
| (referenceSequence) | [ModifiedResidue:9918786] (2S,4R)-4-hydroxyproline at 1376 [ModifiedResidue:9918816] (2S,4R)-4-hydroxyproline at 1348 [ModifiedResidue:9918956] N4-glycosyl-L-asparagine at 433 [ModifiedResidue:9918982] N4-glycosyl-L-asparagine at 183 [ModifiedResidue:9918996] N4-glycosyl-L-asparagine at 347 [ModifiedResidue:9919004] N4-glycosyl-L-asparagine at 905 [ModifiedResidue:9919010] N-myristoylglycine at unknown position [ModifiedResidue:9919018] N4-glycosyl-L-asparagine at 982 [ModifiedResidue:9919940] L-cysteine glutathione disulfide at 3338 [GroupModifiedResidue:9920082] sumoylated lysine (monoSUMO1 [cytosol]) at unknown position |
| [Change default viewing format] | |
No pathways have been reviewed or authored by UniProt:P29990 Unknown (3244616)
