| IED ID | IndEnz0002001471 |
| Enzyme Type ID | protease001471 |
| Protein Name |
Genome polyprotein Cleaved into: Envelope protein E; Non-structural protein 1 NS1 ; Non-structural protein 2A NS2A ; Serine protease NS3 EC 3.4.21.91 EC 3.6.1.15 EC 3.6.4.13 Non-structural protein 3 Fragments |
| Gene Name | |
| Organism | Dengue virus type 2 (strain Tonga/EKB194/1974) (DENV-2) |
| Taxonomic Lineage | Viruses Riboviria Orthornavirae Kitrinoviricota Flasuviricetes Amarillovirales Flaviviridae Flavivirus (arboviruses group B) Dengue virus Dengue virus 2 Dengue virus type 2 (strain Tonga/EKB194/1974) (DENV-2) |
| Enzyme Sequence | MRCIGISNRDFVEGVSGGSWVDIVLEHGSCVTTMAKNKPTLDFELIKTEAKQPATLRKYCIEAKLTNTTTDSRCPTQGEPTLNEEQDKRFVCKHSMVDRGWGNGCGLFGKGGIVTCAMFTCKKNMEGKIVQPENLEYTVVITPHSGEEHAVGNDTGKHGKEVKITPQSSITEAELTGYGTVTMECSPRTGLDFNEMVLLQMEDKAWLVHRQWFLDLPLPWLPGADTQGSNWIQKETLVTFKNPHAKKQDVVVLGSQEGAMHTALTGATEIQMSSGNLLFTGHLKCRLRMDKLQLKGMSYSMCTGKFKIVKEIAETQHGTIVIRVQYEGDGSPCKIPFEIMDLEKRHVLGRLITVNPIVTEKDSPVNIEAEPPFGDSYIIIGVEPGQLKLDWFKKGSSIGQMFETTMRGAKRMAILGDTAWDFGSLGGVFTSIGKALHQVFGAIYGAAFSGVSWTMKILIGVIITWIGMNSRSTSLSVSLVLVGIVTLYLGVMVQADSGCVVSWKNKELKCGSGIFVTDNVHTWTEQYKFQPESPSKLASAIQKAHEEGICGIRSVTRLENLMWKQITSELNHILSENEVKLTIMTGDIKGIMQVGKRSLRPQPTELRYSWKTWGKAKMLSTELHNQTFLIDGPETAECPNTNRAWNSLEVEDYGFGVFTTNIWLRLREKQDVFCDSKLMSAAIKDNRAVHADMGYWIESALNDTWKIEKASFIEVKSCHWPKSHTLWSNGVLESEMVIPKNFAGPVSQHNNRPGYYTQTAGPWHLGKLEMDFDFCEGTTVVVTEDCGNRGPSLRTTTASGKLITEWCCRSCTLPPLRYRGEDGCWYGMEIRPLKEKEENLVSSLVTAGHGQIDNFSLGILGMALFLEEMLRTRVGTKHAILLVAVSFVTLITGNMSFRDLGRVMVMVGATMTDDIGMGVTYLALLAAFRVRPTFAAGLLLRKLTSKELMMTTIGIVLLSQSSIPETILELTDALALGMMVLKMVRNMEKYQLAVTIMAILCVPNAVILQNAWKVSCTILAVVSVSPLLLTSSQQKADWIPLALTIKGLNPTAIFLTTLSRTSKKRAGVLWDVPSPPPVGKAELEDGAYRIKQKGILGYSQIGAGVYKEGTFHTMWHVTRGAVLMHKGKRIEPSWADVKKDLISYGGGWKLEGEWKEGEEVQVLALEPGKNPRAVQTKPGLFRTNTGTIGAVSLDFSPGTSGSPIVDKKGKVVGLYGNGVVTRSGAYVSAIAQTEKSIEDNPEIEDDIFRKRRLTIMDLHPGAGKTKRYLPAIVREAIKRGLRTLILAPTRVVAAEMEEALRGLPIRYQTPAIRAEHTGREIVDLMCHATFTMRLLSPIRVPNYNLIIMDEAHFTDPASIAARGYISTRVEMGEAAGIFMTATPPGSRDPFPQSNAPIMDEEREIPERSWNSGHEWVTDFKGKTVWFVPSIKTGNDIAACLRKNGKRVIQLSRKTFDSEYVKTRTNDWDFVVTTDISEMGANFKAERVIDPRRCMKPVILTDGEERVILAGPMPVTHSSAAQRRGRIGRNPRNENDQYIYMGEPLENDEDCAHWKEAKMLLDNINTPEGIIPSIFEPEREKVDAIDGEYRLRGEARKTFVDLMRRGDLPVWLAYKVAAEGINYADRRWCFDGTRNNQILEENVEVEIWTKEGERKKLKPRWLDARIYSDPLALKEFKEFAAGRK |
| Enzyme Length | 1683 |
| Uniprot Accession Number | P27914 |
| Absorption | |
| Active Site | ACT_SITE 1116; /note=Charge relay system; for serine protease NS3 activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU00860; ACT_SITE 1140; /note=Charge relay system; for serine protease NS3 activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU00860; ACT_SITE 1200; /note=Charge relay system; for serine protease NS3 activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU00860 |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=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.; EC=3.4.21.91; CATALYTIC ACTIVITY: Reaction=a ribonucleoside 5'-triphosphate + H2O = a ribonucleoside 5'-diphosphate + H(+) + phosphate; Xref=Rhea:RHEA:23680, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:43474, ChEBI:CHEBI:57930, ChEBI:CHEBI:61557; EC=3.6.1.15; CATALYTIC ACTIVITY: Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=3.6.4.13; |
| DNA Binding | |
| EC Number | 3.4.21.91; 3.6.1.15; 3.6.4.13 |
| Enzyme Function | FUNCTION: [Envelope protein E]: 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. prM-E cleavage is inefficient, and many virions are only partially matured. These uncleaved prM would play a role in immune evasion. {ECO:0000250|UniProtKB:P17763}.; FUNCTION: [Non-structural protein 1]: 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). {ECO:0000250|UniProtKB:Q9Q6P4}.; FUNCTION: [Non-structural protein 1]: 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. {ECO:0000250|UniProtKB:P17763}.; FUNCTION: [Non-structural protein 2A]: Component of the viral RNA replication complex that functions in virion assembly and antagonizes the host immune response. {ECO:0000250|UniProtKB:P17763}.; FUNCTION: Serine protease subunit NS2B: Required cofactor for the serine protease function of NS3. May have membrane-destabilizing activity and form viroporins (By similarity). {ECO:0000250|UniProtKB:P17763, ECO:0000255|PROSITE-ProRule:PRU00859}.; FUNCTION: [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. {ECO:0000255|PROSITE-ProRule:PRU00860}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | NP_BIND 1258..1265; /note=ATP; /evidence=ECO:0000255|PROSITE-ProRule:PRU00541 |
| Features | Active site (3); Beta strand (29); Chain (5); Disulfide bond (12); Domain (3); Glycosylation (3); Helix (6); Motif (1); Non-adjacent residues (1); Non-terminal residue (2); Nucleotide binding (1); Region (2); Site (5); Topological domain (8); Transmembrane (7); Turn (4) |
| Keywords | 3D-structure;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;Host endoplasmic reticulum;Host membrane;Host-virus interaction;Hydrolase;Membrane;Nucleotide-binding;Protease;Secreted;Serine protease;Suppressor of RNA silencing;Transmembrane;Transmembrane helix;Viral attachment to host cell;Viral envelope protein;Viral nucleoprotein;Viral penetration into host cytoplasm;Virion;Virus endocytosis by host;Virus entry into host cell;Zinc |
| Interact With | |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: [Envelope protein E]: Virion membrane {ECO:0000250|UniProtKB:P17763}; Multi-pass membrane protein {ECO:0000255}. Host endoplasmic reticulum membrane {ECO:0000250|UniProtKB:P17763}; Multi-pass membrane protein {ECO:0000255}.; SUBCELLULAR LOCATION: [Non-structural protein 1]: Secreted {ECO:0000250|UniProtKB:P17763}. Host endoplasmic reticulum membrane; Peripheral membrane protein; Lumenal side {ECO:0000250|UniProtKB:P17763}. Note=Located in RE-derived vesicles hosting the replication complex. {ECO:0000250|UniProtKB:Q9Q6P4}.; SUBCELLULAR LOCATION: [Non-structural protein 2A]: Host endoplasmic reticulum membrane {ECO:0000250|UniProtKB:P17763}; Multi-pass membrane protein {ECO:0000250|UniProtKB:P17763}.; SUBCELLULAR LOCATION: [Serine protease NS3]: Host endoplasmic reticulum membrane {ECO:0000255|PROSITE-ProRule:PRU00860}; Peripheral membrane protein {ECO:0000255|PROSITE-ProRule:PRU00860}; Cytoplasmic side {ECO:0000255|PROSITE-ProRule:PRU00860}. Note=Remains non-covalently associated to serine protease subunit NS2B. {ECO:0000255|PROSITE-ProRule:PRU00860}. |
| Modified Residue | |
| Post Translational Modification | PTM: [Genome polyprotein]: Specific enzymatic cleavages in vivo yield mature proteins. Cleavages in the lumen of endoplasmic reticulum are performed by host signal peptidase, wereas cleavages in the cytoplasmic side are performed by the Serine protease NS3. Signal cleavage at the 2K-4B site requires a prior NS3 protease-mediated cleavage at the 4A-2K site. {ECO:0000250|UniProtKB:P17763}.; PTM: [Non-structural protein 1]: N-glycosylated. The excreted form is glycosylated and this is required for efficient secretion of the protein from infected cells. {ECO:0000250|UniProtKB:P17763}.; PTM: [Envelope protein E]: N-glycosylated. {ECO:0000250|UniProtKB:P17763}.; PTM: [Genome polyprotein]: Specific enzymatic cleavages in vivo yield mature proteins. Cleavages in the lumen of endoplasmic reticulum are performed by host signal peptidase, wereas 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. {ECO:0000250|UniProtKB:P17763}. |
| Signal Peptide | |
| Structure 3D | Electron microscopy (1); X-ray crystallography (1) |
| Cross Reference PDB | 1TG8; 1TGE; |
| Mapped Pubmed ID | - |
| Motif | MOTIF 1349..1352; /note=DEAH box; /evidence=ECO:0000255|PROSITE-ProRule:PRU00541 |
| Gene Encoded By | |
| Mass | 187,440 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | RHEA:23680; RHEA:13065 |
| Cross Reference Brenda |