| IED ID | IndEnz0002007175 |
| Enzyme Type ID | protease007175 |
| Protein Name |
Frameshifted structural polyprotein p130 Cleaved into: Capsid protein EC 3.4.21.90 Coat protein C ; Precursor of protein E3/E2 p62 pE2 ; Assembly protein E3; Spike glycoprotein E2 E2 envelope glycoprotein ; Protein TF |
| Gene Name | |
| Organism | Chikungunya virus (strain S27-African prototype) (CHIKV) |
| Taxonomic Lineage | Viruses Riboviria Orthornavirae Kitrinoviricota Alsuviricetes Martellivirales Togaviridae Alphavirus (arboviruses group A) Chikungunya virus (CHIKV) Chikungunya virus (strain S27-African prototype) (CHIKV) |
| Enzyme Sequence | MEFIPTQTFYNRRYQPRPWTPRPTIQVIRPRPRPQRQAGQLAQLISAVNKLTMRAVPQQKPRKNRKNKKQKQKQQAPQNNTNQKKQPPKKKPAQKKKKPGRRERMCMKIENDCIFEVKHEGKVTGYACLVGDKVMKPAHVKGTIDNADLAKLAFKRSSKYDLECAQIPVHMKSDASKFTHEKPEGYYNWHHGAVQYSGGRFTIPTGAGKPGDSGRPIFDNKGRVVAIVLGGANEGARTALSVVTWNKDIVTKITPEGAEEWSLAIPVMCLLANTTFPCSQPPCIPCCYEKEPEETLRMLEDNVMRPGYYQLLQASLTCSPHRQRRSTKDNFNVYKATRPYLAHCPDCGEGHSCHSPVALERIRNEATDGTLKIQVSLQIGIGTDDSHDWTKLRYMDNHIPADAGRAGLFVRTSAPCTITGTMGHFILARCPKGETLTVGFTDSRKISHSCTHPFHHDPPVIGREKFHSRPQHGKELPCSTYVQSNAATAEEIEVHMPPDTPDRTLLSQQSGNVKITVNSQTVRYKCNCGGSNEGLITTDKVINNCKVDQCHAAVTNHKKWQYNSPLVPRNAELGDRKGKIHIPFPLANVTCMVPKARNPTVTYGKNQVIMLLYPDHPTLLSYRSMGEEPNYQEEWVTHKKEVVLTVPTEGLEVTWGNNEPYKYWPQLSANGTAHGHPHEIILYYYELYPTMTVVVVSVASFILLSMVGMAVGMCMCARRRCITPYELTPGATVPFLLSLICCIRTAKAATYQEAAVYLWNEQQPLFWLQALIPLAALIVLCNCLRLLPCCCKTLAFLSRNEHRCPHCERVRTRNSDPEHGGSTV |
| Enzyme Length | 824 |
| Uniprot Accession Number | P0DOK1 |
| Absorption | |
| Active Site | ACT_SITE 139; /note=Charge relay system; /evidence=ECO:0000255|PROSITE-ProRule:PRU01027; ACT_SITE 161; /note=Charge relay system; /evidence=ECO:0000255|PROSITE-ProRule:PRU01027; ACT_SITE 213; /note=Charge relay system; /evidence=ECO:0000255|PROSITE-ProRule:PRU01027 |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=Autocatalytic release of the core protein from the N-terminus of the togavirus structural polyprotein by hydrolysis of a -Trp-|-Ser- bond.; EC=3.4.21.90; Evidence={ECO:0000250|UniProtKB:P03316}; |
| DNA Binding | |
| EC Number | 3.4.21.90 |
| Enzyme Function | FUNCTION: [Capsid protein]: Forms an icosahedral capsid with a T=4 symmetry composed of 240 copies of the capsid protein surrounded by a lipid membrane through which penetrate 80 spikes composed of trimers of E1-E2 heterodimers (By similarity). The capsid protein binds to the viral RNA genome at a site adjacent to a ribosome binding site for viral genome translation following genome release (By similarity). Possesses a protease activity that results in its autocatalytic cleavage from the nascent structural protein (By similarity). Following its self-cleavage, the capsid protein transiently associates with ribosomes, and within several minutes the protein binds to viral RNA and rapidly assembles into icosahedric core particles (By similarity). The resulting nucleocapsid eventually associates with the cytoplasmic domain of the spike glycoprotein E2 at the cell membrane, leading to budding and formation of mature virions (By similarity). In case of infection, new virions attach to target cells and after clathrin-mediated endocytosis their membrane fuses with the host endosomal membrane (By similarity). This leads to the release of the nucleocapsid into the cytoplasm, followed by an uncoating event necessary for the genomic RNA to become accessible (By similarity). The uncoating might be triggered by the interaction of capsid proteins with ribosomes (By similarity). Binding of ribosomes would release the genomic RNA since the same region is genomic RNA-binding and ribosome-binding (By similarity). Specifically inhibits interleukin-1 receptor-associated kinase 1/IRAK1-dependent signaling during viral entry, representing a means by which the alphaviruses may evade innate immune detection and activation prior to viral gene expression (By similarity). {ECO:0000250|UniProtKB:P03315, ECO:0000250|UniProtKB:P03316, ECO:0000250|UniProtKB:P27284}.; FUNCTION: [Assembly protein E3]: Provides the signal sequence for the translocation of the precursor of protein E3/E2 to the host endoplasmic reticulum. Furin-cleaved E3 remains associated with spike glycoprotein E1 and mediates pH protection of the latter during the transport via the secretory pathway. After virion release from the host cell, the assembly protein E3 is gradually released in the extracellular space. {ECO:0000250|UniProtKB:P03315}.; FUNCTION: [Spike glycoprotein E2]: Plays a role in viral attachment to target host cell, by binding to the cell receptor. Synthesized as a p62 precursor which is processed by furin at the cell membrane just before virion budding, giving rise to E2-E1 heterodimer. The p62-E1 heterodimer is stable, whereas E2-E1 is unstable and dissociate at low pH. p62 is processed at the last step, presumably to avoid E1 fusion activation before its final export to cell surface. E2 C-terminus contains a transitory transmembrane that would be disrupted by palmitoylation, resulting in reorientation of the C-terminal tail from lumenal to cytoplasmic side. This step is critical since E2 C-terminus is involved in budding by interacting with capsid proteins. This release of E2 C-terminus in cytoplasm occurs lately in protein export, and precludes premature assembly of particles at the endoplasmic reticulum membrane. {ECO:0000250|UniProtKB:P03315}.; FUNCTION: [Protein TF]: Plays a role in viral assembly and release. {ECO:0000250|UniProtKB:P0DOK0}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (3); Beta strand (13); Chain (5); Compositional bias (2); Disulfide bond (1); Domain (1); Glycosylation (3); Helix (2); Lipidation (3); Motif (2); Region (9); Site (4); Topological domain (4); Transmembrane (2); Turn (1) |
| Keywords | 3D-structure;Capsid protein;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 cell membrane;Host cytoplasm;Host membrane;Host nucleus;Host-virus interaction;Hydrolase;Lipoprotein;Membrane;Palmitate;Protease;Reference proteome;Ribosomal frameshifting;Serine protease;T=4 icosahedral capsid protein;Transmembrane;Transmembrane helix;Viral attachment to host cell;Viral penetration into host cytoplasm;Virion;Virus entry into host cell |
| Interact With | |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: [Capsid protein]: Virion {ECO:0000250|UniProtKB:P03316}. Host cytoplasm {ECO:0000250|UniProtKB:Q8JUX5}. Host cell membrane {ECO:0000250|UniProtKB:P03316}. Host nucleus {ECO:0000250|UniProtKB:Q8JUX5}. Note=Shuttles between the cytoplasm and the nucleus. {ECO:0000250|UniProtKB:Q8JUX5}.; SUBCELLULAR LOCATION: [Spike glycoprotein E2]: Virion membrane {ECO:0000250|UniProtKB:Q8JUX5}; Single-pass type I membrane protein {ECO:0000255}. Host cell membrane {ECO:0000269|PubMed:21762510}; Single-pass type I membrane protein {ECO:0000250|UniProtKB:Q8JUX5}. |
| Modified Residue | |
| Post Translational Modification | PTM: [Isoform Frameshifted structural polyprotein]: Specific enzymatic cleavages in vivo yield mature proteins. Capsid protein is auto-cleaved during polyprotein translation, unmasking a signal peptide at the N-terminus of the precursor of E3/E2 (By similarity). The remaining polyprotein is then targeted to the host endoplasmic reticulum, where host signal peptidase cleaves it into pE2 and TF. pE2 is further processed to mature E3 and E2 by host furin in trans-Golgi vesicle (By similarity). {ECO:0000250|UniProtKB:P03315}.; PTM: [Spike glycoprotein E2]: Palmitoylated via thioester bonds. These palmitoylations may induce disruption of the C-terminus transmembrane. This would result in the reorientation of E2 C-terminus from lumenal to cytoplasmic side. {ECO:0000250|UniProtKB:P0DOK0}.; PTM: [Protein TF]: Palmitoylated via thioester bonds. {ECO:0000250|UniProtKB:P0DOK0}. |
| Signal Peptide | |
| Structure 3D | X-ray crystallography (1) |
| Cross Reference PDB | 5H23; |
| Mapped Pubmed ID | - |
| Motif | MOTIF 61..99; /note=Nuclear localization signal; /evidence=ECO:0000250|UniProtKB:P09592; MOTIF 144..154; /note=Nuclear export signal; /evidence=ECO:0000250|UniProtKB:P09592 |
| Gene Encoded By | |
| Mass | 92,620 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda |