| IED ID | IndEnz0002013945 |
| Enzyme Type ID | protease013945 |
| Protein Name |
Genome polyprotein Cleaved into: P1; Capsid protein VP0 VP4-VP2 ; Capsid protein VP4 P1A Virion protein 4 ; Capsid protein VP2 P1B Virion protein 2 ; Capsid protein VP3 P1C Virion protein 3 ; Capsid protein VP1 P1D Virion protein 1 ; P2; Protease 2A P2A EC 3.4.22.29 Picornain 2A Protein 2A ; Protein 2B P2B ; Protein 2C P2C EC 3.6.1.15 ; P3; Protein 3AB; Protein 3A P3A ; Viral protein genome-linked VPg Protein 3B P3B ; Protein 3CD EC 3.4.22.28 ; Protease 3C EC 3.4.22.28 Picornain 3C P3C ; RNA-directed RNA polymerase RdRp EC 2.7.7.48 3D polymerase 3Dpol Protein 3D 3D |
| Gene Name | |
| Organism | Coxsackievirus B5 (strain Peterborough / 1954/UK/85) |
| Taxonomic Lineage | Viruses Riboviria Orthornavirae Pisuviricota Pisoniviricetes Picornavirales Picornaviridae Enterovirus Enterovirus B Coxsackievirus B5 Coxsackievirus B5 (strain Peterborough / 1954/UK/85) |
| Enzyme Sequence | MGAQVSTQKTGAHETGLRASGNSIIHYTNINYYKDAASNSANRQEFAQDPGKFTEPVKDIMIKSMPALNSPSAEECGYSDRVRSITLGNSTITTQECANVVVGYGTWPTYLKDEEATAEDQPTQPDVATCRFYTLESVMWQQSSPGWWWKFPDALSNMGLFGQNMQYHYLGRAGYTVHVQCNASKFHQGCLLVVCVPEAEMGCATLANKPDQKSLSNGETANTFDSQNTTGQTAVQANVINAGMGVGVGNLTIFPHQWINLRTNNSATIVMPYINSVPMDNMFRHNNFTLMIIPFAPLSYSTGATTYVPITVTVAPMCAEYNGLRLAGKQGLPTMLTPGSNQFLTSDDFQSPSAMPQFDVTPEMAIPGQVNNLMEIAEVDSVVPVNNTEGKVSSIEAYQIPVQSNSTNGSQVFGFPLIPGASSVLNRTLLGEILNYYTHWSGSIKLTFMFCGSAMATGKFLLAYSPPGAGAPTTRKEAMLGTHVIWDVGLQSSCVLCIPWISQTHYRYVVVDEYTAGGYITCWYQTNIVVPADTQSDCKILCFVSACNDFSVRMLKDTPFIKQDSFYQGPPGEAVERAIARVADTISSGPVNSESIPALTAAETGHTSQVVPADTMQTRHVKNYHSRSESTVENFLCRSACVYYTTYKNHGTDGDNFAYWVINTRQVAQLRRKLEMFTYARFDLELTFVITSTQEQSTIQGQDSPVLTHQIMYVPPGGPVPTKINSYSWQTSTNPSVFWTEGSAPPRISIPFISIGNAYSMFYDGWAKFDKQGTYGINTLNNMGTLYMRHVNDGSPGPIVSTVRIYFKPKHVKTWVPRPPRLCQYQKAGNVNFEPTGVTESRTEITAMQTTGVLGQQTGAICIGNYRVVNRHLATSEDWQRCVWEDYNRDLLVSTTTAHGCDTIARCRCSTGVYFCASRNKHYPVSFEGPGLVEVQESEYYPKRYQSHVLLAAGFSEPGDCGGILRCEHGVIGLVTMGGEGVVGFADVRDLLWLEDDAMEQGVKDYVEQLGNAFGSGFTNQICEQVNLLKESLVGQDSILEKSLKALVKIISALVIVVRNHDDLVTITATLALIGCTSSPWRWLKQKVSQYYGIPMAERQNNNWLKKFTEMTNACKGMEWIAVKIQKFIDWLKVKILPEVKEKHEFLNRLKQLPLLESQIATIEQSAPSQSDQEQLFSNVQYFAHYCRKYAPLYAAEAKRVFSLEKKMSNYIQFKSKCRIEPVCLLLHGSPGAGKSVATNLIGRSLAEKLNSSVYSLPPDPDHFDGYKQQAVVIMDDLCQNPDGGDISLFCQMVSSVDFVPPMAALEEKGILFTSPFVLASTNAGSINAPTVSDSRALARRFHFDMNIEVISMYSQNGKINMPMSVRTCDEECCPVNFKRCCPLVCGKAIQFIDRRTQVRYSLDMLVTEMFREYNHRHSVGATLEALFQGPPIYREIKISVAPDTPPPPAIADLLKSVDSEAVREYCREKGWLVPEINSTLQIEKHVSRAFICLQALTTFVSVAGIIYIIYKLFAGFQGAYTGMPNQKPKVPTLRQAKVQGPAFEFAVAMMKRNSSTVKTEYGEFTMLGIYDRWAVLPRHAKPGPTILMNDQEVGVVDAKELVDKDGTNLELTLLKLSRNEKFRDIRGFLAKEEVEVNEAVLAINTSKFPNMYIPVGQVTDYGFLNLGGTPTKRMLMYNFPTRAGQCGGVLMSTGKVLGIHVGGNGHQGFSAALLKHYFNDEQGEIEFIESSKEAGLPVINTPSKTKLEPSVFHQVFEGNKEPAVLRNGDPRLKANFEEAIFSKYIGNVNTHVDEYMLEAVDHYAGQLATLDISTEPMKLEDAVYGTEGLEALDLTTSAGYPYVALGIKKRDILSKKTKDLTKLKECMDKYGLNLPMVTYVKDELRSAEKVAKGKSRLIEASSLNDSVAMRQTFGNLYKTFHLNPGIVTGSAVGCDPDLFWSKIPVLLDGHLIAFDYSGYDASLSPVWFACLKLLLEKLGYTHKETNYIDYLCNSHHLYRDKHYFVRGGMPSGCSGTSIFNSMINNIIIRTLMLKVYKGIDLDQFRMIAYGDDVIASYPWPIDASLLAEAGKDYGLIMTPADKGECFNEVTWTNVTFLKRYFRADEQYPFLVHPVMPMKDIHESIRWTKDPKNTQDHVRSLCLLAWHNGEHEYEEFIKKIRSVPVGRCLTLPAFSTLRRKWLDSF |
| Enzyme Length | 2185 |
| Uniprot Accession Number | Q03053 |
| Absorption | |
| Active Site | ACT_SITE 872; /note=For protease 2A activity; /evidence=ECO:0000250|UniProtKB:P03300; ACT_SITE 890; /note=For protease 2A activity; /evidence=ECO:0000250|UniProtKB:P03300; ACT_SITE 961; /note=For protease 2A activity; /evidence=ECO:0000250|UniProtKB:P03300; ACT_SITE 1580; /note=For protease 3C activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU01222; ACT_SITE 1611; /note=For protease 3C activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU01222; ACT_SITE 1687; /note=For protease 3C activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU01222 |
| Activity Regulation | ACTIVITY REGULATION: [RNA-directed RNA polymerase]: Replication or transcription is subject to high level of random mutations by the nucleotide analog ribavirin. {ECO:0000250|UniProtKB:P03300}. |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: [Protein 2C]: 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; Evidence={ECO:0000250|UniProtKB:P03300}; CATALYTIC ACTIVITY: [Protease 2A]: Reaction=Selective cleavage of Tyr-|-Gly bond in the picornavirus polyprotein.; EC=3.4.22.29; Evidence={ECO:0000250|UniProtKB:P03300}; CATALYTIC ACTIVITY: [RNA-directed RNA polymerase]: Reaction=a ribonucleoside 5'-triphosphate + RNA(n) = diphosphate + RNA(n+1); Xref=Rhea:RHEA:21248, Rhea:RHEA-COMP:14527, Rhea:RHEA-COMP:17342, ChEBI:CHEBI:33019, ChEBI:CHEBI:61557, ChEBI:CHEBI:140395; EC=2.7.7.48; Evidence={ECO:0000255|PROSITE-ProRule:PRU00539}; CATALYTIC ACTIVITY: [Protease 3C]: Reaction=Selective cleavage of Gln-|-Gly bond in the poliovirus polyprotein. In other picornavirus reactions Glu may be substituted for Gln, and Ser or Thr for Gly.; EC=3.4.22.28; Evidence={ECO:0000255|PROSITE-ProRule:PRU01222}; |
| DNA Binding | |
| EC Number | 3.4.22.29; 3.6.1.15; 3.4.22.28; 3.4.22.28; 2.7.7.48 |
| Enzyme Function | FUNCTION: [Capsid protein VP1]: Forms an icosahedral capsid of pseudo T=3 symmetry with capsid proteins VP2 and VP3 (By similarity). The capsid is 300 Angstroms in diameter, composed of 60 copies of each capsid protein and enclosing the viral positive strand RNA genome (By similarity). Capsid protein VP1 mainly forms the vertices of the capsid (By similarity). Capsid protein VP1 interacts with host cell receptor to provide virion attachment to target host cells (By similarity). This attachment induces virion internalization (By similarity). Tyrosine kinases are probably involved in the entry process (By similarity). After binding to its receptor, the capsid undergoes conformational changes (By similarity). Capsid protein VP1 N-terminus (that contains an amphipathic alpha-helix) and capsid protein VP4 are externalized (By similarity). Together, they shape a pore in the host membrane through which viral genome is translocated to host cell cytoplasm (By similarity). {ECO:0000250|UniProtKB:P03300, ECO:0000250|UniProtKB:P03313}.; FUNCTION: [Capsid protein VP2]: Forms an icosahedral capsid of pseudo T=3 symmetry with capsid proteins VP2 and VP3 (By similarity). The capsid is 300 Angstroms in diameter, composed of 60 copies of each capsid protein and enclosing the viral positive strand RNA genome (By similarity). {ECO:0000250|UniProtKB:P03300}.; FUNCTION: [Capsid protein VP3]: Forms an icosahedral capsid of pseudo T=3 symmetry with capsid proteins VP2 and VP3 (By similarity). The capsid is 300 Angstroms in diameter, composed of 60 copies of each capsid protein and enclosing the viral positive strand RNA genome (By similarity). {ECO:0000250|UniProtKB:P03300}.; FUNCTION: [Capsid protein VP4]: Lies on the inner surface of the capsid shell (By similarity). After binding to the host receptor, the capsid undergoes conformational changes (By similarity). Capsid protein VP4 is released, Capsid protein VP1 N-terminus is externalized, and together, they shape a pore in the host membrane through which the viral genome is translocated into the host cell cytoplasm (By similarity). {ECO:0000250|UniProtKB:P03300}.; FUNCTION: [Capsid protein VP0]: Component of immature procapsids, which is cleaved into capsid proteins VP4 and VP2 after maturation (By similarity). Allows the capsid to remain inactive before the maturation step (By similarity). {ECO:0000250|UniProtKB:P03300}.; FUNCTION: [Protease 2A]: Cysteine protease that cleaves viral polyprotein and specific host proteins (By similarity). It is responsible for the autocatalytic cleavage between the P1 and P2 regions, which is the first cleavage occurring in the polyprotein (By similarity). Cleaves also the host translation initiation factor EIF4G1, in order to shut down the capped cellular mRNA translation (By similarity). Inhibits the host nucleus-cytoplasm protein and RNA trafficking by cleaving host members of the nuclear pores (By similarity). Counteracts stress granule formation probably by antagonizing its assembly or promoting its dissassembly (By similarity). Cleaves and inhibits host IFIH1/MDA5, thereby inhibiting the type-I IFN production and the establishment of the antiviral state (By similarity). Cleaves and inhibits host MAVS, thereby inhibiting the type-I IFN production and the establishment of the antiviral state (By similarity). {ECO:0000250|UniProtKB:P03300, ECO:0000250|UniProtKB:P03313}.; FUNCTION: [Protein 2B]: Plays an essential role in the virus replication cycle by acting as a viroporin. Creates a pore in the host reticulum endoplasmic and as a consequence releases Ca2+ in the cytoplasm of infected cell. In turn, high levels of cytoplasmic calcium may trigger membrane trafficking and transport of viral ER-associated proteins to viroplasms, sites of viral genome replication. {ECO:0000250|UniProtKB:P03300}.; FUNCTION: [Protein 2C]: Induces and associates with structural rearrangements of intracellular membranes. Displays RNA-binding, nucleotide binding and NTPase activities. May play a role in virion morphogenesis and viral RNA encapsidation by interacting with the capsid protein VP3. {ECO:0000250|UniProtKB:P03300}.; FUNCTION: [Protein 3AB]: Localizes the viral replication complex to the surface of membranous vesicles. Together with protein 3CD binds the Cis-Active RNA Element (CRE) which is involved in RNA synthesis initiation. Acts as a cofactor to stimulate the activity of 3D polymerase, maybe through a nucleid acid chaperone activity. {ECO:0000250|UniProtKB:P03300}.; FUNCTION: [Protein 3A]: Localizes the viral replication complex to the surface of membranous vesicles. It inhibits host cell endoplasmic reticulum-to-Golgi apparatus transport and causes the disassembly of the Golgi complex, possibly through GBF1 interaction (By similarity). This would result in depletion of MHC, trail receptors and IFN receptors at the host cell surface (By similarity). Plays an essential role in viral RNA replication by recruiting ACBD3 and PI4KB at the viral replication sites, thereby allowing the formation of the rearranged membranous structures where viral replication takes place (By similarity). {ECO:0000250|UniProtKB:P03300}.; FUNCTION: [Viral protein genome-linked]: Acts as a primer for viral RNA replication and remains covalently bound to viral genomic RNA. VPg is uridylylated prior to priming replication into VPg-pUpU (By similarity). The oriI viral genomic sequence may act as a template for this. The VPg-pUpU is then used as primer on the genomic RNA poly(A) by the RNA-dependent RNA polymerase to replicate the viral genome (By similarity). Following genome release from the infecting virion in the cytoplasm, the VPg-RNA linkage is probably removed by host TDP2 (By similarity). During the late stage of the replication cycle, host TDP2 is excluded from sites of viral RNA synthesis and encapsidation, allowing for the generation of progeny virions (By similarity). {ECO:0000250|UniProtKB:P03300}.; FUNCTION: [Protein 3CD]: Involved in the viral replication complex and viral polypeptide maturation. It exhibits protease activity with a specificity and catalytic efficiency that is different from protease 3C. Protein 3CD lacks polymerase activity. Protein 3CD binds to the 5'UTR of the viral genome. {ECO:0000250|UniProtKB:P03300}.; FUNCTION: [RNA-directed RNA polymerase]: Replicates the viral genomic RNA on the surface of intracellular membranes. May form linear arrays of subunits that propagate along a strong head-to-tail interaction called interface-I. Covalently attaches UMP to a tyrosine of VPg, which is used to prime RNA synthesis. The positive stranded RNA genome is first replicated at virus induced membranous vesicles, creating a dsRNA genomic replication form. This dsRNA is then used as template to synthesize positive stranded RNA genomes. ss(+)RNA genomes are either translated, replicated or encapsidated. {ECO:0000250|UniProtKB:P03300}.; FUNCTION: [Protease 3C]: Major viral protease that mediates proteolytic processing of the polyprotein (By similarity). Cleaves host EIF5B, contributing to host translation shutoff (By similarity). Cleaves also host PABPC1, contributing to host translation shutoff (By similarity). Cleaves host NLRP1, triggers host N-glycine-mediated degradation of the autoinhibitory NLRP1 N-terminal fragment (By similarity). {ECO:0000250|UniProtKB:P03300, ECO:0000250|UniProtKB:P03303}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (6); Chain (18); Domain (3); Initiator methionine (1); Intramembrane (1); Lipidation (1); Metal binding (11); Modified residue (1); Region (6); Site (10); Topological domain (2); Zinc finger (1) |
| Keywords | ATP-binding;Activation of host autophagy by virus;Capsid protein;Covalent protein-RNA linkage;DNA replication;Eukaryotic host gene expression shutoff by virus;Eukaryotic host translation shutoff by virus;Helicase;Host cytoplasm;Host cytoplasmic vesicle;Host gene expression shutoff by virus;Host mRNA suppression by virus;Host membrane;Host nucleus;Host-virus interaction;Hydrolase;Inhibition of host RIG-I by virus;Inhibition of host RLR pathway by virus;Inhibition of host innate immune response by virus;Inhibition of host mRNA nuclear export by virus;Ion channel;Ion transport;Lipoprotein;Magnesium;Membrane;Metal-binding;Myristate;Nucleotide-binding;Nucleotidyltransferase;Phosphoprotein;Pore-mediated penetration of viral genome into host cell;Protease;RNA-binding;RNA-directed RNA polymerase;Repeat;T=pseudo3 icosahedral capsid protein;Thiol protease;Transferase;Transport;Viral RNA replication;Viral attachment to host cell;Viral immunoevasion;Viral ion channel;Viral penetration into host cytoplasm;Virion;Virus endocytosis by host;Virus entry into host cell;Zinc;Zinc-finger |
| Interact With | |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: [Capsid protein VP0]: Virion. Host cytoplasm {ECO:0000305}.; SUBCELLULAR LOCATION: [Capsid protein VP4]: Virion.; SUBCELLULAR LOCATION: [Capsid protein VP2]: Virion {ECO:0000250|UniProtKB:P03300}. Host cytoplasm {ECO:0000305}.; SUBCELLULAR LOCATION: [Capsid protein VP3]: Virion {ECO:0000250|UniProtKB:P03300}. Host cytoplasm {ECO:0000305}.; SUBCELLULAR LOCATION: [Capsid protein VP1]: Virion {ECO:0000250|UniProtKB:P03300}. Host cytoplasm {ECO:0000305}.; SUBCELLULAR LOCATION: [Protein 2B]: Host cytoplasmic vesicle membrane {ECO:0000305}; Peripheral membrane protein {ECO:0000305}; Cytoplasmic side {ECO:0000305}. Note=Probably localizes to the surface of intracellular membrane vesicles that are induced after virus infection as the site for viral RNA replication. These vesicles are derived from the endoplasmic reticulum.; SUBCELLULAR LOCATION: [Protein 2C]: Host cytoplasmic vesicle membrane {ECO:0000305}; Peripheral membrane protein {ECO:0000305}; Cytoplasmic side {ECO:0000305}. Note=Probably localizes to the surface of intracellular membrane vesicles that are induced after virus infection as the site for viral RNA replication. These vesicles are derived from the endoplasmic reticulum.; SUBCELLULAR LOCATION: [Protein 3A]: Host cytoplasmic vesicle membrane {ECO:0000305}; Peripheral membrane protein {ECO:0000305}; Cytoplasmic side {ECO:0000305}. Note=Probably localizes to the surface of intracellular membrane vesicles that are induced after virus infection as the site for viral RNA replication. These vesicles are derived from the endoplasmic reticulum.; SUBCELLULAR LOCATION: [Protein 3AB]: Host cytoplasmic vesicle membrane {ECO:0000305}; Peripheral membrane protein {ECO:0000305}; Cytoplasmic side {ECO:0000305}. Note=Probably localizes to the surface of intracellular membrane vesicles that are induced after virus infection as the site for viral RNA replication. These vesicles are derived from the endoplasmic reticulum.; SUBCELLULAR LOCATION: [Viral protein genome-linked]: Virion {ECO:0000250|UniProtKB:P03300}. Host cytoplasm {ECO:0000250|UniProtKB:Q66478}.; SUBCELLULAR LOCATION: [Protease 3C]: Host cytoplasm.; SUBCELLULAR LOCATION: [Protein 3CD]: Host nucleus {ECO:0000250|UniProtKB:P03300}. Host cytoplasm {ECO:0000250|UniProtKB:P03300}. Host cytoplasmic vesicle membrane {ECO:0000305}; Peripheral membrane protein {ECO:0000305}; Cytoplasmic side {ECO:0000305}. Note=Probably localizes to the surface of intracellular membrane vesicles that are induced after virus infection as the site for viral RNA replication. These vesicles are derived from the endoplasmic reticulum.; SUBCELLULAR LOCATION: [RNA-directed RNA polymerase]: Host cytoplasmic vesicle membrane {ECO:0000305}; Peripheral membrane protein {ECO:0000305}; Cytoplasmic side {ECO:0000305}. Note=Probably localizes to the surface of intracellular membrane vesicles that are induced after virus infection as the site for viral RNA replication. These vesicles are derived from the endoplasmic reticulum. |
| Modified Residue | MOD_RES 1521; /note=O-(5'-phospho-RNA)-tyrosine; /evidence=ECO:0000250|UniProtKB:P03300 |
| Post Translational Modification | PTM: [Genome polyprotein]: Specific enzymatic cleavages in vivo by the viral proteases yield processing intermediates and the mature proteins. {ECO:0000250|UniProtKB:P03300}.; PTM: [Capsid protein VP0]: Myristoylation is required for the formation of pentamers during virus assembly. Further assembly of 12 pentamers and a molecule of genomic RNA generates the provirion. {ECO:0000250|UniProtKB:P03300}.; PTM: [Capsid protein VP0]: During virion maturation, immature virions are rendered infectious following cleavage of VP0 into VP4 and VP2. This maturation seems to be an autocatalytic event triggered by the presence of RNA in the capsid and it is followed by a conformational change infectious virion. {ECO:0000250|UniProtKB:P03300}.; PTM: [Capsid protein VP4]: Myristoylation is required during RNA encapsidation and formation of the mature virus particle. {ECO:0000250|UniProtKB:P03300}.; PTM: [Viral protein genome-linked]: VPg is uridylylated by the polymerase into VPg-pUpU. This acts as a nucleotide-peptide primer for the genomic RNA replication. {ECO:0000250|UniProtKB:P03300}. |
| Signal Peptide | |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | - |
| Motif | |
| Gene Encoded By | |
| Mass | 243,300 |
| Kinetics | |
| Metal Binding | METAL 907; /note=Zinc; structural; /evidence=ECO:0000250|UniProtKB:Q9QF31; METAL 909; /note=Zinc; structural; /evidence=ECO:0000250|UniProtKB:Q9QF31; METAL 967; /note=Zinc; structural; /evidence=ECO:0000250|UniProtKB:Q9QF31; METAL 969; /note=Zinc; via pros nitrogen; structural; /evidence=ECO:0000250|UniProtKB:Q9QF31; METAL 1369; /note=Zinc; /evidence=ECO:0000250|UniProtKB:B9VUU3; METAL 1381; /note=Zinc; /evidence=ECO:0000250|UniProtKB:B9VUU3; METAL 1386; /note=Zinc; /evidence=ECO:0000250|UniProtKB:B9VUU3; METAL 1956; /note=Magnesium 1; catalytic; for RdRp activity; /evidence=ECO:0000250|UniProtKB:P03300; METAL 1956; /note=Magnesium 2; catalytic; for RdRp activity; /evidence=ECO:0000250|UniProtKB:P03300; METAL 2052; /note=Magnesium 1; catalytic; for RdRp activity; /evidence=ECO:0000250|UniProtKB:P03300; METAL 2052; /note=Magnesium 2; catalytic; for RdRp activity; /evidence=ECO:0000250|UniProtKB:P03300 |
| Rhea ID | RHEA:23680; RHEA:21248 |
| Cross Reference Brenda |