| IED ID | IndEnz0002010391 |
| Enzyme Type ID | protease010391 |
| Protein Name |
Genome polyprotein Cleaved into: Leader protein; Capsid protein VP0 VP4-VP2 ; Capsid protein VP4 P1A Rho Virion protein 4 ; Capsid protein VP2 Beta P1B Virion protein 2 ; Capsid protein VP3 Gamma P1C Virion protein 3 ; Capsid protein VP1 Alpha P1D Virion protein 1 ; Protein 2A P2A ; Protein 2B P2B ; Protein 2C P2C EC 3.6.4.13 ; Protein 3A P3A ; VPg Protein 3B P3B Viral protein genome-linked ; Protease 3C P3C EC 3.4.19.12 EC 3.4.22.28 Picornain 3C p22 ; RNA-directed RNA polymerase RdRp EC 2.7.7.48 3D polymerase 3Dpol Protein 3D 3D |
| Gene Name | |
| Organism | Seneca Valley virus (isolate -/United States/SSV-001/2002) (SVV) |
| Taxonomic Lineage | Viruses Riboviria Orthornavirae Pisuviricota Pisoniviricetes Picornavirales Picornaviridae Senecavirus Senecavirus A Seneca Valley virus (isolate -/United States/SSV-001/2002) (SVV) |
| Enzyme Sequence | MQNSHFSFDTASGTFEDVTGTKVKIVEYPRSVNNGVYDSSTHLEILNLQGEIEILRSFNEYQIRAAKQQLGLDIVYELQGNVQTTSKNDFDSRGNNGNMTFNYYANTYQNSVDFSTSSSASGAGPGNSRGGLAGLLTNFSGILNPLGYLKDHNTEEMENSADRVTTQTAGNTAINTQSSLGVLCAYVEDPTKSDPPSSSTDQPTTTFTAIDRWYTGRLNSWTKAVKTFSFQAVPLPGAFLSRQGGLNGGAFTATLHRHFLMKCGWQVQVQCNLTQFHQGALLVAMVPETTLDVKPDGKAKSLQELNEEQWVEMSDDYRTGKNMPFQSLGTYYRPPNWTWGPNFINPYQVTVFPHQILNARTSTSVDINVPYIGETPTQSSETQNSWTLLVMVLVPLDYKEGATTDPEITFSVRPTSPYFNGLRNRYTAGTDEEQGPIPTAPRENSLMFLSTLPDDTVPAYGNVRTPPVNYLPGEITDLLQLARIPTLMAFERVPEPVPASDTYVPYVAVPTQFDDRPLISFPITLSDPVYQNTLVGAISSNFANYRGCIQITLTFCGPMMARGKFLLSYSPPNGTQPQTLSEAMQCTYSIWDIGLNSSWTFVVPYISPSDYRETRAITNSVYSADGWFSLHKLTKITLPPDCPQSPCILFFASAGEDYTLRLPVDCNPSYVFHSTDNAETGVIEAGNTDTDFSGELAAPGSNHTNVKFLFDRSRLLNVIKVLEKDAVFPRPFPTQEGAQQDDGYFCLLTPRPTVASRPATRFGLYANPSGSGVLANTSLDFNFYSLACFTYFRSDLEVTVVSLEPDLEFAVGWFPSGSEYQASSFVYDQLHVPFHFTGRTPRAFASKGGKVSFVLPWNSVSSVLPVRWGGASKLSSATRGLPAHADWGTIYAFVPRPNEKKSTAVKHVAVYIRYKNARAWCPSMLPFRSYKQKMLMQSGDIETNPGPASDNPILEFLEAENDLVTLASLWKMVHSVQQTWRKYVKNDDFWPNLLSELVGEGSVALAATLSNQASVKALLGLHFLSRGLNYTDFYSLLIEKCSSFFTVEPPPPPAENLMTKPSVKSKFRKLFKMQGPMDKVKDWNQIAAGLKNFQFVRDLVKEVVDWLQAWINKEKASPVLQYQLEMKKLGPVALAHDAFMAGSGPPLSDDQIEYLQNLKSLALTLGKTNLAQSLTTMINAKQSSAQRVEPVVVVLRGKPGCGKSLASTLIAQAVSKRLYGSQSVYSLPPDPDFFDGYKGQFVTLMDDLGQNPDGQDFSTFCQMVSTAQFLPNMADLAEKGRPFTSNLIIATTNLPHFSPVTIADPSAVSRRINYDLTLEVSEAYKKHTRLNFDLAFRRTDAPPIYPFAAHVPFVDVAVRFKNGHQNFNLLELVDSICTDIRAKQQGARNMQTLVLQSPNENDDTPVDEALGRVLSPAAVDEALVDLTPEADPVGRLAILAKLGLALAAVTPGLIILAVGLYRYFSGSDADQEETESEGSVKAPRSENAYDGPKKNSKPPGALSLMEMQQPNVDMGFEAAVAKKVVVPITFMVPNRPSGLTQSALLVTGRTFLINEHTWSNPSWTSFTIRGEVHTRDEPFQTVHFTHHGIPTDLMMVRLGPGNSFPNNLDKFGLDQMPARNSRVVGVSSSYGNFFFSGNFLGFVDSITSEQGTYARLFRYRVTTYKGWCGSALVCEAGGVRRIIGLHSAGAAGIGAGTYISKLGLIKALKHLGEPLATMQGLMTELEPGITVHVPRKSKLRKTTAHAVYKPEFEPAVLSKFDPRLNKDVDLDEVIWSKHTANVPYQPPLFYTYMSEYAHRVFSFLGKDNDILTVKEAILGIPGLDPMDPHTAPGLPYAINGLRRTDLVDFVNGTVDAALAVQIQKFLDGDYSDHVFQTFLKDEIRPSEKVRAGKTRIVDVPSLAHCIVGRMLLGRFAAKFQSHPGFLLGSAIGSDPDVFWTVIGAQLEGRKNTYDVDYSAFDSSHGTGSFEALISHFFTVDNGFSPALGPYLRSLAVSVHAYGERRIKITGGLPSGCAATSLLNTVLNNVIIRTALALTYKEFEYDMVDIIAYGDDLLVGTDYDLDFNEVARRAAKLGYKMTPANKGSVFPPTSSLSDAVFLKRKFVQNNDGLYKPVMDLKNLEAMLSYFKPGTLLEKLQSVSMLAQHSGKEEYDRLMHPFADYGAVPSHEYLQARWRALFD |
| Enzyme Length | 2181 |
| Uniprot Accession Number | Q155Z9 |
| Absorption | |
| Active Site | ACT_SITE 1556; /note="For protease 3C activity and deubiquitinase activity"; /evidence="ECO:0000255|PROSITE-ProRule:PRU01222, ECO:0000269|PubMed:30408499"; ACT_SITE 1592; /note="For protease 3C activity"; /evidence="ECO:0000255|PROSITE-ProRule:PRU01222"; ACT_SITE 1668; /note="For protease 3C activity and deubiquitinase activity"; /evidence="ECO:0000255|PROSITE-ProRule:PRU01222, ECO:0000269|PubMed:30408499"; ACT_SITE 1956; /note="For RdRp activity"; /evidence="ECO:0000250|UniProtKB:P12296"; ACT_SITE 2054; /note="For RdRp activity"; /evidence="ECO:0000250|UniProtKB:P12296" |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: 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: 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}; CATALYTIC ACTIVITY: Reaction=Thiol-dependent hydrolysis of ester, thioester, amide, peptide and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-residue protein attached to proteins as an intracellular targeting signal).; EC=3.4.19.12; Evidence={ECO:0000269|PubMed:30408499}; 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; Evidence={ECO:0000305}; |
| DNA Binding | |
| EC Number | 3.6.4.13; 3.4.19.12; 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 (PubMed:18940610). Together they form an icosahedral capsid composed of 60 copies of each VP1, VP2, and VP3, with a diameter of approximately 325 Angstroms (Probable). VP4 lies on the inner surface of the protein shell formed by VP1, VP2 and VP3 (By similarity). All the three latter proteins contain a beta-sheet structure called beta-barrel jelly roll (By similarity). VP1 is situated at the 12 fivefold axes, whereas VP2 and VP3 are located at the quasi-sixfold axes (PubMed:18940610). {ECO:0000250|UniProtKB:P12296, ECO:0000269|PubMed:18940610, ECO:0000305|PubMed:18420805}.; FUNCTION: [Capsid protein VP2]: Forms an icosahedral capsid of pseudo T=3 symmetry with capsid proteins VP2 and VP3 (PubMed:18940610). Together they form an icosahedral capsid composed of 60 copies of each VP1, VP2, and VP3, with a diameter of approximately 270 Angstroms (Probable). VP4 lies on the inner surface of the protein shell formed by VP1, VP2 and VP3 (By similarity). All the three latter proteins contain a beta-sheet structure called beta-barrel jelly roll (By similarity). VP1 is situated at the 12 fivefold axes, whereas VP2 and VP3 are located at the quasi-sixfold axes (PubMed:18940610). {ECO:0000250|UniProtKB:P12296, ECO:0000269|PubMed:18940610, ECO:0000305|PubMed:18420805}.; FUNCTION: [Capsid protein VP3]: Forms an icosahedral capsid of pseudo T=3 symmetry with capsid proteins VP2 and VP3 (Probable). Together they form an icosahedral capsid composed of 60 copies of each VP1, VP2, and VP3, with a diameter of approximately 270 Angstroms (PubMed:18420805). VP4 lies on the inner surface of the protein shell formed by VP1, VP2 and VP3. All the three latter proteins contain a beta-sheet structure called beta-barrel jelly roll (By similarity). VP1 is situated at the 12 fivefold axes, whereas VP2 and VP3 are located at the quasi-sixfold axes (By similarity). {ECO:0000250|UniProtKB:P12296, ECO:0000305|PubMed:18420805}.; FUNCTION: [Capsid protein VP4]: Lies on the inner surface of the capsid shell (PubMed:18940610). 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). After genome has been released, the channel shrinks (By similarity). {ECO:0000250|UniProtKB:P12296, ECO:0000305|PubMed:18940610}.; FUNCTION: [Capsid protein VP0]: VP0 precursor is a component of immature procapsids. {ECO:0000250|UniProtKB:P08617}.; FUNCTION: [Protein 2A]: Mediates self-processing of the polyprotein by a translational effect termed 'ribosome skipping'. Mechanistically, 2A-mediated cleavage occurs between the C-terminal glycine and the proline of the downstream protein 2B. {ECO:0000250|UniProtKB:P03305}.; 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:P03305}.; FUNCTION: [Protein 2C]: Associates with and induces structural rearrangements of intracellular membranes. {ECO:0000250|UniProtKB:P03305}.; FUNCTION: [VPg]: Covalently linked to the 5'-end of both the positive-strand and negative-strand genomic RNAs. Acts as a genome-linked replication primer. {ECO:0000250|UniProtKB:P03305}.; FUNCTION: [Protease 3C]: Cysteine protease that generates mature viral proteins from the precursor polyprotein (By similarity). Inactivates crucial host adapter molecules in order to suppress antiviral type-I interferon (type-I IFN) and NF-kappaB production to escape host antiviral innate immune responses (PubMed:30408499, PubMed:29427864, PubMed:28566380). Deubiquitinase that acts on both lysine-48- and lysine-63-linked polyubiquitin chains and inhibits the ubiquitination of the ATP-dependent RNA helicase DDX58/RIG-I, TANK-binding kinase 1 (TBK1), and TNF receptor-associated factor 3 (TRAF3), thereby blocking the expression of IFN-beta and IFN stimulated gene 54 (ISG54) (PubMed:30408499). Induces host IRF3 and IRF7 degradation thereby suppressing IRF3- and IRF7-induced type-I IFN production (PubMed:29427864). Also decreases host IRF3 phosphorylation leading to negligible IRF3 activation (PubMed:29427864). Cleaves host MAVS, TRIF and TANK, which are then unable to regulate pattern recognition receptor (PRR)-mediated type-I IFN production (PubMed:28566380). {ECO:0000250|UniProtKB:P12296, ECO:0000269|PubMed:28566380, ECO:0000269|PubMed:29427864, ECO:0000269|PubMed:30408499}.; FUNCTION: [RNA-directed RNA polymerase]: Replicates the genomic and antigenomic RNAs by recognizing replications specific signals (By similarity). Performs VPg uridylylation (By similarity). {ECO:0000250|UniProtKB:P12296}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | NP_BIND 1197..1204; /note=ATP; /evidence=ECO:0000255|PROSITE-ProRule:PRU00551 |
| Features | Active site (5); Beta strand (46); Chain (14); Domain (3); Helix (17); Lipidation (1); Modified residue (1); Mutagenesis (2); Nucleotide binding (1); Region (1); Site (9); Turn (7) |
| Keywords | 3D-structure;ATP-binding;Capsid protein;Covalent protein-RNA linkage;Direct protein sequencing;Helicase;Host cytoplasm;Host cytoplasmic vesicle;Host membrane;Host nucleus;Host-virus interaction;Hydrolase;Inhibition of host IRF3 by virus;Inhibition of host IRF7 by virus;Inhibition of host MAVS by virus;Inhibition of host RIG-I by virus;Inhibition of host RLR pathway by virus;Inhibition of host TBK1 by virus;Inhibition of host TLR pathway by virus;Inhibition of host TRAFs by virus;Inhibition of host innate immune response by virus;Ion channel;Ion transport;Lipoprotein;Membrane;Myristate;Nucleotide-binding;Nucleotidyltransferase;Phosphoprotein;Protease;RNA-binding;RNA-directed RNA polymerase;Reference proteome;T=pseudo3 icosahedral capsid protein;Thiol protease;Transferase;Transport;Ubl conjugation pathway;Viral RNA replication;Viral attachment to host cell;Viral immunoevasion;Viral ion channel;Virion;Virus entry into host cell |
| Interact With | |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: [Capsid protein VP2]: Virion {ECO:0000250|UniProtKB:P12296}. Host cytoplasm {ECO:0000250|UniProtKB:B8XTP8}.; SUBCELLULAR LOCATION: [Capsid protein VP3]: Virion {ECO:0000250|UniProtKB:P12296}. Host cytoplasm {ECO:0000250|UniProtKB:B8XTP8}.; SUBCELLULAR LOCATION: [Capsid protein VP1]: Virion {ECO:0000250|UniProtKB:P12296}. Host cytoplasm {ECO:0000250|UniProtKB:B8XTP8}.; SUBCELLULAR LOCATION: [Protein 2A]: Host nucleus, host nucleolus {ECO:0000250|UniProtKB:Q66765}.; SUBCELLULAR LOCATION: [Protein 2B]: Host cytoplasmic vesicle membrane {ECO:0000250|UniProtKB:Q66765}; Peripheral membrane protein {ECO:0000250|UniProtKB:Q66765}; Cytoplasmic side {ECO:0000250|UniProtKB:Q66765}. 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 probably autophagosome-like vesicles. {ECO:0000250|UniProtKB:B8XTP8}.; SUBCELLULAR LOCATION: [Protein 2C]: Host cytoplasmic vesicle membrane {ECO:0000250|UniProtKB:Q66765}; Peripheral membrane protein {ECO:0000250|UniProtKB:Q66765}; Cytoplasmic side {ECO:0000250|UniProtKB:Q66765}. 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 probably autophagosome-like vesicles. {ECO:0000250|UniProtKB:B8XTP8}.; SUBCELLULAR LOCATION: [Protein 3A]: Host cytoplasmic vesicle membrane {ECO:0000250|UniProtKB:P03304}; Peripheral membrane protein {ECO:0000250|UniProtKB:B8XTP8}; Cytoplasmic side {ECO:0000250|UniProtKB:B8XTP8}. 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 probably autophagosome-like vesicles. {ECO:0000250|UniProtKB:B8XTP8}.; SUBCELLULAR LOCATION: [VPg]: Virion {ECO:0000250|UniProtKB:B8XTP8}.; SUBCELLULAR LOCATION: [Protease 3C]: Host cytoplasm {ECO:0000250|UniProtKB:B8XTP8}.; SUBCELLULAR LOCATION: [RNA-directed RNA polymerase]: Host cytoplasmic vesicle membrane {ECO:0000250|UniProtKB:Q66765}; Peripheral membrane protein {ECO:0000250|UniProtKB:Q66765}; Cytoplasmic side {ECO:0000250|UniProtKB:Q66765}. 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 probably autophagosome-like vesicles. {ECO:0000250|UniProtKB:B8XTP8}. |
| Modified Residue | MOD_RES 1489; /note=O-(5'-phospho-RNA)-tyrosine; /evidence=ECO:0000250|UniProtKB:P03300 |
| Post Translational Modification | PTM: [Genome polyprotein]: Specific enzymatic cleavages by the viral protease in vivo yield a variety of precursors and mature proteins (Probable). The polyprotein seems to be cotranslationally cleaved at the 2A/2B junction by a ribosomal skip from one codon to the next without formation of a peptide bond (By similarity). This process would release the P1-2A peptide from the translational complex (By similarity). {ECO:0000250|UniProtKB:P03304, ECO:0000305|PubMed:18420805}.; 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 is followed by a conformational change of the particle. {ECO:0000250|UniProtKB:P03300}.; PTM: [Capsid protein VP4]: Myristoylation is required during RNA encapsidation and formation of the mature virus particle. {ECO:0000250|UniProtKB:Q66282}.; PTM: [VPg]: Uridylylated by the polymerase and is covalently linked to the 5'-end of genomic RNA. This uridylylated form acts as a nucleotide-peptide primer for the polymerase. {ECO:0000250|UniProtKB:P12296}. |
| Signal Peptide | |
| Structure 3D | Electron microscopy (1); X-ray crystallography (2) |
| Cross Reference PDB | 3CJI; 6ADL; 6L0T; |
| Mapped Pubmed ID | 30514821; |
| Motif | |
| Gene Encoded By | |
| Mass | 240,620 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | RHEA:21248; RHEA:13065 |
| Cross Reference Brenda |