| IED ID | IndEnz0002000930 |
| Enzyme Type ID | protease000930 |
| Protein Name |
Genome polyprotein Cleaved into: Leader protein L ; Capsid protein VP0; Capsid protein VP3 P1C Virion protein 3 ; Capsid protein VP1 P1D Virion protein 1 ; Protein 2A P2A ; Protein 2B P2B ; Protein 2C P2C EC 3.6.4.13 ; Protein 3A P3A ; VPg P3B Protein 3B ; 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 | Aichi virus (strain Human/A846/88/1989) (AiV) (Aichi virus (strain A846/88)) |
| Taxonomic Lineage | Viruses Riboviria Orthornavirae Pisuviricota Pisoniviricetes Picornavirales Picornaviridae Kobuvirus Aichi virus (AiV) Aichi virus 1 Aichi virus (strain Human/A846/88/1989) (AiV) (Aichi virus (strain A846/88)) |
| Enzyme Sequence | MAATRVSRSVLAAVAHSAAHRTYHTVLDCYDRLYLNTNPHLSYPLPKNSSFPCPFCQYDEQNEVLSPESLRGEGAEPCWKCSQDKPRRKYNTTPPEDWLYDSDVQSWFYPETYYSDLQQKFFDKLALLSLPGAYQAKTPEERALAGALTQLLNFPSTPPLTLPTTNLQRQGNSVTNIYGNGNNVTTDVGANGWAPTVSTGLGDGPVSASADSLPGRSGGASSEKTHTVSGSSNKVGSRFSKWWEPAAARASESATDSAIEGIDAAGKAASKAITRKLDRPAAPSSTANPQPSLIALNPSATQSGNASILTGSTAPSLLAYPTATPVPLPNPDEPSQPGPSGDRTWLLDTVTWSQEFTRGWNIAGSNGMQWTGLESLIFPVSTDTNWTSTSSPTAYPLPFSFVRAYPDSSWAAMYNTHSMWNCGWRVQVTVNGSQFHAGALILYMVPEATTHAIQTARDNAGFVFPYVILNLYESNTATIEVPYISPTPNTSSGLHAPWTFYLQVLSPLNPPPSLPTSLSCSIYVTPVDSSFHGLRYLAPQHWKTRAVPGAGTFGSAVAGQELPLCGVRAYYPPNAYIPAQVRDWLEFAHRPGLMATVPWTMADEPAERLGIFPVSPSAIAGTGAPISYVISLFSQWRGELAAHLLFTGSAQHYGRLVVCYTPAAPQPPSTMQEAMRGTYTVWDVNAASTLEFTIPFISNSYWKTVDVNNPDALLSTTGYVSIWVQNPLVGPHTAPASALVQAFISAGESFNVRLMQNPALTSQTLTEDLDAPQDTGNIENGAADNSPQPRTTFDYTGNPLPPDTKLENFFSFYRLLPMGGSGAPSLSFPADEGTIIPLNPINWLKGADVSGIAAMLSCFTYIAADLRITLRFSNPNDNPATMLVAFAPPGATIPLKPTRQMLSNFYMAEVPVSAATSTMVSFSIPYTSPLSAIPTSYFGWEDWSGTNFGQLSSGSWGNLMLIPSLSVDSAIPFDFQLSCWVAFGNFKAWVPRPPPPLPPLPTPAANAERTVAVIKQGAASATPDVDPDDRVYIVRAQRPTYVHWAIRKVAPDGSAKQISLSRSGIQALVALEPPEGEPYLEILPSHWTLAELQLGNKWEYSATNNCTHFVSSITGESLPNTGFSLALGIGALTAIAASAAVAVKALPGIRRQGLLTLSADTETNQTLNKITESVNQAAQVVSQFDLSGPANSVSLAASDIREAAHKVASSLNGFTDVIADIKDSLFTRVSDAVESGVATFLTWLVKLFGYLLVLFGSPTPMSISGLLVIICADLAPHAREFFTASGNVLSSLYYWIASKLGLSVTPQECERATLEPQGLKDFNDGALAMRNVEWIGETAWKWAHRLLDWIRGKAKTDPQAKLADVHDEIMLHYSDSILALGSEKLPIDHITKSISRCRELVSIAQEAKSGPHSSFLNQAIKNYTLAISQHRKCQTGPRPEPVVVYLYGPPGTGKSLLASLLAQTLSQRLAGTPDDVYSPSSASCEYFDGYTGQTVHFIDDIGQDPEGRDWANFPNLVSSAPFIVPMASLEEKGTHYTSKVIVVTSNFHEPNERAARSMGALRRRVHLRINVTSNGVPFDPTNALNPIPGTQSKYFTAQTPLTLFQSNTVRLDRDSIWTPTFTNMDELVDAIVTRLDRSTGVSNSLASLIRRQGNRVIDAEPREIPLEYADDLLEAMAHHRPVPCSLGLSQAIANNTPIQQISETFWKYRKPIFTCTTFLAVLGFLCSVIPLARSLWKSKQDTPQEPQAAYSAISHQKPKPKSQKPVPTRHIQRQGISPAVPGISNNVVHVESGNGLNKNVMSGFYIFSRFLLVPTHLREPHHTTLTVGADTYDWATLQTQEFGEITIVHTPTSRQYKDMRRFIGAHPHPTGLLVSQFKAAPLYVRISDNRILDLDFPGVVVCKQAYGYRAATFEGLCGSPLVTDDPSGVKILGLHVAGVAGTSGFSAPIHPILGQITQFATTQQSLIVPTAEVRPGVNVNRMSRLHPSPAYGAFPVKKQPAPLKRNDKRLQEGVDLDTQLFLKHGKGDVTEPWPGLEAAADLYFSTFPTSLPVLTQEQAIHGTPNMEGLDMGQAAGYPWNTLGRSRRSLFDEVEPGVFVPKPELQAEINQTLEDPDYVYSTFLKDELRPTAKVEQGLTRIVEAAPIHAIVAGRMLLGGLIDYMQGRPGEHGSAVGCNPDVHWTSFFYAFSEFSQVYDLDYKCFDATLPSAVFTLVADHLTRITGDPRVGRYIHSIRHSHHIYGNRMYDMIGGNPSGCVATSILNTIINNICVLSALIQHPDFSPSRFHILAYGDDVIYATEPPIHPSFLREFYQKHTPLVVTPANKGQDFPPTSTIYEVTFLKRWFVPDDVRPIYIHPVMDPDTYEQSVMWLRDGDFQDVVTSLCHLAFHSGPKTYAAWCMKVREQCLKSGFAPNFLPYSYLQLRWLNLLAA |
| Enzyme Length | 2432 |
| Uniprot Accession Number | O91464 |
| Absorption | |
| Active Site | ACT_SITE 1816; /note="For protease 3C activity"; /evidence="ECO:0000250|UniProtKB:P03304, ECO:0000255|PROSITE-ProRule:PRU01222"; ACT_SITE 1844; /note="For protease 3C activity"; /evidence="ECO:0000250|UniProtKB:P03304"; ACT_SITE 1917; /note="For protease 3C activity"; /evidence="ECO:0000250|UniProtKB:P03304, ECO:0000255|PROSITE-ProRule:PRU01222"; ACT_SITE 2199; /note="For RdRp activity"; /evidence="ECO:0000250|UniProtKB:P12296"; ACT_SITE 2294; /note="For RdRp activity"; /evidence="ECO:0000250|UniProtKB:P12296" |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | 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=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=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:0000250|UniProtKB:P03300}; |
| DNA Binding | |
| EC Number | 3.6.4.13; 3.4.22.28; 3.4.22.28; 2.7.7.48 |
| Enzyme Function | FUNCTION: [Leader protein]: Required for viral RNA replication and viral RNA encapsidation (PubMed:14512530). Does not have any proteolytic activity (PubMed:14512530). {ECO:0000269|PubMed:14512530}.; FUNCTION: [Capsid protein VP1]: Forms an icosahedral capsid of pseudo T=3 symmetry with capsid proteins VP0 and VP3 (PubMed:27681122, PubMed:27595320). Together they form an icosahedral capsid composed of 60 copies of each VP0, VP1, and VP3 (PubMed:27681122, PubMed:27595320). All the three latter proteins contain a beta-sheet structure called beta-barrel jelly roll (PubMed:27595320). {ECO:0000269|PubMed:27595320, ECO:0000269|PubMed:27681122}.; FUNCTION: [Capsid protein VP0]: Forms an icosahedral capsid of pseudo T=3 symmetry with capsid proteins VP1 and VP3 (PubMed:27681122, PubMed:27595320). Together they form an icosahedral capsid composed of 60 copies of each VP0, VP1, and VP3 (PubMed:27681122, PubMed:27595320). All the three latter proteins contain a beta-sheet structure called beta-barrel jelly roll (PubMed:27595320). {ECO:0000269|PubMed:27595320, ECO:0000269|PubMed:27681122}.; FUNCTION: [Capsid protein VP3]: Forms an icosahedral capsid of pseudo T=3 symmetry with capsid proteins VP0 and VP1 (PubMed:27681122, PubMed:27595320). Together they form an icosahedral capsid composed of 60 copies of each VP0, VP1, and VP3 (PubMed:27681122, PubMed:27595320). All the three latter proteins contain a beta-sheet structure called beta-barrel jelly roll (PubMed:27595320). {ECO:0000269|PubMed:27595320, ECO:0000269|PubMed:27681122}.; FUNCTION: [Protein 2A]: Required for viral RNA replication (PubMed:18653460). Does not have any proteolytic activity (PubMed:18653460). {ECO:0000269|PubMed:18653460}.; FUNCTION: [Protein 2B]: Affects membrane integrity and causes an increase in membrane permeability. {ECO:0000250}.; 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 3A]: Serves as membrane anchor via its hydrophobic domain. Plays an essential role in viral RNA replication by recruiting PI4KB at the viral replication sites, thereby allowing the formation of the rearranged membranous structures where viral replication takes place (PubMed:22124328, PubMed:24672044, PubMed:27989622, PubMed:30755512, PubMed:22258260). Stimulates the enzymatic activity of PI4KB, this activation is sensitized by ACBD3 (PubMed:24672044, PubMed:27989622). {ECO:0000269|PubMed:22124328, ECO:0000269|PubMed:22258260, ECO:0000269|PubMed:24672044, ECO:0000269|PubMed:27989622, ECO:0000269|PubMed:30755512}.; FUNCTION: [VPg]: Forms a primer, VPg-pU, which is utilized by the polymerase for the initiation of RNA chains. {ECO:0000250|UniProtKB:P03304}.; FUNCTION: [Protease 3C]: Cysteine protease that generates mature viral proteins from the precursor polyprotein (By similarity). In addition to its proteolytic activity, it binds to viral RNA, and thus influences viral genome replication. RNA and substrate cooperatively bind to the protease (By similarity). {ECO:0000250|UniProtKB:P03304, ECO:0000250|UniProtKB:P12296}.; 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 1448..1455; /note=ATP; /evidence=ECO:0000255|PROSITE-ProRule:PRU00551 |
| Features | Active site (5); Beta strand (42); Chain (13); Compositional bias (3); Domain (4); Frameshift (1); Helix (15); Lipidation (2); Modified residue (3); Mutagenesis (9); Nucleotide binding (1); Region (5); Sequence conflict (7); Site (10); Transmembrane (1); Turn (8) |
| Keywords | 3D-structure;ATP-binding;Capsid protein;Covalent protein-RNA linkage;Eukaryotic host gene expression shutoff by virus;Eukaryotic host translation shutoff by virus;Helicase;Host Golgi apparatus;Host cytoplasm;Host cytoplasmic vesicle;Host gene expression shutoff by virus;Host mRNA suppression by virus;Host membrane;Host-virus interaction;Hydrolase;Inhibition of host mRNA nuclear export 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;Transmembrane;Transmembrane helix;Transport;Viral RNA replication;Viral attachment to host cell;Viral ion channel;Virion;Virus entry into host cell |
| Interact With | Q9H3P7; Q9H3P7; Q9H3P7; Q9H3P7 |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: [Capsid protein VP0]: Virion {ECO:0000269|PubMed:27595320, ECO:0000269|PubMed:27681122}. Host cytoplasm {ECO:0000250|UniProtKB:P12296}.; SUBCELLULAR LOCATION: [Capsid protein VP3]: Virion {ECO:0000269|PubMed:27595320, ECO:0000269|PubMed:27681122}. Host cytoplasm {ECO:0000250|UniProtKB:P12296}.; SUBCELLULAR LOCATION: [Capsid protein VP1]: Virion {ECO:0000269|PubMed:27595320, ECO:0000269|PubMed:27681122}. Host cytoplasm {ECO:0000250|UniProtKB:P12296}.; SUBCELLULAR LOCATION: [Protein 2B]: Host cytoplasmic vesicle membrane {ECO:0000269|PubMed:22124328, ECO:0000269|PubMed:24672044}; Peripheral membrane protein {ECO:0000250|UniProtKB:P03304}; Cytoplasmic side {ECO:0000250|UniProtKB:P03304}. 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:P03304}.; SUBCELLULAR LOCATION: [Protein 2C]: Host cytoplasmic vesicle membrane {ECO:0000269|PubMed:22124328, ECO:0000269|PubMed:24672044}; Peripheral membrane protein {ECO:0000250|UniProtKB:P03304}; Cytoplasmic side {ECO:0000250|UniProtKB:P03304}. 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:P03304}.; SUBCELLULAR LOCATION: [Protein 3A]: Host cytoplasmic vesicle membrane {ECO:0000269|PubMed:22124328, ECO:0000269|PubMed:24672044}; Single-pass membrane protein {ECO:0000255}. Host Golgi apparatus membrane {ECO:0000269|PubMed:30755512}; Single-pass membrane protein {ECO:0000255}. Note=Probably localizes to intracellular membrane vesicles that are induced after virus infection as the site for viral RNA replication. {ECO:0000250|UniProtKB:P03304}.; SUBCELLULAR LOCATION: [VPg]: Virion {ECO:0000250|UniProtKB:P03304}.; SUBCELLULAR LOCATION: [Protease 3C]: Host cytoplasm {ECO:0000250|UniProtKB:P03304}.; SUBCELLULAR LOCATION: [RNA-directed RNA polymerase]: Host cytoplasmic vesicle membrane {ECO:0000250|UniProtKB:P03304}; Peripheral membrane protein {ECO:0000250|UniProtKB:P03304}; Cytoplasmic side {ECO:0000250|UniProtKB:P03304}. 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:P03304}. |
| Modified Residue | MOD_RES 109; /note=Phosphotyrosine; by host SYK; /evidence=ECO:0000250|UniProtKB:Q66765; MOD_RES 115; /note=Phosphoserine; by host CK2; /evidence=ECO:0000250|UniProtKB:Q66765; MOD_RES 1750; /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 (PubMed:22226945). The leader protein-VP0 junction is cleaved by 3C proteinase (PubMed:14512530). The VP1/2A junction is cleaved by the protein 3CD in association with protein 2A (PubMed:22226945). {ECO:0000269|PubMed:14512530, ECO:0000269|PubMed:22226945}.; 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 (2); X-ray crystallography (2) |
| Cross Reference PDB | 5AOO; 5GKA; 5LVC; 5LZ3; |
| Mapped Pubmed ID | - |
| Motif | |
| Gene Encoded By | |
| Mass | 265,458 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | RHEA:21248; RHEA:13065 |
| Cross Reference Brenda |