| IED ID | IndEnz0002013303 |
| Enzyme Type ID | protease013303 |
| Protein Name |
Genome polyprotein Cleaved into: Capsid protein VP0 P1AB Virion protein 0 ; Capsid protein VP3 P1C Virion protein 3 ; Capsid protein VP1 P1D Virion protein 1 ; Protein 2A P2A ; Protein 2B P2B ; Protein 2C P2C EC 3.6.1.15 ; Protein 3A P3A ; Protein 3B P3B VPg ; Protease 3C P3C EC 3.4.22.28 EC 3.4.22.29 Picornain 3C ; RNA-directed RNA polymerase 3D-POL P3D-POL EC 2.7.7.48 |
| Gene Name | |
| Organism | Human parechovirus 1 (strain Harris) (HPeV-1) (Echovirus 22) |
| Taxonomic Lineage | Viruses Riboviria Orthornavirae Pisuviricota Pisoniviricetes Picornavirales Picornaviridae Parechovirus Parechovirus A Human parechovirus 1 Human parechovirus 1 (strain Harris) (HPeV-1) (Echovirus 22) |
| Enzyme Sequence | METIKSIADMATGVVSSVDSTINAVNEKVESVGNEIGGNLLTKVADDASNILGPNCFATTAEPENKNVVQATTTVNTTNLTQHPSAPTMPFSPDFSNVDNFHSMAYDITTGDKNPSKLVRLETHEWTPSWARGYQITHVELPKVFWDHQDKPAYGQSRYFAAVRCGFHFQVQVNVNQGTAGSALVVYEPKPVVTYDSKLEFGAFTNLPHVLMNLAETTQADLCIPYVADTNYVKTDSSDLGQLKVYVWTPLSIPTGSANQVDVTILGSLLQLDFQNPRVFAQDVNIYDNAPNGKKKNWKKIMTMSTKYKWTRTKIDIAEGPGSMNMANVLCTTGAQSVALVGERAFYDPRTAGSKSRFDDLVKIAQLFSVMADSTTPSENHGVDAKGYFKWSATTAPQSIVHRNIVYLRLFPNLNVFVNSYSYFRGSLVLRLSVYASTFNRGRLRMGFFPNATTDSTSTLDNAIYTICDIGSDNSFEITIPYSFSTWMRKTNGHPIGLFQIEVLNRLTYNSSSPSEVYCIVQGKMGQDARFFCPTGSVVTFQNSWGSQMDLTDPLCIEDDTENCKQTMSPNELGLTSAQDDGPLGQEKPNYFLNFRSMNVDIFTVSHTKVDNLFGRAWFFMEHTFTNEGQWRVPLEFPKQGHGSLSLLFAYFTGELNIHVLFLSERGFLRVAHTYDTSNDRVNFLSSNGVITVPAGEQMTLSAPYYSNKPLRTVRDNNSLGYLMCKPFLTGTSTGKIEVYLSLRCPNFFFPLPAPKVTSSRALRGDMANLTNQSPYGQQPQNRMMKLAYLDRGFYKHYGIIVGDHVYQLDSDDIFKTALTGKAKFTKTKLTSDWVIEEECELDYFRIKYLESAVDSEHIFSVDKNCETIAKDIFGTHTLSQHQAIGLVGTILLTAGLMSTIKTPVNAVTIKEFFNHAIDGDEQGLSLLVQKCTTFFSSAATEILDNDLVKFIVKILVRILCYMVLYCHKPNILTTACLSTLLIMDVTSSSVLSPSCKALMQCLMDGDVKKLAEIVAESMSNTDDDEVKEQICDTVKYTKTILSNQGPFKGFNEVSTAFRHIDWWIHTLLKIKDMVLSVFKPSIESKAIQWLERNKEHVCSILDYASDIIVESKDQSKMKTQDFYQRYSDCLAKFKPIMAICFRSCHNSISNTVYRLFQELARIPNRISTNNDLIRIEPIGIWIQGEPGQGKSFLTHTLSRQLQKSCKLNGVFTNPTASEFMDGYDNQDIHLIDDLGQTRKEKDIEMLCNCISSVPFIVPMAHLEEKGKFYTSKLVVATTNKSDFSSTVLQDSGALKRRFPYIMHIRAAKAYSKAGKLNVSQAMATMSTGECWEVSKNGRDWETLKLKDLVDKITIDYNERVKNYNAWKQQLENQTLDDLDDAVSYIKHNFPDAIPYVDEYLNIEMSTLIEQMEAFIEPKPSVFKCFANKIGSKISKASREVVDWFSDKIKSMLSFVERNKAWLTVVSAVTSAISILLLVTKIFKKEESKDERAYNPTLPVAKPKGTFPVSQREFKNEAPYDGQLEHIISQMAYITGSTTGHMTHCAGYQHDEIILHGHSIKYLEQEDELTLHYKNKVFPIEQPSVTQVTLGGKPMDLAILKCKLPFRFKKNSKYYTNKIGTESMLIWMTEQGIITKEVQRVHHSGGIKTREGTESTKTISYTVKSCKGMCGGLLISKVEGNFKILGMHIAGNGEMGVAIPFNFLKNDMSDQGIVTEITPIQPMYINTKTQIHKSPVYGAVEVKMGPAVLSKSDTRLEEPVECLIKKSASKYRVNKFQVNNELWQGVKACVKSKFREIFGMNGIVDMKTAILGTSHVNSMDLSTSAGYSFVKSGYKKKDLICLEPFSVAPLLERLVQDKFHNLLKGNQITTTFNTCLKDELRKLDKIASGKTRCIEACEVDYCIVYRMIMMEIYDKIYQTPCYYSGLAVGINPYKDWHFMINALNDYNYEMDYSQYDGSLSSMLLWEAVEVLAYCHDSPDLVMQLHKPVIDSDHVVFNERWLIHGGMPSGSPCTTVLNSLCNLMMCIYTTNLISPGIDCLPIVYGDDVILSLDKEIEPEKLQSIMADSFGAEVTGSRKDEPPSLKPRMEVEFLKRKPGYFPESTFIVGKLDTENMIQHLMWMKNFSTFKQQLQSYLMELCLHGKDTYQHYIKILEPYLQEWNITVDDYDVVITKLMPMVFD |
| Enzyme Length | 2180 |
| Uniprot Accession Number | Q66578 |
| Absorption | |
| Active Site | ACT_SITE 1558; /note=For protease 3C activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU01222; ACT_SITE 1596; /note=For protease 3C activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU01222; ACT_SITE 1670; /note=For protease 3C activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU01222; ACT_SITE 2045; /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 Tyr-|-Gly bond in the picornavirus polyprotein.; EC=3.4.22.29; 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=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 | 3.6.1.15; 3.4.22.28; 3.4.22.29; 2.7.7.48 |
| Enzyme Function | FUNCTION: Capsid proteins VP0, VP2, VP3 form a closed capsid enclosing the viral positive strand RNA genome. Capsid proteins interact with host alpha-V/beta-3 integrin heterodimer to provide virion attachment target cell. This attachment induces virion internalization predominantly through clathrin-mediated endocytosis. {ECO:0000269|PubMed:11160695}.; FUNCTION: [Protein 2A]: Is not a protease. {ECO:0000250}.; FUNCTION: [Protein 2B]: Affects membrane integrity and cause an increase in membrane permeability. {ECO:0000250}.; FUNCTION: [Protein 2C]: Associates with and induces structural rearrangements of intracellular membranes. It displays RNA-binding, nucleotide binding and NTPase activities (By similarity). {ECO:0000250}.; FUNCTION: Protein 3A, via its hydrophobic domain, serves as membrane anchor. {ECO:0000250}.; FUNCTION: [Protease 3C]: Cysteine protease that generates mature viral proteins from the precursor polyprotein. In addition to its proteolytic activity, it binds to viral RNA, and thus influences viral genome replication. RNA and substrate bind cooperatively to the protease (By similarity). {ECO:0000250}.; FUNCTION: RNA-directed RNA polymerase 3D-POL replicates genomic and antigenomic RNA by recognizing replications specific signals. {ECO:0000255|PROSITE-ProRule:PRU00539}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | NP_BIND 1185..1192; /note=ATP; /evidence=ECO:0000255|PROSITE-ProRule:PRU00551 |
| Features | Active site (4); Beta strand (37); Chain (10); Domain (4); Helix (18); Modified residue (1); Motif (1); Nucleotide binding (1); Site (1); Turn (2) |
| Keywords | 3D-structure;ATP-binding;Capsid protein;Clathrin-mediated endocytosis of virus by host;Covalent protein-RNA linkage;Direct protein sequencing;Helicase;Host cytoplasm;Host cytoplasmic vesicle;Host membrane;Host-virus interaction;Hydrolase;Ion channel;Ion transport;Lipoprotein;Membrane;Myristate;Nucleotide-binding;Nucleotidyltransferase;Phosphoprotein;Protease;RNA-binding;RNA-directed RNA polymerase;T=pseudo3 icosahedral capsid protein;Thiol protease;Transferase;Transport;Viral RNA replication;Viral attachment to host cell;Viral ion channel;Viral penetration into host cytoplasm;Virion;Virus endocytosis by host;Virus entry into host cell |
| Interact With | |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: [Capsid protein VP3]: Virion {ECO:0000250}. Host cytoplasm {ECO:0000305}.; SUBCELLULAR LOCATION: [Capsid protein VP1]: Virion {ECO:0000250}. 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 (By similarity). {ECO:0000250}.; 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 (By similarity). {ECO:0000250}.; 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 (By similarity). {ECO:0000250}.; SUBCELLULAR LOCATION: [Protein 3B]: Virion {ECO:0000305}.; SUBCELLULAR LOCATION: [Protease 3C]: Host cytoplasm {ECO:0000305}.; SUBCELLULAR LOCATION: [RNA-directed RNA polymerase 3D-POL]: 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 (By similarity). {ECO:0000250}. |
| Modified Residue | MOD_RES 1494; /note=O-(5'-phospho-RNA)-tyrosine; /evidence=ECO:0000250 |
| Post Translational Modification | PTM: VPg is 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 (By similarity). {ECO:0000250}.; PTM: Specific enzymatic cleavages yield mature proteins. All cleavages are catalyzed by P3C.; PTM: The N-terminus of VP0 is blocked. |
| Signal Peptide | |
| Structure 3D | Electron microscopy (1); X-ray crystallography (2) |
| Cross Reference PDB | 4UDF; 4Z92; 5MJV; |
| Mapped Pubmed ID | 26157123; 26581987; 28232749; |
| Motif | MOTIF 764..766; /note=Cell attachment site; /evidence=ECO:0000255 |
| Gene Encoded By | |
| Mass | 245,844 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | RHEA:21248; RHEA:23680 |
| Cross Reference Brenda |