| IED ID | IndEnz0002012931 |
| Enzyme Type ID | protease012931 |
| Protein Name |
Genome polyprotein Cleaved into: Leader protein L ; 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 G ; Protein 2B I P2B ; Protein 2C C P2C EC 3.6.4.13 ; Protein 3A P3A ; VPg P3B H Protein 3B ; Protease 3C P3C EC 3.4.22.28 Picornain 3C p22 ; RNA-directed RNA polymerase RdRp EC 2.7.7.48 3D polymerase 3Dpol E Protein 3D 3D |
| Gene Name | |
| Organism | Encephalomyocarditis virus (strain emc-d diabetogenic) |
| Taxonomic Lineage | Viruses Riboviria Orthornavirae Pisuviricota Pisoniviricetes Picornavirales Picornaviridae Cardiovirus Cardiovirus A Encephalomyocarditis virus Encephalomyocarditis virus (strain emc-d diabetogenic) |
| Enzyme Sequence | MATTMEQEICAHSLTFKGCPKCSALQYRNGFYLLKYDEEWYPEELLTDGEDDVFDPELDMEVVFELQGNSTSSDKNNSSSDGNEGVIINNFYSNQYQNSIDLSANATGSDPPRTYGQFSNLLSGAVNAFSNMIPLLADQNTEEMENLSDRVLQDTAGNTVTNTQSTVGRLVGYGAVHDGEHPASCADTASEKILAVERYYTFKVNDWTSTQKPFEYIRIPLPHVLSGEDGGVFGAALRRHYLVKTGWRVQVQCNASQFHAGSLLVFMAPEYPTLDAFAMDNRWSKDNLPNGTKTQTNRKGPFAMDHQNFWQWTLYPHQFLNLRTNTTVDLEVPYVNIAPTSSWTQHASWTLVIAVVAPLTYSTGASTSLDITASIQPVRPVFNGLRHETLSRQSPIPVTIREHAGTWYSTLPDSTVPIYGKTPVAPANYMVGEYKDFLEIAQIPTFIGNKIPNAVPYIEASNTAVKTQPLATYQVTLSCSCLANTFLAALSRNFAQYRGSLVYTFVFTGTAMMKGKFLIAYTPPGAGKPTSRDQAMQATYAIWDLGLNSSYSFTVPFISPTHFRMVGTDQVNITNVDGWVTVWQLTPLTYPPGCPTSAKILTMVSAGKDFSLKMPISPAPWSPQGVENAERGVTEDTDATADFVAQPVYLPENQTKVAFFYDRSSPIGAFAVKSGSLESGFAPFSNETCPNSVILTPGPQFDPAYDQLRPQRLTEIWGNGNEETSKVFPLKSKQDYSFCLFSPFVYYKCDLEVTLSPHTSGNHGLLVRWCPTGTPAKPTTQVLHEVSSLSEGRTPQVYSAGPGISNQISFVVPYNSPLSVLPAVWYNGHKRFDNTGSLGIAPNSDFGTLFFAGTKPDIKFTVYLRYKNMRVFCPRPTVFFPWPSSGDKIDMTPRAGVLMLESPNALDISRTYPTLHILIQFNHGGLEIRLFRHGMFWAEAHADVILRSRTKQISFLNNGSFPSMDARAPWNPWKNTYHAVLRAEPYRVTMDVYHKRIRPFRLPLVQKEWNVREENVFGLYGIFNAHYAGYFADLLIHDIETNPGPFMAKPKKQVFQTQGAAVSSMAQTLLPNDLASKVMGSAFTALLDANEDAQKAMRIIKTLSSLSDAWENVKETLNNPEFWKQLLSRCVQLIAGMTIAVMHPDPLTLLCLGTLTAAEITSQTSLCEEIVAKFKKIFTTPPPRFPTISLFQQQSPLKQVNDVFSLAKNLDWAVKTVEKVVDWFGTWVVQEEKEQTLDQLLQRFPEHAKRISDLRNGMSAYVECKESFDFFEKLYNQAVKEKRTGIAAVCEKFRQKHDHATARCEPVVIVLRGDAGQGKSLSSQVIAQAVSKTIFGRQSVYSLPPDSDFFDGYENQFAAIMDDLGQNPDGSDFTTFCQMVSTTNFLPNMASLERNGTPFTSQIVVATTNLPEFRPVTIAHYPAVERRITFDYSVSAGPVCSKTEAGYKVLDVERAFRPTGDAPLPCFQNNCLFLEKAGLQFRDNRTKEILSLVDVIERAVARIERKKKVLTTVQTLVAQAPVDEVSFHSVVQQLKARQEATDEQLEELQEAFAKTQERSSVFSDWMKISAMLCAATLALSQVVKMAKTVKQMVRPDLVRVQLDEQEQGPYNEAVRAKPKTLQLLDIQGPNPVMDFEKYVAKFVTAPIDFVYPTGVSTQTCLLVKGRTLAVNRHMAESDWSSIVVRGVTHARSTVRILAIAKAGKETDVSFIRLSSGPLFRDNTSKFVKADDVLPATSAPVIGIMNTDIPMMFTGTFLKAGVSVPVETGQTFNHCIHYKANTRKGWCGSALLADLGGKKKILGMHSAGSMGRTAASIVSQEMICAVVSAFEPQGALERLPDGPRIHVPRKTALRPTVARRVFQPAYAPAVLSKFDPRTEADVDEVAFSKHTSNQESLPPVFRMVAKEYANRVFTLLGRDNGRLTVKQALEGLEGMDPMDKNTSPGLPYTALGMRRTDVVDWESATLIPYAADRLKKMNEGDFSDIVYQTFLKDELRPVEKVQAAKTRIVDVPPFEHCILGRQLLGRFASKFQTQPGLELGSAIGCDPDVHWTAFGVAMQGFERVYDVDYSNFDSTHSVAMFRLLAEEFFTPENGFDPLVKEYLESLAISTHAFEEKRYLITGGLPSGCAATSMLNTIMNNIIIRAGLYLTYKNFEFDDVKVLSYGDDLLVATNYQLNFDKVRASLAKTGYKITPANKTSTFPLDSTLEDVVFLKRKFKKEGPLYRPVMNREALEAMLSYYRPGTLSEKLTSITMLAVHSGKPEYDRLFAPFREVGVVVPSFESVEYRWRSLFW |
| Enzyme Length | 2292 |
| Uniprot Accession Number | P17594 |
| Absorption | |
| Active Site | ACT_SITE 1673; /note=For protease 3C activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU01222; ACT_SITE 1707; /note=For protease 3C activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU01222; ACT_SITE 1786; /note=For protease 3C activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU01222; ACT_SITE 2067; /note=For RdRp activity; /evidence=ECO:0000250|UniProtKB:P12296; ACT_SITE 2165; /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=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}; 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 | 3.6.4.13; 3.4.22.28; 2.7.7.48 |
| Enzyme Function | FUNCTION: [Leader protein]: Forms a complex with host RAN and probably binds to exportins carrying activated MAPK in order to mediate the hyperphosphorylation of host Phe/Gly containing nuclear pore proteins (Nups) resulting in cessation of active nucleocytoplasmic transport (By similarity). Proteins with NLS signals fail to import, cellular mRNAs fail to export, and some proteins small enough for diffusion are not retained anymore (efflux) (By similarity). The resulting inhibition of cellular protein synthesis serves to ensure maximal viral gene expression and to evade host immune response (By similarity). {ECO:0000250|UniProtKB:Q66765}.; FUNCTION: [Capsid protein VP1]: Forms an icosahedral capsid of pseudo T=3 symmetry with capsid proteins VP2 and VP3. Together they form an icosahedral capsid composed of 60 copies of each VP1, VP2, and VP3, with a diameter of approximately 300 Angstroms.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. VP1 is situated at the 12 fivefold axes, whereas VP2 and VP3 are located at the quasi-sixfold axes. {ECO:0000250|UniProtKB:P12296}.; FUNCTION: [Capsid protein VP2]: Forms an icosahedral capsid of pseudo T=3 symmetry with capsid proteins VP2 and VP3. Together they form an icosahedral capsid composed of 60 copies of each VP1, VP2, and VP3, with a diameter of approximately 300 Angstroms.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. VP1 is situated at the 12 fivefold axes, whereas VP2 and VP3 are located at the quasi-sixfold axes. {ECO:0000250|UniProtKB:P12296}.; FUNCTION: [Capsid protein VP3]: Forms an icosahedral capsid of pseudo T=3 symmetry with capsid proteins VP2 and VP3. Together they form an icosahedral capsid composed of 60 copies of each VP1, VP2, and VP3, with a diameter of approximately 300 Angstroms.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. VP1 is situated at the 12 fivefold axes, whereas VP2 and VP3 are located at the quasi-sixfold axes. {ECO:0000250|UniProtKB:P12296}.; 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). After genome has been released, the channel shrinks (By similarity). {ECO:0000250|UniProtKB:P03300, ECO:0000250|UniProtKB:P12296}.; FUNCTION: [Capsid protein VP0]: VP0 precursor is a component of immature procapsids. {ECO:0000250|UniProtKB:P08617}.; FUNCTION: [Protein 2A]: Involved in host translation shutoff by inhibiting cap-dependent mRNA translation (By similarity). Nuclear localization is required for this function (By similarity). The resulting inhibition of cellular protein synthesis serves to ensure maximal viral gene expression and to evade host immune response (By similarity). Inhibits the phosphorylation of the leader protein (By similarity). Binds to the RNA stem-loop essential for the ribosomal frameshift event and trans-activates the production of protein 2B* (By similarity). {ECO:0000250|UniProtKB:P12296, ECO:0000250|UniProtKB:Q66765}.; FUNCTION: [Protein 2B]: Affects membrane integrity and causes an increase in membrane permeability. {ECO:0000250}.; FUNCTION: [Protein 2C]: Associates with and induces structural rearrangements of intracellular membranes (By similarity). It displays RNA-binding, nucleotide binding and NTPase activities (By similarity). Interacts with IFIH1/MDA5 to inhibit the induction of the IFN-beta signal pathway (By similarity). {ECO:0000250|UniProtKB:P03304, ECO:0000250|UniProtKB:P03305, ECO:0000250|UniProtKB:P08545}.; FUNCTION: [Protein 3A]: Serves as membrane anchor via its hydrophobic domain. {ECO:0000250}.; 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. Cleaves host PABP1, this cleavage is important for viral replication (By similarity). Cleaves host TANK and disrupts the TANK-TBK1-IKKepsilon-IRF3 complex, thereby inhibiting the induction of the IFN-beta signal pathway (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 1313..1320; /note=ATP; /evidence=ECO:0000255|PROSITE-ProRule:PRU00551 |
| Features | Active site (5); Chain (14); Domain (3); Lipidation (1); Modified residue (3); Motif (1); Nucleotide binding (1); Region (2); Site (10); Zinc finger (1) |
| Keywords | ATP-binding;Capsid protein;Covalent protein-RNA linkage;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;Membrane;Metal-binding;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 immunoevasion;Viral ion channel;Virion;Virus entry into host cell;Zinc;Zinc-finger |
| Interact With | |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: [Capsid protein VP2]: Virion {ECO:0000250|UniProtKB:P12296}. Host cytoplasm {ECO:0000305}.; SUBCELLULAR LOCATION: [Capsid protein VP3]: Virion {ECO:0000250|UniProtKB:P12296}. Host cytoplasm {ECO:0000305}.; SUBCELLULAR LOCATION: [Capsid protein VP1]: Virion {ECO:0000250|UniProtKB:P12296}. Host cytoplasm {ECO:0000305}.; SUBCELLULAR LOCATION: [Protein 2A]: Host nucleus, host nucleolus {ECO:0000250|UniProtKB:Q66765}.; 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 probably autophagosome-like vesicles. {ECO:0000305}.; 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 probably autophagosome-like vesicles. {ECO:0000305}.; SUBCELLULAR LOCATION: [Protein 3A]: Host cytoplasmic vesicle membrane {ECO:0000250|UniProtKB:P03304}; 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 probably autophagosome-like vesicles. {ECO:0000250|UniProtKB:P03304}.; SUBCELLULAR LOCATION: [VPg]: Virion {ECO:0000305}.; SUBCELLULAR LOCATION: [Protease 3C]: Host cytoplasm {ECO:0000305}.; 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 probably autophagosome-like vesicles. {ECO:0000305}. |
| Modified Residue | MOD_RES 41; /note=Phosphotyrosine; by host SYK; /evidence=ECO:0000250|UniProtKB:Q66765; MOD_RES 47; /note=Phosphothreonine; by host CK2; /evidence=ECO:0000250|UniProtKB:Q66765; MOD_RES 1610; /note=O-(5'-phospho-RNA)-tyrosine; /evidence=ECO:0000250|UniProtKB:P03300 |
| Post Translational Modification | PTM: [Leader protein]: Phosphorylated. {ECO:0000250|UniProtKB:Q66765}.; PTM: [Genome polyprotein]: Specific enzymatic cleavages by the viral protease in vivo yield a variety of precursors and mature proteins (By similarity). 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}.; 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: [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}.; PTM: [Capsid protein VP4]: Myristoylation is required during RNA encapsidation and formation of the mature virus particle. {ECO:0000250|UniProtKB:Q66282}. |
| Signal Peptide | |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | - |
| Motif | MOTIF 995..1003; /note=Nuclear localization signal; /evidence=ECO:0000250|UniProtKB:Q66765 |
| Gene Encoded By | |
| Mass | 255,428 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | RHEA:21248; RHEA:13065 |
| Cross Reference Brenda |