P08544Q88583Q88584Q88585Q88586Q88587Q88588Q88589Q88590Q88591Q88592POLG_TMEVBGenome polyproteinLeader proteinLCapsid protein VP0VP4-VP2Capsid protein VP4P1AVirion protein 4Capsid protein VP2P1BVirion protein 2Capsid protein VP3P1CVirion protein 3Capsid protein VP1P1DVirion protein 1Protein 2AP2AProtein 2BP2BProtein 2CP2C3.6.4.13Protein 3AP3AVPgP3BProtein 3BProtease 3CP3C3.4.22.28Picornain 3CRNA-directed RNA polymeraseRdRp2.7.7.483D polymerase3DpolProtein 3D3DTheiler's murine encephalomyelitis virus (strain BeAn 8386)TMEVVirusesRiboviriaOrthornaviraePisuviricotaPisoniviricetesPicornaviralesPicornaviridaeCaphthovirinaeCardiovirusCardiovirus BMus musculusMouseAnalysis of the complete nucleotide sequence of the picornavirus Theiler's murine encephalomyelitis virus indicates that it is closely related to cardioviruses.NUCLEOTIDE SEQUENCE [GENOMIC RNA]The leader protein of cardioviruses inhibits stress granule assembly.FUNCTION (LEADER PROTEIN)Binding interactions between the encephalomyocarditis virus leader and protein 2A.INTERACTION WITH THE LEADER PROTEIN (PROTEIN 2A)INTERACTION WITH PROTEIN 2A (LEADER PROTEIN)FUNCTION (PROTEIN 2A)Three cardiovirus leader proteins equivalently inhibit four different nucleocytoplasmic trafficking pathways.FUNCTION (LEADER PROTEIN)The Leader Protein of Theiler's Virus Prevents the Activation of PKR.FUNCTIONThree-dimensional structure of Theiler murine encephalomyelitis virus (BeAn strain).X-RAY CRYSTALLOGRAPHY (3.5 ANGSTROMS) OF 148-922Leader proteinForms 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 (Probable). 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). The leader protein also inhibits host interferon regulatory factor 3 (IRF3) dimerization, thereby blocking the transcriptional activation of IFN genes (By similarity). Binds to host RNase L thereby preventing its activation by 2'-5' oligoadenylates in order to counteract the antiviral interferon-inducible OAS/RNase L pathway (By similarity). Inhibits the integrated stress response (ISR) in the infected cell. Inhibits the host EIF2AK2/PKR by rendering this kinase unable to detect double-stranded RNA. Also impairs host stress granule formation probably by acting on a step downstream of EIF2AK2/PKR activation (PubMed:31292248).Capsid protein VP1Forms 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.Capsid protein VP2Forms 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.Capsid protein VP3Forms 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.Capsid protein VP4Lies 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).Capsid protein VP0VP0 precursor is a component of immature procapsids.Protein 2AInvolved 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 (PubMed:25210192).Protein 2BAffects membrane integrity and causes an increase in membrane permeability.Protein 2CAssociates with and induces structural rearrangements of intracellular membranes (By similarity). It displays RNA-binding, nucleotide binding and NTPase activities (By similarity).Protein 3AServes as membrane anchor via its hydrophobic domain.VPgForms a primer, VPg-pU, which is utilized by the polymerase for the initiation of RNA chains.Protease 3CCysteine 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).RNA-directed RNA polymeraseReplicates the genomic and antigenomic RNAs by recognizing replications specific signals (By similarity). Performs VPg uridylylation (By similarity).a ribonucleoside 5'-triphosphate + RNA(n) = diphosphate + RNA(n+1)ATP + H2O = ADP + H(+) + phosphateSelective 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.Protein 2AInteracts with host EIF4E (By similarity). Interacts with the leader protein (PubMed:25210192).Leader proteinInteracts with host RAN; the complex L-RAN recruits cellular kinases responsible for the L-induced nucleocytoplasmic trafficking inhibition (By similarity). The complex L-RAN can further bind to the host exportins XPO1/CRM1 and CSE1L/CAS (By similarity). Interacts with the protein 2A (PubMed:25210192). Interacts with host RNASEL; this interaction prevents RNASEL activation by its substrate 2'-5' oligoadenylates (By similarity).Capsid protein VP2VirionHost cytoplasmCapsid protein VP3VirionHost cytoplasmCapsid protein VP1VirionHost cytoplasmProtein 2AHost nucleusHost nucleolusProtein 2BHost cytoplasmic vesicle membranePeripheral membrane proteinCytoplasmic sideProbably 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.Protein 2CHost cytoplasmic vesicle membranePeripheral membrane proteinCytoplasmic sideProbably 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.Protein 3AHost cytoplasmic vesicle membranePeripheral membrane proteinCytoplasmic sideProbably 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.VPgVirionProtease 3CHost cytoplasmRNA-directed RNA polymeraseHost cytoplasmic vesicle membranePeripheral membrane proteinCytoplasmic sideProbably 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.Leader proteinThe Theilo and zinc-finger regions may both play a role in the inhibition of host nucleocytoplasmic trafficking and IRF-3 dimerization antagonism by the L protein.Leader proteinPhosphorylated.Genome polyproteinSpecific 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).Capsid protein VP0During 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.VPgUridylylated 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.Capsid protein VP4Myristoylation is required during RNA encapsidation and formation of the mature virus particle.Persistent strains of Theiler's virus (e.g. DA, TO, BeAn) cause persistent demyelinating disease whereas neurovirulent strains (such as GDVII) cause acute encephalitis.Belongs to the picornaviruses polyprotein family.Icosahedral capsid structure3D-structureATP-bindingCapsid proteinCovalent protein-RNA linkageDisulfide bondEukaryotic host gene expression shutoff by virusEukaryotic host translation shutoff by virusHelicaseHost cytoplasmHost cytoplasmic vesicleHost gene expression shutoff by virusHost membraneHost nucleusHost-virus interactionHydrolaseInhibition of host innate immune response by virusInhibition of host interferon signaling pathway by virusInhibition of host IRF3 by virusInhibition of host PKR by virusInhibition of host RLR pathway by virusIon channelIon transportLipoproteinMembraneMetal-bindingMyristateNucleotide-bindingNucleotidyltransferasePhosphoproteinProteaseRNA-bindingRNA-directed RNA polymeraseT=pseudo3 icosahedral capsid proteinThiol proteaseTransferaseTransportViral attachment to host cellViral immunoevasionViral ion channelViral RNA replicationVirionVirus entry into host cellZincZinc-fingerATPMACKHGYPDVCPICTAVDATPGFEYLLMADGEWYPTDLLCVDLDDDVFWPSDTSNQSQTMDWTDVPLIRDIVMEPQGNSSSSDKSNSQSSGNEGVIINNFYSNQYQNSIDLSASGGNAGDAPQTNGQLSNILGGAANAFATMAPLLLDQNTEEMENLSDRVASDKAGNSATNTQSTVGRLCGYGKSHHGEHPASCADTATDKVLAAERYYTIDLASWTTSQEAFSHIRIPLPHVLAGEDGGVFGATLRRHYLCKTGWRVQVQCNASQFHAGSLLVFMAPEFYTGKGTKTGTMEPSDPFTMDTEWRSPQGAPTGYRYDSRTGFFATNHQNQWQWTVYPHQILNLRTNTTVDLEVPYVNVAPSSSWTQHANWTLVVAVLSPLQYATGSSPDVQITASLQPVNPVFNGLRHETVIAQSPIPVTVREHKGCFYSTNPDTTVPIYGKTISTPSDYMCGEFSDLLELCKLPTFLGNPNTNNKRYPYFSATNSVPATSMVDYQVALSCSCMANSMLAAVARNFNQYRGSLNFLFVFTGAAMVKGKFLIAYTPPGAGKPTTRDQAMQSTYAIWDLGLNSSFNFTAPFISPTHYRQTSYTSPTITSVDGWVTVWKLTPLTYPSGTPTNSDILTLVSAGDDFTLRMPISPTKWVPQGVDNAEKGKVSNDDASVDFVAEPVKLPENQTRVAFFYDRAVPIGMLRPGQNMETTFNYQENDYRLNCLLLTPLPSFCPDSSSGPQKTKAPVQWRWVRSGGVNGANFPLMTKQDYAFLCFSPFTFYKCDLEVTVSALGMTRVASVLRWAPTGAPADVTDQLIGYTPSLGETRNPHMWLVGAGNSQVSFVVPYNSPLSVLPAAWFNGWSDFGNTKDFGVAPNADFGRLWIQGNTSASVRIRYKKMKVFCPRPTLFFPWPTPTTTKINADNPVPILELENPAALYRIDLFITFTDEFITFDYKVHGRPVLTFRIPGFGLTPAGRMLVCMGEQPAHGPFTSSRSLYHVIFTATCSSFSFSIYKGRYRSWKKPIHDELVDRGYTTFGEFFKAVRGYHADYYRQRLIHDVETNPGPVQSVFQPQGAVLTKSLAPQAGIQNLLLRLLGIDGDCSEVSKAITVVTDLVAAWEKAKTTLVSPEFWSKLILKTTKFIAASVLYLHNPDFTTTVCLSLMTGVDLLTNDSVFDWLKQKLSSFFRTPPPACPNVMQPQGPLREANEGFTFAKNIEWAMKTIQSVVNWLTSWFKQEEDHPQSKLDKLLMEFPDHCRNIMDMRNGRKAYCECTASFKYFDELYNLAVTCKRIPLASLCEKFKNRHDHSVTRPEPVVVVLRGAAGQGKSVTSQIIAQSVSKMAFGRQSVYSMPPDSEYFDGYENQFSVIMDDLGQNPDGEDFTVFCQMVSSTNFLPNMAHLERKGTPFTSSFIVATTNLPKFRPVTVAHYPAVDRRITFDFTVTAGPHCKTPAGMLDVEKAFDEIPGSKPQLACFSADCPLLHKRGVMFTCNRTQTVYNLQQVVKMVNDTITRKTENVKKMNSLVAQSPPDWEHFENILTCLRQNNAALQDQLDELQEAFAQARERSDFLSDWLKVSAIIFAGIASLSAVIKLASKFKESIWPTPVRVELSEGEQAAYAGRARAQKQALQVLDIQGGGKVLAQAGNPVMDFELFCAKNIVAPITFYYPDKAEVTQSCLLLRAHLFVVNRHVAETDWTAFKLKDVRHERHTVALRSVNRSGAKTDLTFIKVTKGPLFKDNVNKFCSNKDDFPARNDTVTGIMNTGLAFVYSGNFLIGNQPVNTTTGACFNHCLHYRAQTRRGWCGSAIICNVNGKKAVYGMHSAGGGGLAAATIITKELIEAAEKSMLALEPQGAIVDIATGSVVHVPRKTKLRRTVAHDVFQPKFEPAVLSRYDPRTDKDVDVVAFSKHTTNMESLPPIFDVVCGEYANRVFTILGKENGLLTVEQAVLGLPGMDPMEKDTSPGLPYTQQGLRRTDLLNFITAKMTPQLDYAHSKLVIGVYDDVVYQSFLKDEIRPIEKIHEAKTRIVDVPPFAHCIWGRQLLGRFASKFQTKPGLELGSAIGTDPDVDWTRYAVELSGFNYVYDVDYSNFDASHSTAMFECLINNFFTEQNGFDRRIAEYLRSLAVSRHAYEDRRVLIRGGLPSGCAATSMLNTIMNNVIIRAALYLTYSNFDFDDIKVLSYGDDLLIGTNYQIDFNLVKERLAPFGYKITPANKTTTFPLTSHLQDVTFLKRRFVRFNSYLFRPQMDAVNLKAMVSYCKPGTLKEKLMSIALLAVHSGPDIYDEIFLPFRNVGIVVPTYSSMLYRWLSLFR
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