| IED ID | IndEnz0002011004 |
| Enzyme Type ID | protease011004 |
| Protein Name |
Genome polyprotein Cleaved into: Protein p48; NTPase EC 3.6.1.15 p41 ; Protein p22; Viral genome-linked protein VPG ; 3C-like protease 3CLpro EC 3.4.22.66 Calicivirin ; RNA-directed RNA polymerase RdRp EC 2.7.7.48 |
| Gene Name | ORF1 |
| Organism | Southampton virus (strain GI/Human/United Kingdom/Southampton/1991) (SHV) (Hu/NV/SHV/1991/UK) |
| Taxonomic Lineage | Viruses Riboviria Orthornavirae Pisuviricota Pisoniviricetes Picornavirales Caliciviridae Norovirus Norwalk virus Norovirus GI Southampton virus Southampton virus (strain GI/Human/United Kingdom/Southampton/1991) (SHV) (Hu/NV/SHV/1991/UK) |
| Enzyme Sequence | MMMASKDVVATNVASNNNANNTSATSRFLSRFKGLGGGASPPSPIKIKSTEMALGLIGRTTPEPTGTAGPPPKQQRDRPPRTQEEVQYGMGWSDRPIDQNVKSWEELDTTVKEEILDNHKEWFDAGGLGPCTMPPTYERVKDDSPPGEQVKWSARDGVNIGVERLTTVSGPEWNLCPLPPIDLRNMEPASEPTIGDMIEFYEGHIYHYSIYIGQGKTVGVHSPQAAFSVARVTIQPIAAWWRVCYIPQPKHRLSYDQLKELENEPWPYAAITNNCFEFCCQVMNLEDTWLQRRLVTSGRFHHPTQSWSQQTPEFQQDSKLELVRDAILAAVNGLVSQPFKNFLGKLKPLNVLNILSNCDWTFMGVVEMVILLLELFGVFWNPPDVSNFIASLLPDFHLQGPEDLARDLVPVILGGIGLAIGFTRDKVTKVMKSAVDGLRAATQLGQYGLEIFSLLKKYFFGGDQTERTLKGIEAAVIDMEVLSSTSVTQLVRDKQAAKAYMNILDNEEEKARKLSAKNADPHVISSTNALISRISMARSALAKAQAEMTSRMRPVVIMMCGPPGIGKTKAAEHLAKRLANEIRPGGKVGLVPREAVDHWDGYHGEEVMLWDDYGMTKILDDCNKLQAIADSAPLTLNCDRIENKGMQFVSDAIVITTNAPGPAPVDFVNLGPVCRRVDFLVYCSAPEVEQIRRVSPGDTSALKDCFKLDFSHLKMELAPQGGFDNQGNTPFGKGTMKPTTINRLLIQAVALTMERQDEFQLQGKMYDFDDDRVSAFTTMARDNGLGILSMAGLGKKLRGVTTMEGLKNALKGYKISACTIKWQAKVYSLESDGNSVNIKEERNILTQQQQSVCTASVALTRLRAARAVAYASCIQSAITSILQIAGSALVVNRAVKRMFGTRTATLSLEGPPREHKCRVHMAKAAGKGPIGHDDVVEKYGLCETEEDEEVAHTEIPSATMEGKNKGKNKKGRGRRNNYNAFSRRGLNDEEYEEYKKIREEKGGNYSIQEYLEDRQRYEEELAEVQAGGDGGIGETEMEIRHRVFYKSKSRKHHQEERRQLGLVTGSDIRKRKPIDWTPPKSAWADDEREVDYNEKISFEAPPTLWSRVTKFGSGWGFWVSPTVFITTTHVIPTSAKEFFGEPLTSIAIHRAGEFTLFRFSKKIRPDLTGMILEEGCPEGTVCSVLIKRDSGELLPLAVRMGAIASMRIQGRLVHGQSGMLLTGANAKGMDLGTIPGDCGAPYVYKRANDWVVCGVHAAATKSGNTVVCAVQASEGETTLEGGDKGHYAGHEIIKHGCGPALSTKTKFWKSSPEPLPPGVYEPAYLGGRDPRVTVGPSLQQVLRDQLKPFAEPRGRMPEPGLLEAAVETVTSSLEQVMDTPVPWSYSDACQSLDKTTSSGFPYHRRKNDDWNGTTFVRELGEQAAHANNMYEQAKSMKPMYTGALKDELVKPEKVYQKVKKRLLWGADLGTVVRAARAFGPFCDAIKSHTIKLPIKVGMNSIEDGPLIYAEHSKYKYHFDADYTAWDSTQNRQIMTESFSIMCRLTASPELASVVAQDLLAPSEMDVGDYVIRVKEGLPSGFPCTSQVNSINHWLITLCALSEVTGLSPDVIQSMSYFSFYGDDEIVSTDIEFDPAKLTQVLREYGLRPTRPDKSEGPIIVRKSVDGLVFLRRTISRDAAGFQGRLDRASIERQIYWTRGPNHSDPFETLVPHQQRKVQLISLLGEASLHGEKFYRKISSKVIQEIKTGGLEMYVPGWQAMFRWMRFHDLGLWTGDRNLLPEFVNDDGV |
| Enzyme Length | 1788 |
| Uniprot Accession Number | Q04544 |
| Absorption | |
| Active Site | ACT_SITE 1129; /note=For 3CLpro activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU00870; ACT_SITE 1153; /note=For 3CLpro activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU00870; ACT_SITE 1238; /note=For 3CLpro activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU00870 |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | 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=Endopeptidase with a preference for cleavage when the P1 position is occupied by Glu-|-Xaa and the P1' position is occupied by Gly-|-Yaa.; EC=3.4.22.66; Evidence={ECO:0000255|PROSITE-ProRule:PRU00870}; 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}; |
| DNA Binding | |
| EC Number | 3.6.1.15; 3.4.22.66; 2.7.7.48 |
| Enzyme Function | FUNCTION: Protein p48 may play a role in viral replication by interacting with host VAPA, a vesicle-associated membrane protein that plays a role in SNARE-mediated vesicle fusion. This interaction may target replication complex to intracellular membranes (By similarity). {ECO:0000250}.; FUNCTION: NTPase presumably plays a role in replication. Despite having similarities with helicases, does not seem to display any helicase activity (By similarity). {ECO:0000250}.; FUNCTION: Protein P22 may play a role in targeting replication complex to intracellular membranes. {ECO:0000250}.; FUNCTION: Viral genome-linked protein is covalently linked to the 5'-end of the positive-strand, negative-strand genomic RNAs and subgenomic RNA. Acts as a genome-linked replication primer. May recruit ribosome to viral RNA thereby promoting viral proteins translation (By similarity). {ECO:0000250}.; FUNCTION: 3C-like protease processes the polyprotein: 3CLpro-RdRp is first released by autocleavage, then all other proteins are cleaved. May cleave polyadenylate-binding protein thereby inhibiting cellular translation. {ECO:0000255|PROSITE-ProRule:PRU00870}.; FUNCTION: RNA-directed RNA polymerase replicates genomic and antigenomic RNA by recognizing replications specific signals. Transcribes also a subgenomic mRNA by initiating RNA synthesis internally on antigenomic RNA. This sgRNA codes for structural proteins. Catalyzes the covalent attachment VPg with viral RNAs (By similarity). {ECO:0000255|PROSITE-ProRule:PRU00539}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | NP_BIND 561..568; /note=ATP; /evidence=ECO:0000255|PROSITE-ProRule:PRU00551 |
| Features | Active site (3); Beta strand (12); Chain (7); Domain (3); Helix (3); Modified residue (1); Nucleotide binding (1); Region (2); Site (5); Turn (1) |
| Keywords | 3D-structure;ATP-binding;Covalent protein-RNA linkage;Host-virus interaction;Hydrolase;Nucleotide-binding;Nucleotidyltransferase;Phosphoprotein;Protease;RNA-directed RNA polymerase;Thiol protease;Transferase;Viral RNA replication |
| Interact With | |
| Induction | |
| Subcellular Location | |
| Modified Residue | MOD_RES 991; /note=O-(5'-phospho-RNA)-tyrosine; /evidence=ECO:0000250 |
| Post Translational Modification | PTM: Specific enzymatic cleavages in vivo yield mature proteins. 3CLpro is first autocatalytically cleaved, then processes the whole polyprotein. {ECO:0000255|PROSITE-ProRule:PRU00870}.; PTM: VPg is uridylylated by the polymerase and is covalently attached to the 5'-end of the polyadenylated genomic and subgenomic RNAs. This uridylylated form acts as a nucleotide-peptide primer for the polymerase (By similarity). {ECO:0000250}. |
| Signal Peptide | |
| Structure 3D | X-ray crystallography (1) |
| Cross Reference PDB | 2IPH; |
| Mapped Pubmed ID | 21128685; |
| Motif | |
| Gene Encoded By | |
| Mass | 198,582 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | RHEA:23680; RHEA:21248 |
| Cross Reference Brenda | 3.4.22.28;3.4.22.66;3.6.1.15; |