| IED ID | IndEnz0002013895 |
| Enzyme Type ID | protease013895 |
| Protein Name |
Replicase polyprotein 1a pp1a ORF1a polyprotein Cleaved into: Non-structural protein 1 nsp1 p9 ; Non-structural protein 2 nsp2 p87 ; Non-structural protein 3 nsp3 EC 3.4.19.12 EC 3.4.22.- PL1-PRO/PL2-PRO PLP1/PLP2 Papain-like proteinases 1/2 p195 ; Non-structural protein 4 nsp4 Peptide HD2 ; 3C-like proteinase 3CL-PRO 3CLp EC 3.4.22.- M-PRO nsp5 p34 ; Non-structural protein 6 nsp6 ; Non-structural protein 7 nsp7 p5 ; Non-structural protein 8 nsp8 p23 ; Non-structural protein 9 nsp9 p12 ; Non-structural protein 10 nsp10 Growth factor-like peptide GFL p14 ; Non-structural protein 11 nsp11 |
| Gene Name | 1a |
| Organism | Porcine epidemic diarrhea virus (strain CV777) (PEDV) |
| Taxonomic Lineage | Viruses Riboviria Orthornavirae Pisuviricota Pisoniviricetes Nidovirales Cornidovirineae Coronaviridae Orthocoronavirinae Alphacoronavirus Pedacovirus Porcine epidemic diarrhea virus Porcine epidemic diarrhea virus (strain CV777) (PEDV) |
| Enzyme Sequence | MASNHVTLAFANDAEISAFGFCTASEAVSYYSEAAASGFMQCRFVSLDLADTVEGLLPEDYVMVVIGTTKLSAYVDTFGSRPRNICGWLLFSNCNYFLEELELTFGRRGGNIVPVDQYMCGADGKPVLQESEWEYTDFFADSEDGQLNIAGITYVKAWIVERSDVSYASQNLTSIKSITYCSTYEHTFLDGTAMKVARTPKIKKNVVLSEPLATIYREIGSPFVDNGSDARSIIRRPVFLHAFVKCKCGSYHWTVGDWTSYVSTCCGFKCKPVLVASCSAMPGSVVVTRAGAGTGVKYYNNMFLRHVADIDGLAFWRILKVQSKDDLACSGKFLEHHEEGFTDPCYFLNDSSLATKLKFDILSGKFSDEVKQAIIAGHVVVGSALVDIVDDALGQPWFIRKLGDLASAPWEQLKAVVRGLGLLSDEVVLFGKRLSCATLSIVNGVFEFLADVPEKLAAAVTVFVNFLNEFFESACDCLKVGGKTFNKVGSYVLFDNALVKLVKAKARGPRQAGICEVRYTSLVVGSTTKVVSKRVENANVNLVVVDEDVTLNTTGRTVVVDGLAFFESDGFYRHLADADVVIEHPVYKSACELKPVFECDPIPDFPLPVAASVAELCVQTDLLLKNYNTPYKTYSCVVRGDKCCITCTLQFKAPSYVEDAVNFVDLCTKNIGTAGFHEFYITAHEQQDLQGFLTTCCTMSGFECFMPTIPQCPAVLEEIDGGSIWRSFITGLNTMWDFCKRLKVSFGLDGIVVTVARKFKRLGALLAEMYNTYLSTVVENLVLAGVSFKYYATSVPKIVLGGCFHSVKSVFASVFQIPVQAGIEKFKVFLNCVHPVVPRVIETSFVELEETTFKPPALNGGIAIVDGFAFYYDGTLYYPTDGNSVVPICFKKKGGGDVKFSDEVSVKTIDPVYKVSLEFEFESETIMAVLNKAVGNRIKVTGGWDDVVEYINVAIEVLKDHVEVPKYYIYDEEGGTDPNLPVMVSQWPLNDDTISQDLLDVEVVTDAPIDSEGDEVDSSAPEKVADVANSEPGDDGLPVAPETNVESEVEEVAATLSFIKDTPSTVTKDPFAFDFVSYGGLKVLRQSHNNCWVTSTLVQLQLLGIVDDPAMELFSAGRVGPMVRKCYESQKAILGSLGDVSACLESLTKDLHTLKITCSVVCGCGTGERIYEGCAFRMTPTLEPFPYGACAQCAQVLMHTFKSIVGTGIFCRDTTALSLDSLVVKPLCAAAFIGKDSGHYVTNFYDAAMAIDGYGRHQIKYDTLNTICVKDVNWTAPLVPAVDSVVEPVVKPFYSYKNVDFYQGDFSDLVKLPCDFVVNAANEKLSHGGGIAKAIDVYTKGMLQKCSNDYIKAHGPIKVGRGVMLEALGLKVFNVVGPRKGKHAPELLVKAYKSVFANSGVALTPLISVGIFSVPLEESLSAFLACVGDRHCKCFCYGDKEREAIIKYMDGLVDAIFKEALVDTTPVQEDVQQVSQKPVLPNFEPFRIEGAHAFYECNPEGLMSLGADKLVLFTNSNLDFCSVGKCLNDVTSGALLEAINVFKKSNKTVPAGNCVTLDCANMISITMVVLPFDGDANYDKNYARAVVKVSKLKGKLVLAVDDATLYSKLSHLSVLGFVSTPDDVERFYANKSVVIKVTEDTRSVKAVKVESTATYGQQIGPCLVNDTVVTDNKPVVADVVAKVVPNANWDSHYGFDKAGEFHMLDHTGFTFPSEVVNGRRVIKTTDNNCWVNVTCLQLQFARFRFKSAGLQAMWESYCTGDVAMFVHWLYWLTGVDKGQPSDSENALNMLSKYIVPAGSVTIERVTHDGCCCSKRVVTAPVVNASVLKLGVEDGLCPHGLNYIGKVVVVKGTTIVVNVGKPVVAPSHLFLKGVSYTTFLDNGNGVVGHYTVFDHGTGMVHDGDAFVPGDLNVSPVTNVVVSEQTAVVIKDPVKKAELDATKLLDTMNYASERFFSFGDFMSRNLITVFLYILSILGLCFRAFRKRDVKVLAGVPQRTGIILRKSMRYNAKALGVFFKLKLYWFKVLGKFSLGIYALYALLFMTIRFTPIGSPVCDDVVAGYANSSFDKNEYCNSVICKVCLYGYQELSDFSHTQVVWQHLRDPLIGNVMPFFYLAFLAIFGGVYVKAITLYFIFQYLNSLGVFLGLQQSIWFLQLVPFDVFGDEIVVFFIVTRVLMFIKHVCLGCDKASCVACSKSARLKRVPVQTIFQGTSKSFYVHANGGSKFCKKHNFFCLNCDSYGPGCTFINDVIATEVGNVVKLNVQPTGPATILIDKVEFSNGFYYLYSGDTFWKYNFDITDSKYTCKEALKNCSIITDFIVFNNNGSNVNQVKNACVYFSQMLCKPVKLVDSALLASLSVDFGASLHSAFVSVLSNSFGKDLSSCNDMQDCKSTLGFDDVPLDTFNAAVAEAHRYDVLLTDMSFNNFTTSYAKPEEKFPVHDIATCMRVGAKIVNHNVLVKDSIPVVWLVRDFIALSEETRKYIIRTTKVKGITFMLTFNDCRMHTTIPTVCIANKKGAGLPSFSKVKKFFWFLCLFIVAAFFALSFLDFSTQVSSDSDYDFKYIESGQLKTFDNPLSCVHNVFINFDQWHDAKFGFTPVNNPSCPIVVGVSDEARTVPGIPAGVYLAGKTLVFAINTIFGTSGLCFDASGVADKGACIFNSACTTLSGLGGTAVYCYKNGLVEGAKLYSELAPHSYYKMVDGNAVSLPEIISRGFGIRTIRTKAMTYCRVGQCVQSAEGVCFGADRFFVYNAESGSDFVCGTGLFTLLMNVISVFSKTVPVTVLSGQILFNCIIAFVAVAVCFLFTKFKRMFGDMSVGVFTVGACTLLNNVSYIVTQNTLGMLGYATLYFLCTKGVRYMWIWHLGFLISYILIAPWWVLMVYAFSAIFEFMPNLFKLKVSTQLFEGDKFVGSFENAAAGTFVLDMHAYERLANSISTEKLRQYASTYNKYKYYSGSASEADYRLACFAHLAKAMMDYASNHNDTLYTPPTVSYNSTLQAGLRKMAQPSGVVEKCIVRVCYGNMALNGLWLGDIVMCPRHVIASSTTSTIDYDYALSVLRLHNFSISSGNVFLGVVSATMRGALLQIKVNQNNVHTPKYTYRTVRPGESFNILACYDGAAAGVYGVNMRSNYTIRGSFINGACGSPGYNINNGTVEFCYLHQLELGSGCHVGSDLDGVMYGGYEDQPTLQVEGASSLFTENVLAFLYAALINGSTWWLSSSRIAVDRFNEWAVHNGMTTVGNTDCFSILAAKTGVDVQRLLASIQSLHKNFGGKQILGHTSLTDEFTTGEVVRQMYGVNLQGGYVSRACRNVLLVGSFLTFFWSELVSYTKFFWVNPGYVTPMFACLSLLSSLLMFTLKHKTLFFQVFLIPALIVTSCINLAFDVEVYNYLAEHFDYHVSLMGFNAQGLVNIFVCFVVTILHGTYTWRFFNTPASSVTYVVALLTAAYNYFYASDILSCAMTLFASVTGNWFVGAVCYKVAVYMALRFPTFVAIFGDIKSVMFCYLVLGYFTCCFYGILYWFNRFFKVSVGVYDYTVSAAEFKYMVANGLRAPTGTLDSLLLSAKLIGIGGERNIKISSVQSKLTDIKCSNVVLLGCLSSMNVSANSTEWAYCVDLHNKINLCNDPEKAQEMLLALLAFFLSKNSAFGLDDLLESYFNDNSMLQSVASTYVGLPSYVIYENARQQYEDAVNNGSPPQLVKQLRHAMNVAKSEFDREASTQRKLDRMAEQAAAQMYKEARAVNRKSKVVSAMHSLLFGMLRRLDMSSVDTILNLAKDGVVPLSVIPAVSATKLNIVTSDIDSYNRIQREGCVHYAGTIWNIIDIKDNDGKVVHVKEVTAQNAESLSWPLVLGCERIVKLQNNEIIPGKLKQRSIKAEGDGIVGEGKALYNNEGGRTFMYAFISDKPDLRVVKWEFDGGCNTIELEPPRKFLVDSPNGAQIKYLYFVRNLNTLRRGAVLGYIGATVRLQAGKQTEQAINSSLLTLCAFAVDPAKTYIDAVKSGHKPVGNCVKMLANGSGNGQAVTNGVEASTNQDSYGGASVCLYCRAHVEHPSMDGFCRLKGKYVQVPLGTVDPIRFVLENDVCKVCGCWLSNGCTCDRSIMQSTDMAYLNEYGALVQLD |
| Enzyme Length | 4117 |
| Uniprot Accession Number | P0C6V6 |
| Absorption | |
| Active Site | ACT_SITE 1091; /note=For PL1-PRO activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU00444; ACT_SITE 1239; /note=For PL1-PRO activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU00444; ACT_SITE 1729; /note=For PL2-PRO activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU00444; ACT_SITE 1888; /note=For PL2-PRO activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU00444; ACT_SITE 3038; /note=For 3CL-PRO activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU00772; ACT_SITE 3141; /note=For 3CL-PRO activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU00772 |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=Thiol-dependent hydrolysis of ester, thioester, amide, peptide and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-residue protein attached to proteins as an intracellular targeting signal).; EC=3.4.19.12; |
| DNA Binding | |
| EC Number | 3.4.19.12; 3.4.22.-; 3.4.22.- |
| Enzyme Function | FUNCTION: The non-structural protein 1 (nsp1) protein plays a role in the inhibition of host interferon and pro-inflammatory cytokines production. Suppresses host RELA/p65 activation by blocking NFKBIA phosphorylation (PubMed:28715653). Targets also the RLR pathway downstream of the IRF3 activation by targeting host CREBBP to proteasomal degradation (PubMed:26773386). {ECO:0000269|PubMed:26773386, ECO:0000269|PubMed:28715653}.; FUNCTION: The papain-like proteinase 1 (PLP1) and papain-like proteinase 2 (PLP2) are responsible for the cleavages located at the N-terminus of the replicase polyprotein. In addition, PLP2 possesses a deubiquitinating/deISGylating activity and processes both 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains from cellular substrates. PLP2 also antagonizes innate immune induction of type I interferon by blocking the nuclear translocation of host IRF-3 (By similarity). {ECO:0000250}.; FUNCTION: [3C-like proteinase]: Responsible for the majority of cleavages as it cleaves the C-terminus of replicase polyprotein at 11 sites. Recognizes substrates containing the core sequence [ILMVF]-Q-|-[SGACN]. Inhibited by the substrate-analog Cbz-Val-Asn-Ser-Thr-Leu-Gln-CMK. Also contains an ADP-ribose-1''-phosphate (ADRP)-binding function (By similarity). {ECO:0000255|PROSITE-ProRule:PRU00772}.; FUNCTION: Nsp7-nsp8 hexadecamer may possibly confer processivity to the polymerase, maybe by binding to dsRNA or by producing primers utilized by the latter. {ECO:0000250}.; FUNCTION: Nsp9 is a ssRNA-binding protein. {ECO:0000250}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (6); Beta strand (16); Chain (12); Domain (12); Helix (11); Metal binding (8); Region (4); Site (10); Transmembrane (19); Turn (1); Zinc finger (3) |
| Keywords | 3D-structure;Activation of host autophagy by virus;Host cytoplasm;Host membrane;Host nucleus;Host-virus interaction;Hydrolase;Inhibition of host IRF3 by virus;Inhibition of host NF-kappa-B by virus;Inhibition of host RLR pathway by virus;Inhibition of host innate immune response by virus;Membrane;Metal-binding;Modulation of host ubiquitin pathway by viral deubiquitinase;Modulation of host ubiquitin pathway by virus;Protease;RNA-binding;Repeat;Ribosomal frameshifting;Thiol protease;Transmembrane;Transmembrane helix;Ubl conjugation pathway;Viral immunoevasion;Zinc;Zinc-finger |
| Interact With | |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: [Non-structural protein 1]: Host cytoplasm {ECO:0000269|PubMed:26773386}. Host nucleus {ECO:0000269|PubMed:26773386}.; SUBCELLULAR LOCATION: [Non-structural protein 3]: Host membrane {ECO:0000305}; Multi-pass membrane protein {ECO:0000305}.; SUBCELLULAR LOCATION: [Non-structural protein 4]: Host membrane {ECO:0000305}; Multi-pass membrane protein {ECO:0000305}.; SUBCELLULAR LOCATION: [Non-structural protein 6]: Host membrane {ECO:0000305}; Multi-pass membrane protein {ECO:0000305}.; SUBCELLULAR LOCATION: [Non-structural protein 7]: Host cytoplasm, host perinuclear region {ECO:0000250}. Note=nsp7, nsp8, nsp9 and nsp10 are localized in cytoplasmic foci, largely perinuclear. Late in infection, they merge into confluent complexes (By similarity). {ECO:0000250}.; SUBCELLULAR LOCATION: [Non-structural protein 8]: Host cytoplasm, host perinuclear region {ECO:0000250}. Note=nsp7, nsp8, nsp9 and nsp10 are localized in cytoplasmic foci, largely perinuclear. Late in infection, they merge into confluent complexes (By similarity). {ECO:0000250}.; SUBCELLULAR LOCATION: [Non-structural protein 9]: Host cytoplasm, host perinuclear region {ECO:0000250}. Note=nsp7, nsp8, nsp9 and nsp10 are localized in cytoplasmic foci, largely perinuclear. Late in infection, they merge into confluent complexes (By similarity). {ECO:0000250}.; SUBCELLULAR LOCATION: [Non-structural protein 10]: Host cytoplasm, host perinuclear region {ECO:0000250}. Note=nsp7, nsp8, nsp9 and nsp10 are localized in cytoplasmic foci, largely perinuclear. Late in infection, they merge into confluent complexes (By similarity). {ECO:0000250}. |
| Modified Residue | |
| Post Translational Modification | PTM: Specific enzymatic cleavages in vivo by its own proteases yield mature proteins. 3CL-PRO and PL-PRO proteinases are autocatalytically processed (By similarity). {ECO:0000250}. |
| Signal Peptide | |
| Structure 3D | X-ray crystallography (1) |
| Cross Reference PDB | 5GWZ; |
| Mapped Pubmed ID | 28287727; |
| Motif | |
| Gene Encoded By | |
| Mass | 452,818 |
| Kinetics | |
| Metal Binding | METAL 4039; /note=Zinc 1; /evidence=ECO:0000255|PROSITE-ProRule:PRU01297; METAL 4042; /note=Zinc 1; /evidence=ECO:0000255|PROSITE-ProRule:PRU01297; METAL 4048; /note=Zinc 1; /evidence=ECO:0000255|PROSITE-ProRule:PRU01297; METAL 4055; /note=Zinc 1; /evidence=ECO:0000255|PROSITE-ProRule:PRU01297; METAL 4081; /note=Zinc 2; /evidence=ECO:0000255|PROSITE-ProRule:PRU01297; METAL 4084; /note=Zinc 2; /evidence=ECO:0000255|PROSITE-ProRule:PRU01297; METAL 4092; /note=Zinc 2; /evidence=ECO:0000255|PROSITE-ProRule:PRU01297; METAL 4094; /note=Zinc 2; /evidence=ECO:0000255|PROSITE-ProRule:PRU01297 |
| Rhea ID | |
| Cross Reference Brenda |