| IED ID | IndEnz0002013888 |
| Enzyme Type ID | protease013888 |
| Protein Name |
Replicase polyprotein 1a pp1a ORF1a polyprotein Cleaved into: Non-structural protein 2 nsp2 p87 ; Papain-like protease PL-PRO EC 3.4.19.12 EC 3.4.22.- Non-structural protein 3 nsp3 p195 ; Non-structural protein 4 nsp4 Peptide HD2 p41 ; 3C-like proteinase 3CL-PRO 3CLp EC 3.4.22.- Main protease Mpro Non-structural protein 5 nsp5 p33 ; Non-structural protein 6 nsp6 p34 ; Non-structural protein 7 nsp7 p9 ; Non-structural protein 8 nsp8 p24 ; Non-structural protein 9 nsp9 p10 ; Non-structural protein 10 nsp10 Growth factor-like peptide GFL p16 ; Non-structural protein 11 nsp11 |
| Gene Name | 1a |
| Organism | Avian infectious bronchitis virus (strain Beaudette) (IBV) |
| Taxonomic Lineage | Viruses Riboviria Orthornavirae Pisuviricota Pisoniviricetes Nidovirales Cornidovirineae Coronaviridae Orthocoronavirinae Gammacoronavirus Igacovirus Avian coronavirus Infectious bronchitis virus Avian infectious bronchitis virus (strain Beaudette) (IBV) |
| Enzyme Sequence | MASSLKQGVSPKPRDVILVSKDIPEQLCDALFFYTSHNPKDYADAFAVRQKFDRSLQTGKQFKFETVCGLFLLKGVDKITPGVPAKVLKATSKLADLEDIFGVSPLARKYRELLKTACQWSLTVEALDVRAQTLDEIFDPTEILWLQVAAKIHVSSMAMRRLVGEVTAKVMDALGSNLSALFQIVKQQIARIFQKALAIFENVNELPQRIAALKMAFAKCARSITVVVVERTLVVKEFAGTCLASINGAVAKFFEELPNGFMGSKIFTTLAFFKEAAVRVVENIPNAPRGTKGFEVVGNAKGTQVVVRGMRNDLTLLDQKADIPVEPEGWSAILDGHLCYVFRSGDRFYAAPLSGNFALSDVHCCERVVCLSDGVTPEINDGLILAAIYSSFSVSELVTALKKGEPFKFLGHKFVYAKDAAVSFTLAKAATIADVLRLFQSARVIAEDVWSSFTEKSFEFWKLAYGKVRNLEEFVKTYVCKAQMSIVILAAVLGEDIWHLVSQVIYKLGVLFTKVVDFCDKHWKGFCVQLKRAKLIVTETFCVLKGVAQHCFQLLLDAIHSLYKSFKKCALGRIHGDLLFWKGGVHKIVQDGDEIWFDAIDSVDVEDLGVVQEKSIDFEVCDDVTLPENQPGHMVQIEDDGKNYMFFRFKKDENIYYTPMSQLGAINVVCKAGGKTVTFGETTVQEIPPPDVVPIKVSIECCGEPWNTIFKKAYKEPIEVDTDLTVEQLLSVIYEKMCDDLKLFPEAPEPPPFENVALVDKNGKDLDCIKSCHLIYRDYESDDDIEEEDAEECDTDSGEAEECDTNSECEEEDEDTKVLALIQDPASIKYPLPLDEDYSVYNGCIVHKDALDVVNLPSGEETFVVNNCFEGAVKPLPQKVVDVLGDWGEAVDAQEQLCQQEPLQHTFEEPVENSTGSSKTMTEQVVVEDQELPVVEQDQDVVVYTPTDLEVAKETAEEVDEFILIFAVPKEEVVSQKDGAQIKQEPIQVVKPQREKKAKKFKVKPATCEKPKFLEYKTCVGDLTVVIAKALDEFKEFCIVNAANEHMTHGSGVAKAIADFCGLDFVEYCEDYVKKHGPQQRLVTPSFVKGIQCVNNVVGPRHGDNNLHEKLVAAYKNVLVDGVVNYVVPVLSLGIFGVDFKMSIDAMREAFEGCTIRVLLFSLSQEHIDYFDVTCKQKTIYLTEDGVKYRSIVLKPGDSLGQFGQVYAKNKIVFTADDVEDKEILYVPTTDKSILEYYGLDAQKYVIYLQTLAQKWNVQYRDNFLILEWRDGNCWISSAIVLLQAAKIRFKGFLTEAWAKLLGGDPTDFVAWCYASCTAKVGDFSDANWLLANLAEHFDADYTNAFLKKRVSCNCGIKSYELRGLEACIQPVRATNLLHFKTQYSNCPTCGANNTDEVIEASLPYLLLFATDGPATVDCDEDAVGTVVFVGSTNSGHCYTQAAGQAFDNLAKDRKFGKKSPYITAMYTRFAFKNETSLPVAKQSKGKSKSVKEDVSNLATSSKASFDNLTDFEQWYDSNIYESLKVQESPDNFDKYVSFTTKEDSKLPLTLKVRGIKSVVDFRSKDGFIYKLTPDTDENSKAPVYYPVLDAISLKAIWVEGNANFVVGHPNYYSKSLHIPTFWENAENFVKMGDKIGGVTMGLWRAEHLNKPNLERIFNIAKKAIVGSSVVTTQCGKLIGKAATFIADKVGGGVVRNITDSIKGLCGITRGHFERKMSPQFLKTLMFFLFYFLKASVKSVVASYKTVLCKVVLATLLIVWFVYTSNPVMFTGIRVLDFLFEGSLCGPYKDYGKDSFDVLRYCADDFICRVCLHDKDSLHLYKHAYSVEQVYKDAASGFIFNWNWLYLVFLILFVKPVAGFVIICYCVKYLVLNSTVLQTGVCFLDWFVQTVFSHFNFMGAGFYFWLFYKIYIQVHHILYCKDVTCEVCKRVARSNRQEVSVVVGGRKQIVHVYTNSGYNFCKRHNWYCRNCDDYGHQNTFMSPEVAGELSEKLKRHVKPTAYAYHVVDEACLVDDFVNLKYKAATPGKDSASSAVKCFSVTDFLKKAVFLKEALKCEQISNDGFIVCNTQSAHALEEAKNAAIYYAQYLCKPILILDQALYEQLVVEPVSKSVIDKVCSILSSIISVDTAALNYKAGTLRDALLSITKDEEAVDMAIFCHNHDVDYTGDGFTNVIPSYGIDTGKLTPRDRGFLINADASIANLRVKNAPPVVWKFSELIKLSDSCLKYLISATVKSGVRFFITKSGAKQVIACHTQKLLVEKKAGGIVSGTFKCFKSYFKWLLIFYILFTACCSGYYYMEVSKSFVHPMYDVNSTLHVEGFKVIDKGVLREIVPEDTCFSNKFVNFDAFWGRPYDNSRNCPIVTAVIDGDGTVATGVPGFVSWVMDGVMFIHMTQTERKPWYIPTWFNREIVGYTQDSIITEGSFYTSIALFSARCLYLTASNTPQLYCFNGDNDAPGALPFGSIIPHRVYFQPNGVRLIVPQQILHTPYVVKFVSDSYCRGSVCEYTRPGYCVSLNPQWVLFNDEYTSKPGVFCGSTVRELMFSMVSTFFTGVNPNIYMQLATMFLILVVVVLIFAMVIKFQGVFKAYATTVFITMLVWVINAFILCVHSYNSVLAVILLVLYCYASLVTSRNTVIIMHCWLVFTFGLIVPTWLACCYLGFIIYMYTPLFLWCYGTTKNTRKLYDGNEFVGNYDLAAKSTFVIRGSEFVKLTNEIGDKFEAYLSAYARLKYYSGTGSEQDYLQACRAWLAYALDQYRNSGVEIVYTPPRYSIGVSRLQSGFKKLVSPSSAVEKCIVSVSYRGNNLNGLWLGDTIYCPRHVLGKFSGDQWNDVLNLANNHEFEVTTQHGVTLNVVSRRLKGAVLILQTAVANAETPKYKFIKANCGDSFTIACAYGGTVVGLYPVTMRSNGTIRASFLAGACGSVGFNIEKGVVNFFYMHHLELPNALHTGTDLMGEFYGGYVDEEVAQRVPPDNLVTNNIVAWLYAAIISVKESSFSLPKWLESTTVSVDDYNKWAGDNGFTPFSTSTAITKLSAITGVDVCKLLRTIMVKNSQWGGDPILGQYNFEDELTPESVFNQIGGVRLQSSFVRKATSWFWSRCVLACFLFVLCAIVLFTAVPLKFYVYAAVILLMAVLFISFTVKHVMAYMDTFLLPTLITVIIGVCAEVPFIYNTLISQVVIFLSQWYDPVVFDTMVPWMFLPLVLYTAFKCVQGCYMNSFNTSLLMLYQFVKLGFVIYTSSNTLTAYTEGNWELFFELVHTTVLANVSSNSLIGLFVFKCAKWMLYYCNATYLNNYVLMAVMVNCIGWLCTCYFGLYWWVNKVFGLTLGKYNFKVSVDQYRYMCLHKINPPKTVWEVFSTNILIQGIGGDRVLPIATVQAKLSDVKCTTVVLMQLLTKLNVEANSKMHVYLVELHNKILASDDVGECMDNLLGMLITLFCIDSTIDLSEYCDDILKRSTVLQSVTQEFSHIPSYAEYERAKNLYEKVLVDSKNGGVTQQELAAYRKAANIAKSVFDRDLAVQKKLDSMAERAMTTMYKEARVTDRRAKLVSSLHALLFSMLKKIDSEKLNVLFDQASSGVVPLATVPIVCSNKLTLVIPDPETWVKCVEGVHVTYSTVVWNIDTVIDADGTELHPTSTGSGLTYCISGANIAWPLKVNLTRNGHNKVDVVLQNNELMPHGVKTKACVAGVDQAHCSVESKCYYTNISGNSVVAAITSSNPNLKVASFLNEAGNQIYVDLDPPCKFGMKVGVKVEVVYLYFIKNTRSIVRGMVLGAISNVVVLQSKGHETEEVDAVGILSLCSFAVDPADTYCKYVAAGNQPLGNCVKMLTVHNGSGFAITSKPSPTPDQDSYGGASVCLYCRAHIAHPGSVGNLDGRCQFKGSFVQIPTTEKDPVGFCLRNKVCTVCQCWIGYGCQCDSLRQPKSSVQSVAGASDFDKNYLNGYGVAVRLG |
| Enzyme Length | 3951 |
| Uniprot Accession Number | P0C6V3 |
| Absorption | |
| Active Site | ACT_SITE 1274; /note=For PL-PRO activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU00444; ACT_SITE 1437; /note=For PL-PRO activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU00444; ACT_SITE 1448; /note=For PL-PRO activity; /evidence=ECO:0000250|UniProtKB:P0C6Y1; ACT_SITE 2820; /note=For 3CL-PRO activity; ACT_SITE 2922; /note=For 3CL-PRO activity |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: [Papain-like protease]: 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; Evidence={ECO:0000250|UniProtKB:P0C6U8}; |
| DNA Binding | |
| EC Number | 3.4.19.12; 3.4.22.-; 3.4.22.- |
| Enzyme Function | FUNCTION: [Isoform Replicase polyprotein 1a]: Multifunctional protein involved in the transcription and replication of viral RNAs. Contains the proteinases responsible for the cleavages of the polyprotein. {ECO:0000305}.; FUNCTION: [Non-structural protein 2]: May play a role in the modulation of host cell survival signaling pathway by interacting with host PHB and PHB2 (By similarity). Indeed, these two proteins play a role in maintaining the functional integrity of the mitochondria and protecting cells from various stresses (By similarity). {ECO:0000250|UniProtKB:P0C6U8}.; FUNCTION: [Papain-like protease]: Responsible for the cleavages located at the N-terminus of the replicase polyprotein (By similarity). In addition, PL-PRO possesses a deubiquitinating/deISGylating activity and processes both 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains from cellular substrates (By similarity). {ECO:0000250|UniProtKB:P0C6U8}.; FUNCTION: [Non-structural protein 4]: Plays a role in host membrane rearrangement that leads to creation of cytoplasmic double-membrane vesicles (DMV) necessary for viral replication (By similarity). Alone is able to induce paired membranes (By similarity). Coexpression of nsp3 and nsp4 does not result in the formation of DMVs (By similarity). {ECO:0000250|UniProtKB:P0C6U8}.; 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. {ECO:0000255|PROSITE-ProRule:PRU00772}.; FUNCTION: [Non-structural protein 7]: Forms a hexadecamer with nsp8 (8 subunits of each) that may participate in viral replication by acting as a primase. Alternatively, may synthesize substantially longer products than oligonucleotide primers. {ECO:0000250|UniProtKB:P0C6U8}.; FUNCTION: [Non-structural protein 8]: Forms a hexadecamer with nsp7 (8 subunits of each) that may participate in viral replication by acting as a primase. Alternatively, may synthesize substantially longer products than oligonucleotide primers. {ECO:0000250|UniProtKB:P0C6U8}.; FUNCTION: [Non-structural protein 9]: Plays an essential role in viral replication by forming a homodimer that binds single-stranded RNA. {ECO:0000250|UniProtKB:P0C6U8}.; FUNCTION: [Non-structural protein 10]: Plays a pivotal role in viral transcription by stimulating both nsp14 3'-5' exoribonuclease and nsp16 2'-O-methyltransferase activities (By similarity). Therefore plays an essential role in viral mRNAs cap methylation (By similarity). {ECO:0000250|UniProtKB:P0C6U8}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (5); Chain (11); Domain (10); Metal binding (8); Mutagenesis (21); Natural variant (17); Region (4); Site (9); Topological domain (13); Transmembrane (12); Zinc finger (3) |
| Keywords | Activation of host autophagy by virus;Host cytoplasm;Host endoplasmic reticulum;Host membrane;Host-virus interaction;Hydrolase;Lyase;Membrane;Metal-binding;Protease;RNA-binding;Reference proteome;Repeat;Ribosomal frameshifting;Thiol protease;Transmembrane;Transmembrane helix;Zinc;Zinc-finger |
| Interact With | Itself |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: [Papain-like protease]: Host endoplasmic reticulum membrane {ECO:0000250|UniProtKB:P0C6Y3}; Multi-pass membrane protein {ECO:0000305}. Host cytoplasm {ECO:0000250|UniProtKB:P0C6U8}. Note=Gammacoronaviruses induce membrane zippering to form zippered endoplasmic reticulum (zER). {ECO:0000250|UniProtKB:P0C6Y3}.; SUBCELLULAR LOCATION: [Non-structural protein 4]: Host endoplasmic reticulum membrane {ECO:0000250|UniProtKB:P0C6Y3}; Multi-pass membrane protein {ECO:0000305}. Host cytoplasm {ECO:0000250|UniProtKB:P0C6U8}. Note=Localizes in virally-induced cytoplasmic double-membrane vesicles (By similarity). Gammacoronaviruses induce membrane zippering to form zippered endoplasmic reticulum (zER) (By similarity). {ECO:0000250|UniProtKB:P0C6U8, ECO:0000250|UniProtKB:P0C6Y3}.; SUBCELLULAR LOCATION: [Non-structural protein 6]: Host endoplasmic reticulum membrane {ECO:0000250|UniProtKB:P0C6Y3}; Multi-pass membrane protein {ECO:0000305}. Note=Gammacoronaviruses induce membrane zippering to form zippered endoplasmic reticulum (zER). {ECO:0000250|UniProtKB:P0C6Y3}.; SUBCELLULAR LOCATION: [Non-structural protein 7]: Host cytoplasm, host perinuclear region {ECO:0000250}. Host cytoplasm {ECO:0000250|UniProtKB:P0DTD1}. Host endoplasmic reticulum {ECO:0000250|UniProtKB:P0DTD1}. Note=nsp7, nsp8, nsp9 and nsp10 are localized in cytoplasmic foci, largely perinuclear. Late in infection, they merge into confluent complexes.; SUBCELLULAR LOCATION: [Non-structural protein 8]: Host cytoplasm, host perinuclear region {ECO:0000250|UniProtKB:P0C6U8}. Host cytoplasm {ECO:0000250|UniProtKB:P0DTD1}. Host endoplasmic reticulum {ECO:0000250|UniProtKB:P0DTD1}. Note=nsp7, nsp8, nsp9 and nsp10 are localized in cytoplasmic foci, largely perinuclear. Late in infection, they merge into confluent complexes.; SUBCELLULAR LOCATION: [Non-structural protein 9]: Host cytoplasm, host perinuclear region {ECO:0000250}. Host cytoplasm {ECO:0000250|UniProtKB:P0DTD1}. Host endoplasmic reticulum {ECO:0000250|UniProtKB:P0DTD1}. Note=nsp7, nsp8, nsp9 and nsp10 are localized in cytoplasmic foci, largely perinuclear. Late in infection, they merge into confluent complexes.; SUBCELLULAR LOCATION: [Non-structural protein 10]: Host cytoplasm, host perinuclear region {ECO:0000250}. Host cytoplasm {ECO:0000250|UniProtKB:P0DTD1}. Host endoplasmic reticulum {ECO:0000250|UniProtKB:P0DTD1}. Note=nsp7, nsp8, nsp9 and nsp10 are localized in cytoplasmic foci, largely perinuclear. Late in infection, they merge into confluent complexes. |
| Modified Residue | |
| Post Translational Modification | PTM: [Isoform Replicase polyprotein 1a]: Specific enzymatic cleavages in vivo by its own proteases yield mature proteins (By similarity). 3C-like proteinase nsp5 liberates nsps 6-16 from the polyprotein (By similarity). Papain-like and 3C-like proteinases are autocatalytically processed. {ECO:0000250|UniProtKB:P0C6U8}.; PTM: [Non-structural protein 4]: N-glycosylated. {ECO:0000250|UniProtKB:P0C6Y1}. |
| Signal Peptide | |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | 16979681; 19022466; 20444893; 20573827; 21799305; 21909766; 22684079; 24991833; 28257598; 29035788; 30200673; |
| Motif | |
| Gene Encoded By | |
| Mass | 441,126 |
| Kinetics | |
| Metal Binding | METAL 3858; /note=Zinc 1; /evidence=ECO:0000255|PROSITE-ProRule:PRU01297; METAL 3861; /note=Zinc 1; /evidence=ECO:0000255|PROSITE-ProRule:PRU01297; METAL 3867; /note=Zinc 1; /evidence=ECO:0000255|PROSITE-ProRule:PRU01297; METAL 3878; /note=Zinc 1; /evidence=ECO:0000255|PROSITE-ProRule:PRU01297; METAL 3904; /note=Zinc 2; /evidence=ECO:0000255|PROSITE-ProRule:PRU01297; METAL 3907; /note=Zinc 2; /evidence=ECO:0000255|PROSITE-ProRule:PRU01297; METAL 3915; /note=Zinc 2; /evidence=ECO:0000255|PROSITE-ProRule:PRU01297; METAL 3917; /note=Zinc 2; /evidence=ECO:0000255|PROSITE-ProRule:PRU01297 |
| Rhea ID | |
| Cross Reference Brenda | 3.4.22.B14; |