| IED ID | IndEnz0002008785 |
| Enzyme Type ID | protease008785 |
| Protein Name |
Replicase polyprotein 1ab ORF1ab polyprotein Cleaved into: Nsp1-alpha papain-like cysteine proteinase EC 3.4.22.- PCP1-alpha ; Nsp1-beta papain-like cysteine proteinase EC 3.4.22.- PCP1-beta ; Nsp2 cysteine proteinase EC 3.4.22.- CP2 CP ; Non-structural protein 3 Nsp3 ; 3C-like serine proteinase 3CLSP EC 3.4.21.- Nsp4 ; Non-structural protein 5-6-7 Nsp5-6-7 ; Non-structural protein 5 Nsp5 ; Non-structural protein 6 Nsp6 ; Non-structural protein 7-alpha Nsp7-alpha ; Non-structural protein 7-beta Nsp7-beta ; Non-structural protein 8 Nsp8 ; RNA-directed RNA polymerase Pol RdRp EC 2.7.7.48 Nsp9 ; Helicase Hel EC 3.6.4.12 EC 3.6.4.13 Nsp10 ; Uridylate-specific endoribonuclease nsp11 EC 4.6.1.- Non-structural protein 11 Nsp11 ; Non-structural protein 12 Nsp12 |
| Gene Name | rep 1a-1b |
| Organism | Lactate dehydrogenase elevating virus (strain C) (LDV) |
| Taxonomic Lineage | Viruses Riboviria Orthornavirae Pisuviricota Pisoniviricetes Nidovirales Arnidovirineae Arteriviridae Variarterivirinae Gammaarterivirus Gammaarterivirus lacdeh Lactate dehydrogenase-elevating virus (LDV) Lactate dehydrogenase elevating virus (strain C) (LDV) |
| Enzyme Sequence | MQSGFDRCLCTPNARVFWERGQVYCTRCLAARPLLPLSQQHPRLGALGLFYRPASPLSWEAPVTYPTKECRPGGMCWLSSIYPIARMTSGNHNFQARLNFIASVVYRDGKLTSKHLEEDFEVYSRGCRWYPITGPVPGIALYANAVHVSDESFPGATHVLSNLPLPQQPLRKGLCPFADARANVWRYKGNTVFVSPQGYLWTTGSNDSVPEPWGEDRRLCEKIISSLPADHLVKINFSNYPFDYSFTGGDGAGFVVFPCKERDTKFSKCWEKIFEDHSGWMAACEEADLADRMGYRTPAGVAGPYLARRLQVRGLRAVVKPENNDYIVWALGVPESYIRHVSRAGEPVEEFFVKVGEFSIVSNCVVTPHPKFRFQTRKYYGYSPPGDGACGLHCISAMLNDIFGDSFTTRLGKCSRDSSEWLSDQDLYQLVMTANLPATIGHCPSAIYKLDCVNQHWTVTKRKGDRAVGRLAPDCLRGVCGECEMGIHIGADTDLSPIVELQLAQDVSPRPGALLWFLELHELCVVDDDFAHAIARAGEEYRRAMGIPRDDWVILAELMTENCRTRHQVLEKLQRGLQLQASSRPSSPASVSPASSVDLSAAGLLLSGTESDKEAVVAVNDGCYTVLGFDKNEATKSEQDLATDLFCDLVKPMETSTTKLESRKILEAAAKALESCKPKRKRSRKKKTRTPSPTCSVDAAVAEPTSVNSLGNQDTRETCASEKKAEKCPTPTPPPRPKRAALKNSNSGCVLKDIIWNQTGPGVKCLTIVEDVRAFLKGITPPGGVLSTRSRITKHIVDHFHSICEQTPELVLAHAEHQAKNLHELLASETAKLILGIGEDPLKKLVGSQRSLPRRLGFGAWLGGQQKTSGGCGEREFKDVGRKSGAERTPSKRDLGVSLGDQLSQDGARRLSSSTACEIKESVPPIIDSGGGLSQKFMAWLNHQVFVLSSHLLAVWSFIFGSRQVLGVFDYVYTLFCLCCVLLCFYLPAIGFMTLVGCVFGSPWRVRLSVFSVWLCVAVVVFQEVLPEPGAVCTSASAERAAALERYTSNGVHRPVNHLSVGLVGTVAGFVARSVGGPRRYWFYFLRLMVLLDLGLVFLAVALRGSCKKCFCKCVRTASHEVQLRVFPSTKVARTTLEAICDMYSAPRVDPIFIATGVRGCWTGSVSPHQVTEKPVSYSNLDDKKISNKTVVPPPTDPQQAVRCLKVLQCGGSIQDVSVPEVKKVTKVPFKAPFFPNVTIDPECYIVVDPVTYSAAMRGGYGVSHLIVGLGDFAEVNGLRFVSGGQIADFVCLGLYVLLNFLLSAWLSSPVSCGRGTNDPWCRNPFSYPVVGQGVMCNSHLCVAEDGLTSPMTLSYSLIDWALMVAIMATVAIFFAKISLLVDVVCVFCCLLMYAFPSLSIAAFGFPFVLCKVSLHPITLVWVQFFLLAVNVWAGVASVVVLISSWFLARATSSLGLITPYDVHMITATPRGASSLASAPEGTYLAAVRRSALTGRCCMFVPTNFGSVLEGSLRTRGCAKNVVSVFGSASGSGGVFTINGNPVVVTASHLLSDGKARVSCVGFSQCLDFKCAGDYAFARVANWKGDAPKAELSHRRGRAYCSPLVGLSLDLLGKNSAFCFTKCGDSGSPVVDEDGNLLGIHTGSNKRGSGMVTTHGGKTLGMANVKLSEMCPHYSGPGVPVSTVKLPKHLVVDVETVSSDLVAVVESLPALEGALSSMQLLCVFFFLWRLIHVPDVPVIRIAFFFLNEILPVMLARLMFSFALSLFFCVHWLFCSSVAVAFGDCCSKSVTGYSVQVLLLRLVIAALNRPCGPFGFSLLGQLSQCCLMLCLLDIELQLLGCLYLGQLLMWPPKEIFFHPTGQFMFLPLFLSLFKRNALADMLVGNGCFDAAFFLKYFAEGNLRDGVSDSCNMTPEGLTAALAITLSDDDLEFLQRHSEFKCFVSASNMRNGAKEFIESAYARALRAQLAATDKIKASKSILAKLESFAGGVVTQVEPGDVVVVLGKKVIGDLVEVVINDAKHVIRVIETRTMAGTQFSVGTICGDLENACEDPSGLVKTSKKQARRQKRTGLGTEVVGTVVIDGVSYNKVWHIATGDVTYEGCLVTENPQLRPLGMTTIGRFQEFIRKHGEKVKTSVEKYPVGKKKSVEFNITTYLLDGEEYDVPDHEPLEWTITIGESDLEAERLTVDQALRHMGHDSLLTAKEKEKLARIIESLNGLQQASALNCLATSGLDRCTRGGLTVSGDAVKLVRYHSRTFSIGDVNLKVMGREEYGRTVGKQGHCLVANLVDGVVVMRKHEPSLVDVLLTGEDADLISPTHGPGNTGVHGFTWDFEAPPTDLELELSEQIITACSIRRGDAPSLDLPYKLHPVRGNPYRDRGVLYNTRFGDIKYLTPQKTKEPLHAAACFNPKGVPVSDSETLVATTLPHGFELYVPTIPQSVLEYLDSRPMHRKCCVRAVVRGLAECDLQKFDLSRQGFVLPGVLYMVRRYLCRLVGIRRRLFLPSTYPAKNSMAGINGNRFPTHVVQSHPDIDALCERACKEHWQTVTPCTLKKQYCSKAKTRTILGTNNFVALGLRSALSGVTQGFMRKGIGSPICLGKNKFTPLPTKVSGRCLEADLASCDRSTPAIIRWFTTNLLFELAGPEEWIPSYVLNCCHDAVSTMSGCFDKRGGLSSGDPVTSVSNTVYSLVIYAQHMVLSAFRCGHKVGGLFLRDSLEMEQLFELQPLLVYSDDVVLYDESSELPNYHFFVDHLDLMLGFKTDRSKTVITSDPQFPGCRIAAGRVLVPQRDRILAALAYHMKASCVSDYFASAAAILMDACACCDYDEDWYFDLVCGIADCARKEGFRFPGPSFYVDMWKRLSVEEKKKCRTCAHCGAPSTLVSSCGLNLCDYHGHGHPHCPVVLPCGHAVGSGVCDGCSSPVMSLNTELDKLLACVPYHPPKVELLSVNDGVSSLPPGRYQARGGVVSVRRDILGNVVDLPDGDYQVMKVAQTCADICMVSINSHILRSQFITGAPGTGKTTYLLSVVRDDDVIYTPTHRTMLDVVKALGTCRFDPPKDTPLEFPVPSRTGPCVRLIRAGFIPGRVSYLDEAAYCNPLDVLKILSKTPLVCVGDLNQLPPVDFIGPCYAFALMLGRQLIEVFRFGPSIVNPIKKFYREELVSRGPDTGVKFLKSYQPYGQVLTPYHRDRVDGAITIDSSQGCTYDVITVYLPTPKSLNSARALVAITRARFYVFVYDPHNQLEQYLNMSEHEPAGAVAFWCGEQPMMISEGRVQRLSGPAQTTDPKLQQLMGLEGTASPLPQVAHNLGFYYSPDLVQFARIPSELCKHWPVVTAQNRTDWPDRLVCSMSKIDKCSRAIFCAGYHVGPSVFLGVPGVVSYYLTKFLKGKPVPLPDSLMSTGRIALNVREYLDEKEMEFSSRCPHAFIGEVKGSNVGGCHHVTSRYLPPVLVPGSVVKIGVSCPGKAAKELCTVTDVYLPELDPYLNPPTKSMDYKLLVDFQPVKLMVWKDATAYFHEGIRPMESMSRFLKVPQEEGVFFDLDEFVTNAKVSKLPCKYSVSANQFLTDVVLSMTHPSLAPPDYELLFARAYCVPGLDVGTLNAYIYRRGPSTYTTSNIARLVKDICCPVGCKGSGYMFPK |
| Enzyme Length | 3637 |
| Uniprot Accession Number | Q06502 |
| Absorption | |
| Active Site | ACT_SITE 76; /note=For Nsp1-alpha papain-like cysteine proteinase activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU00872; ACT_SITE 147; /note=For Nsp1-alpha papain-like cysteine proteinase activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU00872; ACT_SITE 269; /note=For Nsp1-beta papain-like cysteine proteinase activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU00873; ACT_SITE 340; /note=For Nsp1-beta papain-like cysteine proteinase activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU00873; ACT_SITE 390; /note=For Nsp2 cysteine proteinase activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU00871; ACT_SITE 456; /note=For Nsp2 cysteine proteinase activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU00871; ACT_SITE 1549; /note=Charge relay system; for 3C-like serine proteinase activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU00826; ACT_SITE 1574; /note=Charge relay system; for 3C-like serine proteinase activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU00826; ACT_SITE 1626; /note=Charge relay system; for 3C-like serine proteinase activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU00826; ACT_SITE 3422; /evidence=ECO:0000255|PROSITE-ProRule:PRU01303; ACT_SITE 3437; /evidence=ECO:0000255|PROSITE-ProRule:PRU01303; ACT_SITE 3466; /evidence=ECO:0000255|PROSITE-ProRule:PRU01303 |
| 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=3.6.4.12; 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; CATALYTIC ACTIVITY: [Uridylate-specific endoribonuclease nsp11]: Reaction=uridylyl-uridylyl-ribonucleotide-RNA = a 3'-end uridylyl-2',3'-cyclophospho-uridine-RNA + a 5'-end dephospho-ribonucleoside-RNA; Xref=Rhea:RHEA:67732, Rhea:RHEA-COMP:13936, Rhea:RHEA-COMP:17334, Rhea:RHEA-COMP:17335, ChEBI:CHEBI:138284, ChEBI:CHEBI:173079, ChEBI:CHEBI:173080; Evidence={ECO:0000250|UniProtKB:P19811}; |
| DNA Binding | |
| EC Number | 3.4.22.-; 3.4.22.-; 3.4.22.-; 3.4.21.-; 2.7.7.48; 3.6.4.12; 3.6.4.13; 4.6.1.- |
| Enzyme Function | FUNCTION: The replicase polyprotein 1ab is a multifunctional protein: it contains the activities necessary for the transcription of negative stranded RNA, leader RNA, subgenomic mRNAs and progeny virion RNA as well as proteinases responsible for the cleavage of the polyprotein into functional products.; FUNCTION: The Nsp1 chain is essential for viral subgenomic mRNA synthesis. {ECO:0000250}.; FUNCTION: The 3C-like serine proteinase chain is responsible for the majority of cleavages as it cleaves the C-terminus of the polyprotein. {ECO:0000250}.; FUNCTION: The helicase chain, which contains a zinc finger structure, displays RNA and DNA duplex-unwinding activities with 5' to 3' polarity. {ECO:0000250}.; FUNCTION: [Uridylate-specific endoribonuclease nsp11]: Plays a role in viral transcription/replication and prevents the simultaneous activation of host cell dsRNA sensors, such as MDA5/IFIH1, OAS, and PKR (By similarity). Acts by degrading the 5'-polyuridines generated during replication of the poly(A) region of viral genomic and subgenomic RNAs. Catalyzes a two-step reaction in which a 2'3'-cyclic phosphate (2'3'-cP) is first generated by 2'-O transesterification, which is then hydrolyzed to a 3'-phosphate (3'-P) (By similarity). If not degraded, poly(U) RNA would hybridize with poly(A) RNA tails and activate host dsRNA sensors (By similarity). {ECO:0000250|UniProtKB:P0C6X7, ECO:0000250|UniProtKB:P19811}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | NP_BIND 3013..3020; /note=ATP; /evidence=ECO:0000250 |
| Features | Active site (12); Alternative sequence (1); Chain (16); Compositional bias (2); Domain (11); Erroneous initiation (1); Metal binding (12); Nucleotide binding (1); Region (7); Sequence uncertainty (2); Site (12); Transmembrane (12); Zinc finger (1) |
| Keywords | ATP-binding;Endonuclease;Helicase;Host cytoplasm;Host membrane;Hydrolase;Lyase;Membrane;Metal-binding;Nuclease;Nucleotide-binding;Nucleotidyltransferase;Protease;RNA-directed RNA polymerase;Ribosomal frameshifting;Serine protease;Thiol protease;Transferase;Transmembrane;Transmembrane helix;Viral RNA replication;Zinc;Zinc-finger |
| Interact With | |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: [Nsp2 cysteine proteinase]: Host membrane {ECO:0000305}; Multi-pass membrane protein {ECO:0000305}.; SUBCELLULAR LOCATION: [Non-structural protein 3]: Host membrane {ECO:0000305}; Multi-pass membrane protein {ECO:0000305}.; SUBCELLULAR LOCATION: [Non-structural protein 5-6-7]: Host membrane {ECO:0000305}; Multi-pass membrane protein {ECO:0000305}.; SUBCELLULAR LOCATION: [3C-like serine proteinase]: Host cytoplasm {ECO:0000305}.; SUBCELLULAR LOCATION: [RNA-directed RNA polymerase]: Host cytoplasm, host perinuclear region {ECO:0000305}.; SUBCELLULAR LOCATION: [Helicase]: Host cytoplasm, host perinuclear region {ECO:0000305}. |
| Modified Residue | |
| Post Translational Modification | PTM: Specific enzymatic cleavages in vivo by its own proteases yield mature proteins. There are two alternative pathways for processing. Either nsp4-5 is cleaved, which represents the major pathway or the nsp5-6 and nsp6-7 are processed, which represents the minor pathway. The major pathway occurs when nsp2 acts as cofactor for nsp4 (By similarity). {ECO:0000250}. |
| Signal Peptide | |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | - |
| Motif | |
| Gene Encoded By | |
| Mass | 398,663 |
| Kinetics | |
| Metal Binding | METAL 2871; /note=Zinc 1; /evidence=ECO:0000255|PROSITE-ProRule:PRU00985; METAL 2874; /note=Zinc 1; /evidence=ECO:0000255|PROSITE-ProRule:PRU00985; METAL 2884; /note=Zinc 2; /evidence=ECO:0000255|PROSITE-ProRule:PRU00985; METAL 2889; /note=Zinc 1; /evidence=ECO:0000255|PROSITE-ProRule:PRU00985; METAL 2892; /note=Zinc 1; /evidence=ECO:0000255|PROSITE-ProRule:PRU00985; METAL 2894; /note=Zinc 2; /evidence=ECO:0000255|PROSITE-ProRule:PRU00985; METAL 2896; /note=Zinc 2; /evidence=ECO:0000255|PROSITE-ProRule:PRU00985; METAL 2898; /note=Zinc 2; /evidence=ECO:0000255|PROSITE-ProRule:PRU00985; METAL 2905; /note=Zinc 3; /evidence=ECO:0000255|PROSITE-ProRule:PRU00985; METAL 2907; /note=Zinc 3; /evidence=ECO:0000255|PROSITE-ProRule:PRU00985; METAL 2914; /note=Zinc 3; /evidence=ECO:0000255|PROSITE-ProRule:PRU00985; METAL 2917; /note=Zinc 3; /evidence=ECO:0000255|PROSITE-ProRule:PRU00985 |
| Rhea ID | RHEA:21248; RHEA:13065; RHEA:67732 |
| Cross Reference Brenda |