| IED ID | IndEnz0002012870 |
| Enzyme Type ID | protease012870 |
| 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 | Simian hemorrhagic fever virus (SHFV) |
| Taxonomic Lineage | Viruses Riboviria Orthornavirae Pisuviricota Pisoniviricetes Nidovirales Arnidovirineae Arteriviridae Simarterivirinae Deltaarterivirus Hedartevirus Deltaarterivirus hemfev Simian hemorrhagic fever virus (SHFV) |
| Enzyme Sequence | MFCECPRSNLVVMCSGAFCCVLCGHRRRPRPASESDRAKYGPIVQYVEARVAHVYSGLEGRYCALEMIPITYGNKFPYCKPLPVSFVIKTLAGVQGDLTRLEETPLPGGYGVIPCWGPHLAAVGYLSPAHVGRDWFEGATHAIVHIGSYGGHERPTTIPFNTTGGDVYQLGTCTIVETIDHVEWHAGVKPGTAICPLDRIDFAQKVITAFPEGFLANKAWLGDKRGTLKVEADPETAALSFEHGRCWLKLFPDPACELTTASTFGYQLNCGVQGKYIARRLQTNGLKLVQNQEGKFIAYTFHRGSWLGHIGHADESVPPDCQIIARFDVLPYNEWSPLPLLKLPGKTYFGGNASSVSWPEWKYDEQLLYADSLTAGFCWLQLFPPLSRKSEAQRAILAQQVNNYGVTGTYLEYRLRQYGIVLAECDYGEHYIYAAASDSSIRHISPVPIHDRHHVFVTRLTARFGAFDEGFDLGFGTRYGRRRGGGKKSGQSSGVRAPGRTTPDLAGDWGKAVDDQEKTASKVTTDKAMSTSEPAVVQVGCETKPVADAAAVPASVNSTGCALLPVQADPCCTAGVAAKESEPKAVAAPSIPITFGAPAGETLPVAASPLVVKKDKRCISVKLTAKKALPKETFIPPPDGGCGVHAFAAIQYHINTGHWPEQKPVVNWAYEAWTTNEDIGHMICSTETPAALEPCLHARYVVRLDSDHWVVDHYPNRPMCFVEACAHGWCSSLLSEPTGEEGEHLVDCSALYDCLGKFRNGTEFADTVLGLSKTAHCCNKRVPTPRKQAIMSLLNRPNCVPCIAPPSQVRTVDPSQPAAPLPPVPRPRKRKAAAQQVSKVPSEQDPSLAHDPPEKPDSVRPPKLGYLDRAWNNMLARTHKLHNLQQRVFGLYPQLLSMLLPSGARPSTPRLLGCYFSMAVAMFFLFLGSPLFILCAVLAGVIAPSARYPKILCCCLVVVYICTLFADAISSVCDNDDADCRAFLSDLGDRYSTNQPVYITPGPATFFLAVSRNFFVVSVALFPLHLLLLMVDVLLVIGVLCMDGYCFRCFSRCVRKAPEEVSLLTIPQSRVSRRFLLDICDFYSAPPVDIIRLATGLNGCFRGDYSPIGSSTSVITADKIDVKKVSCRTVCSFPSCPSEAVKVLHVLSVRGQMCAHNEQKVEKVDALPCKNPLFPYDLSSKKIVPVDSGTYEILSSIGCDMSHLVIGDGDFFKVMGVPRPSPFTVMRLRACRVVGGGRIFRTALAAAWVLFFVCAGYWVQMSTPCGIGTNDPFCKSSFGVPTYVNQGVCHGQYCASSKGVSRATSILTVRNPAVAPYIVLAACLVYLASVYVPGIIEVSLLVLNALLPAGPAISALRTLVMIIAAPHLSMKYIAFFCCTTAFVDFTSVVVVLTALLVGWILARYTGIGGFVTPYDIHDVVKSQRDGVAVANAPPNTYLGAVRRAALTGKPAFFVANNTGIVLEGLLREKTRASNSVSVYGVTCGSGGLFSDGNNTVCLTATHVCGNNKAVVDYQGTRYEAVFTTKGDYASAVVPIPGAFPPLKFAPQSYTGRAYWYANTGVETGFVGTTGCLVFSGPGDSGSPIITPDGLIVGVHTGSDSKGSGAYTTPNGLTVSGPLSLKEMGAHYEGPIVDVPTRLPRNVHNDTKSVPQPLARLLESSINLEGGLGTIQLIIVAVVLWKYAVDPLSIPFVVAFFLLNEILPKCLIRCFYNYSLFCLAAFSPLASRIFFIRLLTAALNRNPTALICHACFAGIAVLNDFIILGDIRLALRFTSFYVVGVNHDAIAIAVIGALVCVAACCLELFGLPQMASVIGCHGSFDPTFLSRYVHEGIRQGVSSGFGTESLSTALACALSEDELNFLAQAVDHKAIVSAIHVHKTLQDYILSKNAKILRASLASVHANHNASKALASLDKFLQGTSTQLKPGDPVILLGSTSAELVSVFSGDSEYIAEPIRSHPVAGTICTLCVVQAKCEGGLVTQVNGKFSPAKYLAVAGKVLADHPDYKLENDGRFPRTREDRVKDSVQVDTVDIGSHTFKKMWNKTTGDVWYDIIMPESAANPLAVHDLDSAVAAIGMSKEIPEKDMNRLRAIISKLQGLVSSEALNLLTAAGCTSADRSGLVITLDYAKIITHHARTRAFSSIDFKVVSPDEAMRTARLSPSPQPIIASFSDDKFLLLRRHPPSLLDVLTKGLDATCREPLHSPGDQGIDGYLWDFEAPHSKEAIWLSNQIISACAARRGDAPGCYPYKLHPVRGDPYRVGNVLKNTRFGDVTYTAVSDSDSPWLKVASINSGGCPVVTDRVLGSTIPVGSEIYLPTLPESVLDYLDSRPDCPTYYTQHGCEAAALQDLKKFNLSTQGFILPEVLNIVRNYLLGTIGYRPAIYKPSTVPSNDSHAGINGLSFSTKTLQALPDIDELCEKAIAEVWQTVTPVTLKKQFCSKAKTRTILGTNAMASLALRALLSGVTQGFQLAGKNSPICLGKSKFDPCTFEVKGRCLETDLASCDRSTPAIVRHFATKLLFEMACAERALPLYVVNCCHDLIVTQTSAATKRGGLSSGDPVTSIANTIYSLVLYVQHMVLTLLENGHPLSLKFLSGKLNFQDLYKLQAFIVYSDDLILLNESDDLPNFERWVPHLELALGFKVDPKKTVITSNPGFLGCEYRHGWLVPQKQRVLAALAYHVNAKDVHTYYINATAILNDASALSAFEPDWFDDLVIGLADCARKDGYSFPGPAAFREFFSRVSGYQFEGKEVQVCSICCSTARTTSLCGMALCDFCAHRHYHPGCHVLSSFCKHVIGSNTCKMCSIPILKDRTKFAELLASDQYRSVCTVEVTVVDGYTDAAPGRYSYQKKQYMLRKERRGCPLDLPDGKYSMKLLPNSCSGICVPKAQENATLSNFVVGPPGSGKTTFISNLLDDDAVVYCPTHVSLIAYSKSLPAARFSVPRGQDPAEYGTPALSGPTLQLLSAGYVPGAKHYLDEACYANPFDVFKLLSKTPITAIGDPAQLTPVGFDTPLYVFELMKKNALHAIYRFGQNICNAIQPCYSTKLVSQRQGDTEVIFQTKFAPRGKVLTPYHRDRVGAAVTIDSSQGSTYDVVTLYLPTKGSLTLARGLVGITRARERLYVYDPHHQLAKYFNLQPSSTTIRPHAVVIDGKARVMLSDKCYAAPEDFPGMLCTARPATAADRKILEETCLKLDFLESGSLSPLPRVCYNLGFYYSPDITKLLPIPSELAKHWPVATNRNNPEWPNRLVVSATRLSPLSHPAVCAGYYVGDSLFVGTPNVTSYWLTKFLDGRAVPMEDSVYSTGRFEMDIRDYLDSAERDFAAKHPHAFIGDTKGTTVGGCHHITSQYLPHVLPADSVVKVGVSKPGVAHKALCTVTDIYLPMLGSYTSPPTQSKVYKVNVDHKACKLMVWRDQTMYFQEGFDYHTLVDALRFVRLSSDGVYRVAPELTPMIGNRRLDLGAKPLRPVDLAITPWDDPKCEFLVTHASPFDMSDEFLLVNAFDFIKEDLLGKSVTPVYFYKRLSEPLHFDQNLPPHVGAILSKAPRFISLAKVFNFCFTPTACHCKVSVKTATGDHMCKCSLSSDEFLSRFNPTVGTP |
| Enzyme Length | 3595 |
| Uniprot Accession Number | Q68772 |
| Absorption | |
| Active Site | ACT_SITE 63; /note=For Nsp1-alpha papain-like cysteine proteinase activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU00872; ACT_SITE 130; /note=For Nsp1-alpha papain-like cysteine proteinase activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU00872; ACT_SITE 246; /note=For Nsp1-beta papain-like cysteine proteinase activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU00873; ACT_SITE 309; /note=For Nsp1-beta papain-like cysteine proteinase activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU00873; ACT_SITE 378; /note=For Nsp2 cysteine proteinase activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU00871; ACT_SITE 430; /note=For Nsp2 cysteine proteinase activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU00871; ACT_SITE 1502; /note=Charge relay system; for 3C-like serine proteinase activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU00826; ACT_SITE 1527; /note=Charge relay system; for 3C-like serine proteinase activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU00826; ACT_SITE 1580; /note=Charge relay system; for 3C-like serine proteinase activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU00826; ACT_SITE 3325; /evidence=ECO:0000255|PROSITE-ProRule:PRU01303; ACT_SITE 3340; /evidence=ECO:0000255|PROSITE-ProRule:PRU01303; ACT_SITE 3369; /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: [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}.; FUNCTION: The helicase chain, which contains a zinc finger structure, displays RNA and DNA duplex-unwinding activities with 5' to 3' polarity. {ECO:0000250}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | NP_BIND 2897..2904; /note=ATP; /evidence=ECO:0000250 |
| Features | Active site (12); Alternative sequence (1); Chain (16); Compositional bias (1); Domain (11); Metal binding (12); Nucleotide binding (1); Region (5); Site (12); Transmembrane (11); 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;Reference proteome;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 | 391,443 |
| Kinetics | |
| Metal Binding | METAL 2752; /note=Zinc 1; /evidence=ECO:0000255|PROSITE-ProRule:PRU00985; METAL 2755; /note=Zinc 1; /evidence=ECO:0000255|PROSITE-ProRule:PRU00985; METAL 2765; /note=Zinc 2; /evidence=ECO:0000255|PROSITE-ProRule:PRU00985; METAL 2770; /note=Zinc 1; /evidence=ECO:0000255|PROSITE-ProRule:PRU00985; METAL 2773; /note=Zinc 1; /evidence=ECO:0000255|PROSITE-ProRule:PRU00985; METAL 2777; /note=Zinc 2; /evidence=ECO:0000255|PROSITE-ProRule:PRU00985; METAL 2779; /note=Zinc 2; /evidence=ECO:0000255|PROSITE-ProRule:PRU00985; METAL 2782; /note=Zinc 2; /evidence=ECO:0000255|PROSITE-ProRule:PRU00985; METAL 2789; /note=Zinc 3; /evidence=ECO:0000255|PROSITE-ProRule:PRU00985; METAL 2791; /note=Zinc 3; /evidence=ECO:0000255|PROSITE-ProRule:PRU00985; METAL 2798; /note=Zinc 3; /evidence=ECO:0000255|PROSITE-ProRule:PRU00985; METAL 2801; /note=Zinc 3; /evidence=ECO:0000255|PROSITE-ProRule:PRU00985 |
| Rhea ID | RHEA:21248; RHEA:13065; RHEA:67732 |
| Cross Reference Brenda |