| IED ID | IndEnz0002000944 |
| Enzyme Type ID | protease000944 |
| Protein Name |
Genome polyprotein Cleaved into: N-terminal protease N-pro EC 3.4.22.- Autoprotease p20 ; Capsid protein C; E rns glycoprotein gp44/48 ; Envelope glycoprotein E1 gp33 ; Envelope glycoprotein E2 gp55 ; Viroporin p7; Non-structural protein 2-3; Cysteine protease NS2 EC 3.4.22.- Non-structural protein 2 ; Serine protease NS3 EC 3.4.21.113 EC 3.6.1.15 EC 3.6.4.13 Non-structural protein 3 ; Non-structural protein 4A NS4A ; Non-structural protein 4B NS4B ; Non-structural protein 5A NS5A ; RNA-directed RNA polymerase EC 2.7.7.48 NS5B |
| Gene Name | |
| Organism | Bovine viral diarrhea virus (isolate NADL) (BVDV) (Mucosal disease virus) |
| Taxonomic Lineage | Viruses Riboviria Orthornavirae Kitrinoviricota Flasuviricetes Amarillovirales Flaviviridae Pestivirus Pestivirus A Bovine viral diarrhea virus (isolate NADL) (BVDV) (Mucosal disease virus) |
| Enzyme Sequence | MELITNELLYKTYKQKPVGVEEPVYDQAGDPLFGERGAVHPQSTLKLPHKRGERDVPTNLASLPKRGDCRSGNSRGPVSGIYLKPGPLFYQDYKGPVYHRAPLELFEEGSMCETTKRIGRVTGSDGKLYHIYVCIDGCIIIKSATRSYQRVFRWVHNRLDCPLWVTTCSDTKEEGATKKKTQKPDRLERGKMKIVPKESEKDSKTKPPDATIVVEGVKYQVRKKGKTKSKNTQDGLYHNKNKPQESRKKLEKALLAWAIIAIVLFQVTMGENITQWNLQDNGTEGIQRAMFQRGVNRSLHGIWPEKICTGVPSHLATDIELKTIHGMMDASEKTNYTCCRLQRHEWNKHGWCNWYNIEPWILVMNRTQANLTEGQPPRECAVTCRYDRASDLNVVTQARDSPTPLTGCKKGKNFSFAGILMRGPCNFEIAASDVLFKEHERISMFQDTTLYLVDGLTNSLEGARQGTAKLTTWLGKQLGILGKKLENKSKTWFGAYAASPYCDVDRKIGYIWYTKNCTPACLPKNTKIVGPGKFGTNAEDGKILHEMGGHLSEVLLLSLVVLSDFAPETASVMYLILHFSIPQSHVDVMDCDKTQLNLTVELTTAEVIPGSVWNLGKYVCIRPNWWPYETTVVLAFEEVSQVVKLVLRALRDLTRIWNAATTTAFLVCLVKIVRGQMVQGILWLLLITGVQGHLDCKPEFSYAIAKDERIGQLGAEGLTTTWKEYSPGMKLEDTMVIAWCEDGKLMYLQRCTRETRYLAILHTRALPTSVVFKKLFDGRKQEDVVEMNDNFEFGLCPCDAKPIVRGKFNTTLLNGPAFQMVCPIGWTGTVSCTSFNMDTLATTVVRTYRRSKPFPHRQGCITQKNLGEDLHNCILGGNWTCVPGDQLLYKGGSIESCKWCGYQFKESEGLPHYPIGKCKLENETGYRLVDSTSCNREGVAIVPQGTLKCKIGKTTVQVIAMDTKLGPMPCRPYEIISSEGPVEKTACTFNYTKTLKNKYFEPRDSYFQQYMLKGEYQYWFDLEVTDHHRDYFAESILVVVVALLGGRYVLWLLVTYMVLSEQKALGIQYGSGEVVMMGNLLTHNNIEVVTYFLLLYLLLREESVKKWVLLLYHILVVHPIKSVIVILLMIGDVVKADSGGQEYLGKIDLCFTTVVLIVIGLIIARRDPTIVPLVTIMAALRVTELTHQPGVDIAVAVMTITLLMVSYVTDYFRYKKWLQCILSLVSAVFLIRSLIYLGRIEMPEVTIPNWRPLTLILLYLISTTIVTRWKVDVAGLLLQCVPILLLVTTLWADFLTLILILPTYELVKLYYLKTVRTDTERSWLGGIDYTRVDSIYDVDESGEGVYLFPSRQKAQGNFSILLPLIKATLISCVSSKWQLIYMSYLTLDFMYYMHRKVIEEISGGTNIISRLVAALIELNWSMEEEESKGLKKFYLLSGRLRNLIIKHKVRNETVASWYGEEEVYGMPKIMTIIKASTLSKSRHCIICTVCEGREWKGGTCPKCGRHGKPITCGMSLADFEERHYKRIFIREGNFEGMCSRCQGKHRRFEMDREPKSARYCAECNRLHPAEEGDFWAESSMLGLKITYFALMDGKVYDITEWAGCQRVGISPDTHRVPCHISFGSRMPFRQEYNGFVQYTARGQLFLRNLPVLATKVKMLMVGNLGEEIGNLEHLGWILRGPAVCKKITEHEKCHINILDKLTAFFGIMPRGTTPRAPVRFPTSLLKVRRGLETAWAYTHQGGISSVDHVTAGKDLLVCDSMGRTRVVCQSNNRLTDETEYGVKTDSGCPDGARCYVLNPEAVNISGSKGAVVHLQKTGGEFTCVTASGTPAFFDLKNLKGWSGLPIFEASSGRVVGRVKVGKNEESKPTKIMSGIQTVSKNRADLTEMVKKITSMNRGDFKQITLATGAGKTTELPKAVIEEIGRHKRVLVLIPLRAAAESVYQYMRLKHPSISFNLRIGDMKEGDMATGITYASYGYFCQMPQPKLRAAMVEYSYIFLDEYHCATPEQLAIIGKIHRFSESIRVVAMTATPAGSVTTTGQKHPIEEFIAPEVMKGEDLGSQFLDIAGLKIPVDEMKGNMLVFVPTRNMAVEVAKKLKAKGYNSGYYYSGEDPANLRVVTSQSPYVIVATNAIESGVTLPDLDTVIDTGLKCEKRVRVSSKIPFIVTGLKRMAVTVGEQAQRRGRVGRVKPGRYYRSQETATGSKDYHYDLLQAQRYGIEDGINVTKSFREMNYDWSLYEEDSLLITQLEILNNLLISEDLPAAVKNIMARTDHPEPIQLAYNSYEVQVPVLFPKIRNGEVTDTYENYSFLNARKLGEDVPVYIYATEDEDLAVDLLGLDWPDPGNQQVVETGKALKQVTGLSSAENALLVALFGYVGYQALSKRHVPMITDIYTIEDQRLEDTTHLQYAPNAIKTDGTETELKELASGDVEKIMGAISDYAAGGLEFVKSQAEKIKTAPLFKENAEAAKGYVQKFIDSLIENKEEIIRYGLWGTHTALYKSIAARLGHETAFATLVLKWLAFGGESVSDHVKQAAVDLVVYYVMNKPSFPGDSETQQEGRRFVASLFISALATYTYKTWNYHNLSKVVEPALAYLPYATSALKMFTPTRLESVVILSTTIYKTYLSIRKGKSDGLLGTGISAAMEILSQNPVSVGISVMLGVGAIAAHNAIESSEQKRTLLMKVFVKNFLDQAATDELVKENPEKIIMALFEAVQTIGNPLRLIYHLYGVYYKGWEAKELSERTAGRNLFTLIMFEAFELLGMDSQGKIRNLSGNYILDLIYGLHKQINRGLKKMVLGWAPAPFSCDWTPSDERIRLPTDNYLRVETRCPCGYEMKAFKNVGGKLTKVEESGPFLCRNRPGRGPVNYRVTKYYDDNLREIKPVAKLEGQVEHYYKGVTAKIDYSKGKMLLATDKWEVEHGVITRLAKRYTGVGFNGAYLGDEPNHRALVERDCATITKNTVQFLKMKKGCAFTYDLTISNLTRLIELVHRNNLEEKEIPTATVTTWLAYTFVNEDVGTIKPVLGERVIPDPVVDINLQPEVQVDTSEVGITIIGRETLMTTGVTPVLEKVEPDASDNQNSVKIGLDEGNYPGPGIQTHTLTEEIHNRDARPFIMILGSRNSISNRAKTARNINLYTGNDPREIRDLMAAGRMLVVALRDVDPELSEMVDFKGTFLDREALEALSLGQPKPKQVTKEAVRNLIEQKKDVEIPNWFASDDPVFLEVALKNDKYYLVGDVGELKDQAKALGATDQTRIIKEVGSRTYAMKLSSWFLKASNKQMSLTPLFEELLLRCPPATKSNKGHMASAYQLAQGNWEPLGCGVHLGTIPARRVKIHPYEAYLKLKDFIEEEEKKPRVKDTVIREHNKWILKKIRFQGNLNTKKMLNPGKLSEQLDREGRKRNIYNHQIGTIMSSAGIRLEKLPIVRAQTDTKTFHEAIRDKIDKSENRQNPELHNKLLEIFHTIAQPTLKHTYGEVTWEQLEAGVNRKGAAGFLEKKNIGEVLDSEKHLVEQLVRDLKAGRKIKYYETAIPKNEKRDVSDDWQAGDLVVEKRPRVIQYPEAKTRLAITKVMYNWVKQQPVVIPGYEGKTPLFNIFDKVRKEWDSFNEPVAVSFDTKAWDTQVTSKDLQLIGEIQKYYYKKEWHKFIDTITDHMTEVPVITADGEVYIRNGQRGSGQPDTSAGNSMLNVLTMMYGFCESTGVPYKSFNRVARIHVCGDDGFLITEKGLGLKFANKGMQILHEAGKPQKITEGEKMKVAYRFEDIEFCSHTPVPVRWSDNTSSHMAGRDTAVILSKMATRLDSSGERGTTAYEKAVAFSFLLMYSWNPLVRRICLLVLSQQPETDPSKHATYYYKGDPIGAYKDVIGRNLSELKRTGFEKLANLNLSLSTLGVWTKHTSKRIIQDCVAIGKEEGNWLVKPDRLISSKTGHLYIPDKGFTLQGKHYEQLQLRTETNPVMGVGTERYKLGPIVNLLLRRLKILLMTAVGVSS |
| Enzyme Length | 3988 |
| Uniprot Accession Number | P19711 |
| Absorption | |
| Active Site | ACT_SITE 49; /note=For N-terminal protease activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU01224; ACT_SITE 69; /note=For N-terminal protease activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU01224; ACT_SITE 1447; /note=For cysteine protease NS2 activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU01029; ACT_SITE 1461; /note=For cysteine protease NS2 activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU01029; ACT_SITE 1512; /note=For cysteine protease NS2 activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU01029; ACT_SITE 1748; /note=Charge relay system; for serine protease NS3 activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU00868; ACT_SITE 1785; /note=Charge relay system; for serine protease NS3 activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU00868; ACT_SITE 1842; /note=Charge relay system; for serine protease NS3 activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU00868 |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: [Serine protease NS3]: Reaction=Leu is conserved at position P1 for all four cleavage sites. Alanine is found at position P1' of the NS4A-NS4B cleavage site, whereas serine is found at position P1' of the NS3-NS4A, NS4B-NS5A and NS5A-NS5B cleavage sites.; EC=3.4.21.113; CATALYTIC ACTIVITY: [RNA-directed RNA polymerase]: 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: [Serine protease NS3]: 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: [Serine protease NS3]: 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; |
| DNA Binding | |
| EC Number | 3.4.22.-; 3.4.22.-; 3.4.21.113; 3.6.1.15; 3.6.4.13; 2.7.7.48 |
| Enzyme Function | FUNCTION: [N-terminal protease]: Leader cysteine autoprotease that cleaves itself from the nascent polyprotein during translation of the viral mRNA. Once released, plays a role in the inhibition of host innate immune response by interacting with host IRF3 and inducing its proteasomal degradation. {ECO:0000250|UniProtKB:P19712}.; FUNCTION: [Capsid protein C]: Packages viral RNA to form a viral nucleocapsid and thereby protects viral RNA. Plays also a role in transcription regulation. Protects the incoming virus against IFN-induced effectors. {ECO:0000250|UniProtKB:P19712}.; FUNCTION: [E(rns) glycoprotein]: Initial binding to target cell probably involves interaction of E(rns) with glycosaminoglycans. {ECO:0000269|PubMed:10644844}.; FUNCTION: [Envelope glycoprotein E1]: E1 and/or E2 are probably responsible of cell attachment with CD46 and subsequent fusion after internalization of the virion by endocytosis. {ECO:0000305|PubMed:14747544}.; FUNCTION: [Envelope glycoprotein E2]: E1 and/or E2 are probably responsible of cell attachment with CD46 and subsequent fusion after internalization of the virion by endocytosis. {ECO:0000305|PubMed:14747544}.; FUNCTION: [Viroporin p7]: Plays an essential role in the virus replication cycle by acting as a viroporin (By similarity). Forms ion conductive pores, which alters the cell permeability allowing the transport of ions and other small molecules (By similarity). Forms a leader sequence to properly orient NS2 in the membrane. {ECO:0000250|UniProtKB:P19712}.; FUNCTION: [Non-structural protein 2-3]: Uncleaved NS2-3 is required for production of infectious virus.; FUNCTION: [Cysteine protease NS2]: Plays a role in the regulation of viral RNA replication. {ECO:0000250|UniProtKB:P19712}.; FUNCTION: [Serine protease NS3]: Multifunctional protein that contains an N-terminal protease and a C-terminal helicase, playing essential roles in viral polyprotein processing and viral genome replication. The chymotrypsin-like serine protease activity utilizes NS4A as an essential cofactor and catalyzes the cleavage of the polyprotein leading to the release of NS4A, NS4B, NS5A, and NS5B. Interacts with NS5B to enhance RNA-dependent RNA polymerase activity. {ECO:0000250|UniProtKB:P19712}.; FUNCTION: [Non-structural protein 4A]: Acts as a cofactor for the NS3 protease activity. {ECO:0000250|UniProtKB:P19712}.; FUNCTION: [Non-structural protein 4B]: Induces a specific membrane alteration that serves as a scaffold for the virus replication complex. {ECO:0000250|UniProtKB:P19712}.; FUNCTION: [RNA-directed RNA polymerase]: Replicates the viral (+) and (-) genome. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (8); Beta strand (70); Chain (14); Compositional bias (1); Domain (6); Glycosylation (25); Helix (53); Region (3); Site (11); Transmembrane (7); Turn (8) |
| Keywords | 3D-structure;ATP-binding;Activation of host autophagy by virus;Clathrin-mediated endocytosis of virus by host;Direct protein sequencing;Disulfide bond;Fusion of virus membrane with host endosomal membrane;Fusion of virus membrane with host membrane;Glycoprotein;Helicase;Host cytoplasm;Host membrane;Host-virus interaction;Hydrolase;Inhibition of host IRF3 by virus;Inhibition of host RLR pathway by virus;Inhibition of host innate immune response by virus;Ion channel;Ion transport;Membrane;Nucleotide-binding;Nucleotidyltransferase;Protease;RNA-directed RNA polymerase;Reference proteome;Serine protease;Thiol protease;Transferase;Transmembrane;Transmembrane helix;Transport;Viral RNA replication;Viral attachment to host cell;Viral immunoevasion;Viral ion channel;Viral penetration into host cytoplasm;Virion;Virus endocytosis by host;Virus entry into host cell |
| Interact With | Itself; Q95J56; F1MUM9; P68103; Q32PH0 |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: [Capsid protein C]: Virion {ECO:0000250|UniProtKB:P19712}.; SUBCELLULAR LOCATION: [E(rns) glycoprotein]: Host membrane; Peripheral membrane protein. Virion membrane; Peripheral membrane protein {ECO:0000305}. Note=The C-terminus membrane anchor of Erns represents an amphipathic helix embedded in plane into the membrane. {ECO:0000250}.; SUBCELLULAR LOCATION: [Envelope glycoprotein E2]: Host cell surface {ECO:0000269|PubMed:10355762}. Virion membrane {ECO:0000250|UniProtKB:P19712}.; SUBCELLULAR LOCATION: [Cysteine protease NS2]: Host membrane {ECO:0000255|PROSITE-ProRule:PRU01029}; Multi-pass membrane protein {ECO:0000255|PROSITE-ProRule:PRU01029}.; SUBCELLULAR LOCATION: [Serine protease NS3]: Host cytoplasm {ECO:0000250|UniProtKB:P19712}.; SUBCELLULAR LOCATION: [Non-structural protein 4B]: Host cytoplasm {ECO:0000250|UniProtKB:P19712}.; SUBCELLULAR LOCATION: [Non-structural protein 5A]: Host cytoplasm {ECO:0000250|UniProtKB:P19712}. |
| Modified Residue | |
| Post Translational Modification | PTM: [E(rns) glycoprotein]: Heavily glycosylated. {ECO:0000250|UniProtKB:P19712}.; PTM: The viral RNA of pestiviruses is expressed as a single polyprotein which undergoes post-translational proteolytic processing resulting in the production of at least eleven individual proteins. The N-terminal protease cleaves itself from the nascent polyprotein autocatalytically and thereby generates the N-terminus of the adjacent viral capsid protein C (By similarity). {ECO:0000250}.; PTM: [Genome polyprotein]: Cleavage between E2 and p7 is partial. |
| Signal Peptide | |
| Structure 3D | X-ray crystallography (7) |
| Cross Reference PDB | 1S48; 1S49; 1S4F; 4ILD; 4JNT; 5GVU; 5WSO; |
| Mapped Pubmed ID | 15070734; 15720974; 15731218; 16571808; 17098978; 18557898; 18796719; 19776121; 19793904; 20444997; 22031952; 22079882; 23569276; 23838147; 24965446; 27038454; 27529119; 32300930; 34676824; |
| Motif | |
| Gene Encoded By | |
| Mass | 449,163 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | RHEA:21248; RHEA:23680; RHEA:13065 |
| Cross Reference Brenda |