| IED ID | IndEnz0002008307 |
| Enzyme Type ID | protease008307 |
| 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 NS2-3 ; 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 | Classical swine fever virus (strain Brescia) (CSFV) (Hog cholera virus) |
| Taxonomic Lineage | Viruses Riboviria Orthornavirae Kitrinoviricota Flasuviricetes Amarillovirales Flaviviridae Pestivirus Pestivirus C Classical swine fever virus (strain Brescia) (CSFV) (Hog cholera virus) |
| Enzyme Sequence | MELNHFELLYKTNKQKPMGVEEPVYDVTGRPLFGDPSEVHPQSTLKLPHDRGRGNIKTTLKNLPRRGDCRSGNHLGPVSGIYVKPGPVFYQDYMGPVYHRAPLEFFDEAQFCEVTKRIGRVTGSDGKLYHIYVCIDGCILLKLAKRGEPRTLKWIRNLTDCPLWVTSCSDDGASASKEKKPDRINKGKLKIAPKEHEKDSRTKPPDATIVVEGVKYQVKKKGKVKGKNTQDGLYHNKNKPPESRKKLEKALLAWAVIAIMLYQPVAAENITQWNLRDNGTNGIQHAMYLRGVSRSLHGIWPEKICKGVPTYLATDTELREIQGMMVASEGTNYTCCKLQRHEWNKHGWCNWYNIDPWIQLMNRTQANLAEGPPSKECAVTCRYDKNADINVVTQARNRPTTLTGCKKGTNFSFAGTVIEGPCNFNVSVEDILYGDHECGSLLQDTALYLVDGMTNTIERARQGAARVTSWLGRQLRIAGKRLEGRSKTWFGAYALSPYCNVTTKIGYIWYTNNCTPACLPKNTKIIGPGKFDTNAEDGKILHEMGGHLSEFLLLSLVVLSDFAPETASALYLILHYVIPQSHEEPEGCDTNQLNLTVELRTEDVIPSSVWNVGKYVCVRPDWWPYETKVALLFEEAGQVVKLALRALRDLTRVWNSASTTAFLICLIKVLRGQVVQGVIWLLLVTGAQGRLACKEDHRYAISTTNEIGLHGAEGLTTTWKEYNHNLQLDDGTVKAICMAGSFKVTALNVVSRRYLASLHKDALPTSVTFELLFDGTSPLTEEMGDDFGFGLCPYDTSPVVKGKYNTTLLNGSAFYLVCPIGWTGVIECTAVSPTTLRTEVVKTFRREKPFPYRRDCVTTTVENEDLFYCKWGGNWTCVKGEPVTYTGGPVKQCRWCGFDFNEPDGLPHYPIGKCILANETGYRIVDSTDCNRDGVVISTEGSHECLIGNTTVKVHALDERLGPMPCRPKEIVSSAGPVRKTSCTFNYAKTLRNRYYEPRDSYFQQYMLKGEYQYWFDLDVTDRHSDYFAEFIVLVVVALLGGRYVLWLIVTYIVLTEQLAAGLQLGQGEVVLIGNLITHTDIEVVVYFLLLYLVMRDEPIKKWILLLFHAMTNNPVKTITVALLMVSGVAKGGKIDGGWQRLPETNFDIQLALTVIVVAVMLLAKKDPTTVPLVITVATLRTAKITNGLSTDLAIATVSTALLTWTYISDYYKYKTLLQYLISTVTGIFLIRVLKGVGELDLHTPTLPSYRPLFFILVYLISTAVVTRWNLDIAGLLLQCVPTLLMVFTMWADILTLILILPTYELTKLYYLKEVKIGAERGWLWKTNFKRVNDIYEVDQAGEGVYLFPSKQKTGTITGTMLPLIKAILISCISNKWQFIYLLYLIFEVSYYLHKKIIDEIAGGTNFISRLVAALIEANWAFDNEEVRGLKKFFLLSSRVKELIIKHKVRNEVMVHWFGDEEVYGMPKLVGLVKAATLSKNKHCILCTVCENREWRGETCPKCGRFGPPVTCGMTLADFEEKHYKRIFFREDQSEGPVREEYAGYLQYRARGQLFLRNLPVLATKVKMLLVGNLGTEVGDLEHLGWVLRGPAVCKKVTEHEKCTTSIMDKLTAFFGVMPRGTTPRAPVRFPTSLLKIRRGLETGWAYTHQGGISSVDHVTCGKDLLVCDTMGRTRVVCQSNNKMTDESEYGVKTDSGCPEGARCYVFNREAVNISGTKGAMVHLQKTGGEFTCVTASGTPAFFDLKNLKGWSGLPIFEASSGRVVGRVKVGKNEDSKPTKLMSGIQTVSKSTTDLTEMVKKITTMNRGEFRQITLATGAGKTTELPRSVIEEIGRHKRVLVLIPLRAAAESVYQYMRQKHPSIAFNLRIGEMKEGDMATGITYASYGYFCQMPQPKLRAAMVEYSFIFLDEYHCSTPEQLAIMGKIHRFSENLRVVAMTATPAGTVTTTGQKHPIEEYIAPEVMKGEDLGPEYLDIAGLKIPVEEMKSNMLVFVPTRNMAVETAKKLKAKGYNSGYYYSGEDPSNLRVVTSQSPYVVVATNAIESGVTLPDLDVVVDTGLKCEKRIRLSPKMPFIVTGLKRMAVTIGEQAQRRGRVGRVKPGRYYRSQETPVGSKDYHYDLLQAQRYGIEDGINITKSFREMNYDWSLYEEDSLMITQLEILNNLLISEELPMAVKNIMARTDHPEPIQLAYNSYETQVPVLFPKIKNGEVTDSYDNYTFLNARKLGDDVPPYVYATEDEDLAVELLGLDWPDPGNQGTVEAGRALKQVVGLSTAENALLVALFGYVGYQALSKRHIPVVTDIYSIEDHRLEDTTHLQYAPNAIKTEGKETELKELAQGDVQRCMEAMTNYARDGIQFMKSQALKVKETPTYKETMDTVADYVKKFMEALADSKEDIIKYGLWGTHTALYKSIGARLGNETAFATLVVKWLAFGGESIADHVKQAATDLVVYYIINRPQFPGDTETQQEGRKFVASLLVSALATYTYKSWNYNNLSKIVEPALATLPYAATALKLFAPTRLESVVILSTAIYKTYLSIRRGKSDGLLGTGVSAAMEIMSQNPVSVGIAVMLGVGAVAAHNAIEASEQKRTLLMKVFVKNFLDQAATDELVKESPEKIIMALFEAVQTVGNPLRLVYHVYGVFYKGWEAKELAQRTAGRNLFTLIMFEAVELLGVDSEGKIRQLSSNYILELLYKFRDSIKSSVRQMAISWAPAPFSCDWTPTDDRIGLPQDNFLRVETKCPCGYKMKAVKNCAGELRLLEEEGSFLCRNKFGRGSRNYRVTKYYDDNLSEIKPVIRMEGHVELYYKGATIKLDFNNSKTILATDKWEVDHSTLVRVLKRHTGAGYCGAYLGEKPNHKHLIERDCATITKDKVCFLKMKRGCAFTYDLSLHNLTRLIELVHKNNLEDKEIPAVTVTTWLAYTFVNEDIGTIKPAFGEKITPEMQEEITLQPAVLVDATDVTVTVVGETPTMTTGETPTTFTSSGPDPKGQQVLKLGVGEGQYPGTNPQRASLHEAIQSADERPSVLILGSDKATSNRVKTVKNVKVYRGRDPLEVRDMMRRGKILVIALSRVDNALLKFVDYKGTFLTRETLEALSLGRPKKKNITKAEAQWLLRLEDQMEELPDWFAAGEPIFLEANIKHDRYHLVGDIATIKEKAKQLGATDSTKISKEVGAKVYSMKLSNWVMQEENKQSNLTPLFEELLQQCPPGGQNKTAHMVSAYQLAQGNWMPTSCHVFMGTISARRTKTHPYEAYVKLRELVEEHKMKTLCPGSSLRNDNEWVIGKIKYQGNLRTKHMLNPGKVAEQLHREGHRHNVYNKTIGSVMTATGIRLEKLPVVRAQTDTTNFHQAIRDKIDKEENLQTPGLHKKLMEVFNALKRPELESSYDAVEWEELERGINRKGAAGFFERKNIGEILDSEKIKVEEIIDNLKKGRNIKYYETAIPKNEKRDVNDDWTAGDFVDEKKPRVIQYPEAKTRLAITKVMYKWVKQKPVVIPGYEGKTPLFQIFDKVKKEWDQFQNPVAVSFDTKAWDTQVTTNDLELIKDIQKYYFKKKWHKFIDTLTMHMSEVPVITADGEVYIRKGQRGSGQPDTSAGNSMLNVLTMVYAFCEATGVPYKSFDRVAKIHVCGDDGFLITERALGEKFASKGVQILYEAGKPQKITEGDKMKVAYQFADIEFCSHTPIQVRWSDNTSSYMPGRNTTTILAKMATRLDSSGERGTIAYEKAVAFSFLLMYSWNPLIRRICLLVLSTELQVKPGKSTTYYYEGDPISAYKEVIGHNLFDLKRTSFEKLAKLNLSMSVLGAWTRHTSKRLLQDCVNMGVKEGNWLVNADRLVSSKTGNRYVPGEGHTLQGRHYEELALARKQINSFQGTDRYNLGPIVNMVLRRLRVMMMTLIGRGV |
| Enzyme Length | 3898 |
| Uniprot Accession Number | P21530 |
| 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 1658; /note=Charge relay system; for serine protease NS3 activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU00868; ACT_SITE 1695; /note=Charge relay system; for serine protease NS3 activity; /evidence=ECO:0000255|PROSITE-ProRule:PRU00868; ACT_SITE 1752; /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]: Plays a role in viral entry. Interacts with host RPSA that acts as a cellular attachment receptor for the virus. Possesses also intrinsic ribonuclease (RNase) activity that can inhibit the production of type I interferon and assist in the development of persistent infections. {ECO:0000250|UniProtKB:P19712}.; FUNCTION: [Envelope glycoprotein E1]: Plays a role in cell attachment and subsequent fusion of viral and cellular membranes. Therefore, mediates together with envelope glycoprotein E2 the viral entry. {ECO:0000250|UniProtKB:P19712}.; FUNCTION: [Envelope glycoprotein E2]: Plays a role in cell attachment and subsequent fusion of viral and cellular membranes. Therefore, mediates together with envelope glycoprotein E1 the viral entry. {ECO:0000250|UniProtKB:P19712}.; FUNCTION: [Viroporin p7]: Plays an essential role in the virus replication cycle by acting as a viroporin. Forms ion conductive pores, which alters the cell permeability allowing the transport of ions and other small molecules. {ECO:0000250|UniProtKB:P19712}.; FUNCTION: [Non-structural protein 2-3]: Autoprotease that associates with the host chaperone JIV and cleaves the NS2-3 protein between NS2 and NS3. Plays also a role in the formation of infectious particles. {ECO:0000250|UniProtKB:P19712}.; 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. Plays a role in the inhibition of host NF-kappa-B activation by interacting with and inhibiting host TRAF6. 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 (By similarity). Antagonizes host cell apoptosis by interacting with host ferritin heavy chain. The ORF4 protein physically binds host FTH1/FHC, resulting in the reduction of FTH1 protein levels in host cells. Reduction of FTH1 concentration further inhibits the accumulation of reactive oxygen in host cells, leading to reduced apoptosis. {ECO:0000250|UniProtKB:P19712}.; FUNCTION: [Non-structural protein 5A]: Regulates viral RNA replication by interacting with the 3'-untranslated region of viral RNA in a dose-dependent manner. At small concentrations promotes viral synthesis by interacting with the polymerase NS5B while at large concentrations, inhibits replication. {ECO:0000250|UniProtKB:P19712}.; FUNCTION: [RNA-directed RNA polymerase]: Replicates the viral (+) and (-) genome. {ECO:0000255|PROSITE-ProRule:PRU00539}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (8); Chain (14); Domain (6); Glycosylation (28); Region (2); Site (11); Transmembrane (7) |
| Keywords | ATP-binding;Activation of host autophagy by virus;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;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 entry into host cell |
| Interact With | P25963; Q08353; K9IWF9 |
| Induction | INDUCTION: Translated cap independently from an internal ribosome entry site (IRES). {ECO:0000269|PubMed:9573242}. |
| 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:0000250|UniProtKB:P19712}. 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. {ECO:0000250|UniProtKB:P19712}.; PTM: [Genome polyprotein]: Cleavage between E2 and p7 is partial. |
| Signal Peptide | |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | - |
| Motif | |
| Gene Encoded By | |
| Mass | 438,430 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | RHEA:21248; RHEA:23680; RHEA:13065 |
| Cross Reference Brenda |