| IED ID | IndEnz0002000008 |
| Enzyme Type ID | protease000008 |
| Protein Name |
Genome polyprotein Cleaved into: Capsid protein C Core protein ; Protein prM; Peptide pr; Small envelope protein M Matrix protein ; Envelope protein E; Non-structural protein 1 NS1 ; Non-structural protein 2A NS2A ; Non-structural protein 2A-alpha NS2A-alpha ; Serine protease subunit NS2B Flavivirin protease NS2B regulatory subunit Non-structural protein 2B ; Serine protease NS3 EC 3.4.21.91 EC 3.6.1.15 EC 3.6.4.13 Flavivirin protease NS3 catalytic subunit Non-structural protein 3 ; Non-structural protein 4A NS4A ; Peptide 2k; Non-structural protein 4B NS4B ; RNA-directed RNA polymerase NS5 EC 2.1.1.56 EC 2.1.1.57 EC 2.7.7.48 Non-structural protein 5 |
| Gene Name | |
| Organism | Yellow fever virus (strain 17D vaccine) (YFV) |
| Taxonomic Lineage | Viruses Riboviria Orthornavirae Kitrinoviricota Flasuviricetes Amarillovirales Flaviviridae Flavivirus (arboviruses group B) Yellow fever virus Yellow fever virus (strain 17D vaccine) (YFV) |
| Enzyme Sequence | MSGRKAQGKTLGVNMVRRGVRSLSNKIKQKTKQIGNRPGPSRGVQGFIFFFLFNILTGKKITAHLKRLWKMLDPRQGLAVLRKVKRVVASLMRGLSSRKRRSHDVLTVQFLILGMLLMTGGVTLVRKNRWLLLNVTSEDLGKTFSVGTGNCTTNILEAKYWCPDSMEYNCPNLSPREEPDDIDCWCYGVENVRVAYGKCDSAGRSRRSRRAIDLPTHENHGLKTRQEKWMTGRMGERQLQKIERWFVRNPFFAVTALTIAYLVGSNMTQRVVIALLVLAVGPAYSAHCIGITDRDFIEGVHGGTWVSATLEQDKCVTVMAPDKPSLDISLETVAIDRPAEVRKVCYNAVLTHVKINDKCPSTGEAHLAEENEGDNACKRTYSDRGWGNGCGLFGKGSIVACAKFTCAKSMSLFEVDQTKIQYVIRAQLHVGAKQENWNTDIKTLKFDALSGSQEVEFIGYGKATLECQVQTAVDFGNSYIAEMETESWIVDRQWAQDLTLPWQSGSGGVWREMHHLVEFEPPHAATIRVLALGNQEGSLKTALTGAMRVTKDTNDNNLYKLHGGHVSCRVKLSALTLKGTSYKICTDKMFFVKNPTDTGHGTVVMQVKVSKGAPCRIPVIVADDLTAAINKGILVTVNPIASTNDDEVLIEVNPPFGDSYIIVGRGDSRLTYQWHKEGSSIGKLFTQTMKGVERLAVMGDTAWDFSSAGGFFTSVGKGIHTVFGSAFQGLFGGLNWITKVIMGAVLIWVGINTRNMTMSMSMILVGVIMMFLSLGVGADQGCAINFGKRELKCGDGIFIFRDSDDWLNKYSYYPEDPVKLASIVKASFEEGKCGLNSVDSLEHEMWRSRADEINAIFEENEVDISVVVQDPKNVYQRGTHPFSRIRDGLQYGWKTWGKNLVFSPGRKNGSFIIDGKSRKECPFSNRVWNSFQIEEFGTGVFTTRVYMDAVFEYTIDCDGSILGAAVNGKKSAHGSPTFWMGSHEVNGTWMIHTLEALDYKECEWPLTHTIGTSVEESEMFMPRSIGGPVSSHNHIPGYKVQTNGPWMQVPLEVKREACPGTSVIIDGNCDGRGKSTRSTTDSGKVIPEWCCRSCTMPPVSFHGSDGCWYPMEIRPRKTHESHLVRSWVTAGEIHAVPFGLVSMMIAMEVVLRKRQGPKQMLVGGVVLLGAMLVGQVTLLDLLKLTVAVGLHFHEMNNGGDAMYMALIAAFSIRPGLLIGFGLRTLWSPRERLVLTLGAAMVEIALGGVMGGLWKYLNAVSLCILTINAVASRKASNTILPLMALLTPVTMAEVRLAAMFFCAVVIIGVLHQNFKDTSMQKTIPLVALTLTSYLGLTQPFLGLCAFLATRIFGRRSIPVNEALAAAGLVGVLAGLAFQEMENFLGPIAVGGLLMMLVSVAGRVDGLELKKLGEVSWEEEAEISGSSARYDVALSEQGEFKLLSEEKVPWDQVVMTSLALVGAALHPFALLLVLAGWLFHVRGARRSGDVLWDIPTPKIIEECEHLEDGIYGIFQSTFLGASQRGVGVAQGGVFHTMWHVTRGAFLVRNGKKLIPSWASVKEDLVAYGGSWKLEGRWDGEEEVQLIAAVPGKNVVNVQTKPSLFKVRNGGEIGAVALDYPSGTSGSPIVNRNGEVIGLYGNGILVGDNSFVSAISQTEVKEEGKEELQEIPTMLKKGMTTVLDFHPGAGKTRRFLPQILAECARRRLRTLVLAPTRVVLSEMKEAFHGLDVKFHTQAFSAHGSGREVIDAMCHATLTYRMLEPTRVVNWEVIIMDEAHFLDPASIAARGWAAHRARANESATILMTATPPGTSDEFPHSNGEIEDVQTDIPSEPWNTGHDWILADKRPTAWFLPSIRAANVMAASLRKAGKSVVVLNRKTFEREYPTIKQKKPDFILATDIAEMGANLCVERVLDCRTAFKPVLVDEGRKVAIKGPLRISASSAAQRRGRIGRNPNRDGDSYYYSEPTSENNAHHVCWLEASMLLDNMEVRGGMVAPLYGVEGTKTPVSPGEMRLRDDQRKVFRELVRNCDLPVWLSWQVAKAGLKTNDRKWCFEGPEEHEILNDSGETVKCRAPGGAKKPLRPRWCDERVSSDQSALSEFIKFAEGRRGAAEVLVVLSELPDFLAKKGGEAMDTISVFLHSEEGSRAYRNALSMMPEAMTIVMLFILAGLLTSGMVIFFMSPKGISRMSMAMGTMAGCGYLMFLGGVKPTHISYVMLIFFVLMVVVIPEPGQQRSIQDNQVAYLIIGILTLVSAVAANELGMLEKTKEDLFGKKNLIPSSASPWSWPDLDLKPGAAWTVYVGIVTMLSPMLHHWIKVEYGNLSLSGIAQSASVLSFMDKGIPFMKMNISVIMLLVSGWNSITVMPLLCGIGCAMLHWSLILPGIKAQQSKLAQRRVFHGVAENPVVDGNPTVDIEEAPEMPALYEKKLALYLLLALSLASVAMCRTPFSLAEGIVLASAALGPLIEGNTSLLWNGPMAVSMTGVMRGNHYAFVGVMYNLWKMKTGRRGSANGKTLGEVWKRELNLLDKRQFELYKRTDIVEVDRDTARRHLAEGKVDTGVAVSRGTAKLRWFHERGYVKLEGRVIDLGCGRGGWCYYAAAQKEVSGVKGFTLGRDGHEKPMNVQSLGWNIITFKDKTDIHRLEPVKCDTLLCDIGESSSSSVTEGERTVRVLDTVEKWLACGVDNFCVKVLAPYMPDVLEKLELLQRRFGGTVIRNPLSRNSTHEMYYVSGARSNVTFTVNQTSRLLMRRMRRPTGKVTLEADVILPIGTRSVETDKGPLDKEAIEERVERIKSEYMTSWFYDNDNPYRTWHYCGSYVTKTSGSAASMVNGVIKILTYPWDRIEEVTRMAMTDTTPFGQQRVFKEKVDTRAKDPPAGTRKIMKVVNRWLFRHLAREKNPRLCTKEEFIAKVRSHAAIGAYLEEQEQWKTANEAVQDPKFWELVDEERKLHQQGRCRTCVYNMMGKREKKLSEFGKAKGSRAIWYMWLGARYLEFEALGFLNEDHWASRENSGGGVEGIGLQYLGYVIRDLAAMDGGGFYADDTAGWDTRITEADLDDEQEILNYMSPHHKKLAQAVMEMTYKNKVVKVLRPAPGGKAYMDVISRRDQRGSGQVVTYALNTITNLKVQLIRMAEAEMVIHHQHVQDCDESVLTRLEAWLTEHGCDRLKRMAVSGDDCVVRPIDDRFGLALSHLNAMSKVRKDISEWQPSKGWNDWENVPFCSHHFHELQLKDGRRIVVPCREQDELIGRGRVSPGNGWMIKETACLSKAYANMWSLMYFHKRDMRLLSLAVSSAVPTSWVPQGRTTWSIHGKGEWMTTEDMLEVWNRVWITNNPHMQDKTMVKKWRDVPYLTKRQDKLCGSLIGMTNRATWASHIHLVIHRIRTLIGQEKYTDYLTVMDRYSVDADLQLGELI |
| Enzyme Length | 3411 |
| Uniprot Accession Number | P03314 |
| Absorption | |
| Active Site | ACT_SITE 1537; /note=Charge relay system; for serine protease NS3 activity; ACT_SITE 1561; /note=Charge relay system; for serine protease NS3 activity; ACT_SITE 1622; /note=Charge relay system; for serine protease NS3 activity; ACT_SITE 2567; /note=For 2'-O-MTase activity; /evidence=ECO:0000250|UniProtKB:Q6YMS4; ACT_SITE 2652; /note=For 2'-O-MTase activity; /evidence=ECO:0000250|UniProtKB:Q6YMS4; ACT_SITE 2688; /note=For 2'-O-MTase activity; /evidence=ECO:0000250|UniProtKB:Q6YMS4; ACT_SITE 2724; /note=For 2'-O-MTase activity; /evidence=ECO:0000250|UniProtKB:Q6YMS4 |
| Activity Regulation | |
| Binding Site | BINDING 2562; /note=S-adenosyl-L-methionine; /evidence=ECO:0000255|PROSITE-ProRule:PRU00924; BINDING 2592; /note=S-adenosyl-L-methionine; via carbonyl oxygen; /evidence=ECO:0000255|PROSITE-ProRule:PRU00924; BINDING 2593; /note=S-adenosyl-L-methionine; via carbonyl oxygen; /evidence=ECO:0000255|PROSITE-ProRule:PRU00924; BINDING 2610; /note=S-adenosyl-L-methionine; /evidence=ECO:0000255|PROSITE-ProRule:PRU00924; BINDING 2611; /note=S-adenosyl-L-methionine; via carbonyl oxygen; /evidence=ECO:0000255|PROSITE-ProRule:PRU00924; BINDING 2637; /note=S-adenosyl-L-methionine; /evidence=ECO:0000255|PROSITE-ProRule:PRU00924; BINDING 2638; /note=S-adenosyl-L-methionine; via carbonyl oxygen; /evidence=ECO:0000255|PROSITE-ProRule:PRU00924; BINDING 2653; /note=S-adenosyl-L-methionine; /evidence=ECO:0000255|PROSITE-ProRule:PRU00924; BINDING 2726; /note=S-adenosyl-L-methionine; /evidence=ECO:0000255|PROSITE-ProRule:PRU00924 |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=Selective hydrolysis of -Xaa-Xaa-|-Yaa- bonds in which each of the Xaa can be either Arg or Lys and Yaa can be either Ser or Ala.; EC=3.4.21.91; Evidence={ECO:0000269|PubMed:21419753}; 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, ECO:0000269|PubMed:16051820}; CATALYTIC ACTIVITY: 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; Evidence={ECO:0000269|PubMed:16051820}; 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: Reaction=a 5'-end (5'-triphosphoguanosine)-(ribonucleoside) in mRNA + S-adenosyl-L-methionine = a 5'-end (N(7)-methyl 5'-triphosphoguanosine)-ribonucleoside in mRNA + S-adenosyl-L-homocysteine; Xref=Rhea:RHEA:67008, Rhea:RHEA-COMP:17166, Rhea:RHEA-COMP:17167, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:156461, ChEBI:CHEBI:167617; EC=2.1.1.56; Evidence={ECO:0000255|PROSITE-ProRule:PRU00924}; CATALYTIC ACTIVITY: Reaction=a 5'-end (N(7)-methyl 5'-triphosphoguanosine)-ribonucleoside in mRNA + S-adenosyl-L-methionine = a 5'-end (N(7)-methyl 5'-triphosphoguanosine)-(2'-O-methyl-ribonucleoside) in mRNA + H(+) + S-adenosyl-L-homocysteine; Xref=Rhea:RHEA:67020, Rhea:RHEA-COMP:17167, Rhea:RHEA-COMP:17168, ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:156461, ChEBI:CHEBI:167609; EC=2.1.1.57; Evidence={ECO:0000255|PROSITE-ProRule:PRU00924}; |
| DNA Binding | |
| EC Number | 3.4.21.91; 3.6.1.15; 3.6.4.13; 2.1.1.56; 2.1.1.57; 2.7.7.48 |
| Enzyme Function | FUNCTION: [Capsid protein C]: Plays a role in virus budding by binding to the cell membrane and gathering the viral RNA into a nucleocapsid that forms the core of a mature virus particle. During virus entry, may induce genome penetration into the host cytoplasm after hemifusion induced by the surface proteins. Can migrate to the cell nucleus where it modulates host functions. {ECO:0000250|UniProtKB:P17763}.; FUNCTION: [Capsid protein C]: Inhibits RNA silencing by interfering with host Dicer. {ECO:0000269|PubMed:27849599}.; FUNCTION: [Peptide pr]: Prevents premature fusion activity of envelope proteins in trans-Golgi by binding to envelope protein E at pH6.0. After virion release in extracellular space, gets dissociated from E dimers. {ECO:0000250|UniProtKB:P17763}.; FUNCTION: [Protein prM]: Acts as a chaperone for envelope protein E during intracellular virion assembly by masking and inactivating envelope protein E fusion peptide. prM is the only viral peptide matured by host furin in the trans-Golgi network probably to avoid catastrophic activation of the viral fusion activity in acidic Golgi compartment prior to virion release. prM-E cleavage is inefficient, and many virions are only partially matured. These uncleaved prM would play a role in immune evasion. {ECO:0000250|UniProtKB:P17763}.; FUNCTION: [Small envelope protein M]: May play a role in virus budding. Exerts cytotoxic effects by activating a mitochondrial apoptotic pathway through M ectodomain. May display a viroporin activity. {ECO:0000250|UniProtKB:P17763}.; FUNCTION: [Envelope protein E]: Binds to host cell surface receptor and mediates fusion between viral and cellular membranes. Envelope protein is synthesized in the endoplasmic reticulum in the form of heterodimer with protein prM. They play a role in virion budding in the ER, and the newly formed immature particle is covered with 60 spikes composed of heterodimer between precursor prM and envelope protein E. The virion is transported to the Golgi apparatus where the low pH causes dissociation of PrM-E heterodimers and formation of E homodimers. prM-E cleavage is inefficient, and many virions are only partially matured. These uncleaved prM would play a role in immune evasion. {ECO:0000250|UniProtKB:P17763}.; FUNCTION: [Non-structural protein 1]: Involved in immune evasion, pathogenesis and viral replication. Once cleaved off the polyprotein, is targeted to three destinations: the viral replication cycle, the plasma membrane and the extracellular compartment. Essential for viral replication. Required for formation of the replication complex and recruitment of other non-structural proteins to the ER-derived membrane structures. Excreted as a hexameric lipoparticle that plays a role against host immune response. Antagonizing the complement function. Binds to the host macrophages and dendritic cells. Inhibits signal transduction originating from Toll-like receptor 3 (TLR3). {ECO:0000250|UniProtKB:Q9Q6P4, ECO:0000269|PubMed:9371625}.; FUNCTION: [Non-structural protein 2A]: Component of the viral RNA replication complex that functions in virion assembly and antagonizes the host immune response. {ECO:0000250|UniProtKB:P17763}.; FUNCTION: [Serine protease subunit NS2B]: Required cofactor for the serine protease function of NS3. May have membrane-destabilizing activity and form viroporins (By similarity). {ECO:0000250|UniProtKB:P17763, ECO:0000255|PROSITE-ProRule:PRU00859}.; FUNCTION: [Serine protease NS3]: Displays three enzymatic activities: serine protease, NTPase and RNA helicase. NS3 serine protease, in association with NS2B, performs its autocleavage and cleaves the polyprotein at dibasic sites in the cytoplasm: C-prM, NS2A-NS2B, NS2B-NS3, NS3-NS4A, NS4A-2K and NS4B-NS5. NS3 RNA helicase binds RNA and unwinds dsRNA in the 3' to 5' direction. Also plays a role in virus assembly (PubMed:18199634). {ECO:0000255|PROSITE-ProRule:PRU00860, ECO:0000269|PubMed:18199634}.; FUNCTION: [Non-structural protein 4A]: Regulates the ATPase activity of the NS3 helicase activity. NS4A allows NS3 helicase to conserve energy during unwinding. {ECO:0000250|UniProtKB:Q9Q6P4}.; FUNCTION: [Peptide 2k]: Functions as a signal peptide for NS4B and is required for the interferon antagonism activity of the latter. {ECO:0000250|UniProtKB:P17763}.; FUNCTION: [Non-structural protein 4B]: Induces the formation of ER-derived membrane vesicles where the viral replication takes place. Inhibits interferon (IFN)-induced host STAT1 phosphorylation and nuclear translocation, thereby preventing the establishment of cellular antiviral state by blocking the IFN-alpha/beta pathway (PubMed:15956546). {ECO:0000250|UniProtKB:Q9Q6P4, ECO:0000269|PubMed:15956546}.; FUNCTION: [RNA-directed RNA polymerase NS5]: Replicates the viral (+) and (-) RNA genome, and performs the capping of genomes in the cytoplasm (PubMed:19850911). NS5 methylates viral RNA cap at guanine N-7 and ribose 2'-O positions (PubMed:19850911). Besides its role in RNA genome replication, also prevents the establishment of cellular antiviral state by blocking the interferon-alpha/beta (IFN-alpha/beta) signaling pathway (PubMed:25211074). IFN-I induces binding of NS5 to host IFN-activated transcription factor STAT2, preventing its transcriptional activity. Host TRIM23 is the E3 ligase that interacts with and polyubiquitinates NS5 to promote its binding to STAT2 and trigger IFN-I signaling inhibition (PubMed:25211074). {ECO:0000269|PubMed:19850911, ECO:0000269|PubMed:25211074}. |
| Temperature Dependency | |
| PH Dependency | BIOPHYSICOCHEMICAL PROPERTIES: pH dependence: Optimum pH is 9. {ECO:0000269|PubMed:21419753}; |
| Pathway | |
| nucleotide Binding | NP_BIND 1682..1689; /note=ATP; /evidence=ECO:0000255|PROSITE-ProRule:PRU00541 |
| Features | Active site (7); Beta strand (86); Binding site (9); Chain (14); Disulfide bond (14); Domain (5); Glycosylation (4); Helix (64); Intramembrane (3); Metal binding (7); Modified residue (1); Motif (2); Mutagenesis (55); Natural variant (24); Nucleotide binding (1); Peptide (1); Propeptide (1); Region (4); Site (28); Topological domain (20); Transmembrane (16); Turn (15) |
| Keywords | 3D-structure;ATP-binding;Activation of host autophagy by virus;Capsid protein;Clathrin-mediated endocytosis of virus by host;Cleavage on pair of basic residues;Direct protein sequencing;Disulfide bond;Fusion of virus membrane with host endosomal membrane;Fusion of virus membrane with host membrane;GTP-binding;Glycoprotein;Helicase;Host cytoplasm;Host endoplasmic reticulum;Host membrane;Host nucleus;Host-virus interaction;Hydrolase;Inhibition of host STAT2 by virus;Inhibition of host innate immune response by virus;Inhibition of host interferon signaling pathway by virus;Isopeptide bond;Membrane;Metal-binding;Methyltransferase;Multifunctional enzyme;Nucleotide-binding;Nucleotidyltransferase;Phosphoprotein;Protease;RNA-binding;RNA-directed RNA polymerase;Reference proteome;S-adenosyl-L-methionine;Secreted;Serine protease;Suppressor of RNA silencing;Transcription;Transcription regulation;Transferase;Transmembrane;Transmembrane helix;Ubl conjugation;Viral RNA replication;Viral attachment to host cell;Viral envelope protein;Viral immunoevasion;Viral penetration into host cytoplasm;Virion;Virus endocytosis by host;Virus entry into host cell;Zinc;mRNA capping;mRNA processing |
| Interact With | |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: [Capsid protein C]: Virion {ECO:0000250|UniProtKB:P17763}. Host nucleus {ECO:0000250|UniProtKB:P17763}. Host cytoplasm, host perinuclear region {ECO:0000250|UniProtKB:P17763}. Host cytoplasm {ECO:0000250|UniProtKB:P17763}.; SUBCELLULAR LOCATION: [Peptide pr]: Secreted {ECO:0000250|UniProtKB:P17763}.; SUBCELLULAR LOCATION: [Small envelope protein M]: Virion membrane {ECO:0000269|PubMed:15507646}; Multi-pass membrane protein {ECO:0000269|PubMed:15507646}. Host endoplasmic reticulum membrane {ECO:0000269|PubMed:15507646}; Multi-pass membrane protein {ECO:0000255}. Note=ER membrane retention is mediated by the transmembrane domains. {ECO:0000269|PubMed:15507646}.; SUBCELLULAR LOCATION: [Envelope protein E]: Virion membrane {ECO:0000305}; Multi-pass membrane protein {ECO:0000269|PubMed:15507646}. Host endoplasmic reticulum membrane {ECO:0000269|PubMed:3008425}; Multi-pass membrane protein {ECO:0000255}. Note=ER membrane retention is mediated by the transmembrane domains. {ECO:0000269|PubMed:15507646}.; SUBCELLULAR LOCATION: [Non-structural protein 1]: Secreted {ECO:0000250|UniProtKB:P17763}. Host endoplasmic reticulum membrane; Peripheral membrane protein; Lumenal side {ECO:0000250|UniProtKB:P17763}. Note=Located in RE-derived vesicles hosting the replication complex. {ECO:0000250|UniProtKB:Q9Q6P4}.; SUBCELLULAR LOCATION: [Non-structural protein 2A]: Host endoplasmic reticulum membrane {ECO:0000250|UniProtKB:P17763}; Multi-pass membrane protein {ECO:0000250|UniProtKB:P17763}.; SUBCELLULAR LOCATION: [Serine protease subunit NS2B]: Host endoplasmic reticulum membrane; Multi-pass membrane protein {ECO:0000250|UniProtKB:P17763}.; SUBCELLULAR LOCATION: [Serine protease NS3]: Host endoplasmic reticulum membrane {ECO:0000255|PROSITE-ProRule:PRU00860}; Peripheral membrane protein {ECO:0000255|PROSITE-ProRule:PRU00860}; Cytoplasmic side {ECO:0000255|PROSITE-ProRule:PRU00860}. Note=Remains non-covalently associated to serine protease subunit NS2B. {ECO:0000255|PROSITE-ProRule:PRU00860}.; SUBCELLULAR LOCATION: [Non-structural protein 4A]: Host endoplasmic reticulum membrane {ECO:0000250|UniProtKB:P17763}; Multi-pass membrane protein {ECO:0000250|UniProtKB:P17763}. Note=Located in RE-associated vesicles hosting the replication complex. {ECO:0000250|UniProtKB:P17763}.; SUBCELLULAR LOCATION: [Non-structural protein 4B]: Host endoplasmic reticulum membrane {ECO:0000250|UniProtKB:P17763}; Multi-pass membrane protein {ECO:0000250|UniProtKB:P17763}. Note=Located in RE-derived vesicles hosting the replication complex. {ECO:0000250|UniProtKB:Q9Q6P4}.; SUBCELLULAR LOCATION: [RNA-directed RNA polymerase NS5]: Host endoplasmic reticulum membrane; Peripheral membrane protein; Cytoplasmic side. Host nucleus {ECO:0000250|UniProtKB:P17763}. Note=Located in RE-associated vesicles hosting the replication complex. NS5 protein is mainly localized in the nucleus rather than in ER vesicles. {ECO:0000250|UniProtKB:P17763}. |
| Modified Residue | MOD_RES 2562; /note=Phosphoserine; /evidence=ECO:0000269|PubMed:18757072 |
| Post Translational Modification | PTM: [Genome polyprotein]: Specific enzymatic cleavages in vivo yield mature proteins. The nascent capsid protein C contains a C-terminal hydrophobic domain that act as a signal sequence for translocation of prM into the lumen of the ER. Mature capsid protein C is cleaved at a site upstream of this hydrophobic domain by NS3. prM is cleaved in post-Golgi vesicles by a host furin, releasing the mature small envelope protein M, and peptide pr. Non-structural protein 2A-alpha, a C-terminally truncated form of non-structural protein 2A, results from partial cleavage by NS3. Specific enzymatic cleavages in vivo yield mature proteins peptide 2K acts as a signal sequence and is removed from the N-terminus of NS4B by the host signal peptidase in the ER lumen. Signal cleavage at the 2K-4B site requires a prior NS3 protease-mediated cleavage at the 4A-2K site. {ECO:0000269|PubMed:1833562, ECO:0000269|PubMed:21419753, ECO:0000269|PubMed:3008425, ECO:0000269|PubMed:8116234, ECO:0000269|PubMed:8189517, ECO:0000269|PubMed:8421901, ECO:0000269|PubMed:8445732}.; PTM: [Protein prM]: Cleaved in post-Golgi vesicles by a host furin, releasing the mature small envelope protein M, and peptide pr. This cleavage is incomplete as up to 30% of viral particles still carry uncleaved prM. {ECO:0000250|UniProtKB:P17763}.; PTM: [Envelope protein E]: N-glycosylated. {ECO:0000250|UniProtKB:P17763}.; PTM: [Non-structural protein 1]: N-glycosylated. The excreted form is glycosylated and this is required for efficient secretion of the protein from infected cells. {ECO:0000250|UniProtKB:P17763}.; PTM: Polyubiquitinated; ubiquitination is probably mediated by host TRIM23 and is prerequisite for NS5-STAT2 interaction. NS5 is not ISGylated or sumoylated. {ECO:0000269|PubMed:25211074}.; PTM: [RNA-directed RNA polymerase NS5]: Phosphorylated on serines residues. This phosphorylation may trigger NS5 nuclear localization. {ECO:0000269|PubMed:9621090}. |
| Signal Peptide | |
| Structure 3D | Electron microscopy (1); X-ray crystallography (19) |
| Cross Reference PDB | 1NA4; 1YKS; 3EVA; 3EVB; 3EVC; 3EVD; 3EVE; 3EVF; 5FFM; 5N6B; 6EPK; 6IW0; 6IW1; 6IW2; 6IW4; 6QSN; 6SS7; 6SS8; 6SS9; 6SSA; |
| Mapped Pubmed ID | 15831952; 17526891; 19185594; 19846669; 20308361; 21298455; 23800076; 24678844; 26739057; 28044043; 28975614; 30625326; 31043530; 31202975; 31931019; 32645549; |
| Motif | MOTIF 1773..1776; /note=DEAH box; /evidence=ECO:0000255|PROSITE-ProRule:PRU00541; MOTIF 2878..2911; /note=Nuclear localization signal; /evidence=ECO:0000250 |
| Gene Encoded By | |
| Mass | 379,518 |
| Kinetics | |
| Metal Binding | METAL 2945; /note=Zinc 1; /evidence=ECO:0000250|UniProtKB:P14335; METAL 2949; /note=Zinc 1; via tele nitrogen; /evidence=ECO:0000250|UniProtKB:P14335; METAL 2954; /note=Zinc 1; /evidence=ECO:0000250|UniProtKB:P14335; METAL 2957; /note=Zinc 1; /evidence=ECO:0000250|UniProtKB:P14335; METAL 3222; /note=Zinc 2; via tele nitrogen; /evidence=ECO:0000250|UniProtKB:P14335; METAL 3238; /note=Zinc 2; /evidence=ECO:0000250|UniProtKB:P14335; METAL 3357; /note=Zinc 2; /evidence=ECO:0000250|UniProtKB:P14335 |
| Rhea ID | RHEA:21248; RHEA:23680; RHEA:13065; RHEA:67008; RHEA:67020 |
| Cross Reference Brenda | 2.7.7.50;3.4.21.91;3.6.4.13; |