A0A2R3WI59 · A0A2R3WI59_9FLAV

Function

function

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.
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.
Component of the viral RNA replication complex that functions in virion assembly and antagonizes the host immune response.
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.
Functions as a signal peptide for NS4B and is required for the interferon antagonism activity of the latter.
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.
Inhibits RNA silencing by interfering with host Dicer.
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).
May play a role in virus budding. Exerts cytotoxic effects by activating a mitochondrial apoptotic pathway through M ectodomain. May display a viroporin activity.
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.
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.
Regulates the ATPase activity of the NS3 helicase activity. NS4A allows NS3 helicase to conserve energy during unwinding.
Replicates the viral + and - RNA genome, and performs the capping of genomes in the cytoplasm. NS5 methylates viral RNA cap at guanine N-7 and ribose 2'-O positions. 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. 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.
Required cofactor for the serine protease function of NS3. May have membrane-destabilizing activity and form viroporins.

Catalytic activity

Features

Showing features for active site, binding site.

Type
IDPosition(s)Description
Active site1537Charge relay system; for serine protease NS3 activity
Active site1561Charge relay system; for serine protease NS3 activity
Active site1622Charge relay system; for serine protease NS3 activity
Binding site2945Zn2+ 1 (UniProtKB | ChEBI)
Binding site2949Zn2+ 1 (UniProtKB | ChEBI)
Binding site2954Zn2+ 1 (UniProtKB | ChEBI)
Binding site2957Zn2+ 1 (UniProtKB | ChEBI)
Binding site3222Zn2+ 2 (UniProtKB | ChEBI)
Binding site3238Zn2+ 2 (UniProtKB | ChEBI)
Binding site3357Zn2+ 2 (UniProtKB | ChEBI)

GO annotations

AspectTerm
Cellular Componentextracellular region
Cellular Componenthost cell endoplasmic reticulum membrane
Cellular Componenthost cell nucleus
Cellular Componenthost cell perinuclear region of cytoplasm
Cellular Componentmembrane
Cellular Componentviral capsid
Cellular Componentvirion membrane
Molecular FunctionATP binding
Molecular Functiondouble-stranded RNA binding
Molecular FunctionGTP binding
Molecular Functionmetal ion binding
Molecular FunctionmRNA (nucleoside-2'-O-)-methyltransferase activity
Molecular FunctionmRNA 5'-cap (guanine-N7-)-methyltransferase activity
Molecular Functionprotein dimerization activity
Molecular Functionribonucleoside triphosphate phosphatase activity
Molecular FunctionRNA helicase activity
Molecular FunctionRNA-dependent RNA polymerase activity
Molecular Functionserine-type endopeptidase activity
Molecular Functionstructural molecule activity
Biological Processfusion of virus membrane with host endosome membrane
Biological Processproteolysis
Biological Processsymbiont entry into host cell
Biological Processsymbiont-mediated suppression of host innate immune response
Biological Processsymbiont-mediated suppression of host JAK-STAT cascade via inhibition of STAT2 activity
Biological Processsymbiont-mediated suppression of host type I interferon-mediated signaling pathway
Biological Processviral RNA genome replication
Biological Processvirion attachment to host cell
Biological Processvirus-mediated perturbation of host defense response

Keywords

Names & Taxonomy

Protein names

  • Recommended name
    Genome polyprotein

Organism names

  • Taxonomic identifier
  • Organism
  • Strains
    • 1555
    • RJPR4867
    • H191
    • PA193
    • RJ95
  • Taxonomic lineage
    Viruses > Riboviria > Orthornavirae > Kitrinoviricota > Flasuviricetes > Amarillovirales > Flaviviridae > Orthoflavivirus > Orthoflavivirus flavi

Accessions

  • Primary accession
    A0A2R3WI59
  • Secondary accessions
    • A0A2R3XYE9

Subcellular Location

Host endoplasmic reticulum membrane
; Multi-pass membrane protein
Host endoplasmic reticulum membrane
; Peripheral membrane protein
Host endoplasmic reticulum membrane
; Peripheral membrane protein
Host nucleus
Secreted
Virion membrane
; Multi-pass membrane protein

Features

Showing features for transmembrane.

TypeIDPosition(s)Description
Transmembrane105-125Helical
Transmembrane730-751Helical
Transmembrane758-778Helical
Transmembrane1133-1151Helical
Transmembrane1160-1182Helical
Transmembrane1202-1220Helical
Transmembrane1232-1249Helical
Transmembrane1293-1310Helical
Transmembrane1358-1376Helical
Transmembrane1382-1400Helical
Transmembrane1451-1477Helical
Transmembrane2157-2180Helical
Transmembrane2187-2204Helical
Transmembrane2210-2227Helical
Transmembrane2239-2256Helical
Transmembrane2293-2314Helical

Keywords

PTM/Processing

Features

Showing features for disulfide bond.

TypeIDPosition(s)Description
Disulfide bond288↔315
Disulfide bond345↔401
Disulfide bond359↔390
Disulfide bond377↔406
Disulfide bond467↔568
Disulfide bond585↔615

Keywords

Interaction

Subunit

Forms a heterodimer with NS2B. Interacts with non-structural protein 2A (via N-terminus). Interacts with NS4B. Interacts with unphosphorylated RNA-directed RNA polymerase NS5; this interaction stimulates RNA-directed RNA polymerase NS5 guanylyltransferase activity. NS3 interacts with host PDCD6IP; this interaction contributes to virion release.
Forms a heterodimer with serine protease NS3. May form homooligomers.
Forms heterodimers with envelope protein E in the endoplasmic reticulum and Golgi.
Homodimer. Interacts (via N-terminus) with host EXOC1 (via C-terminus); this interaction results in EXOC1 degradation through the proteasome degradation pathway.
Homodimer. Interacts with host STAT2; this interaction prevents the establishment of cellular antiviral state. Interacts with serine protease NS3. Interacts with host TRIM23; this interaction leads to NS5 ubiquitination.
Homodimer; in the endoplasmic reticulum and Golgi. Interacts with protein prM. Interacts with non-structural protein 1.
Interacts (via N-terminus) with serine protease NS3.
Interacts with serine protease NS3.

Family & Domains

Features

Showing features for domain, region.

Type
IDPosition(s)Description
Domain1355-1484Flavivirus NS2B
Domain1485-1665Peptidase S7
Domain1669-1825Helicase ATP-binding
Domain1820-1997Helicase C-terminal
Region1942-1961Disordered
Domain2507-2771MRNA cap 0-1 NS5-type MT
Domain3035-3187RdRp catalytic

Keywords

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Sequence processing
    The displayed sequence is further processed into a mature form.
  • Length
    3,411
  • Mass (Da)
    378,820
  • Last updated
    2018-06-20 v1
  • Checksum
    AD564CC95371CD6F
MSGRKAQGKTLGVNMVRRGVRSLSSKIKQKTKQIGSRPGPSRGVQGFVFFFLFNVLTGKKITAHLKKLWRMLDPRQGLVVLRKVKRVVASLMRGLSSRKRRSQDVLTIQFLILGMLLMVGGVTLVRRNRWLLLNVTSEDLGKTFSVGTGNCTTNILEAKYWCPDSMEYNCPNLSPREEPDDIDCWCYGVENVRVAYGKCDSAGRSRRSRRAIDLPTHENHGLKTRQEKWMTGRMGERQLQKIERWLVRNPFFAATALAIAYLVGSNMTQRVVIALLVLAVGPAYSAHCIGITDRDFIEGVHGGTWVSATLEQDKCVTVMAPDKPSLDISLETVAIDGPAEARKVCYSAVLTNVKINDKCPSTGEAHLEEENEGDNACKRTYSDRGWGNGCGLFGKGSIVACAKFTCAKSMSLFEVDQTKIQYVIRAQLHVGAKQENWNTDIKTLKFDALSGSQEAEFTGYGRATLECQVQTAVDFSNSYIAEMEKESWIVDKQWAQDLTLPWQSGSGGVWREMHHLVEFEPPHAATIKVLALGNQEGSLKTALTGAMRVTKDTNNSKLYKLHGGHVACRVKLSALTLKGTSYKMCTDKMSFVKNPTDTGHGTAVMQVKVPKGAPCRIPVMVADDLTAAVNKGILVTVNPIASTNDDEVLIEVNPPFGDSYIIVGTGDSRLTYQWHKEGSSIGKLFTQTMKGAERLAVMGDAAWDFGSAGGFFTSVGKGIHTVFGSAFQGLFGGLSWITKVIMGVVLIWVGINTRNMTMSMSMILVGVIMMFLSLGVGADQGCAINFGKRELKCGDGIFVFRDSDDWLNKYSYYPEDPVKLASIVKASFEEGKCGLNSVDSLEHEMWRSRADEINAILEENEVDISVVVQDSKNIYQRGTHPFSRIRDGLQYGWKTWGKNLVFSPGRKNGSFIIDGKSRKECPFSNRVWNSFQIEEFGTGVFTTRVYMDAVFEYTMDCDGSILGAAVNGKKSAHGSPTFWMGSHEVNGTWMIHTLETLDYKECEWPLTHTIGTSVEESDMFMPRSIGGPVSSHNHIPGYKVQTNGPWMQVPLEVKREACPGTSVVVDGGCDGRGKSTRSTTDSGKIIPEWCCRSCTMPPVSFHGSDGCWYPMEIRPKKTHDSHLVRSWVTAGEIHAIPFGLVSMMIAMEVVLRKRQGPKQILVGGMVLLGAMLVGQVTILDLLKLTVAVGLHFHEMNNGGDAMYMALIAAFSIRPGLLIGFGLRTLWSPRERLVLTLGAAMVEIALGGMMGGLWKYLNAVSLCILTINAVASRKASNVILPLMALLTPVTMAEVRLATMLFCTVVIIGVLHQNSKDTSMQKTIPLVALTLTSYLGLTQPFLGLCAFMATRIFGRRSIPVNEALAAAGLVGVLAGLAFQEMENFLGPVAVGGILMMLVSVAGRVDGLELRKLGEVSWEEEAEISGSSARYDVTLSEQGEFKLLSEEKVPWDQVVMTSLALVGAAIHPFALLLVLAGWLFHVKGARRSGDVLWDIPTPKIIEECEYLEDGIYGIFQSTFLGASQRGVGVAQGGVFHTMWHVTRGAFLVRNGKKLVPSWASVKEDLVAYGGSWKLDGRWDGEEEVQLIAAAPGKNVVNVQTKPSLFKVKNGGEIGAVALDYPSGTSGSPIVNRNGEVIGLYGNGILVGDNSFVSAISQTEVKEEGKEELQEIPTMLKKGMTTILDFHPGAGKTRRFLPQILAECARRRLRTLVLAPTRVVLSEMKEAFHGLDVKFHTQAFSAHGSGKEVIDAMCHATLTYRMLEPTRVVNWEVIIMDEAHFLDPASIAARGWAAHRARANESATILMTATPPGTSDEFPHSNGEIEDVQTDIPSEPWNTGHDWILADKRPTAWFLPSIRAANVMAASLRKAGKSVVVLNRKTFEKEYPTIKQKKPDFILATDIAEMGANLCVERVLDCRTAFKPVLVDEGRKVAIKGPLRISASSAAQRRGRIGRNPNRDGDSYYYSEPTSEDNAHHVCWLEASMLLDNMEVRGGMVAPLYGIEGTKTPVSPGEMRLRDDQRRVFRELVRNCDLPVWLSWQVAKAGLKTNDRKWCFEGPEEHEILNDSGETVKCRAPGGAKKPLRPRWCDERVSSDQSALADFIKFAEGRRGAAEMLVVLSELPDFLAKKGGEAVDTISVLLHSEEGSRAYRNALSMMPEAMTTVMLFVLAGLLTSGMVVFFMSPKGISRMSMAMGTMAGCGYLMFLGGVKPTHISYIMLIFFVLMVVVVPEPGQQRTIQDNQVAYLIIGILTLISVVAANELGMLEKTKEDLFGKKNLIPSSAAPWSWPDFDLKPGAAWTVYVGIVTMLSPMLHHWIKVEYGNLSLSGIAQSASVLSFMDKGIPFMKMNISVIILLVSGWNSITVMPLLCGIGCAMLHWTLILPGIKAQQSKLAQRRVFHGVAKNPVVDGNPTVDIEEAPEMPALYEKKLALYLLLALSLASVAMCRTPFSLAEGIVLASAALGPLIEGNTSLLWNGPMAVSMTGVMRGNYYAFVGVMYNLWKMKTGRRGRANGKTLGEVWKRELNLLDKQQFELYKRTDIVEVDRDTARRHLAEGKVDTGVAVSRGTAKLRWFHERGYVKLEGRVTDLGCGRGGWCYYAAAQREVSGVRGFTLGKEGHEKPMNVQSLGWNIITFKDKTDVHRLEPIKCDTLLCDIGESSPSSVTEGERTMRVLDTVEKWLSCGVESFCVKVLAPYMPDVLEKLELLQRRFGGTVIRNPLSRNSTHEMYYVSGARSNITFTVNQTSRLLMRRMRRPTGKVTLEADVILPIGTRSVETDKGPLDRAAIEERVERIKSEYTATWFHDSDNPYRTWHYCGSYVTRTSGSAASMINGVIKILTYPWDRIEEVTRMAMTDTTPFGQQRVFKEKVDTRAKDPPAGTRKIMKVVNRWLFRHLAREKNPRLCTKEEFIAKVRSHAAIGAFLEEQEQWKTANEAVQDPKFWELVDEERRLHQQGRCRTCVYNMMGKREKKLSEFGKAKGSRAIWYMWLGARYLEFEALGFLNEDHWASRENSGGGVEGIGLQYLGYVIRDLAALEGGGFYADDTAGWDTRITEADLDDEQEILNYMSPHHRKLALAVMEMTYKNKVVKVLRPAPGGKAYMDVISRRDQRGSGQVVTYALNTITNLKVQLIRMAEAEMVIHHQHVQDCDDTALTKLEAWLAEHGCDRLKRMAVSGDDCVVRPIDDRFGLALSHLNAMSKVRKDISEWQPSKGWDDWESVPFCSHHFHELQLKDGRRIVVPCRDQDELVGRGRVSPGNGWMIKETACLSKAYANMWSLMYFHKRDMRLLSLAVSSAVPTSWVPQGRTTWSVHGKGEWMTTEDMLEVWNRVWITNNPHMQDKTTVKEWRDIPYLTKRQDKLCGSLIGMTNRATWASHIHLVIHRIRTLIGKERYTDYLTVMDRYSVDADLQPGELI

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
MF370548
EMBL· GenBank· DDBJ
ASY08202.1
EMBL· GenBank· DDBJ
Genomic RNA
MF423373
EMBL· GenBank· DDBJ
AVQ67911.1
EMBL· GenBank· DDBJ
Genomic RNA
MF423377
EMBL· GenBank· DDBJ
AVQ67915.1
EMBL· GenBank· DDBJ
Genomic RNA
MF423378
EMBL· GenBank· DDBJ
AVQ67916.1
EMBL· GenBank· DDBJ
Genomic RNA
MF538783
EMBL· GenBank· DDBJ
AVQ94370.1
EMBL· GenBank· DDBJ
Genomic RNA
MF538785
EMBL· GenBank· DDBJ
AVQ94372.1
EMBL· GenBank· DDBJ
Genomic RNA
MF170975
EMBL· GenBank· DDBJ
AWB14997.1
EMBL· GenBank· DDBJ
Genomic RNA
MK333807
EMBL· GenBank· DDBJ
QBK94350.1
EMBL· GenBank· DDBJ
Genomic RNA
MK333809
EMBL· GenBank· DDBJ
QBK94352.1
EMBL· GenBank· DDBJ
Genomic RNA
MN506265
EMBL· GenBank· DDBJ
QLJ58318.1
EMBL· GenBank· DDBJ
Genomic RNA
MN506290
EMBL· GenBank· DDBJ
QLJ58343.1
EMBL· GenBank· DDBJ
Genomic RNA

Similar Proteins

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