A0A8F7CI74 · A0A8F7CI74_9FLAV
- ProteinGenome polyprotein
- StatusUniProtKB unreviewed (TrEMBL)
- Organism
- Amino acids3411 (go to sequence)
- Protein existencePredicted
- Annotation score5/5
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.
Functions as a signal peptide for NS4B and is required for the interferon antagonism activity of the latter.
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.
Required cofactor for the serine protease function of NS3. May have membrane-destabilizing activity and form viroporins.
Catalytic activity
- ATP + H2O = ADP + H+ + phosphate
Features
Showing features for active site, binding site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Active site | 1537 | Charge relay system; for serine protease NS3 activity | ||||
Sequence: H | ||||||
Active site | 1561 | Charge relay system; for serine protease NS3 activity | ||||
Sequence: D | ||||||
Active site | 1622 | Charge relay system; for serine protease NS3 activity | ||||
Sequence: S | ||||||
Binding site | 2945 | Zn2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Binding site | 2949 | Zn2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 2954 | Zn2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 2957 | Zn2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 3222 | Zn2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 3238 | Zn2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 3357 | Zn2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: C |
GO annotations
Keywords
- Molecular function
- Biological process
- Ligand
Names & Taxonomy
Protein names
- Recommended nameGenome polyprotein
Organism names
- Organism
- Strain
- Taxonomic lineageViruses > Riboviria > Orthornavirae > Kitrinoviricota > Flasuviricetes > Amarillovirales > Flaviviridae > Orthoflavivirus > Orthoflavivirus flavi
Accessions
- Primary accessionA0A8F7CI74
Subcellular Location
UniProt Annotation
GO Annotation
Endoplasmic reticulum membrane ; Multi-pass membrane protein
Endoplasmic reticulum membrane ; Peripheral membrane protein
Endoplasmic reticulum membrane ; Peripheral membrane protein
Host endoplasmic reticulum membrane ; Multi-pass membrane protein
Host endoplasmic reticulum membrane ; Peripheral membrane protein
Host endoplasmic reticulum membrane ; Peripheral membrane protein
Membrane ; Multi-pass membrane protein
Membrane ; Peripheral membrane protein
Virion membrane ; Multi-pass membrane protein
Features
Showing features for transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Transmembrane | 43-62 | Helical | ||||
Sequence: GVQGFIFFFLFNVLTGRKIT | ||||||
Transmembrane | 105-125 | Helical | ||||
Sequence: VLTVQFLILGMLLMTGGVTLV | ||||||
Transmembrane | 245-264 | Helical | ||||
Sequence: WLVRNPFFAVTALAIAYLVG | ||||||
Transmembrane | 730-751 | Helical | ||||
Sequence: LFGGLSWITKVIMGAVLIWVGI | ||||||
Transmembrane | 758-778 | Helical | ||||
Sequence: MSMSMILVGVIMMFLSLGVGA | ||||||
Transmembrane | 1160-1181 | Helical | ||||
Sequence: ILVGGIVLLGAMLVGQVTLLDL | ||||||
Transmembrane | 1201-1220 | Helical | ||||
Sequence: AMYMALIAAFSIRPGLLIGF | ||||||
Transmembrane | 1232-1249 | Helical | ||||
Sequence: LVLTLGAAMVEIALGGMM | ||||||
Transmembrane | 1293-1310 | Helical | ||||
Sequence: VRLATMLFCTVVIIGVLH | ||||||
Transmembrane | 1322-1346 | Helical | ||||
Sequence: IPLVALTLTSYLGLTQPFLGLCAFM | ||||||
Transmembrane | 1358-1376 | Helical | ||||
Sequence: VNEALAAAGLVGVLAGLAF | ||||||
Transmembrane | 1382-1400 | Helical | ||||
Sequence: FLGPVAVGGILMMLVSVAG | ||||||
Transmembrane | 1451-1477 | Helical | ||||
Sequence: IVMTSLALVGAAIHPFALMLVLAGWLL | ||||||
Transmembrane | 2157-2180 | Helical | ||||
Sequence: AMTIVMLFVLAGLLTSGMVIFFMS | ||||||
Transmembrane | 2187-2204 | Helical | ||||
Sequence: MSMAMGTMAGCGYLMFLG | ||||||
Transmembrane | 2210-2227 | Helical | ||||
Sequence: HISYIMLIFFVLMVVVVP | ||||||
Transmembrane | 2239-2256 | Helical | ||||
Sequence: QVAYLIIGILTLVSVVAA | ||||||
Transmembrane | 2293-2314 | Helical | ||||
Sequence: GAAWTVYVGIVTMLSPMLHHWI |
Keywords
- Cellular component
PTM/Processing
Features
Showing features for disulfide bond.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Disulfide bond | 288↔315 | |||||
Sequence: CIGITDRDFIEGVHGGTWVSATLEQDKC | ||||||
Disulfide bond | 345↔401 | |||||
Sequence: CYSAVLTHVKVNDKCPSTGEAHLAEENEGDNACKRTYSDRGWGNGCGLFGKGSIVAC | ||||||
Disulfide bond | 359↔390 | |||||
Sequence: CPSTGEAHLAEENEGDNACKRTYSDRGWGNGC | ||||||
Disulfide bond | 377↔406 | |||||
Sequence: CKRTYSDRGWGNGCGLFGKGSIVACAKFTC | ||||||
Disulfide bond | 467↔568 | |||||
Sequence: CQVQTAVDFSNSYIAEMEKESWIVDRQWAQDLTLPWQSGSGGVWREMHHLVEFEPPHAATIKVLALGNQEGSLKTALTGAMRVTKDTNGSNLYKLHGGHVSC | ||||||
Disulfide bond | 585↔615 | |||||
Sequence: CTDKMSFVKNPTDTGHGTAVMQVKVPKGAPC |
Keywords
- PTM
Interaction
Subunit
Forms a heterodimer with serine protease NS3 (By similarity).
May form homooligomers
May form homooligomers
Forms heterodimers with envelope protein E in the endoplasmic reticulum and Golgi.
Homodimer; in the endoplasmic reticulum and Golgi (By similarity).
Interacts with protein prM (By similarity).
Interacts with non-structural protein 1
Interacts with protein prM (By similarity).
Interacts with non-structural protein 1
Interacts with serine protease NS3.
Structure
Family & Domains
Features
Showing features for domain, region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 1355-1484 | Flavivirus NS2B | ||||
Sequence: SIPVNEALAAAGLVGVLAGLAFQEMENFLGPVAVGGILMMLVSVAGRVDGLELRKLGEVSWEEEAEISGSSARYDVALSEQGEFKLLSEEKVPWDQIVMTSLALVGAAIHPFALMLVLAGWLLHVKGARR | ||||||
Domain | 1485-1665 | Peptidase S7 | ||||
Sequence: SGDVLWDIPAPTIVEECEHLEDGIYGIFQSTFLGASQRGVGVAQGGVFHTMWHVTRGAFLVRNGKKLVPTWASVKEDLVAYGGSWKLDGRWDGEEEVQLIAAAPGKNVVNVQTKPSLFKVRNGGEIGAVALDYPSGTSGSPIVNRNGEVIGLYGNGILVGDNSFVSAISQTEAKEEGKEEL | ||||||
Domain | 1669-1825 | Helicase ATP-binding | ||||
Sequence: PTMLKKGMTTILDFHPGAGKTRRFLPQILAECARRRLRTLVLAPTRVVLSEMKEAFHGLDVKFHTQAFSAHGSGKEVIDAMCHATLTYRMLEPTRVVNWEVIIMDEAHFLDPASIAARGWAAHRARANESATILMTATPPGTSDEFPHSNGEIEDVQ | ||||||
Domain | 1820-1997 | Helicase C-terminal | ||||
Sequence: EIEDVQTDIPSEPWNTGHDWILADKRPTAWFLPSIRAANVMAASLRKAGKSVVVLNRKTFEKEYPTIKQKKPDFILATDIAEMGANLCVERVLDCRTAFKPVLVDEGRKVAIKGPLRISASSAAQRRGRIGRNPNRDGDSYYYSEPTSEDNAHHVCWLEASMLLDNMEVRGGMVAPLY | ||||||
Region | 1942-1961 | Disordered | ||||
Sequence: AAQRRGRIGRNPNRDGDSYY | ||||||
Domain | 2507-2771 | MRNA cap 0-1 NS5-type MT | ||||
Sequence: GRANGKTLGEVWKRELNLLDKQQFELYKRTDIVEVDRETARRHLAEGKVDTGVAVSRGTAKLRWFHERGYVKLEGRVTDLGCGRGGWCYYAAAQKEVSGVKGFTLGKEGHEKPMNVQSLGWNIITFKDKTDIHRLEPVKCDTLLCDIGESSPSSVTEGERTMRVLDTVEKWLGCGVESFCVKVLAPYMPDVLEKLELLQRRFGGTVIRNPLSRNSTHEMYYVSGARSNITFTVNQTSRLLMRRMRRPTGKVTLEADVILPIGTRS | ||||||
Domain | 3035-3187 | RdRp catalytic | ||||
Sequence: GGFYADDTAGWDTRITEADLDDEQEILNYMSPHHRKLALAVMEMTYKNKVVKVLRPAPGGKAYMDVISRRDQRGSGQVVTYALNTITNLKVQLIRMAEAEMVVHHQHVQDCDDTVLTKLEAWLAEHGCDRLKRMAVSGDDCVVRPIDDRFGLA |
Keywords
- Domain
Family and domain databases
Sequence
- Sequence statusComplete
- Length3,411
- Mass (Da)378,618
- Last updated2022-01-19 v1
- Checksum148B607E9A048B88