Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Genome polyprotein

Gene
N/A
Organism
West Nile virus (WNV)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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 (By similarity). During virus entry, may induce genome penetration into the host cytoplasm after hemifusion induced by the surface proteins (By similarity). Can migrate to the cell nucleus where it modulates host functions (By similarity). Overcomes the anti-viral effects of host EXOC1 by sequestering and degrading the latter through the proteasome degradation pathway (PubMed:23522008).By similarity1 Publication
Capsid protein C: Inhibits RNA silencing by interfering with host Dicer.By similarity
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.By similarity
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.By similarity
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.By similarity
Envelope protein E: Binds to host cell surface receptor and mediates fusion between viral and cellular membranes (PubMed:15367621). Envelope protein is synthesized in the endoplasmic reticulum in the form of heterodimer with protein prM (By similarity). They play a role in virion budding in the ER, and the newly formed immature particule is covered with 60 spikes composed of heterodimer between precursor prM and envelope protein E (By similarity). The virion is transported to the Golgi apparatus where the low pH causes dissociation of PrM-E heterodimers and formation of E homodimers (By similarity). prM-E cleavage is inefficient, and many virions are only partially matured (By similarity). These uncleaved prM would play a role in immune evasion (By similarity).By similarity
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).By similarity
Non-structural protein 2A: Component of the viral RNA replication complex that functions in virion assembly and antagonizes the host alpha/beta interferon antiviral response.By similarity
Serine protease subunit NS2B: Required cofactor for the serine protease function of NS3. May have membrane-destabilizing activity and form viroporins (By similarity).PROSITE-ProRule annotationBy similarity
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.PROSITE-ProRule annotation
Non-structural protein 4A: Regulates the ATPase activity of the NS3 helicase activity. NS4A allows NS3 helicase to conserve energy during unwinding.By similarity
Peptide 2k: Functions as a signal peptide for NS4B and is required for the interferon antagonism activity of the latter.By similarity
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. Inhibits STAT2 translocation in the nucleus after IFN-alpha treatment.By similarity
RNA-directed RNA polymerase NS5: Replicates the viral (+) and (-) RNA genome, and performs the capping of genomes in the cytoplasm (PubMed:17267492). NS5 methylates viral RNA cap at guanine N-7 and ribose 2'-O positions (PubMed:17267492). 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 (By similarity). Inhibits host TYK2 and STAT2 phosphorylation, thereby preventing activation of JAK-STAT signaling pathway (By similarity).By similarity1 Publication

Catalytic activityi

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.
Nucleoside triphosphate + RNA(n) = diphosphate + RNA(n+1).PROSITE-ProRule annotation
NTP + H2O = NDP + phosphate.
ATP + H2O = ADP + phosphate.By similarity
S-adenosyl-L-methionine + G(5')pppR-RNA = S-adenosyl-L-homocysteine + m7G(5')pppR-RNA.PROSITE-ProRule annotation
S-adenosyl-L-methionine + a 5'-(N7-methyl 5'-triphosphoguanosine)-(purine-ribonucleotide)-[mRNA] = S-adenosyl-L-homocysteine + a 5'-(N7-methyl 5'-triphosphoguanosine)-(2'-O-methyl-purine-ribonucleotide)-[mRNA].PROSITE-ProRule annotation

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei1552Charge relay system; for serine protease NS3 activityPROSITE-ProRule annotation1
Active sitei1576Charge relay system; for serine protease NS3 activityPROSITE-ProRule annotation1
Active sitei1636Charge relay system; for serine protease NS3 activityPROSITE-ProRule annotation1
Sitei1959Involved in NS3 ATPase and RTPase activitiesBy similarity1
Sitei1962Involved in NS3 ATPase and RTPase activitiesBy similarity1
Binding sitei2538mRNA capPROSITE-ProRule annotation1
Binding sitei2541mRNA cap; via carbonyl oxygenPROSITE-ProRule annotation1
Binding sitei2542mRNA capPROSITE-ProRule annotation1
Binding sitei2544mRNA cap; via carbonyl oxygenPROSITE-ProRule annotation1
Sitei2549mRNA cap binding1 Publication1
Binding sitei2553mRNA capPROSITE-ProRule annotation1
Binding sitei2581S-adenosyl-L-methioninePROSITE-ProRule annotation1
Active sitei2586For 2'-O-MTase activityBy similarity1
Sitei2586Essential for 2'-O-methyltransferase activity1
Binding sitei2611S-adenosyl-L-methionine; via carbonyl oxygenPROSITE-ProRule annotation1
Binding sitei2612S-adenosyl-L-methionine; via carbonyl oxygenPROSITE-ProRule annotation1
Binding sitei2629S-adenosyl-L-methioninePROSITE-ProRule annotation1
Binding sitei2630S-adenosyl-L-methionine; via carbonyl oxygenPROSITE-ProRule annotation1
Binding sitei2656S-adenosyl-L-methioninePROSITE-ProRule annotation1
Binding sitei2657S-adenosyl-L-methionine; via carbonyl oxygenPROSITE-ProRule annotation1
Active sitei2671For 2'-O-MTase activityBy similarity1
Sitei2671Essential for 2'-O-methyltransferase and N-7 methyltransferase activity1
Sitei2672S-adenosyl-L-methionine bindingPROSITE-ProRule annotation1
Binding sitei2675mRNA capPROSITE-ProRule annotation1
Active sitei2707For 2'-O-MTase activityBy similarity1
Sitei2707Essential for 2'-O-methyltransferase activity1
Binding sitei2738mRNA capPROSITE-ProRule annotation1
Binding sitei2740mRNA capPROSITE-ProRule annotation1
Active sitei2743For 2'-O-MTase activityBy similarity1
Sitei2743Essential for 2'-O-methyltransferase activity1
Binding sitei2745S-adenosyl-L-methioninePROSITE-ProRule annotation1
Metal bindingi2965Zinc 1By similarity1
Metal bindingi2969Zinc 1; via tele nitrogenBy similarity1
Metal bindingi2974Zinc 1By similarity1
Metal bindingi2977Zinc 1By similarity1
Metal bindingi3242Zinc 2; via tele nitrogenBy similarity1
Metal bindingi3258Zinc 2By similarity1
Metal bindingi3377Zinc 2By similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi1695 – 1702ATPPROSITE-ProRule annotation8

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • ATP-dependent helicase activity Source: InterPro
  • DNA/DNA annealing activity Source: CAFA
  • DNA binding Source: CAFA
  • metal ion binding Source: UniProtKB-KW
  • mRNA (guanine-N7-)-methyltransferase activity Source: UniProtKB-EC
  • mRNA (nucleoside-2'-O-)-methyltransferase activity Source: UniProtKB
  • peptidase activity Source: CACAO
  • protein dimerization activity Source: InterPro
  • RNA binding Source: CAFA
  • RNA-directed 5'-3' RNA polymerase activity Source: UniProtKB-KW
  • RNA helicase activity Source: InterPro
  • RNA strand annealing activity Source: CAFA
  • serine-type endopeptidase activity Source: InterPro
  • serine-type exopeptidase activity Source: InterPro
  • structural molecule activity Source: InterPro

GO - Biological processi

Keywordsi

Molecular functionHelicase, Hydrolase, Methyltransferase, Nucleotidyltransferase, Protease, RNA-binding, RNA-directed RNA polymerase, Serine protease, Suppressor of RNA silencing, Transferase
Biological processActivation of host autophagy by virus, Clathrin-mediated endocytosis of virus by host, Fusion of virus membrane with host endosomal membrane, Fusion of virus membrane with host membrane, Host-virus interaction, Inhibition of host innate immune response by virus, Inhibition of host interferon signaling pathway by virus, Inhibition of host JAK1 by virus, Inhibition of host STAT1 by virus, Inhibition of host STAT2 by virus, Inhibition of host TYK2 by virus, mRNA capping, mRNA processing, Transcription, Transcription regulation, Viral attachment to host cell, Viral immunoevasion, Viral penetration into host cytoplasm, Viral RNA replication, Virus endocytosis by host, Virus entry into host cell
LigandATP-binding, Metal-binding, Nucleotide-binding, S-adenosyl-L-methionine, Zinc

Enzyme and pathway databases

BRENDAi2.7.7.48. 6687.
3.4.21.91. 6687.

Protein family/group databases

MEROPSiS07.003.

Names & Taxonomyi

Protein namesi
Recommended name:
Genome polyprotein
Cleaved into the following 13 chains:
Alternative name(s):
Core protein
Alternative name(s):
Matrix protein
Alternative name(s):
Flavivirin protease NS2B regulatory subunit
Non-structural protein 2B
Serine protease NS3 (EC:3.4.21.91, EC:3.6.1.15By similarity, EC:3.6.4.13By similarity)
Alternative name(s):
Flavivirin protease NS3 catalytic subunit
Non-structural protein 3
RNA-directed RNA polymerase NS5 (EC:2.1.1.56PROSITE-ProRule annotation, EC:2.1.1.57PROSITE-ProRule annotation, EC:2.7.7.48PROSITE-ProRule annotation)
Alternative name(s):
NS5
OrganismiWest Nile virus (WNV)
Taxonomic identifieri11082 [NCBI]
Taxonomic lineageiVirusesssRNA virusesssRNA positive-strand viruses, no DNA stageFlaviviridaeFlavivirusJapanese encephalitis virus group
Virus hostiAedes [TaxID: 7158]
Amblyomma variegatum (Tropical bont tick) [TaxID: 34610]
Aves [TaxID: 8782]
Culex [TaxID: 53527]
Homo sapiens (Human) [TaxID: 9606]
Hyalomma marginatum [TaxID: 34627]
Mansonia uniformis [TaxID: 308735]
Mimomyia [TaxID: 308737]
Rhipicephalus [TaxID: 34630]
Proteomesi
  • UP000008600 Componenti: Genome

Subcellular locationi

Capsid protein C:
  • Virion By similarity
  • Host nucleus By similarity
  • Host cytoplasm 1 Publication
  • host perinuclear region 1 Publication
Peptide pr:
  • Secreted By similarity
Small envelope protein M:
  • Virion membrane By similarity; Multi-pass membrane protein By similarity
  • Host endoplasmic reticulum membrane By similarity; Multi-pass membrane protein Sequence analysis
  • Note: ER membrane retention is mediated by the transmembrane domains.By similarity
Envelope protein E:
  • Virion membrane Curated; Multi-pass membrane protein By similarity
  • Host endoplasmic reticulum membrane By similarity; Multi-pass membrane protein Sequence analysis
  • Note: ER membrane retention is mediated by the transmembrane domains.By similarity
Non-structural protein 1:
  • Secreted By similarity
  • Host endoplasmic reticulum membrane ; Peripheral membrane protein ; Lumenal side By similarity
  • Note: Located in RE-derived vesicles hosting the replication complex.By similarity
Non-structural protein 2A:
Serine protease subunit NS2B:
Serine protease NS3:
  • Host endoplasmic reticulum membrane PROSITE-ProRule annotation; Peripheral membrane protein PROSITE-ProRule annotation; Cytoplasmic side PROSITE-ProRule annotation
  • Note: Remains non-covalently associated to serine protease subunit NS2B.PROSITE-ProRule annotation
Non-structural protein 4A:
  • Host endoplasmic reticulum membrane By similarity; Multi-pass membrane protein By similarity
  • Note: Located in RE-associated vesicles hosting the replication complex.By similarity
Non-structural protein 4B:
  • Host endoplasmic reticulum membrane By similarity; Multi-pass membrane protein By similarity
  • Note: Located in RE-derived vesicles hosting the replication complex.By similarity
RNA-directed RNA polymerase NS5:
  • Host endoplasmic reticulum membrane ; Peripheral membrane protein ; Cytoplasmic side By similarity
  • Host nucleus 1 Publication
  • Note: Located in RE-associated vesicles hosting the replication complex. NS5 protein is mainly localized in the nucleus rather than in ER vesicles.By similarity

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini2 – 105CytoplasmicSequence analysisAdd BLAST104
Transmembranei106 – 126HelicalSequence analysisAdd BLAST21
Topological domaini127 – 248ExtracellularSequence analysisAdd BLAST122
Transmembranei249 – 269HelicalSequence analysisAdd BLAST21
Topological domaini270 – 275CytoplasmicSequence analysis6
Transmembranei276 – 290HelicalCuratedAdd BLAST15
Topological domaini291 – 739ExtracellularSequence analysisAdd BLAST449
Transmembranei740 – 760HelicalSequence analysisAdd BLAST21
Topological domaini761 – 766CytoplasmicSequence analysis6
Transmembranei767 – 787HelicalSequence analysisAdd BLAST21
Topological domaini788 – 1212ExtracellularSequence analysisAdd BLAST425
Transmembranei1213 – 1233HelicalSequence analysisAdd BLAST21
Topological domaini1234 – 1243CytoplasmicSequence analysis10
Transmembranei1244 – 1264HelicalSequence analysisAdd BLAST21
Topological domaini1265 – 1278LumenalSequence analysisAdd BLAST14
Transmembranei1279 – 1299HelicalSequence analysisAdd BLAST21
Topological domaini1300 – 1307CytoplasmicSequence analysis8
Transmembranei1308 – 1328HelicalSequence analysisAdd BLAST21
Topological domaini1329 – 1340LumenalSequence analysisAdd BLAST12
Transmembranei1341 – 1361HelicalSequence analysisAdd BLAST21
Topological domaini1362 – 1371CytoplasmicSequence analysis10
Transmembranei1372 – 1392HelicalSequence analysisAdd BLAST21
Topological domaini1393 – 1395LumenalSequence analysis3
Transmembranei1396 – 1416HelicalSequence analysisAdd BLAST21
Topological domaini1417 – 1473CytoplasmicSequence analysisAdd BLAST57
Intramembranei1474 – 1494HelicalSequence analysisAdd BLAST21
Topological domaini1495 – 2170CytoplasmicSequence analysisAdd BLAST676
Transmembranei2171 – 2191HelicalSequence analysisAdd BLAST21
Topological domaini2192 – 2196LumenalSequence analysis5
Intramembranei2197 – 2217HelicalSequence analysisAdd BLAST21
Topological domaini2218LumenalSequence analysis1
Transmembranei2219 – 2239HelicalSequence analysisAdd BLAST21
Topological domaini2240 – 2254CytoplasmicSequence analysisAdd BLAST15
Transmembranei2255 – 2275Helical; Note=Signal for NS4BSequence analysisAdd BLAST21
Topological domaini2276 – 2309LumenalSequence analysisAdd BLAST34
Intramembranei2310 – 2330HelicalSequence analysisAdd BLAST21
Topological domaini2331 – 2377LumenalSequence analysisAdd BLAST47
Transmembranei2378 – 2398HelicalSequence analysisAdd BLAST21
Topological domaini2399 – 2441CytoplasmicSequence analysisAdd BLAST43
Transmembranei2442 – 2462HelicalSequence analysisAdd BLAST21
Topological domaini2463 – 2467LumenalSequence analysis5
Transmembranei2468 – 2488HelicalSequence analysisAdd BLAST21
Topological domaini2489 – 3430CytoplasmicSequence analysisAdd BLAST942

GO - Cellular componenti

  • cytoplasmic viral factory Source: UniProtKB
  • extracellular region Source: UniProtKB-SubCell
  • host cell endoplasmic reticulum membrane Source: UniProtKB-SubCell
  • host cell nucleus Source: UniProtKB-SubCell
  • host cell perinuclear region of cytoplasm Source: UniProtKB-SubCell
  • integral component of membrane Source: UniProtKB-KW
  • protein-DNA complex Source: CAFA
  • ribonucleoprotein complex Source: CAFA
  • viral capsid Source: UniProtKB-KW
  • viral envelope Source: UniProtKB-KW
  • virion membrane Source: UniProtKB-SubCell

Keywords - Cellular componenti

Capsid protein, Host cytoplasm, Host endoplasmic reticulum, Host membrane, Host nucleus, Membrane, Secreted, Viral envelope protein, Virion

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi14V → A: Loss of interaction between capsid protein C and host EXOC1. 1 Publication1
Mutagenesisi2586K → A: Complete loss of 2'-O-methyltransferase activity. No effect on N-7 methyltransferase activity. 1 Publication1
Mutagenesisi2671D → A: Lethal for the virus. Complete loss of 2'-O and N-7 methyltransferase activies. 1 Publication1
Mutagenesisi2707K → A: Complete loss of 2'-O-methyltransferase activity. No effect on N-7 methyltransferase activity. 1 Publication1
Mutagenesisi2743E → A: Complete loss of 2'-O-methyltransferase activity. No effect on N-7 methyltransferase activity. 1 Publication1

Chemistry databases

ChEMBLiCHEMBL5419.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00004414181 – 3430Genome polyproteinAdd BLAST3430
ChainiPRO_00000377431 – 105Capsid protein C1 PublicationAdd BLAST105
PropeptideiPRO_0000037744106 – 123ER anchor for the capsid protein C, removed in mature form by serine protease NS31 PublicationAdd BLAST18
ChainiPRO_0000405150124 – 290Protein prM1 PublicationAdd BLAST167
ChainiPRO_0000405151124 – 215Peptide pr1 PublicationAdd BLAST92
ChainiPRO_0000037745216 – 290Small envelope protein M1 PublicationAdd BLAST75
ChainiPRO_0000037746291 – 787Envelope protein E1 PublicationAdd BLAST497
ChainiPRO_0000037747788 – 1139Non-structural protein 11 PublicationAdd BLAST352
ChainiPRO_00000377481140 – 1370Non-structural protein 2A1 PublicationAdd BLAST231
ChainiPRO_00000377491371 – 1501Serine protease subunit NS2B1 PublicationAdd BLAST131
ChainiPRO_00000377501502 – 2120Serine protease NS31 PublicationAdd BLAST619
ChainiPRO_00000377512121 – 2246Non-structural protein 4A1 PublicationAdd BLAST126
PeptideiPRO_00004051522247 – 2269Peptide 2k1 PublicationAdd BLAST23
ChainiPRO_00000377522270 – 2525Non-structural protein 4B1 PublicationAdd BLAST256
ChainiPRO_00000377532526 – 3430RNA-directed RNA polymerase NS51 PublicationAdd BLAST905

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi138N-linked (GlcNAc...) asparagine; by hostBy similarity1
Disulfide bondi293 ↔ 3201 Publication
Disulfide bondi350 ↔ 411By similarity
Disulfide bondi350 ↔ 4061 Publication
Disulfide bondi364 ↔ 3951 Publication
Disulfide bondi382 ↔ 4111 Publication
Disulfide bondi382 ↔ 406By similarity
Disulfide bondi476 ↔ 5741 Publication
Disulfide bondi591 ↔ 6221 Publication
Disulfide bondi791 ↔ 802By similarity
Disulfide bondi842 ↔ 930By similarity
Glycosylationi917N-linked (GlcNAc...) asparagine; by hostBy similarity1
Glycosylationi962N-linked (GlcNAc...) asparagine; by hostBy similarity1
Disulfide bondi966 ↔ 1010By similarity
Glycosylationi994N-linked (GlcNAc...) asparagine; by hostBy similarity1
Disulfide bondi1067 ↔ 1116By similarity
Disulfide bondi1078 ↔ 1099By similarity
Disulfide bondi1100 ↔ 1103By similarity
Modified residuei2581PhosphoserineBy similarity1

Post-translational modificationi

Genome polyprotein: Specific enzymatic cleavages in vivo yield mature proteins. Cleavages in the lumen of endoplasmic reticulum are performed by host signal peptidase, whereas cleavages in the cytoplasmic side are performed by serine protease NS3. Signal cleavage at the 2K-4B site requires a prior NS3 protease-mediated cleavage at the 4A-2K site.By similarity1 Publication
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.By similarity
Envelope protein E: Not N-glycosylated.1 Publication
Non-structural protein 1: N-glycosylated. The excreted form is glycosylated and this is required for efficient secretion of the protein from infected cells.By similarity
RNA-directed RNA polymerase NS5: Phosphorylated on serines residues. This phosphorylation may trigger NS5 nuclear localization.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei105 – 106Cleavage; by viral protease NS31 Publication2
Sitei123 – 124Cleavage; by host signal peptidase1 Publication2
Sitei215 – 216Cleavage; by host furin1 Publication2
Sitei290 – 291Cleavage; by host signal peptidase1 Publication2
Sitei787 – 788Cleavage; by host signal peptidase1 Publication2
Sitei1139 – 1140Cleavage; by host1 Publication2
Sitei1370 – 1371Cleavage; by viral protease NS31 Publication2
Sitei1501 – 1502Cleavage; by autolysis1 Publication2
Sitei2120 – 2121Cleavage; by autolysis1 Publication2
Sitei2246 – 2247Cleavage; by viral protease NS31 Publication2
Sitei2269 – 2270Cleavage; by host signal peptidase1 Publication2
Sitei2525 – 2526Cleavage; by viral protease NS31 Publication2

Keywords - PTMi

Cleavage on pair of basic residues, Disulfide bond, Glycoprotein, Phosphoprotein

Interactioni

Subunit structurei

Capsid protein C: Homodimer (By similarity). Interacts (via N-terminus) with host EXOC1 (via C-terminus) (PubMed:19889084, PubMed:23522008); this interaction results in EXOC1 degradation through the proteasome degradation pathway (PubMed:23522008). Protein prM: Forms heterodimers with envelope protein E in the endoplasmic reticulum and Golgi (By similarity). Envelope protein E: Homodimer; in the endoplasmic reticulum and Golgi (By similarity). Non-structural protein 1: Homodimer; Homohexamer when secreted (By similarity). NS1 interacts with NS4B (By similarity). Interacts with host complement protein CFH; this interaction leads to the degradation of C3 (By similarity). Non-structural protein 2A: Interacts (via N-terminus) with serine protease NS3 (By similarity). Non-structural protein 2B: Forms a heterodimer with serine protease NS3. May form homooligomers (By similarity). Serine protease NS3: Forms a heterodimer with NS2B. Interacts with NS4B. Interacts with unphosphorylated RNA-directed RNA polymerase NS5; this interaction stimulates RNA-directed RNA polymerase NS5 guanylyltransferase activity (By similarity). Non-structural protein 4B: Interacts with serine protease NS3. Interacts with NS1 (By similarity). RNA-directed RNA polymerase NS5: Homodimer (By similarity). Interacts with host STAT2; this interaction inhibits the phosphorylation of the latter, and, when all viral proteins are present (polyprotein), targets STAT2 for degradation (By similarity).By similarity2 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

Protein-protein interaction databases

IntActiP06935. 4 interactors.

Chemistry databases

BindingDBiP06935.

Structurei

Secondary structure

13430
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi595 – 603Combined sources9
Beta strandi605 – 607Combined sources3
Beta strandi609 – 615Combined sources7
Beta strandi621 – 623Combined sources3
Beta strandi626 – 631Combined sources6
Beta strandi634 – 637Combined sources4
Beta strandi639 – 643Combined sources5
Beta strandi657 – 662Combined sources6
Beta strandi665 – 673Combined sources9
Beta strandi679 – 685Combined sources7
Beta strandi1422 – 1428Combined sources7
Helixi1434 – 1439Combined sources6
Beta strandi1440 – 1443Combined sources4
Beta strandi1444 – 1449Combined sources6
Beta strandi1451 – 1453Combined sources3
Beta strandi1455 – 1457Combined sources3
Beta strandi1503 – 1505Combined sources3
Beta strandi1521 – 1532Combined sources12
Beta strandi1534 – 1543Combined sources10
Beta strandi1546 – 1549Combined sources4
Helixi1551 – 1554Combined sources4
Beta strandi1559 – 1561Combined sources3
Beta strandi1564 – 1566Combined sources3
Beta strandi1568 – 1572Combined sources5
Turni1573 – 1576Combined sources4
Beta strandi1577 – 1583Combined sources7
Beta strandi1592 – 1594Combined sources3
Beta strandi1596 – 1600Combined sources5
Beta strandi1608 – 1612Combined sources5
Beta strandi1615 – 1618Combined sources4
Beta strandi1623 – 1627Combined sources5
Helixi1633 – 1635Combined sources3
Beta strandi1639 – 1641Combined sources3
Beta strandi1647 – 1650Combined sources4
Beta strandi1654 – 1656Combined sources3
Beta strandi1662 – 1665Combined sources4
Beta strandi1672 – 1674Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2FP7X-ray1.68A1420-1466[»]
B1517-1688[»]
2G05model-D1675-2120[»]
2G2Gmodel-D1675-2120[»]
2GGVX-ray1.80A1419-1525[»]
B1503-1679[»]
2IJOX-ray2.30A1419-1482[»]
B1502-1685[»]
2P5PX-ray2.80A/B/C585-701[»]
2YOLX-ray3.20A1420-1465[»]
A1502-1671[»]
3E90X-ray2.45A/C1420-1463[»]
B/D1502-1685[»]
3I50X-ray3.00E291-688[»]
5IDKX-ray1.50A/B/C1420-1465[»]
DisProtiDP00673.
ProteinModelPortaliP06935.
SMRiP06935.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP06935.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini1502 – 1679Peptidase S7PROSITE-ProRule annotationAdd BLAST178
Domaini1682 – 1838Helicase ATP-bindingPROSITE-ProRule annotationAdd BLAST157
Domaini1849 – 2014Helicase C-terminalPROSITE-ProRule annotationAdd BLAST166
Domaini2526 – 2791mRNA cap 0-1 NS5-type MTPROSITE-ProRule annotationAdd BLAST266
Domaini3055 – 3207RdRp catalyticPROSITE-ProRule annotationAdd BLAST153

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni2 – 15Interaction with host EXOC11 PublicationAdd BLAST14
Regioni37 – 72Hydrophobic; homodimerization of capsid protein CBy similarityAdd BLAST36
Regioni388 – 401Fusion peptideBy similarityAdd BLAST14
Regioni1424 – 1463Interacts with and activates NS3 proteasePROSITE-ProRule annotationAdd BLAST40
Regioni1686 – 1689Important for RNA-bindingBy similarity4
Regioni2165 – 2169Regulates the ATPase activity of NS3 helicaseBy similarity5

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi1786 – 1789DEAH boxPROSITE-ProRule annotation4

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi281 – 284Poly-Leu4
Compositional biasi2675 – 2678Poly-Ser4

Domaini

The transmembrane domains of the small envelope protein M and envelope protein E contain an endoplasmic reticulum retention signal.By similarity

Sequence similaritiesi

In the N-terminal section; belongs to the class I-like SAM-binding methyltransferase superfamily. mRNA cap 0-1 NS5-type methyltransferase family.PROSITE-ProRule annotation

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

OrthoDBiVOG09000016.

Family and domain databases

CDDicd12149. Flavi_E_C. 1 hit.
Gene3Di2.60.40.350. 1 hit.
3.30.387.10. 1 hit.
3.30.67.10. 1 hit.
InterProiView protein in InterPro
IPR011492. DEAD_Flavivir.
IPR000069. Env_glycoprot_M_flavivir.
IPR013755. Flav_gly_cen_dom_subdom1.
IPR001122. Flavi_capsidC.
IPR037172. Flavi_capsidC_sf.
IPR027287. Flavi_E_Ig-like.
IPR026470. Flavi_E_Stem/Anchor_dom.
IPR001157. Flavi_NS1.
IPR000752. Flavi_NS2A.
IPR000487. Flavi_NS2B.
IPR000404. Flavi_NS4A.
IPR001528. Flavi_NS4B.
IPR002535. Flavi_propep.
IPR000336. Flavivir/Alphavir_Ig-like.
IPR001850. Flavivirus_NS3_S7.
IPR014412. Gen_Poly_FLV.
IPR011998. Glycoprot_cen/dimer.
IPR036253. Glycoprot_cen/dimer_sf.
IPR013756. GlyE_cen_dom_subdom2.
IPR014001. Helicase_ATP-bd.
IPR001650. Helicase_C.
IPR014756. Ig_E-set.
IPR026490. mRNA_cap_0/1_MeTrfase.
IPR027417. P-loop_NTPase.
IPR009003. Peptidase_S1_PA.
IPR000208. RNA-dir_pol_flavivirus.
IPR007094. RNA-dir_pol_PSvirus.
IPR002877. rRNA_MeTrfase_FtsJ_dom.
IPR029063. SAM-dependent_MTases.
PfamiView protein in Pfam
PF01003. Flavi_capsid. 1 hit.
PF07652. Flavi_DEAD. 1 hit.
PF02832. Flavi_glycop_C. 1 hit.
PF00869. Flavi_glycoprot. 1 hit.
PF01004. Flavi_M. 1 hit.
PF00948. Flavi_NS1. 1 hit.
PF01005. Flavi_NS2A. 1 hit.
PF01002. Flavi_NS2B. 1 hit.
PF01350. Flavi_NS4A. 1 hit.
PF01349. Flavi_NS4B. 1 hit.
PF00972. Flavi_NS5. 1 hit.
PF01570. Flavi_propep. 1 hit.
PF01728. FtsJ. 1 hit.
PF00949. Peptidase_S7. 1 hit.
PIRSFiPIRSF003817. Gen_Poly_FLV. 1 hit.
SMARTiView protein in SMART
SM00487. DEXDc. 1 hit.
SM00490. HELICc. 1 hit.
SUPFAMiSSF101257. SSF101257. 1 hit.
SSF50494. SSF50494. 1 hit.
SSF52540. SSF52540. 2 hits.
SSF53335. SSF53335. 1 hit.
SSF56983. SSF56983. 1 hit.
SSF81296. SSF81296. 1 hit.
TIGRFAMsiTIGR04240. flavi_E_stem. 1 hit.
PROSITEiView protein in PROSITE
PS51527. FLAVIVIRUS_NS2B. 1 hit.
PS51528. FLAVIVIRUS_NS3PRO. 1 hit.
PS51192. HELICASE_ATP_BIND_1. 1 hit.
PS51194. HELICASE_CTER. 1 hit.
PS50507. RDRP_SSRNA_POS. 1 hit.
PS51591. RNA_CAP01_NS5_MT. 1 hit.

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P06935-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSKKPGGPGK NRAVNMLKRG MPRGLSLIGL KRAMLSLIDG KGPIRFVLAL
60 70 80 90 100
LAFFRFTAIA PTRAVLDRWR GVNKQTAMKH LLSFKKELGT LTSAINRRST
110 120 130 140 150
KQKKRGGTAG FTILLGLIAC AGAVTLSNFQ GKVMMTVNAT DVTDVITIPT
160 170 180 190 200
AAGKNLCIVR AMDVGYLCED TITYECPVLA AGNDPEDIDC WCTKSSVYVR
210 220 230 240 250
YGRCTKTRHS RRSRRSLTVQ THGESTLANK KGAWLDSTKA TRYLVKTESW
260 270 280 290 300
ILRNPGYALV AAVIGWMLGS NTMQRVVFAI LLLLVAPAYS FNCLGMSNRD
310 320 330 340 350
FLEGVSGATW VDLVLEGDSC VTIMSKDKPT IDVKMMNMEA ANLADVRSYC
360 370 380 390 400
YLASVSDLST RAACPTMGEA HNEKRADPAF VCKQGVVDRG WGNGCGLFGK
410 420 430 440 450
GSIDTCAKFA CTTKATGWII QKENIKYEVA IFVHGPTTVE SHGKIGATQA
460 470 480 490 500
GRFSITPSAP SYTLKLGEYG EVTVDCEPRS GIDTSAYYVM SVGEKSFLVH
510 520 530 540 550
REWFMDLNLP WSSAGSTTWR NRETLMEFEE PHATKQSVVA LGSQEGALHQ
560 570 580 590 600
ALAGAIPVEF SSNTVKLTSG HLKCRVKMEK LQLKGTTYGV CSKAFKFART
610 620 630 640 650
PADTGHGTVV LELQYTGTDG PCKVPISSVA SLNDLTPVGR LVTVNPFVSV
660 670 680 690 700
ATANSKVLIE LEPPFGDSYI VVGRGEQQIN HHWHKSGSSI GKAFTTTLRG
710 720 730 740 750
AQRLAALGDT AWDFGSVGGV FTSVGKAIHQ VFGGAFRSLF GGMSWITQGL
760 770 780 790 800
LGALLLWMGI NARDRSIAMT FLAVGGVLLF LSVNVHADTG CAIDIGRQEL
810 820 830 840 850
RCGSGVFIHN DVEAWMDRYK FYPETPQGLA KIIQKAHAEG VCGLRSVSRL
860 870 880 890 900
EHQMWEAIKD ELNTLLKENG VDLSVVVEKQ NGMYKAAPKR LAATTEKLEM
910 920 930 940 950
GWKAWGKSII FAPELANNTF VIDGPETEEC PTANRAWNSM EVEDFGFGLT
960 970 980 990 1000
STRMFLRIRE TNTTECDSKI IGTAVKNNMA VHSDLSYWIE SGLNDTWKLE
1010 1020 1030 1040 1050
RAVLGEVKSC TWPETHTLWG DGVLESDLII PITLAGPRSN HNRRPGYKTQ
1060 1070 1080 1090 1100
NQGPWDEGRV EIDFDYCPGT TVTISDSCEH RGPAARTTTE SGKLITDWCC
1110 1120 1130 1140 1150
RSCTLPPLRF QTENGCWYGM EIRPTRHDEK TLVQSRVNAY NADMIDPFQL
1160 1170 1180 1190 1200
GLMVVFLATQ EVLRKRWTAK ISIPAIMLAL LVLVFGGITY TDVLRYVILV
1210 1220 1230 1240 1250
GAAFAEANSG GDVVHLALMA TFKIQPVFLV ASFLKARWTN QESILLMLAA
1260 1270 1280 1290 1300
AFFQMAYYDA KNVLSWEVPD VLNSLSVAWM ILRAISFTNT SNVVVPLLAL
1310 1320 1330 1340 1350
LTPGLKCLNL DVYRILLLMV GVGSLIKEKR SSAAKKKGAC LICLALASTG
1360 1370 1380 1390 1400
VFNPMILAAG LMACDPNRKR GWPATEVMTA VGLMFAIVGG LAELDIDSMA
1410 1420 1430 1440 1450
IPMTIAGLMF AAFVISGKST DMWIERTADI TWESDAEITG SSERVDVRLD
1460 1470 1480 1490 1500
DDGNFQLMND PGAPWKIWML RMACLAISAY TPWAILPSVI GFWITLQYTK
1510 1520 1530 1540 1550
RGGVLWDTPS PKEYKKGDTT TGVYRIMTRG LLGSYQAGAG VMVEGVFHTL
1560 1570 1580 1590 1600
WHTTKGAALM SGEGRLDPYW GSVKEDRLCY GGPWKLQHKW NGHDEVQMIV
1610 1620 1630 1640 1650
VEPGKNVKNV QTKPGVFKTP EGEIGAVTLD YPTGTSGSPI VDKNGDVIGL
1660 1670 1680 1690 1700
YGNGVIMPNG SYISAIVQGE RMEEPAPAGF EPEMLRKKQI TVLDLHPGAG
1710 1720 1730 1740 1750
KTRKILPQII KEAINKRLRT AVLAPTRVVA AEMSEALRGL PIRYQTSAVH
1760 1770 1780 1790 1800
REHSGNEIVD VMCHATLTHR LMSPHRVPNY NLFIMDEAHF TDPASIAARG
1810 1820 1830 1840 1850
YIATKVELGE AAAIFMTATP PGTSDPFPES NAPISDMQTE IPDRAWNTGY
1860 1870 1880 1890 1900
EWITEYVGKT VWFVPSVKMG NEIALCLQRA GKKVIQLNRK SYETEYPKCK
1910 1920 1930 1940 1950
NDDWDFVITT DISEMGANFK ASRVIDSRKS VKPTIIEEGD GRVILGEPSA
1960 1970 1980 1990 2000
ITAASAAQRR GRIGRNPSQV GDEYCYGGHT NEDDSNFAHW TEARIMLDNI
2010 2020 2030 2040 2050
NMPNGLVAQL YQPEREKVYT MDGEYRLRGE ERKNFLEFLR TADLPVWLAY
2060 2070 2080 2090 2100
KVAAAGISYH DRKWCFDGPR TNTILEDNNE VEVITKLGER KILRPRWADA
2110 2120 2130 2140 2150
RVYSDHQALK SFKDFASGKR SQIGLVEVLG RMPEHFMVKT WEALDTMYVV
2160 2170 2180 2190 2200
ATAEKGGRAH RMALEELPDA LQTIVLIALL SVMSLGVFFL LMQRKGIGKI
2210 2220 2230 2240 2250
GLGGVILGAA TFFCWMAEVP GTKIAGMLLL SLLLMIVLIP EPEKQRSQTD
2260 2270 2280 2290 2300
NQLAVFLICV LTLVGAVAAN EMGWLDKTKN DIGSLLGHRP EARETTLGVE
2310 2320 2330 2340 2350
SFLLDLRPAT AWSLYAVTTA VLTPLLKHLI TSDYINTSLT SINVQASALF
2360 2370 2380 2390 2400
TLARGFPFVD VGVSALLLAV GCWGQVTLTV TVTAAALLFC HYAYMVPGWQ
2410 2420 2430 2440 2450
AEAMRSAQRR TAAGIMKNVV VDGIVATDVP ELERTTPVMQ KKVGQIILIL
2460 2470 2480 2490 2500
VSMAAVVVNP SVRTVREAGI LTTAAAVTLW ENGASSVWNA TTAIGLCHIM
2510 2520 2530 2540 2550
RGGWLSCLSI MWTLIKNMEK PGLKRGGAKG RTLGEVWKER LNHMTKEEFT
2560 2570 2580 2590 2600
RYRKEAITEV DRSAAKHARR EGNITGGHPV SRGTAKLRWL VERRFLEPVG
2610 2620 2630 2640 2650
KVVDLGCGRG GWCYYMATQK RVQEVKGYTK GGPGHEEPQL VQSYGWNIVT
2660 2670 2680 2690 2700
MKSGVDVFYR PSEASDTLLC DIGESSSSAE VEEHRTVRVL EMVEDWLHRG
2710 2720 2730 2740 2750
PKEFCIKVLC PYMPKVIEKM ETLQRRYGGG LIRNPLSRNS THEMYWVSHA
2760 2770 2780 2790 2800
SGNIVHSVNM TSQVLLGRME KKTWKGPQFE EDVNLGSGTR AVGKPLLNSD
2810 2820 2830 2840 2850
TSKIKNRIER LKKEYSSTWH QDANHPYRTW NYHGSYEVKP TGSASSLVNG
2860 2870 2880 2890 2900
VVRLLSKPWD TITNVTTMAM TDTTPFGQQR VFKEKVDTKA PEPPEGVKYV
2910 2920 2930 2940 2950
LNETTNWLWA FLARDKKPRM CSREEFIGKV NSNAALGAMF EEQNQWKNAR
2960 2970 2980 2990 3000
EAVEDPKFWE MVDEEREAHL RGECNTCIYN MMGKREKKPG EFGKAKGSRA
3010 3020 3030 3040 3050
IWFMWLGARF LEFEALGFLN EDHWLGRKNS GGGVEGLGLQ KLGYILKEVG
3060 3070 3080 3090 3100
TKPGGKVYAD DTAGWDTRIT KADLENEAKV LELLDGEHRR LARSIIELTY
3110 3120 3130 3140 3150
RHKVVKVMRP AADGKTVMDV ISREDQRGSG QVVTYALNTF TNLAVQLVRM
3160 3170 3180 3190 3200
MEGEGVIGPD DVEKLGKGKG PKVRTWLFEN GEERLSRMAV SGDDCVVKPL
3210 3220 3230 3240 3250
DDRFATSLHF LNAMSKVRKD IQEWKPSTGW YDWQQVPFCS NHFTELIMKD
3260 3270 3280 3290 3300
GRTLVVPCRG QDELIGRARI SPGAGWNVRD TACLAKSYAQ MWLLLYFHRR
3310 3320 3330 3340 3350
DLRLMANAIC SAVPANWVPT GRTTWSIHAK GEWMTTEDML AVWNRVWIEE
3360 3370 3380 3390 3400
NEWMEDKTPV ERWSDVPYSG KREDIWCGSL IGTRTRATWA ENIHVAINQV
3410 3420 3430
RSVIGEEKYV DYMSSLRRYE DTIVVEDTVL
Length:3,430
Mass (Da):380,110
Last modified:October 24, 2003 - v2
Checksum:i42D71B7CB12DC45B
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M12294 Genomic RNA. Translation: AAA48498.2.
PIRiA25256. GNWVWV.
RefSeqiNP_041724.2. NC_001563.2.

Genome annotation databases

GeneIDi912267.
KEGGivg:912267.

Similar proteinsi

Entry informationi

Entry nameiPOLG_WNV
AccessioniPrimary (citable) accession number: P06935
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 1, 1988
Last sequence update: October 24, 2003
Last modified: October 25, 2017
This is version 174 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Multifunctional enzyme

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families