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Protein

Genome polyprotein

Gene

pol

Organism
Dengue virus type 3 (strain Sri Lanka/1266/2000) (DENV-3)
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. 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. Overcomes the anti-viral effects of host EXOC1 by sequestering and degrading the latter through the proteasome degradation pathway.By similarity
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. 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 particule 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.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 1: Disrupts the host endothelial glycocalyx layer of host pulmonary microvascular endothelial cells, inducing degradation of sialic acid and shedding of heparan sulfate proteoglycans. NS1 induces expression of sialidases, heparanase, and activates cathepsin L, which activates heparanase via enzymatic cleavage. These effects are probably linked to the endothelial hyperpermeability observed in severe dengue disease.By similarity
Non-structural protein 2A: Component of the viral RNA replication complex that functions in virion assembly and antagonizes the host immune 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.By similarity
RNA-directed RNA polymerase NS5: 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. Inhibits host TYK2 and STAT2 phosphorylation, thereby preventing activation of JAK-STAT signaling pathway.By similarity

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 annotation1 Publication
NTP + H2O = NDP + phosphate.
ATP + H2O = ADP + phosphate.
S-adenosyl-L-methionine + G(5')pppR-RNA = S-adenosyl-L-homocysteine + m7G(5')pppR-RNA.PROSITE-ProRule annotation1 Publication
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 annotation1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei1524Charge relay system; for serine protease NS3 activityPROSITE-ProRule annotation1
Active sitei1548Charge relay system; for serine protease NS3 activityPROSITE-ProRule annotation1
Active sitei1608Charge relay system; for serine protease NS3 activityPROSITE-ProRule annotation1
Sitei1931Involved in NS3 ATPase and RTPase activitiesBy similarity1
Sitei1934Involved in NS3 ATPase and RTPase activitiesBy similarity1
Binding sitei2504mRNA capPROSITE-ProRule annotation1
Binding sitei2507mRNA cap; via carbonyl oxygenPROSITE-ProRule annotation1
Binding sitei2508mRNA capPROSITE-ProRule annotation1
Binding sitei2510mRNA cap; via carbonyl oxygenPROSITE-ProRule annotation1
Sitei2515mRNA cap bindingPROSITE-ProRule annotation1
Binding sitei2519mRNA capPROSITE-ProRule annotation1
Binding sitei2546S-adenosyl-L-methioninePROSITE-ProRule annotation1
Active sitei2551For 2'-O-MTase activity1 Publication1
Sitei2551Essential for 2'-O-methyltransferase activityPROSITE-ProRule annotation1
Binding sitei2576S-adenosyl-L-methionine; via carbonyl oxygenPROSITE-ProRule annotation1
Binding sitei2577S-adenosyl-L-methionine; via carbonyl oxygenPROSITE-ProRule annotation1
Binding sitei2594S-adenosyl-L-methioninePROSITE-ProRule annotation1
Binding sitei2595S-adenosyl-L-methionine; via carbonyl oxygenPROSITE-ProRule annotation1
Binding sitei2621S-adenosyl-L-methioninePROSITE-ProRule annotation1
Binding sitei2622S-adenosyl-L-methionine; via carbonyl oxygenPROSITE-ProRule annotation1
Active sitei2636For 2'-O-MTase activity1 Publication1
Sitei2636Essential for 2'-O-methyltransferase and N-7 methyltransferase activityPROSITE-ProRule annotation1
Sitei2637S-adenosyl-L-methionine bindingPROSITE-ProRule annotation1
Binding sitei2640mRNA capPROSITE-ProRule annotation1
Active sitei2670For 2'-O-MTase activity1 Publication1
Sitei2670Essential for 2'-O-methyltransferase activityPROSITE-ProRule annotation1
Binding sitei2701mRNA capPROSITE-ProRule annotation1
Binding sitei2703mRNA capPROSITE-ProRule annotation1
Active sitei2706For 2'-O-MTase activity1 Publication1
Sitei2706Essential for 2'-O-methyltransferase activityPROSITE-ProRule annotation1
Binding sitei2708S-adenosyl-L-methioninePROSITE-ProRule annotation1
Metal bindingi2927Zinc 11 Publication1
Metal bindingi2931Zinc 1; via tele nitrogen1 Publication1
Metal bindingi2936Zinc 11 Publication1
Metal bindingi2939Zinc 11 Publication1
Metal bindingi3202Zinc 2; via tele nitrogen1 Publication1
Metal bindingi3218Zinc 21 Publication1
Metal bindingi3337Zinc 21 Publication1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi1667 – 1674ATPPROSITE-ProRule annotation8

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionHelicase, Hydrolase, Ion channel, Methyltransferase, Nucleotidyltransferase, Protease, RNA-binding, RNA-directed RNA polymerase, Serine protease, Suppressor of RNA silencing, Transferase, Viral ion channel
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 STAT2 by virus, Inhibition of host TYK2 by virus, Ion transport, mRNA capping, mRNA processing, Transcription, Transcription regulation, Transport, 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

BRENDAi3.4.21.91. 9648.

Protein family/group databases

MEROPSiS07.001.

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 annotation1 Publication, EC:2.1.1.57PROSITE-ProRule annotation1 Publication, EC:2.7.7.48PROSITE-ProRule annotation1 Publication)
Alternative name(s):
Non-structural protein 5
Gene namesi
Name:pol
OrganismiDengue virus type 3 (strain Sri Lanka/1266/2000) (DENV-3)
Taxonomic identifieri408692 [NCBI]
Taxonomic lineageiVirusesssRNA virusesssRNA positive-strand viruses, no DNA stageFlaviviridaeFlavivirusDengue virus group
Virus hostiAedimorphus [TaxID: 53540]
Diceromyia [TaxID: 53539]
Erythrocebus patas (Red guenon) (Cercopithecus patas) [TaxID: 9538]
Homo sapiens (Human) [TaxID: 9606]
Stegomyia [TaxID: 53541]
Proteomesi
  • UP000007537 Componenti: Genome
  • UP000096981 Componenti: Genome

Subcellular locationi

Capsid protein C:
  • Virion By similarity
  • Host nucleus By similarity
  • Host cytoplasm By similarity
  • host perinuclear region By similarity
Peptide pr:
  • Secreted By similarity
Small envelope protein M:
Envelope protein E:
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
  • Host nucleus By similarity
  • Note: Located in RE-associated vesicles hosting the replication complex. NS5 protein is mainly localized in the nucleus rather than in ER vesicles, especially in the DENV 2, 3, 4 serotypes.By similarity

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 100CytoplasmicSequence analysisAdd BLAST100
Transmembranei101 – 120HelicalSequence analysisAdd BLAST20
Topological domaini121 – 243ExtracellularSequence analysisAdd BLAST123
Transmembranei244 – 264HelicalSequence analysisAdd BLAST21
Topological domaini265CytoplasmicSequence analysis1
Transmembranei266 – 280HelicalSequence analysisAdd BLAST15
Topological domaini281 – 723ExtracellularSequence analysisAdd BLAST443
Transmembranei724 – 744HelicalSequence analysisAdd BLAST21
Topological domaini745 – 750CytoplasmicSequence analysis6
Transmembranei751 – 771HelicalSequence analysisAdd BLAST21
Topological domaini772 – 1193ExtracellularSequence analysisAdd BLAST422
Transmembranei1194 – 1218HelicalSequence analysisAdd BLAST25
Topological domaini1219 – 1224CytoplasmicSequence analysis6
Transmembranei1225 – 1243HelicalSequence analysisAdd BLAST19
Topological domaini1244 – 1267LumenalSequence analysisAdd BLAST24
Transmembranei1268 – 1288HelicalSequence analysisAdd BLAST21
Topological domaini1289CytoplasmicSequence analysis1
Transmembranei1290 – 1308HelicalSequence analysisAdd BLAST19
Topological domaini1309 – 1315LumenalSequence analysis7
Transmembranei1316 – 1336HelicalSequence analysisAdd BLAST21
Topological domaini1337 – 1344CytoplasmicSequence analysis8
Transmembranei1345 – 1365HelicalSequence analysisAdd BLAST21
Topological domaini1366 – 1368LumenalSequence analysis3
Transmembranei1369 – 1389HelicalSequence analysisAdd BLAST21
Topological domaini1390 – 1443CytoplasmicSequence analysisAdd BLAST54
Intramembranei1444 – 1464HelicalSequence analysisAdd BLAST21
Topological domaini1465 – 2146CytoplasmicSequence analysisAdd BLAST682
Transmembranei2147 – 2167HelicalSequence analysisAdd BLAST21
Topological domaini2168 – 2169LumenalSequence analysis2
Intramembranei2170 – 2190HelicalSequence analysisAdd BLAST21
Topological domaini2191LumenalSequence analysis1
Transmembranei2192 – 2212HelicalSequence analysisAdd BLAST21
Topological domaini2213 – 2227CytoplasmicSequence analysisAdd BLAST15
Transmembranei2228 – 2248Helical; Note=Signal for NS4BSequence analysisAdd BLAST21
Topological domaini2249 – 2273LumenalSequence analysisAdd BLAST25
Intramembranei2274 – 2294HelicalSequence analysisAdd BLAST21
Topological domaini2295 – 2305LumenalSequence analysisAdd BLAST11
Intramembranei2306 – 2326HelicalSequence analysisAdd BLAST21
Topological domaini2327 – 2346LumenalSequence analysisAdd BLAST20
Transmembranei2347 – 2367HelicalSequence analysisAdd BLAST21
Topological domaini2368 – 2412CytoplasmicSequence analysisAdd BLAST45
Transmembranei2413 – 2433HelicalSequence analysisAdd BLAST21
Topological domaini2434 – 2458LumenalSequence analysisAdd BLAST25
Transmembranei2459 – 2479HelicalSequence analysisAdd BLAST21
Topological domaini2480 – 3390CytoplasmicSequence analysisAdd BLAST911

GO - Cellular componenti

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
Mutagenesisi2528R → A: 90% loss of 2'-O-MTase activity. 1 Publication1
Mutagenesisi2532K → A: 25% loss of 2'-O-MTase activity. 1 Publication1
Mutagenesisi2547R → A: Complete loss of 2'-O-MTase activity. 1 Publication1
Mutagenesisi2551K → A: Complete loss of 2'-O-MTase activity. 1 Publication1
Mutagenesisi2574R → A: 40% loss of 2'-O-MTase activity. 1 Publication1
Mutagenesisi2601E → R: Complete loss of 2'-O-MTase activity. Decreased thermostability both in the presence and absence of the RNA ligand. 1 Publication1
Mutagenesisi2636D → A: Complete loss of 2'-O-MTase activity. 1 Publication1
Mutagenesisi2670K → A: Complete loss of 2'-O-MTase activity. 1 Publication1
Mutagenesisi2701R → A: 98% loss of 2'-O-MTase activity. 1 Publication1
Mutagenesisi2706E → A: Complete loss of 2'-O-MTase activity. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00004052251 – 3390Genome polyproteinAdd BLAST3390
ChainiPRO_00002680881 – 100Capsid protein CBy similarityAdd BLAST100
PropeptideiPRO_0000268089101 – 114ER anchor for the capsid protein C, removed in mature form by serine protease NS3By similarityAdd BLAST14
ChainiPRO_0000268090115 – 280Protein prMBy similarityAdd BLAST166
ChainiPRO_0000268091115 – 205Peptide prBy similarityAdd BLAST91
ChainiPRO_0000268092206 – 280Small envelope protein MBy similarityAdd BLAST75
ChainiPRO_0000268093281 – 773Envelope protein EBy similarityAdd BLAST493
ChainiPRO_0000268094774 – 1125Non-structural protein 1By similarityAdd BLAST352
ChainiPRO_00002680951126 – 1343Non-structural protein 2ABy similarityAdd BLAST218
ChainiPRO_00002680971344 – 1473Serine protease subunit NS2BBy similarityAdd BLAST130
ChainiPRO_00002680981474 – 2092Serine protease NS3By similarityAdd BLAST619
ChainiPRO_00002680992093 – 2219Non-structural protein 4ABy similarityAdd BLAST127
PeptideiPRO_00002681002220 – 2242Peptide 2kBy similarityAdd BLAST23
ChainiPRO_00002681012243 – 2490Non-structural protein 4BBy similarityAdd BLAST248
ChainiPRO_00002681022491 – 3390RNA-directed RNA polymerase NS5By similarityAdd BLAST900

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi183N-linked (GlcNAc...) asparagine; by hostPROSITE-ProRule annotation1
Disulfide bondi283 ↔ 310By similarity
Disulfide bondi340 ↔ 401By similarity
Glycosylationi347N-linked (GlcNAc...) asparagine; by hostPROSITE-ProRule annotation1
Disulfide bondi354 ↔ 385By similarity
Disulfide bondi372 ↔ 396By similarity
Glycosylationi433N-linked (GlcNAc...) asparagine; by hostPROSITE-ProRule annotation1
Disulfide bondi463 ↔ 563By similarity
Disulfide bondi580 ↔ 611By similarity
Disulfide bondi777 ↔ 788By similarity
Disulfide bondi828 ↔ 916By similarity
Glycosylationi903N-linked (GlcNAc...) asparagine; by hostPROSITE-ProRule annotation1
Disulfide bondi952 ↔ 996By similarity
Glycosylationi980N-linked (GlcNAc...) asparagine; by hostPROSITE-ProRule annotation1
Disulfide bondi1053 ↔ 1102By similarity
Disulfide bondi1064 ↔ 1086By similarity
Disulfide bondi1085 ↔ 1089By similarity
Glycosylationi1132N-linked (GlcNAc...) asparagine; by hostPROSITE-ProRule annotation1
Glycosylationi1188N-linked (GlcNAc...) asparagine; by hostPROSITE-ProRule annotation1
Glycosylationi2300N-linked (GlcNAc...) asparagine; by hostPROSITE-ProRule annotation1
Glycosylationi2304N-linked (GlcNAc...) asparagine; by hostPROSITE-ProRule annotation1
Glycosylationi2456N-linked (GlcNAc...) asparagine; by hostPROSITE-ProRule annotation1
Modified residuei2546PhosphoserineBy 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 similarity
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: N-glycosylated.By similarity
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: Sumoylation of RNA-directed RNA polymerase NS5 increases NS5 protein stability allowing proper viral RNA replication.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
Sitei100 – 101Cleavage; by viral protease NS3By similarity2
Sitei114 – 115Cleavage; by host signal peptidaseBy similarity2
Sitei205 – 206Cleavage; by host furinSequence analysisBy similarity2
Sitei280 – 281Cleavage; by host signal peptidaseBy similarity2
Sitei773 – 774Cleavage; by host signal peptidaseBy similarity2
Sitei1125 – 1126Cleavage; by hostBy similarity2
Sitei1343 – 1344Cleavage; by viral protease NS3By similarity2
Sitei1473 – 1474Cleavage; by autolysisBy similarity2
Sitei2092 – 2093Cleavage; by autolysisBy similarity2
Sitei2219 – 2220Cleavage; by viral protease NS3By similarity2
Sitei2242 – 2243Cleavage; by host signal peptidaseBy similarity2
Sitei2490 – 2491Cleavage; by viral protease NS3By similarity2

Keywords - PTMi

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

Interactioni

Subunit structurei

Capsid protein C: Homodimer. Interacts (via N-terminus) with host EXOC1 (via C-terminus); this interaction results in EXOC1 degradation through the proteasome degradation pathway (By similarity). 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). Interacts with protein prM. Interacts with non-structural protein 1 (By similarity). Non-structural protein 1: Homodimer; Homohexamer when secreted (By similarity). Interacts with envelope protein E (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 (By similarity). May form homooligomers (By similarity). Serine protease NS3: Forms a heterodimer with NS2B. Interacts with NS4B (By similarity). 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. RNA-directed RNA polymerase NS5: Homodimer (PubMed:24025331). Interacts with host STAT2; this interaction inhibits the phosphorylation of the latter, and, when all viral proteins are present (polyprotein), targets STAT2 for degradation. Interacts with serine protease NS3.By similarity1 Publication

GO - Molecular functioni

Structurei

Secondary structure

13390
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi2499 – 2509Combined sources11
Helixi2512 – 2519Combined sources8
Turni2520 – 2522Combined sources3
Beta strandi2524 – 2527Combined sources4
Helixi2529 – 2536Combined sources8
Helixi2548 – 2557Combined sources10
Beta strandi2565 – 2570Combined sources6
Helixi2576 – 2581Combined sources6
Beta strandi2587 – 2593Combined sources7
Helixi2611 – 2613Combined sources3
Beta strandi2614 – 2617Combined sources4
Helixi2622 – 2624Combined sources3
Beta strandi2631 – 2635Combined sources5
Helixi2644 – 2658Combined sources15
Helixi2659 – 2661Combined sources3
Beta strandi2666 – 2672Combined sources7
Helixi2677 – 2690Combined sources14
Beta strandi2693 – 2695Combined sources3
Beta strandi2707 – 2712Combined sources6
Helixi2717 – 2730Combined sources14
Beta strandi2733 – 2735Combined sources3
Beta strandi2740 – 2743Combined sources4
Helixi2754 – 2756Combined sources3
Helixi2763 – 2776Combined sources14
Turni2777 – 2780Combined sources4
Beta strandi2790 – 2800Combined sources11
Helixi2812 – 2816Combined sources5
Helixi2819 – 2823Combined sources5
Helixi2825 – 2830Combined sources6
Helixi2837 – 2847Combined sources11
Helixi2857 – 2874Combined sources18
Turni2875 – 2877Combined sources3
Helixi2885 – 2893Combined sources9
Helixi2909 – 2916Combined sources8
Helixi2918 – 2932Combined sources15
Beta strandi2941 – 2944Combined sources4
Helixi2961 – 2978Combined sources18
Helixi2980 – 2983Combined sources4
Turni2984 – 2987Combined sources4
Helixi2989 – 2992Combined sources4
Beta strandi2993 – 2995Combined sources3
Turni2997 – 2999Combined sources3
Helixi3001 – 3012Combined sources12
Beta strandi3014 – 3017Combined sources4
Helixi3027 – 3030Combined sources4
Helixi3033 – 3039Combined sources7
Helixi3040 – 3045Combined sources6
Helixi3048 – 3060Combined sources13
Beta strandi3063 – 3073Combined sources11
Beta strandi3076 – 3087Combined sources12
Beta strandi3090 – 3092Combined sources3
Helixi3095 – 3114Combined sources20
Helixi3120 – 3124Combined sources5
Helixi3131 – 3145Combined sources15
Beta strandi3148 – 3151Combined sources4
Beta strandi3154 – 3157Combined sources4
Helixi3162 – 3166Combined sources5
Helixi3169 – 3173Combined sources5
Beta strandi3178 – 3181Combined sources4
Beta strandi3190 – 3192Combined sources3
Helixi3193 – 3195Combined sources3
Beta strandi3201 – 3207Combined sources7
Beta strandi3213 – 3218Combined sources6
Helixi3221 – 3228Combined sources8
Beta strandi3230 – 3234Combined sources5
Helixi3238 – 3255Combined sources18
Helixi3260 – 3272Combined sources13
Beta strandi3294 – 3297Combined sources4
Helixi3299 – 3307Combined sources9
Turni3308 – 3310Combined sources3
Helixi3323 – 3325Combined sources3
Helixi3331 – 3336Combined sources6
Helixi3344 – 3364Combined sources21
Helixi3373 – 3375Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2J7UX-ray1.85A2762-3390[»]
2J7WX-ray2.60A2763-3390[»]
3VWSX-ray2.10A2762-3390[»]
4C11X-ray2.60A/B2753-3390[»]
4HHJX-ray1.79A2762-3390[»]
5DTOX-ray2.60A2496-3385[»]
5EIWX-ray1.61A/C2491-2766[»]
5F3TX-ray2.05A2762-3390[»]
5F3ZX-ray2.00A2762-3390[»]
5F41X-ray2.00A2762-3390[»]
5HMWX-ray2.15A2762-3390[»]
5HMXX-ray2.40A2762-3390[»]
5HMYX-ray2.10A2762-3390[»]
5HMZX-ray1.99A2762-3390[»]
5HN0X-ray2.05A2762-3390[»]
5I3PX-ray2.45A2762-3390[»]
5I3QX-ray1.88A2762-3390[»]
5IQ6X-ray3.00A2763-3390[»]
5JJRX-ray1.99A2494-3385[»]
5JJSX-ray1.65A2494-3385[»]
ProteinModelPortaliQ6YMS4.
SMRiQ6YMS4.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini1474 – 1651Peptidase S7PROSITE-ProRule annotationAdd BLAST178
Domaini1654 – 1810Helicase ATP-bindingPROSITE-ProRule annotationAdd BLAST157
Domaini1820 – 1986Helicase C-terminalPROSITE-ProRule annotationAdd BLAST167
Domaini2492 – 2753mRNA cap 0-1 NS5-type MTPROSITE-ProRule annotationAdd BLAST262
Domaini3018 – 3168RdRp catalyticPROSITE-ProRule annotationAdd BLAST151

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 15Interaction with host EXOC1By similarityAdd BLAST15
Regioni37 – 72Hydrophobic; homodimerization of capsid protein CBy similarityAdd BLAST36
Regioni378 – 391Fusion peptideBy similarityAdd BLAST14
Regioni1396 – 1435Interacts with and activates NS3 proteasePROSITE-ProRule annotationAdd BLAST40
Regioni1658 – 1661Important for RNA-bindingBy similarity4

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi1758 – 1761DEAH boxPROSITE-ProRule annotation4
Motifi2567 – 2570SUMO-interacting motifBy similarity4

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.

Q6YMS4-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MNNQRKKTGK PSINMLKRVR NRVSTGSQLA KRFSKGLLNG QGPMKLVMAF
60 70 80 90 100
IAFLRFLAIP PTAGVLARWG TFKKSGAIKV LKGFKKEISN MLSIINQRKK
110 120 130 140 150
TSLCLMMILP AALAFHLTSR DGEPRMIVGK NERGKSLLFK TASGINMCTL
160 170 180 190 200
IAMDLGEMCD DTVTYKCPHI TEVEPEDIDC WCNLTSTWVT YGTCNQAGEH
210 220 230 240 250
RRDKRSVALA PHVGMGLDTR TQTWMSAEGA WRQVEKVETW ALRHPGFTIL
260 270 280 290 300
ALFLAHYIGT SLTQKVVIFI LLMLVTPSMT MRCVGVGNRD FVEGLSGATW
310 320 330 340 350
VDVVLEHGGC VTTMAKNKPT LDIELQKTEA TQLATLRKLC IEGKITNITT
360 370 380 390 400
DSRCPTQGEA VLPEEQDQNY VCKHTYVDRG WGNGCGLFGK GSLVTCAKFQ
410 420 430 440 450
CLEPIEGKVV QYENLKYTVI ITVHTGDQHQ VGNETQGVTA EITPQASTTE
460 470 480 490 500
AILPEYGTLG LECSPRTGLD FNEMILLTMK NKAWMVHRQW FFDLPLPWAS
510 520 530 540 550
GATTETPTWN RKELLVTFKN AHAKKQEVVV LGSQEGAMHT ALTGATEIQN
560 570 580 590 600
SGGTSIFAGH LKCRLKMDKL ELKGMSYAMC TNTFVLKKEV SETQHGTILI
610 620 630 640 650
KVEYKGEDAP CKIPFSTEDG QGKAHNGRLI TANPVVTKKE EPVNIEAEPP
660 670 680 690 700
FGESNIVIGI GDNALKINWY KKGSSIGKMF EATERGARRM AILGDTAWDF
710 720 730 740 750
GSVGGVLNSL GKMVHQIFGS AYTALFSGVS WVMKIGIGVL LTWIGLNSKN
760 770 780 790 800
TSMSFSCIAI GIITLYLGAV VQADMGCVIN WKGKELKCGS GIFVTNEVHT
810 820 830 840 850
WTEQYKFQAD SPKRLATAIA GAWENGVCGI RSTTRMENLL WKQIANELNY
860 870 880 890 900
ILWENNIKLT VVVGDTLGVL EQGKRTLTPQ PMELKYSWKT WGKAKIVTAE
910 920 930 940 950
TQNSSFIIDG PNTPECPSAS RAWNVWEVED YGFGVFTTNI WLKLREVYTQ
960 970 980 990 1000
LCDHRLMSAA VKDERAVHAD MGYWIESQKN GSWKLEKASL IEVKTCTWPK
1010 1020 1030 1040 1050
SHTLWTNGVL ESDMIIPKSL AGPISQHNYR PGYHTQTAGP WHLGKLELDF
1060 1070 1080 1090 1100
NYCEGTTVVI TESCGTRGPS LRTTTVSGKL IHEWCCRSCT LPPLRYMGED
1110 1120 1130 1140 1150
GCWYGMEIRP ISEKEENMVK SLVSAGSGKV DNFTMGVLCL AILFEEVLRG
1160 1170 1180 1190 1200
KFGKKHMIAG VFFTFVLLLS GQITWRDMAH TLIMIGSNAS DRMGMGVTYL
1210 1220 1230 1240 1250
ALIATFKIQP FLALGFFLRK LTSRENLLLG VGLAMATTLQ LPEDIEQMAN
1260 1270 1280 1290 1300
GVALGLMALK LITQFETYQL WTALVSLTCS NTIFTLTVAW RTATLILAGV
1310 1320 1330 1340 1350
SLLPVCQSSS MRKTDWLPMT VAAMGVPPLP LFIFSLKDTL KRRSWPLNEG
1360 1370 1380 1390 1400
VMAVGLVSIL ASSLLRNDVP MAGPLVAGGL LIACYVITGT SADLTVEKAP
1410 1420 1430 1440 1450
DVTWEEEAEQ TGVSHNLMIT VDDDGTMRIK DDETENILTV LLKTALLIVS
1460 1470 1480 1490 1500
GIFPYSIPAT LLVWHTWQKQ TQRSGVLWDV PSPPETQKAE LEEGVYRIKQ
1510 1520 1530 1540 1550
QGIFGKTQVG VGVQKEGVFH TMWHVTRGAV LTHNGKRLEP NWASVKKDLI
1560 1570 1580 1590 1600
SYGGGWRLSA QWQKGEEVQV IAVEPGKNPK NFQTTPGTFQ TTTGEIGAIA
1610 1620 1630 1640 1650
LDFKPGTSGS PIINREGKVV GLYGNGVVTK NGGYVSGIAQ TNAEPDGPTP
1660 1670 1680 1690 1700
ELEEEMFKKR NLTIMDLHPG SGKTRKYLPA IVREAIKRRL RTLILAPTRV
1710 1720 1730 1740 1750
VAAEMEEALK GLPIRYQTTA TKSEHTGREI VDLMCHATFT MRLLSPVRVP
1760 1770 1780 1790 1800
NYNLIIMDEA HFTDPASIAA RGYISTRVGM GEAAAIFMTA TPPGTADAFP
1810 1820 1830 1840 1850
QSNAPIQDEE RDIPERSWNS GNEWITDFAG KTVWFVPSIK AGNDIANCLR
1860 1870 1880 1890 1900
KNGKKVIQLS RKTFDTEYQK TKLNDWDFVV TTDISEMGAN FKADRVIDPR
1910 1920 1930 1940 1950
RCLKPVILTD GPERVILAGP MPVTAASAAQ RRGRVGRNPQ KENDQYIFTG
1960 1970 1980 1990 2000
QPLNNDEDHA HWTEAKMLLD NINTPEGIIP ALFEPEREKS AAIDGEYRLK
2010 2020 2030 2040 2050
GESRKTFVEL MRRGDLPVWL AHKVASEGIK YTDRKWCFDG QRNNQILEEN
2060 2070 2080 2090 2100
MDVEIWTKEG EKKKLRPRWL DARTYSDPLA LKEFKDFAAG RKSIALDLVT
2110 2120 2130 2140 2150
EIGRVPSHLA HRTRNALDNL VMLHTSEDGG RAYRHAVEEL PETMETLLLL
2160 2170 2180 2190 2200
GLMILLTGGA MLFLISGKGI GKTSIGLICV IASSGMLWMA EVPLQWIASA
2210 2220 2230 2240 2250
IVLEFFMMVL LIPEPEKQRT PQDNQLAYVV IGILTLAATI AANEMGLLET
2260 2270 2280 2290 2300
TKRDLGMSKE PGVVSPTSYL DVDLHPASAW TLYAVATTVI TPMLRHTIEN
2310 2320 2330 2340 2350
STANVSLAAI ANQAVVLMGL DKGWPISKMD LGVPLLALGC YSQVNPLTLT
2360 2370 2380 2390 2400
AAVLLLITHY AIIGPGLQAK ATREAQKRTA AGIMKNPTVD GIMTIDLDSV
2410 2420 2430 2440 2450
IFDSKFEKQL GQVMLLVLCA VQLLLMRTSW ALCEALTLAT GPITTLWEGS
2460 2470 2480 2490 2500
PGKFWNTTIA VSMANIFRGS YLAGAGLAFS IMKSVGTGKR GTGSQGETLG
2510 2520 2530 2540 2550
EKWKKKLNQL SRKEFDLYKK SGITEVDRTE AKEGLKRGET THHAVSRGSA
2560 2570 2580 2590 2600
KLQWFVERNM VVPEGRVIDL GCGRGGWSYY CAGLKKVTEV RGYTKGGPGH
2610 2620 2630 2640 2650
EEPVPMSTYG WNIVKLMSGK DVFYLPPEKC DTLLCDIGES SPSPTVEESR
2660 2670 2680 2690 2700
TIRVLKMVEP WLKNNQFCIK VLNPYMPTVI EHLERLQRKH GGMLVRNPLS
2710 2720 2730 2740 2750
RNSTHEMYWI SNGTGNIVSS VNMVSRLLLN RFTMTHRRPT IEKDVDLGAG
2760 2770 2780 2790 2800
TRHVNAEPET PNMDVIGERI KRIKEEHNST WHYDDENPYK TWAYHGSYEV
2810 2820 2830 2840 2850
KATGSASSMI NGVVKLLTKP WDVVPMVTQM AMTDTTPFGQ QRVFKEKVDT
2860 2870 2880 2890 2900
RTPRPMPGTR KAMEITAEWL WRTLGRNKRP RLCTREEFTK KVRTNAAMGA
2910 2920 2930 2940 2950
VFTEENQWDS AKAAVEDEEF WKLVDREREL HKLGKCGSCV YNMMGKREKK
2960 2970 2980 2990 3000
LGEFGKAKGS RAIWYMWLGA RYLEFEALGF LNEDHWFSRE NSYSGVEGEG
3010 3020 3030 3040 3050
LHKLGYILRD ISKIPGGAMY ADDTAGWDTR ITEDDLHNEE KIIQQMDPEH
3060 3070 3080 3090 3100
RQLANAIFKL TYQNKVVKVQ RPTPTGTVMD IISRKDQRGS GQLGTYGLNT
3110 3120 3130 3140 3150
FTNMEAQLVR QMEGEGVLTK ADLENPHLLE KKITQWLETK GVERLKRMAI
3160 3170 3180 3190 3200
SGDDCVVKPI DDRFANALLA LNDMGKVRKD IPQWQPSKGW HDWQQVPFCS
3210 3220 3230 3240 3250
HHFHELIMKD GRKLVVPCRP QDELIGRARI SQGAGWSLRE TACLGKAYAQ
3260 3270 3280 3290 3300
MWSLMYFHRR DLRLASNAIC SAVPVHWVPT SRTTWSIHAH HQWMTTEDML
3310 3320 3330 3340 3350
TVWNRVWIEE NPWMEDKTPV TTWENVPYLG KREDQWCGSL IGLTSRATWA
3360 3370 3380 3390
QNIPTAIQQV RSLIGNEEFL DYMPSMKRFR KEEESEGAIW
Length:3,390
Mass (Da):377,923
Last modified:July 5, 2004 - v1
Checksum:i14C0E2C0C9189CCB
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural varianti97Q → K. 1
Natural varianti684E → A. 1
Natural varianti867L → I. 1
Natural varianti1006T → S. 1
Natural varianti1148L → M. 1
Natural varianti1252V → I. 1
Natural varianti1400P → A. 1
Natural varianti1585T → M. 1
Natural varianti1871T → S. 1
Natural varianti2063K → R. 1
Natural varianti2128D → H. 1
Natural varianti2239T → I. 1
Natural varianti2399S → P. 1
Natural varianti2402F → Y. 1
Natural varianti2856M → L. 1
Natural varianti2862A → V. 1
Natural varianti2864E → G. 1
Natural varianti2970A → V. 1
Natural varianti3093L → V. 1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY099336 Genomic RNA. Translation: AAM51537.1.
AY662691 Genomic RNA. Translation: AAT75224.1.
RefSeqiYP_001621843.1. NC_001475.2.

Genome annotation databases

GeneIDi5075727.
KEGGivg:5075727.

Similar proteinsi

Entry informationi

Entry nameiPOLG_DEN3S
AccessioniPrimary (citable) accession number: Q6YMS4
Secondary accession number(s): Q6DLV0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 12, 2006
Last sequence update: July 5, 2004
Last modified: October 25, 2017
This is version 113 of the entry and version 1 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