UniProtKB - P27914 (POLG_DEN2T)
Genome polyprotein
Functioni
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.
By similarityInvolved 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 similarityDisrupts 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 similarityComponent of the viral RNA replication complex that functions in virion assembly and antagonizes the host immune response.
By similaritySerine 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 similarityDisplays 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 annotationCatalytic 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. EC:3.4.21.91
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Active sitei | 1116 | Charge relay system; for serine protease NS3 activityPROSITE-ProRule annotation | 1 | |
Active sitei | 1140 | Charge relay system; for serine protease NS3 activityPROSITE-ProRule annotation | 1 | |
Active sitei | 1200 | Charge relay system; for serine protease NS3 activityPROSITE-ProRule annotation | 1 | |
Sitei | 1522 | Involved in NS3 ATPase and RTPase activitiesBy similarity | 1 | |
Sitei | 1525 | Involved in NS3 ATPase and RTPase activitiesBy similarity | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 1258 – 1265 | ATPPROSITE-ProRule annotation | 8 |
GO - Molecular functioni
- ATP binding Source: UniProtKB-KW
- ATP hydrolysis activity Source: RHEA
- double-stranded RNA binding Source: InterPro
- protein dimerization activity Source: InterPro
- RNA helicase activity Source: UniProtKB-EC
- serine-type peptidase activity Source: UniProtKB-KW
GO - Biological processi
- clathrin-dependent endocytosis of virus by host cell Source: UniProtKB-KW
- fusion of virus membrane with host endosome membrane Source: UniProtKB-KW
- virion attachment to host cell Source: UniProtKB-KW
Keywordsi
Protein family/group databases
MEROPSi | S07.001 |
Names & Taxonomyi
Protein namesi | Recommended name: Genome polyproteinCleaved into the following 4 chains: Serine protease NS3 (EC:3.4.21.91, EC:3.6.1.15, EC:3.6.4.13) Alternative name(s): Non-structural protein 3 |
Organismi | Dengue virus type 2 (strain Tonga/EKB194/1974) (DENV-2) |
Taxonomic identifieri | 11067 [NCBI] |
Taxonomic lineagei | Viruses › Riboviria › Orthornavirae › Kitrinoviricota › Flasuviricetes › Amarillovirales › Flaviviridae › Flavivirus › |
Virus hosti | Aedimorphus [TaxID: 53540] Diceromyia [TaxID: 53539] Erythrocebus patas (Red guenon) (Cercopithecus patas) [TaxID: 9538] Homo sapiens (Human) [TaxID: 9606] Stegomyia [TaxID: 53541] |
Subcellular locationi
- Virion membrane By similarity; Multi-pass membrane protein Sequence analysis
- Host endoplasmic reticulum membrane By similarity; Multi-pass membrane protein Sequence analysis
- 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
- Host endoplasmic reticulum membrane By similarity; Multi-pass membrane protein By similarity
- 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
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | ‹1 – 445 | ExtracellularSequence analysisAdd BLAST | ›445 | |
Transmembranei | 446 – 466 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 467 – 472 | CytoplasmicSequence analysis | 6 | |
Transmembranei | 473 – 493 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 494 – 915 | ExtracellularSequence analysisAdd BLAST | 422 | |
Transmembranei | 916 – 940 | HelicalSequence analysisAdd BLAST | 25 | |
Topological domaini | 941 – 946 | CytoplasmicSequence analysis | 6 | |
Transmembranei | 947 – 965 | HelicalSequence analysisAdd BLAST | 19 | |
Topological domaini | 966 – 989 | LumenalSequence analysisAdd BLAST | 24 | |
Transmembranei | 990 – 1010 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 1011 | CytoplasmicSequence analysis | 1 | |
Transmembranei | 1012 – 1030 | HelicalSequence analysisAdd BLAST | 19 | |
Topological domaini | 1031 – 1037 | LumenalSequence analysis | 7 | |
Transmembranei | 1038 – 1058 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 1059 – ›1683 | CytoplasmicSequence analysisAdd BLAST | ›625 |
Keywords - Cellular componenti
Capsid protein, Host endoplasmic reticulum, Host membrane, Membrane, Secreted, Viral envelope protein, VirionPTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000405219 | ‹1 – ›1683 | Genome polyproteinAdd BLAST | ›1683 | |
ChainiPRO_0000037980 | 1 – 495 | Envelope protein EBy similarityAdd BLAST | 495 | |
ChainiPRO_0000037981 | 496 – 847 | Non-structural protein 1By similarityAdd BLAST | 352 | |
ChainiPRO_0000308290 | 848 – 1065 | Non-structural protein 2ABy similarityAdd BLAST | 218 | |
ChainiPRO_0000037983 | 1066 – 1683 | Serine protease NS3By similarityAdd BLAST | 618 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Disulfide bondi | 3 ↔ 30 | By similarity | ||
Disulfide bondi | 60 ↔ 121 | By similarity | ||
Glycosylationi | 67 | N-linked (GlcNAc...) asparagine; by hostSequence analysis | 1 | |
Disulfide bondi | 74 ↔ 105 | By similarity | ||
Disulfide bondi | 92 ↔ 116 | By similarity | ||
Glycosylationi | 153 | N-linked (GlcNAc...) asparagine; by hostSequence analysis | 1 | |
Disulfide bondi | 185 ↔ 285 | By similarity | ||
Disulfide bondi | 302 ↔ 333 | By similarity | ||
Disulfide bondi | 499 ↔ 510 | By similarity | ||
Disulfide bondi | 550 ↔ 638 | By similarity | ||
Disulfide bondi | 674 ↔ 718 | By similarity | ||
Glycosylationi | 702 | N-linked (GlcNAc...) asparagine; by hostSequence analysis | 1 | |
Disulfide bondi | 775 ↔ 824 | By similarity | ||
Disulfide bondi | 786 ↔ 808 | By similarity | ||
Disulfide bondi | 807 ↔ 811 | By similarity |
Post-translational modificationi
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sitei | 495 – 496 | Cleavage; by host signal peptidaseBy similarity | 2 | |
Sitei | 847 – 848 | Cleavage; by hostBy similarity | 2 | |
Sitei | 1065 – 1066 | Cleavage; by autolysisBy similarity | 2 |
Keywords - PTMi
Cleavage on pair of basic residues, Disulfide bond, GlycoproteinInteractioni
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. Protein prM: Forms heterodimers with envelope protein E in the endoplasmic reticulum and Golgi.
By similarityHomodimer; in the endoplasmic reticulum and Golgi.
Interacts with protein prM.
Interacts with non-structural protein 1.
By similarityHomodimer; Homohexamer when secreted.
Interacts with envelope protein E.
By similarityInteracts (via N-terminus) with serine protease NS3. Non-structural protein 2B:
Forms a heterodimer with serine protease NS3. May form homooligomers.
By similarityForms 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.
Interacts with host SHFL.
By similarityGO - Molecular functioni
- protein dimerization activity Source: InterPro
Structurei
Secondary structure
3D structure databases
BMRBi | P27914 |
SMRi | P27914 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | P27914 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 1066 – 1243 | Peptidase S7PROSITE-ProRule annotationAdd BLAST | 178 | |
Domaini | 1245 – 1401 | Helicase ATP-bindingPROSITE-ProRule annotationAdd BLAST | 157 | |
Domaini | 1411 – 1582 | Helicase C-terminalPROSITE-ProRule annotationAdd BLAST | 172 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 98 – 111 | Fusion peptideBy similarityAdd BLAST | 14 | |
Regioni | 1249 – 1252 | Important for RNA-bindingBy similarity | 4 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 1349 – 1352 | DEAH boxPROSITE-ProRule annotation | 4 |
Domaini
Keywords - Domaini
Transmembrane, Transmembrane helixFamily and domain databases
CDDi | cd12149, Flavi_E_C, 1 hit |
Gene3Di | 1.20.1280.260, 1 hit 2.60.40.350, 1 hit 2.60.98.10, 1 hit 3.30.387.10, 1 hit 3.30.67.10, 1 hit 3.40.50.300, 2 hits |
InterProi | View protein in InterPro IPR011492, DEAD_Flavivir IPR013755, Flav_gly_cen_dom_subdom1 IPR027287, Flavi_E_Ig-like IPR026470, Flavi_E_Stem/Anchor_dom IPR038345, Flavi_E_Stem/Anchor_dom_sf IPR001157, Flavi_NS1 IPR000752, Flavi_NS2A IPR000336, Flavivir/Alphavir_Ig-like_sf IPR001850, Flavivirus_NS3_S7 IPR011998, Glycoprot_cen/dimer IPR036253, Glycoprot_cen/dimer_sf IPR038055, Glycoprot_E_dimer_dom IPR013756, GlyE_cen_dom_subdom2 IPR014001, Helicase_ATP-bd IPR001650, Helicase_C IPR014756, Ig_E-set IPR027417, P-loop_NTPase IPR009003, Peptidase_S1_PA |
Pfami | View protein in Pfam PF07652, Flavi_DEAD, 1 hit PF02832, Flavi_glycop_C, 1 hit PF00869, Flavi_glycoprot, 1 hit PF00948, Flavi_NS1, 1 hit PF01005, Flavi_NS2A, 1 hit PF00949, Peptidase_S7, 1 hit |
SMARTi | View protein in SMART SM00487, DEXDc, 1 hit SM00490, HELICc, 1 hit |
SUPFAMi | SSF50494, SSF50494, 1 hit SSF52540, SSF52540, 2 hits SSF56983, SSF56983, 1 hit SSF81296, SSF81296, 1 hit |
TIGRFAMsi | TIGR04240, flavi_E_stem, 1 hit |
PROSITEi | View protein in PROSITE PS51528, FLAVIVIRUS_NS3PRO, 1 hit PS51192, HELICASE_ATP_BIND_1, 1 hit PS51194, HELICASE_CTER, 1 hit |
i Sequence
Sequence statusi: Fragments.
: The displayed sequence is further processed into a mature form. Sequence processingi
10 20 30 40 50
MRCIGISNRD FVEGVSGGSW VDIVLEHGSC VTTMAKNKPT LDFELIKTEA
60 70 80 90 100
KQPATLRKYC IEAKLTNTTT DSRCPTQGEP TLNEEQDKRF VCKHSMVDRG
110 120 130 140 150
WGNGCGLFGK GGIVTCAMFT CKKNMEGKIV QPENLEYTVV ITPHSGEEHA
160 170 180 190 200
VGNDTGKHGK EVKITPQSSI TEAELTGYGT VTMECSPRTG LDFNEMVLLQ
210 220 230 240 250
MEDKAWLVHR QWFLDLPLPW LPGADTQGSN WIQKETLVTF KNPHAKKQDV
260 270 280 290 300
VVLGSQEGAM HTALTGATEI QMSSGNLLFT GHLKCRLRMD KLQLKGMSYS
310 320 330 340 350
MCTGKFKIVK EIAETQHGTI VIRVQYEGDG SPCKIPFEIM DLEKRHVLGR
360 370 380 390 400
LITVNPIVTE KDSPVNIEAE PPFGDSYIII GVEPGQLKLD WFKKGSSIGQ
410 420 430 440 450
MFETTMRGAK RMAILGDTAW DFGSLGGVFT SIGKALHQVF GAIYGAAFSG
460 470 480 490 500
VSWTMKILIG VIITWIGMNS RSTSLSVSLV LVGIVTLYLG VMVQADSGCV
510 520 530 540 550
VSWKNKELKC GSGIFVTDNV HTWTEQYKFQ PESPSKLASA IQKAHEEGIC
560 570 580 590 600
GIRSVTRLEN LMWKQITSEL NHILSENEVK LTIMTGDIKG IMQVGKRSLR
610 620 630 640 650
PQPTELRYSW KTWGKAKMLS TELHNQTFLI DGPETAECPN TNRAWNSLEV
660 670 680 690 700
EDYGFGVFTT NIWLRLREKQ DVFCDSKLMS AAIKDNRAVH ADMGYWIESA
710 720 730 740 750
LNDTWKIEKA SFIEVKSCHW PKSHTLWSNG VLESEMVIPK NFAGPVSQHN
760 770 780 790 800
NRPGYYTQTA GPWHLGKLEM DFDFCEGTTV VVTEDCGNRG PSLRTTTASG
810 820 830 840 850
KLITEWCCRS CTLPPLRYRG EDGCWYGMEI RPLKEKEENL VSSLVTAGHG
860 870 880 890 900
QIDNFSLGIL GMALFLEEML RTRVGTKHAI LLVAVSFVTL ITGNMSFRDL
910 920 930 940 950
GRVMVMVGAT MTDDIGMGVT YLALLAAFRV RPTFAAGLLL RKLTSKELMM
960 970 980 990 1000
TTIGIVLLSQ SSIPETILEL TDALALGMMV LKMVRNMEKY QLAVTIMAIL
1010 1020 1030 1040 1050
CVPNAVILQN AWKVSCTILA VVSVSPLLLT SSQQKADWIP LALTIKGLNP
1060 1070 1080 1090 1100
TAIFLTTLSR TSKKRAGVLW DVPSPPPVGK AELEDGAYRI KQKGILGYSQ
1110 1120 1130 1140 1150
IGAGVYKEGT FHTMWHVTRG AVLMHKGKRI EPSWADVKKD LISYGGGWKL
1160 1170 1180 1190 1200
EGEWKEGEEV QVLALEPGKN PRAVQTKPGL FRTNTGTIGA VSLDFSPGTS
1210 1220 1230 1240 1250
GSPIVDKKGK VVGLYGNGVV TRSGAYVSAI AQTEKSIEDN PEIEDDIFRK
1260 1270 1280 1290 1300
RRLTIMDLHP GAGKTKRYLP AIVREAIKRG LRTLILAPTR VVAAEMEEAL
1310 1320 1330 1340 1350
RGLPIRYQTP AIRAEHTGRE IVDLMCHATF TMRLLSPIRV PNYNLIIMDE
1360 1370 1380 1390 1400
AHFTDPASIA ARGYISTRVE MGEAAGIFMT ATPPGSRDPF PQSNAPIMDE
1410 1420 1430 1440 1450
EREIPERSWN SGHEWVTDFK GKTVWFVPSI KTGNDIAACL RKNGKRVIQL
1460 1470 1480 1490 1500
SRKTFDSEYV KTRTNDWDFV VTTDISEMGA NFKAERVIDP RRCMKPVILT
1510 1520 1530 1540 1550
DGEERVILAG PMPVTHSSAA QRRGRIGRNP RNENDQYIYM GEPLENDEDC
1560 1570 1580 1590 1600
AHWKEAKMLL DNINTPEGII PSIFEPEREK VDAIDGEYRL RGEARKTFVD
1610 1620 1630 1640 1650
LMRRGDLPVW LAYKVAAEGI NYADRRWCFD GTRNNQILEE NVEVEIWTKE
1660 1670 1680
GERKKLKPRW LDARIYSDPL ALKEFKEFAA GRK
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Non-terminal residuei | 1 | 1 | ||
Non-adjacent residuesi | 1065 – 1066 | Curated | 2 | |
Non-terminal residuei | 1683 | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | X54319 Genomic RNA Translation: CAA38217.1 X57469 Genomic RNA Translation: CAA40705.1 X57468 Genomic RNA Translation: CAA40704.1 |
PIRi | PQ0507 S11482 |
Similar proteinsi
Cross-referencesi
Web resourcesi
Virus Pathogen Resource |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | X54319 Genomic RNA Translation: CAA38217.1 X57469 Genomic RNA Translation: CAA40705.1 X57468 Genomic RNA Translation: CAA40704.1 |
PIRi | PQ0507 S11482 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
1TG8 | X-ray | 2.61 | A | 1-395 | [»] | |
1TGE | electron microscopy | 12.50 | A/B/C | 1-395 | [»] | |
BMRBi | P27914 | |||||
SMRi | P27914 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Chemistry databases
DrugBanki | DB04473, alpha-L-fucose |
Protein family/group databases
MEROPSi | S07.001 |
Miscellaneous databases
EvolutionaryTracei | P27914 |
Family and domain databases
CDDi | cd12149, Flavi_E_C, 1 hit |
Gene3Di | 1.20.1280.260, 1 hit 2.60.40.350, 1 hit 2.60.98.10, 1 hit 3.30.387.10, 1 hit 3.30.67.10, 1 hit 3.40.50.300, 2 hits |
InterProi | View protein in InterPro IPR011492, DEAD_Flavivir IPR013755, Flav_gly_cen_dom_subdom1 IPR027287, Flavi_E_Ig-like IPR026470, Flavi_E_Stem/Anchor_dom IPR038345, Flavi_E_Stem/Anchor_dom_sf IPR001157, Flavi_NS1 IPR000752, Flavi_NS2A IPR000336, Flavivir/Alphavir_Ig-like_sf IPR001850, Flavivirus_NS3_S7 IPR011998, Glycoprot_cen/dimer IPR036253, Glycoprot_cen/dimer_sf IPR038055, Glycoprot_E_dimer_dom IPR013756, GlyE_cen_dom_subdom2 IPR014001, Helicase_ATP-bd IPR001650, Helicase_C IPR014756, Ig_E-set IPR027417, P-loop_NTPase IPR009003, Peptidase_S1_PA |
Pfami | View protein in Pfam PF07652, Flavi_DEAD, 1 hit PF02832, Flavi_glycop_C, 1 hit PF00869, Flavi_glycoprot, 1 hit PF00948, Flavi_NS1, 1 hit PF01005, Flavi_NS2A, 1 hit PF00949, Peptidase_S7, 1 hit |
SMARTi | View protein in SMART SM00487, DEXDc, 1 hit SM00490, HELICc, 1 hit |
SUPFAMi | SSF50494, SSF50494, 1 hit SSF52540, SSF52540, 2 hits SSF56983, SSF56983, 1 hit SSF81296, SSF81296, 1 hit |
TIGRFAMsi | TIGR04240, flavi_E_stem, 1 hit |
PROSITEi | View protein in PROSITE PS51528, FLAVIVIRUS_NS3PRO, 1 hit PS51192, HELICASE_ATP_BIND_1, 1 hit PS51194, HELICASE_CTER, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | POLG_DEN2T | |
Accessioni | P27914Primary (citable) accession number: P27914 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | August 1, 1992 |
Last sequence update: | August 1, 1992 | |
Last modified: | February 23, 2022 | |
This is version 155 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Viral Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
3D-structureDocuments
- PDB cross-references
Index of Protein Data Bank (PDB) cross-references