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Protein

Genome polyprotein

Gene
N/A
Organism
Dengue virus type 2 (strain Tonga/EKB194/1974) (DENV-2)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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

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.
NTP + H2O = NDP + phosphate.
ATP + H2O = ADP + phosphate.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei1116Charge relay system; for serine protease NS3 activityPROSITE-ProRule annotation1
Active sitei1140Charge relay system; for serine protease NS3 activityPROSITE-ProRule annotation1
Active sitei1200Charge relay system; for serine protease NS3 activityPROSITE-ProRule annotation1
Sitei1522Involved in NS3 ATPase and RTPase activitiesBy similarity1
Sitei1525Involved in NS3 ATPase and RTPase activitiesBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi1258 – 1265ATPPROSITE-ProRule annotation8

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionHydrolase, Protease, Serine protease, Suppressor of RNA silencing, Viral nucleoprotein
Biological processClathrin-mediated endocytosis of virus by host, Fusion of virus membrane with host endosomal membrane, Fusion of virus membrane with host membrane, Host-virus interaction, Viral attachment to host cell, Viral penetration into host cytoplasm, Virus endocytosis by host, Virus entry into host cell
LigandATP-binding, Nucleotide-binding, Zinc

Names & Taxonomyi

Protein namesi
Recommended name:
Genome polyprotein
Cleaved into the following 4 chains:
Alternative name(s):
Non-structural protein 3
OrganismiDengue virus type 2 (strain Tonga/EKB194/1974) (DENV-2)
Taxonomic identifieri11067 [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]

Subcellular locationi

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 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

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini‹1 – 445ExtracellularSequence analysisAdd BLAST›445
Transmembranei446 – 466HelicalSequence analysisAdd BLAST21
Topological domaini467 – 472CytoplasmicSequence analysis6
Transmembranei473 – 493HelicalSequence analysisAdd BLAST21
Topological domaini494 – 915ExtracellularSequence analysisAdd BLAST422
Transmembranei916 – 940HelicalSequence analysisAdd BLAST25
Topological domaini941 – 946CytoplasmicSequence analysis6
Transmembranei947 – 965HelicalSequence analysisAdd BLAST19
Topological domaini966 – 989LumenalSequence analysisAdd BLAST24
Transmembranei990 – 1010HelicalSequence analysisAdd BLAST21
Topological domaini1011CytoplasmicSequence analysis1
Transmembranei1012 – 1030HelicalSequence analysisAdd BLAST19
Topological domaini1031 – 1037LumenalSequence analysis7
Transmembranei1038 – 1058HelicalSequence analysisAdd BLAST21
Topological domaini1059 – ›1683CytoplasmicSequence analysisAdd BLAST›625

GO - Cellular componenti

Keywords - Cellular componenti

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

Pathology & Biotechi

Chemistry databases

DrugBankiDB04473. Alpha-L-Fucose.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_0000405219‹1 – ›1683Genome polyproteinAdd BLAST›1683
ChainiPRO_00000379801 – 495Envelope protein EBy similarityAdd BLAST495
ChainiPRO_0000037981496 – 847Non-structural protein 1By similarityAdd BLAST352
ChainiPRO_0000308290848 – 1065Non-structural protein 2ABy similarityAdd BLAST218
ChainiPRO_00000379831066 – 1683Serine protease NS3By similarityAdd BLAST618

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi3 ↔ 30By similarity
Disulfide bondi60 ↔ 121By similarity
Glycosylationi67N-linked (GlcNAc...) asparagine; by hostSequence analysis1
Disulfide bondi74 ↔ 105By similarity
Disulfide bondi92 ↔ 116By similarity
Glycosylationi153N-linked (GlcNAc...) asparagine; by hostSequence analysis1
Disulfide bondi185 ↔ 285By similarity
Disulfide bondi302 ↔ 333By similarity
Disulfide bondi499 ↔ 510By similarity
Disulfide bondi550 ↔ 638By similarity
Disulfide bondi674 ↔ 718By similarity
Glycosylationi702N-linked (GlcNAc...) asparagine; by hostSequence analysis1
Disulfide bondi775 ↔ 824By similarity
Disulfide bondi786 ↔ 808By similarity
Disulfide bondi807 ↔ 811By similarity

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, wereas cleavages in the cytoplasmic side are performed by the Serine protease NS3. Signal cleavage at the 2K-4B site requires a prior NS3 protease-mediated cleavage at the 4A-2K site.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
Envelope protein E: N-glycosylated.By similarity
Genome polyprotein: Specific enzymatic cleavages in vivo yield mature proteins. Cleavages in the lumen of endoplasmic reticulum are performed by host signal peptidase, wereas 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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei495 – 496Cleavage; by host signal peptidaseBy similarity2
Sitei847 – 848Cleavage; by hostBy similarity2
Sitei1065 – 1066Cleavage; by autolysisBy similarity2

Keywords - PTMi

Cleavage on pair of basic residues, Disulfide bond, Glycoprotein

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. Protein prM: Forms heterodimers with envelope protein E in the endoplasmic reticulum and Golgi. Envelope protein E: Homodimer; in the endoplasmic reticulum and Golgi. Interacts with protein prM. Interacts with non-structural protein 1. Non-structural protein 1: Homodimer; Homohexamer when secreted. Interacts with envelope protein E. Non-structural protein 2A: Interacts (via N-terminus) with serine protease NS3. Non-structural protein 2B: Forms a heterodimer with serine protease NS3. May form homooligomers. 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

GO - Molecular functioni

Structurei

Secondary structure

11683
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Turni2 – 5Combined sources4
Beta strandi7 – 13Combined sources7
Beta strandi20 – 24Combined sources5
Beta strandi30 – 34Combined sources5
Beta strandi36 – 38Combined sources3
Beta strandi41 – 50Combined sources10
Beta strandi55 – 72Combined sources18
Beta strandi75 – 77Combined sources3
Helixi83 – 85Combined sources3
Beta strandi90 – 100Combined sources11
Helixi101 – 103Combined sources3
Beta strandi109 – 128Combined sources20
Beta strandi135 – 143Combined sources9
Turni148 – 152Combined sources5
Beta strandi159 – 164Combined sources6
Beta strandi171 – 175Combined sources5
Turni176 – 178Combined sources3
Beta strandi179 – 186Combined sources8
Helixi193 – 195Combined sources3
Beta strandi196 – 201Combined sources6
Beta strandi204 – 209Combined sources6
Helixi210 – 214Combined sources5
Beta strandi220 – 222Combined sources3
Helixi234 – 237Combined sources4
Beta strandi238 – 241Combined sources4
Beta strandi249 – 252Combined sources4
Helixi257 – 263Combined sources7
Turni264 – 266Combined sources3
Beta strandi273 – 276Combined sources4
Beta strandi284 – 288Combined sources5
Beta strandi306 – 310Combined sources5
Beta strandi320 – 326Combined sources7
Beta strandi332 – 334Combined sources3
Beta strandi337 – 340Combined sources4
Beta strandi346 – 353Combined sources8
Beta strandi365 – 370Combined sources6
Beta strandi373 – 381Combined sources9
Beta strandi383 – 385Combined sources3
Beta strandi387 – 393Combined sources7

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1TG8X-ray2.61A1-395[»]
1TGEelectron microscopy12.50A/B/C1-395[»]
ProteinModelPortaliP27914.
SMRiP27914.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP27914.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini1066 – 1243Peptidase S7PROSITE-ProRule annotationAdd BLAST178
Domaini1245 – 1401Helicase ATP-bindingPROSITE-ProRule annotationAdd BLAST157
Domaini1411 – 1582Helicase C-terminalPROSITE-ProRule annotationAdd BLAST172

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni98 – 111Fusion peptideBy similarityAdd BLAST14
Regioni1249 – 1252Important for RNA-bindingBy similarity4

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi1349 – 1352DEAH boxPROSITE-ProRule annotation4

Domaini

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

Keywords - Domaini

Transmembrane, Transmembrane helix

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.
IPR013755. Flav_gly_cen_dom_subdom1.
IPR027287. Flavi_E_Ig-like.
IPR026470. Flavi_E_Stem/Anchor_dom.
IPR001157. Flavi_NS1.
IPR000752. Flavi_NS2A.
IPR000336. Flavivir/Alphavir_Ig-like.
IPR001850. Flavivirus_NS3_S7.
IPR011998. Glycoprot_cen/dimer.
IPR013756. GlyE_cen_dom_subdom2.
IPR014001. Helicase_ATP-bd.
IPR001650. Helicase_C.
IPR014756. Ig_E-set.
IPR027417. P-loop_NTPase.
IPR009003. Peptidase_S1_PA.
PfamiView 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.
SMARTiView protein in SMART
SM00487. DEXDc. 1 hit.
SM00490. HELICc. 1 hit.
SUPFAMiSSF50494. SSF50494. 1 hit.
SSF52540. SSF52540. 2 hits.
SSF56983. SSF56983. 1 hit.
SSF81296. SSF81296. 1 hit.
TIGRFAMsiTIGR04240. flavi_E_stem. 1 hit.
PROSITEiView protein in PROSITE
PS51528. FLAVIVIRUS_NS3PRO. 1 hit.
PS51192. HELICASE_ATP_BIND_1. 1 hit.
PS51194. HELICASE_CTER. 1 hit.

Sequencei

Sequence statusi: Fragments.

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

P27914-1 [UniParc]FASTAAdd to basket

« Hide

        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
Length:1,683
Mass (Da):187,440
Last modified:August 1, 1992 - v1
Checksum:i3B0438D96196BFC8
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Non-terminal residuei11
Non-adjacent residuesi1065 – 1066Curated2
Non-terminal residuei16831

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.
PIRiPQ0507.
S11482.

Entry informationi

Entry nameiPOLG_DEN2T
AccessioniPrimary (citable) accession number: P27914
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 1, 1992
Last sequence update: August 1, 1992
Last modified: September 27, 2017
This is version 134 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

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references