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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 binding to host cell surface receptor is followed by virus internalization through clathrin-mediated endocytosis. Envelope protein E is subsequently involved in membrane fusion between virion and host late endosomes. Synthesized as a homodimer with prM which acts as a chaperone for envelope protein E. After cleavage of prM, envelope protein E dissociate from small envelope protein M and homodimerizes (By similarity).By similarity
Non-structural protein 1 is involved in virus replication and regulation of the innate immune response. Soluble and membrane-associated NS1 may activate human complement and induce host vascular leakage. This effect might explain the clinical manifestations of dengue hemorrhagic fever and dengue shock syndrome (By similarity).By similarity
Non-structural protein 2A may be involved viral RNA replication and capsid assembly.Curated
Non-structural protein 2B is a required cofactor for the serine protease function of NS3.By 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 (By similarity).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)LengthDescriptionGraphical viewFeature identifierActions
Active sitei1116 – 11161Charge relay system; for serine protease NS3 activityPROSITE-ProRule annotation
Active sitei1140 – 11401Charge relay system; for serine protease NS3 activityPROSITE-ProRule annotation
Active sitei1200 – 12001Charge relay system; for serine protease NS3 activityPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi1258 – 12658ATPPROSITE-ProRule annotation

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Serine protease

Keywords - Biological processi

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, Viral attachment to host cell, Viral penetration into host cytoplasm, Virus endocytosis by host, Virus entry into host cell

Keywords - Ligandi

ATP-binding, Nucleotide-binding, Viral nucleoprotein

Names & Taxonomyi

Protein namesi
Recommended name:
Genome polyprotein
Cleaved into the following 5 chains:
Non-structural protein 2A-alpha
Short name:
NS2A-alpha
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 :
Non-structural protein 2A-alpha :
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 NS3 protease.PROSITE-ProRule annotation

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini‹1 – 445›445ExtracellularSequence analysisAdd
BLAST
Intramembranei446 – 46621HelicalSequence analysisAdd
BLAST
Topological domaini467 – 4726ExtracellularSequence analysis
Intramembranei473 – 49321HelicalSequence analysisAdd
BLAST
Topological domaini494 – 844351ExtracellularSequence analysisAdd
BLAST
Transmembranei845 – 86521HelicalSequence analysisAdd
BLAST
Topological domaini866 – 87611CytoplasmicSequence analysisAdd
BLAST
Transmembranei877 – 89721HelicalSequence analysisAdd
BLAST
Topological domaini898 – 9025LumenalSequence analysis
Transmembranei903 – 92321HelicalSequence analysisAdd
BLAST
Topological domaini924 – 99168CytoplasmicSequence analysisAdd
BLAST
Transmembranei992 – 101221HelicalSequence analysisAdd
BLAST
Topological domaini1013 – 103725LumenalSequence analysisAdd
BLAST
Transmembranei1038 – 105821HelicalSequence analysisAdd
BLAST
Topological domaini1059 – ›1683›625CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

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

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini‹1 – ›1683›1683Genome polyproteinPRO_0000405219Add
BLAST
Chaini1 – 495495Envelope protein EBy similarityPRO_0000037980Add
BLAST
Chaini496 – 847352Non-structural protein 1By similarityPRO_0000037981Add
BLAST
Chaini848 – 1065218Non-structural protein 2ABy similarityPRO_0000308290Add
BLAST
Chaini848 – 1035188Non-structural protein 2A-alphaBy similarityPRO_0000037982Add
BLAST
Chaini1066 – 1683618Serine protease NS3By similarityPRO_0000037983Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi3 ↔ 30By similarity
Disulfide bondi60 ↔ 121By similarity
Glycosylationi67 – 671N-linked (GlcNAc...); by hostSequence analysis
Disulfide bondi74 ↔ 105By similarity
Disulfide bondi92 ↔ 116By similarity
Glycosylationi153 – 1531N-linked (GlcNAc...); by hostSequence analysis
Disulfide bondi185 ↔ 285By similarity
Disulfide bondi302 ↔ 333By similarity

Post-translational modificationi

Specific enzymatic cleavages in vivo yield mature proteins.By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei495 – 4962Cleavage; by host signal peptidaseSequence analysis

Keywords - PTMi

Cleavage on pair of basic residues, Disulfide bond, Glycoprotein

Interactioni

Subunit structurei

In immature particles, there are 60 icosaedrally organized trimeric spikes on the surface. Each spike consists of three heterodimers of envelope protein M precursor (prM) and envelope protein E. NS1 forms homodimers as well as homohexamers when secreted. NS1 may interact with NS4A. NS3 and NS2B form a heterodimer. NS3 is the catalytic subunit, whereas NS2B strongly stimulates the latter, acting as a cofactor. In the absence of the NS2B, NS3 protease is unfolded and inactive (By similarity).By similarity

Structurei

Secondary structure

1
1683
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Turni2 – 54Combined sources
Beta strandi7 – 137Combined sources
Beta strandi20 – 245Combined sources
Beta strandi30 – 345Combined sources
Beta strandi36 – 383Combined sources
Beta strandi41 – 5010Combined sources
Beta strandi55 – 7218Combined sources
Beta strandi75 – 773Combined sources
Helixi83 – 853Combined sources
Beta strandi90 – 10011Combined sources
Helixi101 – 1033Combined sources
Beta strandi109 – 12820Combined sources
Beta strandi135 – 1439Combined sources
Turni148 – 1525Combined sources
Beta strandi159 – 1646Combined sources
Beta strandi171 – 1755Combined sources
Turni176 – 1783Combined sources
Beta strandi179 – 1868Combined sources
Helixi193 – 1953Combined sources
Beta strandi196 – 2016Combined sources
Beta strandi204 – 2096Combined sources
Helixi210 – 2145Combined sources
Beta strandi220 – 2223Combined sources
Helixi234 – 2374Combined sources
Beta strandi238 – 2414Combined sources
Beta strandi249 – 2524Combined sources
Helixi257 – 2637Combined sources
Turni264 – 2663Combined sources
Beta strandi273 – 2764Combined sources
Beta strandi284 – 2885Combined sources
Beta strandi306 – 3105Combined sources
Beta strandi320 – 3267Combined sources
Beta strandi332 – 3343Combined sources
Beta strandi337 – 3404Combined sources
Beta strandi346 – 3538Combined sources
Beta strandi365 – 3706Combined sources
Beta strandi373 – 3819Combined sources
Beta strandi383 – 3853Combined sources
Beta strandi387 – 3937Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1TG8X-ray2.61A1-395[»]
1TGEelectron microscopy12.50A/B/C1-395[»]
ProteinModelPortaliP27914.
SMRiP27914. Positions 1-394, 1085-1683.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP27914.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini1066 – 1243178Peptidase S7PROSITE-ProRule annotationAdd
BLAST
Domaini1245 – 1401157Helicase ATP-bindingPROSITE-ProRule annotationAdd
BLAST
Domaini1411 – 1582172Helicase C-terminalPROSITE-ProRule annotationAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi1349 – 13524DEAH box

Sequence similaritiesi

Contains 1 helicase ATP-binding domain.PROSITE-ProRule annotation
Contains 1 helicase C-terminal domain.PROSITE-ProRule annotation
Contains 1 peptidase S7 domain.PROSITE-ProRule annotation

Keywords - Domaini

Transmembrane, Transmembrane helix

Family and domain databases

Gene3Di2.60.40.350. 1 hit.
2.60.98.10. 2 hits.
3.30.387.10. 1 hit.
3.40.50.300. 2 hits.
InterProiIPR011492. DEAD_Flavivir.
IPR013755. Flav_gly_cen_dom_subdom1.
IPR026470. Flavi_E_Stem/Anchor_dom.
IPR001157. Flavi_NS1.
IPR000752. Flavi_NS2A.
IPR000336. Flavivir/Alphavir_Ig-like.
IPR001850. Flavivirus_NS3_S7.
IPR027287. Flavovir_Ig-like.
IPR011998. Glycoprot_cen/dimer.
IPR013754. GlyE_dim.
IPR014001. Helicase_ATP-bd.
IPR001650. Helicase_C.
IPR014756. Ig_E-set.
IPR027417. P-loop_NTPase.
IPR009003. Peptidase_S1_PA.
[Graphical view]
PfamiPF07652. 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.
[Graphical view]
SMARTiSM00487. DEXDc. 1 hit.
SM00490. HELICc. 1 hit.
[Graphical view]
SUPFAMiSSF50494. SSF50494. 1 hit.
SSF52540. SSF52540. 2 hits.
SSF56983. SSF56983. 1 hit.
SSF81296. SSF81296. 1 hit.
TIGRFAMsiTIGR04240. flavi_E_stem. 1 hit.
PROSITEiPS51528. FLAVIVIRUS_NS3PRO. 1 hit.
PS51192. HELICASE_ATP_BIND_1. 1 hit.
PS51194. HELICASE_CTER. 1 hit.
[Graphical view]

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)LengthDescriptionGraphical viewFeature identifierActions
Non-terminal residuei1 – 11
Non-adjacent residuesi1065 – 10662Curated
Non-terminal residuei1683 – 16831

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.

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.
PIRiPQ0507.
S11482.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1TG8X-ray2.61A1-395[»]
1TGEelectron microscopy12.50A/B/C1-395[»]
ProteinModelPortaliP27914.
SMRiP27914. Positions 1-394, 1085-1683.
ModBaseiSearch...
MobiDBiSearch...

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Miscellaneous databases

EvolutionaryTraceiP27914.

Family and domain databases

Gene3Di2.60.40.350. 1 hit.
2.60.98.10. 2 hits.
3.30.387.10. 1 hit.
3.40.50.300. 2 hits.
InterProiIPR011492. DEAD_Flavivir.
IPR013755. Flav_gly_cen_dom_subdom1.
IPR026470. Flavi_E_Stem/Anchor_dom.
IPR001157. Flavi_NS1.
IPR000752. Flavi_NS2A.
IPR000336. Flavivir/Alphavir_Ig-like.
IPR001850. Flavivirus_NS3_S7.
IPR027287. Flavovir_Ig-like.
IPR011998. Glycoprot_cen/dimer.
IPR013754. GlyE_dim.
IPR014001. Helicase_ATP-bd.
IPR001650. Helicase_C.
IPR014756. Ig_E-set.
IPR027417. P-loop_NTPase.
IPR009003. Peptidase_S1_PA.
[Graphical view]
PfamiPF07652. 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.
[Graphical view]
SMARTiSM00487. DEXDc. 1 hit.
SM00490. HELICc. 1 hit.
[Graphical view]
SUPFAMiSSF50494. SSF50494. 1 hit.
SSF52540. SSF52540. 2 hits.
SSF56983. SSF56983. 1 hit.
SSF81296. SSF81296. 1 hit.
TIGRFAMsiTIGR04240. flavi_E_stem. 1 hit.
PROSITEiPS51528. FLAVIVIRUS_NS3PRO. 1 hit.
PS51192. HELICASE_ATP_BIND_1. 1 hit.
PS51194. HELICASE_CTER. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. "Nucleotide sequence of the envelope glycoprotein gene of a dengue-2 virus isolated during an epidemic of benign dengue fever in Tonga in 1974."
    Chen W., Maguire T.
    Nucleic Acids Res. 18:5889-5889(1990) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 1-495.
  2. Qu X., Chen W., Maguire T.
    Submitted (MAR-1991) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 496-1683.
  3. Cited for: STRUCTURE BY ELECTRON MICROSCOPY (12.5 ANGSTROMS) OF 1-395, X-RAY CRYSTALLOGRAPHY (2.61 ANGSTROMS) OF 1-395.

Entry informationi

Entry nameiPOLG_DEN2T
AccessioniPrimary (citable) accession number: P27914
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 1, 1992
Last sequence update: August 1, 1992
Last modified: October 14, 2015
This is version 126 of the entry and version 1 of the sequence. [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
  2. Peptidase families
    Classification of peptidase families and list of entries
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.