P27914 (POLG_DEN2T) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names	Recommended name: Genome polyprotein Cleaved into the following 5 chains: Envelope protein E Non-structural protein 1 Short name=NS1 Non-structural protein 2A Short name=NS2A Non-structural protein 2A-alpha Short name=NS2A-alpha 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
Organism	Dengue virus type 2 (strain Tonga/EKB194/1974) (DENV-2)
Taxonomic identifier	11067 [NCBI]
Taxonomic lineage	Viruses › ssRNA positive-strand viruses, no DNA stage › Flaviviridae › Flavivirus › Dengue virus group
Virus host	Erythrocebus patas (Red guenon) (Cercopithecus patas) [TaxID: 9538] Homo sapiens (Human) [TaxID: 9606] Diceromyia [TaxID: 53539] Aedimorphus [TaxID: 53540] Stegomyia [TaxID: 53541]

Protein attributes

Sequence length	1683 AA.
Sequence status	Fragments.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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 an 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. 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. Non-structural protein 2A may be involved viral RNA replication and capsid assembly Potential. 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.
Catalytic activity	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.
Subunit structure	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.
Subcellular location	Envelope protein E: Virion membrane; Multi-pass membrane protein By similarity. Host endoplasmic reticulum membrane; Multi-pass membrane protein By similarity. Non-structural protein 1: Secreted. Host endoplasmic reticulum membrane; Peripheral membrane protein; Lumenal side By similarity. Non-structural protein 2A-alpha: Host endoplasmic reticulum membrane; Multi-pass membrane protein Potential. Non-structural protein 2A: Host endoplasmic reticulum membrane; Multi-pass membrane protein Potential. Serine protease NS3: Host endoplasmic reticulum membrane; Peripheral membrane protein; Cytoplasmic side By similarity. Note: Remains non-covalently associated to NS3 protease By similarity.
Post-translational modification	Specific enzymatic cleavages in vivo yield mature proteins By similarity.
Sequence similarities	Contains 1 helicase ATP-binding domain. Contains 1 helicase C-terminal domain. Contains 1 peptidase S7 domain.

Ontologies

Keywords
Biological process	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 Initiation of viral infection Viral attachment to host cell Viral penetration into host cytoplasm Virus endocytosis by host
Cellular component	Host endoplasmic reticulum Host membrane Membrane Secreted Viral envelope protein Virion
Domain	Transmembrane Transmembrane helix
Ligand	ATP-binding Nucleotide-binding Viral nucleoprotein
Molecular function	Capsid protein Hydrolase Protease Serine protease
PTM	Cleavage on pair of basic residues Disulfide bond Glycoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	interspecies interaction between organisms Inferred from electronic annotation. Source: UniProtKB-KW proteolysis Inferred from electronic annotation. Source: UniProtKB-KW viral genome replication Inferred from electronic annotation. Source: InterPro
Cellular component	host cell endoplasmic reticulum membrane Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW viral capsid Inferred from electronic annotation. Source: UniProtKB-KW viral envelope Inferred from electronic annotation. Source: InterPro virion membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW ATP-dependent helicase activity Inferred from electronic annotation. Source: InterPro RNA helicase activity Inferred from electronic annotation. Source: InterPro double-stranded RNA binding Inferred from electronic annotation. Source: InterPro serine-type peptidase activity Inferred from electronic annotation. Source: UniProtKB-KW structural molecule activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

‹1 – ›1683

›1683

Genome polyprotein

PRO_0000405219

Chain

1 – 495

495

Envelope protein E By similarity

PRO_0000037980

Chain

496 – 847

352

Non-structural protein 1 By similarity

PRO_0000037981

Chain

848 – 1065

218

Non-structural protein 2A By similarity

PRO_0000308290

Chain

848 – 1035

188

Non-structural protein 2A-alpha By similarity

PRO_0000037982

Chain

1066 – 1683

618

Serine protease NS3 By similarity

PRO_0000037983

Regions

Topological domain

‹1 – 445

›445

Extracellular Potential

Intramembrane

446 – 466

21

Helical; Potential

Topological domain

467 – 472

6

Extracellular Potential

Intramembrane

473 – 493

21

Helical; Potential

Topological domain

494 – 844

351

Extracellular Potential

Transmembrane

845 – 865

21

Helical; Potential

Topological domain

866 – 876

11

Cytoplasmic Potential

Transmembrane

877 – 897

21

Helical; Potential

Topological domain

898 – 902

5

Lumenal Potential

Transmembrane

903 – 923

21

Helical; Potential

Topological domain

924 – 991

68

Cytoplasmic Potential

Transmembrane

992 – 1012

21

Helical; Potential

Topological domain

1013 – 1037

25

Lumenal Potential

Transmembrane

1038 – 1058

21

Helical; Potential

Topological domain

1059 – ›1683

›625

Cytoplasmic Potential

Domain

1066 – 1243

178

Peptidase S7

Domain

1245 – 1401

157

Helicase ATP-binding

Domain

1411 – 1582

172

Helicase C-terminal

Nucleotide binding

1258 – 1265

8

ATP Potential

Motif

1349 – 1352

4

DEAH box

Sites

Active site

1116

1

Charge relay system; for serine protease NS3 activity By similarity

Active site

1140

1

Charge relay system; for serine protease NS3 activity By similarity

Active site

1200

1

Charge relay system; for serine protease NS3 activity By similarity

Site

495 – 496

2

Cleavage; by host signal peptidase Potential

Amino acid modifications

Glycosylation

67

1

N-linked (GlcNAc...); by host Potential

Glycosylation

153

1

N-linked (GlcNAc...); by host Potential

Disulfide bond

3 ↔ 30

By similarity

Disulfide bond

60 ↔ 121

By similarity

Disulfide bond

74 ↔ 105

By similarity

Disulfide bond

92 ↔ 116

By similarity

Disulfide bond

185 ↔ 285

By similarity

Disulfide bond

302 ↔ 333

By similarity

Experimental info

Non-adjacent residues

1065 – 1066

2

Non-terminal residue

1

1

Non-terminal residue

1683

1

Secondary structure

1

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1683

Helix Strand Turn

Details...

Turn

2 – 5

4

Beta strand

7 – 13

7

Beta strand

20 – 24

5

Beta strand

30 – 34

5

Beta strand

36 – 38

3

Beta strand

41 – 50

10

Beta strand

55 – 72

18

Beta strand

75 – 77

3

Helix

83 – 85

3

Beta strand

90 – 100

11

Helix

101 – 103

3

Beta strand

109 – 128

20

Beta strand

135 – 143

9

Turn

148 – 152

5

Beta strand

159 – 164

6

Beta strand

171 – 175

5

Turn

176 – 178

3

Beta strand

179 – 186

8

Helix

193 – 195

3

Beta strand

196 – 201

6

Beta strand

204 – 209

6

Helix

210 – 214

5

Beta strand

220 – 222

3

Helix

234 – 237

4

Beta strand

238 – 241

4

Beta strand

249 – 252

4

Helix

257 – 263

7

Turn

264 – 266

3

Beta strand

273 – 276

4

Beta strand

284 – 288

5

Beta strand

306 – 310

5

Beta strand

320 – 326

7

Beta strand

332 – 334

3

Beta strand

337 – 340

4

Beta strand

346 – 353

8

Beta strand

365 – 370

6

Beta strand

373 – 381

9

Beta strand

383 – 385

3

Beta strand

387 – 393

7

Sequences

	Sequence		Length	Mass (Da)
	P27914 [UniParc]. Last modified August 1, 1992. Version 1. Checksum: 3B0438D96196BFC8	FASTA	1,683	187,440
	10 20 30 40 50 60 MRCIGISNRD FVEGVSGGSW VDIVLEHGSC VTTMAKNKPT LDFELIKTEA KQPATLRKYC 70 80 90 100 110 120 IEAKLTNTTT DSRCPTQGEP TLNEEQDKRF VCKHSMVDRG WGNGCGLFGK GGIVTCAMFT 130 140 150 160 170 180 CKKNMEGKIV QPENLEYTVV ITPHSGEEHA VGNDTGKHGK EVKITPQSSI TEAELTGYGT 190 200 210 220 230 240 VTMECSPRTG LDFNEMVLLQ MEDKAWLVHR QWFLDLPLPW LPGADTQGSN WIQKETLVTF 250 260 270 280 290 300 KNPHAKKQDV VVLGSQEGAM HTALTGATEI QMSSGNLLFT GHLKCRLRMD KLQLKGMSYS 310 320 330 340 350 360 MCTGKFKIVK EIAETQHGTI VIRVQYEGDG SPCKIPFEIM DLEKRHVLGR LITVNPIVTE 370 380 390 400 410 420 KDSPVNIEAE PPFGDSYIII GVEPGQLKLD WFKKGSSIGQ MFETTMRGAK RMAILGDTAW 430 440 450 460 470 480 DFGSLGGVFT SIGKALHQVF GAIYGAAFSG VSWTMKILIG VIITWIGMNS RSTSLSVSLV 490 500 510 520 530 540 LVGIVTLYLG VMVQADSGCV VSWKNKELKC GSGIFVTDNV HTWTEQYKFQ PESPSKLASA 550 560 570 580 590 600 IQKAHEEGIC GIRSVTRLEN LMWKQITSEL NHILSENEVK LTIMTGDIKG IMQVGKRSLR 610 620 630 640 650 660 PQPTELRYSW KTWGKAKMLS TELHNQTFLI DGPETAECPN TNRAWNSLEV EDYGFGVFTT 670 680 690 700 710 720 NIWLRLREKQ DVFCDSKLMS AAIKDNRAVH ADMGYWIESA LNDTWKIEKA SFIEVKSCHW 730 740 750 760 770 780 PKSHTLWSNG VLESEMVIPK NFAGPVSQHN NRPGYYTQTA GPWHLGKLEM DFDFCEGTTV 790 800 810 820 830 840 VVTEDCGNRG PSLRTTTASG KLITEWCCRS CTLPPLRYRG EDGCWYGMEI RPLKEKEENL 850 860 870 880 890 900 VSSLVTAGHG QIDNFSLGIL GMALFLEEML RTRVGTKHAI LLVAVSFVTL ITGNMSFRDL 910 920 930 940 950 960 GRVMVMVGAT MTDDIGMGVT YLALLAAFRV RPTFAAGLLL RKLTSKELMM TTIGIVLLSQ 970 980 990 1000 1010 1020 SSIPETILEL TDALALGMMV LKMVRNMEKY QLAVTIMAIL CVPNAVILQN AWKVSCTILA 1030 1040 1050 1060 1070 1080 VVSVSPLLLT SSQQKADWIP LALTIKGLNP TAIFLTTLSR TSKKRAGVLW DVPSPPPVGK 1090 1100 1110 1120 1130 1140 AELEDGAYRI KQKGILGYSQ IGAGVYKEGT FHTMWHVTRG AVLMHKGKRI EPSWADVKKD 1150 1160 1170 1180 1190 1200 LISYGGGWKL EGEWKEGEEV QVLALEPGKN PRAVQTKPGL FRTNTGTIGA VSLDFSPGTS 1210 1220 1230 1240 1250 1260 GSPIVDKKGK VVGLYGNGVV TRSGAYVSAI AQTEKSIEDN PEIEDDIFRK RRLTIMDLHP 1270 1280 1290 1300 1310 1320 GAGKTKRYLP AIVREAIKRG LRTLILAPTR VVAAEMEEAL RGLPIRYQTP AIRAEHTGRE 1330 1340 1350 1360 1370 1380 IVDLMCHATF TMRLLSPIRV PNYNLIIMDE AHFTDPASIA ARGYISTRVE MGEAAGIFMT 1390 1400 1410 1420 1430 1440 ATPPGSRDPF PQSNAPIMDE EREIPERSWN SGHEWVTDFK GKTVWFVPSI KTGNDIAACL 1450 1460 1470 1480 1490 1500 RKNGKRVIQL SRKTFDSEYV KTRTNDWDFV VTTDISEMGA NFKAERVIDP RRCMKPVILT 1510 1520 1530 1540 1550 1560 DGEERVILAG PMPVTHSSAA QRRGRIGRNP RNENDQYIYM GEPLENDEDC AHWKEAKMLL 1570 1580 1590 1600 1610 1620 DNINTPEGII PSIFEPEREK VDAIDGEYRL RGEARKTFVD LMRRGDLPVW LAYKVAAEGI 1630 1640 1650 1660 1670 1680 NYADRRWCFD GTRNNQILEE NVEVEIWTKE GERKKLKPRW LDARIYSDPL ALKEFKEFAA GRK

References

[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: 2216784] [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]	"Conformational changes of the flavivirus E glycoprotein." Zhang Y., Zhang W., Ogata S., Clements D., Strauss J.H., Baker T.S., Kuhn R.J., Rossmann M.G. Structure 12:1607-1618(2004) [PubMed: 15341726] [Abstract] Cited for: STRUCTURE BY ELECTRON MICROSCOPY (12.5 ANGSTROMS) OF 1-395, X-RAY CRYSTALLOGRAPHY (2.61 ANGSTROMS) OF 1-395.
+	Additional computationally mapped references.

Web resources

Virus Pathogen Resource

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X54319 Genomic RNA. Translation: CAA38217.1.
X57469 Genomic RNA. Translation: CAA40705.1.
X57468 Genomic RNA. Translation: CAA40704.1.

PIR

PQ0507.
S11482.

3D structure databases

PDBe
RCSB PDB
PDBj

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	[»]

ProteinModelPortal

P27914.

SMR

P27914. Positions 1-394, 1085-1683.

ModBase

Search...

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Family and domain databases

InterPro

IPR014001. DEAD-like_helicase.
IPR011492. DEAD_Flavivir.
IPR013756. Flav_glyE_cen_dom_subdom2.
IPR013754. Flav_glyE_dim.
IPR001157. Flavi_NS1.
IPR000752. Flavi_NS2A.
IPR000336. Flv_glyE_Ig-like.
IPR011999. GlycoprotE_cen/dimer_Flavivir.
IPR011998. GlycoprotE_cen/dimer_vir.
IPR001650. Helicase_C.
IPR014756. Ig_E-set.
IPR009003. Pept_cys/ser_Trypsin-like.
IPR001850. Peptidase_S7.
[Graphical view]

Gene3D

G3DSA:3.30.67.10. Flav_glyE_cen_2. 1 hit.
G3DSA:2.60.98.10. Flav_glyE_dim. 3 hits.
G3DSA:2.60.40.350. Flv_glyE_Ig-like. 1 hit.

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.
PF00271. Helicase_C. 1 hit.
PF00949. Peptidase_S7. 1 hit.
[Graphical view]

SMART

SM00487. DEXDc. 1 hit.
SM00490. HELICc. 1 hit.
[Graphical view]

SUPFAM

SSF56983. Flavi_glycoprotE. 1 hit.
SSF81296. Ig_E-set. 1 hit.
SSF50494. Pept_Ser_Cys. 1 hit.

PROSITE

PS00690. DEAH_ATP_HELICASE. False negative.
PS51528. FLAVIVIRUS_NS3PRO. 1 hit.
PS51192. HELICASE_ATP_BIND_1. 1 hit.
PS51194. HELICASE_CTER. 1 hit.
[Graphical view]

ProtoNet

Search...

Entry information

Entry name

POLG_DEN2T

Accession

Primary (citable) accession number: P27914

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1992
Last sequence update:	August 1, 1992
Last modified:	November 16, 2011
This is version 99 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Viral Protein Annotation Program