P29990 (POLG_DEN26) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names	Recommended name: Genome polyprotein Cleaved into the following 14 chains: Capsid protein C Alternative name(s): Core protein prM Peptide pr Small envelope protein M Alternative name(s): Matrix protein 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 subunit NS2B Alternative name(s): Flavivirin protease NS2B regulatory subunit Non-structural protein 2B Serine protease NS3 EC=3.4.21.91 EC=3.6.1.15 EC=3.6.4.13 Alternative name(s): Flavivirin protease NS3 catalytic subunit Non-structural protein 3 Non-structural protein 4A Short name=NS4A Peptide 2k Non-structural protein 4B Short name=NS4B RNA-directed RNA polymerase NS5 EC=2.1.1.56 EC=2.1.1.57 EC=2.7.7.48 Alternative name(s): Non-structural protein 5
Organism	Dengue virus type 2 (strain Thailand/16681/1984) (DENV-2) [Complete proteome]
Taxonomic identifier	31634 [NCBI]
Taxonomic lineage	Viruses › ssRNA positive-strand viruses, no DNA stage › Flaviviridae › Flavivirus › Dengue virus group
Virus host	Aedes aegypti (Yellowfever mosquito) (Culex aegypti) [TaxID: 7159] Erythrocebus patas (Red guenon) (Cercopithecus patas) [TaxID: 9538] Homo sapiens (Human) [TaxID: 9606] Aedes furcifer (Mosquito) [TaxID: 299627] Aedes taylori (Mosquito) [TaxID: 299628]

Protein attributes

Sequence length	3391 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	prM acts as a chaperone for envelope protein E during intracellular virion assembly by masking and inactivating envelope protein E fusion peptide. prM is matured in the last step of virion assembly, presumably to avoid catastrophic activation of the viral fusion peptide induced by the acidic pH of the trans-Golgi network. After cleavage by host furin, the pr peptide is released in the extracellular medium and small envelope protein M and envelope protein E homodimers are dissociated By similarity. Ref.5 Ref.6 Ref.9 Ref.11 Ref.12 Ref.13 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. Ref.5 Ref.6 Ref.9 Ref.11 Ref.12 Ref.13 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. Ref.5 Ref.6 Ref.9 Ref.11 Ref.12 Ref.13 Non-structural protein 2A may be involved viral RNA replication and capsid assembly Potential. Ref.5 Ref.6 Ref.9 Ref.11 Ref.12 Ref.13 Non-structural protein 2B is a required cofactor for the serine protease function of NS3 By similarity. Ref.5 Ref.6 Ref.9 Ref.11 Ref.12 Ref.13 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. Ref.5 Ref.6 Ref.9 Ref.11 Ref.12 Ref.13 Non-structural protein 4A induces host endoplasmic reticulum membrane rearrangements leading to the formation of virus-induced membranous vesicles hosting the dsRNA and polymerase, functionning as a replication complex. NS4A might also regulate the ATPase activity of the NS3 helicase By similarity. Ref.5 Ref.6 Ref.9 Ref.11 Ref.12 Ref.13 Peptide 2k functions as a signal peptide for NS4B and is required for the interferon antagonism activity of the latter By similarity. Ref.5 Ref.6 Ref.9 Ref.11 Ref.12 Ref.13 Non-structural protein 4B 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. Ref.5 Ref.6 Ref.9 Ref.11 Ref.12 Ref.13 RNA-directed RNA polymerase NS5 replicates the viral (+) and (-) 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 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. Ref.5 Ref.6 Ref.9 Ref.11 Ref.12 Ref.13 Capsid protein C self-assembles to form an icosahedral capsid about 30 nm in diameter. The capsid encapsulates the genomic RNA By similarity. Ref.5 Ref.6 Ref.9 Ref.11 Ref.12 Ref.13
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. Nucleoside triphosphate + RNA(n) = diphosphate + RNA(n+1). NTP + H2O = NDP + phosphate. ATP + H2O = ADP + phosphate. S-adenosyl-L-methionine + G(5')pppR-RNA = S-adenosyl-L-homocysteine + m7G(5')pppR-RNA. S-adenosyl-L-methionine + m7G(5')pppR-RNA = S-adenosyl-L-homocysteine + m7G(5')pppRm-RNA.
Subunit structure	Capsid protein C forms homodimers. prM and envelope protein E form heterodimers in the endoplasmic reticulum and Golgi. 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. NS3 interacts with unphosphorylated NS5; this interaction stimulates NS5 guanylyltransferase activity. NS5 interacts with host STAT2; this interaction inhibits the phosphorylation of the latter, and, when all viral proteins are present (polyprotein), targets STAT2 for degradation. Ref.2 Ref.4 Ref.11 Ref.12
Subcellular location	Capsid protein C: Virion Potential Ref.7. Peptide pr: Secreted By similarity Ref.7. Small envelope protein M: Virion membrane; Multi-pass membrane protein By similarity. Host endoplasmic reticulum membrane; Multi-pass membrane protein By similarity Ref.7. Envelope protein E: Virion membrane; Multi-pass membrane protein By similarity. Host endoplasmic reticulum membrane; Multi-pass membrane protein By similarity Ref.7. Non-structural protein 1: Secreted. Host endoplasmic reticulum membrane; Peripheral membrane protein; Lumenal side By similarity Ref.7. Non-structural protein 2A-alpha: Host endoplasmic reticulum membrane; Multi-pass membrane protein Potential Ref.7. Non-structural protein 2A: Host endoplasmic reticulum membrane; Multi-pass membrane protein Potential Ref.7. Serine protease subunit NS2B: Host endoplasmic reticulum membrane; Peripheral membrane protein; Cytoplasmic side By similarity Ref.7. Serine protease NS3: Host endoplasmic reticulum membrane; Peripheral membrane protein; Cytoplasmic side By similarity. Note: Remains non-covalently associated to NS3 protease By similarity. Ref.7 Non-structural protein 4A: Host endoplasmic reticulum membrane; Multi-pass membrane protein By similarity. Note: Located in RE-associated vesicles hosting the replication complex. Ref.7 Non-structural protein 4B: Host endoplasmic reticulum membrane; Multi-pass membrane protein By similarity Ref.7. RNA-directed RNA polymerase NS5: Host endoplasmic reticulum membrane; Peripheral membrane protein; Cytoplasmic side By similarity. Host nucleus. Note: Located in RE-associated vesicles hosting the replication complex. Ref.7
Domain	Transmembrane domains of the small envelope protein M and envelope protein E contains an endoplasmic reticulum retention signals By similarity.
Post-translational modification	Specific enzymatic cleavages in vivo yield mature proteins. The nascent protein C contains a C-terminal hydrophobic domain that act as a signal sequence for translocation of prM into the lumen of the ER. Mature protein C is cleaved at a site upstream of this hydrophobic domain by NS3. prM is cleaved in post-Golgi vesicles by a host furin, releasing the mature small envelope protein M, and peptide pr. Non-structural protein 2A-alpha, a C-terminally truncated form of non-structural protein 2A, results from partial cleavage by NS3. Peptide 2K acts as a signal sequence and is removed from the N-terminus of NS4B by the host signal peptidase in the ER lumen. Signal cleavage at the 2K-4B site requires a prior NS3 protease-mediated cleavage at the 4A-2K site By similarity. Ref.3 Ref.8 RNA-directed RNA polymerase NS5 is phosphorylated on serines residues. This phosphorylation may trigger NS5 nuclear localization By similarity. Envelope protein E and non-structural protein 1 are N-glycosylated By similarity.
Sequence similarities	Contains 1 helicase ATP-binding domain. Contains 1 helicase C-terminal domain. Contains 1 peptidase S7 domain. Contains 1 RdRp catalytic 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 Inhibition of host STAT2 by virus Inhibition of host TYK2 by virus Inhibition of host innate immune response by virus Inhibition of host interferon signaling pathway by virus Initiation of viral infection RNA replication Transcription Transcription regulation Viral attachment to host cell Viral immunoevasion Viral penetration into host cytoplasm Virus endocytosis by host
Cellular component	Host endoplasmic reticulum Host membrane Host nucleus Membrane Secreted Viral envelope protein Virion
Domain	Transmembrane Transmembrane helix
Ligand	ATP-binding Metal-binding Nucleotide-binding RNA-binding
Molecular function	Capsid protein Helicase Hydrolase Methyltransferase Nucleotidyltransferase Protease RNA-directed RNA polymerase Serine protease Transferase
PTM	Cleavage on pair of basic residues Disulfide bond Glycoprotein Phosphoprotein
Technical term	3D-structure Complete proteome Multifunctional enzyme
Gene Ontology (GO)
Biological process	evasion by virus of host immune response Inferred from electronic annotation. Source: UniProtKB-KW proteolysis Inferred from electronic annotation. Source: UniProtKB-KW regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW transcription, DNA-dependent 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 host cell nucleus 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 RNA-directed RNA polymerase activity Inferred from electronic annotation. Source: UniProtKB-KW double-stranded RNA binding Inferred from electronic annotation. Source: InterPro mRNA (guanine-N7-)-methyltransferase activity Inferred from electronic annotation. Source: EC mRNA (nucleoside-2'-O-)-methyltransferase activity Inferred from electronic annotation. Source: EC metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW serine-type endopeptidase activity Inferred from electronic annotation. Source: InterPro serine-type exopeptidase activity Inferred from electronic annotation. Source: InterPro 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 – 3391	3391	Genome polyprotein		PRO_0000405213
	Chain	1 – 100	100	Capsid protein C		PRO_0000037925
	Propeptide	101 – 114	14	ER anchor for the protein C, removed in mature form by serine protease NS3		PRO_0000037926
	Chain	115 – 280	166	prM		PRO_0000264673
	Chain	115 – 205	91	Peptide pr		PRO_0000264674
	Chain	206 – 280	75	Small envelope protein M		PRO_0000037927
	Chain	281 – 775	495	Envelope protein E		PRO_0000037928
	Chain	776 – 1127	352	Non-structural protein 1		PRO_0000037929
	Chain	1128 – 1345	218	Non-structural protein 2A		PRO_0000037930
	Chain	1128 – 1315	188	Non-structural protein 2A-alpha		PRO_0000264675
	Chain	1346 – 1475	130	Serine protease subunit NS2B		PRO_0000037931
	Chain	1476 – 2093	618	Serine protease NS3		PRO_0000037932
	Chain	2094 – 2220	127	Non-structural protein 4A		PRO_0000037933
	Peptide	2221 – 2243	23	Peptide 2k		PRO_0000264676
	Chain	2244 – 2491	248	Non-structural protein 4B		PRO_0000037934
	Chain	2492 – 3391	900	RNA-directed RNA polymerase NS5		PRO_0000037935
Regions
	Topological domain	1 – 101	101	Cytoplasmic Potential
	Transmembrane	102 – 119	18	Helical; Potential
	Topological domain	120 – 242	123	Extracellular Potential
	Transmembrane	243 – 260	18	Helical; Potential
	Topological domain	261	1	Cytoplasmic Potential
	Transmembrane	262 – 280	19	Helical; Potential
	Topological domain	281 – 725	445	Extracellular Potential
	Intramembrane	726 – 746	21	Helical; Potential
	Topological domain	747 – 752	6	Extracellular Potential
	Intramembrane	753 – 773	21	Helical; Potential
	Topological domain	774 – 1124	351	Extracellular Potential
	Transmembrane	1125 – 1145	21	Helical; Potential
	Topological domain	1146 – 1156	11	Cytoplasmic Potential
	Transmembrane	1157 – 1177	21	Helical; Potential
	Topological domain	1178 – 1184	7	Lumenal Potential
	Transmembrane	1185 – 1205	21	Helical; Potential
	Topological domain	1206 – 1271	66	Cytoplasmic Potential
	Transmembrane	1272 – 1292	21	Helical; Potential
	Topological domain	1293 – 1317	25	Lumenal Potential
	Transmembrane	1318 – 1338	21	Helical; Potential
	Topological domain	1339 – 1346	8	Cytoplasmic Potential
	Transmembrane	1347 – 1367	21	Helical; Potential
	Topological domain	1368 – 1370	3	Lumenal Potential
	Transmembrane	1371 – 1391	21	Helical; Potential
	Topological domain	1392 – 1447	56	Cytoplasmic Potential
	Intramembrane	1448 – 1468	21	Helical; Potential
	Topological domain	1469 – 2147	679	Cytoplasmic Potential
	Transmembrane	2148 – 2168	21	Helical; Potential
	Topological domain	2169 – 2170	2	Lumenal Potential
	Intramembrane	2171 – 2191	21	Helical; Potential
	Topological domain	2192	1	Lumenal Potential
	Transmembrane	2193 – 2213	21	Helical; Potential
	Topological domain	2214 – 2228	15	Cytoplasmic Potential
	Transmembrane	2229 – 2249	21	Helical; Note=Signal for NS4B; Potential
	Topological domain	2250 – 2277	28	Lumenal Potential
	Intramembrane	2278 – 2295	18	Helical; Potential
	Topological domain	2296 – 2316	21	Lumenal Potential
	Intramembrane	2317 – 2337	21	Helical; Potential
	Topological domain	2338 – 2347	10	Lumenal Potential
	Transmembrane	2348 – 2368	21	Helical; Potential
	Topological domain	2369 – 2413	45	Cytoplasmic Potential
	Transmembrane	2414 – 2434	21	Helical; Potential
	Topological domain	2435 – 2459	25	Lumenal Potential
	Transmembrane	2460 – 2480	21	Helical; Potential
	Topological domain	2481 – 3391	911	Cytoplasmic Potential
	Domain	1476 – 1653	178	Peptidase S7
	Domain	1655 – 1811	157	Helicase ATP-binding
	Domain	1821 – 1988	168	Helicase C-terminal
	Domain	3020 – 3169	150	RdRp catalytic
	Nucleotide binding	1668 – 1675	8	ATP Potential
	Region	33 – 74	42	Hydrophobic; homodimerization of capsid protein C By similarity
	Region	37 – 72	36	Hydrophobic; homodimerization of capsid protein C
	Region	1398 – 1437	40	Interacts with and activates NS3 protease By similarity
	Motif	1759 – 1762	4	DEAH box
	Compositional bias	97 – 100	4	Poly-Arg
	Compositional bias	1434 – 1437	4	Poly-Glu
	Compositional bias	2148 – 2154	7	Poly-Leu
	Compositional bias	3383 – 3386	4	Poly-Glu
Sites
	Active site	1526	1	Charge relay system; for serine protease NS3 activity By similarity
	Active site	1550	1	Charge relay system; for serine protease NS3 activity By similarity
	Active site	1610	1	Charge relay system; for serine protease NS3 activity By similarity
	Active site	2552	1	For 2'-O-methyltransferase activity By similarity
	Active site	2637	1	For 2'-O-methyltransferase and N-7 methyltransferase activity By similarity
	Active site	2672	1	For 2'-O-methyltransferase activity By similarity
	Active site	2708	1	For 2'-O-methyltransferase activity By similarity
	Site	100 – 101	2	Cleavage; by viral protease NS3
	Site	114 – 115	2	Cleavage; by host signal peptidase
	Site	205 – 206	2	Cleavage; by host furin Potential
	Site	280 – 281	2	Cleavage; by host signal peptidase
	Site	775 – 776	2	Cleavage; by host signal peptidase
	Site	1127 – 1128	2	Cleavage; by host
	Site	1345 – 1346	2	Cleavage; by viral protease NS3
	Site	1475 – 1476	2	Cleavage; by autolysis
	Site	2093 – 2094	2	Cleavage; by autolysis
	Site	2220 – 2221	2	Cleavage; by viral protease NS3
	Site	2243 – 2244	2	Cleavage; by host signal peptidase
	Site	2491 – 2492	2	Cleavage; by viral protease NS3
Amino acid modifications
	Glycosylation	183	1	N-linked (GlcNAc...); by host Potential
	Glycosylation	347	1	N-linked (GlcNAc...); by host Potential
	Glycosylation	433	1	N-linked (GlcNAc...); by host Potential
	Glycosylation	982	1	N-linked (GlcNAc...); by host Potential
	Glycosylation	2301	1	N-linked (GlcNAc...); by host Potential
	Glycosylation	2305	1	N-linked (GlcNAc...); by host Potential
	Glycosylation	2457	1	N-linked (GlcNAc...); by host Potential
	Disulfide bond	283 ↔ 310		By similarity
	Disulfide bond	340 ↔ 401		By similarity
	Disulfide bond	354 ↔ 385		By similarity
	Disulfide bond	372 ↔ 396		By similarity
	Disulfide bond	465 ↔ 565		By similarity
	Disulfide bond	582 ↔ 613		By similarity

Sequences

	Sequence		Length	Mass (Da)
	P29990 [UniParc]. Last modified April 1, 1993. Version 1. Checksum: 2E20AD0D6C978ECC	FASTA	3,391	379,547
	10 20 30 40 50 60 MNDQRKKAKN TPFNMLKRER NRVSTVQQLT KRFSLGMLQG RGPLKLYMAL VAFLRFLTIP 70 80 90 100 110 120 PTAGILKRWG TIKKSKAINV LRGFRKEIGR MLNILNRRRR SAGMIIMLIP TVMAFHLTTR 130 140 150 160 170 180 NGEPHMIVSR QEKGKSLLFK TEDGVNMCTL MAMDLGELCE DTITYKCPLL RQNEPEDIDC 190 200 210 220 230 240 WCNSTSTWVT YGTCTTMGEH RRQKRSVALV PHVGMGLETR TETWMSSEGA WKHVQRIETW 250 260 270 280 290 300 ILRHPGFTMM AAILAYTIGT THFQRALIFI LLTAVTPSMT MRCIGMSNRD FVEGVSGGSW 310 320 330 340 350 360 VDIVLEHGSC VTTMAKNKPT LDFELIKTEA KQPATLRKYC IEAKLTNTTT ESRCPTQGEP 370 380 390 400 410 420 SLNEEQDKRF VCKHSMVDRG WGNGCGLFGK GGIVTCAMFR CKKNMEGKVV QPENLEYTIV 430 440 450 460 470 480 ITPHSGEEHA VGNDTGKHGK EIKITPQSST TEAELTGYGT VTMECSPRTG LDFNEMVLLQ 490 500 510 520 530 540 MENKAWLVHR QWFLDLPLPW LPGADTQGSN WIQKETLVTF KNPHAKKQDV VVLGSQEGAM 550 560 570 580 590 600 HTALTGATEI QMSSGNLLFT GHLKCRLRMD KLQLKGMSYS MCTGKFKVVK EIAETQHGTI 610 620 630 640 650 660 VIRVQYEGDG SPCKIPFEIM DLEKRHVLGR LITVNPIVTE KDSPVNIEAE PPFGDSYIII 670 680 690 700 710 720 GVEPGQLKLN WFKKGSSIGQ MFETTMRGAK RMAILGDTAW DFGSLGGVFT SIGKALHQVF 730 740 750 760 770 780 GAIYGAAFSG VSWTMKILIG VIITWIGMNS RSTSLSVTLV LVGIVTLYLG VMVQADSGCV 790 800 810 820 830 840 VSWKNKELKC GSGIFITDNV HTWTEQYKFQ PESPSKLASA IQKAHEEGIC GIRSVTRLEN 850 860 870 880 890 900 LMWKQITPEL NHILSENEVK LTIMTGDIKG IMQAGKRSLR PQPTELKYSW KTWGKAKMLS 910 920 930 940 950 960 TESHNQTFLI DGPETAECPN TNRAWNSLEV EDYGFGVFTT NIWLKLKEKQ DVFCDSKLMS 970 980 990 1000 1010 1020 AAIKDNRAVH ADMGYWIESA LNDTWKIEKA SFIEVKNCHW PKSHTLWSNG VLESEMIIPK 1030 1040 1050 1060 1070 1080 NLAGPVSQHN YRPGYHTQIT GPWHLGKLEM DFDFCDGTTV VVTEDCGNRG PSLRTTTASG 1090 1100 1110 1120 1130 1140 KLITEWCCRS CTLPPLRYRG EDGCWYGMEI RPLKEKEENL VNSLVTAGHG QVDNFSLGVL 1150 1160 1170 1180 1190 1200 GMALFLEEML RTRVGTKHAI LLVAVSFVTL IIGNMSFRDL GRVMVMVGAT MTDDIGMGVT 1210 1220 1230 1240 1250 1260 YLALLAAFKV RPTFAAGLLL RKLTSKALMM TTIGIVLSSQ STTPETILEL TDALALGMMV 1270 1280 1290 1300 1310 1320 LKMVRNMEKY QLAVTIMAIL CVPNAVILQN AWKVSCTILA VVSVSPLFLT SSQQKTDWIP 1330 1340 1350 1360 1370 1380 LALTIKGLNP TAIFLTTLSR TSKKRSWPLN EAIMAVGMVS ILASSLLKND IPMTGPLVAG 1390 1400 1410 1420 1430 1440 GPLTVCYVLT GRSADLELER AADVKWEDQA EISGSSPILS ITISEDGSMS IKNEEEEQTL 1450 1460 1470 1480 1490 1500 TILIRTGLLV ISGLFPVSIP ITAAAWYLWE VKKQRAGVLW DVPSPPPMGK AELEDGAYRI 1510 1520 1530 1540 1550 1560 KQKGILGYSQ IGAGVYKEGT FHTMWHVTRG AVLMHKGKRI EPSWADVKKD LISYGGGWKL 1570 1580 1590 1600 1610 1620 EGEWKEGEEV QVLALEPGKN PRAVQTKPGL FKTNAGTIGA VSLDFSPGTS GSPIIDKKGK 1630 1640 1650 1660 1670 1680 VVGLYGNGVV TRSGAYVSAI AQTEKSIEDN PEIEDDIFRK RRLTIMDLHP GAGKTKRYLP 1690 1700 1710 1720 1730 1740 AIVREAIKRG LRTLILAPTR VVAAEMEEAL RGLPIRYQTP AIRAEHTGRE IVDLMCHATF 1750 1760 1770 1780 1790 1800 TMRLLSPVRV PNYNLIIMDE AHFTDPASIA ARGYISTRVE MGEAAGIFMT ATPPGSRDPF 1810 1820 1830 1840 1850 1860 PQSNAPIIDE EREIPERSWN SGHEWVTDFK GKTVWFVPSI KAGNDIAACL SKNGKKVIQL 1870 1880 1890 1900 1910 1920 SRKTFDSEYA KTRTNDWDFV VTTDISEMGA NFKAERVIDP RRCMKPVILT DGEERVILAG 1930 1940 1950 1960 1970 1980 PMPVTHSSAA QRRGRIGRNP KNENDQYIYM GEPLENDEDC AHWKEAKMLL DNINTPEGII 1990 2000 2010 2020 2030 2040 PSMFEPEREK VDAIDGEYRL RGEARTTFVD LMRRGDLPVW LAYRVAAEGI NYADRRWCFD 2050 2060 2070 2080 2090 2100 GVKNNQILEE NVEVEIWTKE GERKKLKPRW LDARIYSDPL ALKEFKEFAA GRKSLTLNLI 2110 2120 2130 2140 2150 2160 TEMGRLPTFM TQKARDALDN LAVLHTAEAG GRAYNHALSE LPETLETLLL LTLLATVTGG 2170 2180 2190 2200 2210 2220 ILLFLMSGRG IGKMTLGMCC IITASILLWY AQIQPHWIAA SIILEFFLIV LLIPEPEKQR 2230 2240 2250 2260 2270 2280 TPQDNQLTYV VIAILTVVAA TMANEMGFLE KTKKDLGLGS IATQQPESNI LDIDLRPASA 2290 2300 2310 2320 2330 2340 WTLYAVATTF VTPMLRHSIE NSSVNVSLTA IANQATVLMG LGKGWPLSKM DIGVPLLAIG 2350 2360 2370 2380 2390 2400 CYSQVNPTTL TAALFLLVAH YAIIGPALQA KASREAQKRA AAGIMKNPTV DGITVIDLDP 2410 2420 2430 2440 2450 2460 IPYDPKFEKQ LGQVMLLVLC VTQVLMMRTT WALCEVLTLA TGPISTLWEG NPGRFWNTTI 2470 2480 2490 2500 2510 2520 AVSMANIFRG SYLAGAGLLF SIMKNTTNAR RGTGNIGETL GEKWKSRLNA LGKSEFQIYK 2530 2540 2550 2560 2570 2580 KSGIQEVDRT LAKEGIKRGE TDHHAVSRGS AKLRWFVERN MVTPEGKVVD LGCGRGGWSY 2590 2600 2610 2620 2630 2640 YCGGLKNVRE VKGLTKGGPG HEEPIPMSTY GWNLVRLQSG VDVFFIPPEK CDTLLCDIGE 2650 2660 2670 2680 2690 2700 SSPNPTVEAG RTLRVLNLVE NWLNNNTQFC IKVLNPYMPS VIEKMEALQR KYGGALVRNP 2710 2720 2730 2740 2750 2760 LSRNSTHEMY WVSNASGNIV SSVNMISRML INRFTMRYKK ATYEPDVDLG SGTRNIGIES 2770 2780 2790 2800 2810 2820 EIPNLDIIGK RIEKIKQEHE TSWHYDQDHP YKTWAYHGSY ETKQTGSASS MVNGVFRLLT 2830 2840 2850 2860 2870 2880 KPWDVVPMVT QMAMTDTTPF GQQRVFKEKV DTRTQEPKEG TKKLMKITAE WLWKELGKKK 2890 2900 2910 2920 2930 2940 TPRMCTREEF TRKVRSNAAL GAIFTDENKW KSAREAVEDS RFWELVDKER NLHLEGKCET 2950 2960 2970 2980 2990 3000 CVYNIMGKRE KKLGEFGKAK GSRAIWYMWL GARFLEFEAL GFLNEDHWFS RENSLSGVEG 3010 3020 3030 3040 3050 3060 EGLHKLGYIL RDVSKKEGGA MYADDTAGWD TRITLEDLKN EAMVTNHMEG EHKKLAEAIF 3070 3080 3090 3100 3110 3120 KLTYQNKVVR VQRPTPRGTV MDIISRRDQR GSGQVGTYGL NTFTNMEAQL IRQMEGEGVF 3130 3140 3150 3160 3170 3180 KSIQHLTITE EIAVQNWLAR VGRERLSRMA ISGDDCVVKP LDDRLPSALT ALNDTGKIRK 3190 3200 3210 3220 3230 3240 DIQQWEPSRG WNDWTQVPFC SHHFHELIMK DGRVLVVPCR NQDELIGRAR ISQGAGWSLR 3250 3260 3270 3280 3290 3300 ETACLGKSYD QMWSLMYFHR RDLRLAANAI CSAVPSHWVP TSRTTWSIHA KHEWMTTEDM 3310 3320 3330 3340 3350 3360 LTVWNRVWIQ ENPWMEDKTP VESWEEIPYL GKREDQWCGS LIGLTSRATW AKNIQAAINQ 3370 3380 3390 VRSLIGNEEY TDYMPSMKRF RREEEEAGVL W

References

[1]	"Comparison of a dengue-2 virus and its candidate vaccine derivative: sequence relationships with the flaviviruses and other viruses." Blok J., McWilliam S.M., Butler H.C., Gibbs A.J., Weiller G., Herring B.L., Hemsley A.C., Aaskov J.G., Yoksan S., Bhamarapravati N. Virology 187:573-590(1992) [PubMed: 1312269] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
[2]	"Flavivirus capsid is a dimeric alpha-helical protein." Jones C.T., Ma L., Burgner J.W., Groesch T.D., Post C.B., Kuhn R.J. J. Virol. 77:7143-7149(2003) [PubMed: 12768036] [Abstract] Cited for: SUBUNIT.
[3]	"Alterations of pr-M cleavage and virus export in pr-M junction chimeric dengue viruses." Keelapang P., Sriburi R., Supasa S., Panyadee N., Songjaeng A., Jairungsri A., Puttikhunt C., Kasinrerk W., Malasit P., Sittisombut N. J. Virol. 78:2367-2381(2004) [PubMed: 14963133] [Abstract] Cited for: PROTEOLYTIC PROCESSING OF POLYPROTEIN.
[4]	"Identification of the homotypic interaction domain of the core protein of dengue virus type 2." Wang S.H., Syu W.J., Hu S.T. J. Gen. Virol. 85:2307-2314(2004) [PubMed: 15269372] [Abstract] Cited for: SUBUNIT, REGION OF HOMODIMERIZATION OF CAPSID PROTEIN C.
[5]	"Inhibition of alpha/beta interferon signaling by the NS4B protein of flaviviruses." Munoz-Jordan J.L., Laurent-Rolle M., Ashour J., Martinez-Sobrido L., Ashok M., Lipkin W.I., Garcia-Sastre A. J. Virol. 79:8004-8013(2005) [PubMed: 15956546] [Abstract] Cited for: FUNCTION OF NON-STRUCTURAL PROTEIN 4B, FUNCTION OF PEPTIDE 2K.
[6]	"Vascular leakage in severe dengue virus infections: a potential role for the nonstructural viral protein NS1 and complement." Avirutnan P., Punyadee N., Noisakran S., Komoltri C., Thiemmeca S., Auethavornanan K., Jairungsri A., Kanlaya R., Tangthawornchaikul N., Puttikhunt C., Pattanakitsakul S.N., Yenchitsomanus P.T., Mongkolsapaya J., Kasinrerk W., Sittisombut N., Husmann M., Blettner M., Vasanawathana S., Bhakdi S., Malasit P. J. Infect. Dis. 193:1078-1088(2006) [PubMed: 16544248] [Abstract] Cited for: FUNCTION OF NS1.
[7]	"Nuclear localization of flavivirus RNA synthesis in infected cells." Uchil P.D., Kumar A.V., Satchidanandam V. J. Virol. 80:5451-5464(2006) [PubMed: 16699025] [Abstract] Cited for: SUBCELLULAR LOCATION OF SERINE PROTEASE NS3, SUBCELLULAR LOCATION OF RNA-DIRECTED RNA POLYMERASE NS5. Strain: TR 1751.
[8]	"Cleavage preference distinguishes the two-component NS2B-NS3 serine proteinases of Dengue and West Nile viruses." Shiryaev S.A., Kozlov I.A., Ratnikov B.I., Smith J.W., Lebl M., Strongin A.Y. Biochem. J. 401:743-752(2007) [PubMed: 17067286] [Abstract] Cited for: PROTEOLYTIC PROCESSING OF POLYPROTEIN.
[9]	"Dengue virus type 2 antagonizes IFN-alpha but not IFN-gamma antiviral effect via down-regulating Tyk2-STAT signaling in the human dendritic cell." Ho L.J., Hung L.F., Weng C.Y., Wu W.L., Chou P., Lin Y.L., Chang D.M., Tai T.Y., Lai J.H. J. Immunol. 174:8163-8172(2005) [PubMed: 15944325] [Abstract] Cited for: FUNCTION OF RNA-DIRECTED RNA POLYMERASE NS5.
[10]	"Characterization of dengue virus NS1 stably expressed in 293T cell lines." Noisakran S., Dechtawewat T., Rinkaewkan P., Puttikhunt C., Kanjanahaluethai A., Kasinrerk W., Sittisombut N., Malasit P. J. Virol. Methods 142:67-80(2007) [PubMed: 17331594] [Abstract] Cited for: CHARACTERIZATION OF NS1.
[11]	"The flavivirus NS5 protein is a true RNA guanylyltransferase that catalyzes a two-step reaction to form the RNA cap structure." Issur M., Geiss B.J., Bougie I., Picard-Jean F., Despins S., Mayette J., Hobdey S.E., Bisaillon M. RNA 15:2340-2350(2009) [PubMed: 19850911] [Abstract] Cited for: FUNCTION OF RNA-DIRECTED RNA POLYMERASE NS5, INTERACTION OF NS5 WITH NS3.
[12]	"Dengue virus NS5 inhibits interferon-alpha signaling by blocking signal transducer and activator of transcription 2 phosphorylation." Mazzon M., Jones M., Davidson A., Chain B., Jacobs M. J. Infect. Dis. 200:1261-1270(2009) [PubMed: 19754307] [Abstract] Cited for: FUNCTION OF RNA-DIRECTED RNA POLYMERASE NS5, INTERACTION OF NS5 WITH HUMAN STAT2.
[13]	"Characterization of dengue virus entry into HepG2 cells." Suksanpaisan L., Susantad T., Smith D.R. J. Biomed. Sci. 16:17-17(2009) [PubMed: 19272179] [Abstract] Cited for: FUNCTION OF ENVELOPE PROTEIN E.
[14]	"Binding of a neutralizing antibody to dengue virus alters the arrangement of surface glycoproteins." Lok S.M., Kostyuchenko V., Nybakken G.E., Holdaway H.A., Battisti A.J., Sukupolvi-Petty S., Sedlak D., Fremont D.H., Chipman P.R., Roehrig J.T., Diamond M.S., Kuhn R.J., Rossmann M.G. Nat. Struct. Mol. Biol. 15:312-317(2008) [PubMed: 18264114] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.8 ANGSTROMS) OF 578-674.
+	Additional computationally mapped references.

Web resources

Virus Pathogen Resource

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M84727 Genomic RNA. Translation: AAA73185.1.

PIR

GNWV16. A42451.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2R69	X-ray	3.80	A	578-674	[»]

ProteinModelPortal

P29990.

SMR

P29990. Positions 21-100, 115-195, 281-674, 1394-1440, 1495-2093, 2498-2759, 2765-3374.

ModBase

Search...

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Family and domain databases

InterPro

IPR014001. DEAD-like_helicase.
IPR011492. DEAD_Flavivir.
IPR000069. Env_glycoprot_M_flavivir.
IPR013756. Flav_glyE_cen_dom_subdom2.
IPR013754. Flav_glyE_dim.
IPR001122. Flavi_capsidC.
IPR001157. Flavi_NS1.
IPR000752. Flavi_NS2A.
IPR000487. Flavi_NS2B.
IPR000404. Flavi_NS4A.
IPR001528. Flavi_NS4B.
IPR002535. Flavi_propep.
IPR000336. Flv_glyE_Ig-like.
IPR014412. Gen_Poly_FLV.
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.
IPR000208. RNA-dir_pol_flavivirus.
IPR007094. RNA-dir_pol_PSvirus.
IPR002877. rRNA_MeTrfase_RrmJ/FtsJ.
[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

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

PIRSF

PIRSF003817. Gen_Poly_FLV. 1 hit.

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.
PS51527. FLAVIVIRUS_NS2B. 1 hit.
PS51528. FLAVIVIRUS_NS3PRO. 1 hit.
PS51192. HELICASE_ATP_BIND_1. 1 hit.
PS51194. HELICASE_CTER. False negative.
PS50507. RDRP_SSRNA_POS. 1 hit.
[Graphical view]

ProtoNet

Search...

Entry information

Entry name

POLG_DEN26

Accession

Primary (citable) accession number: P29990

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1993
Last sequence update:	April 1, 1993
Last modified:	November 16, 2011
This is version 114 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Viral Protein Annotation Program