POLG_DEN2U
ID POLG_DEN2U Reviewed; 679 AA.
AC P18356;
DT 01-NOV-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 2.
DT 03-AUG-2022, entry version 136.
DE RecName: Full=Genome polyprotein;
DE Contains:
DE RecName: Full=Protein prM;
DE Contains:
DE RecName: Full=Peptide pr;
DE Contains:
DE RecName: Full=Small envelope protein M;
DE AltName: Full=Matrix protein;
DE Contains:
DE RecName: Full=Envelope protein E;
DE Contains:
DE RecName: Full=Non-structural protein 1;
DE Short=NS1;
DE Flags: Fragment;
OS Dengue virus type 2 (strain Thailand/PUO-218/1980) (DENV-2).
OC Viruses; Riboviria; Orthornavirae; Kitrinoviricota; Flasuviricetes;
OC Amarillovirales; Flaviviridae; Flavivirus.
OX NCBI_TaxID=11068;
OH NCBI_TaxID=53540; Aedimorphus.
OH NCBI_TaxID=53539; Diceromyia.
OH NCBI_TaxID=9538; Erythrocebus patas (Red guenon) (Cercopithecus patas).
OH NCBI_TaxID=9606; Homo sapiens (Human).
OH NCBI_TaxID=53541; Stegomyia.
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=3385407; DOI=10.1099/0022-1317-69-6-1391;
RA Gruenberg A., Woo W.S., Biedrzycka A., Wright P.J.;
RT "Partial nucleotide sequence and deduced amino acid sequence of the
RT structural proteins of dengue virus type 2, New Guinea C and PUO-218
RT strains.";
RL J. Gen. Virol. 69:1391-1398(1988).
RN [2]
RP STRUCTURE BY NMR OF 469-577.
RX PubMed=18004779; DOI=10.1002/prot.21806;
RA Huang K.C., Lee M.C., Wu C.W., Huang K.J., Lei H.Y., Cheng J.W.;
RT "Solution structure and neutralizing antibody binding studies of domain III
RT of the dengue-2 virus envelope protein.";
RL Proteins 70:1116-1119(2008).
RN [3]
RP STRUCTURE BY ELECTRON MICROSCOPY (24.0 ANGSTROMS) OF 15-95 AND 181-570.
RX PubMed=18264114; DOI=10.1038/nsmb.1382;
RA Lok S.M., Kostyuchenko V., Nybakken G.E., Holdaway H.A., Battisti A.J.,
RA Sukupolvi-Petty S., Sedlak D., Fremont D.H., Chipman P.R., Roehrig J.T.,
RA Diamond M.S., Kuhn R.J., Rossmann M.G.;
RT "Binding of a neutralizing antibody to dengue virus alters the arrangement
RT of surface glycoproteins.";
RL Nat. Struct. Mol. Biol. 15:312-317(2008).
RN [4]
RP STRUCTURE BY ELECTRON MICROSCOPY (24.0 ANGSTROMS) OF 15-95 AND 181-575.
RX PubMed=19759134; DOI=10.1128/jvi.01637-09;
RA Yu I.M., Holdaway H.A., Chipman P.R., Kuhn R.J., Rossmann M.G., Chen J.;
RT "Association of the pr peptides with dengue virus at acidic pH blocks
RT membrane fusion.";
RL J. Virol. 83:12101-12107(2009).
CC -!- FUNCTION: [Peptide pr]: Prevents premature fusion activity of envelope
CC proteins in trans-Golgi by binding to envelope protein E at pH6.0.
CC After virion release in extracellular space, gets dissociated from E
CC dimers. {ECO:0000250|UniProtKB:P17763}.
CC -!- FUNCTION: [Protein prM]: Acts as a chaperone for envelope protein E
CC during intracellular virion assembly by masking and inactivating
CC envelope protein E fusion peptide. prM is the only viral peptide
CC matured by host furin in the trans-Golgi network probably to avoid
CC catastrophic activation of the viral fusion activity in acidic Golgi
CC compartment prior to virion release. prM-E cleavage is inefficient, and
CC many virions are only partially matured. These uncleaved prM would play
CC a role in immune evasion. {ECO:0000250|UniProtKB:P17763}.
CC -!- FUNCTION: [Small envelope protein M]: May play a role in virus budding.
CC Exerts cytotoxic effects by activating a mitochondrial apoptotic
CC pathway through M ectodomain. May display a viroporin activity.
CC {ECO:0000250|UniProtKB:P17763}.
CC -!- FUNCTION: [Envelope protein E]: Binds to host cell surface receptor and
CC mediates fusion between viral and cellular membranes. Envelope protein
CC is synthesized in the endoplasmic reticulum in the form of heterodimer
CC with protein prM. They play a role in virion budding in the ER, and the
CC newly formed immature particle is covered with 60 spikes composed of
CC heterodimer between precursor prM and envelope protein E. The virion is
CC transported to the Golgi apparatus where the low pH causes dissociation
CC of PrM-E heterodimers and formation of E homodimers. prM-E cleavage is
CC inefficient, and many virions are only partially matured. These
CC uncleaved prM would play a role in immune evasion.
CC {ECO:0000250|UniProtKB:P17763}.
CC -!- FUNCTION: [Non-structural protein 1]: Involved in immune evasion,
CC pathogenesis and viral replication. Once cleaved off the polyprotein,
CC is targeted to three destinations: the viral replication cycle, the
CC plasma membrane and the extracellular compartment. Essential for viral
CC replication. Required for formation of the replication complex and
CC recruitment of other non-structural proteins to the ER-derived membrane
CC structures. Excreted as a hexameric lipoparticle that plays a role
CC against host immune response. Antagonizing the complement function.
CC Binds to the host macrophages and dendritic cells. Inhibits signal
CC transduction originating from Toll-like receptor 3 (TLR3).
CC {ECO:0000250|UniProtKB:Q9Q6P4}.
CC -!- FUNCTION: [Non-structural protein 1]: Disrupts the host endothelial
CC glycocalyx layer of host pulmonary microvascular endothelial cells,
CC inducing degradation of sialic acid and shedding of heparan sulfate
CC proteoglycans. NS1 induces expression of sialidases, heparanase, and
CC activates cathepsin L, which activates heparanase via enzymatic
CC cleavage. These effects are probably linked to the endothelial
CC hyperpermeability observed in severe dengue disease.
CC {ECO:0000250|UniProtKB:P17763}.
CC -!- SUBUNIT: [Protein prM]: Forms heterodimers with envelope protein E in
CC the endoplasmic reticulum and Golgi. {ECO:0000250|UniProtKB:P17763}.
CC -!- SUBUNIT: [Envelope protein E]: Homodimer; in the endoplasmic reticulum
CC and Golgi. Interacts with protein prM. Interacts with non-structural
CC protein 1. {ECO:0000250|UniProtKB:P17763}.
CC -!- SUBCELLULAR LOCATION: [Peptide pr]: Secreted
CC {ECO:0000250|UniProtKB:P17763}.
CC -!- SUBCELLULAR LOCATION: [Small envelope protein M]: Virion membrane
CC {ECO:0000250|UniProtKB:P17763}; Multi-pass membrane protein
CC {ECO:0000255}. Host endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:P17763}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- SUBCELLULAR LOCATION: [Envelope protein E]: Virion membrane
CC {ECO:0000250|UniProtKB:P17763}; Multi-pass membrane protein
CC {ECO:0000255}. Host endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:P17763}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- SUBCELLULAR LOCATION: [Non-structural protein 1]: Secreted
CC {ECO:0000250|UniProtKB:P17763}. Host endoplasmic reticulum membrane;
CC Peripheral membrane protein; Lumenal side
CC {ECO:0000250|UniProtKB:P17763}. Note=Located in RE-derived vesicles
CC hosting the replication complex. {ECO:0000250|UniProtKB:Q9Q6P4}.
CC -!- DOMAIN: The transmembrane domains of the small envelope protein M and
CC envelope protein E contain an endoplasmic reticulum retention signal.
CC {ECO:0000250|UniProtKB:P17763}.
CC -!- PTM: [Protein prM]: Cleaved in post-Golgi vesicles by a host furin,
CC releasing the mature small envelope protein M, and peptide pr. This
CC cleavage is incomplete as up to 30% of viral particles still carry
CC uncleaved prM. {ECO:0000250|UniProtKB:P17763}.
CC -!- PTM: [Envelope protein E]: N-glycosylated.
CC {ECO:0000250|UniProtKB:P17763}.
CC -!- PTM: [Non-structural protein 1]: N-glycosylated. The excreted form is
CC glycosylated and this is required for efficient secretion of the
CC protein from infected cells. {ECO:0000250|UniProtKB:P17763}.
CC -!- PTM: [Genome polyprotein]: Specific enzymatic cleavages in vivo yield
CC mature proteins. Cleavages in the lumen of endoplasmic reticulum are
CC performed by host signal peptidase, wereas cleavages in the cytoplasmic
CC side are performed by serine protease NS3. Signal cleavage at the 2K-4B
CC site requires a prior NS3 protease-mediated cleavage at the 4A-2K site.
CC {ECO:0000250|UniProtKB:P17763}.
CC -!- WEB RESOURCE: Name=Virus Pathogen Resource;
CC URL="https://www.viprbrc.org/brc/home.spg?decorator=flavi_dengue";
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; D00345; BAA00254.1; -; Genomic_RNA.
DR PIR; PS0043; PS0043.
DR PDB; 2JSF; NMR; -; A=469-577.
DR PDB; 2R6P; EM; 24.00 A; A/B/C=181-570.
DR PDB; 3C6R; EM; 25.00 A; A/B/C=181-575, D/E/F=15-95.
DR PDB; 3IXY; EM; -; D/E/F=15-95.
DR PDB; 3IYA; EM; -; A/B/C=181-575, D/E/F=15-95.
DR PDB; 7KV8; EM; 2.50 A; A/B/C=181-675.
DR PDBsum; 2JSF; -.
DR PDBsum; 2R6P; -.
DR PDBsum; 3C6R; -.
DR PDBsum; 3IXY; -.
DR PDBsum; 3IYA; -.
DR PDBsum; 7KV8; -.
DR SMR; P18356; -.
DR ABCD; P18356; 3 sequenced antibodies.
DR EvolutionaryTrace; P18356; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0044167; C:host cell endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0019031; C:viral envelope; IEA:UniProtKB-KW.
DR GO; GO:0019013; C:viral nucleocapsid; IEA:UniProtKB-KW.
DR GO; GO:0055036; C:virion membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0046983; F:protein dimerization activity; IEA:InterPro.
DR GO; GO:0075512; P:clathrin-dependent endocytosis of virus by host cell; IEA:UniProtKB-KW.
DR GO; GO:0039654; P:fusion of virus membrane with host endosome membrane; IEA:UniProtKB-KW.
DR GO; GO:0019062; P:virion attachment to host cell; IEA:UniProtKB-KW.
DR CDD; cd12149; Flavi_E_C; 1.
DR Gene3D; 1.10.8.970; -; 1.
DR Gene3D; 1.20.1280.260; -; 1.
DR Gene3D; 2.60.260.50; -; 1.
DR Gene3D; 2.60.40.350; -; 1.
DR Gene3D; 2.60.98.10; -; 1.
DR Gene3D; 3.30.387.10; -; 1.
DR Gene3D; 3.30.67.10; -; 1.
DR InterPro; IPR000069; Env_glycoprot_M_flavivir.
DR InterPro; IPR038302; Env_glycoprot_M_sf_flavivir.
DR InterPro; IPR013755; Flav_gly_cen_dom_subdom1.
DR InterPro; IPR027287; Flavi_E_Ig-like.
DR InterPro; IPR026470; Flavi_E_Stem/Anchor_dom.
DR InterPro; IPR038345; Flavi_E_Stem/Anchor_dom_sf.
DR InterPro; IPR002535; Flavi_propep.
DR InterPro; IPR038688; Flavi_propep_sf.
DR InterPro; IPR000336; Flavivir/Alphavir_Ig-like_sf.
DR InterPro; IPR011998; Glycoprot_cen/dimer.
DR InterPro; IPR036253; Glycoprot_cen/dimer_sf.
DR InterPro; IPR038055; Glycoprot_E_dimer_dom.
DR InterPro; IPR013756; GlyE_cen_dom_subdom2.
DR InterPro; IPR014756; Ig_E-set.
DR Pfam; PF02832; Flavi_glycop_C; 1.
DR Pfam; PF00869; Flavi_glycoprot; 1.
DR Pfam; PF01004; Flavi_M; 1.
DR Pfam; PF01570; Flavi_propep; 1.
DR SUPFAM; SSF56983; SSF56983; 1.
DR SUPFAM; SSF81296; SSF81296; 1.
DR TIGRFAMs; TIGR04240; flavi_E_stem; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Clathrin-mediated endocytosis of virus by host;
KW Cleavage on pair of basic residues; Disulfide bond;
KW Fusion of virus membrane with host endosomal membrane;
KW Fusion of virus membrane with host membrane; Glycoprotein;
KW Host endoplasmic reticulum; Host membrane; Host-virus interaction;
KW Membrane; Secreted; Suppressor of RNA silencing; Transmembrane;
KW Transmembrane helix; Viral attachment to host cell; Viral envelope protein;
KW Viral nucleoprotein; Viral penetration into host cytoplasm; Virion;
KW Virus endocytosis by host; Virus entry into host cell; Zinc.
FT CHAIN <1..>679
FT /note="Genome polyprotein"
FT /id="PRO_0000405220"
FT PROPEP 1..14
FT /note="ER anchor for the capsid protein C, removed in
FT mature form by serine protease NS3"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT /id="PRO_0000037985"
FT CHAIN 15..180
FT /note="Protein prM"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT /id="PRO_0000308291"
FT CHAIN 15..105
FT /note="Peptide pr"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT /id="PRO_0000308292"
FT CHAIN 106..180
FT /note="Small envelope protein M"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT /id="PRO_0000037986"
FT CHAIN 181..675
FT /note="Envelope protein E"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT /id="PRO_0000037987"
FT CHAIN 676..>679
FT /note="Non-structural protein 1"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT /id="PRO_0000037988"
FT TRANSMEM 2..22
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 23..138
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 139..159
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 160..165
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 166..180
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 181..625
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 626..646
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 647..652
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 653..673
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 674..>679
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT REGION 278..291
FT /note="Fusion peptide"
FT /evidence="ECO:0000250|UniProtKB:P14336"
FT SITE 14..15
FT /note="Cleavage; by host signal peptidase"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT SITE 105..106
FT /note="Cleavage; by host furin"
FT /evidence="ECO:0000250|UniProtKB:P29990, ECO:0000255"
FT SITE 180..181
FT /note="Cleavage; by host signal peptidase"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT SITE 675..676
FT /note="Cleavage; by host signal peptidase"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT CARBOHYD 83
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 247
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 333
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT DISULFID 183..210
FT /evidence="ECO:0000250|UniProtKB:P17763"
FT DISULFID 240..301
FT /evidence="ECO:0000250|UniProtKB:P17763"
FT DISULFID 254..285
FT /evidence="ECO:0000250|UniProtKB:P17763"
FT DISULFID 272..296
FT /evidence="ECO:0000250|UniProtKB:P17763"
FT DISULFID 365..465
FT /evidence="ECO:0000250|UniProtKB:P17763"
FT DISULFID 482..513
FT /evidence="ECO:0000250|UniProtKB:P17763"
FT NON_TER 1
FT NON_TER 679
FT TURN 182..185
FT /evidence="ECO:0007829|PDB:7KV8"
FT STRAND 187..193
FT /evidence="ECO:0007829|PDB:7KV8"
FT STRAND 199..207
FT /evidence="ECO:0007829|PDB:7KV8"
FT STRAND 210..214
FT /evidence="ECO:0007829|PDB:7KV8"
FT STRAND 221..230
FT /evidence="ECO:0007829|PDB:7KV8"
FT STRAND 234..252
FT /evidence="ECO:0007829|PDB:7KV8"
FT HELIX 263..266
FT /evidence="ECO:0007829|PDB:7KV8"
FT STRAND 270..280
FT /evidence="ECO:0007829|PDB:7KV8"
FT HELIX 281..283
FT /evidence="ECO:0007829|PDB:7KV8"
FT STRAND 289..309
FT /evidence="ECO:0007829|PDB:7KV8"
FT HELIX 312..314
FT /evidence="ECO:0007829|PDB:7KV8"
FT STRAND 315..323
FT /evidence="ECO:0007829|PDB:7KV8"
FT STRAND 335..337
FT /evidence="ECO:0007829|PDB:7KV8"
FT STRAND 339..344
FT /evidence="ECO:0007829|PDB:7KV8"
FT STRAND 349..355
FT /evidence="ECO:0007829|PDB:7KV8"
FT TURN 356..358
FT /evidence="ECO:0007829|PDB:7KV8"
FT STRAND 359..366
FT /evidence="ECO:0007829|PDB:7KV8"
FT HELIX 367..369
FT /evidence="ECO:0007829|PDB:7KV8"
FT STRAND 375..380
FT /evidence="ECO:0007829|PDB:7KV8"
FT STRAND 385..389
FT /evidence="ECO:0007829|PDB:7KV8"
FT HELIX 390..394
FT /evidence="ECO:0007829|PDB:7KV8"
FT STRAND 400..402
FT /evidence="ECO:0007829|PDB:7KV8"
FT HELIX 414..417
FT /evidence="ECO:0007829|PDB:7KV8"
FT STRAND 418..421
FT /evidence="ECO:0007829|PDB:7KV8"
FT STRAND 429..432
FT /evidence="ECO:0007829|PDB:7KV8"
FT HELIX 437..443
FT /evidence="ECO:0007829|PDB:7KV8"
FT TURN 444..446
FT /evidence="ECO:0007829|PDB:7KV8"
FT STRAND 447..451
FT /evidence="ECO:0007829|PDB:7KV8"
FT STRAND 455..458
FT /evidence="ECO:0007829|PDB:7KV8"
FT STRAND 461..468
FT /evidence="ECO:0007829|PDB:7KV8"
FT STRAND 486..494
FT /evidence="ECO:0007829|PDB:7KV8"
FT STRAND 496..498
FT /evidence="ECO:0007829|PDB:2JSF"
FT STRAND 500..506
FT /evidence="ECO:0007829|PDB:7KV8"
FT STRAND 508..510
FT /evidence="ECO:0007829|PDB:7KV8"
FT STRAND 512..514
FT /evidence="ECO:0007829|PDB:7KV8"
FT STRAND 517..520
FT /evidence="ECO:0007829|PDB:7KV8"
FT HELIX 522..524
FT /evidence="ECO:0007829|PDB:2JSF"
FT STRAND 526..533
FT /evidence="ECO:0007829|PDB:7KV8"
FT STRAND 537..540
FT /evidence="ECO:0007829|PDB:7KV8"
FT STRAND 545..550
FT /evidence="ECO:0007829|PDB:7KV8"
FT STRAND 553..561
FT /evidence="ECO:0007829|PDB:7KV8"
FT STRAND 563..565
FT /evidence="ECO:0007829|PDB:7KV8"
FT STRAND 567..573
FT /evidence="ECO:0007829|PDB:7KV8"
FT HELIX 577..595
FT /evidence="ECO:0007829|PDB:7KV8"
FT HELIX 596..601
FT /evidence="ECO:0007829|PDB:7KV8"
FT HELIX 608..628
FT /evidence="ECO:0007829|PDB:7KV8"
FT HELIX 633..648
FT /evidence="ECO:0007829|PDB:7KV8"
FT HELIX 654..672
FT /evidence="ECO:0007829|PDB:7KV8"
SQ SEQUENCE 679 AA; 74932 MW; 1B5B881FC015F46B CRC64;
SAGMIIMLIP TVMAFHLTTR NGEPHMIVSR QEKGKSLLFK TEDGVNMCTL MAMDLGELCE
DTITYKCPLL RQNEPEDIDC WCNSTSTWVT YGTCTTTGEH RREKRSVALV PHVGMGLETR
TETWMSSEGA WKHAQRIEIW ILRHPGFTIM AAILAYTIGT THFQRALIFI LLTAVAPSMT
MRCIGISNRD FVEGVSGGSW VDIVLEHGSC VTTMAKNKPT LDFELIKTEA KQPATLRKYC
IEAKLTNTTT ESRCPTQGEP SLNEEQDKRF VCKHSMVDRG WGNGCGLFGK GGIVTCAMFT
CKKNMEGKVV QPENLEYTIV VTPHSGEEHA VGNDTGKHGK EIKVTPQSSI TEAELTGYGT
VTMECSPRTG LDFNEMVLLQ MENKAWLVHR QWFLDLPLPW LPGADTQGSN WIQKETLVTF
KNPHAKKQDV VVLGSQEGAM HTALTGATEI QMSSGNLLFT GHLKCRLRMD KLQLKGMSYS
MCTGKFKVVK EIAETQHGTI VIRVQYEGDG SPCKIPFEIM DLEKRHVLGR LITVNPIVTE
KDSPVNIEAE PPFGDSYIII GVEPGQLKLN WFKKGSSIGQ MFETTMRGAK RMAILGDTAW
DFGSLGGVFT SIGKALHQVF GAIYGAAFSG VSWTMKILIG VIITWIGMNS RSTSLSVSLV
LVGIVTLYLG VMVQADSGC
