POLG_DEN2H
ID POLG_DEN2H Reviewed; 555 AA.
AC P29984;
DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-1993, sequence version 1.
DT 07-OCT-2020, entry version 118.
DE RecName: Full=Genome polyprotein;
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/TH-36/1958) (DENV-2).
OC Viruses; Riboviria; Orthornavirae; Kitrinoviricota; Flasuviricetes;
OC Amarillovirales; Flaviviridae; Flavivirus.
OX NCBI_TaxID=31637;
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=1339466; DOI=10.1099/0022-1317-73-1-207;
RA Shiu S.Y.W., Jiang W.R., Porterfield J.S., Gould E.A.;
RT "Envelope protein sequences of dengue virus isolates TH-36 and TH-Sman, and
RT identification of a type-specific genetic marker for dengue and tick-borne
RT flaviviruses.";
RL J. Gen. Virol. 73:207-212(1992).
RN [2]
RP FUNCTION (ENVELOPE PROTEIN E).
RX PubMed=20949067; DOI=10.1371/journal.ppat.1001131;
RA Zaitseva E., Yang S.T., Melikov K., Pourmal S., Chernomordik L.V.;
RT "Dengue virus ensures its fusion in late endosomes using compartment-
RT specific lipids.";
RL PLoS Pathog. 6:0-0(2010).
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 (PubMed:20949067).
CC Envelope protein is synthesized in the endoplasmic reticulum in the
CC form of heterodimer with protein prM (By similarity). They play a role
CC in virion budding in the ER, and the newly formed immature particle is
CC covered with 60 spikes composed of heterodimer between precursor prM
CC and envelope protein E (By similarity). The virion is transported to
CC the Golgi apparatus where the low pH causes dissociation of PrM-E
CC heterodimers and formation of E homodimers (By similarity). prM-E
CC cleavage is inefficient, and many virions are only partially matured
CC (By similarity). These uncleaved prM would play a role in immune
CC evasion (By similarity). {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: [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 -!- SUBUNIT: [Non-structural protein 1]: Homodimer; Homohexamer when
CC secreted. Interacts with envelope protein E.
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: [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";
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DR EMBL; D10514; BAA01389.1; -; Genomic_RNA.
DR PIR; JQ1404; JQ1404.
DR SMR; P29984; -.
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; 2.60.40.350; -; 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; 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 SUPFAM; SSF56983; SSF56983; 1.
DR SUPFAM; SSF81296; SSF81296; 1.
DR TIGRFAMs; TIGR04240; flavi_E_stem; 1.
PE 3: Inferred from homology;
KW 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..>555
FT /note="Genome polyprotein"
FT /id="PRO_0000405212"
FT CHAIN <1..49
FT /note="Small envelope protein M"
FT /evidence="ECO:0000250"
FT /id="PRO_0000037922"
FT CHAIN 50..544
FT /note="Envelope protein E"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT /id="PRO_0000037923"
FT CHAIN 545..>555
FT /note="Non-structural protein 1"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT /id="PRO_0000037924"
FT TOPO_DOM <1..7
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 8..28
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 29..34
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 35..49
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 50..494
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 495..515
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 516..521
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 522..542
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 543..>555
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT REGION 147..160
FT /note="Fusion peptide"
FT /evidence="ECO:0000250|UniProtKB:P14336"
FT SITE 49..50
FT /note="Cleavage; by host signal peptidase"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT SITE 544..545
FT /note="Cleavage; by host signal peptidase"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT CARBOHYD 116
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 202
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT DISULFID 52..79
FT /evidence="ECO:0000250|UniProtKB:P17763"
FT DISULFID 109..170
FT /evidence="ECO:0000250|UniProtKB:P17763"
FT DISULFID 123..154
FT /evidence="ECO:0000250|UniProtKB:P17763"
FT DISULFID 141..165
FT /evidence="ECO:0000250|UniProtKB:P17763"
FT DISULFID 234..334
FT /evidence="ECO:0000250|UniProtKB:P17763"
FT DISULFID 351..382
FT /evidence="ECO:0000250|UniProtKB:P17763"
FT NON_TER 1
FT NON_TER 555
SQ SEQUENCE 555 AA; 61243 MW; F8DEA740BB4DD8DF CRC64;
KHAQRIETWI LRHPGFTIMA AILAYTIGTT HFQRALIFIL LTAVAPSMTM RCIGISNRDF
VEGVSGGSWV DIVLEHGSCV TTMAKNKPTL DFELIKTEAK QPVTLRKYCI EAKLTNTTTE
SRCPIQGEPS LNEEQDKRFV CKHSMVDRGW GNGCGLFGKG GIVTCAMFTC KKNMKGKVVQ
PENLEYTIVI TPHSGEEHAV GNDTGKHGKE IKITPQSSIT EAELTGYGTV TMECSPRTGL
DFNEMVLLQM ENKAWLVHRQ WFLDLPLPWL PGADTQGSNW IQKETLVTFK NPHAKKQDVV
VLGSQEGAMH TALTGATEIQ MSSGNLLFTG HLKCRLRMDK LQLKGMSYSM CTGKFKVVKE
IAETQHGTIV IRVQYEGDGS PCKIPFEIMD LEKRHVLGRL ITVNPIVTEK DSPVNIEAEP
PFGDSYIIIG VEPEQLKLNW FKKGSSIGQM FETTMRGAKR MAILGDTAWD FGSLGGVFTS
IGKALHQVFG AIYGAAFSGV SWTMKILIGV IITWIGMNSR STSLSVSLVL VGIVTLYLEV
MVQADSGCVV SWKNK
