POLG_DEN1C
ID POLG_DEN1C Reviewed; 791 AA.
AC P27913;
DT 01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1992, sequence version 1.
DT 02-DEC-2020, entry version 127.
DE RecName: Full=Genome polyprotein;
DE Contains:
DE RecName: Full=Capsid protein C;
DE AltName: Full=Core protein;
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 1 (strain Jamaica/CV1636/1977) (DENV-1).
OC Viruses; Riboviria; Orthornavirae; Kitrinoviricota; Flasuviricetes;
OC Amarillovirales; Flaviviridae; Flavivirus.
OX NCBI_TaxID=11058;
OH NCBI_TaxID=7159; Aedes aegypti (Yellowfever mosquito) (Culex aegypti).
OH NCBI_TaxID=7160; Aedes albopictus (Asian tiger mosquito) (Stegomyia albopicta).
OH NCBI_TaxID=9606; Homo sapiens (Human).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=2738579; DOI=10.1099/0022-1317-70-7-1701;
RA Chu M.C., O'Rourke E.J., Trent D.W.;
RT "Genetic relatedness among structural protein genes of dengue 1 virus
RT strains.";
RL J. Gen. Virol. 70:1701-1712(1989).
CC -!- FUNCTION: [Capsid protein C]: Plays a role in virus budding by binding
CC to the cell membrane and gathering the viral RNA into a nucleocapsid
CC that forms the core of a mature virus particle. During virus entry, may
CC induce genome penetration into the host cytoplasm after hemifusion
CC induced by the surface proteins. Can migrate to the cell nucleus where
CC it modulates host functions. Overcomes the anti-viral effects of host
CC EXOC1 by sequestering and degrading the latter through the proteasome
CC degradation pathway. {ECO:0000250|UniProtKB:P17763}.
CC -!- FUNCTION: [Capsid protein C]: Inhibits RNA silencing by interfering
CC with host Dicer. {ECO:0000250|UniProtKB:P03314}.
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: [Capsid protein C]: Homodimer. Interacts (via N-terminus) with
CC host EXOC1 (via C-terminus); this interaction results in EXOC1
CC degradation through the proteasome degradation pathway.
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 -!- SUBUNIT: [Non-structural protein 1]: Homodimer; Homohexamer when
CC secreted. Interacts with envelope protein E.
CC {ECO:0000250|UniProtKB:P17763}.
CC -!- SUBCELLULAR LOCATION: [Capsid protein C]: Virion
CC {ECO:0000250|UniProtKB:P17763}. Host nucleus
CC {ECO:0000250|UniProtKB:P17763}. Host cytoplasm
CC {ECO:0000250|UniProtKB:P17763}. Host cytoplasm, host perinuclear region
CC {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: [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 -!- 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 -!- WEB RESOURCE: Name=Virus Pathogen Resource;
CC URL="https://www.viprbrc.org/brc/home.spg?decorator=flavi_dengue";
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DR EMBL; D00501; BAA00393.1; -; Genomic_RNA.
DR PIR; A32401; A32401.
DR SMR; P27913; -.
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:0042025; C:host cell nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0044220; C:host cell perinuclear region of cytoplasm; 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:0005198; F:structural molecule 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; 1.10.10.930; -; 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; IPR001122; Flavi_capsidC.
DR InterPro; IPR037172; Flavi_capsidC_sf.
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; PF01003; Flavi_capsid; 1.
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; SSF101257; SSF101257; 1.
DR SUPFAM; SSF56983; SSF56983; 1.
DR SUPFAM; SSF81296; SSF81296; 1.
DR TIGRFAMs; TIGR04240; flavi_E_stem; 1.
PE 3: Inferred from homology;
KW Capsid protein; 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; Host cytoplasm;
KW Host endoplasmic reticulum; Host membrane; Host nucleus;
KW Host-virus interaction; Membrane; Secreted; Suppressor of RNA silencing;
KW Transmembrane; Transmembrane helix; Viral attachment to host cell;
KW Viral envelope protein; Viral nucleoprotein;
KW Viral penetration into host cytoplasm; Virion; Virus endocytosis by host;
KW Virus entry into host cell; Zinc.
FT CHAIN 1..>791
FT /note="Genome polyprotein"
FT /id="PRO_0000405205"
FT CHAIN 1..100
FT /note="Capsid protein C"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT /id="PRO_0000037889"
FT PROPEP 101..114
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_0000037890"
FT CHAIN 115..280
FT /note="Protein prM"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT /id="PRO_0000264652"
FT CHAIN 115..205
FT /note="Peptide pr"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT /id="PRO_0000264653"
FT CHAIN 206..280
FT /note="Small envelope protein M"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT /id="PRO_0000037891"
FT CHAIN 281..775
FT /note="Envelope protein E"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT /id="PRO_0000037892"
FT CHAIN 776..>791
FT /note="Non-structural protein 1"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT /id="PRO_0000037893"
FT TOPO_DOM 1..101
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 102..119
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 120..242
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 243..260
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 261
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 262..280
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 281..725
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 726..746
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 747..752
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 753..775
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 776..>791
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT REGION 1..15
FT /note="Interaction with host EXOC1"
FT /evidence="ECO:0000250|UniProtKB:P17763"
FT REGION 37..72
FT /note="Hydrophobic; homodimerization of capsid protein C"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT REGION 378..391
FT /note="Fusion peptide"
FT /evidence="ECO:0000250|UniProtKB:P14336"
FT SITE 100..101
FT /note="Cleavage; by viral protease NS3"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT SITE 114..115
FT /note="Cleavage; by host signal peptidase"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT SITE 205..206
FT /note="Cleavage; by host furin"
FT /evidence="ECO:0000250|UniProtKB:P29990, ECO:0000255"
FT SITE 280..281
FT /note="Cleavage; by host signal peptidase"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT SITE 775..776
FT /note="Cleavage; by host signal peptidase"
FT /evidence="ECO:0000250|UniProtKB:P29990"
FT CARBOHYD 183
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 347
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 433
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT DISULFID 283..310
FT /evidence="ECO:0000250|UniProtKB:P17763"
FT DISULFID 340..401
FT /evidence="ECO:0000250|UniProtKB:P17763"
FT DISULFID 354..385
FT /evidence="ECO:0000250|UniProtKB:P17763"
FT DISULFID 372..396
FT /evidence="ECO:0000250|UniProtKB:P17763"
FT DISULFID 465..565
FT /evidence="ECO:0000250|UniProtKB:P17763"
FT DISULFID 582..613
FT /evidence="ECO:0000250|UniProtKB:P17763"
FT DISULFID 779..790
FT /evidence="ECO:0000250|UniProtKB:P17763"
FT NON_TER 791
SQ SEQUENCE 791 AA; 86845 MW; FFAE6F7E1C42F5C1 CRC64;
MNNQRKKTGR PSFNMLKRAR NRVSTGSQLA KRFSKGLLSG QGPMKLVMAF IAFLRFLAIP
PTAGILARWS SFKKNGAIKV LRGFKKEISS MLNIMNRRKR SVTMLLMLLP TALAFHLTTR
GGEPTLIVSK QERGKSLLFK TSAGVNMCTL IAMDLGELCE DTMTYKCPRI TERQPDDVDC
WCNATDTWVT YGTCSQTGEH RRDKRSVALA PHVGLGLETR TETWMSSEGA WKQIQKVETW
ALRHPGFTVI GLFLAHAIGT SITQKGIIFI LLMLVTPSMA MRCVGIGNRD FVEGLSGATW
VDVVLEHGSC VTTMAKNKPT LDIELLKTEV TNPAVLRKLC IEAKISNTTT DSRCPTQGEA
TLVEEQDANF VCRRTFVDRG WGNGCGLFGK GSFLTCAKFK CVTKLEGKIV QYENLKYSVI
VTVHTGDQHQ VGNETTEHGT IATITPQAPT SEIQLTDYGA LTLDCSPRTG LDFNRVVLLT
MKKKSWLVHK QWFLDLPLPW TSGASTSQET WNRQDLLVTF KTAHAKKQEV VVLGSQEGAM
HTALTGATEI QTSGTTTIFA GHLKCRLKMD KLTLKGMSYV MCTGSFKLEK EVAETQHGTV
LVQVKYEGTD APCKIPFSSQ DEKGVTQNGR LITANPIVID KEKPVNIEAE PPFGESYIVV
GSGEKALKLS WFKKGSSIGK MFEATARGAR RMAILGDTAW DFGSIGGVFT SVGKLIHQIF
GTAYGILFSG VSWTMKIGIG ILLTWLGLNS RSTSLSMTCI AVGMVTLYLG VMVQADSGCV
INWKGKELKC G
