VGP_EBORE
ID VGP_EBORE Reviewed; 677 AA.
AC Q91DD8;
DT 11-JUL-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 23-FEB-2022, entry version 100.
DE RecName: Full=Envelope glycoprotein;
DE AltName: Full=GP1,2;
DE Short=GP;
DE Contains:
DE RecName: Full=GP1;
DE Contains:
DE RecName: Full=GP2;
DE Contains:
DE RecName: Full=Shed GP;
DE AltName: Full=GP1,2-delta;
DE Flags: Precursor;
GN Name=GP;
OS Reston ebolavirus (strain Philippines-96) (REBOV) (Reston Ebola virus).
OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Haploviricotina;
OC Monjiviricetes; Mononegavirales; Filoviridae; Ebolavirus.
OX NCBI_TaxID=129003;
OH NCBI_TaxID=9606; Homo sapiens (Human).
OH NCBI_TaxID=9541; Macaca fascicularis (Crab-eating macaque) (Cynomolgus monkey).
OH NCBI_TaxID=77225; Pteropodinae.
OH NCBI_TaxID=9823; Sus scrofa (Pig).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=11722021; DOI=10.1007/s007050170049;
RA Ikegami T., Calaor A.B., Miranda M.E., Niikura M., Saijo M., Kurane I.,
RA Yoshikawa Y., Morikawa S.;
RT "Genome structure of Ebola virus subtype Reston: differences among Ebola
RT subtypes.";
RL Arch. Virol. 146:2021-2027(2001).
RN [2]
RP FUNCTION (GP1).
RX PubMed=17005688; DOI=10.1128/jvi.01157-06;
RA Shimojima M., Takada A., Ebihara H., Neumann G., Fujioka K., Irimura T.,
RA Jones S., Feldmann H., Kawaoka Y.;
RT "Tyro3 family-mediated cell entry of Ebola and Marburg viruses.";
RL J. Virol. 80:10109-10116(2006).
CC -!- FUNCTION: [Envelope glycoprotein]: Trimeric GP1,2 complexes form the
CC virion surface spikes and mediate the viral entry processes, with GP1
CC acting as the receptor-binding subunit and GP2 as the membrane fusion
CC subunit. At later times of infection, down-regulates the expression of
CC various host cell surface molecules that are essential for immune
CC surveillance and cell adhesion. Down-modulates several integrins
CC including ITGA1, ITGA2, ITGA3, ITGA4, ITGA5, ITGA6, ITGAV and ITGB1.
CC This decrease in cell adhesion molecules may lead to cell detachment,
CC contributing to the disruption of blood vessel integrity and
CC hemorrhages developed during infection (cytotoxicity). Interacts with
CC host TLR4 and thereby stimulates the differentiation and activation of
CC monocytes leading to bystander death of T-lymphocytes. Down-regulates
CC as well the function of host natural killer cells. Counteracts the
CC antiviral effect of host BST2/tetherin that restricts release of
CC progeny virions from infected cells. However, cooperates with VP40 and
CC host BST2 to activate canonical NF-kappa-B pathway in a manner
CC dependent on neddylation. {ECO:0000250|UniProtKB:Q05320}.
CC -!- FUNCTION: [Shed GP]: Functions as a decoy for anti-GP1,2 antibodies
CC thereby contributing to viral immune evasion. Interacts and activates
CC host macrophages and dendritic cells inducing up-regulation of cytokine
CC transcription. This effect is mediated throught activation of host
CC TLR4. {ECO:0000250|UniProtKB:Q05320}.
CC -!- FUNCTION: [GP1]: Responsible for binding to the receptor(s) on target
CC cells. Interacts with CD209/DC-SIGN and CLEC4M/DC-SIGNR which act as
CC cofactors for virus entry into dendritic cells (DCs) and endothelial
CC cells (By similarity). Binding to the macrophage specific lectin
CC CLEC10A also seems to enhance virus infectivity (By similarity).
CC Interaction with FOLR1/folate receptor alpha may be a cofactor for
CC virus entry in some cell types, although results are contradictory (By
CC similarity). Members of the Tyro3 receptor tyrosine kinase family also
CC seem to be cell entry factors in filovirus infection (By similarity)
CC (PubMed:17005688). Once attached, the virions are internalized through
CC clathrin-dependent endocytosis and/or macropinocytosis. After
CC internalization of the virus into the endosomes of the host cell,
CC proteolysis of GP1 by two cysteine proteases, CTSB/cathepsin B and
CC CTSL/cathepsin L removes the glycan cap and allows GP1 binding to the
CC host entry receptor NPC1. NPC1-binding, Ca(2+) and acidic pH induce a
CC conformational change of GP2, which unmasks its fusion peptide and
CC permit membranes fusion (By similarity). {ECO:0000250|UniProtKB:Q05320,
CC ECO:0000250|UniProtKB:Q66814, ECO:0000269|PubMed:17005688}.
CC -!- FUNCTION: [GP2]: Acts as a class I viral fusion protein. Under the
CC current model, the protein has at least 3 conformational states: pre-
CC fusion native state, pre-hairpin intermediate state, and post-fusion
CC hairpin state. During viral and target cell membrane fusion, the coiled
CC coil regions (heptad repeats) assume a trimer-of-hairpins structure,
CC positioning the fusion peptide in close proximity to the C-terminal
CC region of the ectodomain. The formation of this structure appears to
CC drive apposition and subsequent fusion of viral and target cell
CC membranes. Responsible for penetration of the virus into the cell
CC cytoplasm by mediating the fusion of the membrane of the endocytosed
CC virus particle with the endosomal membrane. Low pH in endosomes induces
CC an irreversible conformational change in GP2, releasing the fusion
CC hydrophobic peptide. {ECO:0000250|UniProtKB:Q05320}.
CC -!- SUBUNIT: [Envelope glycoprotein]: Homotrimer; each monomer consists of
CC a GP1 and a GP2 subunit linked by disulfide bonds. The resulting
CC peplomers (GP1,2) protrude from the virus surface as spikes. Interacts
CC with host integrin alpha-V/ITGAV. Interacts with host CLEC10A. Binds
CC also to host CD209 and CLEC4M/DC-SIGN(R). Interacts with host FOLR1.
CC Interacts with BST2; this interaction inhibits the antiviral effect of
CC BST2 and this allows viral release from infected cells. Interacts with
CC host FCN1; this interaction enhances viral entry. Interacts with host
CC TLR4; this interaction induces T-lymphocyte death.
CC {ECO:0000250|UniProtKB:Q05320}.
CC -!- SUBUNIT: [GP1]: Interacts with host entry receptor NPC1.
CC {ECO:0000250|UniProtKB:Q05320}.
CC -!- SUBUNIT: [Shed GP]: GP1 and GP2delta are part of GP1,2delta soluble
CC complexes released by ectodomain shedding.
CC {ECO:0000250|UniProtKB:Q05320}.
CC -!- SUBCELLULAR LOCATION: [GP2]: Virion membrane
CC {ECO:0000250|UniProtKB:Q05320}; Single-pass type I membrane protein
CC {ECO:0000255}. Host cell membrane {ECO:0000250|UniProtKB:Q05320};
CC Single-pass type I membrane protein {ECO:0000255}. Note=In the cell,
CC localizes to the plasma membrane lipid rafts, which probably represent
CC the assembly and budding site. {ECO:0000250|UniProtKB:Q05320}.
CC -!- SUBCELLULAR LOCATION: [GP1]: Virion membrane
CC {ECO:0000250|UniProtKB:Q05320}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:Q05320}. Host cell membrane
CC {ECO:0000250|UniProtKB:Q05320}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:Q05320}. Note=GP1 is not anchored to the viral
CC envelope, but forms a disulfid-linked complex with the extravirion
CC surface GP2. In the cell, both GP1 and GP2 localize to the plasma
CC membrane lipid rafts, which probably represent the assembly and budding
CC site. GP1 can also be shed after proteolytic processing.
CC {ECO:0000250|UniProtKB:Q05320}.
CC -!- SUBCELLULAR LOCATION: [Shed GP]: Secreted
CC {ECO:0000250|UniProtKB:Q05320}. Note=GP2-delta bound to GP1 (GP1,2-
CC delta) is produced by proteolytic cleavage of GP1,2 by host ADAM17 and
CC shed by the virus. {ECO:0000250|UniProtKB:Q05320}.
CC -!- DOMAIN: The mucin-like region seems to be involved in the cytotoxic
CC function. This region is also involved in binding to human CLEC10A (By
CC similarity). {ECO:0000250}.
CC -!- DOMAIN: The coiled coil regions play a role in oligomerization and
CC fusion activity. {ECO:0000250}.
CC -!- PTM: The signal peptide region modulates GP's high mannose
CC glycosylation, thereby determining the efficiency of the interactions
CC with DC-SIGN(R). {ECO:0000250}.
CC -!- PTM: N-glycosylated. {ECO:0000250}.
CC -!- PTM: O-glycosylated in the mucin-like region. {ECO:0000250}.
CC -!- PTM: Palmitoylation of GP2 is not required for its function.
CC {ECO:0000250}.
CC -!- PTM: Specific enzymatic cleavages in vivo yield mature proteins. The
CC precursor is processed into GP1 and GP2 by host cell furin in the trans
CC Golgi, and maybe by other host proteases, to yield the mature GP1 and
CC GP2 proteins. The cleavage site corresponds to the furin optimal
CC cleavage sequence [KR]-X-[KR]-R. This cleavage does not seem to be
CC required for function. After the internalization of the virus into cell
CC endosomes, GP1 C-terminus is removed by the endosomal proteases
CC cathepsin B, cathepsin L, or both, leaving a 19-kDa N-terminal fragment
CC which is further digested by cathepsin B. Proteolytic processing of
CC GP1,2 by host ADAM17 can remove the transmembrane anchor of GP2 and
CC leads to shedding of complexes consisting in GP1 and truncated GP2
CC (GP1,2delta) (By similarity). {ECO:0000250}.
CC -!- RNA EDITING: Modified_positions=296; Note=Partially edited. RNA editing
CC at this position consists of an insertion of one or two adenine
CC nucleotides. The sequence displayed here is the full-length
CC transmembrane glycoprotein GP, derived from the +1A edited RNA. The
CC unedited RNA gives rise to the small secreted glycoprotein sGP (AC
CC Q91DD7), the +2A edited RNA gives rise to the super small secreted
CC glycoprotein ssGP (AC P0C770).;
CC -!- MISCELLANEOUS: Filoviruses entry requires functional lipid rafts at the
CC host cell surface. {ECO:0000250}.
CC -!- MISCELLANEOUS: Essential for infectivity, as it is the sole viral
CC protein expressed at the virion surface.
CC -!- SIMILARITY: Belongs to the filoviruses glycoprotein family.
CC {ECO:0000305}.
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DR EMBL; AB050936; BAB69006.1; -; Genomic_RNA.
DR SMR; Q91DD8; -.
DR Proteomes; UP000002322; Genome.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0020002; C:host cell plasma 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:0055036; C:virion membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0075512; P:clathrin-dependent endocytosis of virus by host cell; IEA:UniProtKB-KW.
DR GO; GO:0098670; P:entry receptor-mediated virion attachment to host cell; IEA:UniProtKB-KW.
DR GO; GO:0039654; P:fusion of virus membrane with host endosome membrane; IEA:UniProtKB-KW.
DR GO; GO:0039587; P:suppression by virus of host tetherin activity; IEA:UniProtKB-KW.
DR GO; GO:0039502; P:suppression by virus of host type I interferon-mediated signaling pathway; IEA:UniProtKB-KW.
DR InterPro; IPR014625; GPC_FiloV.
DR InterPro; IPR002561; GPC_filovir-type_extra_dom.
DR Pfam; PF01611; Filo_glycop; 1.
DR PIRSF; PIRSF036874; GPC_FiloV; 1.
PE 3: Inferred from homology;
KW Clathrin-mediated endocytosis of virus by host;
KW Cleavage on pair of basic residues; Coiled coil; Disulfide bond;
KW Fusion of virus membrane with host endosomal membrane;
KW Fusion of virus membrane with host membrane; Glycoprotein;
KW Host cell membrane; Host membrane; Host-virus interaction;
KW Inhibition of host innate immune response by virus;
KW Inhibition of host interferon signaling pathway by virus;
KW Inhibition of host tetherin by virus; Lipoprotein; Membrane; Palmitate;
KW RNA editing; Secreted; Signal; Transmembrane; Transmembrane helix;
KW Viral attachment to host cell; Viral attachment to host entry receptor;
KW Viral envelope protein; Viral immunoevasion;
KW Viral penetration into host cytoplasm; Virion; Virus endocytosis by host;
KW Virus entry into host cell.
FT SIGNAL 1..33
FT /evidence="ECO:0000255"
FT CHAIN 34..677
FT /note="Envelope glycoprotein"
FT /evidence="ECO:0000250"
FT /id="PRO_0000245057"
FT CHAIN 34..502
FT /note="GP1"
FT /evidence="ECO:0000250"
FT /id="PRO_0000245058"
FT CHAIN 503..677
FT /note="GP2"
FT /evidence="ECO:0000250"
FT /id="PRO_0000245059"
FT CHAIN 503..638
FT /note="Shed GP"
FT /evidence="ECO:0000250"
FT /id="PRO_0000245060"
FT TOPO_DOM 34..651
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 652..672
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 673..677
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 55..202
FT /note="Receptor-binding"
FT /evidence="ECO:0000250"
FT REGION 306..486
FT /note="Mucin-like region"
FT /evidence="ECO:0000250"
FT REGION 315..349
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 370..483
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 489..508
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 525..540
FT /note="Fusion peptide"
FT /evidence="ECO:0000250"
FT COILED 555..596
FT /evidence="ECO:0000255"
FT COILED 616..635
FT /evidence="ECO:0000255"
FT COMPBIAS 315..347
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 58
FT /note="Involved in receptor recognition and/or post-binding
FT events"
FT /evidence="ECO:0000255"
FT SITE 64
FT /note="Involved in receptor recognition and/or post-binding
FT events"
FT /evidence="ECO:0000255"
FT SITE 89
FT /note="Involved in receptor recognition and/or post-binding
FT events"
FT /evidence="ECO:0000255"
FT SITE 96
FT /note="Involved in receptor recognition and/or post-binding
FT events"
FT /evidence="ECO:0000255"
FT SITE 171
FT /note="Involved in receptor recognition and/or post-binding
FT events"
FT /evidence="ECO:0000255"
FT SITE 502..503
FT /note="Cleavage; by host furin"
FT /evidence="ECO:0000250"
FT SITE 638..639
FT /note="Cleavage; by host ADAM17"
FT /evidence="ECO:0000250"
FT LIPID 671
FT /note="S-palmitoyl cysteine; by host"
FT /evidence="ECO:0000250|UniProtKB:Q05320"
FT LIPID 673
FT /note="S-palmitoyl cysteine; by host"
FT /evidence="ECO:0000250|UniProtKB:Q05320"
FT CARBOHYD 41
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 205
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 239
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 258
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 269
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 297
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 317
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 318
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 339
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 406
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 420
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 435
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 463
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 564
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 619
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT DISULFID 54..610
FT /note="Interchain (between GP1 and GP2 chains)"
FT /evidence="ECO:0000250"
FT DISULFID 109..136
FT /evidence="ECO:0000255"
FT DISULFID 122..148
FT /evidence="ECO:0000255"
FT DISULFID 512..557
FT /evidence="ECO:0000255"
FT DISULFID 602..609
FT /evidence="ECO:0000250|UniProtKB:O11457"
SQ SEQUENCE 677 AA; 74330 MW; 7C65D432735D063C CRC64;
MGSGYQLLQL PRERFRKTSF LVWVIILFQR AISMPLGIVT NSTLKATEID QLVCRDKLSS
TSQLKSVGLN LEGNGIATDV PSATKRWGFR SGVPPKVVSY EAGEWAENCY NLEIKKSDGS
ECLPLPPDGV RGFPRCRYVH KVQGTGPCPG DLAFHKNGAF FLYDRLASTV IYRGTTFAEG
VIAFLILSEP KKHFWKATPA HEPVNTTDDS TSYYMTLTLS YEMSNFGGEE SNTLFKVDNH
TYVQLDRPHT PQFLVQLNET LRRNNRLSNS TGRLTWTVDP KIEPDVGEWA FWETKKNFSQ
QLHGENLHFQ ILSTHTNNSS DQSPAGTVQG KISYHPPTNN SELVPTDSPP VVSVLTAGRT
EEMSTQGLTN GETITGFTAN PMTTTIAPSP TMTSEVDNNV PSEQPNNTAS IEDSPPSASN
ETIDHSEMNS IQGSNNSAQS PQTKATPAPT ASPMTLDPQE TANISKPGTS PGSAAGPSQP
GLTINTISKV ADSLSPTRKQ KRSVRQNTAN KCNPDLHYWT AVDEGAAAGL AWIPYFGPAA
EGIYIEGVMH NQNGLICGLR QLANETTQAL QLFLRATTEL RTYSLLNRKA IDFLLQRWGG
TCRILGPSCC IEPHDWTKNI TDEINQIKHD FIDNPLPDHG DDLNLWTGWR QWIPAGIGII
GVIIAIIALL CICKILC
