RecName: Full=Envelope glycoprotein; AltName: Full=GP1,2; Short=GP; Contains: RecName: Full=GP1; Contains: RecName: Full=GP2; Contains: RecName: Full=GP2-delta; Flags: Precursor [Ebola virus - Eckron (Zaire, 1976)]
UniProtKB/Swiss-Prot: P87671.1
LOCUS VGP_EBOEC 676 aa linear VRL 29-OCT-2014
DEFINITION RecName: Full=Envelope glycoprotein; AltName: Full=GP1,2; Short=GP;
Contains: RecName: Full=GP1; Contains: RecName: Full=GP2; Contains:
RecName: Full=GP2-delta; Flags: Precursor.
ACCESSION P87671
VERSION P87671.1 GI:8479505
DBSOURCE UniProtKB: locus VGP_EBOEC, accession P87671;
class: standard.
created: May 30, 2000.
sequence updated: May 1, 1997.
annotation updated: Oct 29, 2014.
xrefs: U81161.1, AAC57992.1, 2QHR_P
xrefs (non-sequence databases): PDBsum:2QHR,
ProteinModelPortal:P87671, SMR:P87671, EvolutionaryTrace:P87671,
GO:0020002, GO:0016021, GO:0019031, GO:0075512, GO:0039654,
GO:0039587, GO:0039502, GO:0019062, InterPro:IPR014625,
InterPro:IPR002561, Pfam:PF01611, PIRSF:PIRSF036874
KEYWORDS 3D-structure; Clathrin-mediated endocytosis of virus by host;
Cleavage on pair of basic residues; Coiled coil; Disulfide bond;
Fusion of virus membrane with host endosomal membrane; Fusion of
virus membrane with host membrane; Glycoprotein; Host cell
membrane; Host membrane; Host-virus interaction; Inhibition of host
innate immune response by virus; Inhibition of host interferon
signaling pathway by virus; Inhibition of host tetherin by virus;
Lipoprotein; Membrane; Palmitate; RNA editing; Secreted; Signal;
Transmembrane; Transmembrane helix; Viral attachment to host cell;
Viral envelope protein; Viral immunoevasion; Viral penetration into
host cytoplasm; Virion; Virus endocytosis by host; Virus entry into
host cell.
SOURCE Ebola virus - Eckron (Zaire, 1976)
ORGANISM Ebola virus - Eckron (Zaire, 1976)
Viruses; ssRNA negative-strand viruses; Mononegavirales;
Filoviridae; Ebolavirus.
REFERENCE 1 (residues 1 to 676)
AUTHORS Volchkov,V., Volchkova,V., Eckel,C., Klenk,H.D., Bouloy,M.,
LeGuenno,B. and Feldmann,H.
TITLE Emergence of subtype Zaire Ebola virus in Gabon
JOURNAL Virology 232 (1), 139-144 (1997)
PUBMED 9185597
REMARK NUCLEOTIDE SEQUENCE [GENOMIC RNA].
COMMENT [FUNCTION] GP1 is responsible for binding to the receptor(s) on
target cells. Interacts with CD209/DC-SIGN and CLEC4M/DC-SIGNR
which act as cofactors for virus entry into the host cell. Binding
to CD209 and CLEC4M, which are respectively found on dendritic
cells (DCs), and on endothelial cells of liver sinusoids and lymph
node sinuses, facilitate infection of macrophages and endothelial
cells. These interactions not only facilitate virus cell entry, but
also allow capture of viral particles by DCs and subsequent
transmission to susceptible cells without DCs infection (trans
infection). Binding to the macrophage specific lectin CLEC10A also
seems to enhance virus infectivity. Interaction with FOLR1/folate
receptor alpha may be a cofactor for virus entry in some cell
types, although results are contradictory. Members of the Tyro3
receptor tyrosine kinase family also seem to be cell entry factors
in filovirus infection. Once attached, the virions are internalized
through clathrin-dependent endocytosis and/or macropinocytosis.
After internalization of the virus into the endosomes of the host
cell, proteolysis of GP1 by two cysteine proteases, CTSB/cathepsin
B and CTSL/cathepsin L presumably induces a conformational change
of GP2, unmasking its fusion peptide and initiating membranes
fusion (By similarity). {ECO:0000250}.
[FUNCTION] GP2 acts as a class I viral fusion protein. Under the
current model, the protein has at least 3 conformational states:
pre-fusion native state, pre-hairpin intermediate state, and
post-fusion hairpin state. During viral and target cell membrane
fusion, the coiled coil regions (heptad repeats) assume a
trimer-of-hairpins structure, positioning the fusion peptide in
close proximity to the C-terminal region of the ectodomain. The
formation of this structure appears to drive apposition and
subsequent fusion of viral and target cell membranes. Responsible
for penetration of the virus into the cell cytoplasm by mediating
the fusion of the membrane of the endocytosed virus particle with
the endosomal membrane. Low pH in endosomes induces an irreversible
conformational change in GP2, releasing the fusion hydrophobic
peptide (By similarity). {ECO:0000250}.
[FUNCTION] GP1,2 mediates endothelial cell activation and decreases
endothelial barrier function. Mediates activation of primary
macrophages. At terminal stages of the viral infection, when its
expression is high, GP1,2 down-modulates the expression of various
host cell surface molecules that are essential for immune
surveillance and cell adhesion. Down-modulates integrins ITGA1,
ITGA2, ITGA3, ITGA4, ITGA5, ITGA6, ITGAV and ITGB1. GP1,2 alters
the cellular recycling of the dimer alpha-V/beta-3 via a
dynamin-dependent pathway. Decrease in the host cell surface
expression of various adhesion molecules may lead to cell
detachment, contributing to the disruption of blood vessel
integrity and hemorrhages developed during Ebola virus infection
(cytotoxicity). This cytotoxicity appears late in the infection,
only after the massive release of viral particles by infected
cells. Down-modulation of host MHC-I, leading to altered
recognition by immune cells, may explain the immune suppression and
inflammatory dysfunction linked to Ebola infection. Also
down-modulates EGFR surface expression (By similarity).
{ECO:0000250}.
[FUNCTION] GP2delta is part of the complex GP1,2delta released by
host ADAM17 metalloprotease. This secreted complex may play a role
in the pathogenesis of the virus by efficiently blocking the
neutralizing antibodies that would otherwise neutralize the virus
surface glycoproteins GP1,2. Might therefore contribute to the lack
of inflammatory reaction seen during infection in spite the of
extensive necrosis and massive virus production. GP1,2delta does
not seem to be involved in activation of primary macrophages (By
similarity). {ECO:0000250}.
[SUBUNIT] Homotrimer; each monomer consists of a GP1 and a GP2
subunit linked by disulfide bonds. The resulting peplomers (GP1,2)
protrude from the virus surface as spikes. GP1 and GP2delta are
part of GP1,2delta soluble complexes released by ectodomain
shedding. GP1,2 interacts with host integrin ITGAV/alpha-V and
CLEC10A. Also binds human CD209 and CLEC4M (collectively referred
to as DC-SIGN(R)), as well as human FOLR1 (By similarity).
{ECO:0000250}.
[SUBCELLULAR LOCATION] GP2: Virion membrane {ECO:0000250};
Single-pass type I membrane protein {ECO:0000250}. Virion membrane
{ECO:0000250}; Lipid-anchor {ECO:0000250}. Host cell membrane
{ECO:0000250}; Single-pass type I membrane protein {ECO:0000250}.
Host cell membrane {ECO:0000250}; Lipid-anchor {ECO:0000250}.
Note=In the cell, localizes to the plasma membrane lipid rafts,
which probably represent the assembly and budding site.
{ECO:0000250}.
[SUBCELLULAR LOCATION] GP1: Virion membrane {ECO:0000250};
Peripheral membrane protein {ECO:0000250}. Host cell membrane
{ECO:0000250}; Peripheral membrane protein {ECO:0000250}. Note=GP1
is not anchored to the viral envelope, but associates with the
extravirion surface through its binding to GP2. In the cell, both
GP1 and GP2 localize to the plasma membrane lipid rafts, which
probably represent the assembly and budding site. GP1 can also be
shed after proteolytic processing (By similarity). {ECO:0000250}.
[SUBCELLULAR LOCATION] GP2-delta: Secreted {ECO:0000250}.
Note=GP2-delta bound to GP1 (GP1,2-delta) is produced by
proteolytic cleavage of GP1,2 by host ADAM17 and shed by the virus.
{ECO:0000250}.
[DOMAIN] The mucin-like region seems to be involved in the
cytotoxic function. This region is also involved in binding to
human CLEC10A (By similarity). {ECO:0000250}.
[DOMAIN] The coiled coil regions play a role in oligomerization and
fusion activity. {ECO:0000250}.
[PTM] The signal peptide region modulates GP's high mannose
glycosylation, thereby determining the efficiency of the
interactions with DC-SIGN(R). {ECO:0000250}.
[PTM] N-glycosylated. {ECO:0000250}.
[PTM] O-glycosylated in the mucin-like region. {ECO:0000250}.
[PTM] Palmitoylation of GP2 is not required for its function.
{ECO:0000250}.
[PTM] Specific enzymatic cleavages in vivo yield mature proteins.
The precursor is processed into GP1 and GP2 by host cell furin in
the trans Golgi, and maybe by other host proteases, to yield the
mature GP1 and GP2 proteins. The cleavage site corresponds to the
furin optimal cleavage sequence [KR]-X-[KR]-R. This cleavage does
not seem to be required for function. After the internalization of
the virus into cell endosomes, GP1 C-terminus is removed by the
endosomal proteases cathepsin B, cathepsin L, or both, leaving a
19-kDa N-terminal fragment which is further digested by cathepsin
B. Proteolytic processing of GP1,2 by host ADAM17 can remove the
transmembrane anchor of GP2 and leads to shedding of complexes
consisting in GP1 and truncated GP2 (GP1,2delta) (By similarity).
{ECO:0000250}.
[RNA EDITING] Modified_positions=295; Note=Partially edited. RNA
editing at this position consists of an insertion of one adenine
nucleotide. The sequence displayed here is the full-length
transmembrane glycoprotein, derived from the edited RNA. The
unedited RNA gives rise to the small secreted glycoprotein (AC
P87670) (By similarity). {ECO:0000250}.
[MISCELLANEOUS] Filoviruses entry requires functional lipid rafts
at the host cell surface. {ECO:0000250}.
[MISCELLANEOUS] Essential for infectivity, as it is the sole viral
protein expressed at the virion surface.
[SIMILARITY] Belongs to the filoviruses glycoprotein family.
{ECO:0000305}.
FEATURES Location/Qualifiers
source 1..676
/organism="Ebola virus - Eckron (Zaire, 1976)"
/host="Epomops franqueti (Franquet's epauleted fruit bat)"
/host="Homo sapiens (Human)"
/host="Myonycteris torquata (Little collared fruit bat)"
/db_xref="taxon:129000"
gene 1..676
/gene="GP"
Protein 1..676
/gene="GP"
/product="Envelope glycoprotein"
/note="GP1,2"
/UniProtKB_evidence="Evidence at protein level"
Region 1..32
/gene="GP"
/region_name="Signal"
/experiment="experimental evidence, no additional details
recorded"
/note="{ECO:0000255}."
Region 33..676
/gene="GP"
/region_name="Mature chain"
/experiment="experimental evidence, no additional details
recorded"
/note="Envelope glycoprotein. /FTId=PRO_0000037461."
Region 33..650
/gene="GP"
/region_name="Topological domain"
/experiment="experimental evidence, no additional details
recorded"
/note="Extracellular. {ECO:0000255}."
Region 33..501
/gene="GP"
/region_name="Mature chain"
/experiment="experimental evidence, no additional details
recorded"
/note="GP1. {ECO:0000250}. /FTId=PRO_0000037462."
Site 40
/gene="GP"
/site_type="glycosylation"
/experiment="experimental evidence, no additional details
recorded"
/note="N-linked (GlcNAc...); by host. {ECO:0000255}."
Bond bond(53,609)
/gene="GP"
/bond_type="disulfide"
/experiment="experimental evidence, no additional details
recorded"
/note="Interchain (between GP1 and GP2 chains).
{ECO:0000250}."
Region 54..201
/gene="GP"
/region_name="Region of interest in the sequence"
/experiment="experimental evidence, no additional details
recorded"
/note="Receptor-binding. {ECO:0000250}."
Site 57
/gene="GP"
/site_type="other"
/experiment="experimental evidence, no additional details
recorded"
/note="Involved in receptor recognition and/or
post-binding events. {ECO:0000255}."
Site 63
/gene="GP"
/site_type="other"
/experiment="experimental evidence, no additional details
recorded"
/note="Involved in receptor recognition and/or
post-binding events. {ECO:0000255}."
Site 64
/gene="GP"
/site_type="other"
/experiment="experimental evidence, no additional details
recorded"
/note="Involved in receptor recognition and/or
post-binding events. {ECO:0000255}."
Site 88
/gene="GP"
/site_type="other"
/experiment="experimental evidence, no additional details
recorded"
/note="Involved in receptor recognition and/or
post-binding events. {ECO:0000255}."
Site 95
/gene="GP"
/site_type="other"
/experiment="experimental evidence, no additional details
recorded"
/note="Involved in receptor recognition and/or
post-binding events. {ECO:0000255}."
Bond bond(108,135)
/gene="GP"
/bond_type="disulfide"
/experiment="experimental evidence, no additional details
recorded"
/note="{ECO:0000255}."
Bond bond(121,147)
/gene="GP"
/bond_type="disulfide"
/experiment="experimental evidence, no additional details
recorded"
/note="{ECO:0000255}."
Site 170
/gene="GP"
/site_type="other"
/experiment="experimental evidence, no additional details
recorded"
/note="Involved in receptor recognition and/or
post-binding events. {ECO:0000255}."
Site 204
/gene="GP"
/site_type="glycosylation"
/experiment="experimental evidence, no additional details
recorded"
/note="N-linked (GlcNAc...); by host. {ECO:0000255}."
Site 228
/gene="GP"
/site_type="glycosylation"
/experiment="experimental evidence, no additional details
recorded"
/note="N-linked (GlcNAc...); by host. {ECO:0000255}."
Site 238
/gene="GP"
/site_type="glycosylation"
/experiment="experimental evidence, no additional details
recorded"
/note="N-linked (GlcNAc...); by host. {ECO:0000255}."
Site 257
/gene="GP"
/site_type="glycosylation"
/experiment="experimental evidence, no additional details
recorded"
/note="N-linked (GlcNAc...); by host. {ECO:0000255}."
Site 268
/gene="GP"
/site_type="glycosylation"
/experiment="experimental evidence, no additional details
recorded"
/note="N-linked (GlcNAc...); by host. {ECO:0000255}."
Site 296
/gene="GP"
/site_type="glycosylation"
/experiment="experimental evidence, no additional details
recorded"
/note="N-linked (GlcNAc...); by host. {ECO:0000255}."
Region 305..485
/gene="GP"
/region_name="Region of interest in the sequence"
/experiment="experimental evidence, no additional details
recorded"
/note="Mucin-like region. {ECO:0000250}."
Site 317
/gene="GP"
/site_type="glycosylation"
/experiment="experimental evidence, no additional details
recorded"
/note="N-linked (GlcNAc...); by host. {ECO:0000255}."
Site 333
/gene="GP"
/site_type="glycosylation"
/experiment="experimental evidence, no additional details
recorded"
/note="N-linked (GlcNAc...); by host. {ECO:0000255}."
Site 346
/gene="GP"
/site_type="glycosylation"
/experiment="experimental evidence, no additional details
recorded"
/note="N-linked (GlcNAc...); by host. {ECO:0000255}."
Site 386
/gene="GP"
/site_type="glycosylation"
/experiment="experimental evidence, no additional details
recorded"
/note="N-linked (GlcNAc...); by host. {ECO:0000255}."
Site 413
/gene="GP"
/site_type="glycosylation"
/experiment="experimental evidence, no additional details
recorded"
/note="N-linked (GlcNAc...); by host. {ECO:0000255}."
Site 436
/gene="GP"
/site_type="glycosylation"
/experiment="experimental evidence, no additional details
recorded"
/note="N-linked (GlcNAc...); by host. {ECO:0000255}."
Site 454
/gene="GP"
/site_type="glycosylation"
/experiment="experimental evidence, no additional details
recorded"
/note="N-linked (GlcNAc...); by host. {ECO:0000255}."
Site 462
/gene="GP"
/site_type="glycosylation"
/experiment="experimental evidence, no additional details
recorded"
/note="N-linked (GlcNAc...); by host. {ECO:0000255}."
Site 501..502
/gene="GP"
/site_type="cleavage"
/experiment="experimental evidence, no additional details
recorded"
/note="Cleavage; by host furin. {ECO:0000250}."
Region 502..676
/gene="GP"
/region_name="Mature chain"
/experiment="experimental evidence, no additional details
recorded"
/note="GP2. {ECO:0000250}. /FTId=PRO_0000037463."
Region 502..637
/gene="GP"
/region_name="Mature chain"
/experiment="experimental evidence, no additional details
recorded"
/note="GP2-delta. {ECO:0000250}. /FTId=PRO_0000245054."
Bond bond(511,556)
/gene="GP"
/bond_type="disulfide"
/experiment="experimental evidence, no additional details
recorded"
/note="{ECO:0000255}."
Region 524..539
/gene="GP"
/region_name="Region of interest in the sequence"
/experiment="experimental evidence, no additional details
recorded"
/note="Fusion peptide. {ECO:0000250}."
Region 554..595
/gene="GP"
/region_name="Coiled-coil region"
/experiment="experimental evidence, no additional details
recorded"
/note="{ECO:0000255}."
Site 563
/gene="GP"
/site_type="glycosylation"
/experiment="experimental evidence, no additional details
recorded"
/note="N-linked (GlcNAc...); by host. {ECO:0000255}."
Bond bond(601,608)
/gene="GP"
/bond_type="disulfide"
/experiment="experimental evidence, no additional details
recorded"
/note="{ECO:0000250}."
Region 615..634
/gene="GP"
/region_name="Coiled-coil region"
/experiment="experimental evidence, no additional details
recorded"
/note="{ECO:0000255}."
Site 618
/gene="GP"
/site_type="glycosylation"
/experiment="experimental evidence, no additional details
recorded"
/note="N-linked (GlcNAc...); by host. {ECO:0000255}."
Site 637..638
/gene="GP"
/site_type="cleavage"
/experiment="experimental evidence, no additional details
recorded"
/note="Cleavage; by host ADAM17. {ECO:0000250}."
Region 651..671
/gene="GP"
/region_name="Transmembrane region"
/experiment="experimental evidence, no additional details
recorded"
/note="Helical. {ECO:0000255}."
Site 670
/gene="GP"
/site_type="lipid-binding"
/experiment="experimental evidence, no additional details
recorded"
/note="S-palmitoyl cysteine; by host. {ECO:0000250}."
Region 672..676
/gene="GP"
/region_name="Topological domain"
/experiment="experimental evidence, no additional details
recorded"
/note="Cytoplasmic. {ECO:0000255}."
Site 672
/gene="GP"
/site_type="lipid-binding"
/experiment="experimental evidence, no additional details
recorded"
/note="S-palmitoyl cysteine; by host. {ECO:0000250}."
ORIGIN
1 mgvtgilqlp rdrfkrtsff lwviilfqrt fsiplgvihn stlqvndvdk lvcrdklsst
61 nqlrsvglnl egngvatdvp satkrwgfrs gvppkvvnye agewaencyn leikkpdgse
121 clpaapdgir gfprcryvhk vsgtgpcagd fafhkegaff lydrlastvi yrgttfaegv
181 vaflilpqak kdffsshplr epvnatedps sgyysttiry qatgfgtnet eylfevdnlt
241 yvqlesrftp qfllqlneti ytsgkrsntt gkliwkvnpe idttigewaf wetkknltrk
301 irseelsftv vsngaknisg qspartssdp gtntttedhk imasenssam vqvhsqgrea
361 avshlttlat istspqsltt kpgpdnsthn tpvykldise atqveqhhrr tdndstasdt
421 psattaagpp kaentntsks tdfldpattt spqnhsetag nnnthhqdtg eesassgklg
481 litntiagva glitggrrtr reaivnaqpk cnpnlhywtt qdegaaigla wipyfgpaae
541 giyteglmhn qnglicglrq lanettqalq lflrattelr tfsilnrkai dfllqrwggt
601 chilgpdcci ephdwtknit dkidqiihdf vdktlpdqgd ndnwwtgwrq wipagigvtg
661 viiavialfc ickfvf
//
VERTAA ssGP fragmenttiin (ORIGIN) 1 mgvtgilqlp rdrfkrtsff lwviilfqrt fsiplgvihn stlqvsdvdk lvcrdklsst 61 nqlrsvglnl egngvatdvp satkrwgfrs gvppkvvnye agewaencyn leikkpdgse 121 clpaapdgir gfprcryvhk vsgtgpcagd fafhkegaff lydrlastvi yrgttfaegv 181 vaflilpqak kdffsshplr epvnatedps sgyysttiry qatgfgtnet eylfevdnlt 241 yvqlesrftp qfllqlneti ytsgkrsntt gkliwkvnpe idttigewaf wetkkph
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