VGP_TAFVC
ID VGP_TAFVC Reviewed; 676 AA.
AC Q66810;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 108.
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=GP2-delta;
DE Flags: Precursor;
GN Name=GP;
OS Tai Forest ebolavirus (strain Cote d'Ivoire-94) (TAFV) (Cote d'Ivoire Ebola
OS virus).
OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Haploviricotina;
OC Monjiviricetes; Mononegavirales; Filoviridae; Ebolavirus.
OX NCBI_TaxID=128999;
OH NCBI_TaxID=77231; Epomops franqueti (Franquet's epauleted fruit bat).
OH NCBI_TaxID=9606; Homo sapiens (Human).
OH NCBI_TaxID=77243; Myonycteris torquata (Little collared fruit bat).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA], AND RNA EDITING.
RX PubMed=8622982; DOI=10.1073/pnas.93.8.3602;
RA Sanchez A., Trappier S.G., Mahy B.W.J., Peters C.J., Nichol S.T.;
RT "The virion glycoproteins of Ebola viruses are encoded in two reading
RT frames and are expressed through transcriptional editing.";
RL Proc. Natl. Acad. Sci. U.S.A. 93:3602-3607(1996).
RN [2]
RP INTERACTION WITH HUMAN CLEC10A.
RX PubMed=14990712; DOI=10.1128/jvi.78.6.2943-2947.2004;
RA Takada A., Fujioka K., Tsuiji M., Morikawa A., Higashi N., Ebihara H.,
RA Kobasa D., Feldmann H., Irimura T., Kawaoka Y.;
RT "Human macrophage C-type lectin specific for galactose and N-
RT acetylgalactosamine promotes filovirus entry.";
RL J. Virol. 78:2943-2947(2004).
CC -!- FUNCTION: GP1 is 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 the host cell. Binding to CD209 and
CC CLEC4M, which are respectively found on dendritic cells (DCs), and on
CC endothelial cells of liver sinusoids and lymph node sinuses, facilitate
CC infection of macrophages and endothelial cells. These interactions not
CC only facilitate virus cell entry, but also allow capture of viral
CC particles by DCs and subsequent transmission to susceptible cells
CC without DCs infection (trans infection). Binding to the macrophage
CC specific lectin CLEC10A also seems to enhance virus infectivity.
CC Interaction with FOLR1/folate receptor alpha may be a cofactor for
CC virus entry in some cell types, although results are contradictory.
CC Members of the Tyro3 receptor tyrosine kinase family also seem to be
CC cell entry factors in filovirus infection. Once attached, the virions
CC are internalized through clathrin-dependent endocytosis and/or
CC macropinocytosis. After internalization of the virus into the endosomes
CC of the host cell, proteolysis of GP1 by two cysteine proteases,
CC CTSB/cathepsin B and CTSL/cathepsin L presumably induces a
CC conformational change of GP2, unmasking its fusion peptide and
CC initiating membranes fusion (By similarity). {ECO:0000250}.
CC -!- FUNCTION: GP2 acts as a class I viral fusion protein. Under the current
CC model, the protein has at least 3 conformational states: pre-fusion
CC native state, pre-hairpin intermediate state, and post-fusion hairpin
CC state. During viral and target cell membrane fusion, the coiled coil
CC 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 (By similarity). {ECO:0000250}.
CC -!- FUNCTION: [Envelope glycoprotein]: GP1,2 which is the disulfid-linked
CC complex of GP1 and GP2, mediates endothelial cell activation and
CC decreases endothelial barrier function. Mediates activation of primary
CC macrophages. At terminal stages of the viral infection, when its
CC expression is high, GP1,2 down-modulates the expression of various host
CC cell surface molecules that are essential for immune surveillance and
CC cell adhesion. Down-modulates integrins ITGA1, ITGA2, ITGA3, ITGA4,
CC ITGA5, ITGA6, ITGAV and ITGB1. GP1,2 alters the cellular recycling of
CC the dimer alpha-V/beta-3 via a dynamin-dependent pathway. Decrease in
CC the host cell surface expression of various adhesion molecules may lead
CC to cell detachment, contributing to the disruption of blood vessel
CC integrity and hemorrhages developed during Ebola virus infection
CC (cytotoxicity). This cytotoxicity appears late in the infection, only
CC after the massive release of viral particles by infected cells. Down-
CC modulation of host MHC-I, leading to altered recognition by immune
CC cells, may explain the immune suppression and inflammatory dysfunction
CC linked to Ebola infection. Also down-modulates EGFR surface expression.
CC Counteracts the antiviral effect of host tetherin (By similarity).
CC {ECO:0000250|UniProtKB:Q05320}.
CC -!- FUNCTION: GP2delta is part of the complex GP1,2delta released by host
CC ADAM17 metalloprotease. This secreted complex may play a role in the
CC pathogenesis of the virus by efficiently blocking the neutralizing
CC antibodies that would otherwise neutralize the virus surface
CC glycoproteins GP1,2. Might therefore contribute to the lack of
CC inflammatory reaction seen during infection in spite the of extensive
CC necrosis and massive virus production. GP1,2delta does not seem to be
CC involved in activation of primary macrophages (By similarity).
CC {ECO:0000250}.
CC -!- SUBUNIT: Homotrimer; each monomer consists of a GP1 and a GP2 subunit
CC linked by disulfide bonds. The resulting peplomers (GP1,2) protrude
CC from the virus surface as spikes. GP1 and GP2delta are part of
CC GP1,2delta soluble complexes released by ectodomain shedding. GP1,2
CC interacts with host integrin ITGAV/alpha-V and CLEC10A. Also binds
CC human CD209 and CLEC4M (collectively referred to as DC-SIGN(R)), as
CC well as human FOLR1. Interacts with host entry receptor NPC1.
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: [GP2-delta]: 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=295 {ECO:0000269|PubMed:8622982};
CC Note=Partially edited. RNA editing at this position consists of an
CC insertion of one adenine nucleotide. The sequence displayed here is the
CC full-length transmembrane glycoprotein, derived from the edited RNA.
CC The unedited RNA gives rise to the small secreted glycoprotein (AC
CC Q66811).;
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; U28006; AAB37093.1; -; Genomic_RNA.
DR BMRB; Q66810; -.
DR SMR; Q66810; -.
DR PRIDE; Q66810; -.
DR ABCD; Q66810; 1 sequenced antibody.
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 1: Evidence at protein level;
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..32
FT /evidence="ECO:0000255"
FT CHAIN 33..676
FT /note="Envelope glycoprotein"
FT /id="PRO_0000037467"
FT CHAIN 33..501
FT /note="GP1"
FT /evidence="ECO:0000250"
FT /id="PRO_0000037468"
FT CHAIN 502..676
FT /note="GP2"
FT /evidence="ECO:0000250"
FT /id="PRO_0000037469"
FT CHAIN 502..637
FT /note="GP2-delta"
FT /evidence="ECO:0000250"
FT /id="PRO_0000245056"
FT TOPO_DOM 33..650
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 651..671
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 672..676
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REGION 54..201
FT /note="Receptor-binding"
FT /evidence="ECO:0000250"
FT REGION 305..485
FT /note="Mucin-like region"
FT /evidence="ECO:0000250"
FT REGION 356..463
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 524..539
FT /note="Fusion peptide"
FT /evidence="ECO:0000250"
FT COILED 554..595
FT /evidence="ECO:0000255"
FT COILED 615..634
FT /evidence="ECO:0000255"
FT COMPBIAS 356..387
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 396..462
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 57
FT /note="Involved in receptor recognition and/or post-binding
FT events"
FT /evidence="ECO:0000255"
FT SITE 63
FT /note="Involved in receptor recognition and/or post-binding
FT events"
FT /evidence="ECO:0000255"
FT SITE 88
FT /note="Involved in receptor recognition and/or post-binding
FT events"
FT /evidence="ECO:0000255"
FT SITE 95
FT /note="Involved in receptor recognition and/or post-binding
FT events"
FT /evidence="ECO:0000255"
FT SITE 170
FT /note="Involved in receptor recognition and/or post-binding
FT events"
FT /evidence="ECO:0000255"
FT SITE 501..502
FT /note="Cleavage; by host furin"
FT /evidence="ECO:0000250"
FT SITE 637..638
FT /note="Cleavage; by host ADAM17"
FT /evidence="ECO:0000250"
FT LIPID 670
FT /note="S-palmitoyl cysteine; by host"
FT /evidence="ECO:0000250|UniProtKB:Q05320"
FT LIPID 672
FT /note="S-palmitoyl cysteine; by host"
FT /evidence="ECO:0000250|UniProtKB:Q05320"
FT CARBOHYD 40
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 204
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 228
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 257
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 268
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 296
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 414
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 441
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 563
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 618
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT DISULFID 53..609
FT /note="Interchain (between GP1 and GP2 chains)"
FT /evidence="ECO:0000250"
FT DISULFID 108..135
FT /evidence="ECO:0000255"
FT DISULFID 121..147
FT /evidence="ECO:0000255"
FT DISULFID 511..556
FT /evidence="ECO:0000255"
FT DISULFID 601..608
FT /evidence="ECO:0000250|UniProtKB:O11457"
SQ SEQUENCE 676 AA; 74722 MW; 9C753510BFADB48D CRC64;
MGASGILQLP RERFRKTSFF VWVIILFHKV FSIPLGVVHN NTLQVSDIDK FVCRDKLSST
SQLKSVGLNL EGNGVATDVP TATKRWGFRA GVPPKVVNYE AGEWAENCYN LAIKKVDGSE
CLPEAPEGVR DFPRCRYVHK VSGTGPCPGG LAFHKEGAFF LYDRLASTII YRGTTFAEGV
IAFLILPKAR KDFFQSPPLH EPANMTTDPS SYYHTTTINY VVDNFGTNTT EFLFQVDHLT
YVQLEARFTP QFLVLLNETI YSDNRRSNTT GKLIWKINPT VDTSMGEWAF WENKKNFTKT
LSSEELSFVP VPETQNQVLD TTATVSPPIS AHNHAGEDHK ELVSEDSTPV VQMQNIKGKD
TMPTTVTGVP TTTPSPFPIN ARNTDHTKSF IGLEGPQEDH STTQPAKTTS QPTNSTESTT
LNPTSEPSSR GTGPSSPTVP NTTESHAELG KTTPTTLPEQ HTAASAIPRA VHPDELSGPG
FLTNTIRGVT NLLTGSRRKR RDVTPNTQPK CNPNLHYWTA LDEGAAIGLA WIPYFGPAAE
GIYTEGIMEN QNGLICGLRQ LANETTQALQ LFLRATTELR TFSILNRKAI DFLLQRWGGT
CHILGPDCCI EPQDWTKNIT DKIDQIIHDF VDNNLPNQND GSNWWTGWKQ WVPAGIGITG
VIIAIIALLC ICKFML
