VGP_EBOSB
ID VGP_EBOSB Reviewed; 676 AA.
AC Q66814;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 25-MAY-2022, entry version 115.
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 Sudan ebolavirus (strain Boniface-76) (SEBOV) (Sudan Ebola virus).
OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Haploviricotina;
OC Monjiviricetes; Mononegavirales; Filoviridae; Ebolavirus.
OX NCBI_TaxID=128948;
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).
RN [3]
RP SIGNAL PEPTIDE (ENVELOPE GLYCOPROTEIN), AND GLYCOSYLATION (ENVELOPE
RP GLYCOPROTEIN).
RX PubMed=16775318; DOI=10.1128/jvi.02545-05;
RA Marzi A., Akhavan A., Simmons G., Gramberg T., Hofmann H., Bates P.,
RA Lingappa V.R., Poehlmann S.;
RT "The signal peptide of the ebolavirus glycoprotein influences interaction
RT with the cellular lectins DC-SIGN and DC-SIGNR.";
RL J. Virol. 80:6305-6317(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. Binding to the macrophage specific lectin CLEC10A also seem to
CC enhance virus infectivity (PubMed:14990712). Interaction with
CC FOLR1/folate receptor alpha may be a cofactor for virus entry in some
CC cell types, although results are contradictory (By similarity). Members
CC of the Tyro3 receptor tyrosine kinase family also seem to be cell entry
CC factors in filovirus infection (By similarity). Once attached, the
CC virions 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 removes the glycan cap and allows
CC GP1 binding to the host entry receptor NPC1. NPC1-binding, Ca(2+) and
CC acidic pH induce a conformational change of GP2, which unmasks its
CC fusion peptide and permit membranes fusion (By similarity).
CC {ECO:0000250|UniProtKB:O11457, ECO:0000250|UniProtKB:Q05320,
CC ECO:0000269|PubMed:14990712}.
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: [Envelope glycoprotein]: The signal peptide region modulates GP's
CC high mannose glycosylation, thereby determining the efficiency of the
CC interactions with DC-SIGN(R). {ECO:0000269|PubMed:16775318}.
CC -!- PTM: [Envelope glycoprotein]: N-glycosylated.
CC {ECO:0000305|PubMed:16775318}.
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 P60172).;
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; U28134; AAB37096.1; -; Genomic_RNA.
DR PDB; 3VE0; X-ray; 3.35 A; I=33-313, J=473-637.
DR PDBsum; 3VE0; -.
DR SMR; Q66814; -.
DR ABCD; Q66814; 2 sequenced antibodies.
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 3D-structure; 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_0000037476"
FT CHAIN 33..501
FT /note="GP1"
FT /evidence="ECO:0000250"
FT /id="PRO_0000037477"
FT CHAIN 502..676
FT /note="GP2"
FT /evidence="ECO:0000250"
FT /id="PRO_0000037478"
FT CHAIN 502..637
FT /note="Shed GP"
FT /evidence="ECO:0000250"
FT /id="PRO_0000245063"
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 313..351
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 406..458
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 318..341
FT /note="Basic and acidic 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 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 208
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 238
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 314
FT /note="N-linked (GlcNAc...) asparagine; by host"
FT /evidence="ECO:0000255"
FT CARBOHYD 366
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 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"
FT STRAND 34..39
FT /evidence="ECO:0007829|PDB:3VE0"
FT STRAND 45..49
FT /evidence="ECO:0007829|PDB:3VE0"
FT HELIX 60..62
FT /evidence="ECO:0007829|PDB:3VE0"
FT STRAND 63..70
FT /evidence="ECO:0007829|PDB:3VE0"
FT HELIX 71..73
FT /evidence="ECO:0007829|PDB:3VE0"
FT HELIX 79..83
FT /evidence="ECO:0007829|PDB:3VE0"
FT STRAND 86..91
FT /evidence="ECO:0007829|PDB:3VE0"
FT STRAND 96..98
FT /evidence="ECO:0007829|PDB:3VE0"
FT STRAND 100..103
FT /evidence="ECO:0007829|PDB:3VE0"
FT STRAND 105..114
FT /evidence="ECO:0007829|PDB:3VE0"
FT STRAND 120..122
FT /evidence="ECO:0007829|PDB:3VE0"
FT STRAND 135..143
FT /evidence="ECO:0007829|PDB:3VE0"
FT STRAND 149..154
FT /evidence="ECO:0007829|PDB:3VE0"
FT STRAND 159..161
FT /evidence="ECO:0007829|PDB:3VE0"
FT STRAND 163..169
FT /evidence="ECO:0007829|PDB:3VE0"
FT STRAND 176..189
FT /evidence="ECO:0007829|PDB:3VE0"
FT STRAND 216..221
FT /evidence="ECO:0007829|PDB:3VE0"
FT STRAND 223..226
FT /evidence="ECO:0007829|PDB:3VE0"
FT STRAND 236..239
FT /evidence="ECO:0007829|PDB:3VE0"
FT HELIX 250..254
FT /evidence="ECO:0007829|PDB:3VE0"
FT TURN 259..262
FT /evidence="ECO:0007829|PDB:3VE0"
FT STRAND 515..520
FT /evidence="ECO:0007829|PDB:3VE0"
FT STRAND 524..526
FT /evidence="ECO:0007829|PDB:3VE0"
FT STRAND 528..532
FT /evidence="ECO:0007829|PDB:3VE0"
FT TURN 533..535
FT /evidence="ECO:0007829|PDB:3VE0"
FT TURN 539..542
FT /evidence="ECO:0007829|PDB:3VE0"
FT STRAND 543..548
FT /evidence="ECO:0007829|PDB:3VE0"
FT HELIX 552..575
FT /evidence="ECO:0007829|PDB:3VE0"
FT STRAND 579..581
FT /evidence="ECO:0007829|PDB:3VE0"
FT HELIX 584..594
FT /evidence="ECO:0007829|PDB:3VE0"
FT STRAND 606..608
FT /evidence="ECO:0007829|PDB:3VE0"
SQ SEQUENCE 676 AA; 74987 MW; 700029BFD67F5E9A CRC64;
MEGLSLLQLP RDKFRKSSFF VWVIILFQKA FSMPLGVVTN STLEVTEIDQ LVCKDHLAST
DQLKSVGLNL EGSGVSTDIP SATKRWGFRS GVPPQVVSYE AGEWAENCYN LEIKKPDGSE
CLPPPPDGVR GFPRCRYVHK AQGTGPCPGD YAFHKDGAFF LYDRLASTVI YRGVNFAEGV
IAFLILAKPK ETFLQSPPIR EAANYTENTS SYYATSYLEY EIENFGAQHS TTLFKINNNT
FVLLDRPHTP QFLFQLNDTI QLHQQLSNTT GKLIWTLDAN INADIGEWAF WENKKNLSEQ
LRGEELSFET LSLNETEDDD ATSSRTTKGR ISDRATRKYS DLVPKDSPGM VSLHVPEGET
TLPSQNSTEG RRVDVNTQET ITETTATIIG TNGNNMQIST IGTGLSSSQI LSSSPTMAPS
PETQTSTTYT PKLPVMTTEE STTPPRNSPG STTEAPTLTT PENITTAVKT VWPQESTSNG
LITSTVTGIL GSLGLRKRSR RQVNTRATGK CNPNLHYWTA QEQHNAAGIA WIPYFGPGAE
GIYTEGLMHN QNALVCGLRQ LANETTQALQ LFLRATTELR TYTILNRKAI DFLLRRWGGT
CRILGPDCCI EPHDWTKNIT DKINQIIHDF IDNPLPNQDN DDNWWTGWRQ WIPAGIGITG
IIIAIIALLC VCKLLC
