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Q66814

- VGP_EBOSB

UniProt

Q66814 - VGP_EBOSB

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Protein

Envelope glycoprotein

Gene

GP

Organism
Sudan ebolavirus (strain Boniface-76) (SEBOV) (Sudan Ebola virus)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

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).By similarity
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).By similarity
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).By similarity
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).By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei57 – 571Involved in receptor recognition and/or post-binding eventsSequence Analysis
Sitei63 – 631Involved in receptor recognition and/or post-binding eventsSequence Analysis
Sitei88 – 881Involved in receptor recognition and/or post-binding eventsSequence Analysis
Sitei170 – 1701Involved in receptor recognition and/or post-binding eventsSequence Analysis
Sitei501 – 5022Cleavage; by host furinBy similarity
Sitei637 – 6382Cleavage; by host ADAM17By similarity

GO - Biological processi

  1. clathrin-mediated endocytosis of virus by host cell Source: UniProtKB-KW
  2. fusion of virus membrane with host endosome membrane Source: UniProtKB-KW
  3. suppression by virus of host tetherin activity Source: UniProtKB-KW
  4. suppression by virus of host type I interferon-mediated signaling pathway Source: UniProtKB-KW
  5. virion attachment to host cell Source: UniProtKB-KW
Complete GO annotation...

Keywords - Biological processi

Clathrin-mediated endocytosis of virus by host, Fusion of virus membrane with host endosomal membrane, Fusion of virus membrane with 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, Viral attachment to host cell, Viral immunoevasion, Viral penetration into host cytoplasm, Virus endocytosis by host, Virus entry into host cell

Names & Taxonomyi

Protein namesi
Recommended name:
Envelope glycoprotein
Alternative name(s):
GP1,2
Short name:
GP
Cleaved into the following 3 chains:
Gene namesi
Name:GP
OrganismiSudan ebolavirus (strain Boniface-76) (SEBOV) (Sudan Ebola virus)
Taxonomic identifieri128948 [NCBI]
Taxonomic lineageiVirusesssRNA negative-strand virusesMononegaviralesFiloviridaeEbolavirus
Virus hostiEpomops franqueti (Franquet's epauleted fruit bat) [TaxID: 77231]
Homo sapiens (Human) [TaxID: 9606]
Myonycteris torquata (Little collared fruit bat) [TaxID: 77243]

Subcellular locationi

Chain GP2 : Virion membrane By similarity; Single-pass type I membrane protein By similarity. Virion membrane By similarity; Lipid-anchor By similarity. Host cell membrane By similarity; Single-pass type I membrane protein By similarity. Host cell membrane By similarity; Lipid-anchor By similarity
Note: In the cell, localizes to the plasma membrane lipid rafts, which probably represent the assembly and budding site.By similarity
Chain GP1 : Virion membrane By similarity; Peripheral membrane protein By similarity. Host cell membrane By similarity; Peripheral membrane protein By similarity
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).By similarity
Chain GP2-delta : Secreted By similarity
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.By similarity

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini33 – 650618ExtracellularSequence AnalysisAdd
BLAST
Transmembranei651 – 67121HelicalSequence AnalysisAdd
BLAST
Topological domaini672 – 6765CytoplasmicSequence Analysis

GO - Cellular componenti

  1. host cell plasma membrane Source: UniProtKB-KW
  2. integral component of membrane Source: UniProtKB-KW
  3. viral envelope Source: UniProtKB-KW
Complete GO annotation...

Keywords - Cellular componenti

Host cell membrane, Host membrane, Membrane, Secreted, Viral envelope protein, Virion

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 3232Sequence AnalysisAdd
BLAST
Chaini33 – 676644Envelope glycoproteinPRO_0000037476Add
BLAST
Chaini33 – 501469GP1By similarityPRO_0000037477Add
BLAST
Chaini502 – 676175GP2By similarityPRO_0000037478Add
BLAST
Chaini502 – 637136GP2-deltaBy similarityPRO_0000245063Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi40 – 401N-linked (GlcNAc...); by hostSequence Analysis
Disulfide bondi53 ↔ 609Interchain (between GP1 and GP2 chains)By similarity
Disulfide bondi108 ↔ 135Sequence Analysis
Disulfide bondi121 ↔ 147Sequence Analysis
Glycosylationi204 – 2041N-linked (GlcNAc...); by hostSequence Analysis
Glycosylationi208 – 2081N-linked (GlcNAc...); by hostSequence Analysis
Glycosylationi238 – 2381N-linked (GlcNAc...); by hostSequence Analysis
Glycosylationi257 – 2571N-linked (GlcNAc...); by hostSequence Analysis
Glycosylationi268 – 2681N-linked (GlcNAc...); by hostSequence Analysis
Glycosylationi296 – 2961N-linked (GlcNAc...); by hostSequence Analysis
Glycosylationi314 – 3141N-linked (GlcNAc...); by hostSequence Analysis
Glycosylationi366 – 3661N-linked (GlcNAc...); by hostSequence Analysis
Glycosylationi463 – 4631N-linked (GlcNAc...); by hostSequence Analysis
Disulfide bondi511 ↔ 556Sequence Analysis
Glycosylationi563 – 5631N-linked (GlcNAc...); by hostSequence Analysis
Disulfide bondi601 ↔ 608By similarity
Glycosylationi618 – 6181N-linked (GlcNAc...); by hostSequence Analysis
Lipidationi670 – 6701S-palmitoyl cysteine; by hostBy similarity
Lipidationi672 – 6721S-palmitoyl cysteine; by hostBy similarity

Post-translational modificationi

The signal peptide region modulates GP's high mannose glycosylation, thereby determining the efficiency of the interactions with DC-SIGN(R).
N-glycosylated.By similarity
O-glycosylated in the mucin-like region.By similarity
Palmitoylation of GP2 is not required for its function.By similarity
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).By similarity

Keywords - PTMi

Cleavage on pair of basic residues, Disulfide bond, Glycoprotein, Lipoprotein, Palmitate

Interactioni

Subunit structurei

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).By similarity

Structurei

Secondary structure

1
676
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi34 – 396Combined sources
Beta strandi45 – 495Combined sources
Helixi60 – 623Combined sources
Beta strandi63 – 708Combined sources
Helixi71 – 733Combined sources
Helixi79 – 835Combined sources
Beta strandi86 – 916Combined sources
Beta strandi96 – 983Combined sources
Beta strandi100 – 1034Combined sources
Beta strandi105 – 11410Combined sources
Beta strandi120 – 1223Combined sources
Beta strandi135 – 1439Combined sources
Beta strandi149 – 1546Combined sources
Beta strandi159 – 1613Combined sources
Beta strandi163 – 1697Combined sources
Beta strandi176 – 18914Combined sources
Beta strandi216 – 2216Combined sources
Beta strandi223 – 2264Combined sources
Beta strandi236 – 2394Combined sources
Helixi250 – 2545Combined sources
Turni259 – 2624Combined sources
Beta strandi515 – 5206Combined sources
Beta strandi524 – 5263Combined sources
Beta strandi528 – 5325Combined sources
Turni533 – 5353Combined sources
Turni539 – 5424Combined sources
Beta strandi543 – 5486Combined sources
Helixi552 – 57524Combined sources
Beta strandi579 – 5813Combined sources
Helixi584 – 59411Combined sources
Beta strandi606 – 6083Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3VE0X-ray3.35I33-313[»]
J473-637[»]
ProteinModelPortaliQ66814.
SMRiQ66814. Positions 32-284, 507-632.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni54 – 201148Receptor-bindingBy similarityAdd
BLAST
Regioni305 – 485181Mucin-like regionBy similarityAdd
BLAST
Regioni524 – 53916Fusion peptideBy similarityAdd
BLAST

Coiled coil

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Coiled coili554 – 59542Sequence AnalysisAdd
BLAST
Coiled coili615 – 63420Sequence AnalysisAdd
BLAST

Domaini

The mucin-like region seems to be involved in the cytotoxic function. This region is also involved in binding to human CLEC10A (By similarity).By similarity
The coiled coil regions play a role in oligomerization and fusion activity.By similarity

Sequence similaritiesi

Belongs to the filoviruses glycoprotein family.Curated

Keywords - Domaini

Coiled coil, Signal, Transmembrane, Transmembrane helix

Family and domain databases

InterProiIPR014625. GPC_FiloV.
IPR002561. GPC_filovir-type_extra_dom.
[Graphical view]
PfamiPF01611. Filo_glycop. 1 hit.
[Graphical view]
PIRSFiPIRSF036874. GPC_FiloV. 1 hit.

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q66814-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MEGLSLLQLP RDKFRKSSFF VWVIILFQKA FSMPLGVVTN STLEVTEIDQ
60 70 80 90 100
LVCKDHLAST DQLKSVGLNL EGSGVSTDIP SATKRWGFRS GVPPQVVSYE
110 120 130 140 150
AGEWAENCYN LEIKKPDGSE CLPPPPDGVR GFPRCRYVHK AQGTGPCPGD
160 170 180 190 200
YAFHKDGAFF LYDRLASTVI YRGVNFAEGV IAFLILAKPK ETFLQSPPIR
210 220 230 240 250
EAANYTENTS SYYATSYLEY EIENFGAQHS TTLFKINNNT FVLLDRPHTP
260 270 280 290 300
QFLFQLNDTI QLHQQLSNTT GKLIWTLDAN INADIGEWAF WENKKNLSEQ
310 320 330 340 350
LRGEELSFET LSLNETEDDD ATSSRTTKGR ISDRATRKYS DLVPKDSPGM
360 370 380 390 400
VSLHVPEGET TLPSQNSTEG RRVDVNTQET ITETTATIIG TNGNNMQIST
410 420 430 440 450
IGTGLSSSQI LSSSPTMAPS PETQTSTTYT PKLPVMTTEE STTPPRNSPG
460 470 480 490 500
STTEAPTLTT PENITTAVKT VWPQESTSNG LITSTVTGIL GSLGLRKRSR
510 520 530 540 550
RQVNTRATGK CNPNLHYWTA QEQHNAAGIA WIPYFGPGAE GIYTEGLMHN
560 570 580 590 600
QNALVCGLRQ LANETTQALQ LFLRATTELR TYTILNRKAI DFLLRRWGGT
610 620 630 640 650
CRILGPDCCI EPHDWTKNIT DKINQIIHDF IDNPLPNQDN DDNWWTGWRQ
660 670
WIPAGIGITG IIIAIIALLC VCKLLC
Length:676
Mass (Da):74,987
Last modified:November 1, 1996 - v1
Checksum:i700029BFD67F5E9A
GO

RNA editingi

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 P60172).

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U28134 Genomic RNA. Translation: AAB37096.1.

Keywords - Coding sequence diversityi

RNA editing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U28134 Genomic RNA. Translation: AAB37096.1 .

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
3VE0 X-ray 3.35 I 33-313 [» ]
J 473-637 [» ]
ProteinModelPortali Q66814.
SMRi Q66814. Positions 32-284, 507-632.
ModBasei Search...
MobiDBi Search...

Protocols and materials databases

Structural Biology Knowledgebase Search...

Family and domain databases

InterProi IPR014625. GPC_FiloV.
IPR002561. GPC_filovir-type_extra_dom.
[Graphical view ]
Pfami PF01611. Filo_glycop. 1 hit.
[Graphical view ]
PIRSFi PIRSF036874. GPC_FiloV. 1 hit.
ProtoNeti Search...

Publicationsi

  1. "The virion glycoproteins of Ebola viruses are encoded in two reading frames and are expressed through transcriptional editing."
    Sanchez A., Trappier S.G., Mahy B.W.J., Peters C.J., Nichol S.T.
    Proc. Natl. Acad. Sci. U.S.A. 93:3602-3607(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA], RNA EDITING.
  2. "Human macrophage C-type lectin specific for galactose and N-acetylgalactosamine promotes filovirus entry."
    Takada A., Fujioka K., Tsuiji M., Morikawa A., Higashi N., Ebihara H., Kobasa D., Feldmann H., Irimura T., Kawaoka Y.
    J. Virol. 78:2943-2947(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH HUMAN CLEC10A.
  3. "The signal peptide of the ebolavirus glycoprotein influences interaction with the cellular lectins DC-SIGN and DC-SIGNR."
    Marzi A., Akhavan A., Simmons G., Gramberg T., Hofmann H., Bates P., Lingappa V.R., Poehlmann S.
    J. Virol. 80:6305-6317(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION OF SIGNAL PEPTIDE.

Entry informationi

Entry nameiVGP_EBOSB
AccessioniPrimary (citable) accession number: Q66814
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: November 1, 1996
Last modified: November 26, 2014
This is version 92 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Miscellaneousi

Miscellaneous

Filoviruses entry requires functional lipid rafts at the host cell surface.By similarity
Essential for infectivity, as it is the sole viral protein expressed at the virion surface.

Keywords - Technical termi

3D-structure

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3