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Q66814 (VGP_EBOSB) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 89. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Envelope glycoprotein
Alternative name(s):
GP1,2
Short name=GP

Cleaved into the following 3 chains:

  1. GP1
  2. GP2
  3. GP2-delta
Gene names
Name:GP
OrganismSudan ebolavirus (strain Boniface-76) (SEBOV) (Sudan Ebola virus)
Taxonomic identifier128948 [NCBI]
Taxonomic lineageVirusesssRNA negative-strand virusesMononegaviralesFiloviridaeEbolavirus
Virus hostEpomops franqueti (Franquet's epauleted fruit bat) [TaxID: 77231]
Homo sapiens (Human) [TaxID: 9606]
Myonycteris torquata (Little collared fruit bat) [TaxID: 77243]

Protein attributes

Sequence length676 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

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. Ref.3

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. Ref.3

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. Ref.3

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. Ref.3

Subunit structure

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. Ref.2

Subcellular location

GP2: Virion membrane; Single-pass type I membrane protein By similarity. Virion membrane; Lipid-anchor By similarity. Host cell membrane; Single-pass type I membrane protein By similarity. Host cell membrane; 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.

GP1: Virion membrane; Peripheral membrane protein By similarity. Host cell membrane; 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.

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.

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.

The coiled coil regions play a role in oligomerization and fusion activity By similarity.

Post-translational modification

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.

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.

Sequence similarities

Belongs to the filoviruses glycoprotein family.

RNA editing

Edited at position 295.
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). Ref.1

Ontologies

Keywords
   Biological processClathrin-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
   Cellular componentHost cell membrane
Host membrane
Membrane
Secreted
Viral envelope protein
Virion
   Coding sequence diversityRNA editing
   DomainCoiled coil
Signal
Transmembrane
Transmembrane helix
   PTMCleavage on pair of basic residues
Disulfide bond
Glycoprotein
Lipoprotein
Palmitate
   Technical term3D-structure
Gene Ontology (GO)
   Biological_processclathrin-mediated endocytosis of virus by host cell

Inferred from electronic annotation. Source: UniProtKB-KW

fusion of virus membrane with host endosome membrane

Inferred from electronic annotation. Source: UniProtKB-KW

suppression by virus of host tetherin activity

Inferred from electronic annotation. Source: UniProtKB-KW

suppression by virus of host type I interferon-mediated signaling pathway

Inferred from electronic annotation. Source: UniProtKB-KW

virion attachment to host cell

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componenthost cell plasma membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

viral envelope

Inferred from electronic annotation. Source: UniProtKB-KW

virion membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 3232 Potential
Chain33 – 676644Envelope glycoprotein
PRO_0000037476
Chain33 – 501469GP1 By similarity
PRO_0000037477
Chain502 – 676175GP2 By similarity
PRO_0000037478
Chain502 – 637136GP2-delta By similarity
PRO_0000245063

Regions

Topological domain33 – 650618Extracellular Potential
Transmembrane651 – 67121Helical; Potential
Topological domain672 – 6765Cytoplasmic Potential
Region54 – 201148Receptor-binding By similarity
Region305 – 485181Mucin-like region By similarity
Region524 – 53916Fusion peptide By similarity
Coiled coil554 – 59542 Potential
Coiled coil615 – 63420 Potential

Sites

Site571Involved in receptor recognition and/or post-binding events Potential
Site631Involved in receptor recognition and/or post-binding events Potential
Site881Involved in receptor recognition and/or post-binding events Potential
Site1701Involved in receptor recognition and/or post-binding events Potential
Site501 – 5022Cleavage; by host furin By similarity
Site637 – 6382Cleavage; by host ADAM17 By similarity

Amino acid modifications

Lipidation6701S-palmitoyl cysteine; by host By similarity
Lipidation6721S-palmitoyl cysteine; by host By similarity
Glycosylation401N-linked (GlcNAc...); by host Potential
Glycosylation2041N-linked (GlcNAc...); by host Potential
Glycosylation2081N-linked (GlcNAc...); by host Potential
Glycosylation2381N-linked (GlcNAc...); by host Potential
Glycosylation2571N-linked (GlcNAc...); by host Potential
Glycosylation2681N-linked (GlcNAc...); by host Potential
Glycosylation2961N-linked (GlcNAc...); by host Potential
Glycosylation3141N-linked (GlcNAc...); by host Potential
Glycosylation3661N-linked (GlcNAc...); by host Potential
Glycosylation4631N-linked (GlcNAc...); by host Potential
Glycosylation5631N-linked (GlcNAc...); by host Potential
Glycosylation6181N-linked (GlcNAc...); by host Potential
Disulfide bond53 ↔ 609Interchain (between GP1 and GP2 chains) By similarity
Disulfide bond108 ↔ 135 Potential
Disulfide bond121 ↔ 147 Potential
Disulfide bond511 ↔ 556 Potential
Disulfide bond601 ↔ 608 By similarity

Secondary structure

........................................................... 676
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q66814 [UniParc].

Last modified November 1, 1996. Version 1.
Checksum: 700029BFD67F5E9A

FASTA67674,987
        10         20         30         40         50         60 
MEGLSLLQLP RDKFRKSSFF VWVIILFQKA FSMPLGVVTN STLEVTEIDQ LVCKDHLAST 

        70         80         90        100        110        120 
DQLKSVGLNL EGSGVSTDIP SATKRWGFRS GVPPQVVSYE AGEWAENCYN LEIKKPDGSE 

       130        140        150        160        170        180 
CLPPPPDGVR GFPRCRYVHK AQGTGPCPGD YAFHKDGAFF LYDRLASTVI YRGVNFAEGV 

       190        200        210        220        230        240 
IAFLILAKPK ETFLQSPPIR EAANYTENTS SYYATSYLEY EIENFGAQHS TTLFKINNNT 

       250        260        270        280        290        300 
FVLLDRPHTP QFLFQLNDTI QLHQQLSNTT GKLIWTLDAN INADIGEWAF WENKKNLSEQ 

       310        320        330        340        350        360 
LRGEELSFET LSLNETEDDD ATSSRTTKGR ISDRATRKYS DLVPKDSPGM VSLHVPEGET 

       370        380        390        400        410        420 
TLPSQNSTEG RRVDVNTQET ITETTATIIG TNGNNMQIST IGTGLSSSQI LSSSPTMAPS 

       430        440        450        460        470        480 
PETQTSTTYT PKLPVMTTEE STTPPRNSPG STTEAPTLTT PENITTAVKT VWPQESTSNG 

       490        500        510        520        530        540 
LITSTVTGIL GSLGLRKRSR RQVNTRATGK CNPNLHYWTA QEQHNAAGIA WIPYFGPGAE 

       550        560        570        580        590        600 
GIYTEGLMHN QNALVCGLRQ LANETTQALQ LFLRATTELR TYTILNRKAI DFLLRRWGGT 

       610        620        630        640        650        660 
CRILGPDCCI EPHDWTKNIT DKINQIIHDF IDNPLPNQDN DDNWWTGWRQ WIPAGIGITG 

       670 
IIIAIIALLC VCKLLC 

« Hide

References

[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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U28134 Genomic RNA. Translation: AAB37096.1.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3VE0X-ray3.35I33-313[»]
J473-637[»]
ProteinModelPortalQ66814.
SMRQ66814. Positions 32-284, 507-632.
ModBaseSearch...
MobiDBSearch...

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Family and domain databases

InterProIPR014625. GPC_FiloV.
IPR002561. GPC_filovir-type_extra_dom.
[Graphical view]
PfamPF01611. Filo_glycop. 1 hit.
[Graphical view]
PIRSFPIRSF036874. GPC_FiloV. 1 hit.
ProtoNetSearch...

Entry information

Entry nameVGP_EBOSB
AccessionPrimary (citable) accession number: Q66814
Entry history
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: November 1, 1996
Last modified: July 9, 2014
This is version 89 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references