Q7T9D9 (VGP_EBOSU) Reviewed, UniProtKB/Swiss-Prot
Last modified February 19, 2014. Version 58. History...
Names and origin
|Protein names||Recommended name:|
|Organism||Sudan ebolavirus (strain Uganda-00) (SEBOV) (Sudan Ebola virus) [Complete proteome]|
|Taxonomic identifier||386033 [NCBI]|
|Taxonomic lineage||Viruses › ssRNA negative-strand viruses › Mononegavirales › Filoviridae › Ebolavirus ›|
|Virus host||Epomops franqueti (Franquet's epauleted fruit bat) [TaxID: 77231]|
Homo sapiens (Human) [TaxID: 9606]
Myonycteris torquata (Little collared fruit bat) [TaxID: 77243]
|Sequence length||676 AA.|
|Sequence processing||The displayed sequence is further processed into a mature form.|
|Protein existence||Evidence at protein level|
General annotation (Comments)
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. 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.
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.
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.
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.
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.
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.
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.
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.
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.
Belongs to the filoviruses glycoprotein family.
Edited at position 295.
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Signal peptide||1 – 32||32||Potential|
|Chain||33 – 676||644||Envelope glycoprotein By similarity||PRO_0000316901|
|Chain||33 – 501||469||GP1 By similarity||PRO_0000316902|
|Chain||502 – 676||175||GP2 By similarity||PRO_0000316903|
|Chain||502 – 637||136||GP2-delta By similarity||PRO_0000316904|
|Topological domain||33 – 650||618||Extracellular Potential|
|Transmembrane||651 – 671||21||Helical; Potential|
|Topological domain||672 – 676||5||Cytoplasmic Potential|
|Region||33 – 185||153||Receptor binding Potential|
|Region||305 – 485||181||Mucin-like region By similarity|
|Region||524 – 539||16||Fusion peptide By similarity|
|Coiled coil||554 – 595||42||Potential|
|Coiled coil||615 – 634||20||Potential|
|Site||57||1||Involved in receptor recognition and/or post-binding events Potential|
|Site||63||1||Involved in receptor recognition and/or post-binding events Potential|
|Site||88||1||Involved in receptor recognition and/or post-binding events Potential|
|Site||95||1||Involved in receptor recognition and/or post-binding events Potential|
|Site||170||1||Involved in receptor recognition and/or post-binding events Potential|
|Site||501 – 502||2||Cleavage; by host furin By similarity|
|Site||637 – 638||2||Cleavage; by host ADAM17 By similarity|
Amino acid modifications
|Lipidation||670||1||S-palmitoyl cysteine; by host By similarity|
|Lipidation||672||1||S-palmitoyl cysteine; by host By similarity|
|Glycosylation||40||1||N-linked (GlcNAc...); by host Potential|
|Glycosylation||204||1||N-linked (GlcNAc...); by host Potential|
|Glycosylation||208||1||N-linked (GlcNAc...); by host Potential|
|Glycosylation||238||1||N-linked (GlcNAc...); by host Potential|
|Glycosylation||257||1||N-linked (GlcNAc...); by host Potential|
|Glycosylation||268||1||N-linked (GlcNAc...); by host Potential|
|Glycosylation||296||1||N-linked (GlcNAc...); by host Potential|
|Glycosylation||314||1||N-linked (GlcNAc...); by host Potential|
|Glycosylation||366||1||N-linked (GlcNAc...); by host Potential|
|Glycosylation||463||1||N-linked (GlcNAc...); by host Potential|
|Glycosylation||563||1||N-linked (GlcNAc...); by host Potential|
|Glycosylation||618||1||N-linked (GlcNAc...); by host Potential|
|Disulfide bond||53 ↔ 609||Interchain (between GP1 and GP2 chains) By similarity|
|Disulfide bond||108 ↔ 135||Potential|
|Disulfide bond||121 ↔ 147||Potential|
|Disulfide bond||511 ↔ 556||Potential|
|Disulfide bond||601 ↔ 608||By similarity|
Helix Strand Turn
|Beta strand||35 – 39||5|
|Beta strand||42 – 47||6|
|Helix||60 – 62||3|
|Beta strand||63 – 70||8|
|Helix||71 – 73||3|
|Helix||79 – 82||4|
|Turn||83 – 85||3|
|Beta strand||86 – 91||6|
|Beta strand||96 – 98||3|
|Beta strand||100 – 103||4|
|Beta strand||105 – 111||7|
|Beta strand||120 – 122||3|
|Beta strand||135 – 141||7|
|Beta strand||149 – 154||6|
|Beta strand||159 – 161||3|
|Beta strand||163 – 169||7|
|Beta strand||176 – 186||11|
|Beta strand||216 – 219||4|
|Beta strand||225 – 229||5|
|Beta strand||233 – 237||5|
|Beta strand||240 – 243||4|
|Helix||250 – 262||13|
|Beta strand||515 – 519||5|
|Turn||533 – 535||3|
|Helix||539 – 541||3|
|Beta strand||544 – 548||5|
|Helix||552 – 575||24|
|Beta strand||579 – 581||3|
|Helix||584 – 597||14|
|||"Analysis of human peripheral blood samples from fatal and nonfatal cases of Ebola (Sudan) hemorrhagic fever: cellular responses, virus load, and nitric oxide levels."|
Sanchez A., Lukwiya M., Bausch D., Mahanty S., Sanchez A.J., Wagoner K.D., Rollin P.E.
J. Virol. 78:10370-10377(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
|||"Rapid diagnosis of Ebola hemorrhagic fever by reverse transcription-PCR in an outbreak setting and assessment of patient viral load as a predictor of outcome."|
Towner J.S., Rollin P.E., Bausch D.G., Sanchez A., Crary S.M., Vincent M., Lee W.F., Spiropoulou C.F., Ksiazek T.G., Lukwiya M., Kaducu F., Downing R., Nichol S.T.
J. Virol. 78:4330-4341(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
|||"Complete genome sequence of an Ebola virus (Sudan species) responsible for a 2000 outbreak of human disease in Uganda."|
Sanchez A., Rollin P.E.
Virus Res. 113:16-25(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
|+||Additional computationally mapped references.|
|AY316199 Genomic RNA. Translation: AAP88031.1.|
AY344234 Genomic RNA. Translation: AAR11463.1.
AY729654 Genomic RNA. Translation: AAU43887.1.
|RefSeq||YP_138523.1. NC_006432.1. |
3D structure databases
|SMR||Q7T9D9. Positions 32-284, 507-632. |
Protein-protein interaction databases
Protocols and materials databases
Genome annotation databases
Family and domain databases
|InterPro||IPR014625. GPC_FiloV. |
|Pfam||PF01611. Filo_glycop. 1 hit. |
|PIRSF||PIRSF036874. GPC_FiloV. 1 hit. |
|Accession||Primary (citable) accession number: Q7T9D9|
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Viral Protein Annotation Program|