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Q66799

- VGP_EBORR

UniProt

Q66799 - VGP_EBORR

Protein

Envelope glycoprotein

Gene

GP

Organism
Reston ebolavirus (strain Reston-89) (REBOV) (Reston Ebola virus)
Status
Reviewed - Annotation score: 5 out of 5- Protein inferred from homologyi
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    • History
      Entry version 92 (01 Oct 2014)
      Sequence version 1 (01 Nov 1996)
      Previous versions | rss
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    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, also this effect is much less pronounced in Reston than in Zaire, Sudan or Cote d'Ivoire strains. 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. This phenomenon is however much less pronounced in Reston than in Zaire, Sudan or Cote d'Ivoire strains. Down-modulates integrins ITGA1, 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
    Sitei58 – 581Involved in receptor recognition and/or post-binding eventsSequence Analysis
    Sitei64 – 641Involved in receptor recognition and/or post-binding eventsSequence Analysis
    Sitei89 – 891Involved in receptor recognition and/or post-binding eventsSequence Analysis
    Sitei96 – 961Involved in receptor recognition and/or post-binding eventsSequence Analysis
    Sitei171 – 1711Involved in receptor recognition and/or post-binding eventsSequence Analysis
    Sitei502 – 5032Cleavage; by host furinBy similarity
    Sitei638 – 6392Cleavage; 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

    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
    OrganismiReston ebolavirus (strain Reston-89) (REBOV) (Reston Ebola virus)
    Taxonomic identifieri386032 [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]
    Sus scrofa (Pig) [TaxID: 9823]
    ProteomesiUP000007207: Genome

    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

    GO - Cellular componenti

    1. host cell plasma membrane Source: UniProtKB-SubCell
    2. integral component of membrane Source: UniProtKB-KW
    3. viral envelope Source: UniProtKB-KW
    4. virion membrane Source: UniProtKB-SubCell

    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 – 3333Sequence AnalysisAdd
    BLAST
    Chaini34 – 677644Envelope glycoproteinPRO_0000037470Add
    BLAST
    Chaini34 – 502469GP1By similarityPRO_0000037471Add
    BLAST
    Chaini503 – 677175GP2By similarityPRO_0000037472Add
    BLAST
    Chaini503 – 638136GP2-deltaBy similarityPRO_0000245061Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi41 – 411N-linked (GlcNAc...); by hostSequence Analysis
    Disulfide bondi54 ↔ 610Interchain (between GP1 and GP2 chains)By similarity
    Disulfide bondi109 ↔ 136Sequence Analysis
    Disulfide bondi122 ↔ 148Sequence Analysis
    Glycosylationi205 – 2051N-linked (GlcNAc...); by hostSequence Analysis
    Glycosylationi229 – 2291N-linked (GlcNAc...); by hostSequence Analysis
    Glycosylationi239 – 2391N-linked (GlcNAc...); by hostSequence Analysis
    Glycosylationi258 – 2581N-linked (GlcNAc...); by hostSequence Analysis
    Glycosylationi269 – 2691N-linked (GlcNAc...); by hostSequence Analysis
    Glycosylationi297 – 2971N-linked (GlcNAc...); by hostSequence Analysis
    Glycosylationi317 – 3171N-linked (GlcNAc...); by hostSequence Analysis
    Glycosylationi318 – 3181N-linked (GlcNAc...); by hostSequence Analysis
    Glycosylationi339 – 3391N-linked (GlcNAc...); by hostSequence Analysis
    Glycosylationi406 – 4061N-linked (GlcNAc...); by hostSequence Analysis
    Glycosylationi420 – 4201N-linked (GlcNAc...); by hostSequence Analysis
    Glycosylationi435 – 4351N-linked (GlcNAc...); by hostSequence Analysis
    Glycosylationi463 – 4631N-linked (GlcNAc...); by hostSequence Analysis
    Disulfide bondi512 ↔ 557Sequence Analysis
    Glycosylationi564 – 5641N-linked (GlcNAc...); by hostSequence Analysis
    Disulfide bondi602 ↔ 609By similarity
    Glycosylationi619 – 6191N-linked (GlcNAc...); by hostSequence Analysis
    Lipidationi671 – 6711S-palmitoyl cysteine; by hostBy similarity
    Lipidationi673 – 6731S-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).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.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

    3D structure databases

    ProteinModelPortaliQ66799.
    SMRiQ66799. Positions 33-285, 507-633.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini34 – 651618ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini673 – 6775CytoplasmicSequence Analysis

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei652 – 67221HelicalSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni55 – 202148Receptor-bindingBy similarityAdd
    BLAST
    Regioni306 – 486181Mucin-like regionBy similarityAdd
    BLAST
    Regioni525 – 54016Fusion peptideBy similarityAdd
    BLAST

    Coiled coil

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Coiled coili555 – 59642Sequence AnalysisAdd
    BLAST
    Coiled coili616 – 63520Sequence 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.

    Q66799-1 [UniParc]FASTAAdd to Basket

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    MGSGYQLLQL PRERFRKTSF LVWVIILFQR AISMPLGIVT NSTLKATEID    50
    QLVCRDKLSS TSQLKSVGLN LEGNGIATDV PSATKRWGFR SGVPPKVVSY 100
    EAGEWAENCY NLEIKKSDGS ECLPLPPDGV RGFPRCRYVH KVQGTGPCPG 150
    DLAFHKNGAF FLYDRLASTV IYRGTTFAEG VVAFLILSEP KKHFWKATPA 200
    HEPVNTTDDS TSYYMTLTLS YEMSNFGGNE SNTLFKVDNH TYVQLDRPHT 250
    PQFLVQLNET LRRNNRLSNS TGRLTWTLDP KIEPDVGEWA FWETKKNFSQ 300
    QLHGENLHFQ ILSTHTNNSS DQSPAGTVQG KISYHPPANN SELVPTDSPP 350
    VVSVLTAGRT EEMSTQGLTN GETITGFTAN PMTTTIAPSP TMTSEVDNNV 400
    PSEQPNNTAS IEDSPPSASN ETIYHSEMDP IQGSNNSAQS PQTKTTPAPT 450
    TSPMTQDPQE TANSSKPGTS PGSAAGPSQP GLTINTVSKV ADSLSPTRKQ 500
    KRSVRQNTAN KCNPDLYYWT AVDEGAAVGL AWIPYFGPAA EGIYIEGVMH 550
    NQNGLICGLR QLANETTQAL QLFLRATTEL RTYSLLNRKA IDFLLQRWGG 600
    TCRILGPSCC IEPHDWTKNI TDEINQIKHD FIDNPLPDHG DDLNLWTGWR 650
    QWIPAGIGII GVIIAIIALL CICKILC 677
    Length:677
    Mass (Da):74,433
    Last modified:November 1, 1996 - v1
    Checksum:i3D22C37CF856F8BA
    GO

    RNA editingi

    Partially edited. RNA editing at this position consists of an insertion of one or two adenine nucleotides. The sequence displayed here is the full-length transmembrane glycoprotein GP, derived from the +1A edited RNA. The unedited RNA gives rise to the small secreted glycoprotein sGP (AC Q66800), the +2A edited RNA gives rise to the super small secreted glycoprotein ssGP (AC P0C771).

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti312 – 3121L → P.

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U23152 Genomic RNA. Translation: AAC54885.1.
    AF034645 Genomic RNA. Translation: AAC24346.1.
    AF522874 Genomic RNA. Translation: AAN04455.1.
    AY769362 Genomic RNA. Translation: AAV48577.1.
    RefSeqiNP_690583.1. NC_004161.1.

    Genome annotation databases

    GeneIDi955190.

    Keywords - Coding sequence diversityi

    RNA editing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U23152 Genomic RNA. Translation: AAC54885.1 .
    AF034645 Genomic RNA. Translation: AAC24346.1 .
    AF522874 Genomic RNA. Translation: AAN04455.1 .
    AY769362 Genomic RNA. Translation: AAV48577.1 .
    RefSeqi NP_690583.1. NC_004161.1.

    3D structure databases

    ProteinModelPortali Q66799.
    SMRi Q66799. Positions 33-285, 507-633.
    ModBasei Search...
    MobiDBi Search...

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    GeneIDi 955190.

    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. Volchkov V.E.
      Submitted (NOV-1997) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
    3. "Molecular characterization of an isolate from the 1989/90 epizootic of Ebola virus Reston among macaques imported into the United States."
      Groseth A., Stroeher U., Theriault S., Feldmann H.
      Virus Res. 87:155-163(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
    4. "A reconstituted replication and transcription system for Ebola virus Reston and comparison with Ebola virus Zaire."
      Boehmann Y., Enterlein S., Randolf A., Muehlberger E.I.
      Virology 332:406-417(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
      Strain: Isolate Pennsylvania-89.
    5. "Ebola virus glycoproteins induce global surface protein down-modulation and loss of cell adherence."
      Simmons G., Wool-Lewis R.J., Baribaud F., Netter R.C., Bates P.
      J. Virol. 76:2518-2528(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: DOWN-MODULATION OF HOST MHC-I; ALPHA/BETA INTEGRINS AND EGFR.

    Entry informationi

    Entry nameiVGP_EBORR
    AccessioniPrimary (citable) accession number: Q66799
    Secondary accession number(s): Q5UAK8, Q8JPX8
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: May 30, 2000
    Last sequence update: November 1, 1996
    Last modified: October 1, 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

    Complete proteome

    Documents

    1. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3