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Q66810

- VGP_EBOIC

UniProt

Q66810 - VGP_EBOIC

Protein

Envelope glycoprotein

Gene

GP

Organism
Ivory Coast ebolavirus (strain Cote d'Ivoire-94) (CIEBOV) (Cote d'Ivoire Ebola virus)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 88 (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. 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
    Sitei95 – 951Involved 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

    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
    OrganismiIvory Coast ebolavirus (strain Cote d'Ivoire-94) (CIEBOV) (Cote d'Ivoire Ebola virus)
    Taxonomic identifieri128999 [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

    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 – 3232Sequence AnalysisAdd
    BLAST
    Chaini33 – 676644Envelope glycoproteinPRO_0000037467Add
    BLAST
    Chaini33 – 501469GP1By similarityPRO_0000037468Add
    BLAST
    Chaini502 – 676175GP2By similarityPRO_0000037469Add
    BLAST
    Chaini502 – 637136GP2-deltaBy similarityPRO_0000245056Add
    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
    Glycosylationi228 – 2281N-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
    Glycosylationi414 – 4141N-linked (GlcNAc...); by hostSequence Analysis
    Glycosylationi441 – 4411N-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).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

    ProteinModelPortaliQ66810.
    SMRiQ66810. Positions 32-308, 506-632.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

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

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei651 – 67121HelicalSequence AnalysisAdd
    BLAST

    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.

    Q66810-1 [UniParc]FASTAAdd to Basket

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    MGASGILQLP RERFRKTSFF VWVIILFHKV FSIPLGVVHN NTLQVSDIDK    50
    FVCRDKLSST SQLKSVGLNL EGNGVATDVP TATKRWGFRA GVPPKVVNYE 100
    AGEWAENCYN LAIKKVDGSE CLPEAPEGVR DFPRCRYVHK VSGTGPCPGG 150
    LAFHKEGAFF LYDRLASTII YRGTTFAEGV IAFLILPKAR KDFFQSPPLH 200
    EPANMTTDPS SYYHTTTINY VVDNFGTNTT EFLFQVDHLT YVQLEARFTP 250
    QFLVLLNETI YSDNRRSNTT GKLIWKINPT VDTSMGEWAF WENKKNFTKT 300
    LSSEELSFVP VPETQNQVLD TTATVSPPIS AHNHAGEDHK ELVSEDSTPV 350
    VQMQNIKGKD TMPTTVTGVP TTTPSPFPIN ARNTDHTKSF IGLEGPQEDH 400
    STTQPAKTTS QPTNSTESTT LNPTSEPSSR GTGPSSPTVP NTTESHAELG 450
    KTTPTTLPEQ HTAASAIPRA VHPDELSGPG FLTNTIRGVT NLLTGSRRKR 500
    RDVTPNTQPK CNPNLHYWTA LDEGAAIGLA WIPYFGPAAE GIYTEGIMEN 550
    QNGLICGLRQ LANETTQALQ LFLRATTELR TFSILNRKAI DFLLQRWGGT 600
    CHILGPDCCI EPQDWTKNIT DKIDQIIHDF VDNNLPNQND GSNWWTGWKQ 650
    WVPAGIGITG VIIAIIALLC ICKFML 676
    Length:676
    Mass (Da):74,722
    Last modified:November 1, 1996 - v1
    Checksum:i9C753510BFADB48D
    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 Q66811).

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U28006 Genomic RNA. Translation: AAB37093.1.

    Keywords - Coding sequence diversityi

    RNA editing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U28006 Genomic RNA. Translation: AAB37093.1 .

    3D structure databases

    ProteinModelPortali Q66810.
    SMRi Q66810. Positions 32-308, 506-632.
    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.

    Entry informationi

    Entry nameiVGP_EBOIC
    AccessioniPrimary (citable) accession number: Q66810
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: May 30, 2000
    Last sequence update: November 1, 1996
    Last modified: October 1, 2014
    This is version 88 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.

    Documents

    1. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3