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Q05320

- VGP_EBOZM

UniProt

Q05320 - VGP_EBOZM

Protein

Envelope glycoprotein

Gene

GP

Organism
Zaire ebolavirus (strain Mayinga-76) (ZEBOV) (Zaire Ebola virus)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 105 (01 Oct 2014)
      Sequence version 1 (01 Feb 1994)
      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 seem 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.
    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.
    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.
    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.

    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
    Sitei64 – 641Involved 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 furin
    Sitei637 – 6382Cleavage; by host ADAM17

    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. viral budding from plasma membrane Source: CACAO
    6. viral entry into host cell Source: CACAO
    7. 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

    Protein family/group databases

    TCDBi1.G.12.2.2. the avian leukosis virus gp95 fusion protein (alv-gp95) family.

    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
    OrganismiZaire ebolavirus (strain Mayinga-76) (ZEBOV) (Zaire Ebola virus)
    Taxonomic identifieri128952 [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]
    ProteomesiUP000007209: Genome

    Subcellular locationi

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

    GO - Cellular componenti

    1. cytoplasm Source: CACAO
    2. host cell endoplasmic reticulum Source: CACAO
    3. host cell plasma membrane Source: UniProtKB-SubCell
    4. integral component of membrane Source: UniProtKB-KW
    5. membrane raft Source: CACAO
    6. viral envelope Source: UniProtKB-KW
    7. virion membrane Source: UniProtKB-SubCell

    Keywords - Cellular componenti

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

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi40 – 401N → D: Induces GP1 secretion. Complete loss of virus capability to enter into host cell. 2 Publications
    Mutagenesisi53 – 531C → G: Induces GP1 secretion. Complete loss of virus capability to enter into host cell. 2 Publications
    Mutagenesisi55 – 551D → A: 80% loss of virus capability to enter into host cell. 1 Publication
    Mutagenesisi55 – 551D → E or K: No effect on viral entry. 1 Publication
    Mutagenesisi57 – 571L → A: Complete loss of virus capability to enter into host cell. 1 Publication
    Mutagenesisi57 – 571L → F, I or K: 90% loss of virus capability to enter into host cell. 1 Publication
    Mutagenesisi63 – 631L → A: 90% loss of virus capability to enter into host cell. 1 Publication
    Mutagenesisi63 – 631L → F: Almost complete loss of virus capability to enter into host cell. 1 Publication
    Mutagenesisi63 – 631L → K: Complete loss of virus capability to enter into host cell. 1 Publication
    Mutagenesisi64 – 641R → A or E: Complete loss of virus capability to enter into host cell. 1 Publication
    Mutagenesisi64 – 641R → K: No loss of virus capability to enter into host cell. 1 Publication
    Mutagenesisi88 – 881F → A or E: Complete loss of virus capability to enter into host cell. 1 Publication
    Mutagenesisi88 – 881F → I: No loss of virus capability to enter into host cell. 1 Publication
    Mutagenesisi95 – 951K → A or E: 80% loss of virus capability to enter into host cell. 1 Publication
    Mutagenesisi95 – 951K → R: 20% loss of virus capability to enter into host cell. 1 Publication
    Mutagenesisi108 – 1081C → G: Almost complete loss of expression of GP1 and GP2. Almost complete loss of virus capability to enter into host cell. 2 Publications
    Mutagenesisi121 – 1211C → G: Reduced levels of expression of GP1 and GP2. 50% loss of virus capability to enter into host cell. 2 Publications
    Mutagenesisi135 – 1351C → S: Almost complete loss of expression of GP1 and GP2. Complete loss of virus capability to enter into host cell. 2 Publications
    Mutagenesisi147 – 1471C → S: Reduced levels of expression of GP1 and GP2. Almost complete loss of virus capability to enter into host cell. 2 Publications
    Mutagenesisi170 – 1701I → A: 90% loss of virus capability to enter into host cell. 1 Publication
    Mutagenesisi170 – 1701I → E: Complete loss of virus capability to enter into host cell. 1 Publication
    Mutagenesisi170 – 1701I → F: 50% loss of virus capability to enter into host cell. 1 Publication
    Mutagenesisi204 – 2041N → D: No effect on GP1 and GP2 expression. No loss of virus capability to enter into host cell. 2 Publications
    Mutagenesisi238 – 2381N → Y: No effect on GP1 and GP2 expression. 12% loss of virus capability to enter into host cell. 2 Publications
    Mutagenesisi257 – 2571N → D: No effect on GP1 and GP2 expression. 12% loss of virus capability to enter into host cell. 2 Publications
    Mutagenesisi296 – 2961N → D: No effect on GP1 and GP2 expression. 18% loss of virus capability to enter into host cell. 2 Publications
    Mutagenesisi497 – 5015RRTRR → AGTAA: Almost complete loss of cleavage between GP1 and GP2. No loss of infectivity. 1 Publication
    Mutagenesisi498 – 5014RTRR → ATAA: No effect on cleavage between GP1 and GP2. 1 Publication
    Mutagenesisi511 – 5111C → G: Induces GP1 secretion. Complete loss of virus capability to enter into host cell. 2 Publications
    Mutagenesisi528 – 5281G → R: Reduced infectivity. 2 Publications
    Mutagenesisi529 – 5291L → A or R: Reduced infectivity. 2 Publications
    Mutagenesisi532 – 5321I → A: Reduced infectivity. 2 Publications
    Mutagenesisi532 – 5321I → R: Almost complete loss of infectivity. No effect on transport of GP to the cell surface and incorporation onto virions. 2 Publications
    Mutagenesisi535 – 5351F → A: Reduced infectivity. 2 Publications
    Mutagenesisi535 – 5351F → R: Almost complete loss of infectivity. No effect on transport of GP to the cell surface and incorporation onto virions. 2 Publications
    Mutagenesisi536 – 5361G → A: Almost complete loss of infectivity. No effect on transport of GP to the cell surface and incorporation onto virions. 2 Publications
    Mutagenesisi537 – 5371P → R: Almost complete loss of infectivity. No effect on transport of GP to the cell surface and incorporation onto virions. 2 Publications
    Mutagenesisi556 – 5561C → S: Induces GP1 secretion. Complete loss of virus capability to enter into host cell. 2 Publications
    Mutagenesisi563 – 5631N → D: Reduced levels of expression of GP, GP1 and GP2. 20% loss of virus capability to enter into host cell. 2 Publications
    Mutagenesisi601 – 6011C → S: Induces GP1 secretion. Complete loss of virus capability to enter into host cell. 2 Publications
    Mutagenesisi608 – 6081C → G: Induces GP1 secretion. Complete loss of virus capability to enter into host cell. 2 Publications
    Mutagenesisi609 – 6091C → G: Induces GP1 secretion. Complete loss of virus capability to enter into host cell. 2 Publications
    Mutagenesisi618 – 6181N → D: Slightly reduced levels of expression of GP1 and GP2. No loss of virus capability to enter into host cell. 2 Publications
    Mutagenesisi632 – 6321D → V: No effect on release of soluble GP1,2delta. 2 Publications
    Mutagenesisi633 – 6331K → R or V: No effect on release of soluble GP1,2delta. 2 Publications
    Mutagenesisi634 – 6341T → I: 50% loss of release of soluble GP1,2delta. 2 Publications
    Mutagenesisi635 – 6351L → V: 60% loss of release of soluble GP1,2delta. 2 Publications
    Mutagenesisi636 – 6361P → A: 60% loss of release of soluble GP1,2delta. 1 Publication
    Mutagenesisi637 – 6371D → E: No effect on release of soluble GP1,2delta. 2 Publications
    Mutagenesisi637 – 6371D → L or V: Increased release of soluble GP1,2delta. 2 Publications
    Mutagenesisi638 – 6381Q → V: No effect on release of soluble GP1,2delta. 2 Publications
    Mutagenesisi639 – 6391G → V: 40% loss of release of soluble GP1,2delta. 2 Publications
    Mutagenesisi640 – 6401D → V: No effect on release of soluble GP1,2delta. 2 Publications
    Mutagenesisi641 – 6411N → A: No effect on release of soluble GP1,2delta. 2 Publications
    Mutagenesisi642 – 6421D → V: No effect on release of soluble GP1,2delta. 2 Publications
    Mutagenesisi643 – 6431N → A: No effect on release of soluble GP1,2delta. 2 Publications
    Mutagenesisi670 – 6701C → A: Reduced palmitoylation. No effect on GP processing and association with retrovirus particle. No loss of virus capability to enter into host cell. 3 Publications
    Mutagenesisi670 – 6701C → F: Slightly reduced levels of expression of GP1 and GP2. Greatly reduced GP processing and association with retrovirus particle. 43% loss of virus capability to enter into host cell. 3 Publications
    Mutagenesisi672 – 6721C → A: Reduced palmitoylation. No effect on GP processing and association with retrovirus particle. No loss of virus capability to enter into host cell. 3 Publications
    Mutagenesisi672 – 6721C → F: Slightly reduced levels of expression of GP1 and GP2. Almost no effect on GP processing and association with retrovirus particle. 24% loss of virus capability to enter into host cell. 3 Publications

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 3232Sequence AnalysisAdd
    BLAST
    Chaini33 – 676644Envelope glycoproteinPRO_0000037485Add
    BLAST
    Chaini33 – 501469GP1PRO_0000037486Add
    BLAST
    Chaini502 – 676175GP2PRO_0000037487Add
    BLAST
    Chaini502 – 637136GP2-deltaPRO_0000245066Add
    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)1 Publication
    Disulfide bondi108 ↔ 135Sequence Analysis
    Disulfide bondi121 ↔ 147Sequence Analysis
    Glycosylationi204 – 2041N-linked (GlcNAc...); by hostSequence Analysis
    Glycosylationi228 – 2281N-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
    Glycosylationi317 – 3171N-linked (GlcNAc...); by hostSequence Analysis
    Glycosylationi333 – 3331N-linked (GlcNAc...); by hostSequence Analysis
    Glycosylationi346 – 3461N-linked (GlcNAc...); by hostSequence Analysis
    Glycosylationi386 – 3861N-linked (GlcNAc...); by hostSequence Analysis
    Glycosylationi413 – 4131N-linked (GlcNAc...); by hostSequence Analysis
    Glycosylationi436 – 4361N-linked (GlcNAc...); by hostSequence Analysis
    Glycosylationi454 – 4541N-linked (GlcNAc...); by hostSequence Analysis
    Glycosylationi462 – 4621N-linked (GlcNAc...); by hostSequence Analysis
    Disulfide bondi511 ↔ 556Sequence Analysis
    Glycosylationi563 – 5631N-linked (GlcNAc...); by hostSequence Analysis
    Disulfide bondi601 ↔ 6081 Publication
    Glycosylationi618 – 6181N-linked (GlcNAc...); by hostSequence Analysis
    Lipidationi670 – 6701S-palmitoyl cysteine; by host1 Publication
    Lipidationi672 – 6721S-palmitoyl cysteine; by host1 Publication

    Post-translational modificationi

    The signal peptide region modulates GP's high mannose glycosylation, thereby determining the efficiency of the interactions with DC-SIGN(R).1 Publication
    N-glycosylated.1 Publication
    O-glycosylated in the mucin-like region.1 Publication
    Palmitoylation of GP2 is not required for its function.1 Publication
    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).5 Publications

    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 FOLR1.5 Publications

    Structurei

    Secondary structure

    1
    676
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi35 – 395
    Beta strandi42 – 465
    Beta strandi48 – 503
    Helixi60 – 623
    Beta strandi63 – 697
    Helixi70 – 734
    Helixi79 – 835
    Beta strandi86 – 927
    Beta strandi96 – 983
    Beta strandi100 – 1034
    Beta strandi105 – 11410
    Beta strandi116 – 1183
    Beta strandi120 – 1223
    Beta strandi135 – 14410
    Beta strandi149 – 1546
    Beta strandi159 – 1613
    Beta strandi163 – 1697
    Beta strandi175 – 18511
    Beta strandi216 – 22914
    Beta strandi231 – 2344
    Beta strandi240 – 2434
    Helixi250 – 26314
    Beta strandi268 – 2703
    Beta strandi273 – 2764
    Beta strandi305 – 3073
    Beta strandi515 – 5206
    Turni528 – 5314
    Beta strandi532 – 5365
    Beta strandi541 – 5488
    Helixi560 – 59435
    Helixi595 – 5973
    Helixi600 – 6045
    Helixi605 – 6095
    Helixi616 – 62813

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    2EBOX-ray1.90A/B/C557-630[»]
    2RLJNMR-A524-539[»]
    3CSYX-ray3.40I/K/M/O32-311[»]
    J/L/N/P502-632[»]
    ProteinModelPortaliQ05320.
    SMRiQ05320. Positions 32-310, 502-634.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ05320.

    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-bindingSequence AnalysisAdd
    BLAST
    Regioni305 – 485181Mucin-like regionAdd
    BLAST
    Regioni524 – 53916Fusion peptideCuratedAdd
    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.
    The coiled coil regions play a role in oligomerization and fusion activity.

    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.

    Q05320-1 [UniParc]FASTAAdd to Basket

    « Hide

    MGVTGILQLP RDRFKRTSFF LWVIILFQRT FSIPLGVIHN STLQVSDVDK    50
    LVCRDKLSST NQLRSVGLNL EGNGVATDVP SATKRWGFRS GVPPKVVNYE 100
    AGEWAENCYN LEIKKPDGSE CLPAAPDGIR GFPRCRYVHK VSGTGPCAGD 150
    FAFHKEGAFF LYDRLASTVI YRGTTFAEGV VAFLILPQAK KDFFSSHPLR 200
    EPVNATEDPS SGYYSTTIRY QATGFGTNET EYLFEVDNLT YVQLESRFTP 250
    QFLLQLNETI YTSGKRSNTT GKLIWKVNPE IDTTIGEWAF WETKKNLTRK 300
    IRSEELSFTV VSNGAKNISG QSPARTSSDP GTNTTTEDHK IMASENSSAM 350
    VQVHSQGREA AVSHLTTLAT ISTSPQSLTT KPGPDNSTHN TPVYKLDISE 400
    ATQVEQHHRR TDNDSTASDT PSATTAAGPP KAENTNTSKS TDFLDPATTT 450
    SPQNHSETAG NNNTHHQDTG EESASSGKLG LITNTIAGVA GLITGGRRTR 500
    REAIVNAQPK CNPNLHYWTT QDEGAAIGLA WIPYFGPAAE GIYIEGLMHN 550
    QDGLICGLRQ LANETTQALQ LFLRATTELR TFSILNRKAI DFLLQRWGGT 600
    CHILGPDCCI EPHDWTKNIT DKIDQIIHDF VDKTLPDQGD NDNWWTGWRQ 650
    WIPAGIGVTG VIIAVIALFC ICKFVF 676
    Length:676
    Mass (Da):74,464
    Last modified:February 1, 1994 - v1
    Checksum:iBE8AB3B339F63261
    GO

    Sequence cautioni

    The sequence AAA96744.1 differs from that shown. Reason: Frameshift at position 296.

    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 P60170), the +2A edited RNA gives rise to the super small secreted glycoprotein ssGP (AC Q9YMG2).

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti65 – 651S → P in strain: Isolate mouse-adapted.
    Natural varianti246 – 2461S → P in strain: Isolate mouse-adapted.
    Natural varianti544 – 5441I → T.

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    L11365 Genomic RNA. Translation: AAB81004.1.
    U31033 Genomic RNA. Translation: AAA96744.1. Frameshift.
    U23187 Genomic RNA. Translation: AAC54887.1.
    AF272001 Genomic RNA. Translation: AAG40168.1.
    AY142960 Genomic RNA. Translation: AAN37507.1.
    AF086833 Genomic RNA. Translation: AAD14585.1.
    AF499101 Genomic RNA. Translation: AAM76034.1.
    PIRiS23155.
    RefSeqiNP_066246.1. NC_002549.1.

    Genome annotation databases

    GeneIDi911829.

    Keywords - Coding sequence diversityi

    RNA editing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    L11365 Genomic RNA. Translation: AAB81004.1 .
    U31033 Genomic RNA. Translation: AAA96744.1 . Frameshift.
    U23187 Genomic RNA. Translation: AAC54887.1 .
    AF272001 Genomic RNA. Translation: AAG40168.1 .
    AY142960 Genomic RNA. Translation: AAN37507.1 .
    AF086833 Genomic RNA. Translation: AAD14585.1 .
    AF499101 Genomic RNA. Translation: AAM76034.1 .
    PIRi S23155.
    RefSeqi NP_066246.1. NC_002549.1.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    2EBO X-ray 1.90 A/B/C 557-630 [» ]
    2RLJ NMR - A 524-539 [» ]
    3CSY X-ray 3.40 I/K/M/O 32-311 [» ]
    J/L/N/P 502-632 [» ]
    ProteinModelPortali Q05320.
    SMRi Q05320. Positions 32-310, 502-634.
    ModBasei Search...
    MobiDBi Search...

    Protein family/group databases

    TCDBi 1.G.12.2.2. the avian leukosis virus gp95 fusion protein (alv-gp95) family.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    GeneIDi 911829.

    Miscellaneous databases

    EvolutionaryTracei Q05320.

    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. "Sequence analysis of the Ebola virus genome: organization, genetic elements, and comparison with the genome of Marburg virus."
      Sanchez A., Kiley M.P., Holloway B.P., Auperin D.D.
      Virus Res. 29:215-240(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
    2. "GP mRNA of Ebola virus is edited by the Ebola virus polymerase and by T7 and vaccinia virus polymerases."
      Volchkov V.E., Becker S., Volchkova V.A., Ternovoj V.A., Kotov A.N., Netesov S.V., Klenk H.-D.
      Virology 214:421-430(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA / MRNA], RNA EDITING.
    3. "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.
    4. "Molecular characterization of guinea pig-adapted variants of Ebola virus."
      Volchkov V.E., Chepurnov A.A., Volchkova V.A., Ternovoj V.A., Klenk H.D.
      Virology 277:147-155(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
      Strain: Isolate guinea pig-adapted.
    5. Volchkov V.E.
      Submitted (JUN-2000) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
    6. Wilson J.A., Kondig J.P., Kuehne A.I., Hart M.K.
      Submitted (APR-2002) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
      Strain: Isolate mouse-adapted.
    7. "The envelope glycoprotein of Ebola virus contains an immunosuppressive-like domain similar to oncogenic retroviruses."
      Volchkov V.E., Blinov V.M., Netesov S.V.
      FEBS Lett. 305:181-184(1992) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA] OF 359-676.
    8. "Processing of the Ebola virus glycoprotein by the proprotein convertase furin."
      Volchkov V.E., Feldmann H., Volchkova V.A., Klenk H.-D.
      Proc. Natl. Acad. Sci. U.S.A. 95:5762-5767(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEOLYTIC PROCESSING OF ENVELOPE GLYCOPROTEIN.
    9. "Release of viral glycoproteins during Ebola virus infection."
      Volchkov V.E., Volchkova V.A., Slenczka W., Klenk H.-D., Feldmann H.
      Virology 245:110-119(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEOLYTIC PROCESSING OF ENVELOPE GLYCOPROTEIN.
    10. "Phosphatidylinositol-dependent membrane fusion induced by a putative fusogenic sequence of Ebola virus."
      Ruiz-Arguello M.B., Goni F.M., Pereira F.B., Nieva J.L.
      J. Virol. 72:1775-1781(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: DOMAIN FUSION PEPTIDE.
    11. "Mutational analysis of the putative fusion domain of Ebola virus glycoprotein."
      Ito H., Watanabe S., Sanchez A., Whitt M.A., Kawaoka Y.
      J. Virol. 73:8907-8912(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: DOMAIN FUSION PEPTIDE, MUTAGENESIS OF GLY-528; LEU-529; ILE-532; PHE-535; GLY-536 AND PRO-537.
    12. "Endoproteolytic processing of the ebola virus envelope glycoprotein: cleavage is not required for function."
      Wool-Lewis R.J., Bates P.
      J. Virol. 73:1419-1426(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEOLYTIC PROCESSING OF ENVELOPE GLYCOPROTEIN, MUTAGENESIS OF 498-ARG--ARG-501.
    13. "Identification of the Ebola virus glycoprotein as the main viral determinant of vascular cell cytotoxicity and injury."
      Yang Z.-Y., Duckers H.J., Sullivan N.J., Sanchez A., Nabel E.G., Nabel G.J.
      Nat. Med. 6:886-889(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, DOMAIN MUCIN/LIKE REGION.
    14. "Downregulation of beta1 integrins by Ebola virus glycoprotein: implication for virus entry."
      Takada A., Watanabe S., Ito H., Okazaki K., Kida H., Kawaoka Y.
      Virology 278:20-26(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: DOWN-MODULATION OF HOST ITGB1/BETA-1 INTEGRIN.
    15. "Ebola virus glycoprotein: proteolytic processing, acylation, cell tropism, and detection of neutralizing antibodies."
      Ito H., Watanabe S., Takada A., Kawaoka Y.
      J. Virol. 75:1576-1580(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEOLYTIC PROCESSING OF ENVELOPE GLYCOPROTEIN, PALMITOYLATION, MUTAGENESIS OF 497-ARG--ARG-501; CYS-670 AND CYS-672.
    16. "Functional importance of the coiled-coil of the Ebola virus glycoprotein."
      Watanabe S., Takada A., Watanabe T., Ito H., Kida H., Kawaoka Y.
      J. Virol. 74:10194-10201(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: COILED-COIL DOMAIN.
    17. "Folate receptor-alpha is a cofactor for cellular entry by Marburg and Ebola viruses."
      Chan S.Y., Empig C.J., Welte F.J., Speck R.F., Schmaljohn A., Kreisberg J.F., Goldsmith M.A.
      Cell 106:117-126(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH HUMAN FOLR1.
    18. "Covalent modifications of the ebola virus glycoprotein."
      Jeffers S.A., Sanders D.A., Sanchez A.
      J. Virol. 76:12463-12472(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: DISULFIDE BONDS, GLYCOSYLATION, MUTAGENESIS OF ASN-40; CYS-53; CYS-108; CYS-121; CYS-135; CYS-147; ASN-204; ASN-238; ASN-257; ASN-296; CYS-511; CYS-556; ASN-563; CYS-601; CYS-608; CYS-609; ASN-618; CYS-670 AND CYS-672.
    19. "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.
    20. "Lipid raft microdomains: a gateway for compartmentalized trafficking of Ebola and Marburg viruses."
      Bavari S., Bosio C.M., Wiegand E., Ruthel G., Will A.B., Geisbert T.W., Hevey M., Schmaljohn C., Schmaljohn A., Aman M.J.
      J. Exp. Med. 195:593-602(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION.
    21. "C-type lectins DC-SIGN and L-SIGN mediate cellular entry by Ebola virus in cis and in trans."
      Alvarez C.P., Lasala F., Carrillo J., Muniz O., Corbi A.L., Delgado R.
      J. Virol. 76:6841-6844(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH HUMAN CD209 AND CLEC4M, ROLE IN TRANS INFECTION.
    22. "Folate receptor alpha and caveolae are not required for Ebola virus glycoprotein-mediated viral infection."
      Simmons G., Rennekamp A.J., Chai N., Vandenberghe L.H., Riley J.L., Bates P.
      J. Virol. 77:13433-13438(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: PUTATIVE ROLE OF FOLR1 IN VIRUS ENTRY INTO THE CELL.
    23. "DC-SIGN and DC-SIGNR bind ebola glycoproteins and enhance infection of macrophages and endothelial cells."
      Simmons G., Reeves J.D., Grogan C.C., Vandenberghe L.H., Baribaud F., Whitbeck J.C., Burke E., Buchmeier M.J., Soilleux E.J., Riley J.L., Doms R.W., Bates P., Poehlmann S.
      Virology 305:115-123(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH HUMAN CD209 AND CLEC4M.
    24. Cited for: CLEAVAGE BY HOST ADAM17, MUTAGENESIS OF ASP-632; LYS-633; THR-634; LEU-635; ASP-637; GLN-638; GLY-639; ASP-640; ASN-641; ASP-642 AND ASN-643.
    25. "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.
    26. "Effects of Ebola virus glycoproteins on endothelial cell activation and barrier function."
      Wahl-Jensen V.M., Afanasieva T.A., Seebach J., Stroeher U., Feldmann H., Schnittler H.J.
      J. Virol. 79:10442-10450(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN ENDOTHELIAL CELLS ACTIVATION.
    27. "Endosomal proteolysis of the Ebola virus glycoprotein is necessary for infection."
      Chandran K., Sullivan N.J., Felbor U., Whelan S.P., Cunningham J.M.
      Science 308:1643-1645(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEOLYSIS OF GP1.
    28. "Role of Ebola virus secreted glycoproteins and virus-like particles in activation of human macrophages."
      Wahl-Jensen V., Kurz S.K., Hazelton P.R., Schnittler H.J., Stroeher U., Burton D.R., Feldmann H.
      J. Virol. 79:2413-2419(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION OF GP1,2DELTA.
    29. "Ebola virus glycoprotein toxicity is mediated by a dynamin-dependent protein-trafficking pathway."
      Sullivan N.J., Peterson M., Yang Z.-Y., Kong W.-P., Duckers H., Nabel E., Nabel G.J.
      J. Virol. 79:547-553(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: DOWN-MODULATION OF HOST INTEGRIN DIMER ALPHA-V/BETA-3, INTERACTION WITH HUMAN INTEGRIN ITGAV.
    30. "Role of endosomal cathepsins in entry mediated by the Ebola virus glycoprotein."
      Schornberg K., Matsuyama S., Kabsch K., Delos S., Bouton A., White J.
      J. Virol. 80:4174-4178(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEOLYSIS OF GP1.
    31. "Ebola virus glycoprotein GP is not cytotoxic when expressed constitutively at a moderate level."
      Alazard-Dany N., Volchkova V., Reynard O., Carbonnelle C., Dolnik O., Ottmann M., Khromykh A., Volchkov V.E.
      J. Gen. Virol. 87:1247-1257(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    32. "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.
    33. "Conserved receptor-binding domains of Lake Victoria marburgvirus and Zaire ebolavirus bind a common receptor."
      Kuhn J.H., Radoshitzky S.R., Guth A.C., Warfield K.L., Li W., Vincent M.J., Towner J.S., Nichol S.T., Bavari S., Choe H., Aman M.J., Farzan M.
      J. Biol. Chem. 281:15951-15958(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: RECEPTOR-BINDING REGION.
    34. "Cellular entry of ebola virus involves uptake by a macropinocytosis-like mechanism and subsequent trafficking through early and late endosomes."
      Saeed M.F., Kolokoltsov A.A., Albrecht T., Davey R.A.
      PLoS Pathog. 6:0-0(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    35. "Ebola virus uses clathrin-mediated endocytosis as an entry pathway."
      Bhattacharyya S., Warfield K.L., Ruthel G., Bavari S., Aman M.J., Hope T.J.
      Virology 401:18-28(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    36. "Core structure of the envelope glycoprotein GP2 from Ebola virus at 1.9-A resolution."
      Malashkevich V.N., Schneider B.J., McNally M.L., Milhollen M.A., Pang J.X., Kim P.S.
      Proc. Natl. Acad. Sci. U.S.A. 96:2662-2667(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 557-630.

    Entry informationi

    Entry nameiVGP_EBOZM
    AccessioniPrimary (citable) accession number: Q05320
    Secondary accession number(s): Q66818
    , Q77LU5, Q8B9S1, Q8JS62
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: February 1, 1994
    Last sequence update: February 1, 1994
    Last modified: October 1, 2014
    This is version 105 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.
    Essential for infectivity, as it is the sole viral protein expressed at the virion surface.

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    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