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Q66799

- VGP_EBORR

UniProt

Q66799 - VGP_EBORR

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Protein
Envelope glycoprotein
Gene
GP
Organism
Reston ebolavirus (strain Reston-89) (REBOV) (Reston Ebola virus)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at transcript leveli

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.
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. 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.
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.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei58 – 581Involved in receptor recognition and/or post-binding events Reviewed prediction
Sitei64 – 641Involved in receptor recognition and/or post-binding events Reviewed prediction
Sitei89 – 891Involved in receptor recognition and/or post-binding events Reviewed prediction
Sitei96 – 961Involved in receptor recognition and/or post-binding events Reviewed prediction
Sitei171 – 1711Involved in receptor recognition and/or post-binding events Reviewed prediction
Sitei502 – 5032Cleavage; by host furin By similarity
Sitei638 – 6392Cleavage; by host ADAM17 By 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
Complete GO annotation...

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; 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.
Chain 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.
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.

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini34 – 651618Extracellular Reviewed prediction
Add
BLAST
Transmembranei652 – 67221Helical; Reviewed prediction
Add
BLAST
Topological domaini673 – 6775Cytoplasmic Reviewed prediction

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
Complete GO annotation...

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 – 3333 Reviewed prediction
Add
BLAST
Chaini34 – 677644Envelope glycoprotein
PRO_0000037470Add
BLAST
Chaini34 – 502469GP1 By similarity
PRO_0000037471Add
BLAST
Chaini503 – 677175GP2 By similarity
PRO_0000037472Add
BLAST
Chaini503 – 638136GP2-delta By similarity
PRO_0000245061Add
BLAST

Amino acid modifications

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

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.

Structurei

3D structure databases

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

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni55 – 202148Receptor-binding By similarity
Add
BLAST
Regioni306 – 486181Mucin-like region By similarity
Add
BLAST
Regioni525 – 54016Fusion peptide By similarity
Add
BLAST

Coiled coil

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Coiled coili555 – 59642 Reviewed prediction
Add
BLAST
Coiled coili616 – 63520 Reviewed prediction
Add
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.
The coiled coil regions play a role in oligomerization and fusion activity By similarity.

Sequence similaritiesi

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).1 Publication

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...

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: February 19, 2014
This is version 91 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

Similar proteinsi