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Protein

Envelope glycoprotein

Gene

GP

Organism
Sudan ebolavirus (strain Uganda-00) (SEBOV) (Sudan Ebola virus)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein 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 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, allowing its binding to the host entry receptor NPC1 and unmasking its fusion peptide to initiate 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
Envelope glycoprotein: GP1,2 which is the disulfid-linked complex of GP1 and GP2, 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. Counteracts the antiviral effect of host tetherin.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)DescriptionActionsGraphical viewLength
Sitei57Involved in receptor recognition and/or post-binding eventsSequence analysis1
Sitei63Involved in receptor recognition and/or post-binding eventsSequence analysis1
Sitei88Involved in receptor recognition and/or post-binding eventsSequence analysis1
Sitei95Involved in receptor recognition and/or post-binding eventsSequence analysis1
Sitei170Involved in receptor recognition and/or post-binding eventsSequence analysis1

GO - Biological processi

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 attachment to host entry receptor, 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
OrganismiSudan ebolavirus (strain Uganda-00) (SEBOV) (Sudan Ebola virus)
Taxonomic identifieri386033 [NCBI]
Taxonomic lineageiVirusesssRNA virusesssRNA 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]
Proteomesi
  • UP000000277 Componenti: Genome

Subcellular locationi

GP2 :
  • Virion membrane By similarity; Single-pass type I membrane protein Sequence analysis
  • Host cell membrane By similarity; Single-pass type I membrane protein Sequence analysis

  • Note: In the cell, localizes to the plasma membrane lipid rafts, which probably represent the assembly and budding site.By similarity
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 forms a disulfid-linked complex with the extravirion surface 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
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)DescriptionActionsGraphical viewLength
Topological domaini33 – 650ExtracellularSequence analysisAdd BLAST618
Transmembranei651 – 671HelicalSequence analysisAdd BLAST21
Topological domaini672 – 676CytoplasmicSequence analysis5

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

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

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 32Sequence analysisAdd BLAST32
ChainiPRO_000031690133 – 676Envelope glycoproteinBy similarityAdd BLAST644
ChainiPRO_000031690233 – 501GP1By similarityAdd BLAST469
ChainiPRO_0000316903502 – 676GP2By similarityAdd BLAST175
ChainiPRO_0000316904502 – 637GP2-deltaBy similarityAdd BLAST136

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi40N-linked (GlcNAc...); by hostSequence analysis1
Disulfide bondi53 ↔ 609Interchain (between GP1 and GP2 chains)By similarity
Disulfide bondi108 ↔ 135Sequence analysis
Disulfide bondi121 ↔ 147Sequence analysis
Glycosylationi204N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi208N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi238N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi257N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi268N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi296N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi314N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi366N-linked (GlcNAc...); by hostSequence analysis1
Glycosylationi463N-linked (GlcNAc...); by hostSequence analysis1
Disulfide bondi511 ↔ 556Sequence analysis
Glycosylationi563N-linked (GlcNAc...); by hostSequence analysis1
Disulfide bondi601 ↔ 608By similarity
Glycosylationi618N-linked (GlcNAc...); by hostSequence analysis1
Lipidationi670S-palmitoyl cysteine; by hostBy similarity1
Lipidationi672S-palmitoyl cysteine; by hostBy similarity1
Lipidationi676S-palmitoyl cysteine; by hostCurated1

Post-translational modificationi

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei501 – 502Cleavage; by host furinBy similarity2
Sitei637 – 638Cleavage; by host ADAM17By similarity2

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. Interacts with host entry receptor NPC1.By similarity

Protein-protein interaction databases

DIPiDIP-59447N.

Structurei

Secondary structure

1676
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi35 – 39Combined sources5
Beta strandi42 – 47Combined sources6
Helixi60 – 62Combined sources3
Beta strandi63 – 70Combined sources8
Helixi71 – 73Combined sources3
Helixi79 – 82Combined sources4
Turni83 – 85Combined sources3
Beta strandi86 – 91Combined sources6
Beta strandi96 – 98Combined sources3
Beta strandi100 – 103Combined sources4
Beta strandi105 – 111Combined sources7
Beta strandi120 – 122Combined sources3
Beta strandi135 – 141Combined sources7
Beta strandi149 – 154Combined sources6
Beta strandi159 – 161Combined sources3
Beta strandi163 – 169Combined sources7
Beta strandi176 – 186Combined sources11
Beta strandi216 – 219Combined sources4
Beta strandi225 – 229Combined sources5
Beta strandi233 – 237Combined sources5
Beta strandi240 – 243Combined sources4
Helixi250 – 262Combined sources13
Beta strandi515 – 519Combined sources5
Turni533 – 535Combined sources3
Helixi539 – 541Combined sources3
Beta strandi544 – 548Combined sources5
Helixi552 – 575Combined sources24
Beta strandi579 – 581Combined sources3
Helixi584 – 597Combined sources14

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3S88X-ray3.35I32-313[»]
J473-637[»]
ProteinModelPortaliQ7T9D9.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni33 – 185Receptor bindingSequence analysisAdd BLAST153
Regioni305 – 485Mucin-like regionBy similarityAdd BLAST181
Regioni524 – 539Fusion peptideBy similarityAdd BLAST16

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili554 – 595Sequence analysisAdd BLAST42
Coiled coili615 – 634Sequence analysisAdd BLAST20

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.

Q7T9D9-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGGLSLLQLP RDKFRKSSFF VWVIILFQKA FSMPLGVVTN STLEVTEIDQ
60 70 80 90 100
LVCKDHLAST DQLKSVGLNL EGSGVSTDIP SATKRWGFRS GVPPKVVSYE
110 120 130 140 150
AGEWAENCYN LEIKKPDGSE CLPPPPDGVR GFPRCRYVHK AQGTGPCPGD
160 170 180 190 200
YAFHKDGAFF LYDRLASTVI YRGVNFAEGV IAFLILAKPK ETFLQSPPIR
210 220 230 240 250
EAVNYTENTS SYYATSYLEY EIENFGAQHS TTLFKIDNNT FVRLDRPHTP
260 270 280 290 300
QFLFQLNDTI HLHQQLSNTT GRLIWTLDAN INADIGEWAF WENKKNLSEQ
310 320 330 340 350
LRGEELSFEA LSLNETEDDD AASSRITKGR ISDRATRKYS DLVPKNSPGM
360 370 380 390 400
VPLHIPEGET TLPSQNSTEG RRVGVNTQET ITETAATIIG TNGNHMQIST
410 420 430 440 450
IGIRPSSSQI PSSSPTTAPS PEAQTPTTHT SGPSVMATEE PTTPPGSSPG
460 470 480 490 500
PTTEAPTLTT PENITTAVKT VLPQESTSNG LITSTVTGIL GSLGLRKRSR
510 520 530 540 550
RQTNTKATGK CNPNLHYWTA QEQHNAAGIA WIPYFGPGAE GIYTEGLMHN
560 570 580 590 600
QNALVCGLRQ LANETTQALQ LFLRATTELR TYTILNRKAI DFLLRRWGGT
610 620 630 640 650
CRILGPDCCI EPHDWTKNIT DKINQIIHDF IDNPLPNQDN DDNWWTGWRQ
660 670
WIPAGIGITG IIIAIIALLC VCKLLC
Length:676
Mass (Da):74,594
Last modified:October 1, 2003 - v1
Checksum:i3852217579859E84
GO

RNA editingi

Edited at position 295.
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 Q7T9E0), the +2A edited RNA gives rise to the super small secreted glycoprotein ssGP (AC P0C772).

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY316199 Genomic RNA. Translation: AAP88031.1.
AY344234 Genomic RNA. Translation: AAR11463.1.
AY729654 Genomic RNA. Translation: AAU43887.1.
RefSeqiYP_138523.1. NC_006432.1.

Genome annotation databases

GeneIDi3160774.
KEGGivg:3160774.

Keywords - Coding sequence diversityi

RNA editing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY316199 Genomic RNA. Translation: AAP88031.1.
AY344234 Genomic RNA. Translation: AAR11463.1.
AY729654 Genomic RNA. Translation: AAU43887.1.
RefSeqiYP_138523.1. NC_006432.1.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3S88X-ray3.35I32-313[»]
J473-637[»]
ProteinModelPortaliQ7T9D9.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

DIPiDIP-59447N.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi3160774.
KEGGivg:3160774.

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.
ProtoNetiSearch...

Entry informationi

Entry nameiVGP_EBOSU
AccessioniPrimary (citable) accession number: Q7T9D9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 5, 2008
Last sequence update: October 1, 2003
Last modified: November 2, 2016
This is version 70 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

3D-structure, Complete proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.