Q05320 (VGP_EBOZM) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Envelope glycoprotein

Alternative name(s):
GP1,2
Short name=GP

Cleaved into the following 3 chains:

1. GP1
2. GP2
3. GP2-delta

Gene names

Name:

GP

Organism

Zaire ebolavirus (strain Mayinga-76) (ZEBOV) (Zaire Ebola virus) [Reference proteome]

Taxonomic identifier

128952 [NCBI]

Taxonomic lineage

Viruses › ssRNA viruses › ssRNA negative-strand viruses › Mononegavirales › Filoviridae › Ebolavirus › Zaire ebolavirus

Virus host

Epomops franqueti (Franquet's epauleted fruit bat) [TaxID: 77231]
Homo sapiens (Human) [TaxID: 9606]
Myonycteris torquata (Little collared fruit bat) [TaxID: 77243]

Protein attributes

Sequence length	676 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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. Ref.13 Ref.21 Ref.26 Ref.28 Ref.31 Ref.32 Ref.34 Ref.35 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. Ref.13 Ref.21 Ref.26 Ref.28 Ref.31 Ref.32 Ref.34 Ref.35 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. Ref.13 Ref.21 Ref.26 Ref.28 Ref.31 Ref.32 Ref.34 Ref.35 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. Ref.13 Ref.21 Ref.26 Ref.28 Ref.31 Ref.32 Ref.34 Ref.35
Subunit structure	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. Ref.17 Ref.21 Ref.23 Ref.25 Ref.29
Subcellular location	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. Ref.20 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. Ref.20 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. Ref.20
Domain	The mucin-like region seems to be involved in the cytotoxic function. This region is also involved in binding to human CLEC10A. Ref.10 Ref.11 Ref.13 Ref.16 The coiled coil regions play a role in oligomerization and fusion activity. Ref.10 Ref.11 Ref.13 Ref.16
Post-translational modification	The signal peptide region modulates GP's high mannose glycosylation, thereby determining the efficiency of the interactions with DC-SIGN(R). N-glycosylated. Ref.18 O-glycosylated in the mucin-like region. Ref.18 Palmitoylation of GP2 is not required for its function. Ref.15 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).
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.
Sequence similarities	Belongs to the filoviruses glycoprotein family.
RNA editing	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 P60170), the +2A edited RNA gives rise to the super small secreted glycoprotein ssGP (AC Q9YMG2). Ref.2 Ref.3
Sequence caution	The sequence AAA96744.1 differs from that shown. Reason: Frameshift at position 296.

Ontologies

Keywords
Biological process	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
Cellular component	Host cell membrane Host membrane Membrane Secreted Viral envelope protein Virion
Coding sequence diversity	RNA editing
Domain	Coiled coil Signal Transmembrane Transmembrane helix
PTM	Cleavage on pair of basic residues Disulfide bond Glycoprotein Lipoprotein Palmitate
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	suppression by virus of host tetherin activity Inferred from electronic annotation. Source: UniProtKB-KW suppression by virus of host type I interferon-mediated signaling pathway Inferred from electronic annotation. Source: UniProtKB-KW viral attachment to host cell Inferred from electronic annotation. Source: UniProtKB-KW viral entry into host cell via clathrin-mediated endocytosis Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	host cell plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW viral envelope Inferred from electronic annotation. Source: UniProtKB-KW virion membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 32

32

Potential

Chain

33 – 676

644

Envelope glycoprotein

PRO_0000037485

Chain

33 – 501

469

GP1

PRO_0000037486

Chain

502 – 676

175

GP2

PRO_0000037487

Chain

502 – 637

136

GP2-delta

PRO_0000245066

Regions

Topological domain

33 – 650

618

Extracellular Potential

Transmembrane

651 – 671

21

Helical; Potential

Topological domain

672 – 676

5

Cytoplasmic Potential

Region

54 – 201

148

Receptor-binding Potential

Region

305 – 485

181

Mucin-like region

Region

524 – 539

16

Fusion peptide Probable

Coiled coil

554 – 595

42

Potential

Coiled coil

615 – 634

20

Potential

Sites

Site

57

1

Involved in receptor recognition and/or post-binding events Potential

Site

63

1

Involved in receptor recognition and/or post-binding events Potential

Site

64

1

Involved in receptor recognition and/or post-binding events Potential

Site

88

1

Involved in receptor recognition and/or post-binding events Potential

Site

95

1

Involved in receptor recognition and/or post-binding events Potential

Site

170

1

Involved in receptor recognition and/or post-binding events Potential

Site

501 – 502

2

Cleavage; by host furin

Site

637 – 638

2

Cleavage; by host ADAM17

Amino acid modifications

Lipidation

670

1

S-palmitoyl cysteine; by host Ref.15

Lipidation

672

1

S-palmitoyl cysteine; by host Ref.15

Glycosylation

40

1

N-linked (GlcNAc...); by host Potential

Glycosylation

204

1

N-linked (GlcNAc...); by host Potential

Glycosylation

228

1

N-linked (GlcNAc...); by host Potential

Glycosylation

238

1

N-linked (GlcNAc...); by host Potential

Glycosylation

257

1

N-linked (GlcNAc...); by host Potential

Glycosylation

268

1

N-linked (GlcNAc...); by host Potential

Glycosylation

296

1

N-linked (GlcNAc...); by host Potential

Glycosylation

317

1

N-linked (GlcNAc...); by host Potential

Glycosylation

333

1

N-linked (GlcNAc...); by host Potential

Glycosylation

346

1

N-linked (GlcNAc...); by host Potential

Glycosylation

386

1

N-linked (GlcNAc...); by host Potential

Glycosylation

413

1

N-linked (GlcNAc...); by host Potential

Glycosylation

436

1

N-linked (GlcNAc...); by host Potential

Glycosylation

454

1

N-linked (GlcNAc...); by host Potential

Glycosylation

462

1

N-linked (GlcNAc...); by host Potential

Glycosylation

563

1

N-linked (GlcNAc...); by host Potential

Glycosylation

618

1

N-linked (GlcNAc...); by host Potential

Disulfide bond

53 ↔ 609

Interchain (between GP1 and GP2 chains) Ref.18

Disulfide bond

108 ↔ 135

Potential

Disulfide bond

121 ↔ 147

Potential

Disulfide bond

511 ↔ 556

Potential

Disulfide bond

601 ↔ 608

Ref.18

Natural variations

Natural variant

65

1

S → P in strain: Isolate mouse-adapted.

Natural variant

246

1

S → P in strain: Isolate mouse-adapted.

Natural variant

544

1

I → T.

Experimental info

Mutagenesis

40

1

N → D: Induces GP1 secretion. Complete loss of virus capability to enter into host cell. Ref.18

Mutagenesis

53

1

C → G: Induces GP1 secretion. Complete loss of virus capability to enter into host cell. Ref.18

Mutagenesis

55

1

D → A: 80% loss of virus capability to enter into host cell.

Mutagenesis

55

1

D → E or K: No effect on viral entry.

Mutagenesis

57

1

L → A: Complete loss of virus capability to enter into host cell.

Mutagenesis

57

1

L → F, I or K: 90% loss of virus capability to enter into host cell.

Mutagenesis

63

1

L → A: 90% loss of virus capability to enter into host cell.

Mutagenesis

63

1

L → F: Almost complete loss of virus capability to enter into host cell.

Mutagenesis

63

1

L → K: Complete loss of virus capability to enter into host cell.

Mutagenesis

64

1

R → A or E: Complete loss of virus capability to enter into host cell.

Mutagenesis

64

1

R → K: No loss of virus capability to enter into host cell.

Mutagenesis

88

1

F → A or E: Complete loss of virus capability to enter into host cell.

Mutagenesis

88

1

F → I: No loss of virus capability to enter into host cell.

Mutagenesis

95

1

K → A or E: 80% loss of virus capability to enter into host cell.

Mutagenesis

95

1

K → R: 20% loss of virus capability to enter into host cell.

Mutagenesis

108

1

C → G: Almost complete loss of expression of GP1 and GP2. Almost complete loss of virus capability to enter into host cell. Ref.18

Mutagenesis

121

1

C → G: Reduced levels of expression of GP1 and GP2. 50% loss of virus capability to enter into host cell. Ref.18

Mutagenesis

135

1

C → S: Almost complete loss of expression of GP1 and GP2. Complete loss of virus capability to enter into host cell. Ref.18

Mutagenesis

147

1

C → S: Reduced levels of expression of GP1 and GP2. Almost complete loss of virus capability to enter into host cell. Ref.18

Mutagenesis

170

1

I → A: 90% loss of virus capability to enter into host cell.

Mutagenesis

170

1

I → E: Complete loss of virus capability to enter into host cell.

Mutagenesis

170

1

I → F: 50% loss of virus capability to enter into host cell.

Mutagenesis

204

1

N → D: No effect on GP1 and GP2 expression. No loss of virus capability to enter into host cell. Ref.18

Mutagenesis

238

1

N → Y: No effect on GP1 and GP2 expression. 12% loss of virus capability to enter into host cell. Ref.18

Mutagenesis

257

1

N → D: No effect on GP1 and GP2 expression. 12% loss of virus capability to enter into host cell. Ref.18

Mutagenesis

296

1

N → D: No effect on GP1 and GP2 expression. 18% loss of virus capability to enter into host cell. Ref.18

Mutagenesis

497 – 501

5

RRTRR → AGTAA: Almost complete loss of cleavage between GP1 and GP2. No loss of infectivity. Ref.15

Mutagenesis

498 – 501

4

RTRR → ATAA: No effect on cleavage between GP1 and GP2. Ref.12

Mutagenesis

511

1

C → G: Induces GP1 secretion. Complete loss of virus capability to enter into host cell. Ref.18

Mutagenesis

528

1

G → R: Reduced infectivity. Ref.11

Mutagenesis

529

1

L → A or R: Reduced infectivity. Ref.11

Mutagenesis

532

1

I → A: Reduced infectivity. Ref.11

Mutagenesis

532

1

I → R: Almost complete loss of infectivity. No effect on transport of GP to the cell surface and incorporation onto virions. Ref.11

Mutagenesis

535

1

F → A: Reduced infectivity. Ref.11

Mutagenesis

535

1

F → R: Almost complete loss of infectivity. No effect on transport of GP to the cell surface and incorporation onto virions. Ref.11

Mutagenesis

536

1

G → A: Almost complete loss of infectivity. No effect on transport of GP to the cell surface and incorporation onto virions. Ref.11

Mutagenesis

537

1

P → R: Almost complete loss of infectivity. No effect on transport of GP to the cell surface and incorporation onto virions. Ref.11

Mutagenesis

556

1

C → S: Induces GP1 secretion. Complete loss of virus capability to enter into host cell. Ref.18

Mutagenesis

563

1

N → D: Reduced levels of expression of GP, GP1 and GP2. 20% loss of virus capability to enter into host cell. Ref.18

Mutagenesis

601

1

C → S: Induces GP1 secretion. Complete loss of virus capability to enter into host cell. Ref.18

Mutagenesis

608

1

C → G: Induces GP1 secretion. Complete loss of virus capability to enter into host cell. Ref.18

Mutagenesis

609

1

C → G: Induces GP1 secretion. Complete loss of virus capability to enter into host cell. Ref.18

Mutagenesis

618

1

N → D: Slightly reduced levels of expression of GP1 and GP2. No loss of virus capability to enter into host cell. Ref.18

Mutagenesis

632

1

D → V: No effect on release of soluble GP1,2delta. Ref.24

Mutagenesis

633

1

K → R or V: No effect on release of soluble GP1,2delta. Ref.24

Mutagenesis

634

1

T → I: 50% loss of release of soluble GP1,2delta. Ref.24

Mutagenesis

635

1

L → V: 60% loss of release of soluble GP1,2delta. Ref.24

Mutagenesis

636

1

P → A: 60% loss of release of soluble GP1,2delta.

Mutagenesis

637

1

D → E: No effect on release of soluble GP1,2delta. Ref.24

Mutagenesis

637

1

D → L or V: Increased release of soluble GP1,2delta. Ref.24

Mutagenesis

638

1

Q → V: No effect on release of soluble GP1,2delta. Ref.24

Mutagenesis

639

1

G → V: 40% loss of release of soluble GP1,2delta. Ref.24

Mutagenesis

640

1

D → V: No effect on release of soluble GP1,2delta. Ref.24

Mutagenesis

641

1

N → A: No effect on release of soluble GP1,2delta. Ref.24

Mutagenesis

642

1

D → V: No effect on release of soluble GP1,2delta. Ref.24

Mutagenesis

643

1

N → A: No effect on release of soluble GP1,2delta. Ref.24

Mutagenesis

670

1

C → A: Reduced palmitoylation. No effect on GP processing and association with retrovirus particle. No loss of virus capability to enter into host cell. Ref.15 Ref.18

Mutagenesis

670

1

C → 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. Ref.15 Ref.18

Mutagenesis

672

1

C → A: Reduced palmitoylation. No effect on GP processing and association with retrovirus particle. No loss of virus capability to enter into host cell. Ref.15 Ref.18

Mutagenesis

672

1

C → 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. Ref.15 Ref.18

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

676

Helix Strand Turn

Details...

Helix

532 – 534

3

Helix

560 – 594

35

Helix

595 – 597

3

Helix

600 – 604

5

Helix

605 – 609

5

Helix

616 – 628

13

Sequences

	Sequence		Length	Mass (Da)
	Q05320 [UniParc]. Last modified February 1, 1994. Version 1. Checksum: BE8AB3B339F63261	FASTA	676	74,464
	10 20 30 40 50 60 MGVTGILQLP RDRFKRTSFF LWVIILFQRT FSIPLGVIHN STLQVSDVDK LVCRDKLSST 70 80 90 100 110 120 NQLRSVGLNL EGNGVATDVP SATKRWGFRS GVPPKVVNYE AGEWAENCYN LEIKKPDGSE 130 140 150 160 170 180 CLPAAPDGIR GFPRCRYVHK VSGTGPCAGD FAFHKEGAFF LYDRLASTVI YRGTTFAEGV 190 200 210 220 230 240 VAFLILPQAK KDFFSSHPLR EPVNATEDPS SGYYSTTIRY QATGFGTNET EYLFEVDNLT 250 260 270 280 290 300 YVQLESRFTP QFLLQLNETI YTSGKRSNTT GKLIWKVNPE IDTTIGEWAF WETKKNLTRK 310 320 330 340 350 360 IRSEELSFTV VSNGAKNISG QSPARTSSDP GTNTTTEDHK IMASENSSAM VQVHSQGREA 370 380 390 400 410 420 AVSHLTTLAT ISTSPQSLTT KPGPDNSTHN TPVYKLDISE ATQVEQHHRR TDNDSTASDT 430 440 450 460 470 480 PSATTAAGPP KAENTNTSKS TDFLDPATTT SPQNHSETAG NNNTHHQDTG EESASSGKLG 490 500 510 520 530 540 LITNTIAGVA GLITGGRRTR REAIVNAQPK CNPNLHYWTT QDEGAAIGLA WIPYFGPAAE 550 560 570 580 590 600 GIYIEGLMHN QDGLICGLRQ LANETTQALQ LFLRATTELR TFSILNRKAI DFLLQRWGGT 610 620 630 640 650 660 CHILGPDCCI EPHDWTKNIT DKIDQIIHDF VDKTLPDQGD NDNWWTGWRQ WIPAGIGVTG 670 VIIAVIALFC ICKFVF

References

[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]	"Ectodomain shedding of the glycoprotein GP of Ebola virus." Dolnik O., Volchkova V., Garten W., Carbonnelle C., Becker S., Kahnt J., Stroeher U., Klenk H.-D., Volchkov V. EMBO J. 23:2175-2184(2004) [PubMed] [Europe PMC] [Abstract] 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.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

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.

PIR

S23155.

RefSeq

NP_066246.1. NC_002549.1.

3D structure databases

PDBe
RCSB PDB
PDBj

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	32-501	[»]
			J/L/N/P	502-632	[»]

ProteinModelPortal

Q05320.

SMR

Q05320. Positions 32-310, 502-634.

ModBase

Search...

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

GeneID

911829.

Family and domain databases

InterPro

IPR014625. GPC_FiloV.
IPR002561. GPC_filovir-type_extra_dom.
[Graphical view]

Pfam

PF01611. Filo_glycop. 1 hit.
[Graphical view]

PIRSF

PIRSF036874. GPC_FiloV. 1 hit.

ProtoNet

Search...

Other

EvolutionaryTrace

Q05320.

Entry information

Entry name

VGP_EBOZM

Accession

Primary (citable) accession number: Q05320
Secondary accession number(s): Q66818 , Q77LU5, Q8B9S1, Q8JS62

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1994
Last sequence update:	February 1, 1994
Last modified:	April 3, 2013
This is version 99 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Viral Protein Annotation Program