Q05320 · VGP_EBOZM
- ProteinEnvelope glycoprotein
- GeneGP
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids676 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Envelope glycoprotein
Trimeric GP1,2 complexes form the virion surface spikes and mediate the viral entry processes, with GP1 acting as the receptor-binding subunit and GP2 as the membrane fusion subunit. At later times of infection, down-regulates the expression of various host cell surface molecules that are essential for immune surveillance and cell adhesion (PubMed:11836430).
Down-modulates several integrins including ITGA1, ITGA2, ITGA3, ITGA4, ITGA5, ITGA6, ITGAV and ITGB1 (PubMed:11112476).
This decrease in cell adhesion molecules may lead to cell detachment, contributing to the disruption of blood vessel integrity and hemorrhages developed during infection (cytotoxicity) (Probable). Interacts with host TLR4 and thereby stimulates the differentiation and activation of monocytes leading to bystander death of T-lymphocytes (PubMed:28542576).
Down-regulates as well the function of host natural killer cells (PubMed:30013549).
Counteracts the antiviral effect of host BST2/tetherin that restricts release of progeny virions from infected cells (PubMed:26516900, PubMed:27707924, PubMed:29669839).
However, cooperates with VP40 and host BST2 to activate canonical NF-kappa-B pathway in a manner dependent on neddylation (PubMed:28878074).
Down-modulates several integrins including ITGA1, ITGA2, ITGA3, ITGA4, ITGA5, ITGA6, ITGAV and ITGB1 (PubMed:11112476).
This decrease in cell adhesion molecules may lead to cell detachment, contributing to the disruption of blood vessel integrity and hemorrhages developed during infection (cytotoxicity) (Probable). Interacts with host TLR4 and thereby stimulates the differentiation and activation of monocytes leading to bystander death of T-lymphocytes (PubMed:28542576).
Down-regulates as well the function of host natural killer cells (PubMed:30013549).
Counteracts the antiviral effect of host BST2/tetherin that restricts release of progeny virions from infected cells (PubMed:26516900, PubMed:27707924, PubMed:29669839).
However, cooperates with VP40 and host BST2 to activate canonical NF-kappa-B pathway in a manner dependent on neddylation (PubMed:28878074).
Shed GP
Functions as a decoy for anti-GP1,2 antibodies thereby contributing to viral immune evasion. Interacts and activates host macrophages and dendritic cells inducing up-regulation of cytokine transcription. This effect is mediated throught activation of host TLR4.
GP1
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 dendritic cells (DCs) and endothelial cells (PubMed:16051836).
Binding to the macrophage specific lectin CLEC10A also seems to enhance virus infectivity (By similarity).
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 (By similarity).
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 removes the glycan cap and allows GP1 binding to the host entry receptor NPC1 (PubMed:21866103, PubMed:32040508).
NPC1-binding, Ca2+ and acidic pH induce a conformational change of GP2, which unmasks its fusion peptide and permit membranes fusion (PubMed:21866103, PubMed:22031933, PubMed:32040508).
Binding to the macrophage specific lectin CLEC10A also seems to enhance virus infectivity (By similarity).
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 (By similarity).
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 removes the glycan cap and allows GP1 binding to the host entry receptor NPC1 (PubMed:21866103, PubMed:32040508).
NPC1-binding, Ca2+ and acidic pH induce a conformational change of GP2, which unmasks its fusion peptide and permit membranes fusion (PubMed:21866103, PubMed:22031933, PubMed:32040508).
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.
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.
Features
Showing features for site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Site | 57 | Involved in receptor recognition and/or post-binding events | ||||
Sequence: L | ||||||
Site | 63 | Involved in receptor recognition and/or post-binding events | ||||
Sequence: L | ||||||
Site | 64 | Involved in receptor recognition and/or post-binding events | ||||
Sequence: R | ||||||
Site | 88 | Involved in receptor recognition and/or post-binding events | ||||
Sequence: F | ||||||
Site | 95 | Involved in receptor recognition and/or post-binding events | ||||
Sequence: K | ||||||
Site | 170 | Involved in receptor recognition and/or post-binding events | ||||
Sequence: I | ||||||
Site | 501-502 | Cleavage; by host furin | ||||
Sequence: RE | ||||||
Site | 637-638 | Cleavage; by host ADAM17 | ||||
Sequence: DQ |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | extracellular region | |
Cellular Component | host cell cytoplasm | |
Cellular Component | host cell endoplasmic reticulum | |
Cellular Component | host cell plasma membrane | |
Cellular Component | membrane raft | |
Cellular Component | viral envelope | |
Cellular Component | virion membrane | |
Molecular Function | identical protein binding | |
Molecular Function | lipid binding | |
Biological Process | clathrin-dependent endocytosis of virus by host cell | |
Biological Process | entry receptor-mediated virion attachment to host cell | |
Biological Process | fusion of virus membrane with host endosome membrane | |
Biological Process | suppression by virus of host tetherin activity | |
Biological Process | symbiont entry into host cell | |
Biological Process | symbiont-mediated suppression of host innate immune response | |
Biological Process | viral budding from plasma membrane |
Keywords
- Biological process
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameEnvelope glycoprotein
- Alternative names
- Cleaved into 3 chains
Gene names
Organism names
- Strains
- Taxonomic lineageViruses > Riboviria > Orthornavirae > Negarnaviricota > Haploviricotina > Monjiviricetes > Mononegavirales > Filoviridae > Orthoebolavirus > Orthoebolavirus zairense > Zaire ebolavirus
- Virus hosts
Accessions
- Primary accessionQ05320
- Secondary accessions
Proteomes
Subcellular Location
UniProt Annotation
GO Annotation
GP2
Virion membrane ; Single-pass type I membrane protein
Host cell membrane ; Single-pass type I membrane protein
Note: In the cell, localizes to the plasma membrane lipid rafts, which probably represent the assembly and budding site.
GP1
Virion membrane ; Peripheral membrane protein
Host cell membrane ; Peripheral membrane protein
Note: GP1 is not anchored to the viral envelope, but forms a disulfid-linked complex with the extravirion surface GP2 (PubMed:9576958).
In the cell, both GP1 and GP2 localize to the plasma membrane lipid rafts, which probably represent the assembly and budding site (PubMed:11877482).
GP1 can also be shed after proteolytic processing
In the cell, both GP1 and GP2 localize to the plasma membrane lipid rafts, which probably represent the assembly and budding site (PubMed:11877482).
GP1 can also be shed after proteolytic processing
Shed GP
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.
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 33-650 | Extracellular | ||||
Sequence: IPLGVIHNSTLQVSDVDKLVCRDKLSSTNQLRSVGLNLEGNGVATDVPSATKRWGFRSGVPPKVVNYEAGEWAENCYNLEIKKPDGSECLPAAPDGIRGFPRCRYVHKVSGTGPCAGDFAFHKEGAFFLYDRLASTVIYRGTTFAEGVVAFLILPQAKKDFFSSHPLREPVNATEDPSSGYYSTTIRYQATGFGTNETEYLFEVDNLTYVQLESRFTPQFLLQLNETIYTSGKRSNTTGKLIWKVNPEIDTTIGEWAFWETKKNLTRKIRSEELSFTVVSNGAKNISGQSPARTSSDPGTNTTTEDHKIMASENSSAMVQVHSQGREAAVSHLTTLATISTSPQSLTTKPGPDNSTHNTPVYKLDISEATQVEQHHRRTDNDSTASDTPSATTAAGPPKAENTNTSKSTDFLDPATTTSPQNHSETAGNNNTHHQDTGEESASSGKLGLITNTIAGVAGLITGGRRTRREAIVNAQPKCNPNLHYWTTQDEGAAIGLAWIPYFGPAAEGIYIEGLMHNQDGLICGLRQLANETTQALQLFLRATTELRTFSILNRKAIDFLLQRWGGTCHILGPDCCIEPHDWTKNITDKIDQIIHDFVDKTLPDQGDNDNWWTGWRQ | ||||||
Transmembrane | 651-671 | Helical | ||||
Sequence: WIPAGIGVTGVIIAVIALFCI | ||||||
Topological domain | 672-676 | Cytoplasmic | ||||
Sequence: CKFVF |
Keywords
- Cellular component
Phenotypes & Variants
Features
Showing features for mutagenesis, natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 40 | Induces GP1 secretion. Complete loss of virus capability to enter into host cell. | ||||
Sequence: N → D | ||||||
Mutagenesis | 53 | Induces GP1 secretion. Complete loss of virus capability to enter into host cell. | ||||
Sequence: C → G | ||||||
Mutagenesis | 55 | 80% loss of virus capability to enter into host cell. | ||||
Sequence: D → A | ||||||
Mutagenesis | 55 | No effect on viral entry. | ||||
Sequence: D → E or K | ||||||
Mutagenesis | 57 | Complete loss of virus capability to enter into host cell. | ||||
Sequence: L → A | ||||||
Mutagenesis | 57 | 90% loss of virus capability to enter into host cell. | ||||
Sequence: L → F, I, or K | ||||||
Mutagenesis | 63 | 90% loss of virus capability to enter into host cell. | ||||
Sequence: L → A | ||||||
Mutagenesis | 63 | Almost complete loss of virus capability to enter into host cell. | ||||
Sequence: L → F | ||||||
Mutagenesis | 63 | Complete loss of virus capability to enter into host cell. | ||||
Sequence: L → K | ||||||
Mutagenesis | 64 | Complete loss of virus capability to enter into host cell. | ||||
Sequence: R → A or E | ||||||
Mutagenesis | 64 | No loss of virus capability to enter into host cell. | ||||
Sequence: R → K | ||||||
Natural variant | 65 | in strain: Isolate mouse-adapted | ||||
Sequence: S → P | ||||||
Mutagenesis | 88 | Complete loss of virus capability to enter into host cell. | ||||
Sequence: F → A or E | ||||||
Mutagenesis | 88 | About 50% loss of ability to counteract host BST2. | ||||
Sequence: F → A | ||||||
Mutagenesis | 88 | No loss of virus capability to enter into host cell. | ||||
Sequence: F → I | ||||||
Mutagenesis | 95 | 80% loss of virus capability to enter into host cell. | ||||
Sequence: K → A or E | ||||||
Mutagenesis | 95 | 20% loss of virus capability to enter into host cell. | ||||
Sequence: K → R | ||||||
Mutagenesis | 108 | Almost complete loss of expression of GP1 and GP2. Almost complete loss of virus capability to enter into host cell. | ||||
Sequence: C → G | ||||||
Mutagenesis | 111 | About 60% loss of ability to counteract host BST2. | ||||
Sequence: L → A | ||||||
Mutagenesis | 121 | Reduced levels of expression of GP1 and GP2. 50% loss of virus capability to enter into host cell. | ||||
Sequence: C → G | ||||||
Mutagenesis | 122 | About 60% loss of ability to counteract host BST2. | ||||
Sequence: L → A | ||||||
Mutagenesis | 135 | Almost complete loss of expression of GP1 and GP2. Complete loss of virus capability to enter into host cell. | ||||
Sequence: C → S | ||||||
Mutagenesis | 147 | Reduced levels of expression of GP1 and GP2. Almost complete loss of virus capability to enter into host cell. | ||||
Sequence: C → S | ||||||
Mutagenesis | 170 | 90% loss of virus capability to enter into host cell. | ||||
Sequence: I → A | ||||||
Mutagenesis | 170 | Complete loss of virus capability to enter into host cell. | ||||
Sequence: I → E | ||||||
Mutagenesis | 170 | 50% loss of virus capability to enter into host cell. | ||||
Sequence: I → F | ||||||
Mutagenesis | 204 | No effect on GP1 and GP2 expression. No loss of virus capability to enter into host cell. | ||||
Sequence: N → D | ||||||
Mutagenesis | 238 | No effect on GP1 and GP2 expression. 12% loss of virus capability to enter into host cell. | ||||
Sequence: N → Y | ||||||
Natural variant | 246 | in strain: Isolate mouse-adapted | ||||
Sequence: S → P | ||||||
Mutagenesis | 257 | No effect on GP1 and GP2 expression. 12% loss of virus capability to enter into host cell. | ||||
Sequence: N → D | ||||||
Mutagenesis | 296 | No effect on GP1 and GP2 expression. 18% loss of virus capability to enter into host cell. | ||||
Sequence: N → D | ||||||
Mutagenesis | 497-501 | Almost complete loss of cleavage between GP1 and GP2. No loss of infectivity. | ||||
Sequence: RRTRR → AGTAA | ||||||
Mutagenesis | 498-501 | No effect on cleavage between GP1 and GP2. | ||||
Sequence: RTRR → ATAA | ||||||
Mutagenesis | 511 | Induces GP1 secretion. Complete loss of virus capability to enter into host cell. | ||||
Sequence: C → G | ||||||
Mutagenesis | 528 | Reduced infectivity. | ||||
Sequence: G → R | ||||||
Mutagenesis | 529 | Reduced infectivity. | ||||
Sequence: L → A or R | ||||||
Mutagenesis | 532 | Reduced infectivity. | ||||
Sequence: I → A | ||||||
Mutagenesis | 532 | Almost complete loss of infectivity. No effect on transport of GP to the cell surface and incorporation onto virions. | ||||
Sequence: I → R | ||||||
Mutagenesis | 535 | Reduced infectivity. | ||||
Sequence: F → A | ||||||
Mutagenesis | 535 | Almost complete loss of infectivity. No effect on transport of GP to the cell surface and incorporation onto virions. | ||||
Sequence: F → R | ||||||
Mutagenesis | 536 | Almost complete loss of infectivity. No effect on transport of GP to the cell surface and incorporation onto virions. | ||||
Sequence: G → A | ||||||
Mutagenesis | 537 | Almost complete loss of infectivity. No effect on transport of GP to the cell surface and incorporation onto virions. | ||||
Sequence: P → R | ||||||
Natural variant | 544 | |||||
Sequence: I → T | ||||||
Mutagenesis | 556 | Induces GP1 secretion. Complete loss of virus capability to enter into host cell. | ||||
Sequence: C → S | ||||||
Mutagenesis | 563 | Reduced levels of expression of GP, GP1 and GP2. 20% loss of virus capability to enter into host cell. | ||||
Sequence: N → D | ||||||
Mutagenesis | 601 | Induces GP1 secretion. Complete loss of virus capability to enter into host cell. | ||||
Sequence: C → S | ||||||
Mutagenesis | 608 | Induces GP1 secretion. Complete loss of virus capability to enter into host cell. | ||||
Sequence: C → G | ||||||
Mutagenesis | 609 | Induces GP1 secretion. Complete loss of virus capability to enter into host cell. | ||||
Sequence: C → G | ||||||
Mutagenesis | 618 | Slightly reduced levels of expression of GP1 and GP2. No loss of virus capability to enter into host cell. | ||||
Sequence: N → D | ||||||
Mutagenesis | 632 | No effect on release of soluble GP1,2delta. | ||||
Sequence: D → V | ||||||
Mutagenesis | 633 | No effect on release of soluble GP1,2delta. | ||||
Sequence: K → R or V | ||||||
Mutagenesis | 634 | 50% loss of release of soluble GP1,2delta. | ||||
Sequence: T → I | ||||||
Mutagenesis | 635 | 60% loss of release of soluble GP1,2delta. | ||||
Sequence: L → V | ||||||
Mutagenesis | 635 | Increased GP shedding. | ||||
Sequence: L → V | ||||||
Mutagenesis | 636 | 60% loss of release of soluble GP1,2delta. | ||||
Sequence: P → A | ||||||
Mutagenesis | 637 | No effect on release of soluble GP1,2delta. | ||||
Sequence: D → E | ||||||
Mutagenesis | 637 | Increased release of soluble GP1,2delta. | ||||
Sequence: D → L or V | ||||||
Mutagenesis | 637 | Decreased GP shedding. | ||||
Sequence: D → V | ||||||
Mutagenesis | 638 | No effect on release of soluble GP1,2delta. | ||||
Sequence: Q → V | ||||||
Mutagenesis | 639 | 40% loss of release of soluble GP1,2delta. | ||||
Sequence: G → V | ||||||
Mutagenesis | 640 | No effect on release of soluble GP1,2delta. | ||||
Sequence: D → V | ||||||
Mutagenesis | 641 | No effect on release of soluble GP1,2delta. | ||||
Sequence: N → A | ||||||
Mutagenesis | 642 | No effect on release of soluble GP1,2delta. | ||||
Sequence: D → V | ||||||
Mutagenesis | 643 | No effect on release of soluble GP1,2delta. | ||||
Sequence: N → A | ||||||
Mutagenesis | 660 | About 60% loss of viral release; when associated with L-664. | ||||
Sequence: G → L | ||||||
Mutagenesis | 664 | About 60% loss of viral release; when associated with L-660. | ||||
Sequence: A → L | ||||||
Mutagenesis | 670 | Reduced palmitoylation. No effect on GP processing and association with retrovirus particle. No loss of virus capability to enter into host cell. Loss of localization to the rafts; when associated with A-670. | ||||
Sequence: C → A | ||||||
Mutagenesis | 670 | 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. Loss of localization to the rafts; when associated with A-672. | ||||
Sequence: C → F | ||||||
Mutagenesis | 672 | Reduced palmitoylation. No effect on GP processing and association with retrovirus particle. No loss of virus capability to enter into host cell. | ||||
Sequence: C → A | ||||||
Mutagenesis | 672 | 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. | ||||
Sequence: C → F |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 3 variants from UniProt as well as other sources including ClinVar and dbSNP.
Chemistry
PTM/Processing
Features
Showing features for signal, chain, glycosylation, disulfide bond, lipidation.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Signal | 1-32 | |||||
Sequence: MGVTGILQLPRDRFKRTSFFLWVIILFQRTFS | ||||||
Chain | PRO_0000037486 | 33-501 | GP1 | |||
Sequence: IPLGVIHNSTLQVSDVDKLVCRDKLSSTNQLRSVGLNLEGNGVATDVPSATKRWGFRSGVPPKVVNYEAGEWAENCYNLEIKKPDGSECLPAAPDGIRGFPRCRYVHKVSGTGPCAGDFAFHKEGAFFLYDRLASTVIYRGTTFAEGVVAFLILPQAKKDFFSSHPLREPVNATEDPSSGYYSTTIRYQATGFGTNETEYLFEVDNLTYVQLESRFTPQFLLQLNETIYTSGKRSNTTGKLIWKVNPEIDTTIGEWAFWETKKNLTRKIRSEELSFTVVSNGAKNISGQSPARTSSDPGTNTTTEDHKIMASENSSAMVQVHSQGREAAVSHLTTLATISTSPQSLTTKPGPDNSTHNTPVYKLDISEATQVEQHHRRTDNDSTASDTPSATTAAGPPKAENTNTSKSTDFLDPATTTSPQNHSETAGNNNTHHQDTGEESASSGKLGLITNTIAGVAGLITGGRRTRR | ||||||
Chain | PRO_0000445686 | 33-637 | Shed GP | |||
Sequence: IPLGVIHNSTLQVSDVDKLVCRDKLSSTNQLRSVGLNLEGNGVATDVPSATKRWGFRSGVPPKVVNYEAGEWAENCYNLEIKKPDGSECLPAAPDGIRGFPRCRYVHKVSGTGPCAGDFAFHKEGAFFLYDRLASTVIYRGTTFAEGVVAFLILPQAKKDFFSSHPLREPVNATEDPSSGYYSTTIRYQATGFGTNETEYLFEVDNLTYVQLESRFTPQFLLQLNETIYTSGKRSNTTGKLIWKVNPEIDTTIGEWAFWETKKNLTRKIRSEELSFTVVSNGAKNISGQSPARTSSDPGTNTTTEDHKIMASENSSAMVQVHSQGREAAVSHLTTLATISTSPQSLTTKPGPDNSTHNTPVYKLDISEATQVEQHHRRTDNDSTASDTPSATTAAGPPKAENTNTSKSTDFLDPATTTSPQNHSETAGNNNTHHQDTGEESASSGKLGLITNTIAGVAGLITGGRRTRREAIVNAQPKCNPNLHYWTTQDEGAAIGLAWIPYFGPAAEGIYIEGLMHNQDGLICGLRQLANETTQALQLFLRATTELRTFSILNRKAIDFLLQRWGGTCHILGPDCCIEPHDWTKNITDKIDQIIHDFVDKTLPD | ||||||
Chain | PRO_0000037485 | 33-676 | Envelope glycoprotein | |||
Sequence: IPLGVIHNSTLQVSDVDKLVCRDKLSSTNQLRSVGLNLEGNGVATDVPSATKRWGFRSGVPPKVVNYEAGEWAENCYNLEIKKPDGSECLPAAPDGIRGFPRCRYVHKVSGTGPCAGDFAFHKEGAFFLYDRLASTVIYRGTTFAEGVVAFLILPQAKKDFFSSHPLREPVNATEDPSSGYYSTTIRYQATGFGTNETEYLFEVDNLTYVQLESRFTPQFLLQLNETIYTSGKRSNTTGKLIWKVNPEIDTTIGEWAFWETKKNLTRKIRSEELSFTVVSNGAKNISGQSPARTSSDPGTNTTTEDHKIMASENSSAMVQVHSQGREAAVSHLTTLATISTSPQSLTTKPGPDNSTHNTPVYKLDISEATQVEQHHRRTDNDSTASDTPSATTAAGPPKAENTNTSKSTDFLDPATTTSPQNHSETAGNNNTHHQDTGEESASSGKLGLITNTIAGVAGLITGGRRTRREAIVNAQPKCNPNLHYWTTQDEGAAIGLAWIPYFGPAAEGIYIEGLMHNQDGLICGLRQLANETTQALQLFLRATTELRTFSILNRKAIDFLLQRWGGTCHILGPDCCIEPHDWTKNITDKIDQIIHDFVDKTLPDQGDNDNWWTGWRQWIPAGIGVTGVIIAVIALFCICKFVF | ||||||
Glycosylation | 40 | N-linked (GlcNAc...) asparagine; by host | ||||
Sequence: N | ||||||
Disulfide bond | 53↔609 | Interchain (between GP1 and GP2 chains) | ||||
Sequence: CRDKLSSTNQLRSVGLNLEGNGVATDVPSATKRWGFRSGVPPKVVNYEAGEWAENCYNLEIKKPDGSECLPAAPDGIRGFPRCRYVHKVSGTGPCAGDFAFHKEGAFFLYDRLASTVIYRGTTFAEGVVAFLILPQAKKDFFSSHPLREPVNATEDPSSGYYSTTIRYQATGFGTNETEYLFEVDNLTYVQLESRFTPQFLLQLNETIYTSGKRSNTTGKLIWKVNPEIDTTIGEWAFWETKKNLTRKIRSEELSFTVVSNGAKNISGQSPARTSSDPGTNTTTEDHKIMASENSSAMVQVHSQGREAAVSHLTTLATISTSPQSLTTKPGPDNSTHNTPVYKLDISEATQVEQHHRRTDNDSTASDTPSATTAAGPPKAENTNTSKSTDFLDPATTTSPQNHSETAGNNNTHHQDTGEESASSGKLGLITNTIAGVAGLITGGRRTRREAIVNAQPKCNPNLHYWTTQDEGAAIGLAWIPYFGPAAEGIYIEGLMHNQDGLICGLRQLANETTQALQLFLRATTELRTFSILNRKAIDFLLQRWGGTCHILGPDCC | ||||||
Disulfide bond | 108↔135 | |||||
Sequence: CYNLEIKKPDGSECLPAAPDGIRGFPRC | ||||||
Disulfide bond | 121↔147 | |||||
Sequence: CLPAAPDGIRGFPRCRYVHKVSGTGPC | ||||||
Glycosylation | 204 | N-linked (GlcNAc...) asparagine; by host | ||||
Sequence: N | ||||||
Glycosylation | 228 | N-linked (GlcNAc...) asparagine; by host | ||||
Sequence: N | ||||||
Glycosylation | 238 | N-linked (GlcNAc...) asparagine; by host | ||||
Sequence: N | ||||||
Glycosylation | 257 | N-linked (GlcNAc...) asparagine; by host | ||||
Sequence: N | ||||||
Glycosylation | 268 | N-linked (GlcNAc...) asparagine; by host | ||||
Sequence: N | ||||||
Glycosylation | 296 | N-linked (GlcNAc...) asparagine; by host | ||||
Sequence: N | ||||||
Glycosylation | 317 | N-linked (GlcNAc...) asparagine; by host | ||||
Sequence: N | ||||||
Glycosylation | 333 | N-linked (GlcNAc...) asparagine; by host | ||||
Sequence: N | ||||||
Glycosylation | 346 | N-linked (GlcNAc...) asparagine; by host | ||||
Sequence: N | ||||||
Glycosylation | 386 | N-linked (GlcNAc...) asparagine; by host | ||||
Sequence: N | ||||||
Glycosylation | 413 | N-linked (GlcNAc...) asparagine; by host | ||||
Sequence: N | ||||||
Glycosylation | 436 | N-linked (GlcNAc...) asparagine; by host | ||||
Sequence: N | ||||||
Glycosylation | 454 | N-linked (GlcNAc...) asparagine; by host | ||||
Sequence: N | ||||||
Glycosylation | 462 | N-linked (GlcNAc...) asparagine; by host | ||||
Sequence: N | ||||||
Chain | PRO_0000037487 | 502-676 | GP2 | |||
Sequence: EAIVNAQPKCNPNLHYWTTQDEGAAIGLAWIPYFGPAAEGIYIEGLMHNQDGLICGLRQLANETTQALQLFLRATTELRTFSILNRKAIDFLLQRWGGTCHILGPDCCIEPHDWTKNITDKIDQIIHDFVDKTLPDQGDNDNWWTGWRQWIPAGIGVTGVIIAVIALFCICKFVF | ||||||
Disulfide bond | 511↔556 | |||||
Sequence: CNPNLHYWTTQDEGAAIGLAWIPYFGPAAEGIYIEGLMHNQDGLIC | ||||||
Glycosylation | 563 | N-linked (GlcNAc...) asparagine; by host | ||||
Sequence: N | ||||||
Disulfide bond | 601↔608 | |||||
Sequence: CHILGPDC | ||||||
Glycosylation | 618 | N-linked (GlcNAc...) asparagine; by host | ||||
Sequence: N | ||||||
Lipidation | 670 | S-palmitoyl cysteine; by host | ||||
Sequence: C | ||||||
Lipidation | 672 | S-palmitoyl cysteine; by host | ||||
Sequence: C |
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.
Shed GP
Glycosylated; glycosylation is essential for the activation of dendritic cells and macrophages.
GP1
O-glycosylated in the mucin-like region.
GP2
Palmitoylation is not required for its function.
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 (PubMed:9576958, PubMed:9614872, PubMed:9882347).
The cleavage site corresponds to the furin optimal cleavage sequence [KR]-X-[KR]-R (PubMed:9576958).
This cleavage does not seem to be required for function (PubMed:9576958).
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 (PubMed:16571833).
This cleaved 19-kDa GP1 can then bind to the host entry receptor NPC1 (PubMed:21866103).
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) (PubMed:15103332).
The cleavage site corresponds to the furin optimal cleavage sequence [KR]-X-[KR]-R (PubMed:9576958).
This cleavage does not seem to be required for function (PubMed:9576958).
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 (PubMed:16571833).
This cleaved 19-kDa GP1 can then bind to the host entry receptor NPC1 (PubMed:21866103).
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) (PubMed:15103332).
Keywords
- PTM
PTM databases
Interaction
Subunit
Envelope glycoprotein
Homotrimer; each monomer consists of a GP1 and a GP2 subunit linked by disulfide bonds (PubMed:35303429).
The resulting peplomers (GP1,2) protrude from the virus surface as spikes. Interacts with host integrin alpha-V/ITGAV (PubMed:15596847).
Interacts with host CLEC10A (PubMed:14990712).
Binds also to host CD209 and CLEC4M/DC-SIGN(R) (PubMed:12050398, PubMed:12504546).
Interacts with host FOLR1 (PubMed:11461707).
Interacts with BST2; this interaction inhibits the antiviral effect of BST2 and this allows viral release from infected cells (PubMed:27707924).
Interacts with host FCN1; this interaction enhances viral entry (PubMed:26984723).
Interacts with host TLR4; this interaction induces cell death in T-lymphocytes or proinflammatory cytokines and SOCS1 production in monocytes (PubMed:19846529, PubMed:28542576).
The resulting peplomers (GP1,2) protrude from the virus surface as spikes. Interacts with host integrin alpha-V/ITGAV (PubMed:15596847).
Interacts with host CLEC10A (PubMed:14990712).
Binds also to host CD209 and CLEC4M/DC-SIGN(R) (PubMed:12050398, PubMed:12504546).
Interacts with host FOLR1 (PubMed:11461707).
Interacts with BST2; this interaction inhibits the antiviral effect of BST2 and this allows viral release from infected cells (PubMed:27707924).
Interacts with host FCN1; this interaction enhances viral entry (PubMed:26984723).
Interacts with host TLR4; this interaction induces cell death in T-lymphocytes or proinflammatory cytokines and SOCS1 production in monocytes (PubMed:19846529, PubMed:28542576).
GP1
Interacts with host entry receptor NPC1.
Shed GP
GP1 and GP2delta are part of GP1,2delta soluble complexes released by ectodomain shedding.
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q05320 | GP Q05320 | 3 | EBI-16200230, EBI-16200230 |
Protein-protein interaction databases
Chemistry
Family & Domains
Features
Showing features for region, compositional bias, coiled coil, motif.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 54-201 | Receptor-binding | ||||
Sequence: RDKLSSTNQLRSVGLNLEGNGVATDVPSATKRWGFRSGVPPKVVNYEAGEWAENCYNLEIKKPDGSECLPAAPDGIRGFPRCRYVHKVSGTGPCAGDFAFHKEGAFFLYDRLASTVIYRGTTFAEGVVAFLILPQAKKDFFSSHPLRE | ||||||
Region | 305-485 | Mucin-like region | ||||
Sequence: ELSFTVVSNGAKNISGQSPARTSSDPGTNTTTEDHKIMASENSSAMVQVHSQGREAAVSHLTTLATISTSPQSLTTKPGPDNSTHNTPVYKLDISEATQVEQHHRRTDNDSTASDTPSATTAAGPPKAENTNTSKSTDFLDPATTTSPQNHSETAGNNNTHHQDTGEESASSGKLGLITNT | ||||||
Region | 315-337 | Disordered | ||||
Sequence: AKNISGQSPARTSSDPGTNTTTE | ||||||
Region | 373-392 | Disordered | ||||
Sequence: TSPQSLTTKPGPDNSTHNTP | ||||||
Region | 402-479 | Disordered | ||||
Sequence: TQVEQHHRRTDNDSTASDTPSATTAAGPPKAENTNTSKSTDFLDPATTTSPQNHSETAGNNNTHHQDTGEESASSGKL | ||||||
Compositional bias | 416-479 | Polar residues | ||||
Sequence: TASDTPSATTAAGPPKAENTNTSKSTDFLDPATTTSPQNHSETAGNNNTHHQDTGEESASSGKL | ||||||
Region | 524-539 | Fusion peptide | ||||
Sequence: GAAIGLAWIPYFGPAA | ||||||
Coiled coil | 554-595 | |||||
Sequence: LICGLRQLANETTQALQLFLRATTELRTFSILNRKAIDFLLQ | ||||||
Coiled coil | 615-634 | |||||
Sequence: WTKNITDKIDQIIHDFVDKT | ||||||
Motif | 660-664 | Important role for host BST2/tetherin antagonism | ||||
Sequence: GVIIA |
Domain
GP1
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 similarities
Belongs to the filoviruses glycoprotein family.
Keywords
- Domain
Family and domain databases
Sequence
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
- Length676
- Mass (Da)74,464
- Last updated1994-02-01 v1
- ChecksumBE8AB3B339F63261
Sequence caution
Features
Showing features for compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 416-479 | Polar residues | ||||
Sequence: TASDTPSATTAAGPPKAENTNTSKSTDFLDPATTTSPQNHSETAGNNNTHHQDTGEESASSGKL |
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)
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
L11365 EMBL· GenBank· DDBJ | AAB81004.1 EMBL· GenBank· DDBJ | Genomic RNA | ||
U31033 EMBL· GenBank· DDBJ | AAA96744.1 EMBL· GenBank· DDBJ | Genomic RNA | Frameshift | |
U23187 EMBL· GenBank· DDBJ | AAC54887.1 EMBL· GenBank· DDBJ | Genomic RNA | ||
AF272001 EMBL· GenBank· DDBJ | AAG40168.1 EMBL· GenBank· DDBJ | Genomic RNA | ||
AY142960 EMBL· GenBank· DDBJ | AAN37507.1 EMBL· GenBank· DDBJ | Genomic RNA | ||
AF086833 EMBL· GenBank· DDBJ | AAD14585.1 EMBL· GenBank· DDBJ | Genomic RNA | ||
AF499101 EMBL· GenBank· DDBJ | AAM76034.1 EMBL· GenBank· DDBJ | Genomic RNA |