Q05128 · VP40_EBOZM
- ProteinMatrix protein VP40
- GeneVP40
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids326 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Plays an essential role virus particle assembly and budding (PubMed:16719918, PubMed:33673144).
Acts by interacting with viral ribonucleocapsid and host members of the ESCRT (endosomal sorting complex required for transport) system such as host VPS4, PDCD6IP/ALIX, NEDD4 or TGS101 (PubMed:15892969, PubMed:16719918, PubMed:23637409, PubMed:25786915, PubMed:26753796, PubMed:27489272).
The interaction with host E3 ubiquitin ligase SMURF2 also facilitates virus budding (PubMed:33673144).
May play a role in immune cell dysfunction by being packaged into exosomes that can decrease the viability of recipient cells (via RNAi suppression and exosome-bystander apoptosis) (PubMed:27872619).
Acts by interacting with viral ribonucleocapsid and host members of the ESCRT (endosomal sorting complex required for transport) system such as host VPS4, PDCD6IP/ALIX, NEDD4 or TGS101 (PubMed:15892969, PubMed:16719918, PubMed:23637409, PubMed:25786915, PubMed:26753796, PubMed:27489272).
The interaction with host E3 ubiquitin ligase SMURF2 also facilitates virus budding (PubMed:33673144).
May play a role in immune cell dysfunction by being packaged into exosomes that can decrease the viability of recipient cells (via RNAi suppression and exosome-bystander apoptosis) (PubMed:27872619).
Miscellaneous
Most abundant protein in the virion.
GO annotations
all annotations | all molecular function | virus receptor activity | dna binding | rna binding | cytoskeletal motor activity | catalytic activity | gtpase activity | structural molecule activity | transporter activity | cytoskeletal protein binding | lipid binding | cyclase activity | antioxidant activity | oxidoreductase activity | transferase activity | hydrolase activity | lyase activity | isomerase activity | ligase activity | protein tag activity | cargo receptor activity | histone binding | protein folding chaperone | translation regulator activity | nutrient reservoir activity | receptor ligand activity | molecular transducer activity | molecular adaptor activity | toxin activity | cell adhesion mediator activity | molecular function regulator activity | virus coreceptor activity | catalytic activity, acting on a protein | catalytic activity, acting on dna | catalytic activity, acting on rna | molecular carrier activity | transcription regulator activity | general transcription initiation factor activity | molecular sensor activity | molecular sequestering activity | atp-dependent activity | other molecular function | all biological process | mitotic cell cycle | cytokinesis | cytoplasmic translation | immune system process | muscle system process | circulatory system process | renal system process | respiratory system process | carbohydrate metabolic process | generation of precursor metabolites and energy | dna replication | dna repair | dna recombination | chromatin organization | dna-templated transcription | regulation of dna-templated transcription | trna metabolic process | protein folding | protein glycosylation | amino acid metabolic process | modified amino acid metabolic process | lipid metabolic process | vitamin metabolic process | sulfur compound metabolic process | intracellular protein transport | nucleocytoplasmic transport | autophagy | inflammatory response | mitochondrion organization | cytoskeleton organization | microtubule-based movement | peroxisome organization | lysosome organization | chromosome segregation | cell adhesion | establishment or maintenance of cell polarity | programmed cell death | photosynthesis | mrna metabolic process | snrna metabolic process | vesicle-mediated transport | reproductive process | digestive system process | signaling | cell differentiation | protein catabolic process | extracellular matrix organization | regulatory ncrna-mediated gene silencing | telomere organization | cell junction organization | wound healing | ribosome biogenesis | cilium organization | anatomical structure development | cell motility | nervous system process | endocrine process | protein maturation | transmembrane transport | nucleobase-containing small molecule metabolic process | hepaticobiliary system process | membrane organization | protein-containing complex assembly | cell wall organization or biogenesis | nitrogen cycle metabolic process | protein localization to plasma membrane | defense response to other organism | detoxification | meiotic nuclear division | mitotic nuclear division | mitochondrial gene expression | carbohydrate derivative metabolic process | other biological process | all cellular component | nuclear chromosome | extracellular region | extracellular space | cell wall | nucleus | nuclear envelope | nucleoplasm | chromosome | nucleolus | mitochondrion | lysosome | endosome | vacuole | peroxisome | endoplasmic reticulum | golgi apparatus | lipid droplet | microtubule organizing center | cytosol | ribosome | cytoskeleton | plasma membrane | cilium | plastid | thylakoid | external encapsulating structure | extracellular matrix | cytoplasmic vesicle | organelle | other cellular component | |||
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Aspect | Term | |
---|---|---|
Cellular Component | extracellular region | |
Cellular Component | host cell | |
Cellular Component | host cell endomembrane system | |
Cellular Component | host cell late endosome membrane | |
Cellular Component | host cell membrane | |
Cellular Component | host cell plasma membrane | |
Cellular Component | membrane raft | |
Cellular Component | ribonucleoprotein complex | |
Cellular Component | virion membrane | |
Molecular Function | identical protein binding | |
Molecular Function | RNA binding | |
Molecular Function | structural constituent of virion | |
Biological Process | intracellular transport of virus | |
Biological Process | symbiont-mediated suppression of host defenses | |
Biological Process | symbiont-mediated suppression of host RNAi-mediated antiviral immune response | |
Biological Process | viral budding | |
Biological Process | viral budding from plasma membrane | |
Biological Process | viral budding via host ESCRT complex | |
Biological Process | virus-mediated perturbation of host defense response |
Keywords
- Molecular function
- Biological process
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameMatrix protein VP40
- Alternative names
Gene names
Organism names
- Strain
- Taxonomic lineageViruses > Riboviria > Orthornavirae > Negarnaviricota > Haploviricotina > Monjiviricetes > Mononegavirales > Filoviridae > Orthoebolavirus > Orthoebolavirus zairense > Zaire ebolavirus
- Virus hosts
Accessions
- Primary accessionQ05128
Proteomes
Subcellular Location
UniProt Annotation
GO Annotation
Virion membrane ; Peripheral membrane protein
Host late endosome membrane ; Peripheral membrane protein
Host cell membrane ; Peripheral membrane protein
Host endomembrane system ; Peripheral membrane protein
Note: In virion, localizes on the inner side of the membrane. In the host cell, it is found associated with virus-induced membrane proliferation foci and probably also in multivesicular bodies. These VP40-enriched membrane clusters are then redistributed to the plasma membrane where budding takes place.
Keywords
- Cellular component
Phenotypes & Variants
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 7 | Partial loss of budding. | ||||
Sequence: P → A | ||||||
Mutagenesis | 10-11 | 90% loss of budding. | ||||
Sequence: PP → AA | ||||||
Mutagenesis | 10-13 | Abolishes interaction with host SMURF2. | ||||
Sequence: PPEY → AAEA | ||||||
Mutagenesis | 11 | Complete loss of budding. | ||||
Sequence: P → A | ||||||
Mutagenesis | 13 | Complete loss of interaction with WW domain containing proteins. | ||||
Sequence: Y → A | ||||||
Mutagenesis | 125 | Partial loss of RNA-binding. Complete loss of virus infectivity. | ||||
Sequence: F → A | ||||||
Mutagenesis | 134 | Complete loss of RNA-binding. Complete loss of virus infectivity. | ||||
Sequence: R → A | ||||||
Mutagenesis | 212 | 40% loss of budding efficiency. No effect on oligomerization. | ||||
Sequence: K → A | ||||||
Mutagenesis | 212-213 | 84% loss of budding efficiency. Impaired oligomerization. | ||||
Sequence: KL → AA | ||||||
Mutagenesis | 212-214 | 85% loss of budding efficiency. Impaired oligomerization. | ||||
Sequence: KLR → AAA | ||||||
Mutagenesis | 212-214 | 80% loss of budding efficiency. No effect on oligomerization. | ||||
Sequence: KLR → ALA | ||||||
Mutagenesis | 213 | 87% loss of budding efficiency. Impaired oligomerization. | ||||
Sequence: L → A | ||||||
Mutagenesis | 213 | 40% loss of budding efficiency. | ||||
Sequence: L → I | ||||||
Mutagenesis | 213-214 | 84% loss of budding efficiency. Impaired oligomerization. | ||||
Sequence: LR → AA | ||||||
Mutagenesis | 214 | 65% loss of budding efficiency. No effect on oligomerization. | ||||
Sequence: R → A | ||||||
Mutagenesis | 326 | Complete loss of sumoylation. | ||||
Sequence: K → R |
PTM/Processing
Features
Showing features for chain, cross-link.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000222164 | 1-326 | Matrix protein VP40 | |||
Sequence: MRRVILPTAPPEYMEAIYPVRSNSTIARGGNSNTGFLTPESVNGDTPSNPLRPIADDTIDHASHTPGSVSSAFILEAMVNVISGPKVLMKQIPIWLPLGVADQKTYSFDSTTAAIMLASYTITHFGKATNPLVRVNRLGPGIPDHPLRLLRIGNQAFLQEFVLPPVQLPQYFTFDLTALKLITQPLPAATWTDDTPTGSNGALRPGISFHPKLRPILLPNKSGKKGNSADLTSPEKIQAIMTSLQDFKIVPIDPTKNIMGIEVPETLVHKLTGKKVTSKNGQPIIPVLLPKYIGLDPVAPGDLTMVITQDCDTCHSPASLPAVIEK | ||||||
Cross-link | 326 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in host SUMO1 or SUMO2) | ||||
Sequence: K |
Post-translational modification
Sumoylated with host SUMO1, SUMO2. Sumoylation provides stability to VP40 (PubMed:27849047).
Acetylated by host EP300 in vitro (PubMed:30205953).
Acetylated by host EP300 in vitro (PubMed:30205953).
Ubiquitinated by host WWP1. This modification mediates efficient viral budding.
Keywords
- PTM
Interaction
Subunit
Homodimer (PubMed:23953110).
Homohexamer (PubMed:11118208, PubMed:23953110).
Homooctamer (PubMed:12919741).
Exists as a dimer until it reorganizes at the plasma membrane into a hexameric form using phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) (PubMed:23953110, PubMed:25159197, PubMed:26753796, PubMed:29950600).
Hexamers are critical for budding (PubMed:23953110).
Octamers function in genome replication and RNA binding (PubMed:12919741).
Interacts with host TSG101 (PubMed:12559917).
As a homohexamer, interacts with the WW domain 3 of host NEDD4 (PubMed:11095724, PubMed:12559917).
Interacts with the nucleoprotein/NP (PubMed:17229682, PubMed:21987757).
Interacts (via YPx(n)L/I motif) with host PDCD6IP/ALIX; this interaction supports efficient egress of viral particles (PubMed:25786915).
Interacts with VP35 (PubMed:16698994).
Interacts with host ITCH; this interaction is required for efficient egress (PubMed:27489272).
Interacts (via PPXY motif) with host SMURF2 (via WW domains); the interaction positively regulates virus budding (PubMed:33673144).
Homohexamer (PubMed:11118208, PubMed:23953110).
Homooctamer (PubMed:12919741).
Exists as a dimer until it reorganizes at the plasma membrane into a hexameric form using phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) (PubMed:23953110, PubMed:25159197, PubMed:26753796, PubMed:29950600).
Hexamers are critical for budding (PubMed:23953110).
Octamers function in genome replication and RNA binding (PubMed:12919741).
Interacts with host TSG101 (PubMed:12559917).
As a homohexamer, interacts with the WW domain 3 of host NEDD4 (PubMed:11095724, PubMed:12559917).
Interacts with the nucleoprotein/NP (PubMed:17229682, PubMed:21987757).
Interacts (via YPx(n)L/I motif) with host PDCD6IP/ALIX; this interaction supports efficient egress of viral particles (PubMed:25786915).
Interacts with VP35 (PubMed:16698994).
Interacts with host ITCH; this interaction is required for efficient egress (PubMed:27489272).
Interacts (via PPXY motif) with host SMURF2 (via WW domains); the interaction positively regulates virus budding (PubMed:33673144).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q05128 | VP40 Q05128 | 4 | EBI-25753960, EBI-25753960 |
Protein-protein interaction databases
Family & Domains
Features
Showing features for motif, region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Motif | 7-10 | PTAP/PSAP motif | ||||
Sequence: PTAP | ||||||
Motif | 10-13 | PPXY motif | ||||
Sequence: PPEY | ||||||
Motif | 18-26 | Essential for interaction with host PDCD6IP/ALIX | ||||
Sequence: YPVRSNSTI | ||||||
Region | 212-214 | Important for oligomerization | ||||
Sequence: KLR | ||||||
Region | 213-326 | Membrane-binding | ||||
Sequence: LRPILLPNKSGKKGNSADLTSPEKIQAIMTSLQDFKIVPIDPTKNIMGIEVPETLVHKLTGKKVTSKNGQPIIPVLLPKYIGLDPVAPGDLTMVITQDCDTCHSPASLPAVIEK |
Domain
Late-budding domains (L domains) are short sequence motifs essential for viral particle budding. They recruit proteins of the host ESCRT machinery (Endosomal Sorting Complex Required for Transport) or ESCRT-associated proteins. VP40 contains two overlapping L domains: a PTAP/PSAP motif, which interacts with the UEV domain of TSG101 and a PPXY motif which interacts with the WW domain 3 of NEDD4 E3 ubiquitin ligase and the three WW domains of SMURF2 E3 ubiquitin ligase.
Sequence similarities
Belongs to the filoviridae matrix protein VP40 family.
Family and domain databases
Sequence
- Sequence statusComplete
- Length326
- Mass (Da)35,183
- Last updated1994-02-01 v1
- Checksum1AB132C0DB8E9003
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
X61274 EMBL· GenBank· DDBJ | CAA43579.1 EMBL· GenBank· DDBJ | Genomic RNA | ||
L11365 EMBL· GenBank· DDBJ | AAB81003.1 EMBL· GenBank· DDBJ | Genomic RNA | ||
AF086833 EMBL· GenBank· DDBJ | AAD14583.1 EMBL· GenBank· DDBJ | Genomic RNA | ||
AF272001 EMBL· GenBank· DDBJ | AAG40166.1 EMBL· GenBank· DDBJ | Genomic RNA | ||
AF499101 EMBL· GenBank· DDBJ | AAM76033.1 EMBL· GenBank· DDBJ | Genomic RNA | ||
AY142960 EMBL· GenBank· DDBJ | AAN37506.1 EMBL· GenBank· DDBJ | Genomic RNA |