Q05128 · VP40_EBOZM

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).

Miscellaneous

Most abundant protein in the virion.

Caution

Acetylation has been show in vitro using purified recombinant proteins. This PTM is unsure util proven in vivo.

GO annotations

all annotationsall molecular functionvirus receptor activitydna bindingrna bindingcytoskeletal motor activitycatalytic activitygtpase activitystructural molecule activitytransporter activitycytoskeletal protein bindinglipid bindingcyclase activityantioxidant activityoxidoreductase activitytransferase activityhydrolase activitylyase activityisomerase activityligase activityprotein tag activitycargo receptor activityhistone bindingprotein folding chaperonetranslation regulator activitynutrient reservoir activityreceptor ligand activitymolecular transducer activitymolecular adaptor activitytoxin activitycell adhesion mediator activitymolecular function regulator activityvirus coreceptor activitycatalytic activity, acting on a proteincatalytic activity, acting on dnacatalytic activity, acting on rnamolecular carrier activitytranscription regulator activitygeneral transcription initiation factor activitymolecular sensor activitymolecular sequestering activityatp-dependent activityother molecular functionall biological processmitotic cell cyclecytokinesiscytoplasmic translationimmune system processmuscle system processcirculatory system processrenal system processrespiratory system processcarbohydrate metabolic processgeneration of precursor metabolites and energydna replicationdna repairdna recombinationchromatin organizationdna-templated transcriptionregulation of dna-templated transcriptiontrna metabolic processprotein foldingprotein glycosylationamino acid metabolic processmodified amino acid metabolic processlipid metabolic processvitamin metabolic processsulfur compound metabolic processintracellular protein transportnucleocytoplasmic transportautophagyinflammatory responsemitochondrion organizationcytoskeleton organizationmicrotubule-based movementperoxisome organizationlysosome organizationchromosome segregationcell adhesionestablishment or maintenance of cell polarityprogrammed cell deathphotosynthesismrna metabolic processsnrna metabolic processvesicle-mediated transportreproductive processdigestive system processsignalingcell differentiationprotein catabolic processextracellular matrix organizationregulatory ncrna-mediated gene silencingtelomere organizationcell junction organizationwound healingribosome biogenesiscilium organizationanatomical structure developmentcell motilitynervous system processendocrine processprotein maturationtransmembrane transportnucleobase-containing small molecule metabolic processhepaticobiliary system processmembrane organizationprotein-containing complex assemblycell wall organization or biogenesisnitrogen cycle metabolic processprotein localization to plasma membranedefense response to other organismdetoxificationmeiotic nuclear divisionmitotic nuclear divisionmitochondrial gene expressioncarbohydrate derivative metabolic processother biological processall cellular componentnuclear chromosomeextracellular regionextracellular spacecell wallnucleusnuclear envelopenucleoplasmchromosomenucleolusmitochondrionlysosomeendosomevacuoleperoxisomeendoplasmic reticulumgolgi apparatuslipid dropletmicrotubule organizing centercytosolribosomecytoskeletonplasma membraneciliumplastidthylakoidexternal encapsulating structureextracellular matrixcytoplasmic vesicleorganelleother cellular component
Cell color indicative of number of GO terms
AspectTerm
Cellular Componentextracellular region
Cellular Componenthost cell
Cellular Componenthost cell endomembrane system
Cellular Componenthost cell late endosome membrane
Cellular Componenthost cell membrane
Cellular Componenthost cell plasma membrane
Cellular Componentmembrane raft
Cellular Componentribonucleoprotein complex
Cellular Componentvirion membrane
Molecular Functionidentical protein binding
Molecular FunctionRNA binding
Molecular Functionstructural constituent of virion
Biological Processintracellular transport of virus
Biological Processsymbiont-mediated suppression of host defenses
Biological Processsymbiont-mediated suppression of host RNAi-mediated antiviral immune response
Biological Processviral budding
Biological Processviral budding from plasma membrane
Biological Processviral budding via host ESCRT complex
Biological Processvirus-mediated perturbation of host defense response

Keywords

Protein family/group databases

Names & Taxonomy

Protein names

  • Recommended name
    Matrix protein VP40
  • Alternative names
    • Ebola VP40
      (eVP40
      )
    • Membrane-associated protein VP40

Gene names

    • Name
      VP40

Organism names

Accessions

  • Primary accession
    Q05128

Proteomes

Subcellular Location

Host cytoplasm
Host cell membrane
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

Phenotypes & Variants

Features

Showing features for mutagenesis.

TypeIDPosition(s)Description
Mutagenesis7Partial loss of budding.
Mutagenesis10-1190% loss of budding.
Mutagenesis10-13Abolishes interaction with host SMURF2.
Mutagenesis11Complete loss of budding.
Mutagenesis13Complete loss of interaction with WW domain containing proteins.
Mutagenesis125Partial loss of RNA-binding. Complete loss of virus infectivity.
Mutagenesis134Complete loss of RNA-binding. Complete loss of virus infectivity.
Mutagenesis21240% loss of budding efficiency. No effect on oligomerization.
Mutagenesis212-21384% loss of budding efficiency. Impaired oligomerization.
Mutagenesis212-21485% loss of budding efficiency. Impaired oligomerization.
Mutagenesis212-21480% loss of budding efficiency. No effect on oligomerization.
Mutagenesis21387% loss of budding efficiency. Impaired oligomerization.
Mutagenesis21340% loss of budding efficiency.
Mutagenesis213-21484% loss of budding efficiency. Impaired oligomerization.
Mutagenesis21465% loss of budding efficiency. No effect on oligomerization.
Mutagenesis326Complete loss of sumoylation.

PTM/Processing

Features

Showing features for chain, cross-link.

TypeIDPosition(s)Description
ChainPRO_00002221641-326Matrix protein VP40
Cross-link326Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in host SUMO1 or SUMO2)

Post-translational modification

Sumoylated with host SUMO1, SUMO2. Sumoylation provides stability to VP40 (PubMed:27849047).
Acetylated by host EP300 in vitro (PubMed:30205953).
Ubiquitinated by host WWP1. This modification mediates efficient viral budding.

Keywords

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).

Binary interactions

TypeEntry 1Entry 2Number of experimentsIntact
BINARY Q05128VP40 Q051284EBI-25753960, EBI-25753960

Protein-protein interaction databases

Family & Domains

Features

Showing features for motif, region.

TypeIDPosition(s)Description
Motif7-10PTAP/PSAP motif
Motif10-13PPXY motif
Motif18-26Essential for interaction with host PDCD6IP/ALIX
Region212-214Important for oligomerization
Region213-326Membrane-binding

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

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    326
  • Mass (Da)
    35,183
  • Last updated
    1994-02-01 v1
  • Checksum
    1AB132C0DB8E9003
MRRVILPTAPPEYMEAIYPVRSNSTIARGGNSNTGFLTPESVNGDTPSNPLRPIADDTIDHASHTPGSVSSAFILEAMVNVISGPKVLMKQIPIWLPLGVADQKTYSFDSTTAAIMLASYTITHFGKATNPLVRVNRLGPGIPDHPLRLLRIGNQAFLQEFVLPPVQLPQYFTFDLTALKLITQPLPAATWTDDTPTGSNGALRPGISFHPKLRPILLPNKSGKKGNSADLTSPEKIQAIMTSLQDFKIVPIDPTKNIMGIEVPETLVHKLTGKKVTSKNGQPIIPVLLPKYIGLDPVAPGDLTMVITQDCDTCHSPASLPAVIEK

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
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

Genome annotation databases

Similar Proteins

Disclaimer

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