UniProt functional annotation for Q05128



	UniProt functional annotation for Q05128

UniProt code: Q05128.

Organism: Zaire ebolavirus (strain Mayinga-76) (ZEBOV) (Zaire Ebola virus).

Taxonomy: Viruses; Riboviria; Orthornavirae; Negarnaviricota; Haploviricotina; Monjiviricetes; Mononegavirales; Filoviridae; Ebolavirus.

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). {ECO:0000269|PubMed:15892969, ECO:0000269|PubMed:16719918, ECO:0000269|PubMed:23637409, ECO:0000269|PubMed:25786915, ECO:0000269|PubMed:26753796, ECO:0000269|PubMed:27489272, ECO:0000269|PubMed:27872619, ECO:0000269|PubMed:33673144}.

Subunit: Homodimer (PubMed:23953110). Homohexamer (PubMed:23953110, PubMed:11118208). 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). {ECO:0000269|PubMed:11095724, ECO:0000269|PubMed:11118208, ECO:0000269|PubMed:12559917, ECO:0000269|PubMed:12919741, ECO:0000269|PubMed:16698994, ECO:0000269|PubMed:17229682, ECO:0000269|PubMed:21987757, ECO:0000269|PubMed:23953110, ECO:0000269|PubMed:25159197, ECO:0000269|PubMed:25786915, ECO:0000269|PubMed:26753796, ECO:0000269|PubMed:27489272, ECO:0000269|PubMed:29950600, ECO:0000269|PubMed:33673144}.

Subcellular location: Host cytoplasm {ECO:0000269|PubMed:21987757}. Host cell membrane {ECO:0000269|PubMed:21987757, ECO:0000269|PubMed:26753796, ECO:0000269|PubMed:28768865}. Virion membrane {ECO:0000250|UniProtKB:P35260}; Peripheral membrane protein {ECO:0000250|UniProtKB:P35260}. Host late endosome membrane {ECO:0000250|UniProtKB:P35260}; Peripheral membrane protein {ECO:0000250|UniProtKB:P35260}. Host cell membrane {ECO:0000250|UniProtKB:P35260}; Peripheral membrane protein {ECO:0000250|UniProtKB:P35260}; Cytoplasmic side {ECO:0000250|UniProtKB:P35260}. Host endomembrane system {ECO:0000250|UniProtKB:P35260}; Peripheral membrane protein {ECO:0000250|UniProtKB:P35260}. Secreted, extracellular exosome {ECO:0000269|PubMed:27872619}. 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. {ECO:0000250|UniProtKB:P35260}.

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. {ECO:0000269|PubMed:11095724, ECO:0000269|PubMed:12559917, ECO:0000269|PubMed:33673144}.

Ptm: Sumoylated with host SUMO1, SUMO2. Sumoylation provides stability to VP40 (PubMed:27849047). Acetylated by host EP300 in vitro (PubMed:30205953). {ECO:0000269|PubMed:27849047, ECO:0000269|PubMed:30205953}.

Ptm: Ubiquitinated by host WWP1. This modification mediates efficient viral budding. {ECO:0000269|PubMed:28768865}.

Miscellaneous: Most abundant protein in the virion.

Similarity: Belongs to the filoviridae matrix protein VP40 family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Zaire ebolavirus (strain Mayinga-76) (ZEBOV) (Zaire Ebola virus).
Taxonomy:		Viruses; Riboviria; Orthornavirae; Negarnaviricota; Haploviricotina; Monjiviricetes; Mononegavirales; Filoviridae; Ebolavirus.



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). {ECO:0000269\|PubMed:15892969, ECO:0000269\|PubMed:16719918, ECO:0000269\|PubMed:23637409, ECO:0000269\|PubMed:25786915, ECO:0000269\|PubMed:26753796, ECO:0000269\|PubMed:27489272, ECO:0000269\|PubMed:27872619, ECO:0000269\|PubMed:33673144}.


Subunit:		Homodimer (PubMed:23953110). Homohexamer (PubMed:23953110, PubMed:11118208). 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). {ECO:0000269\|PubMed:11095724, ECO:0000269\|PubMed:11118208, ECO:0000269\|PubMed:12559917, ECO:0000269\|PubMed:12919741, ECO:0000269\|PubMed:16698994, ECO:0000269\|PubMed:17229682, ECO:0000269\|PubMed:21987757, ECO:0000269\|PubMed:23953110, ECO:0000269\|PubMed:25159197, ECO:0000269\|PubMed:25786915, ECO:0000269\|PubMed:26753796, ECO:0000269\|PubMed:27489272, ECO:0000269\|PubMed:29950600, ECO:0000269\|PubMed:33673144}.
Subcellular location:		Host cytoplasm {ECO:0000269\|PubMed:21987757}. Host cell membrane {ECO:0000269\|PubMed:21987757, ECO:0000269\|PubMed:26753796, ECO:0000269\|PubMed:28768865}. Virion membrane {ECO:0000250\|UniProtKB:P35260}; Peripheral membrane protein {ECO:0000250\|UniProtKB:P35260}. Host late endosome membrane {ECO:0000250\|UniProtKB:P35260}; Peripheral membrane protein {ECO:0000250\|UniProtKB:P35260}. Host cell membrane {ECO:0000250\|UniProtKB:P35260}; Peripheral membrane protein {ECO:0000250\|UniProtKB:P35260}; Cytoplasmic side {ECO:0000250\|UniProtKB:P35260}. Host endomembrane system {ECO:0000250\|UniProtKB:P35260}; Peripheral membrane protein {ECO:0000250\|UniProtKB:P35260}. Secreted, extracellular exosome {ECO:0000269\|PubMed:27872619}. 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. {ECO:0000250\|UniProtKB:P35260}.
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. {ECO:0000269\|PubMed:11095724, ECO:0000269\|PubMed:12559917, ECO:0000269\|PubMed:33673144}.
Ptm:		Sumoylated with host SUMO1, SUMO2. Sumoylation provides stability to VP40 (PubMed:27849047). Acetylated by host EP300 in vitro (PubMed:30205953). {ECO:0000269\|PubMed:27849047, ECO:0000269\|PubMed:30205953}.
Ptm:		Ubiquitinated by host WWP1. This modification mediates efficient viral budding. {ECO:0000269\|PubMed:28768865}.
Miscellaneous:		Most abundant protein in the virion.
Similarity:		Belongs to the filoviridae matrix protein VP40 family. {ECO:0000305}.