ID   VP40_EBOG4              Reviewed;         326 AA.
AC   Q2PDK5; Q913A4;
DT   11-JUL-2006, integrated into UniProtKB/Swiss-Prot.
DT   07-FEB-2006, sequence version 1.
DT   27-MAR-2024, entry version 85.
DE   RecName: Full=Matrix protein VP40;
DE   AltName: Full=Ebola VP40 {ECO:0000250|UniProtKB:Q05128};
DE            Short=eVP40 {ECO:0000250|UniProtKB:Q05128};
DE   AltName: Full=Membrane-associated protein VP40;
GN   Name=VP40;
OS   Zaire ebolavirus (strain Gabon-94) (ZEBOV) (Zaire Ebola virus).
OC   Viruses; Riboviria; Orthornavirae; Negarnaviricota; Haploviricotina;
OC   Monjiviricetes; Mononegavirales; Filoviridae; Orthoebolavirus;
OC   Orthoebolavirus zairense; Zaire ebolavirus.
OX   NCBI_TaxID=128947;
OH   NCBI_TaxID=77231; Epomops franqueti (Franquet's epauletted fruit bat) (Epomophorus franqueti).
OH   NCBI_TaxID=9606; Homo sapiens (Human).
OH   NCBI_TaxID=77243; Myonycteris torquata (Little collared fruit bat).
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RA   Prehaud C.J.;
RT   "VP40 of Ebola virus Gabon 94 strain.";
RL   Submitted (OCT-1997) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=Isolate Bouee-96;
RX   PubMed=11752702; DOI=10.1099/0022-1317-83-1-67;
RA   Leroy E.M., Baize S., Mavoungou E., Apetrei C.;
RT   "Sequence analysis of the GP, NP, VP40 and VP24 genes of Ebola virus
RT   isolated from deceased, surviving and asymptomatically infected individuals
RT   during the 1996 outbreak in Gabon: comparative studies and phylogenetic
RT   characterization.";
RL   J. Gen. Virol. 83:67-73(2002).
CC   -!- FUNCTION: Plays an essential role virus particle assembly and budding.
CC       Acts by interacting with viral ribonucleocapsid and host members of the
CC       ESCRT (endosomal sorting complex required for transport) system such as
CC       host VPS4, PDCD6IP/ALIX, NEDD4 or TGS101. The interaction with host E3
CC       ubiquitin ligase SMURF2 also facilitates virus budding. May play a role
CC       in immune cell dysfunction by being packaged into exosomes that can
CC       decrease the viability of recipient cells (via RNAi suppression and
CC       exosome-bystander apoptosis). {ECO:0000250|UniProtKB:Q05128}.
CC   -!- SUBUNIT: Homodimer. Homohexamer. Homooctamer. Exists as a dimer until
CC       it reorganizes at the plasma membrane into a hexameric form using
CC       phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2). Hexamers are
CC       critical for budding. Octamers function in genome replication and RNA
CC       binding. Interacts with host TSG101. As a homohexamer, interacts with
CC       the WW domain 3 of host NEDD4. Interacts with the nucleoprotein/NP.
CC       Interacts (via YPx(n)L/I motif) with host PDCD6IP/ALIX; this
CC       interaction supports efficient egress of viral particles. Interacts
CC       with VP35. Interacts with host ITCH; this interaction is required for
CC       efficient egress. Interacts (via PPXY motif) with host SMURF2 (via WW
CC       domains); the interaction positively regulates virus budding.
CC       {ECO:0000250|UniProtKB:Q05128}.
CC   -!- SUBCELLULAR LOCATION: Host cytoplasm {ECO:0000250|UniProtKB:Q05128}.
CC       Host cell membrane {ECO:0000250|UniProtKB:Q05128}. Virion membrane
CC       {ECO:0000250|UniProtKB:P35260}; Peripheral membrane protein
CC       {ECO:0000250|UniProtKB:P35260}. Host late endosome membrane
CC       {ECO:0000250|UniProtKB:P35260}; Peripheral membrane protein
CC       {ECO:0000250|UniProtKB:P35260}. Host cell membrane
CC       {ECO:0000250|UniProtKB:P35260}; Peripheral membrane protein
CC       {ECO:0000250|UniProtKB:P35260}; Cytoplasmic side
CC       {ECO:0000250|UniProtKB:P35260}. Host endomembrane system
CC       {ECO:0000250|UniProtKB:P35260}; Peripheral membrane protein
CC       {ECO:0000250|UniProtKB:P35260}. Secreted, extracellular exosome
CC       {ECO:0000250|UniProtKB:Q05128}. Note=In virion, localizes on the inner
CC       side of the membrane. In the host cell, it is found associated with
CC       virus-induced membrane proliferation foci and probably also in
CC       multivesicular bodies. These VP40-enriched membrane clusters are then
CC       redistributed to the plasma membrane where budding takes place.
CC       {ECO:0000250|UniProtKB:P35260}.
CC   -!- DOMAIN: Late-budding domains (L domains) are short sequence motifs
CC       essential for viral particle budding. They recruit proteins of the host
CC       ESCRT machinery (Endosomal Sorting Complex Required for Transport) or
CC       ESCRT-associated proteins. VP40 contains two overlapping L domains: a
CC       PTAP/PSAP motif, which interacts with the UEV domain of TSG101 and a
CC       PPXY motif which interacts with the WW domain 3 of NEDD4 E3 ubiquitin
CC       ligase and the three WW domains of SMURF2 E3 ubiquitin ligase.
CC       {ECO:0000250|UniProtKB:Q05128}.
CC   -!- PTM: Sumoylated with host SUMO1, SUMO2. Sumoylation provides stability
CC       to VP40. {ECO:0000250|UniProtKB:Q05128}.
CC   -!- PTM: Ubiquitinated by host WWP1. This modification mediates efficient
CC       viral budding. {ECO:0000250|UniProtKB:Q05128}.
CC   -!- MISCELLANEOUS: Most abundant protein in the virion.
CC       {ECO:0000250|UniProtKB:Q05128}.
CC   -!- SIMILARITY: Belongs to the filoviridae matrix protein VP40 family.
CC       {ECO:0000305}.
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DR   EMBL; AJ001707; CAC79598.1; -; mRNA.
DR   EMBL; AY058896; AAL25816.1; -; mRNA.
DR   SMR; Q2PDK5; -.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0033645; C:host cell endomembrane system; IEA:UniProtKB-SubCell.
DR   GO; GO:0044185; C:host cell late endosome membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0016020; C:membrane; IEA:UniProtKB-KW.
DR   GO; GO:1990904; C:ribonucleoprotein complex; IEA:UniProtKB-KW.
DR   GO; GO:0055036; C:virion membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
DR   GO; GO:0039660; F:structural constituent of virion; IEA:UniProtKB-KW.
DR   GO; GO:0039702; P:viral budding via host ESCRT complex; IEA:UniProtKB-KW.
DR   Gene3D; 2.60.510.10; EV matrix protein; 1.
DR   Gene3D; 2.70.20.20; Matrix protein VP40, N-terminal domain; 1.
DR   InterPro; IPR008986; EV_matrix.
DR   InterPro; IPR035092; EV_matrix_protein_C.
DR   InterPro; IPR043079; EV_matrix_protein_N.
DR   InterPro; IPR038057; EV_matrix_sf.
DR   Pfam; PF07447; VP40; 1.
DR   PIRSF; PIRSF018327; VP40_FiloV; 1.
DR   SUPFAM; SSF50012; EV matrix protein; 2.
PE   2: Evidence at transcript level;
KW   Host cell membrane; Host cytoplasm; Host endosome; Host membrane;
KW   Host-virus interaction; Inhibition of host innate immune response by virus;
KW   Isopeptide bond; Membrane; Ribonucleoprotein; RNA-binding; Secreted;
KW   Suppressor of RNA silencing; Ubl conjugation; Viral budding;
KW   Viral budding via the host ESCRT complexes; Viral immunoevasion;
KW   Viral matrix protein; Viral release from host cell; Viral RNA replication;
KW   Virion.
FT   CHAIN           1..326
FT                   /note="Matrix protein VP40"
FT                   /id="PRO_0000245079"
FT   REGION          212..214
FT                   /note="Important for oligomerization"
FT                   /evidence="ECO:0000250"
FT   REGION          213..326
FT                   /note="Membrane-binding"
FT                   /evidence="ECO:0000250"
FT   MOTIF           7..10
FT                   /note="PTAP/PSAP motif"
FT   MOTIF           10..13
FT                   /note="PPXY motif"
FT   VARIANT         65
FT                   /note="T -> I (in strain: Isolate Bouee-96)"
FT   VARIANT         233
FT                   /note="F -> S (in strain: Isolate Bouee-96)"
FT   VARIANT         247
FT                   /note="L -> F (in strain: Isolate Bouee-96)"
SQ   SEQUENCE   326 AA;  35209 MW;  8C67320BA6FAD51F CRC64;
     MRRVILPTAP PEYMEAIYPV RSNSTIARGG NSNTGFLTPE SVNGDTPSNP LRPIADDTID
     HASHTPGSVS SAFILEAMVN VISGPKVLMK QIPIWLPLGV ADQKTYSFDS TTAAIMLASY
     TITHFGKATN PLVRVNRLGP GIPDHPLRLL RIGNQAFLQE FVLPPVQLPQ YFTFDLTALK
     LITQPLPAAT WTDDTPTGSN GALRPGISFH PKLRPILLPN KSGKKGNSAD LTFPEKIQAI
     MTSLQDLKIV PIDPTKNIMG IEVPETLVHK LTGKKVTSKN GQPIIPVLLP KYIGLDPVAP
     GDLTMVITQD CDTCHSPASL PAVIEK
//