ID VP40_EBORR Reviewed; 331 AA. AC Q8JPX9; Q5UAK9; DT 11-JUL-2006, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-2002, sequence version 1. DT 27-MAR-2024, entry version 104. 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 Reston ebolavirus (strain Reston-89) (REBOV) (Reston Ebola virus). OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Haploviricotina; OC Monjiviricetes; Mononegavirales; Filoviridae; Orthoebolavirus; OC Orthoebolavirus restonense; Reston ebolavirus. OX NCBI_TaxID=386032; 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). OH NCBI_TaxID=9823; Sus scrofa (Pig). RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC RNA]. RX PubMed=12191779; DOI=10.1016/s0168-1702(02)00087-4; RA Groseth A., Stroeher U., Theriault S., Feldmann H.; RT "Molecular characterization of an isolate from the 1989/90 epizootic of RT Ebola virus Reston among macaques imported into the United States."; RL Virus Res. 87:155-163(2002). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC RNA]. RC STRAIN=Isolate Pennsylvania-89; RX PubMed=15661171; DOI=10.1016/j.virol.2004.11.018; RA Boehmann Y., Enterlein S., Randolf A., Muehlberger E.I.; RT "A reconstituted replication and transcription system for Ebola virus RT Reston and comparison with Ebola virus Zaire."; RL Virology 332:406-417(2005). 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: Virion membrane {ECO:0000250|UniProtKB:P35260}; CC Peripheral membrane protein {ECO:0000250|UniProtKB:P35260}. Host late CC endosome membrane {ECO:0000250|UniProtKB:P35260}; Peripheral membrane CC protein {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}. Note=In virion, localizes on the CC intravirional side of the membrane. In the host cell, it is found CC associated with virus-induced membrane proliferation foci and probably CC also in multivesicular bodies. These VP40-enriched membrane clusters CC are then redistributed to the plasma membrane where budding takes CC place. {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 -!- MISCELLANEOUS: Most abundant protein in the virion. {ECO:0000250}. CC -!- SIMILARITY: Belongs to the filoviridae matrix protein VP40 family. CC {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF522874; AAN04450.1; -; Genomic_RNA. DR EMBL; AY769362; AAV48576.1; -; Genomic_RNA. DR RefSeq; NP_690582.1; NC_004161.1. DR SMR; Q8JPX9; -. DR GeneID; 955192; -. DR KEGG; vg:955192; -. DR Proteomes; UP000007207; Segment. DR Proteomes; UP000138664; Genome. 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 3: Inferred from homology; KW Host cell membrane; Host endosome; Host membrane; Host-virus interaction; KW Inhibition of host innate immune response by virus; Membrane; KW Ribonucleoprotein; RNA-binding; Suppressor of RNA silencing; 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..331 FT /note="Matrix protein VP40" FT /id="PRO_0000245081" FT REGION 212..214 FT /note="Important for oligomerization" FT /evidence="ECO:0000250" FT REGION 213..331 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 147 FT /note="L -> F (in strain: Isolate Pennsylvania-89)" FT VARIANT 154..155 FT /note="NQ -> KK (in strain: Isolate Pennsylvania-89)" FT VARIANT 159..160 FT /note="QE -> PG (in strain: Isolate Pennsylvania-89)" FT VARIANT 321 FT /note="P -> T (in strain: Isolate Pennsylvania-89)" SQ SEQUENCE 331 AA; 35821 MW; 921510B11D204799 CRC64; MRRGVLPTAP PAYNDIAYPM SILPTRPSVI VNETKSDVLA VPGADVPSNS MRPVADDNID HSSHTPSGVA SAFILEATVN VISGTKVLMK QIPIWLPLGV ADQKIYSFDS TTAAIMLASY TVTHFGKISN PLVRVNRLGP GIPDHPLRLL RLGNQAFLQE FVLPPVQLPQ YFTFDLTALK LITQPLPAAT WTDETPAGAV NALRPGLSLH PKLRPILLPG KTGKKGHASD LTSPDKIQTI MNAIPDLKIV PIDPTKNIVG IEVPELLVQR LTGKKPQPKN GQPIIPVLLP KYVGLDPISP GDLTMVITQD CDSCHSPASH PYHMDKQNSY Q //