ID VP40_EBOZM Reviewed; 326 AA. AC Q05128; DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot. DT 01-FEB-1994, sequence version 1. DT 27-MAR-2024, entry version 133. DE RecName: Full=Matrix protein VP40; DE AltName: Full=Ebola VP40 {ECO:0000303|PubMed:28768865}; DE Short=eVP40 {ECO:0000303|PubMed:28768865}; DE AltName: Full=Membrane-associated protein VP40; GN Name=VP40; OS Zaire ebolavirus (strain Mayinga-76) (ZEBOV) (Zaire Ebola virus). OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Haploviricotina; OC Monjiviricetes; Mononegavirales; Filoviridae; Orthoebolavirus; OC Orthoebolavirus zairense; Zaire ebolavirus. OX NCBI_TaxID=128952; 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 [GENOMIC RNA]. RX PubMed=8482365; DOI=10.1016/0014-5793(93)81107-b; RA Bukreyev A.A., Volchkov V.E., Blinov V.M., Netesov S.V.; RT "The VP35 and VP40 proteins of filoviruses. Homology between Marburg and RT Ebola viruses."; RL FEBS Lett. 322:41-46(1993). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC RNA]. RX PubMed=8237108; DOI=10.1016/0168-1702(93)90063-s; RA Sanchez A., Kiley M.P., Holloway B.P., Auperin D.D.; RT "Sequence analysis of the Ebola virus genome: organization, genetic RT elements, and comparison with the genome of Marburg virus."; RL Virus Res. 29:215-240(1993). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC RNA]. RX PubMed=10073695; DOI=10.1099/0022-1317-80-2-355; RA Volchkov V.E., Volchkova V.A., Chepurnov A.A., Blinov V.M., Netesov S.V., RA Feldmann H.; RT "Characterization of the L gene and 5' trailer region of Ebola virus."; RL J. Gen. Virol. 80:355-362(1999). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC RNA]. RC STRAIN=Isolate guinea pig-adapted; RX PubMed=11062045; DOI=10.1006/viro.2000.0572; RA Volchkov V.E., Chepurnov A.A., Volchkova V.A., Ternovoj V.A., Klenk H.D.; RT "Molecular characterization of guinea pig-adapted variants of Ebola RT virus."; RL Virology 277:147-155(2000). RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC RNA]. RA Wilson J.A., Kondig J.P., Kuehne A.I., Hart M.K.; RL Submitted (AUG-2002) to the EMBL/GenBank/DDBJ databases. RN [6] RP SUBUNIT. RX PubMed=11118208; DOI=10.1093/emboj/19.24.6732; RA Scianimanico S., Schoehn G., Timmins J., Ruigrok R.H., Klenk H.D., RA Weissenhorn W.; RT "Membrane association induces a conformational change in the Ebola virus RT matrix protein."; RL EMBO J. 19:6732-6741(2000). RN [7] RP INTERACTION WITH WW DOMAINS OF HOST UBIQUITIN LIGASES, AND MUTAGENESIS OF RP TYR-13. RX PubMed=11095724; DOI=10.1073/pnas.250277297; RA Harty R.N., Brown M.E., Wang G., Huibregtse J., Hayes F.P.; RT "A PPxY motif within the VP40 protein of Ebola virus interacts physically RT and functionally with a ubiquitin ligase: implications for filovirus RT budding."; RL Proc. Natl. Acad. Sci. U.S.A. 97:13871-13876(2000). RN [8] RP SUBUNIT. RX PubMed=12919741; DOI=10.1016/s0042-6822(03)00260-5; RA Timmins J., Schoehn G., Kohlhaas C., Klenk H.D., Ruigrok R.W., RA Weissenhorn W.; RT "Oligomerization and polymerization of the filovirus matrix protein VP40."; RL Virology 312:359-368(2003). RN [9] RP INTERACTION WITH HUMAN TSG101 AND NEDD4. RX PubMed=12559917; DOI=10.1016/s0022-2836(02)01406-7; RA Timmins J., Schoehn G., Ricard-Blum S., Scianimanico S., Vernet T., RA Ruigrok R.W., Weissenhorn W.; RT "Ebola virus matrix protein VP40 interaction with human cellular factors RT Tsg101 and Nedd4."; RL J. Mol. Biol. 326:493-502(2003). RN [10] RP MUTAGENESIS OF PRO-7 AND 10-PRO-PRO-11. RX PubMed=16051823; DOI=10.1128/jvi.79.16.10300-10307.2005; RA Neumann G., Ebihara H., Takada A., Noda T., Kobasa D., Jasenosky L.D., RA Watanabe S., Kim J.H., Feldmann H., Kawaoka Y.; RT "Ebola virus VP40 late domains are not essential for viral replication in RT cell culture."; RL J. Virol. 79:10300-10307(2005). RN [11] RP SUBUNIT. RX PubMed=15908231; DOI=10.1016/j.jsb.2005.02.013; RA Nguyen T.L., Schoehn G., Weissenhorn W., Hermone A.R., Burnett J.C., RA Panchal R.G., McGrath C., Zaharevitz D.W., Aman M.J., Gussio R., Bavari S.; RT "An all-atom model of the pore-like structure of hexameric VP40 from Ebola: RT structural insights into the monomer-hexamer transition."; RL J. Struct. Biol. 151:30-40(2005). RN [12] RP MUTAGENESIS OF PHE-125 AND ARG-134. RX PubMed=15650213; DOI=10.1128/jvi.79.3.1898-1905.2005; RA Hoenen T., Volchkov V., Kolesnikova L., Mittler E., Timmins J., Ottmann M., RA Reynard O., Becker S., Weissenhorn W.; RT "VP40 octamers are essential for Ebola virus replication."; RL J. Virol. 79:1898-1905(2005). RN [13] RP FUNCTION. RX PubMed=15892969; DOI=10.1016/j.virol.2005.03.027; RA Irie T., Licata J.M., Harty R.N.; RT "Functional characterization of Ebola virus L-domains using VSV RT recombinants."; RL Virology 336:291-298(2005). RN [14] RP FUNCTION. RX PubMed=16719918; DOI=10.1186/1743-422x-3-31; RA Johnson R.F., Bell P., Harty R.N.; RT "Effect of Ebola virus proteins GP, NP and VP35 on VP40 VLP morphology."; RL Virol. J. 3:31-31(2006). RN [15] RP INTERACTION WITH VP35. RX PubMed=16698994; DOI=10.1128/jvi.01857-05; RA Johnson R.F., McCarthy S.E., Godlewski P.J., Harty R.N.; RT "Ebola virus VP35-VP40 interaction is sufficient for packaging 3E-5E RT minigenome RNA into virus-like particles."; RL J. Virol. 80:5135-5144(2006). RN [16] RP INTERACTION WITH THE NUCLEOPROTEIN. RX PubMed=17229682; DOI=10.1128/jvi.02183-06; RA Noda T., Watanabe S., Sagara H., Kawaoka Y.; RT "Mapping of the VP40-binding regions of the nucleoprotein of Ebola virus."; RL J. Virol. 81:3554-3562(2007). RN [17] RP MUTAGENESIS OF 212-LYS--ARG-214. RX PubMed=17699576; DOI=10.1128/jvi.00853-07; RA McCarthy S.E., Johnson R.F., Zhang Y.-A., Sunyer J.O., Harty R.N.; RT "Role for amino acids 212KLR214 of Ebola virus VP40 in assembly and RT budding."; RL J. Virol. 81:11452-11460(2007). RN [18] RP INTERACTION WITH NP, AND SUBCELLULAR LOCATION. RX PubMed=21987757; DOI=10.1093/infdis/jir293; RA Liu Y., Stone S., Harty R.N.; RT "Characterization of filovirus protein-protein interactions in mammalian RT cells using bimolecular complementation."; RL J. Infect. Dis. 204:817-824(2011). RN [19] RP FUNCTION, INTERACTION WITH HOST IQGAP1, AND SUBCELLULAR LOCATION. RX PubMed=23637409; DOI=10.1128/jvi.00470-13; RA Lu J., Qu Y., Liu Y., Jambusaria R., Han Z., Ruthel G., Freedman B.D., RA Harty R.N.; RT "Host IQGAP1 and Ebola virus VP40 interactions facilitate virus-like RT particle egress."; RL J. Virol. 87:7777-7780(2013). RN [20] RP SUBUNIT. RX PubMed=23953110; DOI=10.1016/j.cell.2013.07.015; RA Bornholdt Z.A., Noda T., Abelson D.M., Halfmann P., Wood M.R., Kawaoka Y., RA Saphire E.O.; RT "Structural rearrangement of ebola virus VP40 begets multiple functions in RT the virus life cycle."; RL Cell 154:763-774(2013). RN [21] RP REVIEW. RX PubMed=25159197; DOI=10.1002/pro.2541; RA Radzimanowski J., Effantin G., Weissenhorn W.; RT "Conformational plasticity of the Ebola virus matrix protein."; RL Protein Sci. 23:1519-1527(2014). RN [22] RP FUNCTION, INTERACTION WITH HOST PDCD6IP/ALIX, AND MOTIF. RX PubMed=25786915; DOI=10.1093/infdis/jiu838; RA Han Z., Madara J.J., Liu Y., Liu W., Ruthel G., Freedman B.D., Harty R.N.; RT "ALIX Rescues Budding of a Double PTAP/PPEY L-Domain Deletion Mutant of RT Ebola VP40: A Role for ALIX in Ebola Virus Egress."; RL J. Infect. Dis. 212:S138-S145(2015). RN [23] RP FUNCTION, AND INTERACTION WITH HOST ITCH. RX PubMed=27489272; DOI=10.1128/jvi.01078-16; RA Han Z., Sagum C.A., Bedford M.T., Sidhu S.S., Sudol M., Harty R.N.; RT "ITCH E3 Ubiquitin Ligase Interacts with Ebola Virus VP40 To Regulate RT Budding."; RL J. Virol. 90:9163-9171(2016). RN [24] RP SUBCELLULAR LOCATION, SUBUNIT, AND FUNCTION. RX PubMed=26753796; DOI=10.1038/srep19125; RA Johnson K.A., Taghon G.J., Scott J.L., Stahelin R.V.; RT "The Ebola Virus matrix protein, VP40, requires phosphatidylinositol 4,5- RT bisphosphate (PI(4,5)P2) for extensive oligomerization at the plasma RT membrane and viral egress."; RL Sci. Rep. 6:19125-19125(2016). RN [25] RP SUMOYLATION AT LYS-326, AND MUTAGENESIS OF LYS-326. RX PubMed=27849047; DOI=10.1038/srep37258; RA Baz-Martinez M., El Motiam A., Ruibal P., Condezo G.N., RA de la Cruz-Herrera C.F., Lang V., Collado M., San Martin C., RA Rodriguez M.S., Munoz-Fontela C., Rivas C.; RT "Regulation of Ebola virus VP40 matrix protein by SUMO."; RL Sci. Rep. 6:37258-37258(2016). RN [26] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=27872619; DOI=10.3389/fmicb.2016.01765; RA Pleet M.L., Mathiesen A., DeMarino C., Akpamagbo Y.A., Barclay R.A., RA Schwab A., Iordanskiy S., Sampey G.C., Lepene B., Nekhai S., Aman M.J., RA Kashanchi F.; RT "Ebola VP40 in Exosomes Can Cause Immune Cell Dysfunction."; RL Front. Microbiol. 7:1765-1765(2016). RN [27] RP SUBCELLULAR LOCATION, UBIQUITINATION BY HOST WWP1, AND NOMENCLATURE. RX PubMed=28768865; DOI=10.1128/jvi.00812-17; RA Han Z., Sagum C.A., Takizawa F., Ruthel G., Berry C.T., Kong J., RA Sunyer J.O., Freedman B.D., Bedford M.T., Sidhu S.S., Sudol M., Harty R.N.; RT "Ubiquitin Ligase WWP1 Interacts with Ebola Virus VP40 To Regulate RT Egress."; RL J. Virol. 91:0-0(2017). RN [28] RP REVIEW. RX PubMed=28177658; DOI=10.1089/dna.2017.3639; RA Pleet M.L., DeMarino C., Lepene B., Aman M.J., Kashanchi F.; RT "The Role of Exosomal VP40 in Ebola Virus Disease."; RL DNA Cell Biol. 36:243-248(2017). RN [29] RP SUBUNIT. RX PubMed=29950600; DOI=10.1038/s41598-018-28077-7; RA Pavadai E., Gerstman B.S., Chapagain P.P.; RT "A cylindrical assembly model and dynamics of the Ebola virus VP40 RT structural matrix."; RL Sci. Rep. 8:9776-9776(2018). RN [30] RP ACETYLATION. RX PubMed=30205953; DOI=10.1016/j.bbrc.2018.09.007; RA Hatakeyama D., Ohmi N., Saitoh A., Makiyama K., Morioka M., Okazaki H., RA Kuzuhara T.; RT "Acetylation of lysine residues in the recombinant nucleoprotein and VP40 RT matrix protein of Zaire Ebolavirus by eukaryotic histone RT acetyltransferases."; RL Biochem. Biophys. Res. Commun. 504:635-640(2018). RN [31] RP FUNCTION. RX PubMed=29339477; DOI=10.1073/pnas.1712263115; RA Takamatsu Y., Kolesnikova L., Becker S.; RT "Ebola virus proteins NP, VP35, and VP24 are essential and sufficient to RT mediate nucleocapsid transport."; RL Proc. Natl. Acad. Sci. U.S.A. 115:1075-1080(2018). RN [32] RP FUNCTION, INTERACTION WITH HOST SMURF2, DOMAIN, AND MUTAGENESIS OF RP 10-PRO--TYR-13. RX PubMed=33673144; DOI=10.3390/v13020288; RA Shepley-McTaggart A., Schwoerer M.P., Sagum C.A., Bedford M.T., RA Jaladanki C.K., Fan H., Cassel J., Harty R.N.; RT "Ubiquitin Ligase SMURF2 Interacts with Filovirus VP40 and Promotes Egress RT of VP40 VLPs."; RL Viruses 13:0-0(2021). RN [33] RP X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 55-194 IN COMPLEX WITH RNA. RX PubMed=12679020; DOI=10.1016/s0969-2126(03)00050-9; RA Gomis-Ruth F.X., Dessen A., Timmins J., Bracher A., Kolesnikowa L., RA Becker S., Klenk H.D., Weissenhorn W.; RT "The matrix protein VP40 from Ebola virus octamerizes into pore-like RT structures with specific RNA binding properties."; RL Structure 11:423-433(2003). CC -!- FUNCTION: Plays an essential role virus particle assembly and budding CC (PubMed:16719918, PubMed:33673144). Acts by interacting with viral CC ribonucleocapsid and host members of the ESCRT (endosomal sorting CC complex required for transport) system such as host VPS4, PDCD6IP/ALIX, CC NEDD4 or TGS101 (PubMed:15892969, PubMed:16719918, PubMed:23637409, CC PubMed:25786915, PubMed:26753796, PubMed:27489272). The interaction CC with host E3 ubiquitin ligase SMURF2 also facilitates virus budding CC (PubMed:33673144). May play a role in immune cell dysfunction by being CC packaged into exosomes that can decrease the viability of recipient CC cells (via RNAi suppression and exosome-bystander apoptosis) CC (PubMed:27872619). {ECO:0000269|PubMed:15892969, CC ECO:0000269|PubMed:16719918, ECO:0000269|PubMed:23637409, CC ECO:0000269|PubMed:25786915, ECO:0000269|PubMed:26753796, CC ECO:0000269|PubMed:27489272, ECO:0000269|PubMed:27872619, CC ECO:0000269|PubMed:33673144}. CC -!- SUBUNIT: Homodimer (PubMed:23953110). Homohexamer (PubMed:23953110, CC PubMed:11118208). Homooctamer (PubMed:12919741). Exists as a dimer CC until it reorganizes at the plasma membrane into a hexameric form using CC phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) (PubMed:23953110, CC PubMed:25159197, PubMed:26753796, PubMed:29950600). Hexamers are CC critical for budding (PubMed:23953110). Octamers function in genome CC replication and RNA binding (PubMed:12919741). Interacts with host CC TSG101 (PubMed:12559917). As a homohexamer, interacts with the WW CC domain 3 of host NEDD4 (PubMed:11095724, PubMed:12559917). Interacts CC with the nucleoprotein/NP (PubMed:17229682, PubMed:21987757). Interacts CC (via YPx(n)L/I motif) with host PDCD6IP/ALIX; this interaction supports CC efficient egress of viral particles (PubMed:25786915). Interacts with CC VP35 (PubMed:16698994). Interacts with host ITCH; this interaction is CC required for efficient egress (PubMed:27489272). Interacts (via PPXY CC motif) with host SMURF2 (via WW domains); the interaction positively CC regulates virus budding (PubMed:33673144). CC {ECO:0000269|PubMed:11095724, ECO:0000269|PubMed:11118208, CC ECO:0000269|PubMed:12559917, ECO:0000269|PubMed:12919741, CC ECO:0000269|PubMed:16698994, ECO:0000269|PubMed:17229682, CC ECO:0000269|PubMed:21987757, ECO:0000269|PubMed:23953110, CC ECO:0000269|PubMed:25159197, ECO:0000269|PubMed:25786915, CC ECO:0000269|PubMed:26753796, ECO:0000269|PubMed:27489272, CC ECO:0000269|PubMed:29950600, ECO:0000269|PubMed:33673144}. CC -!- INTERACTION: CC Q05128; Q05128: VP40; NbExp=4; IntAct=EBI-25753960, EBI-25753960; CC -!- SUBCELLULAR LOCATION: Host cytoplasm {ECO:0000269|PubMed:21987757}. CC Host cell membrane {ECO:0000269|PubMed:21987757, CC ECO:0000269|PubMed:26753796, ECO:0000269|PubMed:28768865}. Virion CC membrane {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:0000269|PubMed:27872619}. 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:0000269|PubMed:11095724, ECO:0000269|PubMed:12559917, CC ECO:0000269|PubMed:33673144}. CC -!- PTM: Sumoylated with host SUMO1, SUMO2. Sumoylation provides stability CC to VP40 (PubMed:27849047). Acetylated by host EP300 in vitro CC (PubMed:30205953). {ECO:0000269|PubMed:27849047, CC ECO:0000269|PubMed:30205953}. CC -!- PTM: Ubiquitinated by host WWP1. This modification mediates efficient CC viral budding. {ECO:0000269|PubMed:28768865}. CC -!- MISCELLANEOUS: Most abundant protein in the virion. CC -!- SIMILARITY: Belongs to the filoviridae matrix protein VP40 family. CC {ECO:0000305}. CC -!- CAUTION: Acetylation has been show in vitro using purified recombinant CC proteins. This PTM is unsure util proven in vivo. CC {ECO:0000269|PubMed:30205953}. 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; X61274; CAA43579.1; -; Genomic_RNA. DR EMBL; L11365; AAB81003.1; -; Genomic_RNA. DR EMBL; AF086833; AAD14583.1; -; Genomic_RNA. DR EMBL; AF272001; AAG40166.1; -; Genomic_RNA. DR EMBL; AF499101; AAM76033.1; -; Genomic_RNA. DR EMBL; AY142960; AAN37506.1; -; Genomic_RNA. DR RefSeq; NP_066245.1; NC_002549.1. DR PDB; 1H2C; X-ray; 1.60 A; A=55-194. DR PDB; 1H2D; X-ray; 2.60 A; A/B=31-212. DR PDB; 2KQ0; NMR; -; B=5-16. DR PDB; 4EJE; X-ray; 2.20 A; C/D=5-13. DR PDB; 4LDB; X-ray; 3.10 A; A/B/C/D=44-326. DR PDB; 4LDD; X-ray; 3.50 A; A/B/C=44-326. DR PDB; 4LDI; X-ray; 4.15 A; A/B=44-326. DR PDB; 4LDM; X-ray; 1.85 A; A=44-188. DR PDB; 7JZJ; X-ray; 2.46 A; A/B/C/D=43-326. DR PDB; 7JZT; X-ray; 3.77 A; A/B/C/D=43-326. DR PDB; 7K5D; X-ray; 1.78 A; A=44-194. DR PDB; 7K5L; X-ray; 1.38 A; A=44-194. DR PDBsum; 1H2C; -. DR PDBsum; 1H2D; -. DR PDBsum; 2KQ0; -. DR PDBsum; 4EJE; -. DR PDBsum; 4LDB; -. DR PDBsum; 4LDD; -. DR PDBsum; 4LDI; -. DR PDBsum; 4LDM; -. DR PDBsum; 7JZJ; -. DR PDBsum; 7JZT; -. DR PDBsum; 7K5D; -. DR PDBsum; 7K5L; -. DR BMRB; Q05128; -. DR EMDB; EMD-11660; -. DR EMDB; EMD-11661; -. DR EMDB; EMD-11662; -. DR EMDB; EMD-3872; -. DR SMR; Q05128; -. DR ELM; Q05128; -. DR MoonProt; Q05128; -. DR TCDB; 9.A.73.1.1; the virus matrix protein (vmp) family. DR DNASU; 911825; -. DR GeneID; 911825; -. DR KEGG; vg:911825; -. DR EvolutionaryTrace; Q05128; -. DR Proteomes; UP000007209; Genome. DR Proteomes; UP000109874; Genome. DR Proteomes; UP000149419; Genome. DR Proteomes; UP000150973; Genome. 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:0033644; C:host cell membrane; IDA:CACAO. DR GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell. DR GO; GO:0045121; C:membrane raft; IDA:CACAO. DR GO; GO:1990904; C:ribonucleoprotein complex; IEA:UniProtKB-KW. DR GO; GO:0055036; C:virion membrane; IEA:UniProtKB-SubCell. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. 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:0075733; P:intracellular transport of virus; IMP:CACAO. DR GO; GO:0044414; P:suppression of host defenses by symbiont; IMP:CACAO. DR GO; GO:0140533; P:suppression of host RNAi-mediated antiviral immune response; IMP:GO_Central. DR GO; GO:0046755; P:viral budding; IMP:CACAO. DR GO; GO:0046761; P:viral budding from plasma membrane; IDA:UniProtKB. DR GO; GO:0039702; P:viral budding via host ESCRT complex; IEA:UniProtKB-KW. DR GO; GO:0019049; P:virus-mediated perturbation of host defense response; IEA:UniProtKB-KW. DR DisProt; DP02967; -. 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 1: Evidence at protein level; KW 3D-structure; Host cell membrane; Host cytoplasm; Host endosome; KW Host membrane; Host-virus interaction; KW Inhibition of host innate immune response by virus; Isopeptide bond; KW Membrane; Reference proteome; 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_0000222164" FT REGION 212..214 FT /note="Important for oligomerization" FT REGION 213..326 FT /note="Membrane-binding" FT /evidence="ECO:0000250" FT MOTIF 7..10 FT /note="PTAP/PSAP motif" FT /evidence="ECO:0000269|PubMed:15892969" FT MOTIF 10..13 FT /note="PPXY motif" FT /evidence="ECO:0000269|PubMed:15892969" FT MOTIF 18..26 FT /note="Essential for interaction with host PDCD6IP/ALIX" FT /evidence="ECO:0000269|PubMed:25786915" FT CROSSLNK 326 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in host SUMO1 or SUMO2)" FT /evidence="ECO:0000269|PubMed:27849047" FT MUTAGEN 7 FT /note="P->A: Partial loss of budding." FT /evidence="ECO:0000269|PubMed:16051823" FT MUTAGEN 10..13 FT /note="PPEY->AAEA: Abolishes interaction with host SMURF2." FT /evidence="ECO:0000269|PubMed:33673144" FT MUTAGEN 10..11 FT /note="PP->AA: 90% loss of budding." FT /evidence="ECO:0000269|PubMed:16051823" FT MUTAGEN 11 FT /note="P->A: Complete loss of budding." FT MUTAGEN 13 FT /note="Y->A: Complete loss of interaction with WW domain FT containing proteins." FT /evidence="ECO:0000269|PubMed:11095724" FT MUTAGEN 125 FT /note="F->A: Partial loss of RNA-binding. Complete loss of FT virus infectivity." FT /evidence="ECO:0000269|PubMed:15650213" FT MUTAGEN 134 FT /note="R->A: Complete loss of RNA-binding. Complete loss of FT virus infectivity." FT /evidence="ECO:0000269|PubMed:15650213" FT MUTAGEN 212..214 FT /note="KLR->AAA: 85% loss of budding efficiency. Impaired FT oligomerization." FT /evidence="ECO:0000269|PubMed:17699576" FT MUTAGEN 212..214 FT /note="KLR->ALA: 80% loss of budding efficiency. No effect FT on oligomerization." FT /evidence="ECO:0000269|PubMed:17699576" FT MUTAGEN 212..213 FT /note="KL->AA: 84% loss of budding efficiency. Impaired FT oligomerization." FT MUTAGEN 212 FT /note="K->A: 40% loss of budding efficiency. No effect on FT oligomerization." FT MUTAGEN 213..214 FT /note="LR->AA: 84% loss of budding efficiency. Impaired FT oligomerization." FT MUTAGEN 213 FT /note="L->A: 87% loss of budding efficiency. Impaired FT oligomerization." FT MUTAGEN 213 FT /note="L->I: 40% loss of budding efficiency." FT MUTAGEN 214 FT /note="R->A: 65% loss of budding efficiency. No effect on FT oligomerization." FT MUTAGEN 326 FT /note="K->R: Complete loss of sumoylation." FT /evidence="ECO:0000269|PubMed:27849047" FT HELIX 61..64 FT /evidence="ECO:0007829|PDB:7JZJ" FT STRAND 71..84 FT /evidence="ECO:0007829|PDB:7K5L" FT STRAND 87..101 FT /evidence="ECO:0007829|PDB:7K5L" FT STRAND 103..106 FT /evidence="ECO:0007829|PDB:7K5L" FT HELIX 108..117 FT /evidence="ECO:0007829|PDB:7K5L" FT STRAND 120..126 FT /evidence="ECO:0007829|PDB:7K5L" FT STRAND 128..130 FT /evidence="ECO:0007829|PDB:7JZJ" FT STRAND 132..139 FT /evidence="ECO:0007829|PDB:7K5L" FT HELIX 148..151 FT /evidence="ECO:0007829|PDB:7K5L" FT STRAND 153..158 FT /evidence="ECO:0007829|PDB:7K5L" FT HELIX 159..162 FT /evidence="ECO:0007829|PDB:7K5L" FT STRAND 173..185 FT /evidence="ECO:0007829|PDB:7K5L" FT TURN 198..200 FT /evidence="ECO:0007829|PDB:4LDB" FT STRAND 202..209 FT /evidence="ECO:0007829|PDB:7JZJ" FT STRAND 211..213 FT /evidence="ECO:0007829|PDB:4LDB" FT HELIX 234..243 FT /evidence="ECO:0007829|PDB:7JZJ" FT HELIX 244..246 FT /evidence="ECO:0007829|PDB:7JZJ" FT STRAND 248..253 FT /evidence="ECO:0007829|PDB:4LDB" FT HELIX 254..256 FT /evidence="ECO:0007829|PDB:7JZJ" FT STRAND 258..262 FT /evidence="ECO:0007829|PDB:7JZJ" FT HELIX 265..272 FT /evidence="ECO:0007829|PDB:7JZJ" FT STRAND 284..288 FT /evidence="ECO:0007829|PDB:7JZJ" FT STRAND 304..309 FT /evidence="ECO:0007829|PDB:7JZJ" FT TURN 317..319 FT /evidence="ECO:0007829|PDB:7JZJ" SQ SEQUENCE 326 AA; 35183 MW; 1AB132C0DB8E9003 CRC64; MRRVILPTAP PEYMEAIYPV RSNSTIARGG NSNTGFLTPE SVNGDTPSNP LRPIADDTID HASHTPGSVS SAFILEAMVN VISGPKVLMK QIPIWLPLGV ADQKTYSFDS TTAAIMLASY TITHFGKATN PLVRVNRLGP GIPDHPLRLL RIGNQAFLQE FVLPPVQLPQ YFTFDLTALK LITQPLPAAT WTDDTPTGSN GALRPGISFH PKLRPILLPN KSGKKGNSAD LTSPEKIQAI MTSLQDFKIV PIDPTKNIMG IEVPETLVHK LTGKKVTSKN GQPIIPVLLP KYIGLDPVAP GDLTMVITQD CDTCHSPASL PAVIEK //