VP40_EBOZ5
ID VP40_EBOZ5 Reviewed; 326 AA.
AC Q77DJ6;
DT 11-JUL-2006, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 94.
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 Kikwit-95) (ZEBOV) (Zaire Ebola virus).
OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Haploviricotina;
OC Monjiviricetes; Mononegavirales; Filoviridae; Ebolavirus.
OX NCBI_TaxID=128951;
OH NCBI_TaxID=77231; Epomops franqueti (Franquet's epauleted fruit bat).
OH NCBI_TaxID=9606; Homo sapiens (Human).
OH NCBI_TaxID=77243; Myonycteris torquata (Little collared fruit bat).
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RA Chain P.S.G., Ichou M.A., Malfatti S.A., Hajjaj A., Vergez L.M.,
RA Paragas J., Do L.H., Jahrling P.B., Smith K.L., McCready P.M.,
RA Ibrahim M.S.;
RL Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 31-326.
RX PubMed=10944105; DOI=10.1093/emboj/19.16.4228;
RA Dessen A., Volchkov V., Dolnik O., Klenk H.-D., Weissenhorn W.;
RT "Crystal structure of the matrix protein VP40 from Ebola virus.";
RL EMBO J. 19:4228-4236(2000).
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; AY354458; AAQ55047.1; -; Genomic_RNA.
DR RefSeq; NP_066245.1; NC_002549.1.
DR PDB; 1ES6; X-ray; 2.00 A; A=31-326.
DR PDBsum; 1ES6; -.
DR SMR; Q77DJ6; -.
DR ABCD; Q77DJ6; 2 sequenced antibodies.
DR DNASU; 911825; -.
DR GeneID; 911825; -.
DR KEGG; vg:911825; -.
DR EvolutionaryTrace; Q77DJ6; -.
DR Proteomes; UP000007208; 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:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; 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; -; 1.
DR Gene3D; 2.70.20.20; -; 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; SSF50012; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Host cell membrane; Host cytoplasm; Host endosome;
KW Host membrane; Host-virus interaction; Isopeptide bond; Membrane;
KW Reference proteome; Ribonucleoprotein; RNA-binding; Secreted;
KW Suppressor of RNA silencing; Ubl conjugation; Viral budding;
KW Viral budding via the host ESCRT complexes; Viral matrix protein;
KW Viral release from host cell; Viral RNA replication; Virion.
FT CHAIN 1..326
FT /note="Matrix protein VP40"
FT /id="PRO_0000245083"
FT REGION 212..214
FT /note="Important for oligomerization"
FT /evidence="ECO:0000250"
FT REGION 213..326
FT /note="Membrane-binding"
FT MOTIF 7..10
FT /note="PTAP/PSAP motif"
FT MOTIF 10..13
FT /note="PPXY motif"
FT HELIX 61..63
FT /evidence="ECO:0007829|PDB:1ES6"
FT STRAND 71..83
FT /evidence="ECO:0007829|PDB:1ES6"
FT STRAND 86..101
FT /evidence="ECO:0007829|PDB:1ES6"
FT STRAND 103..106
FT /evidence="ECO:0007829|PDB:1ES6"
FT HELIX 108..116
FT /evidence="ECO:0007829|PDB:1ES6"
FT STRAND 120..125
FT /evidence="ECO:0007829|PDB:1ES6"
FT STRAND 128..130
FT /evidence="ECO:0007829|PDB:1ES6"
FT STRAND 132..137
FT /evidence="ECO:0007829|PDB:1ES6"
FT HELIX 148..152
FT /evidence="ECO:0007829|PDB:1ES6"
FT STRAND 153..158
FT /evidence="ECO:0007829|PDB:1ES6"
FT HELIX 159..162
FT /evidence="ECO:0007829|PDB:1ES6"
FT STRAND 173..185
FT /evidence="ECO:0007829|PDB:1ES6"
FT STRAND 203..208
FT /evidence="ECO:0007829|PDB:1ES6"
FT HELIX 228..231
FT /evidence="ECO:0007829|PDB:1ES6"
FT HELIX 234..243
FT /evidence="ECO:0007829|PDB:1ES6"
FT HELIX 244..246
FT /evidence="ECO:0007829|PDB:1ES6"
FT STRAND 248..253
FT /evidence="ECO:0007829|PDB:1ES6"
FT HELIX 254..256
FT /evidence="ECO:0007829|PDB:1ES6"
FT STRAND 258..262
FT /evidence="ECO:0007829|PDB:1ES6"
FT HELIX 265..271
FT /evidence="ECO:0007829|PDB:1ES6"
FT STRAND 284..288
FT /evidence="ECO:0007829|PDB:1ES6"
FT TURN 298..301
FT /evidence="ECO:0007829|PDB:1ES6"
FT STRAND 304..310
FT /evidence="ECO:0007829|PDB:1ES6"
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
