VP40_MABVM
ID VP40_MABVM Reviewed; 303 AA.
AC P35260; Q38L43; Q6T6U1; Q6T6U8;
DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT 15-JAN-2008, sequence version 3.
DT 23-FEB-2022, entry version 90.
DE RecName: Full=Matrix protein VP40;
DE AltName: Full=Marburg VP40 {ECO:0000303|PubMed:28580138};
DE Short=mVP40 {ECO:0000303|PubMed:28580138};
DE AltName: Full=Membrane-associated protein VP40;
GN Name=VP40;
OS Lake Victoria marburgvirus (strain Musoke-80) (MARV) (Marburg virus (strain
OS Kenya/Musoke/1980)).
OC Viruses; Riboviria; Orthornavirae; Negarnaviricota; Haploviricotina;
OC Monjiviricetes; Mononegavirales; Filoviridae; Marburgvirus.
OX NCBI_TaxID=33727;
OH NCBI_TaxID=9534; Chlorocebus aethiops (Green monkey) (Cercopithecus aethiops).
OH NCBI_TaxID=9606; Homo sapiens (Human).
OH NCBI_TaxID=9407; Rousettus aegyptiacus (Egyptian rousette) (Egyptian fruit bat).
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Isolate Feldmann;
RX PubMed=1626422; DOI=10.1016/0168-1702(92)90027-7;
RA Feldmann H., Muehlberger E., Randolf A., Will C., Kiley M.P., Sanchez A.,
RA Klenk H.-D.;
RT "Marburg virus, a filovirus: messenger RNAs, gene order, and regulatory
RT elements of the replication cycle.";
RL Virus Res. 24:1-19(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RC STRAIN=pp3/guinea pig lethal, and pp4/guinea pig nonlethal;
RA Chain P.S.G., Malfatti S.A., Hajjaj A., Vergez L.M., Do L.H., Smith K.L.,
RA McCready P.M.;
RL Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RC STRAIN=pp3/guinea pig lethal, and pp4/guinea pig nonlethal;
RA Ichou M.A., Paragas J., Jahrling P.B., Ibrahim M.S., Lofts L., Hevey M.,
RA Schmaljohn A.;
RL Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC RNA].
RX PubMed=16379005; DOI=10.1128/jvi.80.2.1038-1043.2006;
RA Enterlein S., Volchkov V., Weik M., Kolesnikova L., Volchkova V.,
RA Klenk H.-D., Muehlberger E.;
RT "Rescue of recombinant Marburg virus from cDNA is dependent on nucleocapsid
RT protein VP30.";
RL J. Virol. 80:1038-1043(2006).
RN [5]
RP SUBCELLULAR LOCATION.
RX PubMed=11799178; DOI=10.1128/jvi.76.4.1825-1838.2002;
RA Kolesnikova L., Bugany H., Klenk H.-D., Becker S.;
RT "VP40, the matrix protein of Marburg virus, is associated with membranes of
RT the late endosomal compartment.";
RL J. Virol. 76:1825-1838(2002).
RN [6]
RP SUBCELLULAR LOCATION.
RX PubMed=14963134; DOI=10.1128/jvi.78.5.2382-2393.2004;
RA Kolesnikova L., Bamberg S., Berghofer B., Becker S.;
RT "The matrix protein of Marburg virus is transported to the plasma membrane
RT along cellular membranes: exploiting the retrograde late endosomal
RT pathway.";
RL J. Virol. 78:2382-2393(2004).
RN [7]
RP LATE-BUDDING DOMAIN, INTERACTION WITH HOST TSG101, AND MUTAGENESIS OF
RP PRO-16; PRO-17 AND TYR-19.
RX PubMed=17301151; DOI=10.1128/jvi.02829-06;
RA Urata S., Noda T., Kawaoka Y., Morikawa S., Yokosawa H., Yasuda J.;
RT "Interaction of Tsg101 with Marburg virus VP40 depends on the PPPY motif,
RT but not the PT/SAP motif as in the case of Ebola virus, and Tsg101 plays a
RT critical role in the budding of Marburg virus-like particles induced by
RT VP40, NP, and GP.";
RL J. Virol. 81:4895-4899(2007).
RN [8]
RP LATE-BUDDING DOMAIN.
RX PubMed=20504928; DOI=10.1128/jvi.00476-10;
RA Dolnik O., Kolesnikova L., Stevermann L., Becker S.;
RT "Tsg101 is recruited by a late domain of the nucleocapsid protein to
RT support budding of Marburg virus-like particles.";
RL J. Virol. 84:7847-7856(2010).
RN [9]
RP SUBCELLULAR LOCATION, DIMERIZATION, AND NOMENCLATURE.
RX PubMed=28580138; DOI=10.1039/c7ra02940c;
RA Bhattarai N., Gc J.B., Gerstman B.S., Stahelin R.V., Chapagain P.P.;
RT "Plasma membrane association facilitates conformational changes in the
RT Marburg virus protein VP40 dimer.";
RL RSC Adv. 7:22741-22748(2017).
RN [10]
RP FUNCTION, INTERACTION WITH HOST SMURF2, DOMAIN, AND MUTAGENESIS OF
RP 16-PRO--GLY-23.
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 [11] {ECO:0007744|PDB:5B0V}
RP X-RAY CRYSTALLOGRAPHY (2.81 ANGSTROMS) OF 2-303.
RX PubMed=26656687; DOI=10.1128/jvi.01597-15;
RA Oda S., Noda T., Wijesinghe K.J., Halfmann P., Bornholdt Z.A.,
RA Abelson D.M., Armbrust T., Stahelin R.V., Kawaoka Y., Saphire E.O.;
RT "Crystal Structure of Marburg Virus VP40 Reveals a Broad, Basic Patch for
RT Matrix Assembly and a Requirement of the N-Terminal Domain for
RT Immunosuppression.";
RL J. Virol. 90:1839-1848(2016).
CC -!- FUNCTION: Plays an essential role virus particle assembly and budding
CC (PubMed:33673144). Promotes virus assembly and budding by interacting
CC with host proteins of the multivesicular body pathway. The interaction
CC with host E3 ubiquitin ligase SMURF2 facilitates virus budding
CC (PubMed:33673144). The interaction with the nucleocapsid and the plasma
CC membrane may also facilitate virus budding. Specific interactions with
CC membrane-associated GP and VP24 during the budding process may also
CC occur (By similarity). May play a role in genome replication (By
CC similarity). {ECO:0000250, ECO:0000269|PubMed:33673144}.
CC -!- SUBUNIT: Exists as a dimer until it reorganizes at the plasma membrane
CC into multimeric form (PubMed:28580138). Interacts with host TSG101
CC (PubMed:17301151). Interacts (via PPXY motif) with SMURF2 (via WW
CC domains); the interaction positively regulates virus budding
CC (PubMed:33673144). {ECO:0000269|PubMed:17301151,
CC ECO:0000269|PubMed:28580138, ECO:0000269|PubMed:33673144}.
CC -!- SUBCELLULAR LOCATION: Virion membrane {ECO:0000269|PubMed:14963134};
CC Peripheral membrane protein. Host late endosome membrane
CC {ECO:0000269|PubMed:11799178}; Peripheral membrane protein
CC {ECO:0000305|PubMed:14963134}. Host cell membrane
CC {ECO:0000269|PubMed:11799178, ECO:0000269|PubMed:28580138}; Peripheral
CC membrane protein; Cytoplasmic side {ECO:0000305|PubMed:14963134}. Host
CC endomembrane system {ECO:0000269|PubMed:11799178}; Peripheral membrane
CC protein. Note=In virion, localizes on the intravirional side of the
CC membrane. In the host cell, it is found associated with virus-induced
CC membrane proliferation foci and probably also in multivesicular bodies.
CC These VP40-enriched membrane clusters are then redistributed to the
CC plasma membrane where budding takes place.
CC {ECO:0000269|PubMed:14963134}.
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 one L domain: a PPXY motif
CC which potentially 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, ECO:0000269|PubMed:33673144}.
CC -!- MISCELLANEOUS: Most abundant protein in the virion.
CC -!- SIMILARITY: Belongs to the filoviridae matrix protein VP40 family.
CC {ECO:0000305}.
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DR EMBL; Z12132; CAA78116.1; -; mRNA.
DR EMBL; AY430365; AAR85462.1; -; Genomic_RNA.
DR EMBL; AY430366; AAR85455.1; -; Genomic_RNA.
DR EMBL; DQ217792; ABA87126.1; -; Genomic_RNA.
DR RefSeq; YP_001531155.1; NC_001608.3.
DR PDB; 5B0V; X-ray; 2.81 A; A/B=2-303.
DR PDBsum; 5B0V; -.
DR SMR; P35260; -.
DR ELM; P35260; -.
DR DNASU; 920947; -.
DR GeneID; 920947; -.
DR KEGG; vg:920947; -.
DR Proteomes; UP000007771; Genome.
DR Proteomes; UP000137266; Genome.
DR Proteomes; UP000160614; Genome.
DR Proteomes; UP000180448; 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:0055036; C:virion membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0039660; F:structural constituent of virion; IEA:UniProtKB-KW.
DR GO; GO:0039576; P:suppression by virus of host JAK-STAT cascade via inhibition of JAK1 activity; IEA:UniProtKB-KW.
DR GO; GO:0039502; P:suppression by virus of host type I interferon-mediated signaling pathway; IEA:UniProtKB-KW.
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 Gene3D; 2.70.20.20; -; 1.
DR InterPro; IPR008986; EV_matrix.
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; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Host cell membrane; Host endosome; Host membrane;
KW Host-virus interaction; Inhibition of host innate immune response by virus;
KW Inhibition of host interferon signaling pathway by virus;
KW Inhibition of host JAK1 by virus; Membrane; Reference proteome;
KW Viral budding; Viral budding via the host ESCRT complexes;
KW Viral immunoevasion; Viral matrix protein; Viral release from host cell;
KW Virion.
FT CHAIN 1..303
FT /note="Matrix protein VP40"
FT /id="PRO_0000222165"
FT MOTIF 16..19
FT /note="PPXY motif"
FT VARIANT 16
FT /note="P -> S (in strain: Isolate Feldmann)"
FT VARIANT 184
FT /note="D -> N (in strain: pp3/guinea pig lethal)"
FT MUTAGEN 16..23
FT /note="PPPYADHG->AAAPAADH: Abolishes interaction with host
FT SMURF2."
FT /evidence="ECO:0000269|PubMed:33673144"
FT MUTAGEN 16
FT /note="P->A: 30% loss of virus-like particles."
FT /evidence="ECO:0000269|PubMed:17301151"
FT MUTAGEN 17
FT /note="P->A: 50% loss of virus-like particles."
FT /evidence="ECO:0000269|PubMed:17301151"
FT MUTAGEN 19
FT /note="Y->A: 70% loss of virus-like particles."
FT /evidence="ECO:0000269|PubMed:17301151"
FT STRAND 42..45
FT /evidence="ECO:0007829|PDB:5B0V"
FT HELIX 49..51
FT /evidence="ECO:0007829|PDB:5B0V"
FT STRAND 58..72
FT /evidence="ECO:0007829|PDB:5B0V"
FT STRAND 77..90
FT /evidence="ECO:0007829|PDB:5B0V"
FT HELIX 91..93
FT /evidence="ECO:0007829|PDB:5B0V"
FT HELIX 96..105
FT /evidence="ECO:0007829|PDB:5B0V"
FT STRAND 108..117
FT /evidence="ECO:0007829|PDB:5B0V"
FT STRAND 119..125
FT /evidence="ECO:0007829|PDB:5B0V"
FT HELIX 136..140
FT /evidence="ECO:0007829|PDB:5B0V"
FT STRAND 141..146
FT /evidence="ECO:0007829|PDB:5B0V"
FT HELIX 147..149
FT /evidence="ECO:0007829|PDB:5B0V"
FT STRAND 161..173
FT /evidence="ECO:0007829|PDB:5B0V"
FT HELIX 183..187
FT /evidence="ECO:0007829|PDB:5B0V"
FT STRAND 191..198
FT /evidence="ECO:0007829|PDB:5B0V"
FT HELIX 211..214
FT /evidence="ECO:0007829|PDB:5B0V"
FT TURN 220..222
FT /evidence="ECO:0007829|PDB:5B0V"
FT HELIX 223..229
FT /evidence="ECO:0007829|PDB:5B0V"
FT HELIX 230..234
FT /evidence="ECO:0007829|PDB:5B0V"
FT STRAND 237..239
FT /evidence="ECO:0007829|PDB:5B0V"
FT STRAND 243..250
FT /evidence="ECO:0007829|PDB:5B0V"
FT TURN 253..255
FT /evidence="ECO:0007829|PDB:5B0V"
FT STRAND 259..261
FT /evidence="ECO:0007829|PDB:5B0V"
FT STRAND 272..276
FT /evidence="ECO:0007829|PDB:5B0V"
FT HELIX 283..285
FT /evidence="ECO:0007829|PDB:5B0V"
FT STRAND 290..296
FT /evidence="ECO:0007829|PDB:5B0V"
FT HELIX 298..300
FT /evidence="ECO:0007829|PDB:5B0V"
SQ SEQUENCE 303 AA; 33794 MW; 00DA12CE6BB4A354 CRC64;
MASSSNYNTY MQYLNPPPYA DHGANQLIPA DQLSNQQGIT PNYVGDLNLD DQFKGNVCHA
FTLEAIIDIS AYNERTVKGV PAWLPLGIMS NFEYPLAHTV AALLTGSYTI TQFTHNGQKF
VRVNRLGTGI PAHPLRMLRE GNQAFIQNMV IPRNFSTNQF TYNLTNLVLS VQKLPDDAWR
PSKDKLIGNT MHPAVSIHPN LPPIVLPTVK KQAYRQHKNP NNGPLLAISG ILHQLRVEKV
PEKTSLFRIS LPADMFSVKE GMMKKRGENS PVVYFQAPEN FPLNGFNNRQ VVLAYANPTL
SAV
