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Q05128 (VP40_EBOZM) Reviewed, UniProtKB/Swiss-Prot

Last modified February 19, 2014. Version 81. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Matrix protein VP40
Alternative name(s):
Membrane-associated protein VP40
Gene names
Name:VP40
OrganismZaire ebolavirus (strain Mayinga-76) (ZEBOV) (Zaire Ebola virus) [Reference proteome]
Taxonomic identifier128952 [NCBI]
Taxonomic lineageVirusesssRNA negative-strand virusesMononegaviralesFiloviridaeEbolavirus
Virus hostEpomops franqueti (Franquet's epauleted fruit bat) [TaxID: 77231]
Homo sapiens (Human) [TaxID: 9606]
Myonycteris torquata (Little collared fruit bat) [TaxID: 77243]

Protein attributes

Sequence length326 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Promotes virus assembly and budding by interacting with host proteins of the multivesicular body pathway. May facilitate virus budding by interacting with the nucleocapsid and the plasma membrane. Specific interactions with membrane-associated GP and VP24 during the budding process may also occur. The hexamer form seems to be involved in budding. The octamer form binds RNA, and may play a role in genome replication. Ref.13 Ref.14

Subunit structure

Monomer, homo-hexamer or homo-octamer. Membrane association induces conformational switch from monomer to hexamer. Interacts with host TSG101. Homo-hexamer interacts with the WW domain 3 of host NEDD4. Interacts with the nucleoprotein. May interact with VP35. Ref.6 Ref.7 Ref.8 Ref.9 Ref.11 Ref.15 Ref.16

Subcellular location

Virion membrane; Peripheral membrane protein. Host endomembrane system; Peripheral membrane protein. Host cell membrane; Peripheral membrane protein; Cytoplasmic side By similarity. Note: In virion, localizes on the intravirional side of the membrane. In the host cell, it is found associated with virus-induced membrane proliferation foci and probably also in multivesicular bodies. These VP40-enriched membrane clusters are then redistributed to the plasma membrane where budding takes place By similarity.

Domain

Late-budding domains (L domains) are short sequence motifs essential for viral particle budding. They recruit proteins of the host ESCRT machinery (Endosomal Sorting Complex Required for Transport) or ESCRT-associated proteins. VP40 contains two overlapping L domains: a PTAP/PSAP motif, which interacts with the UEV domain of TSG101 and a PPXY motif which interacts with the WW domain 3 of NEDD4. Ref.7

Miscellaneous

Most abundant protein in the virion.

Sequence similarities

Belongs to the filoviridae matrix protein VP40 family.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 326326Matrix protein VP40
PRO_0000222164

Regions

Region212 – 2143Important for oligomerization
Region213 – 326114Membrane-binding By similarity
Motif7 – 104PTAP/PSAP motif
Motif10 – 134PPXY motif

Experimental info

Mutagenesis71P → A: Partial loss of budding. Ref.10
Mutagenesis10 – 112PP → AA: 90% loss of budding.
Mutagenesis111P → A: Complete loss of budding.
Mutagenesis131Y → A: Complete loss of interaction with WW domain containing proteins. Ref.7
Mutagenesis1251F → A: Partial loss of RNA-binding. Complete loss of virus infectivity. Ref.12
Mutagenesis1341R → A: Complete loss of RNA-binding. Complete loss of virus infectivity. Ref.12
Mutagenesis212 – 2143KLR → AAA: 85% loss of budding efficiency. Impaired oligomerization. Ref.17
Mutagenesis212 – 2143KLR → ALA: 80% loss of budding efficiency. No effect on oligomerization. Ref.17
Mutagenesis212 – 2132KL → AA: 84% loss of budding efficiency. Impaired oligomerization.
Mutagenesis2121K → A: 40% loss of budding efficiency. No effect on oligomerization.
Mutagenesis213 – 2142LR → AA: 84% loss of budding efficiency. Impaired oligomerization.
Mutagenesis2131L → A: 87% loss of budding efficiency. Impaired oligomerization.
Mutagenesis2131L → I: 40% loss of budding efficiency.
Mutagenesis2141R → A: 65% loss of budding efficiency. No effect on oligomerization.

Secondary structure

............................................ 326
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q05128 [UniParc].

Last modified February 1, 1994. Version 1.
Checksum: 1AB132C0DB8E9003

FASTA32635,183
        10         20         30         40         50         60 
MRRVILPTAP PEYMEAIYPV RSNSTIARGG NSNTGFLTPE SVNGDTPSNP LRPIADDTID 

        70         80         90        100        110        120 
HASHTPGSVS SAFILEAMVN VISGPKVLMK QIPIWLPLGV ADQKTYSFDS TTAAIMLASY 

       130        140        150        160        170        180 
TITHFGKATN PLVRVNRLGP GIPDHPLRLL RIGNQAFLQE FVLPPVQLPQ YFTFDLTALK 

       190        200        210        220        230        240 
LITQPLPAAT WTDDTPTGSN GALRPGISFH PKLRPILLPN KSGKKGNSAD LTSPEKIQAI 

       250        260        270        280        290        300 
MTSLQDFKIV PIDPTKNIMG IEVPETLVHK LTGKKVTSKN GQPIIPVLLP KYIGLDPVAP 

       310        320 
GDLTMVITQD CDTCHSPASL PAVIEK 

« Hide

References

[1]"The VP35 and VP40 proteins of filoviruses. Homology between Marburg and Ebola viruses."
Bukreyev A.A., Volchkov V.E., Blinov V.M., Netesov S.V.
FEBS Lett. 322:41-46(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
[2]"Sequence analysis of the Ebola virus genome: organization, genetic elements, and comparison with the genome of Marburg virus."
Sanchez A., Kiley M.P., Holloway B.P., Auperin D.D.
Virus Res. 29:215-240(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
[3]"Characterization of the L gene and 5' trailer region of Ebola virus."
Volchkov V.E., Volchkova V.A., Chepurnov A.A., Blinov V.M., Netesov S.V., Feldmann H.
J. Gen. Virol. 80:355-362(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
[4]"Molecular characterization of guinea pig-adapted variants of Ebola virus."
Volchkov V.E., Chepurnov A.A., Volchkova V.A., Ternovoj V.A., Klenk H.D.
Virology 277:147-155(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
Strain: Isolate guinea pig-adapted.
[5]Wilson J.A., Kondig J.P., Kuehne A.I., Hart M.K.
Submitted (AUG-2002) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC RNA].
[6]"Membrane association induces a conformational change in the Ebola virus matrix protein."
Scianimanico S., Schoehn G., Timmins J., Ruigrok R.H., Klenk H.D., Weissenhorn W.
EMBO J. 19:6732-6741(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: MULTIMERIZATION.
[7]"A PPxY motif within the VP40 protein of Ebola virus interacts physically and functionally with a ubiquitin ligase: implications for filovirus budding."
Harty R.N., Brown M.E., Wang G., Huibregtse J., Hayes F.P.
Proc. Natl. Acad. Sci. U.S.A. 97:13871-13876(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH WW DOMAINS OF HOST UBIQUITIN LIGASES, MUTAGENESIS OF TYR-13.
[8]"Oligomerization and polymerization of the filovirus matrix protein VP40."
Timmins J., Schoehn G., Kohlhaas C., Klenk H.D., Ruigrok R.W., Weissenhorn W.
Virology 312:359-368(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: MULTIMERIZATION.
[9]"Ebola virus matrix protein VP40 interaction with human cellular factors Tsg101 and Nedd4."
Timmins J., Schoehn G., Ricard-Blum S., Scianimanico S., Vernet T., Ruigrok R.W., Weissenhorn W.
J. Mol. Biol. 326:493-502(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HUMAN TSG101 AND NEDD4.
[10]"Ebola virus VP40 late domains are not essential for viral replication in cell culture."
Neumann G., Ebihara H., Takada A., Noda T., Kobasa D., Jasenosky L.D., Watanabe S., Kim J.H., Feldmann H., Kawaoka Y.
J. Virol. 79:10300-10307(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF PRO-7 AND 10-PRO-PRO-11.
[11]"An all-atom model of the pore-like structure of hexameric VP40 from Ebola: structural insights into the monomer-hexamer transition."
Nguyen T.L., Schoehn G., Weissenhorn W., Hermone A.R., Burnett J.C., Panchal R.G., McGrath C., Zaharevitz D.W., Aman M.J., Gussio R., Bavari S.
J. Struct. Biol. 151:30-40(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: MULTIMERIZATION.
[12]"VP40 octamers are essential for Ebola virus replication."
Hoenen T., Volchkov V., Kolesnikova L., Mittler E., Timmins J., Ottmann M., Reynard O., Becker S., Weissenhorn W.
J. Virol. 79:1898-1905(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF PHE-125 AND ARG-134.
[13]"Functional characterization of Ebola virus L-domains using VSV recombinants."
Irie T., Licata J.M., Harty R.N.
Virology 336:291-298(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[14]"Effect of Ebola virus proteins GP, NP and VP35 on VP40 VLP morphology."
Johnson R.F., Bell P., Harty R.N.
Virol. J. 3:31-31(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[15]"Ebola virus VP35-VP40 interaction is sufficient for packaging 3E-5E minigenome RNA into virus-like particles."
Johnson R.F., McCarthy S.E., Godlewski P.J., Harty R.N.
J. Virol. 80:5135-5144(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH VP35.
[16]"Mapping of the VP40-binding regions of the nucleoprotein of Ebola virus."
Noda T., Watanabe S., Sagara H., Kawaoka Y.
J. Virol. 81:3554-3562(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH THE NUCLEOPROTEIN.
[17]"Role for amino acids 212KLR214 of Ebola virus VP40 in assembly and budding."
McCarthy S.E., Johnson R.F., Zhang Y.-A., Sunyer J.O., Harty R.N.
J. Virol. 81:11452-11460(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF 212-LYS--ARG-214.
[18]"The matrix protein VP40 from Ebola virus octamerizes into pore-like structures with specific RNA binding properties."
Gomis-Ruth F.X., Dessen A., Timmins J., Bracher A., Kolesnikowa L., Becker S., Klenk H.D., Weissenhorn W.
Structure 11:423-433(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 55-194 IN COMPLEX WITH RNA.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X61274 Genomic RNA. Translation: CAA43579.1.
L11365 Genomic RNA. Translation: AAB81003.1.
AF086833 Genomic RNA. Translation: AAD14583.1.
AF272001 Genomic RNA. Translation: AAG40166.1.
AF499101 Genomic RNA. Translation: AAM76033.1.
AY142960 Genomic RNA. Translation: AAN37506.1.
RefSeqNP_066245.1. NC_002549.1.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1H2CX-ray1.60A55-194[»]
1H2DX-ray2.60A/B31-212[»]
2KQ0NMR-B5-16[»]
4EJEX-ray2.20C/D5-13[»]
4LDBX-ray3.10A/B/C/D44-326[»]
4LDDX-ray3.50A/B/C44-326[»]
4LDIX-ray4.15A/B44-326[»]
4LDMX-ray1.85A44-188[»]
ProteinModelPortalQ05128.
SMRQ05128. Positions 44-321.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

MINTMINT-151825.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID911825.

Family and domain databases

InterProIPR008986. EV_matrix.
[Graphical view]
PfamPF07447. VP40. 1 hit.
[Graphical view]
PIRSFPIRSF018327. VP40_FiloV. 1 hit.
SUPFAMSSF50012. SSF50012. 2 hits.
ProtoNetSearch...

Other

EvolutionaryTraceQ05128.

Entry information

Entry nameVP40_EBOZM
AccessionPrimary (citable) accession number: Q05128
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: February 1, 1994
Last modified: February 19, 2014
This is version 81 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references