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Q05127 (VP35_EBOZM) Reviewed, UniProtKB/Swiss-Prot

Last modified May 14, 2014. Version 67. 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

Protein attributes

Sequence length340 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Acsts as a polymerase cofactor in the RNA polymerase transcription and replication complex. Prevents establishment of cellular antiviral state by blocking virus-induced phosphorylation and activation of interferon regulatory factor 3 (IRF3), a transcription factor critical for the induction of interferons alpha and beta. This blockage is produced through the interaction with and inhibition of host IKBKE and TBK1, producing a strong inhibition of the phosphorylation and activation of IRF3. Also inhibits the antiviral effect mediated by the host interferon-induced, double-stranded RNA-activated protein kinase EIF2AK2/PKR. Ref.6 Ref.7 Ref.9 Ref.14 Ref.15 Ref.16

Subunit structure

Homooligomer. Homomultimerizes via the coiled coil domain. Found in a trimeric complex in which VP35 bridges L and the nucleoprotein By similarity. May interact with VP40. Interacts with host IKBKE and TBK1; the interactions lead to inhibition of cellular antiviral response by blocking necessary interactions of IKBKE and TBK1 with their substrate IRF3. Ref.8 Ref.11 Ref.13 Ref.16

Subcellular location

Virion. Host cytoplasm.

Post-translational modification

Phosphorylated by host IKBKE. Ref.16

Sequence similarities

Belongs to the filoviridae polymerase cofactor VP35 family.

Ontologies

Keywords
   Biological processHost-virus interaction
Inhibition of host IKBKE by virus
Inhibition of host innate immune response by virus
Inhibition of host IRF7 by virus
Inhibition of host RLR pathway by virus
Inhibition of host TBK1 by virus
Inhibition of host TLR pathway by virus
Interferon antiviral system evasion
Transcription
Viral immunoevasion
Viral RNA replication
   Cellular componentHost cytoplasm
Virion
   DomainCoiled coil
   LigandRNA-binding
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processevasion or tolerance by virus of host immune response

Inferred from direct assay PubMed 19828757. Source: CACAO

negative regulation of gene expression

Inferred from direct assay Ref.9. Source: CACAO

negative regulation of gene silencing by miRNA

Inferred from direct assay PubMed 22238300. Source: CACAO

suppression by virus of host IKBKE activity

Inferred from electronic annotation. Source: UniProtKB-KW

suppression by virus of host IRF3 activity by inhibition of IRF3 phosphorylation

Inferred from direct assay Ref.9. Source: CACAO

suppression by virus of host IRF7 activity by positive regulation of IRF7 sumoylation

Inferred from mutant phenotype PubMed 19557165. Source: CACAO

suppression by virus of host TBK1 activity

Inferred from electronic annotation. Source: UniProtKB-KW

suppression by virus of host antigen processing and presentation of peptide antigen via MHC class II

Inferred from mutant phenotype PubMed 19828757. Source: CACAO

suppression by virus of host cytokine production

Inferred from direct assay PubMed 19828757. Source: CACAO

suppression by virus of host toll-like receptor signaling pathway

Inferred from electronic annotation. Source: UniProtKB-KW

suppression by virus of host type I interferon production

Inferred from mutant phenotype Ref.12. Source: CACAO

suppression of host defenses

Inferred from mutant phenotype PubMed 21228243. Source: CACAO

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componenthost cell cytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

ribonucleoprotein complex

Inferred from direct assay PubMed 19041915. Source: CACAO

viral nucleocapsid

Inferred from direct assay Ref.8. Source: CACAO

   Molecular_functionRNA binding

Inferred from electronic annotation. Source: UniProtKB-KW

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 340340Polymerase cofactor VP35
PRO_0000222161

Regions

Coiled coil96 – 11621 Potential

Natural variations

Natural variant121A → V in strain: Isolate mouse-adapted.

Experimental info

Mutagenesis90 – 934LASL → AASA: Complete loss of homotrimerization; when associated with A-107. Ref.11
Mutagenesis1071L → A: Complete loss of homotrimerization; when associated with 90-AASA-93. Ref.11
Mutagenesis3051R → A: No effect on IRF3 promoter inhibition. Ref.10
Mutagenesis3091K → A: Partial loss of IRF3 promoter inhibition. Complete loss of dsRNA-binding. Ref.10 Ref.12
Mutagenesis3121R → A: Complete loss of IRF3 promoter inhibition. Complete loss of dsRNA-binding. Ref.10 Ref.12

Secondary structure

......................... 340
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q05127 [UniParc].

Last modified February 1, 1994. Version 1.
Checksum: B171C7FDBB5B1FBD

FASTA34037,362
        10         20         30         40         50         60 
MTTRTKGRGH TAATTQNDRM PGPELSGWIS EQLMTGRIPV SDIFCDIENN PGLCYASQMQ 

        70         80         90        100        110        120 
QTKPNPKTRN SQTQTDPICN HSFEEVVQTL ASLATVVQQQ TIASESLEQR ITSLENGLKP 

       130        140        150        160        170        180 
VYDMAKTISS LNRVCAEMVA KYDLLVMTTG RATATAAATE AYWAEHGQPP PGPSLYEESA 

       190        200        210        220        230        240 
IRGKIESRDE TVPQSVREAF NNLNSTTSLT EENFGKPDIS AKDLRNIMYD HLPGFGTAFH 

       250        260        270        280        290        300 
QLVQVICKLG KDSNSLDIIH AEFQASLAEG DSPQCALIQI TKRVPIFQDA APPVIHIRSR 

       310        320        330        340 
GDIPRACQKS LRPVPPSPKI DRGWVCVFQL QDGKTLGLKI 

« 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].
Strain: Isolate mouse-adapted.
[6]"Comparison of the transcription and replication strategies of marburg virus and Ebola virus by using artificial replication systems."
Muhlberger E., Weik M., Volchkov V.E., Klenk H.D., Becker S.
J. Virol. 73:2333-2342(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN VIRAL REPLICATION.
[7]"The Ebola virus VP35 protein functions as a type I IFN antagonist."
Basler C.F., Wang X., Muhlberger E., Volchkov V.E., Paragas J., Klenk H.D., Garcia-Sastre A., Palese P.
Proc. Natl. Acad. Sci. U.S.A. 97:12289-12294(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[8]"The assembly of Ebola virus nucleocapsid requires virion-associated proteins 35 and 24 and posttranslational modification of nucleoprotein."
Huang Y., Xu L., Sun Y., Nabel G.J.
Mol. Cell 10:307-316(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH THE NUCLEOPROTEIN.
[9]"The Ebola virus VP35 protein inhibits activation of interferon regulatory factor 3."
Basler C.F., Mikulasova A., Martinez-Sobrido L., Paragas J., Muhlberger E., Bray M., Klenk H.D., Palese P., Garcia-Sastre A.
J. Virol. 77:7945-7956(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[10]"A C-terminal basic amino acid motif of Zaire ebolavirus VP35 is essential for type I interferon antagonism and displays high identity with the RNA-binding domain of another interferon antagonist, the NS1 protein of influenza A virus."
Hartman A.L., Towner J.S., Nichol S.T.
Virology 328:177-184(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF ARG-305; LYS-309 AND ARG-312.
[11]"Homo-oligomerization facilitates the interferon-antagonist activity of the ebolavirus VP35 protein."
Reid S.P., Cardenas W.B., Basler C.F.
Virology 341:179-189(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: HOMOTRIMERIZATION, MUTAGENESIS OF 90-LEU--LEU-93 AND LEU-107.
[12]"Ebola virus VP35 Protein binds double-Stranded RNA and inhibits alpha/beta interferon production induced by RIG-I signaling."
Cardenas W.B., Loo Y.M., Gale M. Jr., Hartman A.L., Kimberlin C.R., Martinez-Sobrido L., Saphire E.O., Basler C.F.
J. Virol. 80:5168-5178(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF RNA-BINDING ACTIVITY, MUTAGENESIS OF LYS-309 AND ARG-312.
[13]"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 VP40.
[14]"VP35 knockdown inhibits Ebola virus amplification and protects against lethal infection in mice."
Enterlein S., Warfield K.L., Swenson D.L., Stein D.A., Smith J.L., Gamble C.S., Kroeker A.D., Iversen P.L., Bavari S., Muhlberger E.
Antimicrob. Agents Chemother. 50:984-993(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[15]"The VP35 protein of Ebola virus inhibits the antiviral effect mediated by double-stranded RNA-dependent protein kinase PKR."
Feng Z., Cerveny M., Yan Z., He B.
J. Virol. 81:182-192(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[16]"Ebola virus protein VP35 impairs the function of interferon regulatory factor-activating kinases IKKepsilon and TBK-1."
Prins K.C., Cardenas W.B., Basler C.F.
J. Virol. 83:3069-3077(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH HOST IKBKE AND TBK1, PHOSPHORYLATION BY HOST IKBKE.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X61274 Genomic RNA. Translation: CAA43578.1.
L11365 Genomic RNA. Translation: AAB81002.1.
AF086833 Genomic RNA. Translation: AAD14582.1.
AF272001 Genomic RNA. Translation: AAG40165.1.
AY142960 Genomic RNA. Translation: AAN37505.1.
AF499101 Genomic RNA. Translation: AAM76032.1.
RefSeqNP_066244.1. NC_002549.1.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3FKEX-ray1.40A/B215-340[»]
3L25X-ray2.00A/B/D/E215-340[»]
3L26X-ray2.40A/B215-340[»]
3L27X-ray1.95A/B/C/D215-340[»]
3L28X-ray2.40A/B/C/D/E/F215-338[»]
3L29X-ray1.70A/B215-340[»]
4IBBX-ray1.75A/B215-340[»]
4IBCX-ray1.74A/B215-340[»]
4IBDX-ray1.84A/B215-340[»]
4IBEX-ray1.95A/B215-340[»]
4IBFX-ray2.29A/B215-340[»]
4IBGX-ray1.41A/B215-340[»]
4IBIX-ray1.47A/B215-340[»]
4IBJX-ray1.54A/B215-340[»]
4IBKX-ray1.85A/B215-340[»]
4IJEX-ray1.90A/B/C/D218-340[»]
4IJFX-ray2.51A218-340[»]
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

DIPDIP-48771N.
IntActQ05127. 54 interactions.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID911827.

Family and domain databases

InterProIPR002953. Filo_VP35.
[Graphical view]
PfamPF02097. Filo_VP35. 1 hit.
[Graphical view]
PIRSFPIRSF018326. VP35_FiloV. 1 hit.
PRINTSPR01240. FILOVP35.
ProtoNetSearch...

Other

EvolutionaryTraceQ05127.

Entry information

Entry nameVP35_EBOZM
AccessionPrimary (citable) accession number: Q05127
Secondary accession number(s): Q77LU7, Q8JS63
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: February 1, 1994
Last modified: May 14, 2014
This is version 67 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