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Protein

Polymerase cofactor VP35

Gene

VP35

Organism
Zaire ebolavirus (strain Mayinga-76) (ZEBOV) (Zaire Ebola virus)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Acts 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.6 Publications

GO - Molecular functioni

GO - Biological processi

  • evasion or tolerance by virus of host immune response Source: CACAO
  • negative regulation of gene expression Source: CACAO
  • negative regulation of gene silencing by miRNA Source: CACAO
  • suppression by virus of host antigen processing and presentation of peptide antigen via MHC class II Source: CACAO
  • suppression by virus of host cytokine production Source: CACAO
  • suppression by virus of host IKBKE activity Source: UniProtKB-KW
  • suppression by virus of host IRF3 activity by inhibition of IRF3 phosphorylation Source: CACAO
  • suppression by virus of host IRF7 activity by positive regulation of IRF7 sumoylation Source: CACAO
  • suppression by virus of host TBK1 activity Source: UniProtKB-KW
  • suppression by virus of host toll-like receptor signaling pathway Source: UniProtKB-KW
  • suppression by virus of host type I interferon production Source: CACAO
  • suppression of host defenses Source: CACAO
  • transcription, DNA-templated Source: UniProtKB-KW
Complete GO annotation...

Keywords - Biological processi

Host-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

Keywords - Ligandi

RNA-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Polymerase cofactor VP35
Gene namesi
Name:VP35
OrganismiZaire ebolavirus (strain Mayinga-76) (ZEBOV) (Zaire Ebola virus)
Taxonomic identifieri128952 [NCBI]
Taxonomic lineageiVirusesssRNA virusesssRNA negative-strand virusesMononegaviralesFiloviridaeEbolavirus
Virus hostiEpomops franqueti (Franquet's epauleted fruit bat) [TaxID: 77231]
Homo sapiens (Human) [TaxID: 9606]
Myonycteris torquata (Little collared fruit bat) [TaxID: 77243]
Proteomesi
  • UP000007209 Componenti: Genome

Subcellular locationi

GO - Cellular componenti

  • host cell cytoplasm Source: UniProtKB-SubCell
  • viral nucleocapsid Source: CACAO
Complete GO annotation...

Keywords - Cellular componenti

Host cytoplasm, Virion

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi90 – 934LASL → AASA: Complete loss of homotrimerization; when associated with A-107. 1 Publication
Mutagenesisi107 – 1071L → A: Complete loss of homotrimerization; when associated with 90-AASA-93. 1 Publication
Mutagenesisi305 – 3051R → A: No effect on IRF3 promoter inhibition. 1 Publication
Mutagenesisi309 – 3091K → A: Partial loss of IRF3 promoter inhibition. Complete loss of dsRNA-binding. 2 Publications
Mutagenesisi312 – 3121R → A: Complete loss of IRF3 promoter inhibition. Complete loss of dsRNA-binding. 2 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 340340Polymerase cofactor VP35PRO_0000222161Add
BLAST

Post-translational modificationi

Phosphorylated by host IKBKE.1 Publication

Interactioni

Subunit structurei

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.By similarity3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
IKBKEQ141643EBI-6148294,EBI-307369From a different organism.
ILF3Q129066EBI-6148294,EBI-78756From a different organism.
NPP182722EBI-6148294,EBI-9820219
PRKRAO755692EBI-6148294,EBI-713955From a different organism.
TBK1Q9UHD22EBI-6148294,EBI-356402From a different organism.

Protein-protein interaction databases

DIPiDIP-48771N.
IntActiQ05127. 62 interactions.

Structurei

Secondary structure

1
340
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi28 – 347Combined sources
Helixi40 – 423Combined sources
Helixi221 – 2299Combined sources
Beta strandi232 – 2365Combined sources
Helixi238 – 25215Combined sources
Helixi256 – 26914Combined sources
Helixi273 – 28311Combined sources
Helixi285 – 2873Combined sources
Beta strandi294 – 2996Combined sources
Helixi300 – 3023Combined sources
Helixi305 – 3106Combined sources
Helixi320 – 3223Combined sources
Beta strandi324 – 3307Combined sources
Beta strandi331 – 3333Combined sources
Beta strandi335 – 3395Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
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[»]
4YPIX-ray3.71E/F/G/H20-47[»]
4ZTAX-ray2.40A15-59[»]
4ZTGX-ray2.80A15-59[»]
4ZTIX-ray2.40A/B15-59[»]
ProteinModelPortaliQ05127.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ05127.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini215 – 340126VP35 IIDPROSITE-ProRule annotationAdd
BLAST

Coiled coil

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Coiled coili96 – 11621Sequence analysisAdd
BLAST

Sequence similaritiesi

Belongs to the filoviridae polymerase cofactor VP35 family.PROSITE-ProRule annotationCurated
Contains 1 VP35 IID (interferon inhibitory) domain.PROSITE-ProRule annotation

Keywords - Domaini

Coiled coil

Family and domain databases

InterProiIPR002953. Filo_VP35.
IPR031163. VP35_IID.
[Graphical view]
PfamiPF02097. Filo_VP35. 1 hit.
[Graphical view]
PIRSFiPIRSF018326. VP35_FiloV. 1 hit.
PRINTSiPR01240. FILOVP35.
PROSITEiPS51735. VP35_IID. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q05127-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MTTRTKGRGH TAATTQNDRM PGPELSGWIS EQLMTGRIPV SDIFCDIENN
60 70 80 90 100
PGLCYASQMQ QTKPNPKTRN SQTQTDPICN HSFEEVVQTL ASLATVVQQQ
110 120 130 140 150
TIASESLEQR ITSLENGLKP VYDMAKTISS LNRVCAEMVA KYDLLVMTTG
160 170 180 190 200
RATATAAATE AYWAEHGQPP PGPSLYEESA IRGKIESRDE TVPQSVREAF
210 220 230 240 250
NNLNSTTSLT EENFGKPDIS AKDLRNIMYD HLPGFGTAFH QLVQVICKLG
260 270 280 290 300
KDSNSLDIIH AEFQASLAEG DSPQCALIQI TKRVPIFQDA APPVIHIRSR
310 320 330 340
GDIPRACQKS LRPVPPSPKI DRGWVCVFQL QDGKTLGLKI
Length:340
Mass (Da):37,362
Last modified:February 1, 1994 - v1
Checksum:iB171C7FDBB5B1FBD
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti12 – 121A → V in strain: Isolate mouse-adapted.

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
RefSeqiNP_066244.1. NC_002549.1.

Genome annotation databases

GeneIDi911827.
KEGGivg:911827.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
RefSeqiNP_066244.1. NC_002549.1.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
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[»]
4YPIX-ray3.71E/F/G/H20-47[»]
4ZTAX-ray2.40A15-59[»]
4ZTGX-ray2.80A15-59[»]
4ZTIX-ray2.40A/B15-59[»]
ProteinModelPortaliQ05127.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

DIPiDIP-48771N.
IntActiQ05127. 62 interactions.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi911827.
KEGGivg:911827.

Miscellaneous databases

EvolutionaryTraceiQ05127.

Family and domain databases

InterProiIPR002953. Filo_VP35.
IPR031163. VP35_IID.
[Graphical view]
PfamiPF02097. Filo_VP35. 1 hit.
[Graphical view]
PIRSFiPIRSF018326. VP35_FiloV. 1 hit.
PRINTSiPR01240. FILOVP35.
PROSITEiPS51735. VP35_IID. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiVP35_EBOZM
AccessioniPrimary (citable) accession number: Q05127
Secondary accession number(s): Q77LU7, Q8JS63
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: February 1, 1994
Last modified: January 20, 2016
This is version 76 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.