UniProt functional annotation for Q05127



	UniProt functional annotation for Q05127

UniProt code: Q05127.

Organism: Zaire ebolavirus (strain Mayinga-76) (ZEBOV) (Zaire Ebola virus).

Taxonomy: Viruses; Riboviria; Orthornavirae; Negarnaviricota; Haploviricotina; Monjiviricetes; Mononegavirales; Filoviridae; Ebolavirus.

Function: Plays an essential role in viral RNA synthesis and also a role in suppressing innate immune signaling (PubMed:11027311). Acts as a polymerase cofactor in the RNA polymerase transcription and replication complexes (PubMed:9971816, PubMed:16495261, PubMed:24495995). Serves as nucleoprotein/NP monomer chaperone prior to the formation of the large oligomeric RNA-bound complexes (By similarity). Regulates RNA synthesis by modulating NP-RNA interactions and interacting with DYNLL1 (PubMed:25741013). VP35-NP interaction controls the switch between RNA-bound NP and free NP and thus the switch between genome replication and genome packaging into the nucleocapsid (PubMed:25865894). Prevents establishment of cellular antiviral state, thereby suppressing host DC maturation (PubMed:26962215). Acts by inhibiting host DDX58/RIG-I activation both by shielding dsRNA from detection and by preventing PRKRA binding to DDX58 (PubMed:23870315). Blocks virus-induced phosphorylation and activation of interferon regulatory factor 3/IRF3, a transcription factor critical for the induction of interferons alpha and beta (PubMed:12829834). 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 (PubMed:12829834). Also inhibits the antiviral effect mediated by the host interferon-induced, double-stranded RNA-activated protein kinase EIF2AK2/PKR (PubMed:17065211). Increases PIAS1-mediated SUMOylation of IRF7, thereby repressing interferon transcription (PubMed:19557165). Also acts as a suppressor of RNA silencing by interacting with host DICER1, TARBP2/TRBP and PRKRA/PACT (By similarity). As a dimer, binds and sequesters dsRNA contributing to the inhibition of interferon production (By similarity). {ECO:0000250|UniProtKB:Q5XX07, ECO:0000250|UniProtKB:Q6V1Q9, ECO:0000250|UniProtKB:Q8JPY0, ECO:0000269|PubMed:11027311, ECO:0000269|PubMed:12829834, ECO:0000269|PubMed:16495261, ECO:0000269|PubMed:17065211, ECO:0000269|PubMed:19557165, ECO:0000269|PubMed:23870315, ECO:0000269|PubMed:24495995, ECO:0000269|PubMed:25741013, ECO:0000269|PubMed:25865894, ECO:0000269|PubMed:26962215, ECO:0000269|PubMed:9971816}.

Subunit: Homodimer (By similarity). Homooligomer; via the coiled coil domain (PubMed:16095644). Interacts with nucleoprotein NP and polymerase L; VP35 bridges L and NP and allows the formation of the polymerase complex (PubMed:25865894) (Probable). Also interacts with VP30; this interaction is regulated by VP30 phosphorylation (PubMed:23493393). 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. Interacts with host DYNLL1; this interaction stabilizes VP35 N-terminal oligomerization domain, enhances viral RNA synthesis but does not participate in suppressing the host innate immune response (PubMed:19403681, PubMed:25741013). Interacts with host PRKRA; this interaction inhibits the interaction between DDX58 and PRKRA. Interacts with dsRNA (PubMed:19122151, PubMed:20071589, PubMed:23870315). Interacts with host TRIM6; this interaction plays an important role in promoting efficient viral replication (PubMed:28679761). Interacts with host STAU1 (PubMed:30301857). Interacts with host IRF7, PIAS1 and UBE2I/UBC9; these interactions mediate the sumoylation of IRF7 and contribute to the inhibition of IFN-type I production (PubMed:19557165). Interacts with host DICER1; this interaction prevents TARBP2/TRBP binding to DICER1 and thus allows the virus to counteract host RNA silencing (By similarity). Interacts with host TARBP2/TRBP and PRKRA/PACT; these interactions prevent TARBP2 and PRKRA binding to DICER1 and thus allows the virus to counteract host RNA silencing (By similarity). {ECO:0000250|UniProtKB:Q6V1Q9, ECO:0000250|UniProtKB:Q8JPY0, ECO:0000269|PubMed:16095644, ECO:0000269|PubMed:19122151, ECO:0000269|PubMed:19403681, ECO:0000269|PubMed:19557165, ECO:0000269|PubMed:20071589, ECO:0000269|PubMed:23493393, ECO:0000269|PubMed:23870315, ECO:0000269|PubMed:25741013, ECO:0000269|PubMed:25865894, ECO:0000269|PubMed:28679761, ECO:0000269|PubMed:30301857, ECO:0000305|PubMed:31562565}.

Subcellular location: Virion. Host cytoplasm {ECO:0000269|PubMed:23493393, ECO:0000269|PubMed:28679761}.

Domain: The interferon inhibitory domain (IID) binds dsRNA. {ECO:0000269|PubMed:19122151}.

Ptm: Phosphorylated by host IKBKE (PubMed:19153231). Phosphorylation contributes to efficient viral replication and transcription (PubMed:31694758, PubMed:31562565). {ECO:0000269|PubMed:19153231, ECO:0000269|PubMed:31562565, ECO:0000269|PubMed:31694758}.

Similarity: Belongs to the filoviridae polymerase cofactor VP35 family. {ECO:0000255|PROSITE-ProRule:PRU01071}.

Annotations taken from UniProtKB at the EBI.


Organism:		Zaire ebolavirus (strain Mayinga-76) (ZEBOV) (Zaire Ebola virus).
Taxonomy:		Viruses; Riboviria; Orthornavirae; Negarnaviricota; Haploviricotina; Monjiviricetes; Mononegavirales; Filoviridae; Ebolavirus.



Function:		Plays an essential role in viral RNA synthesis and also a role in suppressing innate immune signaling (PubMed:11027311). Acts as a polymerase cofactor in the RNA polymerase transcription and replication complexes (PubMed:9971816, PubMed:16495261, PubMed:24495995). Serves as nucleoprotein/NP monomer chaperone prior to the formation of the large oligomeric RNA-bound complexes (By similarity). Regulates RNA synthesis by modulating NP-RNA interactions and interacting with DYNLL1 (PubMed:25741013). VP35-NP interaction controls the switch between RNA-bound NP and free NP and thus the switch between genome replication and genome packaging into the nucleocapsid (PubMed:25865894). Prevents establishment of cellular antiviral state, thereby suppressing host DC maturation (PubMed:26962215). Acts by inhibiting host DDX58/RIG-I activation both by shielding dsRNA from detection and by preventing PRKRA binding to DDX58 (PubMed:23870315). Blocks virus-induced phosphorylation and activation of interferon regulatory factor 3/IRF3, a transcription factor critical for the induction of interferons alpha and beta (PubMed:12829834). 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 (PubMed:12829834). Also inhibits the antiviral effect mediated by the host interferon-induced, double-stranded RNA-activated protein kinase EIF2AK2/PKR (PubMed:17065211). Increases PIAS1-mediated SUMOylation of IRF7, thereby repressing interferon transcription (PubMed:19557165). Also acts as a suppressor of RNA silencing by interacting with host DICER1, TARBP2/TRBP and PRKRA/PACT (By similarity). As a dimer, binds and sequesters dsRNA contributing to the inhibition of interferon production (By similarity). {ECO:0000250\|UniProtKB:Q5XX07, ECO:0000250\|UniProtKB:Q6V1Q9, ECO:0000250\|UniProtKB:Q8JPY0, ECO:0000269\|PubMed:11027311, ECO:0000269\|PubMed:12829834, ECO:0000269\|PubMed:16495261, ECO:0000269\|PubMed:17065211, ECO:0000269\|PubMed:19557165, ECO:0000269\|PubMed:23870315, ECO:0000269\|PubMed:24495995, ECO:0000269\|PubMed:25741013, ECO:0000269\|PubMed:25865894, ECO:0000269\|PubMed:26962215, ECO:0000269\|PubMed:9971816}.


Subunit:		Homodimer (By similarity). Homooligomer; via the coiled coil domain (PubMed:16095644). Interacts with nucleoprotein NP and polymerase L; VP35 bridges L and NP and allows the formation of the polymerase complex (PubMed:25865894) (Probable). Also interacts with VP30; this interaction is regulated by VP30 phosphorylation (PubMed:23493393). 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. Interacts with host DYNLL1; this interaction stabilizes VP35 N-terminal oligomerization domain, enhances viral RNA synthesis but does not participate in suppressing the host innate immune response (PubMed:19403681, PubMed:25741013). Interacts with host PRKRA; this interaction inhibits the interaction between DDX58 and PRKRA. Interacts with dsRNA (PubMed:19122151, PubMed:20071589, PubMed:23870315). Interacts with host TRIM6; this interaction plays an important role in promoting efficient viral replication (PubMed:28679761). Interacts with host STAU1 (PubMed:30301857). Interacts with host IRF7, PIAS1 and UBE2I/UBC9; these interactions mediate the sumoylation of IRF7 and contribute to the inhibition of IFN-type I production (PubMed:19557165). Interacts with host DICER1; this interaction prevents TARBP2/TRBP binding to DICER1 and thus allows the virus to counteract host RNA silencing (By similarity). Interacts with host TARBP2/TRBP and PRKRA/PACT; these interactions prevent TARBP2 and PRKRA binding to DICER1 and thus allows the virus to counteract host RNA silencing (By similarity). {ECO:0000250\|UniProtKB:Q6V1Q9, ECO:0000250\|UniProtKB:Q8JPY0, ECO:0000269\|PubMed:16095644, ECO:0000269\|PubMed:19122151, ECO:0000269\|PubMed:19403681, ECO:0000269\|PubMed:19557165, ECO:0000269\|PubMed:20071589, ECO:0000269\|PubMed:23493393, ECO:0000269\|PubMed:23870315, ECO:0000269\|PubMed:25741013, ECO:0000269\|PubMed:25865894, ECO:0000269\|PubMed:28679761, ECO:0000269\|PubMed:30301857, ECO:0000305\|PubMed:31562565}.
Subcellular location:		Virion. Host cytoplasm {ECO:0000269\|PubMed:23493393, ECO:0000269\|PubMed:28679761}.
Domain:		The interferon inhibitory domain (IID) binds dsRNA. {ECO:0000269\|PubMed:19122151}.
Ptm:		Phosphorylated by host IKBKE (PubMed:19153231). Phosphorylation contributes to efficient viral replication and transcription (PubMed:31694758, PubMed:31562565). {ECO:0000269\|PubMed:19153231, ECO:0000269\|PubMed:31562565, ECO:0000269\|PubMed:31694758}.
Similarity:		Belongs to the filoviridae polymerase cofactor VP35 family. {ECO:0000255\|PROSITE-ProRule:PRU01071}.