F5HF68 · VIRF1_HHV8P
- ProteinVIRF-1
- GenevIRF-1
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids449 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Plays a role in the inhibition of host innate response by repressing the expression of interferon-inducible genes and blocking host IRF1- and IRF3-mediated transcription. Blocks the interaction between host IRF3 and CREBBP. Regulates the host cellular metabolism by increasing glucose uptake, ATP production and lactate secretion through down-regulation of heterogeneous nuclear ribonuclear protein Q1/SYNCRIP. Mechanistically, induces ubiquitination and degradation of SYNCRIP through the ubiquitin-proteasome pathway by recruiting KLHL3/CUL3 ubiquitin ligase complex (PubMed:35538151).
Disrupts host TP53 signaling pathway during viral infection by interacting with host USP7 and thereby decreasing the availability of USP7 for deubiquitinating and stabilizing TP53 (PubMed:26786098).
Plays a role in the global inhibition of protein ISGylation by interacting with host HERC5 leading to its inhibition (PubMed:26355087).
Promotes its own propionylation by blocking SIRT6 interaction with ubiquitin-specific peptidase 10/USP10 leading to SIRT6 degradation via a ubiquitin-proteasome pathway (PubMed:37023208).
In turn, propionylation is required to block IRF3-CBP/p300 recruitment and to repress the STING DNA sensing pathway (PubMed:37023208).
Plays a role in the activation of mitophagy during infection via interaction with the host proteins NIX/BNIP3L, TUFM and GABARAPL1 thereby inhibiting antiviral responses and contributing to productive replication (PubMed:31324791, PubMed:37459327).
Disrupts host TP53 signaling pathway during viral infection by interacting with host USP7 and thereby decreasing the availability of USP7 for deubiquitinating and stabilizing TP53 (PubMed:26786098).
Plays a role in the global inhibition of protein ISGylation by interacting with host HERC5 leading to its inhibition (PubMed:26355087).
Promotes its own propionylation by blocking SIRT6 interaction with ubiquitin-specific peptidase 10/USP10 leading to SIRT6 degradation via a ubiquitin-proteasome pathway (PubMed:37023208).
In turn, propionylation is required to block IRF3-CBP/p300 recruitment and to repress the STING DNA sensing pathway (PubMed:37023208).
Plays a role in the activation of mitophagy during infection via interaction with the host proteins NIX/BNIP3L, TUFM and GABARAPL1 thereby inhibiting antiviral responses and contributing to productive replication (PubMed:31324791, PubMed:37459327).
Features
Showing features for dna binding.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
DNA binding | 89-195 | IRF tryptophan pentad repeat | ||||
Sequence: KASIKDWIVCQVNSGKFPGVEWEDEERTRFRIPVTPLADPCFEWRRDGELGVVYIRERGNMPVDASFKGTRGRRRMLAALRRTRGLQEIGKGISQDGHHFLVFRVRK |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | host cell cytoplasm | |
Cellular Component | host cell nucleus | |
Molecular Function | DNA-binding transcription factor activity, RNA polymerase II-specific | |
Molecular Function | protein domain specific binding | |
Molecular Function | protein sequestering activity | |
Molecular Function | RNA polymerase II cis-regulatory region sequence-specific DNA binding | |
Biological Process | symbiont-mediated perturbation of host cellular process | |
Biological Process | symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of IRF3 activity | |
Biological Process | symbiont-mediated suppression of host innate immune response | |
Biological Process | virus-mediated perturbation of host defense response |
Keywords
- Biological process
In host cells, VIRF-1 binds directly to NIX and activates NIX-mediated mitophagy.
In host cells, VIRF-1 localizes to mitochondria and inhibits MAVS-mediated antiviral signaling.
In host cells, VIRF-1 binds to BID and inhibits BID-induced apoptosis.
In host cells, VIRF-1 binds to and sequesters BimEL into the nucleus to inhibit BimEL-induced apoptosis.
Names & Taxonomy
Protein names
- Recommended nameVIRF-1
Gene names
- Community suggested namesVIRF-1; HHV-8 K9.
- Community suggested namesVIRF-1; HHV-8 K9.
- Community suggested namesVIRF-1; HHV-8 K9.
- Community suggested namesVIRF-1; HHV-8 K9.
Organism names
- Taxonomic lineageViruses > Duplodnaviria > Heunggongvirae > Peploviricota > Herviviricetes > Herpesvirales > Orthoherpesviridae > Gammaherpesvirinae > Rhadinovirus > Rhadinovirus humangamma8 > Human herpesvirus 8
- Virus hosts
Accessions
- Primary accessionF5HF68
Proteomes
Subcellular Location
Phenotypes & Variants
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 406 | Strong loss of propionylation. | ||||
Sequence: K → R | ||||||
Mutagenesis | 442 | Strong loss of propionylation. | ||||
Sequence: K → R |
PTM/Processing
Features
Showing features for chain, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000423778 | 1-449 | VIRF-1 | |||
Sequence: MDPGQRPNPFGAPGAIPKKPCLSQGSPGTSGSGAPCDEPSRSESPGEGPSGTGGSAAAGDITRQAVVAAITEWSRTRQLRISTGASEGKASIKDWIVCQVNSGKFPGVEWEDEERTRFRIPVTPLADPCFEWRRDGELGVVYIRERGNMPVDASFKGTRGRRRMLAALRRTRGLQEIGKGISQDGHHFLVFRVRKPEEEQCVECGVVAGAVHDFNNMARLLQEGFFSPGQCLPGEIVTPVPSCTTAEGQEAVIDWGRLFIRMYYNGEQVHELLTTSQSGCRISSALRRDPAVHYCAVGSPGQVWLPNVPNLACEIAKRELCDTLDACAKGILLTSSCNGIFCVCYHNGPVHFIGNTVPPDSGPLLLPQGKPTRIFNPNTFLVGLANSPLPAPSHVTCPLVKLWLGKPVAVGKLEPHAPSPRDFAARCSNFSDACVVLEIMPKPLWDAMQ | ||||||
Modified residue | 406 | N6-propionyllysine; by host | ||||
Sequence: K | ||||||
Modified residue | 442 | N6-propionyllysine; by host | ||||
Sequence: K |
Post-translational modification
ISGylated.
Propionylated in lysine residues Lys-406 and Lys-442, which is required for effective inhibition of IFN-beta production and antiviral signaling.
Keywords
- PTM
Interaction
Subunit
Forms homodimers (PubMed:37459327).
Interacts with host IRF3, IRF7, and CREBBP (PubMed:11314014).
Interacts with host SYNCRIP (PubMed:35538151).
Interacts with host USP7 (PubMed:26786098).
Interacts (via C-terminus) with host HERC5 (PubMed:26355087).
Interacts with host GABARAPL1 (PubMed:37459327).
Interacts with host SIRT6 (PubMed:37023208).
Interacts with host IRF3, IRF7, and CREBBP (PubMed:11314014).
Interacts with host SYNCRIP (PubMed:35538151).
Interacts with host USP7 (PubMed:26786098).
Interacts (via C-terminus) with host HERC5 (PubMed:26355087).
Interacts with host GABARAPL1 (PubMed:37459327).
Interacts with host SIRT6 (PubMed:37023208).
Protein-protein interaction databases
Structure
Family & Domains
Features
Showing features for region, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-60 | Disordered | ||||
Sequence: MDPGQRPNPFGAPGAIPKKPCLSQGSPGTSGSGAPCDEPSRSESPGEGPSGTGGSAAAGD | ||||||
Compositional bias | 23-37 | Polar residues | ||||
Sequence: SQGSPGTSGSGAPCD |
Sequence similarities
Belongs to the IRF family.
Family and domain databases
Sequence
- Sequence statusComplete
- Length449
- Mass (Da)48,460
- Last updated2011-06-28 v1
- Checksum3C6A4E48FD57521A
Features
Showing features for compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 23-37 | Polar residues | ||||
Sequence: SQGSPGTSGSGAPCD |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF148805 EMBL· GenBank· DDBJ | ABD28909.1 EMBL· GenBank· DDBJ | Genomic DNA |