F5HDE4 · ORF45_HHV8P
- ProteinProtein ORF45
- GeneORF45
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids407 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Prevents the establishment of cellular antiviral state by blocking virus-induced phosphorylation and activation of host interferon regulatory factor 7/IRF7, a transcription factor critical for the induction of interferons alpha and beta (PubMed:11943871, PubMed:20485504, PubMed:22787218).
Mechanistically, ORF45 competes with the associated IRF7 and inhibits its phosphorylation by IKBKE or TBK1 by acting as an alternative substrate (PubMed:11943871, PubMed:22787218).
Acts as an activator of the NLRP1 inflammasome via interaction with the N-terminal part of host NLRP1: interaction promotes translocation of the N-terminal part of NLRP1 into the nucleus, relieving autoinhibition of the NLRP1 inflammasome and leading to its activation (PubMed:35618833).
Also plays a role in promoting the late transcription and translation of viral lytic genes by constitutively activating host extracellular signal-regulated kinase (ERK)-p90 ribosomal S6 kinase/RPS6KA1 (PubMed:30842327).
In addition, supports the viral replication cycle by modulating host p53/TP53 signaling pathway (PubMed:34523970).
Interacts with host p53/TP53 and prevents its interaction with the deubiquitinase USP7, leading to sequestration of P53/TP53 in the host cytoplasm thereby diminishing its transcriptional activity (PubMed:34523970).
Mechanistically, ORF45 competes with the associated IRF7 and inhibits its phosphorylation by IKBKE or TBK1 by acting as an alternative substrate (PubMed:11943871, PubMed:22787218).
Acts as an activator of the NLRP1 inflammasome via interaction with the N-terminal part of host NLRP1: interaction promotes translocation of the N-terminal part of NLRP1 into the nucleus, relieving autoinhibition of the NLRP1 inflammasome and leading to its activation (PubMed:35618833).
Also plays a role in promoting the late transcription and translation of viral lytic genes by constitutively activating host extracellular signal-regulated kinase (ERK)-p90 ribosomal S6 kinase/RPS6KA1 (PubMed:30842327).
In addition, supports the viral replication cycle by modulating host p53/TP53 signaling pathway (PubMed:34523970).
Interacts with host p53/TP53 and prevents its interaction with the deubiquitinase USP7, leading to sequestration of P53/TP53 in the host cytoplasm thereby diminishing its transcriptional activity (PubMed:34523970).
GO annotations
all annotations | all molecular function | virus receptor activity | dna binding | rna binding | cytoskeletal motor activity | catalytic activity | gtpase activity | structural molecule activity | transporter activity | cytoskeletal protein binding | lipid binding | cyclase activity | antioxidant activity | oxidoreductase activity | transferase activity | hydrolase activity | lyase activity | isomerase activity | ligase activity | protein tag activity | cargo receptor activity | histone binding | protein folding chaperone | translation regulator activity | nutrient reservoir activity | receptor ligand activity | molecular transducer activity | molecular adaptor activity | toxin activity | cell adhesion mediator activity | molecular function regulator activity | virus coreceptor activity | catalytic activity, acting on a protein | catalytic activity, acting on dna | catalytic activity, acting on rna | molecular carrier activity | transcription regulator activity | general transcription initiation factor activity | molecular sensor activity | molecular sequestering activity | atp-dependent activity | other molecular function | all biological process | mitotic cell cycle | cytokinesis | cytoplasmic translation | immune system process | muscle system process | circulatory system process | renal system process | respiratory system process | carbohydrate metabolic process | generation of precursor metabolites and energy | dna replication | dna repair | dna recombination | chromatin organization | dna-templated transcription | regulation of dna-templated transcription | trna metabolic process | protein folding | protein glycosylation | amino acid metabolic process | modified amino acid metabolic process | lipid metabolic process | vitamin metabolic process | sulfur compound metabolic process | intracellular protein transport | nucleocytoplasmic transport | autophagy | inflammatory response | mitochondrion organization | cytoskeleton organization | microtubule-based movement | peroxisome organization | lysosome organization | chromosome segregation | cell adhesion | establishment or maintenance of cell polarity | programmed cell death | photosynthesis | mrna metabolic process | snrna metabolic process | vesicle-mediated transport | reproductive process | digestive system process | signaling | cell differentiation | protein catabolic process | extracellular matrix organization | regulatory ncrna-mediated gene silencing | telomere organization | cell junction organization | wound healing | ribosome biogenesis | cilium organization | anatomical structure development | cell motility | nervous system process | endocrine process | protein maturation | transmembrane transport | nucleobase-containing small molecule metabolic process | hepaticobiliary system process | membrane organization | protein-containing complex assembly | cell wall organization or biogenesis | nitrogen cycle metabolic process | protein localization to plasma membrane | defense response to other organism | detoxification | meiotic nuclear division | mitotic nuclear division | mitochondrial gene expression | carbohydrate derivative metabolic process | other biological process | all cellular component | nuclear chromosome | extracellular region | extracellular space | cell wall | nucleus | nuclear envelope | nucleoplasm | chromosome | nucleolus | mitochondrion | lysosome | endosome | vacuole | peroxisome | endoplasmic reticulum | golgi apparatus | lipid droplet | microtubule organizing center | cytosol | ribosome | cytoskeleton | plasma membrane | cilium | plastid | thylakoid | external encapsulating structure | extracellular matrix | cytoplasmic vesicle | organelle | other cellular component | |||
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Aspect | Term | |
---|---|---|
Cellular Component | host cell Golgi apparatus | |
Cellular Component | host cell nucleus | |
Cellular Component | viral tegument | |
Biological Process | symbiont-mediated perturbation of host innate immune response | |
Biological Process | symbiont-mediated suppression of host cytoplasmic pattern recognition receptor signaling pathway via inhibition of IRF7 activity | |
Biological Process | virus-mediated perturbation of host defense response |
Keywords
- Biological process
Names & Taxonomy
Protein names
- Recommended nameProtein ORF45
Gene names
Organism names
- Taxonomic lineageViruses > Duplodnaviria > Heunggongvirae > Peploviricota > Herviviricetes > Herpesvirales > Orthoherpesviridae > Gammaherpesvirinae > Rhadinovirus > Rhadinovirus humangamma8 > Human herpesvirus 8
- Virus hosts
Accessions
- Primary accessionF5HDE4
Proteomes
Subcellular Location
UniProt Annotation
GO Annotation
Keywords
- Cellular component
Phenotypes & Variants
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 41 | Impairs the inhibition of host IRF7 transactivation activity. | ||||
Sequence: S → A | ||||||
Mutagenesis | 66 | Loss of sustained host ERK-RSK activation and decreases lytic replication. | ||||
Sequence: F → A | ||||||
Mutagenesis | 162 | Impairs the inhibition of host IRF7 transactivation activity. | ||||
Sequence: S → A | ||||||
Mutagenesis | 223 | Loss of p53/TP53 sequestration to the host cytoplasm; when associated with A-226. | ||||
Sequence: E → A | ||||||
Mutagenesis | 226 | Loss of p53/TP53 sequestration to the host cytoplasm; when associated with A-223. | ||||
Sequence: S → A |
PTM/Processing
Features
Showing features for chain, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000423770 | 1-407 | Protein ORF45 | |||
Sequence: MAMFVRTSSSTHDEERMLPIEGAPRRRPPVKFIFPPPPLSSLPGFGRPRGYAGPTVIDMSAPDDVFAEDTPSPPATPLDLQISPDQSSGESEYDEDEEDEDEEENDDVQEEDEPEGYPADFFQPLSHLRPRPLARRAHTPKPVAVVAGRVRSSTDTAESEASMGWVSQDDGFSPAGLSPSDDEGVAILEPMAAYTGTGAYGLSPASRNSVPGTQSSPYSDPDEGPSWRPLRAAPTAIVDLTSDSDSDDSSNSPDVNNEAAFTDARHFSHQPPSSEEDGEDQGEVLSQRIGLMDVGQKRKRQSTASSGSEDVVRCQRQPNLSRKAVASVIIISSGSDTDEEPSSAVSVIVSPSSTKGHLPTQSPSTSAHSISSGSTTTAGSRCSDPTRILASTPPLCGNGAYNWPWLD | ||||||
Modified residue | 41 | Phosphoserine; by host TBK1 and IKKE | ||||
Sequence: S | ||||||
Modified residue | 162 | Phosphoserine; by host TBK1 and IKKE | ||||
Sequence: S |
Post-translational modification
Phosphorylated on Ser-41 and Ser-162 by host IKBKE and TBK1.
Keywords
- PTM
PTM databases
Expression
Keywords
- Developmental stage
Interaction
Subunit
Interacts with host IRF7 (PubMed:11943871).
Interacts with host RPS6KA1 (PubMed:30842327).
Interacts with host RAB11FIP5; this interaction results in the lysosomal degradation of ORF45 and the inhibition of viral particle release (PubMed:33315947).
Interacts with host p53/TP53; this interaction down-regulates p53/TP53 signaling pathway (PubMed:34523970).
Interacts with the N-terminal part of host NLRP1; relieving autoinhibition of the NLRP1 inflammasome (PubMed:35618833).
Interacts with host RPS6KA1 (PubMed:30842327).
Interacts with host RAB11FIP5; this interaction results in the lysosomal degradation of ORF45 and the inhibition of viral particle release (PubMed:33315947).
Interacts with host p53/TP53; this interaction down-regulates p53/TP53 signaling pathway (PubMed:34523970).
Interacts with the N-terminal part of host NLRP1; relieving autoinhibition of the NLRP1 inflammasome (PubMed:35618833).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
XENO | F5HDE4 | IRF7 Q92985 | 3 | EBI-8843990, EBI-968267 |
Protein-protein interaction databases
Family & Domains
Features
Showing features for region, compositional bias, motif.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-183 | Disordered | ||||
Sequence: MAMFVRTSSSTHDEERMLPIEGAPRRRPPVKFIFPPPPLSSLPGFGRPRGYAGPTVIDMSAPDDVFAEDTPSPPATPLDLQISPDQSSGESEYDEDEEDEDEEENDDVQEEDEPEGYPADFFQPLSHLRPRPLARRAHTPKPVAVVAGRVRSSTDTAESEASMGWVSQDDGFSPAGLSPSDDE | ||||||
Compositional bias | 29-43 | Pro residues | ||||
Sequence: PVKFIFPPPPLSSLP | ||||||
Compositional bias | 89-117 | Acidic residues | ||||
Sequence: GESEYDEDEEDEDEEENDDVQEEDEPEGY | ||||||
Region | 196-318 | Disordered | ||||
Sequence: GTGAYGLSPASRNSVPGTQSSPYSDPDEGPSWRPLRAAPTAIVDLTSDSDSDDSSNSPDVNNEAAFTDARHFSHQPPSSEEDGEDQGEVLSQRIGLMDVGQKRKRQSTASSGSEDVVRCQRQP | ||||||
Compositional bias | 201-221 | Polar residues | ||||
Sequence: GLSPASRNSVPGTQSSPYSDP | ||||||
Compositional bias | 239-258 | Polar residues | ||||
Sequence: DLTSDSDSDDSSNSPDVNNE | ||||||
Motif | 284-294 | Nuclear export signal | ||||
Sequence: VLSQRIGLMDV | ||||||
Motif | 297-300 | Nuclear localization signal | ||||
Sequence: KRKR | ||||||
Compositional bias | 298-318 | Polar residues | ||||
Sequence: RKRQSTASSGSEDVVRCQRQP | ||||||
Compositional bias | 332-387 | Polar residues | ||||
Sequence: SSGSDTDEEPSSAVSVIVSPSSTKGHLPTQSPSTSAHSISSGSTTTAGSRCSDPTR | ||||||
Region | 332-407 | Disordered | ||||
Sequence: SSGSDTDEEPSSAVSVIVSPSSTKGHLPTQSPSTSAHSISSGSTTTAGSRCSDPTRILASTPPLCGNGAYNWPWLD |
Family and domain databases
Sequence
- Sequence statusComplete
- Length407
- Mass (Da)43,327
- Last updated2011-06-28 v1
- ChecksumF8F5876EFDA2BB35
Features
Showing features for compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 29-43 | Pro residues | ||||
Sequence: PVKFIFPPPPLSSLP | ||||||
Compositional bias | 89-117 | Acidic residues | ||||
Sequence: GESEYDEDEEDEDEEENDDVQEEDEPEGY | ||||||
Compositional bias | 201-221 | Polar residues | ||||
Sequence: GLSPASRNSVPGTQSSPYSDP | ||||||
Compositional bias | 239-258 | Polar residues | ||||
Sequence: DLTSDSDSDDSSNSPDVNNE | ||||||
Compositional bias | 298-318 | Polar residues | ||||
Sequence: RKRQSTASSGSEDVVRCQRQP | ||||||
Compositional bias | 332-387 | Polar residues | ||||
Sequence: SSGSDTDEEPSSAVSVIVSPSSTKGHLPTQSPSTSAHSISSGSTTTAGSRCSDPTR |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF148805 EMBL· GenBank· DDBJ | ABD28895.1 EMBL· GenBank· DDBJ | Genomic DNA |