| IED ID | IndEnz0002015344 |
| Enzyme Type ID | protease015344 |
| Protein Name |
E3 ubiquitin-protein ligase ICP0 EC 2.3.2.27 Alpha-0 protein Immediate-early protein IE110 RING-type E3 ubiquitin transferase ICP0 Trans-acting transcriptional protein ICP0 VMW110 |
| Gene Name | ICP0 IE110 |
| Organism | Human herpesvirus 1 (strain 17) (HHV-1) (Human herpes simplex virus 1) |
| Taxonomic Lineage | Viruses Duplodnaviria Heunggongvirae Peploviricota Herviviricetes Herpesvirales Herpesviridae Alphaherpesvirinae Simplexvirus Human herpesvirus 1 (HHV-1) (Human herpes simplex virus 1) Human herpesvirus 1 (strain 17) (HHV-1) (Human herpes simplex virus 1) |
| Enzyme Sequence | MEPRPGASTRRPEGRPQREPAPDVWVFPCDRDLPDSSDSEAETEVGGRGDADHHDDDSASEADSTDTELFETGLLGPQGVDGGAVSGGSPPREEDPGSCGGAPPREDGGSDEGDVCAVCTDEIAPHLRCDTFPCMHRFCIPCMKTWMQLRNTCPLCNAKLVYLIVGVTPSGSFSTIPIVNDPQTRMEAEEAVRAGTAVDFIWTGNQRFAPRYLTLGGHTVRALSPTHPEPTTDEDDDDLDDADYVPPAPRRTPRAPPRRGAAAPPVTGGASHAAPQPAAARTAPPSAPIGPHGSSNTNTTTNSSGGGGSRQSRAAAPRGASGPSGGVGVGVGVVEAEAGRPRGRTGPLVNRPAPLANNRDPIVISDSPPASPHRPPAAPMPGSAPRPGPPASAAASGPARPRAAVAPCVRAPPPGPGPRAPAPGAEPAARPADARRVPQSHSSLAQAANQEQSLCRARATVARGSGGPGVEGGHGPSRGAAPSGAAPLPSAASVEQEAAVRPRKRRGSGQENPSPQSTRPPLAPAGAKRAATHPPSDSGPGGRGQGGPGTPLTSSAASASSSSASSSSAPTPAGAASSAAGAASSSASASSGGAVGALGGRQEETSLGPRAASGPRGPRKCARKTRHAETSGAVPAGGLTRYLPISGVSSVVALSPYVNKTITGDCLPILDMETGNIGAYVVLVDQTGNMATRLRAAVPGWSRRTLLPETAGNHVMPPEYPTAPASEWNSLWMTPVGNMLFDQGTLVGALDFRSLRSRHPWSGEQGASTRDEGKQ |
| Enzyme Length | 775 |
| Uniprot Accession Number | P08393 |
| Absorption | |
| Active Site | |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.; EC=2.3.2.27; |
| DNA Binding | |
| EC Number | 2.3.2.27 |
| Enzyme Function | FUNCTION: SUMO-targeted ubiquitin ligase that plays an essential role in nuclear antiviral defense evasion triggered by dsDNA viruses (PubMed:32001251). Acts during the initial stages of lytic infection and the reactivation of latent viral genome. Prevents the antiviral effect of nuclear bodies by degrading host PML, SP100 and MORC3 (PubMed:27440897, PubMed:34759314). Prevents antiviral response to viral DNA induced by IFI16 by degrading it. Additionally, inhibits host IRF3 nuclear signaling to prevent interferon production by the infected cells. Interestingly, the E3 ubiquitin ligase activity associated with the RING finger domain does not seem to be directly required to inhibit the activation of IRF3 but instead plays a critical role in modulating the cellular localization of ICP0. Upon reactivation of latent genome, suppresses the silencing of viral DNA by dissociating either HDAC1 or HDAC2 from the HDAC-RCOR1-REST-KDM1A complex localized at the ND10 structures and causes their dispersal. Two cellular histone ubiquitin ligases RNF8 and RNF168 are also targeted by ICP0 for degradation, leading to a loss of ubiquitinated forms of H2A, a relief of transcriptional repression, and the activation of latent viral genomes. Enhances the localization of host CCND3 to ND10 bodies that serve as precursors of replication compartments to enable efficient viral replication. Like many RING-finger E3 ubiquitin ligases, ICP0 can induce its own ubiquitination, an activity that promotes its instability due to its targeting to the 26S proteasome for degradation. ICP0 restricts this process by recruiting the cellular ubiquitin-specific protease USP7 that cleaves the anchored ubiquitin chains from ICP0, thereby promoting its stabilization. {ECO:0000269|PubMed:15897453, ECO:0000269|PubMed:16160161, ECO:0000269|PubMed:20075863, ECO:0000269|PubMed:20106921, ECO:0000269|PubMed:20454685, ECO:0000269|PubMed:22405594, ECO:0000269|PubMed:23027953, ECO:0000269|PubMed:27440897, ECO:0000269|PubMed:34759314}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Beta strand (1); Chain (1); Compositional bias (7); Modified residue (1); Mutagenesis (1); Region (2); Zinc finger (1) |
| Keywords | 3D-structure;Activator;DNA-binding;Early protein;Host cytoplasm;Host nucleus;Host-virus interaction;Inhibition of host IRF3 by virus;Inhibition of host RLR pathway by virus;Inhibition of host innate immune response by virus;Inhibition of host mitotic exit by virus;Metal-binding;Modulation of host cell cycle by virus;Modulation of host ubiquitin pathway by viral E3 ligase;Modulation of host ubiquitin pathway by virus;Phosphoprotein;Reference proteome;Transcription;Transcription regulation;Transferase;Ubl conjugation;Ubl conjugation pathway;Viral immunoevasion;Viral latency;Viral reactivation from latency;Zinc;Zinc-finger |
| Interact With | P30281; O15379; P56524; Q9UQL6; Q8WUI4; Q9UKL0; Q93008 |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Host cytoplasm {ECO:0000269|PubMed:20454685}. Host nucleus {ECO:0000269|PubMed:20454685}. |
| Modified Residue | MOD_RES 67; /note="Phosphothreonine; by host; by CK1"; /evidence="ECO:0000269|PubMed:22405594, ECO:0000269|PubMed:32001251" |
| Post Translational Modification | PTM: Phosphorylated at Thr-67, leading to promote interaction with host RNF8 (PubMed:22405594). Phosphorylated by host CHEK2; leading to increased SUMO-targeted ubiquitin ligase activity of ICP0 (PubMed:32001251). {ECO:0000269|PubMed:22405594, ECO:0000269|PubMed:32001251}.; PTM: Auto-ubiquitinated. Deubiquitinated by host USP7; leading to stabilize it. {ECO:0000269|PubMed:15247261, ECO:0000269|PubMed:18590780}. |
| Signal Peptide | |
| Structure 3D | NMR spectroscopy (4); X-ray crystallography (3) |
| Cross Reference PDB | 4WPH; 4WPI; 5C56; 6JXU; 6JXV; 6JXW; 6JXX; |
| Mapped Pubmed ID | 15194749; 15824310; 22810585; 26046769; 26210801; 8995681; 9034339; 9311810; |
| Motif | |
| Gene Encoded By | |
| Mass | 78,457 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda |