US3
Function
Multifunctional serine/threonine kinase that plays a role in several processes including egress of virus particles from the nucleus, modulation of the actin cytoskeleton and inhibition of host immune response (PubMed:25907557, PubMed:31249678, PubMed:34935440). Phosphorylates UL31 and UL34, two critical regulators of capsid budding from nucleus to endoplasmic reticulum, thereby facilitating virion egress (PubMed:15994828, PubMed:1656069). Modulates and redistributes host components of the nuclear envelope, including LMNA, emerin/EMD and the nuclear matrix protein MATR3 (PubMed:20962082). In turn, facilitates nuclear pore impairment and capsid release through impaired nuclear envelope (PubMed:31249678). Phosphorylates envelope glycoprotein B (gB), probably to direct it to the cell surface (PubMed:19846518). Promotes virus intracellular spread by restructuring host cell cytoskeleton. Blocks host apoptosis to extend cell survival and allow efficient viral replication. Promotes viral gene expression by phosphorylating host HDAC2 to reduce viral genome silencing (PubMed:20660201). Strongly inhibits TCR-activated signal transduction in T-cells by reducing the ubiquitination of LAT and TRAF6, leading to a suboptimal activation of LAT (PubMed:25907557). Subverts host antiviral innate immunity by inhibiting type I interferon production through hyperphosphorylation of beta-catenin/CTNNB1 (PubMed:31801859). In addition, phosphorylates the RNA sensor RIGI and the transcription factor IRF3 to prevent the RLR-mediated antiviral signaling pathway (PubMed:24049179, PubMed:34935440). Hyperphosphorylates host RELA and thereby dampens NF-kappa-B signaling (PubMed:24807716).
Post-translational modifications
Phosphorylated by UL13; this phosphorylation regulates subsequent phosphorylation of UL31 and UL34 by US3. Autophosphorylated.
Sequence Similarities
Belongs to the protein kinase superfamily. Ser/Thr protein kinase family.
Cellular localization
- Host cytoplasm
- Host nucleus
Alternative names
Serine/threonine-protein kinase US3, US3