Protein: Serine/threonine-protein kinase US3 (P04413)
Organism: Human herpesvirus 1 (strain 17) (HHV-1) (Human herpes simplex virus 1)
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. Phosphorylates UL31 and UL34, two critical regulators of capsid budding from nucleus to endoplasmic reticulum, thereby facilitating virion egress. Modulates and redistributes host components of the nuclear envelope, including LMNA, emerin/EMD and the nuclear matrix protein MATR3. In turn, facilitates nuclear pore impairment and capsid release through impaired nuclear envelope. Phosphorylates envelope glycoprotein B (gB), probably to direct it to the cell surface. 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. Strongly inhibits TCR-activated signal transduction in T-cells by reducing the ubiquitination of LAT and TRAF6, leading to a suboptimal activation of LAT. Subverts host antiviral innate immunity by inhibiting type I interferon production through hyperphosphorylation of beta-catenin/CTNNB1. In addition, phosphorylates the RNA sensor RIGI and the transcription factor IRF3 to prevent the RLR-mediated antiviral signaling pathway. Hyperphosphorylates host RELA and thereby dampens NF-kappa-B signaling. Acts as an immunoevasin partly responsible for inhibition of MR1 expression and antigen presentation in response to bacterial infection
Subcellular location: Host cytoplasm. Host nucleus
Sequence: MACRKFCRVYGGQGRRKEEAVPPETKPSRVFPHGPFYTPAEDACLDSPPPETPKPSHTTPPSEAERLCHLQEILAQMYGNQDYPIEDDPSADAADDVDEDAPDDVAYPEEYAEELFLPGDATGPLIGANDHIPPPCGASPPGIRRRSRDEIGATGFTAEELDAMDREAARAISRGGKPPSTMAKLVTGMGFTIHGALTPGSEGCVFDSSHPDYPQRVIVKAGWYTSTSHEARLLRRLDHPAILPLLDLHVVSGVTCLVLPKYQADLYTYLSRRLNPLGRPQIAAVSRQLLSAVDYIHRQGIIHRDIKTENIFINTPEDICLGDFGAACFVQGSRSSPFPYGIAGTIDTNAPEVLAGDPYTTTVDIWSAGLVIFETAVHNASLFSAPRGPKRGPCDSQITRIIRQAQVHVDEFSPHPESRLTSRYRSRAAGNNRPPYTRPAWTRYYKMDIDVEYLVCKALTFDGALRPSAAELLCLPLFQQK
InterPro domains: - IPR008271: Serine/threonine-protein kinase, active site (active_site) [301-313]
- IPR050660: NEK Serine/Threonine Protein Kinase (family) [228-479]
- IPR011009: Protein kinase-like domain superfamily (homologous_superfamily) [190-480]
- IPR000719: Protein kinase domain (domain) [191-478]
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0005515 (protein binding)
Biological Process (BP): GO:0008150 (biological process), GO:0065007 (biological regulation), GO:0050789 (regulation of biological process), GO:0048519 (negative regulation of biological process), GO:0016032 (viral process), GO:0044419 (biological process involved in interspecies interaction between organisms), GO:0009892 (negative regulation of metabolic process), GO:0035821 (modulation of process of another organism), GO:0044068 (modulation by symbiont of host cellular process), GO:0019222 (regulation of metabolic process), GO:0019048 (modulation by virus of host process), GO:0044403 (biological process involved in symbiotic interaction), GO:0050794 (regulation of cellular process), GO:0051701 (biological process involved in interaction with host), GO:0060255 (regulation of macromolecule metabolic process), GO:0010605 (negative regulation of macromolecule metabolic process), GO:0039657 (suppression by virus of host gene expression), GO:0019054 (modulation by virus of host cellular process), GO:0044003 (modulation by symbiont of host process), GO:0052026 (modulation by symbiont of host transcription), GO:0019056 (modulation by virus of host transcription), GO:0039656 (modulation by virus of host gene expression), GO:0010629 (negative regulation of gene expression), GO:0010468 (regulation of gene expression)
Cellular Component (CC): GO:0005575 (cellular component), GO:0044423 (virion component), GO:0019033 (viral tegument)