VRK3: Human vaccinia related kinase 3
PDB Code: 2JII
VRK3 belongs together with VRK1 and VRK2 to the vaccinia related kinase (VRK) protein family, which is characterized by notable sequence homology to the vaccinia virus-encoded B1 kinase (vvB1). Whereas VRK1 and VRK2 show kinase activity VRK3 has key amino acid substitutions that disrupt invariant motifs required for catalytic activity. It has therefore been suggested that VRK3 is catalytically inactive but enzymatic studies are lacking so far. The NH2-terminal region of the VRK3 contains a bipartite nuclear localization signal, which directs the protein to the nucleus.
In human VRK3 is widely expressed in liver, kidney, muscle, thymus, bone marrow and spleen. High VRK3 levels have also been detected in fetal liver where expression is developmentally regulated.
VRK3 has been shown to interact with the nuclear phosphatase VHR (vaccinia H1-related, DUSP3). Binding results in activation of VHR by a mechanism independent of kinase activity and complex formation with ERK. De-phosphorylation of ERK by VHR leads to ERK inactivation in the nucleus. We solved the structure of the VRK3 kinases domain at 2.0 Å resolution. This structure gives for the first time insight in the architecture of a pseudo-kinase domain, a presumably inactive catalytic domain that are found in many kinases families.
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