VRK3 Human

Vaccinia Related Kinase 3 (VRK3) is a member of the vaccinia-related kinase family, which includes three proteins: VRK1, VRK2, and VRK3. Unlike VRK1 and VRK2, which are catalytically active, VRK3 is a pseudokinase due to substitutions in key residues within its catalytic domain, rendering it inactive as a kinase .

The vaccinia-related kinase family was first described by Manning et al. in 2002. VRK3, specifically, was identified as a pseudokinase by Nichols and Traktman in 2004 . Despite its lack of kinase activity, VRK3 plays a significant role in cellular signaling through protein-protein interactions.

The human VRK3 gene is located on chromosome 19q13.33 and consists of 15 exons. Its mRNA is approximately 1.9 kilobases in length . VRK3 expression varies across different tissues and developmental stages. In mice, VRK3 mRNA is expressed throughout embryonic hematopoietic development, with peak expression in the liver during days E11.5 to E12.5 . In adult mice, VRK3 mRNA is expressed at similar levels in the liver, kidney, muscle, thymus, and bone marrow, with lower expression in the spleen .

The VRK3 protein consists of 474 amino acids and has a molecular weight of approximately 52.8 kilodaltons . Although VRK3 lacks kinase activity, it can modulate mitogen-activated protein kinase (MAPK) signaling in the nucleus by activating phosphatases such as VHR. This dephosphorylates extracellular signal-regulated protein kinase (ERK), reducing its ability to activate transcription .

VRK3 is involved in various cellular processes through its interactions with other proteins. It has been shown to deactivate MAPK signaling pathways, which are crucial for cell growth, differentiation, and survival . Interestingly, ERK activity promotes the transcription of VRK3, suggesting a feedback inhibition mechanism .

Recombinant VRK3 is produced using human embryonic kidney (HEK293) cells, which are commonly used in the production of biopharmaceuticals . These cells are transformed with sheared adenovirus type 5 DNA, allowing for the expression of recombinant proteins such as VRK3 .