VCPKMT Human

Valosin Containing Protein Lysine Methyltransferase (VCPKMT), also known as METTL21D, is a member of the Methyltransferase Family 16. This enzyme is responsible for the trimethylation of lysine 315 (K315) in the valosin-containing protein (VCP), also known as p97 . VCP is a crucial ATPase involved in various cellular processes, including membrane fusion and proteolysis .

VCPKMT is characterized by its seven β-strand structure, which is typical of lysine-specific methyltransferases . The enzyme specifically targets VCP, a homohexameric ATPase, and catalyzes the addition of methyl groups to the lysine residue at position 315 . This post-translational modification is essential for the proper functioning of VCP, which plays a critical role in maintaining cellular homeostasis, especially in the nervous system .

VCP is involved in a multitude of cellular processes, including the dismantling of protein aggregates and the removal of dysfunctional organelles . These functions are vital for preventing the malfunction of the brain and other parts of the nervous system. Mutations in VCP have been linked to various neurodegenerative diseases, highlighting the importance of VCPKMT in maintaining proteostasis .

Recent studies have shown that VCPKMT is ubiquitously expressed in all tissues and is localized to the cytoplasm . Knockout studies in mice have demonstrated that while VCPKMT is essential for the methylation of K315 in VCP, it is not critical for development or survival under unstressed conditions . This suggests that VCPKMT could be a potential target for therapeutic interventions in diseases where VCP function is compromised.