Valosin-containing protein lysine methyltransferase (VCPKMT)

Valosin-containing protein lysine methyltransferase (VCPKMT, also known as METTL21D) is a class I protein lysine methyltransferase that specifically trimethylates lysine 315 on valosin-containing protein (VCP/p97), an essential and highly conserved ATPase involved in diverse cellular processes such as cell cycle regulation, membrane fusion, autophagy, and ubiquitin-mediated protein degradation[1][2][3][5]. VCPKMT is a highly specific enzyme for this substrate, ubiquitously expressed, and localizes to the cytoplasm[3][5]. Loss of VCPKMT abolishes VCP K315 trimethylation but does not produce overt pathology in mice under unstressed conditions[3][5]. VCPKMT and its methylation of VCP have been implicated in tumor metastasis and cellular migration, as well as in the regulation of VCP-related pathways important for cell growth and stress response, and may modulate susceptibility to cancer and neurodegenerative diseases via its substrate[1][4]. No direct drugs targeting VCPKMT are currently known, but the modification status of VCP-K315me3 may serve as a useful biomarker for activity or function in research and potentially for future therapeutic development[1][5].

Other names

METTL21DProtein N-lysine methyltransferase METTL21DC14orf138VCP-KMTmethyltransferase-like protein 21Dprotein-lysine methyltransferase METTL21D

Catalyzes trimethylation of Lys315 on VCP, regulating ATPase and chaperone functions of VCP