SET domain containing 6, protein lysine methyltransferase (SETD6)

SET domain containing 6, protein lysine methyltransferase (SETD6), is an enzyme that catalyzes the mono-methylation of specific lysine residues on both histone and non-histone proteins, notably transcription factors like RelA (subunit of NF-κB), and regulatory proteins such as PLK1, PAK4, and BRD4[2][1][3][4]. Through lysine methylation, SETD6 acts as an epigenetic regulator, influencing chromatin state and repressing or activating gene transcription in response to cellular signals. For example, SETD6-dependent monomethylation of RelA at lysine 310 recruits GLP, which further modifies chromatin and silences NF-κB target genes under basal conditions[1][4]. In addition, SETD6 negatively regulates mitotic progression by methylating PLK1, modulates Wnt/β-catenin signaling via PAK4 methylation, and controls mRNA translation gene expression by methylating BRD4[2][3][4]. Dysregulation of SETD6 can affect cell proliferation, inflammation, and oxidative stress responses, implicating this enzyme in cancer and other diseases[1][2]. Currently, there are no known specific drugs targeting SETD6, but its central role in epigenetic regulation and key signaling pathways makes it a notable target in disease biology.

Other names

SETD6N-lysine methyltransferase SETD6FLJ21148SET domain-containing protein 6

Mono-methylation of lysine residues on target proteins (e.g., RelA, PLK1, BRD4, PAK4); Regulation of transcriptional repression or activation via chromatin modulation