JMJD6 Human

Jumonji Domain Containing 6 (JMJD6) is a member of the large family of Jumonji C (JmjC) domain-containing metalloenzymes. These proteins are ferrous iron (Fe²⁺)- and 2-oxoglutarate (2OG)-dependent dioxygenases that catalyze hydroxylation and demethylation reactions on protein and nucleic acid substrates . JMJD6 has been reported to catalyze both lysyl hydroxylation and arginyl demethylation on diverse protein substrates .

The JmjC domain was first described by Takeuchi and colleagues, who isolated a gene in the mouse which they called jumonji (meaning cruciform in Japanese), in regard to an abnormal phenotype visible in mutant embryos during neural plate development . JMJD6 was initially annotated to encode a transmembrane receptor for the engulfment of apoptotic cells, but this annotation was later corrected .

JMJD6 is one of the smallest JmjC proteins and appears to interact with multiple protein substrates in distinct molecular pathways . It contributes to the regulation of histone demethylation, transcriptional polymerase II promoter pause release, and mRNA splicing . The protein contains a conserved double-stranded β-helix (DSBH) fold and a HxDx_n_H facial triad as structural motifs .

JMJD6 plays a crucial role in various cellular processes. It has been implicated in lysyl hydroxylation and N-methyl argininyl demethylation, which are important for transcriptional control, chromatin structure, epigenetic inheritance, and genome integrity . The enzyme’s ability to catalyze arginine demethylation is particularly significant, as arginine methylation is one of the most extensive protein methylation reactions in mammalian cells .

Comparative genomic analysis has provided insights into the evolution of JMJD6 and other related members of the JmjC domain-containing protein family . This analysis has identified homologous sequences in 62 species across all major phyla, highlighting the evolutionary conservation of these proteins .

Recent studies have explored the diverse functions of JMJD6, including its roles in cancer and immune biology . The increased knowledge of JMJD6 functions has wider implications for our general understanding of the JmjC protein family.