Jumonji domain-containing protein 6 (JMJD6)

Jumonji domain-containing protein 6 (JMJD6) is a member of the JmjC family of Fe(II) and 2-oxoglutarate-dependent oxygenases with dual enzymatic activities in arginine demethylation and lysine hydroxylation. It modifies both histone and non-histone substrates, notably impacting chromatin structure, transcription regulation, RNA splicing, and epigenetic control. JMJD6 interacts with multiple regulatory proteins (including BRD4, U2AF65, Luc7L3, SRSF11) and single-stranded RNA, integrating it into varied cellular processes such as cell proliferation, differentiation, angiogenesis, immune signaling, and apoptosis. Overexpressed in numerous cancers, JMJD6 is linked to tumorigenesis and may represent a future therapeutic target—though its broad biological roles pose challenges for drug development. Initial characterization as a cell surface phosphatidylserine receptor has evolved due to evidence of nuclear, enzymatic activity; knockout models show that it is essential for normal development. Much research continues to clarify its substrate specificity, druggability, and impact on disease.

Other names

JMJD6KIAA0585PTDSRPTDSR1Bifunctional arginine demethylase and lysyl-hydroxylase JMJD6Histone arginine demethylase JMJD6JmjC domain-containing protein 6Lysyl-hydroxylase JMJD6Peptide-lysine 5-dioxygenase JMJD6Phosphatidylserine receptorProtein PTDSR

Enzyme inhibition: Blocking Fe(II)/2OG-dependent dioxygenase activity (demethylation and/or hydroxylation). Epigenetic modulation: Inhibition affects histone methylation status and gene transcription.