Human UTY(KDM6C) is a male-specific Nϵ-methyl lysyl demethylase

Louise J Walport, Richard J Hopkinson, Melanie Vollmar, Sarah K Madden, Carina Gileadi, Udo Oppermann, Christopher J Schofield, Catrine Johansson

Research output: Contribution to journalArticlepeer-review

157 Citations (SciVal)


The Jumonji C lysine demethylases (KDMs) are 2-oxoglutarate- and Fe(II)-dependent oxygenases. KDM6A (UTX) and KDM6B (JMJD3) are KDM6 subfamily members that catalyze demethylation of N(ϵ)-methylated histone 3 lysine 27 (H3K27), a mark important for transcriptional repression. Despite reports stating that UTY(KDM6C) is inactive as a KDM, we demonstrate by biochemical studies, employing MS and NMR, that UTY(KDM6C) is an active KDM. Crystallographic analyses reveal that the UTY(KDM6C) active site is highly conserved with those of KDM6B and KDM6A. UTY(KDM6C) catalyzes demethylation of H3K27 peptides in vitro, analogously to KDM6B and KDM6A, but with reduced activity, due to point substitutions involved in substrate binding. The results expand the set of human KDMs and will be of use in developing selective KDM inhibitors.

Original languageEnglish
Pages (from-to)18302-13
Number of pages12
JournalThe Journal of biological chemistry
Issue number26
Publication statusE-pub ahead of print - 5 May 2014

Bibliographical note

© 2014 by The American Society for Biochemistry and Molecular Biology, Inc.


  • Amino Acid Sequence
  • Crystallography, X-Ray
  • Histones/chemistry
  • Humans
  • Lysine/metabolism
  • Male
  • Methylation
  • Minor Histocompatibility Antigens
  • Models, Molecular
  • Molecular Sequence Data
  • Nuclear Proteins/chemistry
  • Protein Structure, Tertiary
  • Sequence Alignment
  • Species Specificity


Dive into the research topics of 'Human UTY(KDM6C) is a male-specific Nϵ-methyl lysyl demethylase'. Together they form a unique fingerprint.

Cite this