UDP-N-acetylglucosamine--peptide N-acetylglucosaminyltransferase 110 kDa subunit

O-GlcNAc transferase (OGT) is an N-acetylglucosamine transferase that catalyzes the addition of O-linked N-acetylglucosamine to serine and threonine residues of cytoplasmic and nuclear proteins (UniProt: O15294). This post-translational modification regulates numerous cellular processes including transcription, chromatin remodeling, glycolysis, mitochondrial motility, and autophagy, affecting diverse substrates such as MAPT/TAU, histones, and mTORC1 signaling components. OGT also plays roles in circadian clock regulation and glucose homeostasis.

OGT functions broadly across multiple cellular pathways and tissues. UniProt documents an association with X-linked intellectual developmental disorder 106 (XLID106), highlighting its importance in neurodevelopment. The protein interacts with chromatin-modifying complexes and serves as a component of transcriptional regulatory machinery alongside THAP and HCFC1 proteins.

In Alzheimer's disease, OGT is downregulated in human post-mortem AD brain tissue compared to age-matched controls (Chaparral AD proteomics), with a mean log2 fold-change of −0.50 across a single subcellular fraction. This reduced expression may affect O-GlcNAcylation of disease-relevant proteins including tau (MAPT), potentially influencing tau pathology and synaptic dysfunction in AD.