The UDP-N-acetylglucosamine--peptide N-acetylglucosaminyltransferase (OGT; ) is a heterotrimer of one 78kDa subunit and two 110kDa subunits. OGT catalyzes the transfer of a single N-acetylglucosamine from UDP-GlcNAc to a serine or threonine residue in a protein. Substrate proteins include histone H2B, AKT1, EZH2, PFKL, KMT2E/MLL5, MAPT/TAU and HCFC1. The consequences of this form of glycosylation are diverse, including insulin resistance in muscle and adipocyte cells (brought about by inhibiting the 'Thr-308' phosphorylation of AKT1) []; regulation of glycolysis by inhibiting PFKL activity []; in the cell cycle O-glycosylation stabilizes ARNTL/BMAL1 and CLOCK, preventing their ubiquitination and subsequent degradation []; glycosylation of HCFC1 and interaction with TET proteins promotes binding of the SET1/COMPASS methyltransferase SETD1A to chromatin []; and H2B GlcNAcylation is a histone modification that facilitates H2BK120 monoubiquitination []. It is a component of several complexes, including MLL5-L, NSL []and THAP1/THAP3-HCFC1-OGT [].This entry represents the 110kDa subunit which has thirteen tetratricopeptide (TPR) repeats that are required for substrate binding and oligomerization [].The NSL complex is involved in acetylation of nucleosomal histone H4 on several lysine residues and therefore may be involved in the regulation of transcription. The complex is composed of at least MOF/KAT8, KANSL1, KANSL2, KANSL3, MCRS1, PHF20, OGT1/OGT, WDR5 and HCFC1 [].
This entry represents the C-terminal domain of the O-linked beta-N-acetylglucosamine transferase (OGT, also known as UDP-N-acetylglucosamine--peptide N-acetylglucosaminyltransferase), which catalyses the transfer of a single GlcNAc to the Ser or Thr of nucleocytoplasmic proteins []. OGTs have two known domains: the N-terminal tetratricopeptide repeat domain and the C-terminal glycosyltransferase domain []. Deletions of the C-terminal domain result in a complete loss of the enzyme activity []. In animals, OGT is an essential protein that modifies transcription factors, nuclear pore proteins, kinases, and many other proteins. Abnormalities in OGT activities have been associated with type 2 diabetes [].
The pattern of DNA methylation at cytosine bases in the genome is tightly linked to gene expression []. TET proteins, including TET1/2/3, convert 5-methylcytosine to 5-hydroxymethylcytosine. They can also convert 5-methylcytosine to 5-formylcytosine and 5-carboxylcytosine []. They play roles in epigenetic regulation [, ]. Human TET2 mutations have been linked to various leukaemias. TET2 and TET3 interact with O-GlcNAc transferase (OGT) and promotes OGT-mediated GlcNAcylation []. The double epigenetic modifications on both DNA and histones by TET2 and OGT coordinate together for the regulation of gene transcription [].
