Catalyzes the transfer of a single N-acetylglucosamine from UDP-GlcNAc to a serine or threonine residue in cytoplasmic and nuclear proteins resulting in their modification with a beta- linked N-acetylglucosamine (O-GlcNAc). Glycosylates a large and diverse number of proteins including histone H2B, AKT1, MLL5, MAPT/TAU and HCFC1. Can regulate their cellular processes via cross-talk between glycosylation and phosphorylation or by affecting proteolytic processing. Involved in insulin resistance in muscle and adipocyte cells via glycosylating insulin signaling components and inhibiting the 'Thr-308' phosphorylation of AKT1, enhancing IRS1 phosphorylation and attenuating insulin signaling. Component of a THAP1/THAP3-HCFC1-OGT complex that is required for the regulation of the transcriptional activity of RRM1. As part of the NSL complex it may be involved in acetylation of nucleosomal histone H4 on several lysine residues. Heterotrimer; consists of one 78 kDa subunit and two 110 kDa subunits dimerized via TPR repeats 6 and 7. Interacts (via TPR repeats 6 and 7) with ATXN10. Component of the MLL5-L complex, at least composed of MLL5, STK38, PPP1CA, PPP1CB, HCFC1, PPP1CC and ACTB. Component of a THAP1/THAP3-HCFC1-OGT complex. Component of the NSL complex at least composed of MOF/KAT8, KANSL1, KANSL2, KANSL3, MCRS1, PHF20, OGT1/OGT, WDR5 and HCFC1. Interacts directly with HCFC1; the interaction O- glycosylates HCFC1, regulates its proteolytic processing and transcriptional activity and, in turn, stabilizes OGT in the nucleus. Interacts (via TPRs 1-6) with SIN3A; the interaction mediates transcriptional repression in parallel with histone deacetylase. Induction of the nucleocytoplasmic OGT (ncOGT) isoform in the liver on glucose deprivation is mediated by the decreased hexosamine biosynthesis pathway (HBP) flux. Highly expressed in pancreas and to a lesser extent in skeletal muscle, heart, brain and placenta. Present in trace amounts in lung and liver. Subject to product inhibition by UDP. Belongs to the O-GlcNAc transferase family. 4 isoforms of the human protein are produced by alternative splicing. Note: This description may include information from UniProtKB.
Molecular Function: acetylglucosaminyltransferase activity; protein binding; phosphatidylinositol-3,4,5-triphosphate binding; protein N-acetylglucosaminyltransferase activity; enzyme activator activity; histone acetyltransferase activity (H4-K16 specific)
Biological Process: positive regulation of catalytic activity; regulation of Rac protein signal transduction; protein amino acid O-linked glycosylation; establishment and/or maintenance of chromatin architecture; regulation of insulin receptor signaling pathway; phosphoinositide-mediated signaling; apoptosis; positive regulation of proteolysis; regulation of glycolysis; positive regulation of granulocyte differentiation; positive regulation of transcription from RNA polymerase II promoter; positive regulation of histone H3-K4 methylation; signal transduction; response to nutrient; response to insulin stimulus
SS: The number of records in which this modification site was determined using site-specific methods. SS methods include amino acid sequencing, site-directed mutagenesis, modification site-specific antibodies, specific MS strategies, etc.