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

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)^{1,2,3,4,5,6,7,8,9,10,11,12,13}. Glycosylates a large and diverse number of proteins including histone H2B, AKT1, AMPK, ATG4B, CAPRIN1, EZH2, FNIP1, GSDMD, KRT7, LMNA, LMNB1, LMNB2, RPTOR, HOXA1, PFKL, KMT2E/MLL5, MAPT/TAU, TET2, RBL2, RET, NOD2 and HCFC1^{14,15,16,17,18,19,20,21,22,23,24,25,26,27,28}. Can regulate their cellular processes via cross-talk between glycosylation and phosphorylation or by affecting proteolytic processing²⁹. 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 (By similarity). Involved in glycolysis regulation by mediating glycosylation of 6-phosphofructokinase PFKL, inhibiting its activity³⁰. Plays a key role in chromatin structure by mediating O-GlcNAcylation of 'Ser-112' of histone H2B: recruited to CpG-rich transcription start sites of active genes via its interaction with TET proteins (TET1, TET2 or TET3)^31,32. As part of the NSL complex indirectly involved in acetylation of nucleosomal histone H4 on several lysine residues³³. O-GlcNAcylation of 'Ser-75' of EZH2 increases its stability, and facilitating the formation of H3K27me3 by the PRC2/EED-EZH2 complex³⁴. Stabilizes KMT2E/MLL5 by mediating its glycosylation, thereby preventing KMT2E/MLL5 ubiquitination³⁵. Regulates circadian oscillation of the clock genes and glucose homeostasis in the liver (By similarity). Stabilizes clock proteins BMAL1 and CLOCK through O-glycosylation, which prevents their ubiquitination and subsequent degradation (By similarity). Promotes the CLOCK-BMAL1-mediated transcription of genes in the negative loop of the circadian clock such as PER1/2 and CRY1/2. O-glycosylates HCFC1 and regulates its proteolytic processing and transcriptional activity^36,37,38. Component of a THAP1/THAP3-HCFC1-OGT complex that is required for the regulation of the transcriptional activity of RRM1³⁹. Regulates mitochondrial motility in neurons by mediating glycosylation of TRAK1 (By similarity). Promotes autophagy by mediating O-glycosylation of ATG4B⁴⁰. Acts as a regulator of mTORC1 signaling by mediating O-glycosylation of RPTOR and FNIP1: O-GlcNAcylation of RPTOR in response to glucose sufficiency promotes activation of the mTORC1 complex^41,42. The mitochondrial isoform (mOGT) is cytotoxic and triggers apoptosis in several cell types including INS1, an insulinoma cell line. Has N-acetylglucosaminyltransferase activity: glycosylates proteins, such as HNRNPU, NEUROD1, NUP62 and PDCD6IP⁴³. Displays specific substrate selectivity compared to other isoforms⁴⁴.

AlphaFold DB , UniProt , Accession O15294, Species HUMAN (Homo sapiens, Human), Gene OGT, Length 1,046 aa.