Human O-Linked-N-Acetylglucosamine Transferase,OGT ELI

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) (PubMed:26678539, PubMed:23103939, PubMed:21240259, PubMed:21285374, PubMed:15361863).

Glycosylates a large and diverse number of proteins including histone H2B, AKT1, EZH2, PFKL, KMT2E/MLL5, MAPT/TAU and HCFC1.

Can regulate their cellular processes via cross-talk between glycosylation and phosphorylation or by affecting proteolytic processing (PubMed:21285374).

Probably by glycosylating KMT2E/MLL5, stabilizes KMT2E/MLL5 by preventing its ubiquitination (PubMed:26678539).

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 activity (PubMed:22923583).

Component of a THAP1/THAP3-HCFC1-OGT complex that is required for the regulation of the transcriptional activity of RRM1.

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) (PubMed:22121020, PubMed:23353889).

As part of the NSL complex indirectly involved in acetylation of nucleosomal histone H4 on several lysine residues (PubMed:20018852).

O-GlcNAcylation of 'Ser-75' of EZH2 increases its stability, and facilitating the formation of H3K27me3 by the PRC2/EED-EZH2 complex (PubMed:24474760).

Regulates circadian oscillation of the clock genes and glucose homeostasis in the liver.

Stabilizes clock proteins ARNTL/BMAL1 and CLOCK through O-glycosylation, which prevents their ubiquitination and subsequent degradation.

Promotes the CLOCK-ARNTL/BMAL1-mediated transcription of genes in the negative loop of the circadian clock such as PER1/2 and CRY1/2 (PubMed:12150998, PubMed:19451179, PubMed:20018868, PubMed:20200153, PubMed:21285374, PubMed:15361863).

O-glycosylates HCFC1 and regulates its proteolytic processing and transcriptional activity (PubMed:21285374, PubMed:28584052, PubMed:28302723).

Regulates mitochondrial motility in neurons by mediating glycosylation of TRAK1 (By similarity).

Glycosylates HOXA1 (By similarity).

O-glycosylates FNIP1 (PubMed:30699359).

{ECO:0000250|UniProtKB:P56558, ECO:0000250|UniProtKB:Q8CGY8, ECO:0000269|PubMed:12150998, ECO:0000269|PubMed:15361863, ECO:0000269|PubMed:19451179, ECO:0000269|PubMed:20018852, ECO:0000269|PubMed:20018868, ECO:0000269|PubMed:20200153, ECO:0000269|PubMed:21240259, ECO:0000269|PubMed:21285374, ECO:0000269|PubMed:22121020, ECO:0000269|PubMed:22923583, ECO:0000269|PubMed:23103939, ECO:0000269|PubMed:23353889, ECO:0000269|PubMed:24474760, ECO:0000269|PubMed:26678539, ECO:0000269|PubMed:28302723, ECO:0000269|PubMed:28584052, ECO:0000269|PubMed:30699359}.; [Isoform 2]: the mitochondrial isoform (mOGT) is cytotoxic and triggers apoptosis in several cell types including INS1, an insulinoma cell line.

{ECO:0000269|PubMed:20824293}.