OGT
GeneName
OGT
Summary
OGT, also known as MGMT or hMGMT, is a 117 kDa protein that functions primarily as an O-linked N-acetylglucosaminyltransferase. It is expressed in various cellular compartments including the nucleus, cytoplasm, and mitochondria, and plays a critical role in the modification of proteins through O-GlcNAcylation. This post-translational modification is involved in numerous biological processes, including chromatin organisation, cellular responses to glucose, and the regulation of transcription by RNA polymerase II. OGT is also associated with cellular structures such as the histone acetyltransferase complex and glutamatergic synapses, highlighting its involvement in both gene expression regulation and neuronal function.
Importance
OGT is relevant to: - The regulation of gene expression and chromatin dynamics, impacting cellular responses to nutrient availability and stress. - The modulation of signalling pathways, including those related to insulin and glucose metabolism, which are critical in metabolic diseases. - The maintenance of stem cell populations and their differentiation, influencing developmental biology and regenerative medicine. - The regulation of synaptic functions and neuronal health, which has implications in neurodegenerative diseases and synaptic plasticity.
Top Products
For researchers investigating OGT, we recommend two excellent primary antibodies. The first is the well-cited polyclonal antibody, Anti-OGT / O-Linked N-Acetylglucosamine Transferase antibody (ab96718), which has garnered 65 citations, highlighting its reliability in the field. This antibody is suitable for various applications, including Western blotting (WB), immunohistochemistry (IHC), immunocytochemistry (ICC), and immunoprecipitation (IP). Additionally, we offer the recombinant antibody, Anti-OGT / O-Linked N-Acetylglucosamine Transferase antibody [EPR12713] (ab177941). This product has been validated in multiple applications, such as WB, IHC, ICC, and flow cytometry (FC), making it a versatile option for researchers seeking consistent performance across experiments. With 35 citations, it is also gaining recognition in the research community. Together, these antibodies provide robust tools for studying OGT effectively.
Abcam Product Citation Summary
The data indicates that OGT is being studied in various contexts, particularly in relation to cancer, hypoxia, and metabolic processes. The use of Abcam antibodies in both human and mouse models highlights the relevance of OGT in understanding gene expression changes under different physiological conditions, including tumorigenesis and lipid metabolism.
Abcam Product Citation Table
Domain
The TPR repeat domain is required for substrate binding and oligomerization.
Function
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:12150998, PubMed:15361863, PubMed:19451179, PubMed:20018868, PubMed:21240259, PubMed:21285374, PubMed:23103939, PubMed:26237509, PubMed:26369908, PubMed:26678539, PubMed:27713473, PubMed:37541260, PubMed:37962578). 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 (PubMed:19451179, PubMed:20200153, PubMed:21285374, PubMed:22923583, PubMed:23353889, PubMed:24474760, PubMed:26237509, PubMed:26369908, PubMed:26678539, PubMed:27527864, PubMed:30699359, PubMed:34074792, PubMed:34667079, PubMed:37541260, PubMed:37962578). Can regulate their cellular processes via cross-talk between glycosylation and phosphorylation or by affecting proteolytic processing (PubMed:21285374). 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). 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). Stabilizes KMT2E/MLL5 by mediating its glycosylation, thereby preventing KMT2E/MLL5 ubiquitination (PubMed:26678539). 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 (PubMed:21285374, PubMed:28302723, PubMed:28584052). Component of a THAP1/THAP3-HCFC1-OGT complex that is required for the regulation of the transcriptional activity of RRM1 (PubMed:20200153). Regulates mitochondrial motility in neurons by mediating glycosylation of TRAK1 (By similarity). Promotes autophagy by mediating O-glycosylation of ATG4B (PubMed:27527864). 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 (PubMed:30699359, PubMed:37541260).
Isoform 2
The mitochondrial isoform (mOGT) is cytotoxic and triggers apoptosis in several cell types including INS1, an insulinoma cell line.
Isoform 4
Has N-acetylglucosaminyltransferase activity: glycosylates proteins, such as HNRNPU, NEUROD1, NUP62 and PDCD6IP (PubMed:31527085). Displays specific substrate selectivity compared to other isoforms (PubMed:31527085).
Involvement in disease
Regulation of OGT activity and altered O-GlcNAcylations are implicated in diabetes and Alzheimer disease. O-GlcNAcylation of AKT1 affects insulin signaling and, possibly diabetes. Reduced O-GlcNAcylations and resulting increased phosphorylations of MAPT/TAU are observed in Alzheimer disease (AD) brain cerebrum.
Intellectual developmental disorder, X-linked 106
XLID106
A form of intellectual disability, a disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. Intellectual deficiency is the only primary symptom of non-syndromic X-linked forms, while syndromic forms present with associated physical, neurological and/or psychiatric manifestations.
None
The disease is caused by variants affecting the gene represented in this entry.
Pathway
Protein modification; protein glycosylation.
Post-translational modifications
Ubiquitinated, leading to its proteasomal degradation.
Phosphorylation on Ser-3 or Ser-4 by GSK3-beta positively regulates its activity (By similarity). Phosphorylation at Thr-454 by AMPK promotes nuclear localization (PubMed:24563466).
Glycosylated via autocatalysis; O-GlcNAcylation at Ser-399 promotes nuclear localization.
Isoform 4
Glycosylated via autocatalysis; does not affect the enzyme activity but regulates substrate selectivity.
Sequence Similarities
Belongs to the glycosyltransferase 41 family. O-GlcNAc transferase subfamily.
Tissue Specificity
Highly expressed in pancreas and to a lesser extent in skeletal muscle, heart, brain and placenta. Present in trace amounts in lung and liver.
Cellular localization
- Nucleus
- Cytoplasm
- Predominantly localizes to the nucleus (PubMed:26678539). Translocates into the nucleus via association with importin KPNA1 (PubMed:27713473).
- Isoform 2
- Mitochondrion
- Membrane
- Associates with the mitochondrial inner membrane.
- Isoform 3
- Cytoplasm
- Nucleus
- Cell membrane
- Mitochondrion membrane
- Cell projection
- Mostly in the nucleus. Retained in the nucleus via interaction with HCFC1 (PubMed:21285374). After insulin induction, translocated from the nucleus to the cell membrane via phosphatidylinositide binding. Colocalizes with AKT1 at the plasma membrane. TRAK1 recruits this protein to mitochondria. In the absence of TRAK1, localizes in cytosol and nucleus (By similarity).
- Isoform 4
- Cytoplasm
- Nucleus
Alternative names
UDP-N-acetylglucosamine--peptide N-acetylglucosaminyltransferase 110 kDa subunit, O-GlcNAc transferase subunit p110, O-linked N-acetylglucosamine transferase 110 kDa subunit, OGT