page_title: O-linked glycosylation
section_title: O-N-acetylglucosamine (O-GlcNAc)
hierarchical_section_title: O-linked glycosylation / Common types of O-glycosylation / O-N-acetylglucosamine (O-GlcNAc)
caption_attribution_description: English: O-GlcNAc transferase (OGT) adds O-GlcNAc onto proteins, O-GlcNAcase (OGA) removes this sugar addition. Addition and removal occurs continuously in a cycle.
context_page_description: O-linked glycosylation is the attachment of a sugar molecule to the oxygen atom of serine or threonine residues in a protein. O-glycosylation is a post-translational modification that occurs after the protein has been synthesised. In eukaryotes, it occurs in the endoplasmic reticulum, Golgi apparatus and occasionally in the cytoplasm; in prokaryotes, it occurs in the cytoplasm. Several different sugars can be added to the serine or threonine, and they affect the protein in different ways by changing protein stability and regulating protein activity. O-glycans, which are the sugars added to the serine or threonine, have numerous functions throughout the body, including trafficking of cells in the immune system, allowing recognition of foreign material, controlling cell metabolism and providing cartilage and tendon flexibility. Because of the many functions they have, changes in O-glycosylation are important in many diseases including cancer, diabetes and Alzheimer's. O-glycosylation occurs in all domains of life, including eukaryotes, archaea and a number of pathogenic bacteria including Burkholderia cenocepacia, Neisseria gonorrhoeae and Acinetobacter baumannii.
context_section_description: Addition of N-acetylglucosamine (O-GlcNAc) to serine and threonine residues usually occurs on cytoplasmic and nuclear proteins that remain in the cell, while O-GalNAc modifications usually occur on proteins that will be secreted. The modification was only recently discovered, but the number of proteins with it is increasing rapidly. It is the first example of glycosylation that does not occur on secretory proteins.
  O-GlcNAcylation differs from other O-glycosylation processes because there are usually no sugars added onto the core structure and because the sugar can be attached or removed from a protein several times. This addition and removal occurs in cycles and is performed by two very specific enzymes. O-GlcNAc is added by O-GlcNAc transferase (OGT)  and removed by O-GlcNAcase (OGA). Because there are only two enzymes that affect this specific modification, they are very tightly regulated and depend on a lot of other factors.
  Because O-GlcNAc can be added and removed, it is known as a dynamic modification and has a lot of similarities to phosphorylation. O-GlcNAcylation and phosphorylation can occur on the same threonine and serine residues, suggesting a complex relationship between these modifications that can affect many functions of the cell. The modification affects processes like the cells response to cellular stress, the cell cycle, protein stability and protein turnover. It may be implicated in neurodegenerative diseases like Parkinson’s and late-onset Alzheimer’s   and has been found to play a role in diabetes.
  Additionally, O-GlcNAcylation can enhance the Warburg Effect, which is defined as the change that occurs in the metabolism of cancer cells to favour their growth. Because both O-GlcNAcylation and phosphorylation can affect specific residues and therefore both have important functions in regulating signalling pathways, both of these processes provide interesting targets for cancer research.
caption: O-GlcNAc is added to the protein by O-GlcNAc transferase and is removed by O-GlcNAcase in a continuous cycle.
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