Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
additional information | Drosophila melanogaster | O-GlcNAc is added to Notch by an enzymatic activity distinct from the well-known nuclear/cytoplasmic O-GlcNAc transferase, OGT, EC 2.4.1.255 | ? | - |
? | |
additional information | Mus musculus | O-GlcNAc is added to Notch by an enzymatic activity distinct from the well-known nuclear/cytoplasmic O-GlcNAc transferase, OGT, EC 2.4.1.255 | ? | - |
? | |
[Notch]-fucose + UDP-alpha-D-N-acetylglucosamine | Drosophila melanogaster | - |
[Notch]-(3-O-beta-D-N-acetylglucosaminyl)fucose + UDP | - |
? | |
[Notch]-fucose + UDP-alpha-D-N-acetylglucosamine | Mus musculus | - |
[Notch]-(3-O-beta-D-N-acetylglucosaminyl)fucose + UDP | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Drosophila melanogaster | - |
- |
- |
Mus musculus | - |
- |
- |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
additional information | O-GlcNAc is added to Notch by an enzymatic activity distinct from the well-known nuclear/cytoplasmic O-GlcNAc transferase, OGT, EC 2.4.1.255 | Drosophila melanogaster | ? | - |
? | |
additional information | O-GlcNAc is added to Notch by an enzymatic activity distinct from the well-known nuclear/cytoplasmic O-GlcNAc transferase, OGT, EC 2.4.1.255 | Mus musculus | ? | - |
? | |
[Notch]-fucose + UDP-alpha-D-N-acetylglucosamine | - |
Drosophila melanogaster | [Notch]-(3-O-beta-D-N-acetylglucosaminyl)fucose + UDP | - |
? | |
[Notch]-fucose + UDP-alpha-D-N-acetylglucosamine | - |
Mus musculus | [Notch]-(3-O-beta-D-N-acetylglucosaminyl)fucose + UDP | - |
? |
General Information | Comment | Organism |
---|---|---|
malfunction | eliminating any of three highly conserved O-fucose sites at EGF 12, 26, or 27 within mouse Notch1 alters the activity in cell-based Notch signaling assays. EGF 12 is part of the ligand-binding region of Notch, a mouse line carrying a point mutation in the O-fucosylation site of EGF 12 in endogenous Notch1 shows loss of this site which results in a mild Notch phenotype with defects in T cell development | Mus musculus |
metabolism | O-GlcNAc is added to Notch by an enzymatic activity distinct from the well-known nuclear/cytoplasmic O-GlcNAc transferase, OGT, EC 2.4.1.255. The structure GlcNAcbeta1-3Fucalpha1-OSer/Thr can be further elongated in mammals to the tetrasaccharide by sequential action of a beta1-4galactosyltransferase and an alpha2-3 or alpha2-6sialyltransferase | Mus musculus |
additional information | Fringe elongation to the GlcNAc-beta1,3-fucose causes a significant conformational shift of several residues within the O-fucose consensus region. This may provide a mechanism for how Fringe modification indirectly exerts its effects on Notch activity at EGF 12 | Mus musculus |
physiological function | the O-fucose and O-glucose glycans on Notch occur at specific consensus sequences within the context of EGF repeats, which make up the majority of the Notch extracellulr domain. O-GlcNAc modification, a third form of O-glycosylation, occurs on EGF repeats, on hydroxy amino acids between the fifth and sixth conserved Cys of an EGF repeat. Similar to O-fucosylation, the major effect of Fringe-mediated O-fucose elongation appears to be modulation of Notch-ligand binding, whereby Delta activation of Notch is potentiated, while signaling via Serrate is inhibited. GlcNAc is the terminal sugar added to O-fucose residues on Drosophila Notch, and the disaccharide is sufficient for observing a Fringe effect, In vitro extension to trisaccharide causes no change in in vitro ligand binding as assessed in vitro | Drosophila melanogaster |
physiological function | the O-fucose and O-glucose glycans on Notch occur at specific consensus sequences within the context of EGF repeats, which make up the majority of the Notch extracellulr domain. O-GlcNAc modification, a third form of O-glycosylation, occurs on EGF repeats, on hydroxy amino acids between the fifth and sixth conserved Cys of an EGF repeat. Similar to O-fucosylation, the major effect of Fringe-mediated O-fucose elongation appears to be modulation of Notch-ligand binding, whereby Delta activation of Notch is potentiated, while signaling via Serrate is inhibited. Mammalian Fringe modification also alters ligand binding. Elongation beyond GlcNAc to the trisaccharide (Galbeta1-4GlcNAcbeta1-3-Fucosealpha1-O-Ser/Thr) is necessary to see a Fringe effect in a mammalian cell system | Mus musculus |