Take a look at the notch signaling pathway in human from KEGG :


I want to know what is Fringe activating. It is not pointing to another gene or protein, it is pointing to an interaction. What does that mean?


1 Answer 1


Usually, in such depictions where a species is pointing to a reaction or an interaction, the arrows mean that the species affects that reaction (for example, catalysis by an enzyme ). Generally pointy arrow heads denote positive effect (enhancing the reaction, for example an enzyme) and flat heads denote a negative interaction (repression). An arrow from one molecule to another can be used to depict a conversion (like glucose converting to glucose 6 phosphate).

There are no real standards on how to depict a pathway. So, it can be confusing.

In this case, Fringe actually alters Notch signalling (see below). So the arrow makes sense. However, the figure also has an arrow from Delta to Notch which can be interpreted as Delta getting converted to Notch. They also show an arrow from Notch to NICD which actually means a conversion. I would say that the depictions in this figure are inconsistent.

From NCBI Gene entry on Human homolog of Fringe, LFNG:

This gene is a member of the glycosyltransferase 31 gene family. Members of this gene family, which also includes the MFNG (GeneID: 4242) and RFNG (GeneID: 5986) genes, encode evolutionarily conserved glycosyltransferases that act in the Notch signaling pathway to define boundaries during embryonic development. While their genomic structure is distinct from other glycosyltransferases, these proteins have a fucose-specific beta-1,3-N-acetylglucosaminyltransferase activity that leads to elongation of O-linked fucose residues on Notch, which alters Notch signaling. The protein encoded by this gene is predicted to be a single-pass type II Golgi membrane protein but it may also be secreted and proteolytically processed like the related proteins in mouse and Drosophila (PMID: 9187150). Mutations in this gene have been associated with autosomal recessive spondylocostal dysostosis 3. [provided by RefSeq, May 2018]

From Shao et al (2002):

Recent studies have demonstrated that O-fucose modifications play an essential role in Notch function. Reduction of O-fucosyltransferase expression in Drosophila using RNAi (11) or in mice by gene ablation2 causes Notch-like phenotypes, suggesting that O-fucose modifications are essential for Notch function. In addition, we and others have shown that Notch activation is modulated by extension of O-fucose on Notch with the fucose-specific β1,3-N-acetylglucosaminyltransferase Fringe (for recent reviews, see Refs. 12 and 13). Fringe was first identified in Drosophila and shown to inhibit Notch's ability to respond to Serrate but to potentiate its ability to respond to Delta (14). Three Drosophila Fringe homologues have been identified in mammals: Lunatic fringe (Lfng), Manic fringe (Mfng), and Radical fringe (Rfng) (15). The β1,3-N-acetylglucosaminyltransferase activity of Fringe proteins is essential for their biological activity in Drosophila (16-18) and in cell-based Notch signaling assays (19), and the O-fucose residues are required for Fringe to modulate Notch activity (16, 19). Thus, Fringe mediates its effects on Notch signaling by the addition of GlcNAc to O-fucose moieties. Nonetheless, neither the specific role ofO-fucose in Notch function nor the mechanism of how a change in sugar structure alters Notch function is known.


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