Defective LFNG does not transfer GlcNAc to Pre-NOTCH

Stable Identifier
R-HSA-5096538
Type
Reaction [transition]
Species
Homo sapiens
Compartment
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The Fringe family (CAZy family GT31) of glycosyltransferases in mammals includes LFNG (lunatic fringe; MIM:602576), MFNG (manic fringe; MIM:602577) and RFNG (radical fringe; MIM:602578). Fringe enzymes function in the Golgi apparatus where they initiate the elongation of O -inked fucose on fucosylated peptides by the addition of a beta-1,3-N-acetylglucosaminyl group (GlcNAc) (Moloney et al. 2000). Fringe enzymes elongate conserved O fucosyl residues conjugated to EGF repeats of NOTCH, modulating NOTCH activity (Cohen et al. 1997, Johnston et al. 1997) by decreasing the affinity of NOTCH extracellular domain for JAG ligands (Bruckner et al. 2000).

The spondylocostal dysostoses (SCDs) are a group of disorders that arise during embryonic development by a disruption of somitogenesis. The Notch signalling pathway is essential for somitogenesis, the precursors of vertebra and associated musculature. Defects in one of the Fringe enzymes, beta-1,3-N-acetylglucosaminyltransferase lunatic fringe (LFNG), can cause spondylocostal dysostosis, autosomal recessive 3 (SCDO3; MIM:609813), a condition of variable severity associated with vertebral and rib segmentation defects (Sparrow et al. 2006). The missense mutation F188L can result in SCDO3 by not being able to modulate Notch activity (Sparrow et al. 2006).

Literature References
PubMed ID Title Journal Year
10734111 Mammalian Notch1 is modified with two unusual forms of O-linked glycosylation found on epidermal growth factor-like modules

Moloney, DJ, Shair, LH, Lu, FM, Xia, J, Locke, R, Matta, KL, Haltiwanger, RS

J. Biol. Chem. 2000
16385447 Mutation of the LUNATIC FRINGE gene in humans causes spondylocostal dysostosis with a severe vertebral phenotype

Sparrow, DB, Chapman, G, Wouters, MA, Whittock, NV, Ellard, S, Fatkin, D, Turnpenny, PD, Kusumi, K, Sillence, D, Dunwoodie, SL

Am. J. Hum. Genet. 2006
10935637 Glycosyltransferase activity of Fringe modulates Notch-Delta interactions

Br├╝ckner, K, Perez, L, Clausen, H, Cohen, S

Nature 2000
9207795 Fringe boundaries coincide with Notch-dependent patterning centres in mammals and alter Notch-dependent development in Drosophila

Cohen, B, Bashirullah, A, Dagnino, L, Campbell, C, Fisher, WW, Leow, CC, Whiting, E, Ryan, D, Zinyk, D, Boulianne, G, Hui, CC, Gallie, B, Phillips, RA, Lipshitz, HD, Egan, SE

Nat Genet 1997
9187150 A family of mammalian Fringe genes implicated in boundary determination and the Notch pathway

Johnston, SH, Rauskolb, C, Wilson, R, Prabhakaran, B, Irvine, KD, Vogt, TF

Development 1997
Participants
Participant Of
Catalyst Activity
Catalyst Activity
Title
O-fucosylpeptide 3-beta-N-acetylglucosaminyltransferase activity of LFNG F188L [Golgi membrane]
Physical Entity
Activity
Normal reaction
Disease
Name Identifier Synonyms
spondylocostal dysostosis 0050568 SPONDYLOTHORACIC DYSPLASIA, JARCHO-LEVIN SYNDROME, SPONDYLOTHORACIC DYSOSTOSIS
Authored
Reviewed
Created