Disorders of O-Fuc Glycosylation

Congenital Disorders of Glycosylation (CDG) are a group of clinically heterogeneous disorders characterized by defects in the Synthesis of Glycans and their association with proteins and lipids during glycosylation. CD BioGlyco has developed a specialized Glycoproteomics Platform and provides fast and efficient N-glycosylation and O-glycosylation analysis services.

Overview of Fucosylation

Fucose (Fuc) is an unusual sugar. It can not only incorporate into the terminal part of N-, O- or lipid-linked oligosaccharide chains, modify the core of complex N-glycans, but directly attach to serine or threonine (Ser/Thr) residues of proteins. This process is catalyzed by fucosyltransferases. In mammals, fucosylation of N-Glycans is closely related to the ABO blood group, host-microbe interaction, leukocyte trafficking, cancer metastasis, inflammation, immune response, etc. For example, membrane-bound glycans of α-1,3-linked Fuc molecules can initiate a cascade of reactions leading to the extravasation of leukocytes into perivascular inflamed tissues. O-Fucosylation is essential for fertilization, growth, and development.

In mammals, both N-fucosylation and O-fucosylation depend on guanidine 5'-diphosphate-β-L-fucose (GDP-Fuc). GDP-Fuc can be synthesized through two pathways: de novo synthesis and salvage pathway. About 90% of GDP-Fuc in mammals is produced through de novo synthesis pathway involving three-step reactions catalyzed by two enzymes. The salvage pathway is the conversion of free fucose from dietary or added to the culture medium to GDP-Fuc. Once synthesized, GDP-Fuc may be transported by the GDP-Fuc transporter (SLC35C1) to the Golgi apparatus for core and antennal fucosylation of N-glycans. Alternatively, GDP-Fuc is taken up by SLC35C2 into the lumen of the endoplasmic reticulum (ER) to catalyze protein fucosylation in an O-linked manner.

The fucosylation of N-glycans and O-fucosylation.Fig.1 The fucosylation of N-glycans and O-fucosylation. (Hüllen, et al, 2021)

Defects of O-Fucosylation

O-Fucosylation is the direct addition of fucose to Ser/Thr residues within the consensus sequence in the epidermal growth factor-like (EGF) repeat and thrombospondin type 1 repeat (TSR). This process is catalyzed by the protein O-fucosyltransferase 1/2 (POFUT1/2). POFUT1 transfers Fuc from GDP-Fuc to correctly folded EGF repeats containing the consensus sequence C2XXXX(S/T)C3. O-Fuc can be elongated by β1-3 N-acetylglucosaminyltransferase (β3GlcNAcT). POFUT2 transfers Fuc to Ser/Thr of TSR. The study found that POFUT1/2 only modifies correctly folded EGF repeats and TSRs. There are more than 100 potential human protein targets with multiple functions containing EGF repeats and approximately 50 proteins with TSR consensus sequences. In conclusion, Fuc modification is involved in many important biological processes such as cancer and immunity. Glycan Profiling and Glycan Structure Analysis is the most useful method for identifying glycosylation changes in disease. Here we describe the biological importance of O-fucosylation and the associated diseases caused by their defects.

The features of EGF repeats and TSRs.Fig.2 The features of EGF repeats and TSRs. (Schneider, et al, 2017)

  • Defects of O-Fucosylation in the EGF

In humans, heterozygous mutations in POFUT1 are associated with Dowling-Degos disease, a rare autosomal dominant skin disorder. While amplification of POFUT1 is also considered a prognostic marker and potential drug target in various cancers, such as breast cancer, oral squamous cell carcinoma, and hepatocellular carcinoma. Pofut1 knockout mice have been reported to exhibit severe growth retardation with defects in the neural tube, heart, and vascular development during early embryogenesis, similar to Notch1 knockout. In addition, Fringe enzyme can elongate O-Fuc residues with N-acetylglucosamine (GlcNAc) to further modulate Notch signaling. Fringe mutations in Drosophila affect Notch function leading to development defects in the wing, eye, and leg.

  • Defects of O-Fucosylation in the TSR

Like Pofut1, knockout of Pofut2 in mice is embryonic lethal, causing abnormalities in gastrulation and axis elongation. β3-Glucosyltransferase (B3GLCT) can add glucose (Glc) to O-Fuc residues of the TSR domain. Mutations in B3GLCT cause the human disease Peters Plus syndrome (PPS), characterized by numerous defects in eye, limb, and intellectual development.

CD BioGlyco has developed a reliable and sensitive Glycomics Platform to help researchers better understand the biological attribute of the complex glycosylation mechanisms. Our high-quality scientific services will greatly improve your research efficiency and accelerate research progress. If you are interested in our services, please contact us in time.


  1. Hüllen, A.; et al. Congenital disorders of glycosylation with defective fucosylation. Journal of inherited metabolic disease. 2021, 44(6): 1441-1452.
  2. Schneider, M.; et al. Biological functions of fucose in mammals. Glycobiology. 2017, 27(7): 601-618.
This service is for Research Use Only, not intended for any clinical use.

About Us

CD BioGlyco is a world-class biotechnology company with offices in many countries. Our products and services provide a viable option to what is otherwise available.

Contact Us

Copyright © CD BioGlyco. All rights reserved.