C-Mannosylation is a unique type of protein glycosylation. A C-C bond is formed between the C1 atom of an α-mannose and the C2 atom of the indole ring of a tryptophan residue via mannosyl-transferases.

NoHC6H11O5Av: 162.1408
M: 162.0528
Physicochemical properties of C-mannosylation that are stored in the modification database of Prot pi (NC: Native charge; H: Relative hydrophobicity; AA: Modified amino acid; Pattern: Regex for sequence-motif recognition).

In-depth mechanism

Glycosylations of proteins are one of the most common and widespread post-translational modifications. Best known are N– and O-glycosylations. More than 25 years ago, a new type of glycosylation, C-mannosylation, was discovered. C-Mannosylation differs fundamentally from previously described types of glycosylation. A C-C bond is formed between the C1 atom of an α-mannose and the C2 atom of the indole ring of a tryptophan residue. The reaction is catalysed by mannosyltransferases, which use dolychyl-phosphate-mannose as donor for the mannose moiety​1,2​. Dolychyl-phosphate-mannose is formed from GDP-mannose and dolichol-phosphate on the cytosolic side of the endoplasmatic reticulum​3​. The mechanism of C-mannosylation is shownin figure 1.

Figure 1: Mechanism of C-mannosylation. A mannose moiety is transferred from dolychyl-phosphate-mannose to the first tryptophan of a W-X-X-W motif via mannosyltransferases. A C-C bond is formed between the C1 atom of an α-mannose and the C2 atom of the indole ring of the tryptophan residue.

Mannosyltransferases recognize W-X-X-W motifs and C-mannosylate the first tryptophan in the sequence. However, this pattern can vary slightly from organism to organism​2​. The exchange of the second tryptophan residue for other amino acids strongly restricts or even completely prevents C-mannosylation. The influence of the two amino acids between the tryptophan residues is still the subject of current studies​1​. The W-X-X-W motif occurs in many proteins, which suggests that C-mannosylation is a common an widespread post-translational modification. The function of C-mannosylation is still largely unknown today​1,2​. The hydrophobicity of a protein is not altered by C-mannosylation.


  1. 1.
    Furmanek A, Hofsteenge J. Protein C-mannosylation: facts and questions. Acta biochimica Polonica. 2000;47:781–789.
  2. 2.
    Lafite P, Daniellou R. Rare and unusual glycosylation of peptides and proteins. Natural Product Reports. 2012;29:729–738. doi:10.1039/C2NP20030A
  3. 3.
    Maeda Y, Kinoshita T. Dolichol-phosphate mannose synthase: structure, function and regulation. Biochimica et biophysica acta. 2008;1780:861–868. doi:10.1016/j.bbagen.2008.03.005


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