C-Mannosylation: Modification on Tryptophan in Cellular Proteins

Yoshito Ihara, Yoko Inai, Midori Ikezaki, In Sook L. Matsui, Shino Manabe, Yukishige Ito

Research output: Chapter in Book/Report/Conference proceedingChapter

21 Citations (Scopus)


C-Mannosylation is a unique glycosylation in which an α-mannose attaches to the indole C2 carbon atom of a tryptophan (Trp) residue to produce C-mannosyltryptophan. C-Mannosylation usually occurs at the first Trp in the consensus amino acid sequence Trp-x-x-Trp (W-x-x-W) in proteins through an enzymatic reaction with a specific mannosyltransferase. Recently, Caenorhabditis elegans DPY-19 was identified as a C-mannosyltransferase. Most substrates for C-mannosylation are part of either the thrombospondin type-1 repeat (TSR) superfamily or the type I cytokine receptor family, suggesting a functional role for C-mannosylation in specific substrate proteins. Although the functions of C-mannosylation have not been fully clarified, site-directed mutagenesis of the C-mannosylation potential site in the W-x-x-W motif has revealed it to be important in the folding or targeting of substrate proteins, such as mucins and ADAMTS-like 1, in the cell. By using chemically synthesized C-mannosylated TSR-derived peptides, it was revealed that C-mannosylated peptides could modulate lipopolysaccharide-induced cellular signaling to produce tumor necrosis factor-α. These accumulated findings indicate that C-mannosylation plays important roles in modulating the functions of acceptor proteins in the cell.

Original languageEnglish
Title of host publicationGlycoscience
Subtitle of host publicationBiology and Medicine
PublisherSpringer Japan
Number of pages10
ISBN (Electronic)9784431548416
ISBN (Print)9784431548409
Publication statusPublished - 2015 Jan 1
Externally publishedYes


  • C-Mannosyl-tryptophan
  • C-Mannosylation
  • Cytokine receptor
  • Thrombospondin

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)


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