Protein C-mannosylation and C-mannosyl tryptophan in chemical biology and medicine

Shiho Minakata, Shino Manabe, Yoko Inai, Midori Ikezaki, Kazuchika Nishitsuji, Yukishige Ito, Yoshito Ihara

Research output: Contribution to journalReview articlepeer-review

2 Citations (Scopus)

Abstract

C-Mannosylation is a post-translational modification of proteins in the endoplasmic retic-ulum. Monomeric α-mannose is attached to specific Trp residues at the first Trp in the Trp-x-x-Trp/Cys (W-x-x-W/C) motif of substrate proteins, by the action of C-mannosyltransferases, DPY19-related gene products. The acceptor substrate proteins are included in the thrombospondin type I repeat (TSR) superfamily, cytokine receptor type I family, and others. Previous studies demon-strated that C-mannosylation plays critical roles in the folding, sorting, and/or secretion of substrate proteins. A C-mannosylation-defective gene mutation was identified in humans as the disease-as-sociated variant affecting a C-mannosylation motif of W-x-x-W of ADAMTSL1, which suggests the involvement of defects in protein C-mannosylation in human diseases such as developmental glau-coma, myopia, and/or retinal defects. On the other hand, monomeric C-mannosyl Trp (C-Man-Trp), a deduced degradation product of C-mannosylated proteins, occurs in cells and extracellular fluids. Several studies showed that the level of C-Man-Trp is upregulated in blood of patients with renal dysfunction, suggesting that the metabolism of C-Man-Trp may be involved in human kidney dis-eases. Together, protein C-mannosylation is considered to play important roles in the biosynthesis and functions of substrate proteins, and the altered regulation of protein C-manosylation may be involved in the pathophysiology of human diseases. In this review, we consider the biochemical and biomedical knowledge of protein C-mannosylation and C-Man-Trp, and introduce recent studies concerning their significance in biology and medicine.

Original languageEnglish
Article number5258
JournalMolecules
Volume26
Issue number17
DOIs
Publication statusPublished - 2021 Sep 1

Keywords

  • C-mannosyl tryptophan
  • C-mannosylation
  • Cy-tokine receptor type I
  • DPY19
  • Thrombospondin type I repeat

ASJC Scopus subject areas

  • Analytical Chemistry
  • Chemistry (miscellaneous)
  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery
  • Physical and Theoretical Chemistry
  • Organic Chemistry

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