Destabilization of vitelline membrane outer layer protein 1 homolog (VMO1) by C-mannosylation

Satoshi Yoshimoto, Takehiro Suzuki, Naoki Otani, Daisuke Takahashi, Kazunobu Toshima, Naoshi Dohmae, Siro Simizu

Research output: Contribution to journalArticlepeer-review


C-mannosylation is a rare type of protein glycosylation whereby a single mannose is added to the first tryptophan in the consensus sequence Trp-Xaa-Xaa-Trp/Cys (in which Xaa represents any amino acid). Its consensus sequence is mainly found in proteins containing a thrombospondin type-1 repeat (TSR1) domain and in type I cytokine receptors. In these proteins, C-mannosylation affects protein secretion, intracellular localization, and protein stability; however, the role of C-mannosylation in proteins that are not type I cytokine receptors and/or do not contain a TSR1 domain is less well explored. In this study, we focused on human vitelline membrane outer layer protein 1 homolog (VMO1). VMO1, which possesses two putative C-mannosylation sites, is a 21-kDa secreted protein that does not contain a TSR1 domain and is not a type I cytokine receptor. Mass spectrometry analyses revealed that VMO1 is C-mannosylated at Trp105 but not at Trp44. Although C-mannosylation does not affect the extracellular secretion of VMO1, it destabilizes the intracellular VMO1. In addition, a structural comparison between VMO1 and C-mannosylated VMO1 showed that the modification of the mannose changes the conformation of three loops in VMO1. Taken together, our results demonstrate the first example of C-mannosylation for protein destabilization of VMO1.

Original languageEnglish
Pages (from-to)490-499
Number of pages10
JournalFEBS Open Bio
Issue number3
Publication statusPublished - 2023 Mar


  • C-mannosylation
  • VMO1
  • mass spectrometry
  • protein stability
  • secretion

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


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