Protein <i>C</i>-Mannosylation and <i>C</i>-Mannosyl Tryptophan in Chemical Biology and Medicine
<i>C</i>-Mannosylation is a post-translational modification of proteins in the endoplasmic reticulum. 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 <i>C</i>-mannosyltr...
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2021-08-01
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| author | Shiho Minakata Shino Manabe Yoko Inai Midori Ikezaki Kazuchika Nishitsuji Yukishige Ito Yoshito Ihara |
| author_facet | Shiho Minakata Shino Manabe Yoko Inai Midori Ikezaki Kazuchika Nishitsuji Yukishige Ito Yoshito Ihara |
| author_sort | Shiho Minakata |
| collection | DOAJ |
| description | <i>C</i>-Mannosylation is a post-translational modification of proteins in the endoplasmic reticulum. 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 <i>C</i>-mannosyltransferases, <i>DPY19</i>-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 demonstrated that <i>C</i>-mannosylation plays critical roles in the folding, sorting, and/or secretion of substrate proteins. A <i>C</i>-mannosylation-defective gene mutation was identified in humans as the disease-associated variant affecting a <i>C</i>-mannosylation motif of W-x-x-W of ADAMTSL1, which suggests the involvement of defects in protein <i>C</i>-mannosylation in human diseases such as developmental glaucoma, myopia, and/or retinal defects. On the other hand, monomeric <i>C</i>-mannosyl Trp (<i>C</i>-Man-Trp), a deduced degradation product of <i>C</i>-mannosylated proteins, occurs in cells and extracellular fluids. Several studies showed that the level of <i>C</i>-Man-Trp is upregulated in blood of patients with renal dysfunction, suggesting that the metabolism of <i>C</i>-Man-Trp may be involved in human kidney diseases. Together, protein <i>C</i>-mannosylation is considered to play important roles in the biosynthesis and functions of substrate proteins, and the altered regulation of protein <i>C</i>-manosylation may be involved in the pathophysiology of human diseases. In this review, we consider the biochemical and biomedical knowledge of protein <i>C</i>-mannosylation and <i>C</i>-Man-Trp, and introduce recent studies concerning their significance in biology and medicine. |
| first_indexed | 2024-03-10T08:07:01Z |
| format | Article |
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| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T08:07:01Z |
| publishDate | 2021-08-01 |
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| spelling | doaj.art-91c100ab07794f949b77fff93781ebc62023-11-22T11:01:27ZengMDPI AGMolecules1420-30492021-08-012617525810.3390/molecules26175258Protein <i>C</i>-Mannosylation and <i>C</i>-Mannosyl Tryptophan in Chemical Biology and MedicineShiho Minakata0Shino Manabe1Yoko Inai2Midori Ikezaki3Kazuchika Nishitsuji4Yukishige Ito5Yoshito Ihara6Department of Biochemistry, Wakayama Medical University, 811-1 Kimiidera, Wakayama, Wakayama 641-0012, JapanPharmaceutical Department, The Institute of Medicinal Chemistry, Hoshi University, 2-4-41 Ebara, Shinagawa, Tokyo 142-8501, JapanDepartment of Biochemistry, Wakayama Medical University, 811-1 Kimiidera, Wakayama, Wakayama 641-0012, JapanDepartment of Biochemistry, Wakayama Medical University, 811-1 Kimiidera, Wakayama, Wakayama 641-0012, JapanDepartment of Biochemistry, Wakayama Medical University, 811-1 Kimiidera, Wakayama, Wakayama 641-0012, JapanDepartment of Chemistry, Graduate School of Science, Osaka University, 1-1 Machikaneyama, Toyonaka, Osaka 560-0043, JapanDepartment of Biochemistry, Wakayama Medical University, 811-1 Kimiidera, Wakayama, Wakayama 641-0012, Japan<i>C</i>-Mannosylation is a post-translational modification of proteins in the endoplasmic reticulum. 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 <i>C</i>-mannosyltransferases, <i>DPY19</i>-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 demonstrated that <i>C</i>-mannosylation plays critical roles in the folding, sorting, and/or secretion of substrate proteins. A <i>C</i>-mannosylation-defective gene mutation was identified in humans as the disease-associated variant affecting a <i>C</i>-mannosylation motif of W-x-x-W of ADAMTSL1, which suggests the involvement of defects in protein <i>C</i>-mannosylation in human diseases such as developmental glaucoma, myopia, and/or retinal defects. On the other hand, monomeric <i>C</i>-mannosyl Trp (<i>C</i>-Man-Trp), a deduced degradation product of <i>C</i>-mannosylated proteins, occurs in cells and extracellular fluids. Several studies showed that the level of <i>C</i>-Man-Trp is upregulated in blood of patients with renal dysfunction, suggesting that the metabolism of <i>C</i>-Man-Trp may be involved in human kidney diseases. Together, protein <i>C</i>-mannosylation is considered to play important roles in the biosynthesis and functions of substrate proteins, and the altered regulation of protein <i>C</i>-manosylation may be involved in the pathophysiology of human diseases. In this review, we consider the biochemical and biomedical knowledge of protein <i>C</i>-mannosylation and <i>C</i>-Man-Trp, and introduce recent studies concerning their significance in biology and medicine.https://www.mdpi.com/1420-3049/26/17/5258<i>C</i>-mannosylation<i>C</i>-mannosyl tryptophanDPY19thrombospondin type I repeatcytokine receptor type I |
| spellingShingle | Shiho Minakata Shino Manabe Yoko Inai Midori Ikezaki Kazuchika Nishitsuji Yukishige Ito Yoshito Ihara Protein <i>C</i>-Mannosylation and <i>C</i>-Mannosyl Tryptophan in Chemical Biology and Medicine Molecules <i>C</i>-mannosylation <i>C</i>-mannosyl tryptophan DPY19 thrombospondin type I repeat cytokine receptor type I |
| title | Protein <i>C</i>-Mannosylation and <i>C</i>-Mannosyl Tryptophan in Chemical Biology and Medicine |
| title_full | Protein <i>C</i>-Mannosylation and <i>C</i>-Mannosyl Tryptophan in Chemical Biology and Medicine |
| title_fullStr | Protein <i>C</i>-Mannosylation and <i>C</i>-Mannosyl Tryptophan in Chemical Biology and Medicine |
| title_full_unstemmed | Protein <i>C</i>-Mannosylation and <i>C</i>-Mannosyl Tryptophan in Chemical Biology and Medicine |
| title_short | Protein <i>C</i>-Mannosylation and <i>C</i>-Mannosyl Tryptophan in Chemical Biology and Medicine |
| title_sort | protein i c i mannosylation and i c i mannosyl tryptophan in chemical biology and medicine |
| topic | <i>C</i>-mannosylation <i>C</i>-mannosyl tryptophan DPY19 thrombospondin type I repeat cytokine receptor type I |
| url | https://www.mdpi.com/1420-3049/26/17/5258 |
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