NetCGlyc 1.0: Prediction of mammalian C-mannosylation sites
Abstract
C-mannosylation is the attachment of an alpha-mannopyranose to a tryptophan via a C-C linkage. The sequence WXXW, in which the first Trp becomes mannosylated, has been suggested as a consensus motif for the modification, but only two-thirds of known sites follow this rule. We have gathered a data set of 69 experimentally verified C-mannosylation sites from the literature. We analyzed these for sequence context and found that apart from Trp in position +3, Cys is accepted in the same position. We also find a clear preference in position +1, where a small and/or polar residue (Ser, Ala, Gly, and Thr) is preferred and a Phe or a Leu residue discriminated against. The Protein Data Bank was searched for structural information, and five structures of C-mannosylated proteins were obtained. We showed that modified tryptophan residues are at least partly solvent exposed. A method predicting the location of C-mannosylation sites in proteins was developed using a neural network approach. The best overall network used a 21-residue sequence input window and information on the presence/absence of the WXXW motif. NetCGlyc 1.0 correctly predicts 93% of both positive and negative C-mannosylation sites. This is a significant improvement over the WXXW consensus motif itself, which only identifies 67% of positive sites. NetCGlyc 1.0 is available at http://www.cbs.dtu.dk/services/NetCGlyc/. Using NetCGlyc 1.0, we scanned the human genome and found 2573 exported or transmembrane transcripts with at least one predicted C-mannosylation site.
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C-mannosylation is an important process in the secretion of proteins which are retained in the ER if they do not undergo this type of glycosylation.
“Numerous studies have shown that C-mannosylation is an important process in the secretion of proteins which are retained in the ER, if they do not undergo this type of glycosylation [176].”
From GANAB and N-Glycans Substrates Are Relevant in Human Physiology, Polycystic Pathology and Multiple Sclerosis: A Review (2022) · cites this paper as [176]
C-mannosylation concerns only 18% of human proteins because the sugar is linked to a carbon atom, a species that is less reactive than nitrogen or oxygen.
“C-linked glycosylation or C-mannosylation concerns only 18% of human proteins because the sugar is linked to a carbon atom, a species that is less reactive than nitrogen or oxygen [176].”
From GANAB and N-Glycans Substrates Are Relevant in Human Physiology, Polycystic Pathology and Multiple Sclerosis: A Review (2022) · cites this paper as [176]
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“Numerous studies have shown that C-mannosylation is an important process in the secretion of proteins which are retained in the ER, if they do not undergo this type of glycosylation [176].”
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- Authors
- Julenius, K.
- Affiliations
- Stockholm University (SE)
- Corresponding author
- Julenius, Karin
- Venue
- Glycobiology
- Publisher
- Oxford University Press (OUP)
- Published
- 2007-05-09
- Volume
- 17
- Issue
- 8
- Pages
- 868-876
- ISSN
- 0959-6658 (ISSN-L)
- 1460-2423
- OpenAlex
- W2152890174
- Cited by
- 174
- References
- 50
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 11 · 2023: 3 · 2022: 8 · 2021: 11 · 2020: 15 · 2019: 8 · 2018: 11 · 2017: 15 · 2016: 15 · 2015: 6 · 2014: 14 · 2013: 8 · 2012: 9
- FWCI
- 2.65
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Glycobiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Knut och Alice Wallenbergs Stiftelse
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glycosylation and Glycoproteins Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Machine Learning in Bioinformatics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
- Keywords
- C-mannosylation, glycosylation site prediction, sequence context, solvent exposure, neural network classifier, mammalian proteins, human genome, transmembrane proteins
- MeSH terms
- Algorithms, Amino Acid Sequence, Animals, Glycoproteins, Humans, Mammals, Mannose, Models, Molecular, Molecular Sequence Data, Genome, Human, Neural Networks, Computer, Amino Acid Motifs, Databases, Protein
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