NetCGlyc 1.0: prediction of mammalian C-mannosylation sites.
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.
Julenius
Karin
K
Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE-171 77 Stockholm, Sweden. karin.julenius@sbc.su.se
D000465:Algorithms; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D030562:Databases, Protein; D015894:Genome, Human; D006023:Glycoproteins / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008322:Mammals; D008358:Mannose / Q000032:analysis* / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016571:Neural Networks, Computer
D006023:Glycoproteins; D008358:Mannose