In silico determination of intracellular glycosylation and phosphorylation sites in human selectins: Implications for biological function

Abstract

Post-translational modifications provide the proteins with the possibility to perform functions in addition to those determined by their primary sequence. However, analysis of multifunctional protein structures in the environment of cells and body fluids is made especially difficult by the presence of other interacting proteins. Bioinformatics tools are therefore helpful to predict protein multifunctionality through the identification of serine and threonine residues wherein the hydroxyl group is likely to become modified by phosphorylation or glycosylation. Moreover, serines and threonines where both modifications are likely to occur can also be predicted (YinYang sites), to suggest further functional versatility. Structural modifications of hydroxyl groups of P-, E-, and L-selectins have been predicted and possible functions resulting from such modifications are proposed. Functional changes of the three selectins are based on the assumption that transitory and reversible protein modifications by phosphate and O-GlcNAc cause specific conformational changes and generate binding sites for other proteins. The computer-assisted prediction of glycosylation and phosphorylation sites in selectins should be helpful to assess the contribution of dynamic protein modifications in selectin-mediated inflammatory responses and cell-cell adhesion processes that are difficult to determine experimentally.

Post‐translational modifications in activation and inhibition of oct‐1–DNA binding complex in H2B and other diverse gene regulation: Prediction of interplay sites

“…De‐phosphorylation of the Ser/Thr may result in a possibility of an addition of O GlcNAc on the OH function of the same Ser/Thr. Thus, blocking the phosphorylation on those specific sites, consequently resulting in blocking of the function regulated by phosphorylation such as described earlier [Ahmad et al, 2006, 2007].…”

First description of French V. tubiashii strains pathogenic to mollusk: II. Characterization of properties of the proteolytic fraction of extracellular products

“…In addition, glycosylation and phosphorylation motifs were identified on the metalloprotease sequence. The presence of these motifs suggested that the 07/ 118 T2 metalloprotease could be subject to post-translational modifications which can enable it to perform functions other than those determined by its primary sequence (Ahmad et al, 2007). Furthermore, it was shown that the HEXXH metalloprotease family is the only family of this protease group that is extensively modified post-translationally by both N-glycosylation and glycosyl phosphatidylinositol (McGwire and Chang, 1996).…”

Cardiac Na Channels

“…Multiple putative asparagines have been identified in Na V 1.5 as potential N-linked glycosylation sites (Ahmad et al, 2007). However, thus far only asparagines in the ancillary Na V β1 subunit have been demonstrated to functionally modify the cardiac Na + current, by causing leftward shifts of the inactivation and activation curves, promoting fast inactivation, and slowing RFI (Ednie et al, 2013; Stocker & Bennett, 2006; Ufret-Vincenty et al, 2001).…”