AUTHOR=Manwar Hussain Muhammad Ramzan , Iqbal Zeeshan , Qazi Wajahat M. , Hoessli Daniel C. 

TITLE=Charge and Polarity Preferences for N-Glycosylation: A Genome-Wide In Silico Study and Its Implications Regarding Constitutive Proliferation and Adhesion of Carcinoma Cells

JOURNAL=Frontiers in Oncology

VOLUME=8

YEAR=2018

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2018.00029

DOI=10.3389/fonc.2018.00029

ISSN=2234-943X

ABSTRACT=<p>The structural and functional diversity of the human proteome is mediated by <italic>N</italic>- and <italic>O-</italic>linked glycosylations that define the individual properties of extracellular and membrane-associated proteins. In this study, we utilized different computational tools to perform <italic>in silico</italic> based genome-wide mapping of 1,117 human proteins and unravel the contribution of both penultimate and vicinal amino acids for the asparagine-based, site-specific <italic>N</italic>-glycosylation. Our results correlate the non-canonical involvement of charge and polarity environment of classified amino acids (designated as L, O, A, P, and N groups) in the <italic>N</italic>-glycosylation process, as validated by NetNGlyc predictions, and 130 literature-reported human proteins. From our results, particular charge and polarity combinations of non-polar aliphatic, acidic, basic, and aromatic polar side chain environment of both penultimate and vicinal amino acids were found to promote the <italic>N</italic>-glycosylation process. However, the alteration in side-chain charge and polarity environment of genetic variants, particularly in the vicinity of Asn-containing epitope, may induce constitutive glycosylation (e.g., aberrant glycosylation at preferred and non-preferred sites) of membrane proteins causing constitutive proliferation and triggering epithelial-to-mesenchymal transition. The current genome-wide mapping of 1,117 proteins (2,909 asparagine residues) was used to explore charge- and polarity-based mechanistic constraints in <italic>N</italic>-glycosylation, and discuss alterations of the neoplastic phenotype that can be ascribed to <italic>N</italic>-glycosylation at preferred and non-preferred sites.</p>