MUC16/CA125 in the context of modular proteins with an annotated role in adhesion-related processes: in silico analysis

Abstract

Mucin 16 (MUC16) is a type I transmembrane protein, the extracellular portion of which is shed after proteolytic degradation and is denoted as CA125 antigen, a well known tumor marker for ovarian cancer. Regarding its polypeptide and glycan structures, as yet there is no detailed insight into their heterogeneity and ligand properties, which may greatly influence its function and biomarker potential. This study was aimed at obtaining further insight into the biological capacity of MUC16/CA125, using in silico analysis of corresponding mucin sequences, including similarity searches as well as GO (gene ontology)-based function prediction. The results obtained pointed to the similarities within extracellular serine/threonine rich regions of MUC16 to sequences of proteins expressed in evolutionary distant taxa, all having in common an annotated role in adhesion-related processes. Specifically, a homology to conserved domains from the family of herpesvirus major outer envelope protein (BLLF1) was found. In addition, the possible involvement of MUC16/CA125 in carbohydrate-binding interactions or cellular transport of protein/ion was suggested.

Keywords: CA125; MUC16; adhesion; conserved domain; herpesvirus; in silico; ion transport; sugar-binding; yeast.

Figure 1

CA125-immunoreactivity of Herpesvirus antigens. Mouse monoclonal anti-human CA125 antibodies: clone X306 (OC125-like) and clone X325 (M-11 like) were allowed to react with immobilized Epstein-Barr Virus (EBV) capsid antigens or Herpes simplex virus type 1 antigens (HSV1). Binding was detected using biotinylated goat anti-mouse IgG and Vectastain Elite ABC reagent. The absorbance was measured at 450 nm. Non-specific binding was estimated using an irrelevant monoclonal anti-hCG antibody (c).