What are post-translational modifications?
Post-translational modifications (PTMs) are changes that proteins undergo in order to coordinate with other proteins and diversity their functions. Abnormal PTMs are associated with human diseases, so it is important to consider the role PTMs have when studying disease . Figure 1 below shows the different types of PTMs that can occur on a protein, but I will be focusing on phosphorylation since it is a commonly studied PTM and plays a role in C4A regulation.
To determine the commonly phosphorylated sites of C4A, the amino acid sequence was entered into NetPhos, which then displays the predicted phosphorylation sites on the polypeptide in the form of a graph (as shown below).
There are many possible phosphorylation sites on the C4A protein and although none have been specifically associated with increased or decreased risk of developing schizophrenia thus far, the possible sites fall within every C4A domain. It is interesting to note that there is a small ~50 amino acid region (sequence position is around 850 to 950) that does not get phosphorylated in human, mouse, or zebrafish C4A despite the presence of several threonines and tyrosines. The effects of phosphorylating amino acid residues in this region would be interesting to explore in future studies.