Protein kinase <scp>FAM20C</scp> —when subcellular localization matters

Protein kinases achieve signaling specificity through consensus sequence recognition and subcellular localization. Although motif analysis can predict potential substrates, this method is insufficient if the spatial context in which the kinase operates is not considered. FAM20C, an acidophilic kinase that is primarily localized to the Golgi lumen, is an example of this. Its preference for the SXE motif informs substrate selection, but only within compartments accessible to the enzyme. Assigning substrates based solely on motif presence can be misleading and requires integrative experimental strategies to determine whether specific conditions enable kinase-substrate proximity.