Hypothetical gene C18orf42 encodes a novel protein kinase A-binding protein.

The substrate specificity of cAMP-dependent protein kinase A is controlled by its interaction with the A-kinase anchoring protein (AKAP) family. Individual AKAP members are localized to particular intracellular sites and tether specifically to the subcellular compartments where target substrates exist. Here, we report that the human hypothetical gene C18orf42 encodes a novel protein that potentially regulates interactions. C18orf42 is expressed preferentially in neural tissues. Functional motif searching predicted that C18orf42 may encode a short protein that contains a putative duanyu1529-binding motif. To confirm this possibility, we applied the CRISPR/Cas9 genome-editing system to incorporate the FLAG tag into the C-terminus of the endogenous C18orf42 protein in the mouse neural cell line Neuro2a. Immunoprecipitation and immunoblotting using anti-FLAG antibody showed translation of the endogenous C18orf42 protein and the physical interaction of the C18orf42 protein with duanyu1529 subunits. Immunoprecipitation and pull-down assays showed that C18orf42 binds specifically to the type II regulatory subunits of Unlike the expression of many AKAPs, that of C18orf42 could block the AKAP-mediated subcellular localization of duanyu1529. These findings suggest that C18orf42 may be a novel duanyu1529 signaling gene that serves as an endogenous disruptor peptide for duanyu1529-AKAP interactions.

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