Ubiquitin-protein ligase E3 C (UBE3C) is a poorly understood member of the Homologous to E6AP Carboxyl Terminus (HECT) E3 ubiquitin ligase family, unique in the fact that it contains an N-terminal IQ motif. Upregulation of UBE3C has been linked to numerous types of diseases including cancers, neurological disorders, and asthma, though further studies are required to understand the exact role of the enzyme in these diseases. The presence of an IQ motif within UBE3C’s structure presents a potential point of regulation for enzymatic activity through the binding of calmodulin (CaM). CaM is a calcium binding protein that undergoes conformational changes in response to environmental calcium concentrations, allowing for differential binding to over 300 intracellular substrates. The CaM/IQ motif complex has been observed in various systems, typically occurring in the absence of calcium, and following a general binding trend where the C-terminal lobe of CaM plays a significant role in the interaction. To study this UBE3C-CaM interaction, we obtained a synthetic peptide of the IQ motif of UBE3C (UBE3CIQ) for use in biophysical studies, including isothermal titration calorimetry (ITC), circular dichroism (CD), and multidimensional nuclear magnetic resonance (NMR) spectroscopy. Preliminary NMR spectra and ITC data suggest that the binding interface between UBE3CIQ and Apo-CaM differs from the trends observed in previously solved CaM-IQ complexes, with the binding being more dependent on the N-terminal lobe of CaM. By gaining a complete understanding of the binding interface between UBE3CIQ and Apo-CaM, the potential regulation of UBE3C enzymatic activity by calcium concentration can be further understood and examined as a potential therapeutic target.