ATXN3, which has deubiquitinase activity and act as a component of the ubiquitin proteasome system, plays a role in transcriptional regulation and neuroprotection. ATXN3 interacts with RAD23, HHR23A and HHR23B, involves in the pathology of MJD. ATXN3 is a mixed-linkage, chain-editing enzyme and that the UIM region of ATXN3 regulates its substrate specificity. Contains an N-terminal deubiquitinating domain, called the Josephin domain, followed by 2 ubiquitin-interacting motifs (UIMs) and a polyQ tract near the C terminus. ATXN3 can be phosphorylated in a protein casein kinase-2-dependent manner, thus the MW would be larger than the predicted one.