E3 ubiquitin-protein ligase. Plays an important role in regulating the surface level of MUSK on myotubes. Mediates the ubiquitination of MUSK, promoting its endocytosis and lysosomal degradation. Might contribute to terminal myogenic differentiation. S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine. Protein modification; protein ubiquitination. Interacts with NLGN1 and EFNB2 (By similarity). Interacts with UBE2D2 and with MUSK via the first PDZ domain. In myotubes, the interaction between PDZRN3 and MUSK is enhanced upon agrin stimulation. Localizes to the postsynaptic region of neuromuscular junctions. Highly expressed in skeletal and cardiac muscle and at lower levels in spinal cord and brain (at protein level). Also expressed in kidney and lung. In muscles, concentrated at the neuromuscular junction (NMJ). First detected at the NMJ at approximately 16.5 dpc, when NMJs have just formed. As the NMJ grows and matures, expression levels increase in concert with that of acetylcholine receptors. Levels stay relatively high until 14 days after birth, but decrease significantly by 21 days. Up-regulated during myogenic differentiation in C2C12 cells and during injury-induced muscle regeneration. The RING-type zinc finger domain is required for E3 ligase activity. Auto-ubiquitinated. Truncated C-terminus.