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E3 Ubiquitin-Protein Ligase CHIP is a cytoplasmic protein. CHIP is highly expressed in skeletal muscle, heart, pancreas, brain and placenta. CHIP interacts with the molecular chaperones Hsc70-Hsp70 and Hsp90 through its TPR domain; lead to in client substrate ubiquitylation and degradation by the proteasome. CHIP targets misfolded chaperone substrates towards proteasomal degradation. CHIP mediates transfer of non-canonical short ubiquitin chains to HSPA8 that have no effect on HSPA8 degradation. CHIP plays a role in base-excision repair: catalyzes polyubiquitination by amplifying the HUWE1/ARF-BP1-dependent monoubiquitination and leading to POLB-degradation by the proteasome. It also may regulate the receptor stability and activity through proteasomal degradation.