The CUE (coupling of ubiquitin conjugation to endoplasmic reticulum degradation) domain is an evolutionarily conserved, approximately 40 amino acid monoubiquitin-binding domain that mediates intramolecular monoubiquitylation. CUE domains are present in eukaryotic proteins that are involved in ubiquitination and protein trafficking pathways and may be required for ubiquitination of the proteins in which they are found. CUEDC2 (CUE domain-containing protein 2) was found through a yeast two-hybrid screening as a protein that interacts with the progesterone receptor (PR) and promotes progesterone-induced PR degradation by the ubiquitin-proteasome pathway. CUEDC2 also decreases the sumoylation of PR. CUEDC2 has also been found to interact with IKK-alpha and IKK-beta and decrease the activation of NF-kappa-B by decreasing the activation of IKK.
CUE domain-containing protein 2