Ubiquitin-protein ligase E3B (UBE3B)

Ubiquitin-protein ligase E3B (UBE3B) is a member of the HECT family of E3 ubiquitin ligases that catalyzes the transfer of ubiquitin from E2 ubiquitin-conjugating enzymes to specific substrate proteins, marking them for degradation via the ubiquitin-proteasome system[1][2][3][6][7]. UBE3B is essential for normal protein turnover, metabolic process regulation, and is highly expressed in the nervous system as well as other tissues[1][3][5]. UBE3B contains an N-terminal IQ motif for calmodulin binding and a C-terminal HECT domain, which is its catalytic core[3][6][7]. Mutations in UBE3B cause a rare developmental disorder called Kaufman oculocerebrofacial syndrome, characterized by intellectual disability, facial dysmorphisms, and organ dysfunction[1][2][4][5][7]. UBE3B also interacts with metabolic regulators (such as BCKDK) and proteins involved in neuronal development and mitochondrial dynamics; loss or disruption of UBE3B can result in defective protein homeostasis, abnormal neuronal structure, impaired metabolism, and increased susceptibility to apoptosis[3][5]. There are currently no approved drugs specifically targeting UBE3B.

Other names

BPIDSKOSHECT-type ubiquitin transferase E3Bubiquitin-protein ligase E3B isoform 1ubiquitin-protein ligase E3B isoform 3

Drugs would potentially act by modulating ubiquitin ligase activity, protein degradation, or downstream signaling pathways relevant to UBE3B substrates (such as regulation of targets like BCKDK in metabolism)[5][3].