E3 ubiquitin-protein ligase RNF182 (RNF182)

E3 ubiquitin-protein ligase RNF182 (RNF182) is a brain-enriched enzyme belonging to the RING finger domain-containing E3 ubiquitin ligases[1][3][5]. It is expressed primarily in the nervous system—including the cortex, hippocampus, cerebellum, and spinal cord—and is involved in tagging substrate proteins for proteasomal degradation via ubiquitination[1][3][6]. Substrates include ATP6V0C, a component involved in neurotransmitter release, and p65, a NF-κB subunit involved in regulating PDL1 transcription[1][2]. RNF182 expression is upregulated in Alzheimer's disease and under cellular injury stress; its overexpression can accelerate cell death in neuronal models, while its downregulation appears protective[1][3]. Recent evidence suggests it acts as a tumor suppressor by reducing immune evasion in lung adenocarcinoma via NF-κB p65 degradation and suppression of PDL1 expression[2]. RNF182 is also implicated in Rett syndrome and other neurodevelopmental disorders due to its influence on brain cell viability and homeostasis[3].

Other names

RNF182Ring finger protein 182RING-type E3 ubiquitin transferase RNF182MGC33993

Ubiquitinates substrate proteins (e.g., ATP6V0C, NF-κB p65), targeting them for proteasomal degradation[1][2]. Suppresses PDL1 transcription by promoting p65 ubiquitination, reducing immune evasion in cancer[2].