Identification of MKRN1 as a second E3 ligase for Eag1 potassium channels reveals regulation via differential degradation.

Mutations in the human gene encoding the neuron-specific Eag1 voltage-gated K channel are associated with neurodevelopmental diseases, indicating an important role of Eag1 during brain development. A disease-causing Eag1 mutation is linked to decreased protein stability that involves enhanced protein degradation by the E3 ubiquitin ligase cullin 7 (CUL7). The general mechanisms governing protein homeostasis of plasma membrane- and endoplasmic reticulum (ER)-localized Eag1 K channels, however, remain unclear.

Cullin 7 mediates proteasomal and lysosomal degradations of rat Eag1 potassium channels.

Mammalian Eag1 (Kv10.1) potassium (K) channels are widely expressed in the brain. Several mutations in the gene encoding human Eag1 K channel have been associated with congenital neurodevelopmental anomalies.