Potassium channel tetramerization domain-containing protein 17 (KCTD17)

Potassium channel tetramerization domain-containing protein 17 (KCTD17) is an adaptor protein, not an ion channel, that mediates targeted protein degradation by functioning as a substrate adaptor for Cullin3-based ubiquitin E3 ligase complexes. It plays key roles in ciliogenesis (as part of axoneme extension via trichoplein degradation), regulation of neuronal calcium signaling pathways (with mutations causing autosomal dominant myoclonic dystonia 26), and metabolic regulation in the liver by promoting degradation of PHLPP2 and enhancing lipogenesis. Recent studies show its C-terminal region is sufficient to bind Gβγ subunits, enabling modulation of G protein-coupled receptor signaling and cAMP production. Structural studies reveal KCTD17 adopts a closed pentameric architecture via its BTB domain. KCTD17 is not a common direct therapeutic target and no established drugs or clinical biomarkers are associated with it, although dysregulation can contribute to movement and metabolic disorders.

Other names

BTB/POZ domain-containing protein KCTD17FLJ12242KCD17_HUMAN

Acts as an adaptor promoting ubiquitin-mediated degradation of target proteins (e.g., trichoplein, PHLPP2) via CUL3-RING ligase. Modulates G protein-coupled receptor (GPCR) signaling through direct interaction with Gβγ subunits, dampening cAMP pathway activity.