H1 domain found in potassium channel tetramerization domain-containing proteins
The H1 domain is found in potassium channel tetramerization domain-containing proteins such as KCTD8, KCTD12 (also called predominantly fetal expressed T1 domain/Pfetin), KCTD12b, and KCTD16. They serve as auxiliary gamma-aminobutyric acid type B (GABA-B) receptor subunits that constitute receptor subtypes with distinct functional properties. KCTD12 and -12b generate desensitizing receptor responses while KCTD8 and -16 generate largely non-desensitizing receptor responses. They control GABA-B signaling and regulate the rise time and duration of G protein-coupled inwardly rectifying potassium (GIRK) currents, as well as enhance receptor expression levels. KCTD12 regulates agonist potency and kinetics of GABA-B receptor signaling. It promotes tumorigenesis by facilitating CDC25B/CDK1/Aurora A-dependent G2/M transition. KCTD16 interacts with amyloid beta precursor protein (APP), a type I transmembrane protein involved in a variety of cellular processes such as cell adhesion and axon guidance. Members of this family consist of an N-terminal BTB domain followed by a region called the H1 domain. The BTB domain mediates interaction with the receptor. The C-terminal H1 domain, which possesses a beta-propeller-like fold, engages in interactions with G-protein beta-gamma subunits and is responsible for desensitization. This model corresponds to the H1 domain.
Jiyao W et al.(2023). "The conserved domain database in 2023.",