Interaction between the TBC1D24 TLDc domain and the KIBRA C2 domain is disrupted by two epilepsy-associated TBC1D24 missense variants.

ABSTRACT: Mutations of human TBC1D24 are associated with deafness, epilepsy, or DOORS syndrome (deafness, onychodystrophy, osteodystrophy, cognitive disability, and seizures). The causal relationships between TBC1D24 variants and the different clinical phenotypes are not understood. Our hypothesis is that phenotypic heterogeneity of missense mutations of TBC1D24 results, in part, from perturbed binding of different protein partners. To discover novel protein partners of TBC1D24, we conducted yeast two-hybrid (Y2H) screen using mouse full-length TBC1D24 as bait. Kidney and brain protein (KIBRA), a scaffold protein encoded by Wwc1, was identified as a partner of TBC1D24. KIBRA functions in the Hippo signaling pathway and is important for human cognition and memory. The TBC1D24 TLDc domain binds to KIB

SUBMITTER: Tona R 

PROVIDER: S-EPMC11465063 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature