Abstract

The KCTD family includes tetramerization (T1) domain containing proteins with diverse biological effects. We identified a novel member of the KCTD family, BTBD10. A comprehensive analysis of protein-protein interactions (PPIs) allowed us to put forth a number of testable hypotheses concerning the biological functions for individual KCTD proteins. In particular, we predict that KCTD20 participates in the AKT-mTOR-p70 S6k signaling cascade, KCTD5 plays a role in cytokinesis in a NEK6 and ch-TOG-dependent manner, KCTD10 regulates the RhoA/RhoB pathway. Developmental regulator KCTD15 represses AP-2α and contributes to energy homeostasis by suppressing early adipogenesis. TNFAIP1-like KCTD proteins may participate in post-replication DNA repair through PCNA ubiquitination. KCTD12 may suppress the proliferation of gastrointestinal cells through interference with GABAb signaling. KCTD9 deserves experimental attention as the only eukaryotic protein with a DNA-like pentapeptide repeat domain. The value of manual curation of PPIs and analysis of existing high-throughput data should not be underestimated.

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