Protein partners of KCTD proteins provide insights about their functional roles in cell differentiation and vertebrate development

Bioessays. 2013 Jul;35(7):586-96. doi: 10.1002/bies.201300002. Epub 2013 Apr 17.


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.

MeSH terms

  • Animals
  • Cell Differentiation / genetics*
  • DNA Replication
  • Gene Expression Regulation, Developmental
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • NIMA-Related Kinases
  • Nuclear Proteins / genetics
  • Nuclear Proteins / physiology*
  • Potassium Channels / genetics
  • Potassium Channels / physiology
  • Potassium Channels, Voltage-Gated / genetics
  • Potassium Channels, Voltage-Gated / physiology
  • Proliferating Cell Nuclear Antigen / genetics
  • Proliferating Cell Nuclear Antigen / physiology
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / physiology
  • Repressor Proteins / genetics
  • Repressor Proteins / physiology*
  • Ribosomal Protein S6 Kinases, 70-kDa / genetics
  • Ribosomal Protein S6 Kinases, 70-kDa / physiology
  • Signal Transduction
  • TOR Serine-Threonine Kinases / genetics
  • TOR Serine-Threonine Kinases / physiology
  • Ubiquitination
  • Vertebrates / genetics*


  • BTBD10 protein, human
  • Intracellular Signaling Peptides and Proteins
  • KCTD10 protein, human
  • KCTD15 protein, human
  • KCTD5 protein, human
  • KCTD9 protein, human
  • Nuclear Proteins
  • Potassium Channels
  • Potassium Channels, Voltage-Gated
  • Proliferating Cell Nuclear Antigen
  • Repressor Proteins
  • MTOR protein, human
  • NEK6 protein, human
  • NIMA-Related Kinases
  • Protein Serine-Threonine Kinases
  • Ribosomal Protein S6 Kinases, 70-kDa
  • TOR Serine-Threonine Kinases