KCTD10

Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex that mediates the ubiquitination of multiple substrates, leading to either their proteasomal or lysosomal degradation, or modulating their activity through non-degradative ubiquitination. Controls endothelial barrier function by mediating 'Lys-63'-linked polyubiquitination of RHOB, promoting its lysosomal degradation. Mediates polyubiquitination of CEP97, targeting it for proteasomal degradation. CEP97 degradation upon serum starvation is essential for primary cilium formation by enabling removal of the CEP97-CP110 complex from mother centrioles. Acts as a positive regulator of ferroptosis by destabilizing SLC7A11. Decreased SLC7A11 levels reduce cystine uptake and glutathione (GSH) biosynthesis, thereby promoting iron-dependent lipid peroxidation and ferroptotic cell death. In the innate immune response, mediates 'Lys-27'-linked polyubiquitination of TICAM1/TRIF at Lys-523 upon stimulation with LPS. This ubiquitination is essential for recruitment of TICAM1 to TLR3/4, thereby promoting TLR3/4-mediated immune signaling. Negatively regulates KCTD13 stability through the ubiquitin/proteasome degradation pathway within the developing brain to control neuronal progenitor cell proliferation and differentiation (By similarity). Acts as a sensor for co-directional transcription-replication conflicts, where it helps coordinate the interaction between the replication machinery and RNA polymerase to allow DNA replication to continue through actively transcribed regions. Promotes recruitment of ubiquitin ligase complexes that remove stalled transcription factors, thereby maintaining genome stability by resolving these conflicts. Ubiquitinates TCEA2 to remodel the RNAP complex..

Function from UniProtKB (Q9H3F6), read 2026-09-23. CC BY 4.0.