COMM Domain Containing Protein 6 (COMMD6)

COMMD6 belongs to a family of NF-kappa-B-inhibiting proteins characterized by the presence of a COMM domain.Mutation analysis revealed that the C-terminal portion of the COMM domain of both proteins was essential for the interaction. Protein pull-down assays showed that COMMD1 could dimerize with both COMMD6 isoforms, whereas COMMD6 could homodimerize with COMMD6, and not with COMMD6A. Both COMMD1 and COMMD6 inhibited TNF-induced activation of NF-kappa-B, but in a nonsynergistic manner. Mutation analysis revealed that trp24 and pro41 in the COMM domain of COMMD6 were required for its inhibitory effect on TNF-induced NF-kappa-B activation, but mutation of these residues did not affect interaction of COMMD6 with either COMMD1 or the NF-kappa-B subunit RELA.