COMMD Proteins, a Novel Family of Structural and Functional Homologs of MURR1

MURR1 is a multifunctional protein that inhibits nuclear factor κB (NF-κB), a transcription factor with pleiotropic functions affecting innate and adaptive immunity, apoptosis, cell cycle regulation, and oncogenesis. Here we report the discovery of a new family of proteins with homology to MURR1. These proteins form multimeric complexes and were identified in a biochemical screen for MURR1-associated factors. The family is defined by the presence of a conserved and unique motif termed the COMM (copper metabolism gene MURR1) domain, which functions as an interface for protein-protein interactions. Like MURR1, several of these factors also associate with and inhibit NF-κB. The proteins designated as COMMD or COMM domain containing 1–10 are extensively conserved in multicellular eukaryotic organisms and define a novel family of structural and functional homologs of MURR1. The prototype of this family, MURR1/COMMD1, suppresses NF-κB not by affecting nuclear translocation or binding of NF-κB to cognate motifs; rather, it functions in the nucleus by affecting the association of NF-κB with chromatin.