Unique structural features of the pentameric matrix protein COMP sustain its dynamic regulation of extra- and intracellular activities: A review

The macromolecule COMP -Cartilage Oligomeric Matrix Protein- was originally discovered as an essential regulator of the assembly, integrity and homeostatic remodeling of cartilage tissue ECMs. Later, however, it was found to have a more widespread distribution, to attain different subcellular topographies and play a pivotal role as an integral component of fibrotic and cancer-associated matrices. The homopentameric configuration of COMP remains distinctive within the human proteome and confers to the protein a multivalent functionality exploitable by the cells under physiological and pathological conditions. The structural-functional properties of COMP show limited overlap with those of other members of thrombospondin family and its multifaceted nature extends beyond its function in matrix assembly to embrace signal transducing interactions with the cell surface, the sequestering of signaling molecules, and the binding of components of the immunological/complement system. Mutated chondrocyte variants of COMP and isoforms aberrantly expressed by transformed cells are retained intracellularly to engage interactions with a variety of cytoplasmic molecules and convert the macromolecule from a structural ECM component to a regulator of homeostatic and transformative events. We discuss here how the unique structural traits of COMP may endow it with multifunctionality and explain its active participation in highly diverse biological processes.