Human COMP/Thrombospondin‑5 Antibody

Cartilage Oligomeric Matrix Protein (COMP), also known as Thrombospondin-5, is a 110 kDa multidomain calcium binding protein that associates with other extracellular matrix molecules. Thrombospondin-1 and -2 constitute subgroup A and form homotrimers, whereas Thrombospondin-3, -4, and COMP constitute subgroup B and form homopentamers (1-4). The human COMP cDNA encodes a 757 amino acid (aa) precursor that includes a 20 aa signal sequence followed by a non-collagenous
coiled‑coil domain, four EGF-like repeats, seven TSP type-3 repeats, and a globular TSP C-terminal domain (5). Human COMP shares 86-93% aa sequence identity with rat, mouse, equine, bovine, and canine COMP. Within the TSP type-3 repeats and TSP C-terminal domain, human COMP shares 60%, 61%, 74%, and 80% aa sequence identity with human Thrombospondin-1, -2, -3, and -4, respectively. The coiled coil domain mediates the association of COMP into disulfide-linked homopentamers with a central hub and peripheral globular domains connected by flexible strands (6, 7). An axial pore is formed by the coiled coil assembly and binds vitamin D₃ which is involved in bone and cartilage metabolism (8). An RGD sequence in the third TSP type-3 repeat mediates chondrocyte attachment via Integrin alpha 5 beta 1, although when reduced and in the absence of calcium, attachment is mediated via Integrin alpha V beta 3 (9). COMP is upregulated in rheumatoid arthritis and osteoarthritis, hepatocellular carcinomas, chronic pancreatitis, and pancreatic carcinomas (10-12). Elevated circulating COMP levels are used as a biomarker for early onset of some skeletal disorders (10). Several mutations are associated with skeletal dysplasias, and the most common, a point mutation in the third TSP type-3 repeat, results in diminished calcium binding ability (13, 14).