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 alpha5 beta1, although when reduced and in the absence of calcium, attachment is mediated via Integrin alphaV beta3 (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).