Thrombospondins are multimeric multidomain glycoproteins that function at cell surfaces and in the extracellular matrix milieu. They act as regulators of cell interactions in vertebrates. They are divided into two subfamilies, A and B, according to their overall molecular organization. The subgroup A proteins TSP-1 and -2 contain an N-terminal domain, a VWFC domain (see <PDOC00928>), three TSP1 repeats (see<PDOC50092>), three EGF-like domains (see <PDOC00021>), TSP3 repeats (see <PDOC51234>) and a C-terminal domain. They are assembled as trimer. The subgroup B thrombospondins designated TSP-3 -4 and COMP (cartilage oligomeric matrix protein, also designated TSP-5) are distinct in that they contain unique N-terminal regions, lack the VWFC domain and TSP1 repeats, contain four copies of EGF-like domains, and are assembled as pentamers [1]. EGF, TSP3 repeats and the C-terminal domain are thus the hallmark of a thrombospondin.

The globular C-terminal domain is a β sandwich of two curved antiparallel β-sheets (see <PDB:1UX6>) [2]. The fold is an elaboration of the jelly role topology, with strand B3-B7, B11 and B14-B15 forming the eight-stranded jelly roll motif. The function of the C-terminal domain is not yet known.

The profile we developed covers the entire thrombospondin C-terminal domain.