Proteins from the CCN family are intercellular signalling proteins that includes six homologous members: cysteine-rich 61(Cyr61)/CCN1, connective tissue growth factor (Ctgf)/CCN2, nephroblastoma overexpressed gene (Nov)/CCN3, Wnt-induced secreted protein 1 (Wisp1)/CCN4, Wisp2/CCN5, and Wisp3/CCN6. They are involved in many biological processes, such as angiogenesis, wound healing, and tumorigenesis, by regulating the proliferation, migration, and differentiation of the target cells []. They interact with extracellular matrix components and growth factors via one of their four domains. In particular CNN3 (previously known as Nov) plays an important role in the generation of various types of tissues, such as muscle, fat, cartilage, and bone. CCN3 is expressed in notochord and presomitic mesoderm in early stage development, and in adults it is expressed in diverse tissues, including the nervous system, muscle, cartilage, and bone [].This entry represents a sub-type of thrombospondin module 1 (TSP1) domains found in matricellular CCN proteins which shares a similar three-stranded fold with the thrombospondin type 1 repeats of thrombospondin-1 and spondin-1. This domain has an alternative disulphide binding pattern compared to the canonical TSP1 domain and a conserved charged cluster in the centre of the domain which suggests to have a potential functional binding site for heparan sulfate [].
