This entry represents a group of IGFBP (insulin-like growth fac-tor (IGF) binding proteins)-related proteins, which have been annotated as the CNN family [, ]. Members of the CCN family are composed of an N-terminal secretory signal peptide followed by four conserved domains with homology to insulin-like growth factor binding protein, von Willebrand factor type C repeat, thrombospondin type 1 repeat, and a C-terminal domain (CT) with heparin-binding motifs and sequence similarity to the C termini of von Willebrand factor and mucin. The CCN family includes CCN1 (CYR61) [], CCN2 (CTGF), CCN3 [], CCN4 (WISP-1) [], CCN5 (WISP-2), and CCN6 (WISP-3).
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 [].
