Until now, three genes have been identified and isolated as members of WISP sub-family. WISP-1/CCN4, WISP-2/CCN5 and WISP-3/CCN6 genes were localized in human chromosomes 8q24.1-q24.3, 20q12-q13 and 6q22-23, respectively and exhibit tissue specific patterns of expression. Nucleotide and protein sequence alignment studies have demonstrated a 30-40% sequence homology within WISP genes and their modular architecture is similar except in their C-terminal domains, which is absent in the WISP-2 gene.

The translation products of most of the CCN family members are secreted proteins of 35-40 kDa and have been shown to contain four distinct structural modules: 1) an IGF-binding protein type (IGFBP) domain, 2) a Von Willebrand type C (VWC) domain; 3) a Thrombospondin-1 (TSP-1) domain and 4) a C-terminal Cysteine-knot (CT) domain (10). Although the functional roles of these multiple modules are unclear, they raise interesting questions as to the contribution of each individual module to the biological properties of the full-length proteins.

Epithelial cells and vascular smooth muscle cells

Adrenal gland, breast, colon, pancreas, uterus and ovary.

Positive regulator of epithelial cells and negative regulator of vascular smooth muscle cells.

Amplified in breast tumor cells.