Human WISP‑1/CCN4 Antibody

Human WISP-1 (Wnt-induced secreted protein-1; also CNN4) is a 40 kDa, secreted, heparin-binding glycoprotein that is a member of the CCN (or CTGF/Cyr61/Nov) cysteine-rich protein family (1 - 5).  It is synthesized as a 367 aa precursor that contains a series of structural homology modules.  Following a 22 amino acid (aa) signal sequence, there is a 68 aa IGFBP-like domain (aa 53 - 120), a 57 aa von Willebrand factor type C (VWC) module (aa 126 - 182), a 40 aa TSP type I domain (aa 220 - 259) and a 75 aa, C-terminal cysteine knot motif (aa 273 - 347).  The VWC module is associated with protein-protein interaction, the TSP domain binds sulfated glycoconjugates, and the cysteine knot mediates dimerization and receptor binding (4).  It is likely that WISP-1 normally circulates as an 80 kDa homodimer (2).  At least five alternative splice forms are known for WISP-1.  One is 30 kDa in size, 258 aa in length, and shows a substitution of a His for aa 95 - 182.  This removes the VWC domain (2, 6).  A second isoform is 155 aa in length and shows a frameshift at Arg 117 with a unique 38 aa C-terminal extension.  A third is 195 aa in length and shows a 31 aa substitution for the first 203 aa of the full length precursor (6).  This retains the VWC and cysteine knot domains.  A fourth shows a 43 aa substitution for aa 117 - 367 for a total length of 163 aa.  This effectively removes everything but the IGFBP-like domain (7).  The last splice form contains a deletion of aa 25 - 269 for a total length of 122 aa.  Thus, only the signal sequence and cysteine knot motifs are retained (8).  This leaves only the IGFBP-like domain (9).  Full-length mature human WISP-1 is 85% aa identical to both mouse and rat WISP-1.  WISP-1 is expressed by osteoblasts and may contribute to fracture healing by promoting bone cell formation (10, 11).