The cysteine-rich-domain (CRD) is an essential part of the secreted frizzled related protein 2 (SFRP2), which has a role in development of the neural system, eyes, muscles and limbs. As a Wnt antagonist, SFRP2 regulates Nkx2.2 expression in the ventral spinal cord and anteroposterior axis elongation [].In general, SFRPs antagonize the activation of Wnt signaling by binding to the CRD domains of frizzled (Fz) proteins, thereby preventing Wnt proteins from binding to these receptors. SFRPs are also known to have functions unrelated to Wnt, as enhancers of procollagen cleavage by the TLD proteinases []. SFRPs and Fz proteins both contain CRD domains, but SFRPs lack the seven-pass transmembrane domain which is an integral part of Fzs [, ].
