DAB2 is a protein of 770 amino acid residues with a predicted molecular weight of 85.5kDa. This gene was initially named DOC2 (for Differentially expressed in Ovarian Cancer) and is distinct from the DOC2A and DOC2B genes (for double C2-like domains, alpha and beta). Human DAB2 has an overall 83% identify with the mouse p96 protein, a putative mitogen-responsive phosphoprotein; homology is strongest in the amino-terminal end of the protein in a region corresponding to the phosphotyrosine interaction domain (PID), and contains multiple SH3 binding motifs. Chromosomal localization by FISH showed that the DAB2 gene is located on 5p13. The expression of DAB2 is down-regulated or absent in all the carcinoma cell lines examined, including prostate and ovarian carcinoma cell lines. The N-terminal domain of DAB2 interacts with Dishevelled-3 (Dvl-3), a signaling mediator of the Wnt pathway. Ectopic expression of DAB2 attenuates canonical Wnt/catenin-mediated signaling, including accumulation of catenin and cyclin D1 induction. DAB2 suppresses both protein kinase C and peptide growth factor-elicited signal pathways via the Ras-mitogen-activated protein kinase pathway. The proline-rich domain of DAB2 also interacts with proteins containing SH3 domain, such as Src and Fgr. The binding of DAB2 to c-Src resultes in the inactivation of c-Src. All data suggest that DAB2 is a potent tumor suppressor in many cancer types.