CLONING AND SEQUENCE-ANALYSIS OF HUMAN BREAST EPITHELIAL ANTIGEN BA46REVEALS AN RGD CELL-ADHESION SEQUENCE PRESENTED ON AN EPIDERMAL GROWTH FACTOR-LIKE DOMAIN

The BA46 antigen of the human milk fat globule (HMFG) membrane is expr essed in human breast carcinomas and has been used successfully as a t arget for experimental breast cancer radioimmunotherapy. To characteri ze this antigen further, we obtained the entire cDNA sequence and focu sed on its possible role in cell adhesion. The derived protein sequenc e of BA46 encodes a 387-residue precursor composed of a putative signa l peptide, an amino-terminal epidermal growth factor (EGF)-like domain containing the cell adhesion tripeptide arginine-glycine-aspartic aci d (RGD), and human factor V and factor VIII C1/C2-like domains. The EG F-like domain of BA46 is similar to the calcium-binding EGF-like domai ns of several coagulation factors, but the BA46 domain lacks a residue required for calcium binding and the coagulation factor domains do no t include an RGD sequence. Assuming that all EGF-like domains fold int o a similar structure, the RGD-containing sequence in BA46 is inserted between two antiparallel beta strands, This positioning suggests a no vel function for the EGF-like domain as a scaffold for RGD presentatio n.