Cloning a cDNA for human IgGFc binding protein (FcgammaBP) from human colonic epithelial cells reveals an mRNA and coding region of 17 and 16.2 kilobases, respectively. The predicted amino acid sequence contains 12 occurrences of a 400-amino acid cysteine-rich unit resembling that found in mucin. A motif (CGLCGN) in FcgammaBP is conserved in MUC2 and prepro-von Willebrand factor. The N-terminal 450-amino acid sequences are necessary and sufficient to confer IgG Fc binding activity. FcgammaBP mRNA is expressed only in placenta and colonic epithelial cells. These results suggest that FcgammaBP may play an important role in immune protection and inflammation in the intestines of primates.