A novel immunoglobulin-type protein expressed in blood vessels has been identified. The cDNA for AAMP (angio-associated, migratory cell protein) was first isolated from a human melanoma cell line during a search for motility-associated cell surface proteins. Upon analysis of the tissue distribution of AAMP, it was found to be expressed strongly in endothelial cells, cytotrophoblasts, and poorly differentiated colon adenocarcinoma cells found in lymphatics. The sequence of AAMP predicts a protein (M(r) 49,000) with distant identity (25%) to known proteins. It contains immunoglobulin-like domains [one with multiple homologies to deleted in colon carcinoma (DCC) protein], the WD40 repeat motif, and a heparin-binding consensus sequence. A 1.6-kilobase mRNA transcript of AAMP is detected in tissue culture cell lines and tissues. Affinity-purified polyclonal antibodies, anti-recombinant AAMP, and anti-peptide 189 (AAMP derived) recognize a M(r) 52,000 protein in human tissue and cellular extracts. The protein size is in keeping with the mRNA and predicted sequence. The AAMP-derived peptide, P189, contains a heparin-binding domain (dissociation constant, 14 pmol) and mediates heparin-sensitive cell adhesion. The shared expression of AAMP in endothelial cells, trophoblasts, and tumor cells implies a common function in migrating cells.