Angio-associated migratory cell protein (AAMP) is a newly discovered protein that is widely distributed with strong expression in endothelial cells and others with migratory potential (cytotrophoblasts, carcinoma cells, etc). AAMP is 52 kd with an isoelectric point of 5.2. Its sequence contains immunoglobulin type domains, WD40 repeats, a large acidic region with an acid box, a potential transmembrane region, potential serine/threonine phosphorylation sites, and a positively charged amino-terminal region with strong heparin binding potential (Kd = 14 pmol). Human umbilical vein endothelial cells cultured on Matrigel, a basement membrane material, form endothelial tubes (capillary-like structures). Anti-recombinant AAMP (anti-rAAMP) (1 to 10 microg/ml) inhibits this process under conditions that favor cross-linking of its ligand (AAMP). Immunofluorescent staining has shown that AAMP is distributed both intracellularly and extracellularly in cultures of endothelial cells and tubes. Molecular analysis of AAMP's protein sequence shows a striking evolutionary relationship with the YCR072c protein in Saccharomyces cerevisiae. Both the human and yeast proteins show an unusual and almost identical arrangement of immunoglobulin type domains, WD40 repeats, a protein kinase C phosphorylation consensus site in the carboxyl region, and a positively charged amino-terminal region that in AAMP has heparin binding potential. Detection of YCR072c's immunoglobulin type domains is new. Thus, AAMP is a protein that has been highly conserved in evolution and may function in the regulation of endothelial tube formation.