Angiopoietin-1 (Ang-1) is a secreted ligand for Tie-2, a cell surface receptor tyrosine kinase expressed in endothelial and hemopoietic cells. Ang-1 is an angiogenic factor that mediates blood vessel maturation and may be involved in endothelial development. A related protein, angiopoietin-2 (Ang-2), is a naturally occurring antagonist of Ang-1 activation of Tie-2. In adult tissue, Ang-2 expression is restricted to sites of vascular remodeling. Ang-3 and Ang-4 represent the mouse and human counterparts of the same gene locus. The structural divergence of Ang-3 and Ang-4 cause their divergent functions. Ang-3 and Ang-4 have very different distributions in their respective species, and Ang-3 appears to act as an antagonist while Ang-4 appears to function as an agonist. Ang-3 and Ang-4 share all the main structural characteristics of Ang-1 and Ang-2 and are homologous throughout the signal peptide, N-terminal region, coiled-coil segment and Fibrinogen-like domain.