ANG-2 binds to the endothelial cell specific receptor Tie-2, but, in contrast to ANG-1, does not induce tyrosine phosphorylation. Consequently, ANG-2 modulates ANG-1 activation of Tie-2 and, depending on the physiological and biochemical environment, can act either as an agonist or antagonist of Tie-2 induced angiogenesis. The signaling interactions of ANG-1, ANG-2 and Tie-2, along with less characterized ANG-3 and ANG-4, are required for embryonic and adult angiogenesis. Physiologically, ANG-1 and ANG-2 are associated with sprouting, tube formation, and structural integrity of newly formed blood vessels. Mature human ANG-2 is a secreted protein containing 480 amino acid residues. ANG-2 is composed of an alpha-helix-rich "coiled coil" N-terminal domain and fibrinogen-like C-terminal domain. ANG-2 exists predominantly in the form of a disulfide-linked dimer. Recombinant Human ANG-2 is a C-terminal histidine-tagged glycoprotein which migrates with an apparent molecular mass of 60.0-70.0 kDa by SDS-PAGE under reducing conditions. Sequencing analysis shows an N-terminal sequence starting with residue 68 (D) of the ANG-2 precursor protein. The calculated molecular weight of Recombinant Human ANG-2 is 50.1 kDa.