Figure 3. Increased acidity of the low-affinity, high-capacity Ca²⁺-binding N-terminal domain I during evolution. Domain I of SPARC in invertebrates has an almost equal number of acidic and basic amino acid residues. However, despite the presence of several basic amino acids in vertebrates, this domain can bind with low affinity to several Ca²⁺ ions (Maurer and Hohenester, 1997). Interestingly, basic amino acid residues are not found in Domain I of vertebrate SPARC, suggesting that SPARC may have been recruited during vertebrate evolution to function in the formation of mineralized tissues. Acidic amino acids (red), basic amino acids (blue), cysteine residues (amber).