(a) We compared interfaces of structurally similar protein complexes. We examined whether interface properties of one complex were predictive of the same property in its homologues, given different levels of sequence identity between them. (b) We first compared the interaction propensity of interfaces. Higher values indicate interfaces with a high fraction of residues normally enriched at interfaces while lower values correspond to interfaces chemically close to solvent-exposed surfaces. (c) We then compared the hydrophobicity of interface pairs, defined as the ratio of non-polar residues to the total number of interface residues. (d) Finally, we compared evolutionary conservation of interface residues relative to surface residues. Values below 1 correspond to complexes where the interface is more conserved than the surface. The right-most plot summarizes the squared correlation coefficient (R2) for each property considered, calculated for pairs of proteins binned by shared sequence identity: < 30%, 30-45%, 45-60%, 60-75% and 75-90%. All properties show very low correlation values for pairs sharing less than 30% identity, showing that despite being structurally similar, interfaces can differ dramatically in their chemistry and evolutionary properties. One thousand random data points were sampled for each plot to ease visualization.