This level of the CATH hierarchy groups together protein domains which are thought to share a common ancestor and can therefore be described as homologous. Similarities are identified either by high sequence identity or structure comparison using SSAP. Structures are clustered into the same homologous superfamily if they satisfy two or more of the following criteria:

• Sequence identity >= 35%, overlap >= 60% of larger structure equivalent to smaller.
• SSAP score >= 80.0, sequence identity >= 20%, overlap 60% of larger structure equivalent to smaller.
• SSAP score >= 70.0, overlap 60% of larger structure equivalent to smaller; domains which have related functions, which is informed by the literature and Pfam protein family database.
• Significant similarity from HMM-sequence searches and HMM-HMM comparisons using SAM, HMMER (http://hmmer.wustl.edu) and PRC (http://supfam.org/PRC).