Protein superfamily
![Above, secondary structural conservation of 80 members of the PA protease clan (superfamily). H indicates α-helix, E indicates β-sheet, L indicates loop. Below, sequence conservation for the same alignment. Arrows indicate catalytic triad residues. Aligned on the basis of structure by DALI](/Images/godic/202502/13/Structure_vs_sequence_in_the_PA_clan4525.png")
![A sequence alignment of mammalian histone proteins. The similarity of the sequences implies that they evolved by gene duplication. Residues that are conserved across all sequences are highlighted in grey. Below the protein sequences is a key denoting conserved sequence (*), conservative mutations (:), semi-conservative mutations (.), and non-conservative mutations ( ).[3]](/Images/godic/202502/13/Histone_Alignment4525.png")
![Structural homology in the PA superfamily (PA clan). The double β-barrel that characterises the superfamily is highlighted in red. Shown are representative structures from several families within the PA superfamily. Note that some proteins show partially modified structural. Chymotrypsin (1gg6), tobacco etch virus protease (1lvm), calicivirin (1wqs), west nile virus protease (1fp7), exfoliatin toxin (1exf), HtrA protease (1l1j), snake venom plasminogen activator (1bqy), chloroplast protease (4fln) and equine arteritis virus protease (1mbm).](/Images/godic/202502/13/Structural_homology_of_the_PA_clan4525.png")
A protein superfamily is the largest grouping (clade) of proteins for which common ancestry can be inferred (see homology). Usually this common ancestry is based on structural alignment and mechanistic similarity even though no sequence similarity is evident. Superfamilies typically contain several protein families which show sequence similarity within the family. The term protein clan is commonly used for protease superfamilies based on the MEROPS protease classification system.