The VCBS superfamily forms a third supercluster of β-propellers that includes tachylectin and integrins.

Motivation β-Propellers are found in great variety across all kingdoms of life. They assume many cellular roles, primarily as scaffolds for macromolecular interactions and catalysis. Despite their diversity, most β-propeller families clearly originated by amplification from the same ancient peptide-the "blade". In cluster analyses, β-propellers of the WD40 superfamily always formed the largest group, to which some important families, such as the α-integrin, Asp-box, and glycoside hydrolase β-propellers connected weakly. Motivated by the dramatic growth of sequence databases we revisited these connections, with a special focus on VCBS-like β-propellers, which have not been analysed for their evolutionary relationships so far. Results We found that VCBS-like form a supercluster with integrin-like β-propellers and tachylectins, clearly delimited from the superclusters formed by WD40 and Asp-Box β-propellers. Connections between the three superclusters are made mainly through PQQ-like β-propeller. Our results present a new, greatly expanded view of the β-propeller classification landscape. Supplementary information Supplementary data are available at Bioinformatics online.