The Pfam database is an important tool in genome annotation, since it provides a 
collection of curated protein families. However, a subset of these families, 
known as domains of unknown function (DUFs), remains poorly characterized. We 
have related sequences from DUF404, DUF407, DUF482, DUF608, DUF810, DUF853, 
DUF976 and DUF1111 to homologs in PDB, within the midnight zone (9-20%) of 
sequence identity. These relationships were extended to provide functional 
annotation by sequence analysis and model building. Also described are examples 
of residue plasticity within enzyme active sites, and change of function within 
homologous sequences of a DUF.