Domain of unknown function

A Domain of unknown function (DUF) is a protein domain that has no characterised function. These families have been collected together in the Pfam database using the prefix DUF followed by a number, with examples being DUF2992 and DUF1220. There are now over 3,000 DUF families within the Pfam database representing over 20% of known families.

History
The DUF naming scheme was introduced by Chris Ponting, through the addition of DUF1 and DUF2 to the SMART database. These two domains were found to be widely distributed in bacterial signaling proteins. Subsequently, the functions of these domains were identified and they have since been renamed as the GGDEF domain and EAL domain respectively.

Structure
Structural genomics programmes have attempted to understand the function of DUFs through structure determination. The structures of over 250 DUF families have been solved. This work showed that about two thirds of DUF families had a structure similar to a previously solved one and therefore likely to be divergent members of existing protein superfamilies, whereas about one third possessed a novel protein fold.