Domain of unknown function
Encyclopedia
A Domain of unknown function (DUF) is a protein domain
Protein domain
A protein domain is a part of protein sequence and structure that can evolve, function, and exist independently of the rest of the protein chain. Each domain forms a compact three-dimensional structure and often can be independently stable and folded. Many proteins consist of several structural...

 that has no characterised function. These families have been collected together in the Pfam
Pfam
Pfam is a database of protein families that includes their annotations and multiple sequence alignments generated using hidden Markov models.- Features :For each family in Pfam one can:* Look at multiple alignments* View protein domain architectures...

 database using the prefix DUF followed by a number, with examples being DUF2992 and DUF1220
DUF1220
DUF1220 is a protein domain of unknown function that shows a striking human-specific increase in copy number and may be important to human brain evolution. The copy number of DUF1220 domains increases generally as a function of a species evolutionary proximity to humans. DUF1220 copy number is...

. 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
GGDEF domain
In molecular biology, the GGDEF domain is a protein domain which appears to be ubiquitous in bacteria and is often linked to a regulatory domain, such as a phosphorylation receiver or oxygen sensing domain. Its function is to synthesize cyclic di-GMP, which is used as an intracellular signalling...

 and EAL domain
EAL domain
In molecular biology, the EAL domain is a conserved protein domain. It is found in diverse bacterial signalling proteins. It is named EAL after its conserved residues. The EAL domain may function as a diguanylate phosphodiesterase. The domain contains many conserved acidic residues that could...

 respectively.

Structure

Structural genomics
Structural genomics
Structural genomics seeks to describe the 3-dimensional structure of every protein encoded by a given genome. This genome-based approach allows for a high-throughput method of structure determination by a combination of experimental and modeling approaches...

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.

External links

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