Biology: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. As of 2019, there are almost 4,000 DUF families within the Pfam database representing over 22% of known families. Some DUFs are not named using the nomenclature due to popular usage but are nevertheless DUFs.[1] The DUF designation is tentative, and such families tend to be renamed to a more specific name (or merged to an existing domain) after a function is identified.[2][3]
History
The DUF naming scheme was introduced by Chris Ponting, through the addition of DUF1 and DUF2 to the SMART database.[4] 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.[2]
Characterisation
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 (2009) 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.[5]
Some DUF families share remote sequence homology with domains that has characterized function. Computational work can be used to link these relationships. A 2015 work was able to assign 20% of the DUFs to characterized structural superfamilies.[6] Pfam also continuously perform the (manually-verified) assignment in "clan" superfamily entries.[1]
Frequency and conservation
More than 20% of all protein domains were annotated as DUFs in 2013. About 2,700 DUFs are found in bacteria compared with just over 1,500 in eukaryotes. Over 800 DUFs are shared between bacteria and eukaryotes, and about 300 of these are also present in archaea. A total of 2,786 bacterial Pfam domains even occur in animals, including 320 DUFs.[7]
Role in biology
Many DUFs are highly conserved, indicating an important role in biology. However, many such DUFs are not essential, hence their biological role often remains unknown. For instance, DUF143 is present in most bacteria and eukaryotic genomes.[8] However, when it was deleted in Escherichia coli no obvious phenotype was detected. Later it was shown that the proteins that contain DUF143, are ribosomal silencing factors that block the assembly of the two ribosomal subunits.[8] While this function is not essential, it helps the cells to adapt to low nutrient conditions by shutting down protein biosynthesis. As a result, these proteins and the DUF only become relevant when the cells starve.[8] It is thus believed that many DUFs (or proteins of unknown function, PUFs) are only required under certain conditions.
Essential DUFs
Goodacre et al. identified 238 DUFs in 355 essential proteins (in 16 model bacterial species), most of which represent single-domain proteins, clearly establishing the biological essentiality of DUFs. These DUFs are called "essential DUFs" or eDUFs.[7]
External links
References
- ↑ 1.0 1.1 "The Pfam protein families database in 2019". Nucleic Acids Research 47 (D1): D427–D432. January 2019. doi:10.1093/nar/gky995. PMID 30357350.
- ↑ 2.0 2.1 "DUFs: families in search of function". Acta Crystallographica. Section F, Structural Biology and Crystallization Communications 66 (Pt 10): 1148–52. October 2010. doi:10.1107/S1744309110001685. PMID 20944204.
- ↑ "The Pfam protein families database". Nucleic Acids Research 40 (Database issue): D290-301. January 2012. doi:10.1093/nar/gkr1065. PMID 22127870.
- ↑ "SMART, a simple modular architecture research tool: identification of signaling domains". Proceedings of the National Academy of Sciences of the United States of America 95 (11): 5857–64. May 1998. doi:10.1073/pnas.95.11.5857. PMID 9600884. Bibcode: 1998PNAS...95.5857S.
- ↑ "Exploration of uncharted regions of the protein universe". PLOS Biology 7 (9): e1000205. September 2009. doi:10.1371/journal.pbio.1000205. PMID 19787035.
- ↑ "De-DUFing the DUFs: Deciphering distant evolutionary relationships of Domains of Unknown Function using sensitive homology detection methods". Biology Direct 10 (1): 38. July 2015. doi:10.1186/s13062-015-0069-2. PMID 26228684.
- ↑ 7.0 7.1 7.2 "Protein domains of unknown function are essential in bacteria". mBio 5 (1): e00744-13. December 2013. doi:10.1128/mBio.00744-13. PMID 24381303.
- ↑ 8.0 8.1 8.2 Hughes, Diarmaid, ed (2012). "RsfA (YbeB) proteins are conserved ribosomal silencing factors". PLOS Genetics 8 (7): e1002815. doi:10.1371/journal.pgen.1002815. PMID 22829778.
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