Summary: Domain of unknown function (DUF4121)
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Domain of unknown function Edit Wikipedia article
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.
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.
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.
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.
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. 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. 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. It is thus believed that many DUFs (or proteins of unknown function, PUFs) are only required under certain conditions.
Essential DUFs (eDUFs)
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.
- Bateman A, Coggill P, Finn RD (October 2010). "DUFs: families in search of function". Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun. 66 (Pt 10): 1148–52. doi:10.1107/S1744309110001685. PMC 2954198. PMID 20944204.
- Schultz J, Milpetz F, Bork P, Ponting CP (May 1998). "SMART, a simple modular architecture research tool: identification of signaling domains". Proc. Natl. Acad. Sci. U.S.A. 95 (11): 5857–64. doi:10.1073/pnas.95.11.5857. PMC 34487. PMID 9600884.
- Jaroszewski L, Li Z, Krishna SS; et al. (September 2009). "Exploration of uncharted regions of the protein universe". PLoS Biol. 7 (9): e1000205. doi:10.1371/journal.pbio.1000205. PMC 2744874. PMID 19787035.
- Goodacre, N. F.; Gerloff, D. L.; Uetz, P. (2013). "Protein Domains of Unknown Function Are Essential in Bacteria". MBio 5 (1): e00744–e00713. doi:10.1128/mBio.00744-13. PMID 24381303.
- Häuser, R.; Pech, M.; Kijek, J.; Yamamoto, H.; Titz, B. R.; Naeve, F.; Tovchigrechko, A.; Yamamoto, K.; Szaflarski, W.; Takeuchi, N.; Stellberger, T.; Diefenbacher, M. E.; Nierhaus, K. H.; Uetz, P. (2012). Hughes, Diarmaid, ed. "RsfA (YbeB) Proteins Are Conserved Ribosomal Silencing Factors". PLoS Genetics 8 (7): e1002815. doi:10.1371/journal.pgen.1002815. PMC 3400551. PMID 22829778.
"DUF" families are annotated with the Domain of unknown function Wikipedia article. This is a general article, with no specific information about individual Pfam DUFs. If you have information about this particular DUF, please let us know using the "Add annotation" button below.
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Based on Bacteroides thetaiotaomicron gene BT_2588, a putative uncharacterised protein. As seen in gene expression experiments (http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE2231), it appears to be upregulated in the presence of host or vs when in culture [1,2].
Sonnenburg ED, Sonnenburg JL, Manchester JK, Hansen EE et al., Proc Natl Acad Sci U S A 2006 Jun 6;103(23):8834-9. : A hybrid two-component system protein of a prominent human gut symbiont couples glycan sensing in vivo to carbohydrate metabolism. PUBMED:16735464 EPMC:16735464
This tab holds annotation information from the InterPro database.
InterPro entry IPR025189The function of this protein is not known, but the Bacteroides thetaiotaomicron gene appears to be upregulated in the presence of host or other bacterial species compared to pure culture [PUBMED:15790854, PUBMED:16735464].
- the number of sequences which exhibit this architecture
a textual description of the architecture, e.g. Gla, EGF x 2, Trypsin.
This example describes an architecture with one
Gladomain, followed by two consecutive
EGFdomains, and finally a single
- the UniProt description of the protein sequence
- the number of residues in the sequence
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We make a range of alignments for each Pfam-A family:
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Curation and family details
|Seed source:||Bacteroides thetaiotaomicron: BT_2588|
|Author:||Ellrott K, Bakolitsa C|
|Number in seed:||8|
|Number in full:||15|
|Average length of the domain:||261.10 aa|
|Average identity of full alignment:||38 %|
|Average coverage of the sequence by the domain:||94.29 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 11927849 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||3|
|Download:||download the raw HMM for this family|
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