Summary: Putative metallopeptidase domain
This is the Wikipedia entry entitled "Domain of unknown function". More...
The Wikipedia text that you see displayed here is a download from Wikipedia. This means that the information we display is a copy of the information from the Wikipedia database. The button next to the article title ("Edit Wikipedia article") takes you to the edit page for the article directly within Wikipedia. You should be aware you are not editing our local copy of this information. Any changes that you make to the Wikipedia article will not be displayed here until we next download the article from Wikipedia. We currently download new content on a nightly basis.
Does Pfam agree with the content of the Wikipedia entry ?
Pfam has chosen to link families to Wikipedia articles. In some case we have created or edited these articles but in many other cases we have not made any direct contribution to the content of the article. The Wikipedia community does monitor edits to try to ensure that (a) the quality of article annotation increases, and (b) vandalism is very quickly dealt with. However, we would like to emphasise that Pfam does not curate the Wikipedia entries and we cannot guarantee the accuracy of the information on the Wikipedia page.
Editing Wikipedia articles
Before you edit for the first time
Wikipedia is a free, online encyclopedia. Although anyone can edit or contribute to an article, Wikipedia has some strong editing guidelines and policies, which promote the Wikipedia standard of style and etiquette. Your edits and contributions are more likely to be accepted (and remain) if they are in accordance with this policy.
You should take a few minutes to view the following pages:
How your contribution will be recorded
Anyone can edit a Wikipedia entry. You can do this either as a new user or you can register with Wikipedia and log on. When you click on the "Edit Wikipedia article" button, your browser will direct you to the edit page for this entry in Wikipedia. If you are a registered user and currently logged in, your changes will be recorded under your Wikipedia user name. However, if you are not a registered user or are not logged on, your changes will be logged under your computer's IP address. This has two main implications. Firstly, as a registered Wikipedia user your edits are more likely seen as valuable contribution (although all edits are open to community scrutiny regardless). Secondly, if you edit under an IP address you may be sharing this IP address with other users. If your IP address has previously been blocked (due to being flagged as a source of 'vandalism') your edits will also be blocked. You can find more information on this and creating a user account at Wikipedia.
If you have problems editing a particular page, contact us at email@example.com and we will try to help.
The community annotation is a new facility of the Pfam web site. If you have problems editing or experience problems with these pages please contact us.
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 obvious. 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 becomes 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): 1148â€“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): 5857â€“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): e00744â€“e00713. doi:10.1128/mBio.00744-13. PMID 24381303.
- HÃ¤user, 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.
Putative metallopeptidase domain Provide feedback
This domain, found in various hypothetical bacterial proteins, has no known function. However, it is related to PF01435.
External database links
- 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
- the Pfam graphic itself.
Loading domain graphics...
Clan MA is one of two zinc-dependent metallopeptidases that contain the HEXXH motif. The two histidines are zinc ligands. The structures of this clan show the active site is between its two sub-domains.
The clan contains the following 58 members:Aspzincin_M35 Astacin BSP DUF1570 DUF2201_N DUF2268 DUF3152 DUF3267 DUF3633 DUF3810 DUF4157 DUF4344 DUF45 DUF4953 DUF955 HRXXH Peptidase_M1 Peptidase_M10 Peptidase_M11 Peptidase_M13 Peptidase_M2 Peptidase_M27 Peptidase_M3 Peptidase_M30 Peptidase_M32 Peptidase_M35 Peptidase_M36 Peptidase_M4 Peptidase_M41 Peptidase_M43 Peptidase_M48 Peptidase_M4_C Peptidase_M50 Peptidase_M50B Peptidase_M54 Peptidase_M56 Peptidase_M57 Peptidase_M6 Peptidase_M60 Peptidase_M61 Peptidase_M64 Peptidase_M66 Peptidase_M7 Peptidase_M8 Peptidase_M9 Peptidase_M91 Peptidase_Mx Peptidase_Mx1 Peptidase_U49 Reprolysin Reprolysin_2 Reprolysin_3 Reprolysin_4 Reprolysin_5 SprT-like WLM Zn_peptidase Zn_peptidase_2
We make a range of alignments for each Pfam-A family:
- the curated alignment from which the HMM for the family is built
- the alignment generated by searching the sequence database using the HMM
- Representative Proteomes (RPs) at 15%, 35%, 55% and 75% co-membership thresholds
- alignment generated by searching the NCBI sequence database using the family HMM
- alignment generated by searching the metagenomics sequence database using the family HMM
You can see the alignments as HTML or in three different sequence viewers:
- Pfam viewer
- an HTML-based viewer that uses DAS to retrieve alignment fragments on request
1Cannot generate PP/Heatmap alignments for seeds; no PP data available
Key: available, not generated, — not available.
Format an alignment
If you find these logos useful in your own work, please consider citing the following article:
Note: You can also download the data file for the tree.
Curation and family details
|Seed source:||COGs (COG4900)|
|Author:||COGs, Finn RD, Sammut SJ, Bateman A|
|Number in seed:||8|
|Number in full:||1041|
|Average length of the domain:||240.40 aa|
|Average identity of full alignment:||19 %|
|Average coverage of the sequence by the domain:||55.56 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 80369284 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||2|
|Download:||download the raw HMM for this family|
Weight segments by...
Change the size of the sunburst
selected sequences to HMM
a FASTA-format file
- 0 sequences
- 0 species
How the sunburst is generated
Colouring and labels
Anomalies in the taxonomy tree
Missing taxonomic levels
Unmapped species names
Too many species/sequences
The tree shows the occurrence of this domain across different species. More...
You can use the tree controls to manipulate how the interactive tree is displayed:
- show/hide the summary boxes
- highlight species that are represented in the seed alignment
- expand/collapse the tree or expand it to a given depth
- select a sub-tree or a set of species within the tree and view them graphically or as an alignment
- save a plain text representation of the tree