Summary: YhcG PDDEXK nuclease domain
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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. 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]
Contents
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. An 2015 work was able to assign 20% of the DUFs to characterized structual 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
- ^ a b El-Gebali S, Mistry J, Bateman A, Eddy SR, Luciani A, Potter SC, Qureshi M, Richardson LJ, Salazar GA, Smart A, Sonnhammer EL, Hirsh L, Paladin L, Piovesan D, Tosatto SC, Finn RD (January 2019). "The Pfam protein families database in 2019". Nucleic Acids Research. 47 (D1): D427–D432. doi:10.1093/nar/gky995. PMC 6324024. PMID 30357350.
- ^ a b Bateman A, Coggill P, Finn RD (October 2010). "DUFs: families in search of function". Acta Crystallographica. Section F, Structural Biology and Crystallization Communications. 66 (Pt 10): 1148–52. doi:10.1107/S1744309110001685. PMC 2954198. PMID 20944204.
- ^ Punta M, Coggill PC, Eberhardt RY, Mistry J, Tate J, Boursnell C, Pang N, Forslund K, Ceric G, Clements J, Heger A, Holm L, Sonnhammer EL, Eddy SR, Bateman A, Finn RD (January 2012). "The Pfam protein families database". Nucleic Acids Research. 40 (Database issue): D290–301. doi:10.1093/nar/gkr1065. PMC 3245129. PMID 22127870.
- ^ Schultz J, Milpetz F, Bork P, Ponting CP (May 1998). "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. Bibcode:1998PNAS...95.5857S. doi:10.1073/pnas.95.11.5857. PMC 34487. PMID 9600884.
- ^ Jaroszewski L, Li Z, Krishna SS, Bakolitsa C, Wooley J, Deacon AM, Wilson IA, Godzik A (September 2009). "Exploration of uncharted regions of the protein universe". PLoS Biology. 7 (9): e1000205. doi:10.1371/journal.pbio.1000205. PMC 2744874. PMID 19787035.
- ^ Mudgal R, Sandhya S, Chandra N, Srinivasan N (July 2015). "De-DUFing the DUFs: Deciphering distant evolutionary relationships of Domains of Unknown Function using sensitive homology detection methods". Biology Direct. 10 (1): 38. doi:10.1186/s13062-015-0069-2. PMC 4520260. PMID 26228684.
- ^ a b c Goodacre NF, Gerloff DL, Uetz P (December 2013). "Protein domains of unknown function are essential in bacteria". mBio. 5 (1): e00744–13. doi:10.1128/mBio.00744-13. PMC 3884060. PMID 24381303.
- ^ a b c Häuser R, Pech M, Kijek J, Yamamoto H, Titz B, Naeve F, Tovchigrechko A, Yamamoto K, Szaflarski W, Takeuchi N, Stellberger T, Diefenbacher ME, Nierhaus KH, Uetz P (2012). Hughes D (ed.). "RsfA (YbeB) proteins are conserved ribosomal silencing factors". PLoS Genetics. 8 (7): e1002815. doi:10.1371/journal.pgen.1002815. PMC 3400551. PMID 22829778.
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This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.
YhcG PDDEXK nuclease domain Provide feedback
This domain can be found in uncharacterised proteins in viruses, archaea and bacteria, most notably it is found in YhcG proteins found in E.coli. This entry represents the C-terminal PDDEXK domain belonging to the PD-(D/E)XK superfamily of nucleases involved in DNA recombination and repair [1]. Profile HMM analysis identified a relationship between this C-terminal domain of YhcG and PF01939 , a family of NucS endonucleases [2]. YHcG was identified in association with DNA processing enzymes, including the restriction complexes HsdMRS and McrABC, the integrases IntF and IntS, and the recombinase PinE [1].
Literature references
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Hu P, Janga SC, Babu M, Diaz-Mejia JJ, Butland G, Yang W, Pogoutse O, Guo X, Phanse S, Wong P, Chandran S, Christopoulos C, Nazarians-Armavil A, Nasseri NK, Musso G, Ali M, Nazemof N, Eroukova V, Golshani A, Paccanaro A, Greenblatt JF, Moreno-Hagelsieb G, Emili A;, PLoS Biol. 2009;7:e96.: Global functional atlas of Escherichia coli encompassing previously uncharacterized proteins. PUBMED:19402753 EPMC:19402753
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Kosinski J, Feder M, Bujnicki JM;, BMC Bioinformatics. 2005;6:172.: The PD-(D/E)XK superfamily revisited: identification of new members among proteins involved in DNA metabolism and functional predictions for domains of (hitherto) unknown function. PUBMED:16011798 EPMC:16011798
Internal database links
| SCOOP: | HSDR_N_2 NucS |
This tab holds annotation information from the InterPro database.
InterPro entry IPR009362
This domain can be found in uncharacterised proteins in viruses, archaea and bacteria, most notably it is found in YhcG protein from E.coli. This entry represents the C-terminal PDDEXK domain belonging to the PD-(D/E)XK superfamily of nucleases involved in DNA recombination and repair [ PUBMED:19402753 ]. Profile HMM analysis identified a relationship between this C-terminal domain of YhcG and endonuclease NucS [ PUBMED:16011798 ]. YhcG was identified in association with DNA processing enzymes, including the restriction complexes HsdMRS and McrABC, the integrases IntF and IntS, and the recombinase PinE [ PUBMED:19402753 ].
Domain organisation
Below is a listing of the unique domain organisations or architectures in which this domain is found. More...
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Pfam Clan
This family is a member of clan PDDEXK (CL0236), which has the following description:
This clan includes a large number of nuclease families related to holliday junction resolvases [1,2].
The clan contains the following 145 members:
AHJR-like ArenaCapSnatch BamHI BpuJI_N BpuSI_N Bse634I BsuBI_PstI_RE Cas_APE2256 Cas_Cas02710 Cas_Cas4 Cas_Csm6 Cas_DxTHG Cas_NE0113 CdiA_C CdiA_C_tRNase CoiA Csa1 Dna2 DpnI DpnII DpnII-MboI DUF1780 DUF1887 DUF2034 DUF2161 DUF234 DUF2357 DUF2726 DUF2800 DUF2887 DUF3799 DUF3883 DUF4143 DUF4263 DUF4420 DUF559 DUF5614 DUF6035 DUF6293 EC042_2821 EcoRI EcoRII-C eIF-3_zeta Endonuc-BglII Endonuc-BsobI Endonuc-EcoRV Endonuc-FokI_C Endonuc-HincII Endonuc-MspI Endonuc-PvuII Endonuc_BglI Endonuc_Holl ERCC4 Exo5 Flu_PA Herpes_UL24 Hjc HSDR_N HSDR_N_2 L_protein_N McrBC MepB MmcB-like Mrr_cat Mrr_cat_2 MTES_1575 MutH MvaI_BcnI NaeI NERD NgoMIV_restric NotI NucS PDCD9 PDDEXK_1 PDDEXK_10 PDDEXK_2 PDDEXK_3 PDDEXK_4 PDDEXK_5 PDDEXK_7 PDDEXK_9 Pet127 Phage_endo_I PND R-HINP1I Rad10 RAI1 RAP RE_AlwI RE_ApaLI RE_Bpu10I RE_BsaWI RE_Bsp6I RE_CfrBI RE_Eco47II RE_EcoO109I RE_endonuc RE_HaeII RE_HindIII RE_HindVP RE_HpaII RE_LlaJI RE_LlaMI RE_MjaI RE_NgoBV RE_NgoPII RE_SacI RE_ScaI RE_SinI RE_TaqI RE_TdeIII RE_XamI RE_XcyI RecC_C RecU RestrictionMunI RestrictionSfiI RmuC RNA_pol_Rpb5_N Sen15 SfsA Spo0A_C TBPIP_N ThaI Tn7_Tnp_TnsA_N Tox-REase-2 Tox-REase-3 Tox-REase-5 Tox-REase-7 Tox-REase-9 Transposase_31 tRNA_int_endo Tsp45I Uma2 UPF0102 Viral_alk_exo VirArc_Nuclease VRR_NUC Vsr XhoI XisH YaeQ YhcG_C YqaJAlignments
We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets and the UniProtKB sequence database. More...
View options
We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.
| Seed (32) |
Full (2255) |
Representative proteomes | UniProt (12844) |
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|---|---|---|---|---|---|---|---|
| RP15 (339) |
RP35 (1198) |
RP55 (2305) |
RP75 (4460) |
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| Jalview | |||||||
| HTML | |||||||
| PP/heatmap | 1 | ||||||
1Cannot generate PP/Heatmap alignments for seeds; no PP data available
Key:
available,
not generated,
— not available.
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Download options
We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.
| Seed (32) |
Full (2255) |
Representative proteomes | UniProt (12844) |
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|---|---|---|---|---|---|---|---|
| RP15 (339) |
RP35 (1198) |
RP55 (2305) |
RP75 (4460) |
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| Raw Stockholm | |||||||
| Gzipped | |||||||
You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.
HMM logo
HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...
Trees
This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.
Note: You can also download the data file for the tree.
Curation and family details
This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.
Curation
| Seed source: | Pfam-B_9571 (release 9.0) |
| Previous IDs: | DUF1016; |
| Type: | Domain |
| Sequence Ontology: | SO:0000417 |
| Author: |
Finn RD  , Bateman A , El-Gebali S
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| Number in seed: | 32 |
| Number in full: | 2255 |
| Average length of the domain: | 146.40 aa |
| Average identity of full alignment: | 38 % |
| Average coverage of the sequence by the domain: | 45.28 % |
HMM information
| HMM build commands: |
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 57096847 -E 1000 --cpu 4 HMM pfamseq
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| Model details: |
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| Model length: | 155 | ||||||||||||
| Family (HMM) version: | 13 | ||||||||||||
| Download: | download the raw HMM for this family |
Species distribution
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Colour assignments
Archea
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Eukaryota
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Bacteria
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Other sequences
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Viruses
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Unclassified
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Viroids
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Unclassified sequence
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This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the adjacent tab. More...
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