Please note: this site relies heavily on the use of javascript. Without a javascript-enabled browser, this site will not function correctly. Please enable javascript and reload the page, or switch to a different browser.
15  structures 556  species 1  interaction 1044  sequences 3  architectures

Family: VitK2_biosynth (PF02621)

Summary: Menaquinone biosynthesis

Pfam includes annotations and additional family information from a range of different sources. These sources can be accessed via the tabs below.

This is the Wikipedia entry entitled "Domain of unknown function". More...

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.[1]

History[edit]

The DUF naming scheme was introduced by Chris Ponting, through the addition of DUF1 and DUF2 to the SMART database.[2] 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.

Structure[edit]

Structural genomics programmes have attempted to understand the function of DUFs through structure determination. The structures of over 250 DUF families have been solved.[3] 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[edit]

Protein domains and DUFs in different domains of life. Left: Annotated domains. Right: domains of unknown function. Not all overlaps shown.[4]

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.[4]

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.[5] 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.[5] 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.[5]

Essential DUFs (eDUFs)[edit]

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.[4]

External links[edit]

References[edit]

  1. ^ 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. 
  2. ^ 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. 
  3. ^ 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. 
  4. ^ a b c 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.  edit
  5. ^ a b c 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). "RsfA (YbeB) Proteins Are Conserved Ribosomal Silencing Factors". In Hughes, Diarmaid. PLoS Genetics 8 (7): e1002815. doi:10.1371/journal.pgen.1002815. PMC 3400551. PMID 22829778.  edit

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

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.

Menaquinone biosynthesis Provide feedback

This family includes two enzymes which are involved in menaquinone biosynthesis. One which catalyses the conversion of cyclic de-hypoxanthine futalosine to 1,4-dihydroxy-6-naphthoate, and one which may be involved in the conversion of chorismate to futalosine [1]. These enzymes comprise two domains with alpha/beta structures, a large domain and a small domain. A pocket between the two domains may form the active site, a conserved histidine located within this pocket could be the catalytic base [2].

Literature references

  1. Hiratsuka T, Furihata K, Ishikawa J, Yamashita H, Itoh N, Seto H, Dairi T;, Science. 2008;321:1670-1673.: An alternative menaquinone biosynthetic pathway operating in microorganisms. PUBMED:18801996 EPMC:18801996

  2. Arai R, Murayama K, Uchikubo-Kamo T, Nishimoto M, Toyama M, Kuramitsu S, Terada T, Shirouzu M, Yokoyama S;, J Struct Biol. 2009;168:575-581.: Crystal structure of MqnD (TTHA1568), a menaquinone biosynthetic enzyme from Thermus thermophilus HB8. PUBMED:19602440 EPMC:19602440


External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR003773

This family includes two enzymes which are involved in menaquinone (vitamin K2) biosynthesis. One which catalyses the conversion of cyclic de-hypoxanthine futalosine to 1,4-dihydroxy-6-naphthoate, and one which may be involved in the conversion of chorismate to futalosine [PUBMED:18801996]. These enzymes comprise two domains with alpha/beta structures, a large domain and a small domain. A pocket between the two domains may form the active site, a conserved histidine located within this pocket could be the catalytic base [PUBMED:19602440].

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

Loading domain graphics...

Pfam Clan

This family is a member of clan PBP (CL0177), which has the following description:

Periplasmic binding proteins (PBPs) consist of two large lobes that close around the bound ligand. This architecture is reiterated in transcriptional regulators, such as the lac repressors. In the process of evolution, genes encoding the PBPs have fused with genes for integral membrane proteins. Thus, diverse mammalian receptors contain extracellular ligand binding domains that are homologous to the PBPs; these include glutamate/glycine-gated ion channels such as the NMDA receptor, G protein-coupled receptors, including metabotropic glutamate, GABA-B, calcium sensing, and pheromone receptors, and atrial natriuretic peptide-guanylate cyclase receptors [2].

The clan contains the following 23 members:

DUF3834 HisG Lig_chan-Glu_bd Lipoprotein_8 Lipoprotein_9 LysR_substrate Mycoplasma_p37 NMT1 NMT1_2 OpuAC PBP_like PBP_like_2 Phosphonate-bd SBP_bac_1 SBP_bac_11 SBP_bac_3 SBP_bac_5 SBP_bac_6 SBP_bac_7 SBP_bac_8 TctC Transferrin VitK2_biosynth

Alignments

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 using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the NCBI sequence database, and our metagenomics 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
(131)
Full
(1044)
Representative proteomes NCBI
(1003)
Meta
(282)
RP15
(156)
RP35
(292)
RP55
(345)
RP75
(368)
Jalview View  View  View  View  View  View  View  View 
HTML View  View  View  View  View  View     
PP/heatmap 1 View  View  View  View  View     
Pfam viewer View  View             

1Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: ✓ available, x not generated, not available.

Format an alignment

  Seed
(131)
Full
(1044)
Representative proteomes NCBI
(1003)
Meta
(282)
RP15
(156)
RP35
(292)
RP55
(345)
RP75
(368)
Alignment:
Format:
Order:
Sequence:
Gaps:
Download/view:

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
(131)
Full
(1044)
Representative proteomes NCBI
(1003)
Meta
(282)
RP15
(156)
RP35
(292)
RP55
(345)
RP75
(368)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download   Download  
Gzipped Download   Download   Download   Download   Download   Download   Download   Download  

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

External links

MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER3.

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 View help on the curation process

Seed source: COG1427
Previous IDs: DUF178;
Type: Domain
Author: Mian N, Bateman A, Eberhardt R
Number in seed: 131
Number in full: 1044
Average length of the domain: 248.00 aa
Average identity of full alignment: 24 %
Average coverage of the sequence by the domain: 91.99 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 21.1 21.1
Trusted cut-off 21.1 21.2
Noise cut-off 21.0 21.0
Model length: 251
Family (HMM) version: 9
Download: download the raw HMM for this family

Species distribution

Sunburst controls

Show

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...

Loading sunburst data...

Tree controls

Hide

The tree shows the occurrence of this domain across different species. More...

Loading...

Please note: for large trees this can take some time. While the tree is loading, you can safely switch away from this tab but if you browse away from the family page entirely, the tree will not be loaded.

Interactions

There is 1 interaction for this family. More...

VitK2_biosynth

Structures

For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the VitK2_biosynth domain has been found. There are 15 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.

Loading structure mapping...