Summary: Protein of unknown function (DUF444)

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

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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 DUF188 and DUF1000. There are now over 3,000 DUF families within the Pfam database representing over 20% of known families.

History

The DUF naming scheme was introduced by Chris Ponting, through the addition of DUF1 and DUF2 to the SMART database.^[1] 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

Structural genomics programmes have attempted to understand the function of DUFs through structure determination. The structures of over 250 DUF families have been solved.^[2]

External Links

List of Pfam familes beginning with the letter D, including DUF families

References

^ Schultz J, Milpetz F, Bork P, Ponting CP (1998). "SMART, a simple modular architecture research tool: identification of signaling domains". Proc. Natl. Acad. Sci. U.S.A. 95 (11): 5857â€“64. PMCÂ 34487. PMIDÂ 9600884. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
^ Jaroszewski L, Li Z, Krishna SS; etÂ al. (2009). "Exploration of uncharted regions of the protein universe". PLoS Biol. 7 (9): e1000205. doi:10.1371/journal.pbio.1000205. PMCÂ 2744874. PMIDÂ 19787035. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)

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

"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.

Protein of unknown function (DUF444) Provide feedback

Bacterial protein of unknown function. One family member (Q97LI1) is predicted to contain a von Willebrand factor (vWF) type A domain ( Smart:VWA). Another family member YeaH is predicted to be part of a conserved signalling pathway with the kinase YeaG and the SpoVR protein YcgB. The pathway may be involved in nitrogen metabolism (see Supplementary note 5 in [1].)

Literature references

Price MN, Wetmore KM, Waters RJ, Callaghan M, Ray J, Liu H, Kuehl JV, Melnyk RA, Lamson JS, Suh Y, Carlson HK, Esquivel Z, Sadeeshkumar H, Chakraborty R, Zane GM, Rubin BE, Wall JD, Visel A, Bristow J, Blow MJ, Arkin AP, Deutschbauer AM;, Nature. 2018;557:503-509.: Mutant phenotypes for thousands of bacterial genes of unknown function. PUBMED:29769716 EPMC:29769716

Internal database links

SCOOP:	VWA_CoxE
Similarity to PfamA using HHSearch:	VWA_2

This tab holds annotation information from the InterPro database.

InterPro entry IPR006698

This family consists of bacterial proteins of unknown function.

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 vWA-like (CL0128), which has the following description:

To add.

The clan contains the following 19 members:

CobT_C Copine DUF1194 DUF2201 DUF444 DUF58 Integrin_beta ivWA Ku_N Med25_VWA Sec23_trunk Ssl1 Ste5_C Tfb4 VWA vWA-TerF-like VWA_2 VWA_3 VWA_CoxE

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 (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets and the UniProtKB sequence database. More...

There are various ways to view or download the sequence alignments that we store. We provide several sequence viewers and a plain-text Stockholm-format file for download.

Alignment types

We make a range of alignments for each Pfam-A family:

seed: the curated alignment from which the HMM for the family is built
full: the alignment generated by searching the sequence database using the HMM
RP15/RP35/RP55/RP75: Representative Proteomes (RPs) at 15%, 35%, 55% and 75% co-membership thresholds
UniProt: alignment generated by searching the UniProtKB sequence database using the family HMM

Viewing

You can see the alignments as HTML or in three different sequence viewers:

jalview: a Java applet developed at the University of Dundee. You will need Java installed before running jalview
HTML: an HTML page showing the whole alignment.Please note: full Pfam alignments can be very large. These HTML views are extremely large and often cause problems for browsers. Please use either jalview or the Pfam viewer if you have trouble viewing the HTML version
PP/Heatmap: an HTML-based representation of the alignment, coloured according to the posterior-probability (PP) values from the HMM. As for the standard HTML view, heatmap alignments can also be very large and slow to render.

Reformatting

You can download (or view in your browser) a text representation of a Pfam alignment in various formats:

Selex
Stockholm
FASTA
MSF

You can also change the order in which sequences are listed in the alignment, change how insertions are represented, alter the characters that are used to represent gaps in sequences and, finally, choose whether to download the alignment or to view it in your browser directly.

Downloading

You may find that large alignments cause problems for the viewers and the reformatting tool, so we also provide all alignments in Stockholm format. You can download either the plain text alignment, or a gzipped version of it.

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 (91)	Full (2893)	Representative proteomes				UniProt (14283)
	Seed (91)	Full (2893)	RP15 (404)	RP35 (1503)	RP55 (2985)	RP75 (5184)	UniProt (14283)
Jalview	View	View	View	View	View	View	View
HTML	View	View
PP/heatmap	₁	View

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

Key: available, not generated, — not available.

Format an alignment

	Seed (91)	Full (2893)	Representative proteomes				UniProt (14283)
	Seed (91)	Full (2893)	RP15 (404)	RP35 (1503)	RP55 (2985)	RP75 (5184)	UniProt (14283)
Alignment:
Format:
Order:	Tree Alphabetical
Sequence:	Inserts lower case All upper case
Gaps:
Download/view:	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 (91)	Full (2893)	Representative proteomes				UniProt (14283)
	Seed (91)	Full (2893)	RP15 (404)	RP35 (1503)	RP55 (2985)	RP75 (5184)	UniProt (14283)
Raw Stockholm	Download	Download	Download	Download	Download	Download	Download
Gzipped	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.

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:

COG2718

Previous IDs:

none

Type:

Family

Sequence Ontology:

SO:0100021

Author:

Kerrison ND

Number in seed:

91

Number in full:

2893

Average length of the domain:

283 aa

Average identity of full alignment:

30 %

Average coverage of the sequence by the domain:

97.22 %

HMM information

HMM build commands:

build method: hmmbuild -o /dev/null HMM SEED

search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq

Model details:

Parameter	Sequence	Domain
Gathering cut-off	27.0	27.0
Trusted cut-off	31.2	27.3
Noise cut-off	25.8	26.7

Model length:

421

Family (HMM) version:

15

Download:

download the raw HMM for this family

Species distribution

Sunburst
Tree

Sunburst controls

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number of sequences
number of species

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Colour assignments

Archea	Eukaryota
Bacteria	Other sequences
Viruses	Unclassified
Viroids	Unclassified sequence

Selections

Generate a FASTA-format file

Clear selection

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...

This chart is a modified "sunburst" visualisation of the species tree for this family. It shows each node in the tree as a separate arc, arranged radially with the superkingdoms at the centre and the species arrayed around the outermost ring.

How the sunburst is generated

The tree is built by considering the taxonomic lineage of each sequence that has a match to this family. For each node in the resulting tree, we draw an arc in the sunburst. The radius of the arc, its distance from the root node at the centre of the sunburst, shows the taxonomic level ("superkingdom", "kingdom", etc). The length of the arc represents either the number of sequences represented at a given level, or the number of species that are found beneath the node in the tree. The weighting scheme can be changed using the sunburst controls.

In order to reduce the complexity of the representation, we reduce the number of taxonomic levels that we show. We consider only the following eight major taxonomic levels:

superkingdom
kingdom
phylum
class
order
family
genus
species

Colouring and labels

Segments of the tree are coloured approximately according to their superkingdom. For example, archeal branches are coloured with shades of orange, eukaryotes in shades of purple, etc. The colour assignments are shown under the sunburst controls. Where space allows, the name of the taxonomic level will be written on the arc itself.

As you move your mouse across the sunburst, the current node will be highlighted. In the top section of the controls panel we show a summary of the lineage of the currently highlighed node. If you pause over an arc, a tooltip will be shown, giving the name of the taxonomic level in the title and a summary of the number of sequences and species below that node in the tree.

Anomalies in the taxonomy tree

There are some situations that the sunburst tree cannot easily handle and for which we have work-arounds in place.

Missing taxonomic levels

Some species in the taxonomic tree may not have one or more of the main eight levels that we display. For example, Bos taurus is not assigned an order in the NCBI taxonomic tree. In such cases we mark the omitted level with, for example, "No order", in both the tooltip and the lineage summary.

Unmapped species names

The tree is built by looking at each sequence in the full alignment for the family. We take the name of the species given by UniProt and try to map that to the full taxonomic tree from NCBI. In some cases, the name chosen by UniProt does not map to any node in the NCBI tree, perhaps because the chosen name is listed as a synonym or a misspelling in the NCBI taxonomy.

So that these nodes are not simply omitted from the sunburst tree, we group them together in a separate branch (or segment of the sunburst tree). Since we cannot determine the lineage for these unmapped species, we show all levels between the superkingdom and the species as "uncategorised".

Sub-species

Since we reduce the species tree to only the eight main taxonomic levels, sequences that are mapped to the sub-species level in the tree would not normally be shown. Rather than leave out these species, we map them instead to their parent species. So, for example, for sequences belonging to one of the Vibrio cholerae sub-species in the NCBI taxonomy, we show them instead as belonging to the species Vibrio cholerae.

Too many species/sequences

For large species trees, you may see blank regions in the outer layers of the sunburst. These occur when there are large numbers of arcs to be drawn in a small space. If an arc is less than approximately one pixel wide, it will not be drawn and the space will be left blank. You may still be able to get some information about the species in that region by moving your mouse across the area, but since each arc will be very small, it will be difficult to accurately locate a particular species.

Loading sunburst data...

Tree controls

Hide

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

Species trees

We show the species tree in one of two ways. For smaller trees we try to show an interactive representation, which allows you to select specific nodes in the tree and view them as an alignment or as a set of Pfam domain graphics.

Unfortunately we have found that there are problems viewing the interactive tree when the it becomes larger than a certain limit. Furthermore, we have found that Internet Explorer can become unresponsive when viewing some trees, regardless of their size. We therefore show a text representation of the species tree when the size is above a certain limit or if you are using Internet Explorer to view the site.

If you are using IE you can still load the interactive tree by clicking the "Generate interactive tree" button, but please be aware of the potential problems that the interactive species tree can cause.

Interactive tree

For all of the domain matches in a full alignment, we count the number that are found on all sequences in the alignment. This total is shown in the purple box.

We also count the number of unique sequences on which each domain is found, which is shown in green. Note that a domain may appear multiple times on the same sequence, leading to the difference between these two numbers.

Finally, we group sequences from the same organism according to the NCBI code that is assigned by UniProt, allowing us to count the number of distinct sequences on which the domain is found. This value is shown in the pink boxes.

We use the NCBI species tree to group organisms according to their taxonomy and this forms the structure of the displayed tree. Note that in some cases the trees are too large (have too many nodes) to allow us to build an interactive tree, but in most cases you can still view the tree in a plain text, non-interactive representation. Those species which are represented in the seed alignment for this domain are highlighted.

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

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.

AlphaFold Structure Predictions

The list of proteins below match this family and have AlphaFold predicted structures. Click on the protein accession to view the predicted structure.

Protein	Predicted structure	External Information
A0A0H3GN29	View 3D Structure	Click here
A1SY50	View 3D Structure	Click here
A4VHH5	View 3D Structure	Click here
A4XZJ9	View 3D Structure	Click here
A5N5W4	View 3D Structure	Click here
A6T7Q4	View 3D Structure	Click here
A9MFI1	View 3D Structure	Click here
B2VJ29	View 3D Structure	Click here
B3PL49	View 3D Structure	Click here
B8I6I0	View 3D Structure	Click here
C3K332	View 3D Structure	Click here
C3MB23	View 3D Structure	Click here
C5B9W9	View 3D Structure	Click here
C5BPC3	View 3D Structure	Click here
P45742	View 3D Structure	Click here
P59348	View 3D Structure	Click here
P59350	View 3D Structure	Click here
P59351	View 3D Structure	Click here
P59352	View 3D Structure	Click here
P76235	View 3D Structure	Click here
Q11LR5	View 3D Structure	Click here
Q1QPM0	View 3D Structure	Click here
Q1QZ69	View 3D Structure	Click here
Q21MT5	View 3D Structure	Click here
Q3SJH5	View 3D Structure	Click here
Q4K4X0	View 3D Structure	Click here
Q5WHZ3	View 3D Structure	Click here
Q6D4P1	View 3D Structure	Click here
Q7MJ13	View 3D Structure	Click here
Q81I66	View 3D Structure	Click here
Q81YT1	View 3D Structure	Click here
Q87R12	View 3D Structure	Click here
Q88A51	View 3D Structure	Click here
Q8XDT8	View 3D Structure	Click here
Q8XKR1	View 3D Structure	Click here
Q8ZEL2	View 3D Structure	Click here
Q8ZPW3	View 3D Structure	Click here
Q92QD3	View 3D Structure	Click here
Q97LI1	View 3D Structure	Click here
Q9HRD6	View 3D Structure	Click here

Showing 40 matches

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Family: DUF444 (PF04285)

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