Summary: ML domain

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

Wikipedia: ML domain
Pfam
InterPro

This is the Wikipedia entry entitled "ML domain". 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 pfam-help@sanger.ac.uk and we will try to help.

Contact us

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.

ML domain Edit Wikipedia article

ML domain

Identifiers

Symbol

E1_DerP2_DerF2

1a9v / SCOPe / SUPFAM

OPM protein

1nep

Available protein structures:
Pfam Â	structures / ECOD Â
PDB	RCSB PDB; PDBe; PDBj
PDBsum	structure summary
PDB	1t2zA:30-155 1nepA:20-147 2f08A:18-143 1xwvA:18-143 1ahm :18-143 1ahk :18-143 1wrfA:18-143 1ktjA:20-143 1a9v :19-143

MD-2-related lipid-recognition

Identifiers

Symbol

MD-2_lipid-recog

Available protein structures:
Pfam Â	structures / ECOD Â
PDB	RCSB PDB; PDBe; PDBj
PDBsum	structure summary
PDB	PDB: 1a9vâ€‹ PDB: 1ahkâ€‹ PDB: 1ahmâ€‹ PDB: 1g13â€‹ PDB: 1ktjâ€‹ PDB: 1nepâ€‹ PDB: 1pu5â€‹ PDB: 1pubâ€‹ PDB: 1tjjâ€‹ PDB: 1wrfâ€‹

The MD-2-related lipid-recognition (ML) domain is implicated in lipid recognition, particularly in the recognition of pathogen related products. It has an immunoglobulin-like beta-sandwich fold similar to that of E-set Ig domains. This domain is present in the following proteins:

Epididymal secretory protein E1 (also known as Niemann-Pick C2 protein), which is known to bind cholesterol. Niemann-Pick disease type C2 is a fatal hereditary disease characterised by accumulation of low-density lipoprotein-derived cholesterol in lysosomes^[1].
House-dust mite allergen proteins such as Der f 2 from Dermatophagoides farinae and Der p 2 from Dermatophagoides pteronyssinus^[2].

Human proteins containing this domain

LY86; LY96; MMD-1;

References

^ Lobel P, Stock AM, Friedland N, Liou HL (2003). "Structure of a cholesterol-binding protein deficient in Niemann-Pick type C2 disease". Proc. Natl. Acad. Sci. U.S.A. 100 (5): -. PMIDÂ 12591954.{{cite journal}}: CS1 maint: multiple names: authors list (link)
^ Kristensen O, Kastrup JS, Skov LK, Gajhede M, Larsen JN, Johannessen BR, Bolwig C, Spangfort M, Lund K (2005). "Structure of the house dust mite allergen Der f 2: implications for function and molecular basis of IgE cross-reactivity". FEBS Lett. 579 (5): -. PMIDÂ 15710415.{{cite journal}}: CS1 maint: multiple names: authors list (link)

This article incorporates text from the public domain Pfam and InterPro: IPR003172

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.

ML domain Provide feedback

ML domain - MD-2-related lipid recognition domain. This family consists of proteins from plants, animals and fungi, including dust mite allergen Der P 2 (P49278). It has been implicate in lipid recognition, particularly in the recognition of pathogen related products. A mutation in Npc2 (Q15668) causes a rare form of Niemann-Pick type C2 disease. This domain has a similar topology to immunoglobulin domains.

Literature references

Mueller GA, Benjamin DC, Rule GS; , Biochemistry 1998;37:12707-12714.: Tertiary structure of the major house dust mite allergen Der p 2: sequential and structural homologies. PUBMED:9737847 EPMC:9737847

Internal database links

SCOOP:	DUF1091 TRP_N
Similarity to PfamA using HHSearch:	TRP_N

External database links

SCOP:

1a9v

This tab holds annotation information from the InterPro database.

InterPro entry IPR003172

The MD-2-related lipid-recognition (ML) domain is implicated in lipid recognition, particularly in the recognition of pathogen related products. It has an immunoglobulin-like beta-sandwich fold similar to that of E-set Ig domains. This domain is present in proteins from plants, animals and fungi, including the following proteins:

Epididymal secretory protein E1 (also known as Niemann-Pick C2 protein - Npc2), which is known to bind cholesterol. Niemann-Pick disease type C2 is a fatal hereditary disease characterised by accumulation of low-density lipoprotein-derived cholesterol in lysosomes [ PUBMED:12591954 ].
House-dust mite allergen proteins such as Der f 2 from Dermatophagoides farinae and Der p 2 from Dermatophagoides pteronyssinus [ PUBMED:15710415 ].

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 LIG (CL0532), which has the following description:

This superfamily includes a number of lipid binding families that have a similar topology to the immunoglobulin fold. The family includes The ML domain Pfam:PF02221. It includes the uncharacterised family Pfam:PF06477.

The clan contains the following 3 members:

DUF1091 E1_DerP2_DerF2 TRP_N

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 (75)	Full (4239)	Representative proteomes				UniProt (7857)
	Seed (75)	Full (4239)	RP15 (1207)	RP35 (2155)	RP55 (3490)	RP75 (4385)	UniProt (7857)
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 (75)	Full (4239)	Representative proteomes				UniProt (7857)
	Seed (75)	Full (4239)	RP15 (1207)	RP35 (2155)	RP55 (3490)	RP75 (4385)	UniProt (7857)
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 (75)	Full (4239)	Representative proteomes				UniProt (7857)
	Seed (75)	Full (4239)	RP15 (1207)	RP35 (2155)	RP55 (3490)	RP75 (4385)	UniProt (7857)
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:

Yeats C

Previous IDs:

none

Type:

Domain

Sequence Ontology:

SO:0000417

Author:

Bateman A

, Yeats C

Number in seed:

75

Number in full:

4239

Average length of the domain:

127 aa

Average identity of full alignment:

19 %

Average coverage of the sequence by the domain:

65.03 %

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	22.7	22.7
Trusted cut-off	22.7	22.7
Noise cut-off	22.6	22.6

Model length:

134

Family (HMM) version:

18

Download:

download the raw HMM for this family

Species distribution

Sunburst
Tree

Sunburst controls

Hide

Weight segments by...

number of sequences
number of species

Change the size of the sunburst

Small

Large

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.

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 E1_DerP2_DerF2 domain has been found. There are 78 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 sequence.

Loading structure mapping...

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
A0A077Z0I4	View 3D Structure	Click here
A0A077Z3A9	View 3D Structure	Click here
A0A077ZBC2	View 3D Structure	Click here
A0A077ZES0	View 3D Structure	Click here
A0A077ZIB9	View 3D Structure	Click here
A0A0D2E5H0	View 3D Structure	Click here
A0A0K0E416	View 3D Structure	Click here
A0A0K0EAD9	View 3D Structure	Click here
A0A0K0EBH5	View 3D Structure	Click here
A0A0K0ESC0	View 3D Structure	Click here
A0A0R0H3H7	View 3D Structure	Click here
A0A175VV36	View 3D Structure	Click here
A0A1C1CSA2	View 3D Structure	Click here
A0A1D6F9G8	View 3D Structure	Click here
A0A286YA46	View 3D Structure	Click here
A0A2K6VGW0	View 3D Structure	Click here
A0A3P7DUG1	View 3D Structure	Click here
A0A3P7F1E8	View 3D Structure	Click here
A0A3Q0KU93	View 3D Structure	Click here
B3DFW4	View 3D Structure	Click here
B4FEI9	View 3D Structure	Click here
C0NNF2	View 3D Structure	Click here
C1GYS5	View 3D Structure	Click here
C6SXR8	View 3D Structure	Click here
C6SZX0	View 3D Structure	Click here
C6T049	View 3D Structure	Click here
D4AYQ6	View 3D Structure	Click here
F4J7G5	View 3D Structure	Click here
F7FJQ3	View 3D Structure	Click here
I1JGG0	View 3D Structure	Click here
K7LVU6	View 3D Structure	Click here
O17271	View 3D Structure	Click here
O48704	View 3D Structure	Click here
O94183	View 3D Structure	Click here
O97763	View 3D Structure	Click here
P0CP28	View 3D Structure	Click here
P17900	View 3D Structure	Click here
P49278	View 3D Structure	Click here
P58754	View 3D Structure	Click here
P61916	View 3D Structure	Click here

Showing 40 matches

<<

<

Page 1 of 3

>

>>

Family: E1_DerP2_DerF2 (PF02221)

Jump to...