Summary: Leucine rich repeat

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Wikipedia: Leucine-rich repeat
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This is the Wikipedia entry entitled "Leucine-rich repeat". More...

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Leucine-rich repeat Edit Wikipedia article

An example of a leucine-rich repeat protein, a porcine ribonuclease inhibitor (PDB ID 2BNH).

A leucine-rich repeat (LRR) is a protein structural motif that forms an Î±/Î² horseshoe fold. It is composed of repeating 20-30 amino acid stretches that are unusually rich in the hydrophobic amino acid leucine. Typically, each repeat unit has beta strand-turn-alpha helix structure, and the assembled domain, composed of many such repeats, has a horseshoe shape with an interior parallel beta sheet and an exterior array of helices. One face of the beta sheet and one side of the helix array are exposed to solvent and are therefore dominated by hydrophilic residues. The region between the helices and sheets is the protein's hydrophobic core and is tighly sterically packed with leucine residues.

Examples

Leucine-rich repeat motifs have been identified in a large number of functionally unrelated proteins. The best-known example is the ribonuclease inhibitor, but other proteins such as the tropomyosin regulator tropomodulin also share the motif.

Although the canonical LRR protein contains approximately one helix for every beta strand, variants that form beta-alpha superhelix folds sometimes have long loops rather than helices linking successive beta strands.

External links

References

Branden C, Tooze J. (1999). Introduction to Protein Structure 2nd ed. Garland Publishing: New York, NY.

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

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No Pfam abstract.

Internal database links

SCOOP:	DUF285 FBXL18_LRR LRR_12 LRR_3 LRR_4 LRR_5 LRR_6 LRR_9 LRRNT PK_Tyr_Ser-Thr
Similarity to PfamA using HHSearch:	LRR_1 LRR_4 LRR_4 LRR_5 LRR_5 LRR_9

This tab holds annotation information from the InterPro database.

InterPro entry IPR001611

Leucine-rich repeats (LRR) consist of 2-45 motifs of 20-30 amino acids in length that generally folds into an arc or horseshoe shape [ PUBMED:14747988 ]. LRRs occur in proteins ranging from viruses to eukaryotes, and appear to provide a structural framework for the formation of protein-protein interactions [ PUBMED:11751054 , PUBMED:1657640 ].Proteins containing LRRs include tyrosine kinase receptors, cell-adhesion molecules, virulence factors, and extracellular matrix-binding glycoproteins, and are involved in a variety of biological processes, including signal transduction, cell adhesion, DNA repair, recombination, transcription, RNA processing, disease resistance, apoptosis, and the immune response [ PUBMED:2176636 , PUBMED:21606681 ].

Sequence analyses of LRR proteins suggested the existence of several different subfamilies of LRRs. The significance of this classification is that repeats from different subfamilies never occur simultaneously and have most probably evolved independently. It is, however, now clear that all major classes of LRR have curved horseshoe structures with a parallel beta sheet on the concave side and mostly helical elements on the convex side. At least six families of LRR proteins, characterised by different lengths and consensus sequences of the repeats, have been identified. Eleven-residue segments of the LRRs (LxxLxLxxN/CxL), corresponding to the beta-strand and adjacent loop regions, are conserved in LRR proteins, whereas the remaining parts of the repeats (herein termed variable) may be very different. Despite the differences, each of the variable parts contains two half-turns at both ends and a "linear" segment (as the chain follows a linear path overall), usually formed by a helix, in the middle. The concave face and the adjacent loops are the most common protein interaction surfaces on LRR proteins. 3D structure of some LRR proteins-ligand complexes show that the concave surface of LRR domain is ideal for interaction with alpha-helix, thus supporting earlier conclusions that the elongated and curved LRR structure provides an outstanding framework for achieving diverse protein-protein interactions [ PUBMED:11751054 ]. Molecular modeling suggests that the conserved pattern LxxLxL, which is shorter than the previously proposed LxxLxLxxN/CxL is sufficient to impart the characteristic horseshoe curvature to proteins with 20- to 30-residue repeats [ PUBMED:11967365 ].

Gene Ontology

The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.

Molecular function

protein binding (GO:0005515)

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 LRR (CL0022), which has the following description:

Each Leucine Rich Repeat is composed of a beta-alpha unit. These units form elongated non-globular structures. Leucine Rich Repeats are often flanked by cysteine rich domains. This Pfam entry contains Leucine Rich Repeats not recognised by the Pfam:PF00560 model.

The clan contains the following 18 members:

DUF285 FBXL18_LRR FNIP LRR_1 LRR_10 LRR_11 LRR_12 LRR_2 LRR_3 LRR_4 LRR_5 LRR_6 LRR_8 LRR_9 LRR_RI_capping Recep_L_domain Transp_inhibit TTSSLRR

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 (62)	Full (426470)	Representative proteomes				UniProt (766209)
	Seed (62)	Full (426470)	RP15 (66686)	RP35 (179784)	RP55 (340436)	RP75 (453924)	UniProt (766209)
Jalview	View	View	View	View	View	View	View
HTML	View
PP/heatmap	₁

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

Key: available, not generated, — not available.

Format an alignment

	Seed (62)	Full (426470)	Representative proteomes				UniProt (766209)
	Seed (62)	Full (426470)	RP15 (66686)	RP35 (179784)	RP55 (340436)	RP75 (453924)	UniProt (766209)
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 (62)	Full (426470)	Representative proteomes				UniProt (766209)
	Seed (62)	Full (426470)	RP15 (66686)	RP35 (179784)	RP55 (340436)	RP75 (453924)	UniProt (766209)
Raw Stockholm	Download		Download	Download	Download
Gzipped	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:

Jackhmer:JCS-Target417241

Previous IDs:

none

Type:

Repeat

Sequence Ontology:

SO:0001068

Author:

Coggill P

Number in seed:

62

Number in full:

426470

Average length of the domain:

59.1 aa

Average identity of full alignment:

28 %

Average coverage of the sequence by the domain:

20.85 %

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	27.0	27.0
Noise cut-off	26.9	26.9

Model length:

61

Family (HMM) version:

9

Download:

download the raw HMM for this family

Species distribution

Sunburst
Tree

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Colour assignments

Archea	Eukaryota
Bacteria	Other sequences
Viruses	Unclassified
Viroids	Unclassified sequence

Selections

Generate a FASTA-format file

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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...

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

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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

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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 LRR_8 domain has been found. There are 1934 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
A0A044QJN0	View 3D Structure	Click here
A0A044R6P6	View 3D Structure	Click here
A0A044R8Y5	View 3D Structure	Click here
A0A044R999	View 3D Structure	Click here
A0A044S3Q3	View 3D Structure	Click here
A0A044SB21	View 3D Structure	Click here
A0A044SN00	View 3D Structure	Click here
A0A044SZE0	View 3D Structure	Click here
A0A044T3S7	View 3D Structure	Click here
A0A044T4Z0	View 3D Structure	Click here
A0A044T6G0	View 3D Structure	Click here
A0A044TAZ4	View 3D Structure	Click here
A0A044TEZ1	View 3D Structure	Click here
A0A044TGV4	View 3D Structure	Click here
A0A044TJA8	View 3D Structure	Click here
A0A044TM04	View 3D Structure	Click here
A0A044TMW2	View 3D Structure	Click here
A0A044TMW5	View 3D Structure	Click here
A0A044TMW9	View 3D Structure	Click here
A0A044TYG7	View 3D Structure	Click here
A0A044U7M9	View 3D Structure	Click here
A0A044U9V0	View 3D Structure	Click here
A0A044UIA8	View 3D Structure	Click here
A0A044UX15	View 3D Structure	Click here
A0A044UYZ0	View 3D Structure	Click here
A0A044UZ90	View 3D Structure	Click here
A0A044V751	View 3D Structure	Click here
A0A044V9J4	View 3D Structure	Click here
A0A044VDX9	View 3D Structure	Click here
A0A077YVH5	View 3D Structure	Click here
A0A077YVQ7	View 3D Structure	Click here
A0A077YWH1	View 3D Structure	Click here
A0A077YZ14	View 3D Structure	Click here
A0A077YZC5	View 3D Structure	Click here
A0A077Z045	View 3D Structure	Click here
A0A077Z106	View 3D Structure	Click here
A0A077Z151	View 3D Structure	Click here
A0A077Z174	View 3D Structure	Click here
A0A077Z1K5	View 3D Structure	Click here
A0A077Z1Q4	View 3D Structure	Click here

Showing 40 matches

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Family: LRR_8 (PF13855)

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