Summary: Leucine Rich Repeat

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Wikipedia: Leucine-rich repeat
Wikipedia: Ribonuclease inhibitor
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Leucine-rich repeat Edit Wikipedia article

An example of a leucine-rich repeat protein, a porcine ribonuclease inhibitor

Identifiers

Symbol

LRR_1

Pfam clan

Available protein structures:
Pfam	structures
PDB	RCSB PDB; PDBe
PDBsum	structure summary

Leucine rich repeat variant

a leucine-rich repeat variant with a novel repetitive protein structural motif

Identifiers

Symbol

LRV

Pfam clan

Available protein structures:
Pfam	structures
PDB	RCSB PDB; PDBe
PDBsum	structure summary

LRR adjacent

internalin h: crystal structure of fused n-terminal domains.

Identifiers

Symbol

LRR_adjacent

Available protein structures:
Pfam	structures
PDB	RCSB PDB; PDBe
PDBsum	structure summary

Leucine rich repeat N-terminal domain

dimeric bovine tissue-extracted decorin, crystal form 2

Identifiers

Symbol

LRRNT

Available protein structures:
Pfam	structures
PDB	RCSB PDB; PDBe
PDBsum	structure summary

Leucine rich repeat N-terminal domain

the crystal structure of pgip (polygalacturonase inhibiting protein), a leucine rich repeat protein involved in plant defense

Identifiers

Symbol

LRRNT_2

Available protein structures:
Pfam	structures
PDB	RCSB PDB; PDBe
PDBsum	structure summary

Leucine rich repeat C-terminal domain

third lrr domain of drosophila slit

Identifiers

Symbol

LRRCT

Available protein structures:
Pfam	structures
PDB	RCSB PDB; PDBe
PDBsum	structure summary

LRV protein FeS4 cluster

a leucine-rich repeat variant with a novel repetitive protein structural motif

Identifiers

Symbol

LRV_FeS

Pfam clan

Available protein structures:
Pfam	structures
PDB	RCSB PDB; PDBe
PDBsum	structure summary

A leucine-rich repeat (LRR) is a protein structural motif that forms an α/β horseshoe fold.^[1]^[2] It is composed of repeating 20–30 amino acid stretches that are unusually rich in the hydrophobic amino acid leucine. These repeats commonly fold together to form a solenoid protein domain, termed leucine-rich repeat domain. 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 tightly sterically packed with leucine residues.

Leucine-rich repeats are frequently involved in the formation of protein–protein interactions.^[3]^[4]

[edit] Examples

Leucine-rich repeat motifs have been identified in a large number of functionally unrelated proteins.^[5] The best-known example is the ribonuclease inhibitor, but other proteins such as the tropomyosin regulator tropomodulin and the toll-like receptor also share the motif. In fact, the toll-like receptor possesses 10 successive LRR motifs which serve to bind pathogen- and danger-associated molecular patterns.

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.

One leucine-rich repeat variant domain (LRV) has a novel repetitive structural motif consisting of alternating alpha- and 3(10)-helices arranged in a right-handed superhelix, with the absence of the beta-sheets present in other leucine-rich repeats.^[6]

[edit] Associated domains

Leucine-rich repeats are often flanked by N-terminal and C-terminal cysteine-rich domains.

They also co-occur with LRR adjacent domains. These are small, all beta strand domains, which have been structurally described for the protein Internalin (InlA) and related proteins InlB, InlE, InlH from the pathogenic bacterium Listeria monocytogenes. Their function appears to be mainly structural: They are fused to the C-terminal end of leucine-rich repeats, significantly stabilising the LRR, and forming a common rigid entity with the LRR. They are themselves not involved in protein-protein-interactions but help to present the adjacent LRR-domain for this purpose. These domains belong to the family of Ig-like domains in that they consist of two sandwiched beta sheets that follow the classical connectivity of Ig-domains. The beta strands in one of the sheets is, however, much smaller than in most standard Ig-like domains, making it somewhat of an outlier.^[7]^[8]^[9]

An iron sulphur cluster is found at the N-terminus of some proteins containing the leucine-rich repeat variant domain (LRV). These proteins have a two-domain structure, composed of a small N-terminal domain containing a cluster of four Cysteine residues that houses the 4Fe:4S cluster, and a larger C-terminal domain containing the LRV repeats.^[6] Biochemical studies revealed that the 4Fe:4S cluster is sensitive to oxygen, but does not appear to have reversible redox activity.

[edit] See also

Leucine zipper

[edit] References

^ Kobe B, Deisenhofer J (October 1994). "The leucine-rich repeat: a versatile binding motif". Trends Biochem. Sci. 19 (10): 415–21. doi:10.1016/0968-0004(94)90090-6. PMID 7817399.
^ Enkhbayar P, Kamiya M, Osaki M, Matsumoto T, Matsushima N (February 2004). "Structural principles of leucine-rich repeat (LRR) proteins". Proteins 54 (3): 394–403. doi:10.1002/prot.10605. PMID 14747988.
^ Kobe B, Kajava AV (December 2001). "The leucine-rich repeat as a protein recognition motif". Curr. Opin. Struct. Biol. 11 (6): 725–32. doi:10.1016/S0959-440X(01)00266-4. PMID 11751054. http://linkinghub.elsevier.com/retrieve/pii/S0959-440X(01)00266-4.
^ Gay NJ, Packman LC, Weldon MA, Barna JC (October 1991). "A leucine-rich repeat peptide derived from the Drosophila Toll receptor forms extended filaments with a beta-sheet structure". FEBS Lett. 291 (1): 87–91. doi:10.1016/0014-5793(91)81110-T. PMID 1657640. http://linkinghub.elsevier.com/retrieve/pii/0014-5793(91)81110-T.
^ Rothberg JM, Jacobs JR, Goodman CS, Artavanis-Tsakonas S (December 1990). "slit: an extracellular protein necessary for development of midline glia and commissural axon pathways contains both EGF and LRR domains". Genes Dev. 4 (12A): 2169–87. doi:10.1101/gad.4.12a.2169. PMID 2176636. http://www.genesdev.org/cgi/pmidlookup?view=long&pmid=2176636.
^ ^a ^b Peters JW, Stowell MH, Rees DC (December 1996). "A leucine-rich repeat variant with a novel repetitive protein structural motif". Nat. Struct. Biol. 3 (12): 991–4. doi:10.1038/nsb1296-991. PMID 8946850.
^ Schubert WD, Gobel G, Diepholz M, Darji A, Kloer D, Hain T, Chakraborty T, Wehland J, Domann E, Heinz DW (September 2001). "Internalins from the human pathogen Listeria monocytogenes combine three distinct folds into a contiguous internalin domain". J. Mol. Biol. 312 (4): 783–94. doi:10.1006/jmbi.2001.4989. PMID 11575932.
^ Schubert WD, Urbanke C, Ziehm T, Beier V, Machner MP, Domann E, Wehland J, Chakraborty T, Heinz DW (December 2002). "Structure of internalin, a major invasion protein of Listeria monocytogenes, in complex with its human receptor E-cadherin". Cell 111 (6): 825–36. doi:10.1016/S0092-8674(02)01136-4. PMID 12526809.
^ Freiberg A, Machner MP, Pfeil W, Schubert WD, Heinz DW, Seckler R (March 2004). "Folding and stability of the leucine-rich repeat domain of internalin B from Listeri monocytogenes". J. Mol. Biol. 337 (2): 453–61. doi:10.1016/j.jmb.2004.01.044. PMID 15003459.

[edit] Further reading

Tooze, John; Brändén, Carl-Ivar (1999). Introduction to Protein Structure (2nd ed.). New York: Garland Publishing. ISBN 0-8153-2305-0.
Wei T, Gong J, Jamitzky F, Heckl WM, Stark RW, Roessle SC (November 2008). "LRRML: a conformational database and an XML description of leucine-rich repeats (LRRs)". BMC Struct. Biol. 8 (1): 47. doi:10.1186/1472-6807-8-47. PMC 2645405. PMID 18986514. //www.ncbi.nlm.nih.gov/pmc/articles/PMC2645405/.

[edit] External links

v t e Protein domains

BAR BIR BZIP CARD C1 C2 DED ENTH FYVE HEAT Kringle LIM LRR NACHT PAS PDZ Pyrin PH PX SH2 SH3 SUN TRIO WD40 zinc finger

v t e Protein tertiary structure

General	Structural domain Protein folding Structure determination methods

All-α folds:	Helix bundle Globin fold Homeodomain fold Alpha solenoid

All-β folds:	Immunoglobulin domain Beta barrel Beta-propeller

α/β folds:	TIM barrel Leucine-rich repeat Flavodoxin fold Rossmann fold Thioredoxin fold Trefoil knot fold

α+β folds:	DNA clamp Ferredoxin fold Ribonuclease A SH2-like fold

Irregular folds:	Conotoxin

←Secondary structure Quaternary structure→

This article incorporates text from the public domain Pfam and InterPro IPR012569

This article incorporates text from the public domain Pfam and InterPro IPR013210

This article incorporates text from the public domain Pfam and InterPro IPR000372

This article incorporates text from the public domain Pfam and InterPro IPR000483

This article incorporates text from the public domain Pfam and InterPro IPR004830

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

This is the Wikipedia entry entitled "Ribonuclease inhibitor". 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.

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Ribonuclease inhibitor Edit Wikipedia article

Leucine Rich Repeat

Top view of porcine ribonuclease inhibitor, showing its horseshoe shape.^[1] The outer layer is composed of α-helices and the inner layer of parallel β-strands. The inner and outer diameters are roughly 2.1 nm and 6.7 nm, respectively.

Identifiers

Symbol

LRR_1

Pfam clan

Available protein structures:
Pfam	structures
PDB	RCSB PDB; PDBe
PDBsum	structure summary

Ribonuclease inhibitor (RI) is a large (~450 residues, ~49 kDa), acidic (pI ~4.7), leucine-rich repeat protein that forms extremely tight complexes with certain ribonucleases. It is a major cellular protein, comprising ~0.1% of all cellular protein by weight, and appears to play an important role in regulating the lifetime of RNA.^[2]

RI has a surprisingly high cysteine content (~6.5%, cf. 1.7% in typical proteins) and is sensitive to oxidation. RI is also rich in leucine (21.5%, compared to 9% in typical proteins) and commensurately lower in other hydrophobic residues, esp. valine, isoleucine, methionine, tyrosine, and phenylalanine.

[edit] Structure

Side view of porcine ribonuclease inhibitor;^[1] ribbon is colored from blue (N-terminus) to red (C-terminus).

RI is the classic leucine-rich repeat protein, consisting of alternating α-helices and β-strands along its backbone. These secondary structure elements wrap around in a curved, right-handed solenoid that resembles a horseshoe. The parallel β-strands and α-helices form the inner and outer wall of the horseshoe, respectively. The structure appears to be stabilized by buried asparagines at the base of each turn, as it passes from α-helix to β-strand. The αβ repeats alternate between 28 and 29 residues in length, effectively forming a 57-residue unit that corresponds to its genetic structure (each exon codes for a 57-residue unit).

[edit] Binding to ribonucleases

The affinity of RI for ribonucleases is perhaps the highest for any protein-protein interaction; the dissociation constant of the RI-RNase A complex is roughly 20 fM under physiological conditions while that for the RI-angiogenin complex is even smaller (<1 fM). Remarkably, RI is able to bind a wide variety of RNases, despite having low sequence identity. Structural studies indicate that RNases bind like a "cork in the bottle", associating especially with the C-terminal end of RI; the interaction is largely electrostatic but also buries a lot of surface area (>25 nm²). Efforts to mutate RNases to lower their affinity for RI while maintaining their enzymatic activity have had limited success. However, mammalian RI seems unable to bind a few amphibian ribonucleases^{[citation needed]}, such as ranpirnase (also known as Onconase).

RI's affinity for ribonucleases is important, since ribonucleases have cytotoxic and cytostatic effects (especially against cancer cells), and are under investigation as potential cancer therapeutics. Successful evasion of the ubiquitous RI would be essential for the success of a ribonuclease drug, (since it would be ineffective bound to RI). The frog protein Onconase is under investigation for treatment of skin cancers; unfortunately, the antigenicity of amphibian proteins makes them unsuitable for treating internal human cancers. Modifications of human ribonucleases that evade RI but retain their enzymatic activity have also been studied.

[edit] References

^ ^a ^b PDB 2BNH; Kobe B, Deisenhofer J (1993). "Crystal structure of porcine ribonuclease inhibitor, a protein with leucine-rich repeats". Nature 366 (6457): 751–6. doi:10.1038/366751a0. PMID 8264799.
^ Shapiro R (2001). "Cytoplasmic ribonuclease inhibitor". Meth. Enzymol. 341: 611–28. doi:10.1016/S0076-6879(01)41180-3. PMID 11582809.

[edit] Further reading

Kobe B, Deisenhofer J (March 1995). "A structural basis of the interactions between leucine-rich repeats and protein ligands". Nature 374 (6518): 183–6. doi:10.1038/374183a0. PMID 7877692.
Kobe B, Deisenhofer J (December 1996). "Mechanism of ribonuclease inhibition by ribonuclease inhibitor protein based on the crystal structure of its complex with ribonuclease A". J. Mol. Biol. 264 (5): 1028–43. doi:10.1006/jmbi.1996.0694. PMID 9000628.
Papageorgiou AC, Shapiro R, Acharya KR (September 1997). "Molecular recognition of human angiogenin by placental ribonuclease inhibitor--an X-ray crystallographic study at 2.0 A resolution". EMBO J. 16 (17): 5162–77. doi:10.1093/emboj/16.17.5162. PMC 1170149. PMID 9311977. //www.ncbi.nlm.nih.gov/pmc/articles/PMC1170149/.
Suzuki M, Saxena SK, Boix E, Prill RJ, Vasandani VM, Ladner JE, Sung C, Youle RJ (March 1999). "Engineering receptor-mediated cytotoxicity into human ribonucleases by steric blockade of inhibitor interaction". Nat. Biotechnol. 17 (3): 265–70. doi:10.1038/7010. PMID 10096294.
Shapiro R, Ruiz-Gutierrez M, Chen CZ (September 2000). "Analysis of the interactions of human ribonuclease inhibitor with angiogenin and ribonuclease A by mutagenesis: importance of inhibitor residues inside versus outside the C-terminal "hot spot"". J. Mol. Biol. 302 (2): 497–519. doi:10.1006/jmbi.2000.4075. PMID 10970748.
Bretscher LE, Abel RL, Raines RT (April 2000). "A ribonuclease A variant with low catalytic activity but high cytotoxicity". J. Biol. Chem. 275 (14): 9893–6. doi:10.1074/jbc.275.14.9893. PMID 10744660.
Yakovlev G. I., Mitkevich V. A. & Makarov A. A. (2006). Ribonuclease inhibitors. 40. pp. 867–874. doi:10.1134/S0026893306060045. http://www.springerlink.com/index/10.1134/S0026893306060045.

Pharmacology: enzyme inhibition

Class

Substrate

Oxidoreductase (EC 1)	1.1 Aldose reductase HMG-CoA reductase 1.3 5-alpha-reductase 1.4 Monoamine oxidase 1.5 Dihydrofolate reductase 1.13 Lipoxygenase 1.14 Aromatase COX-2 1.17 Xanthine oxidase Ribonucleotide reductase

Transferase (EC 2)	2.1 COMT Thymidylate synthase 2.4 PARP 2.5 Dihydropteroate synthetase Farnesyltransferase 2.6 GABA transaminase 2.7 Nucleotidyltransferase Integrase Reverse transcriptase Protein kinase Tyrosine-kinase Janus kinase

Hydrolase (EC 3)	3.1 Phosphodiesterase Acetylcholinesterase Ribonuclease 3.2 Polygalacturonase Neuraminidase Alpha-glucosidase 3.4 Protease: Exopeptidase Dipeptidyl peptidase-4 ACE Endopeptidase Trypsin Renin Matrix metalloproteinase 3.5 Histone deacetylase Beta-lactamase

Lyase (EC 4)	4.1 Dopa decarboxylase 4.2 Carbonic anhydrase

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.

Leucine Rich Repeat Provide feedback

CAUTION: This Pfam may not find all Leucine Rich Repeats in a protein. Leucine Rich Repeats are short sequence motifs present in a number of proteins with diverse functions and cellular locations. These repeats are usually involved in protein-protein interactions. 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.

Literature references

Kobe B, Deisenhofer J; , Trends Biochem Sci 1994;19:415-421.: The leucine-rich repeat: a versatile binding motif. PUBMED:7817399 EPMC:7817399
Kobe B, Deisenhofer J; , Nature 1993;366:751-756.: Crystal structure of porcine ribonuclease inhibitor, a protein with leucine-rich repeats. PUBMED:8264799 EPMC:8264799

Internal database links

Similarity to PfamA using HHSearch:

LRR_4 LRR_7 LRR_6 LRR_8

External database links

HOMSTRAD:	LRR internalin
PANDIT:	PF00560
Pseudofam:	PF00560
SCOP:	1bnh
SYSTERS:	LRR_1

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].

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 contains the following 11 members:

DUF285 FNIP LRR_1 LRR_2 LRR_3 LRR_4 LRR_5 LRR_6 LRR_7 LRR_8 LRR_9

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...

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RP15/RP35/RP55/RP75: Representative Proteomes (RPs) at 15%, 35%, 55% and 75% co-membership thresholds
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meta: alignment generated by searching the metagenomics sequence database using the family HMM

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	Seed (2414)	Full (25597)	Representative proteomes				NCBI (96601)	Meta (2712)
	Seed (2414)	Full (25597)	RP15 (2975)	RP35 (8467)	RP55 (11049)	RP75 (13545)	NCBI (96601)	Meta (2712)
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Format an alignment

	Seed (2414)	Full (25597)	Representative proteomes				NCBI (96601)	Meta (2712)
	Seed (2414)	Full (25597)	RP15 (2975)	RP35 (8467)	RP55 (11049)	RP75 (13545)	NCBI (96601)	Meta (2712)
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	Seed (2414)	Full (25597)	Representative proteomes				NCBI (96601)	Meta (2712)
	Seed (2414)	Full (25597)	RP15 (2975)	RP35 (8467)	RP55 (11049)	RP75 (13545)	NCBI (96601)	Meta (2712)
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External links

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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:

Reference 1

Previous IDs:

LRR;

Type:

Repeat

Author:

Bateman A

Number in seed:

2414

Number in full:

25597

Average length of the domain:

23.30 aa

Average identity of full alignment:

33 %

Average coverage of the sequence by the domain:

5.68 %

HMM information

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	20.6	9.3
Trusted cut-off	20.6	9.3
Noise cut-off	20.5	9.2

Model length:

22

Family (HMM) version:

28

Download:

download the raw HMM for this family

Species distribution

Sunburst
Tree

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...

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.

Interactions

There are 13 interactions for this family. More...

TIG VWA Trypsin RabGGT_insert RnaseA Cadherin LRR_adjacent Sema E1_DerP2_DerF2 Tap-RNA_bind I-set LRR_1 LRRNT

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_1 domain has been found. There are 82 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...

Archea	Eukaryota
Bacteria	Other sequences
Viruses	Unclassified
Viroids	Unclassified sequence

Family: LRR_1 (PF00560)

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Summary: Leucine Rich Repeat

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Leucine-rich repeat Edit Wikipedia article

Contents

[edit] Examples

[edit] Associated domains

[edit] See also

[edit] References

[edit] Further reading

[edit] External links

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Ribonuclease inhibitor Edit Wikipedia article

Contents

[edit] Structure

[edit] Binding to ribonucleases

[edit] References

[edit] Further reading

Leucine Rich Repeat Provide feedback

Literature references

Internal database links

External database links

InterPro entry IPR001611

Gene Ontology

Domain organisation

Pfam Clan

Alignments

Alignment types

Viewing

Reformatting

Downloading

View options

Format an alignment

Download options

External links

HMM logo

Trees

Curation and family details

Curation

HMM information

Species distribution

Sunburst controls

Weight segments by...

Change the size of the sunburst

Colour assignments

Selections

Currently selected:

How the sunburst is generated

Colouring and labels

Anomalies in the taxonomy tree

Missing taxonomic levels

Unmapped species names

Sub-species

Too many species/sequences

Tree controls

Annotation

Download tree

Selected sequences

Species trees

Interactive tree

Interactions

Structures