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186  structures 890  species 0  interactions 26691  sequences 2552  architectures

Family: LRR_1 (PF00560)

Summary: Leucine Rich Repeat

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

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

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 α/β 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.


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


  • 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.

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

Ribonuclease inhibitor Edit Wikipedia article

Ribonuclease inhibitor (RI) is a large (~450 residues, ~42 kDa), 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.


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. RI has a surprisingly high cysteine content and is sensitive to oxidation.

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. 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 (>1500 ). Efforts to mutate RNases to lower their affinity for RI while maintaining their enzymatic activity have had limited success.


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

  1. Kobe B, Deisenhofer J; , Trends Biochem Sci 1994;19:415-421.: The leucine-rich repeat: a versatile binding motif. PUBMED:7817399 EPMC:7817399

  2. 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

External database links

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.

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


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...

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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.

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Representative proteomes UniProt

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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.

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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...


This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

Note: You can also download the data file for the tree.

Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation View help on the curation process

Seed source: Reference 1
Previous IDs: LRR;
Type: Repeat
Sequence Ontology: SO:0001068
Author: Bateman A
Number in seed: 2294
Number in full: 26691
Average length of the domain: 23.8 aa
Average identity of full alignment: 39 %
Average coverage of the sequence by the domain: 3.82 %

HMM information View help on HMM parameters

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 20.6 9.3
Trusted cut-off 20.6 10.5
Noise cut-off 20.5 -1000000.0
Model length: 23
Family (HMM) version: 36
Download: download the raw HMM for this family

Species distribution

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Colour assignments

Archea Archea Eukaryota Eukaryota
Bacteria Bacteria Other sequences Other sequences
Viruses Viruses Unclassified Unclassified
Viroids Viroids Unclassified sequence Unclassified sequence


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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...

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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 186 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.

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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
A0A044S3Q3 View 3D Structure Click here
A0A044SN00 View 3D Structure Click here
A0A044U7M9 View 3D Structure Click here
A0A077Z1K5 View 3D Structure Click here
A0A077ZE25 View 3D Structure Click here
A0A0G2KM01 View 3D Structure Click here
A0A0H5S9G4 View 3D Structure Click here
A0A0K0EI02 View 3D Structure Click here
A0A0K0JZD0 View 3D Structure Click here
A0A0N4UK45 View 3D Structure Click here
A0A0N7KPJ8 View 3D Structure Click here
A0A0N7KSN8 View 3D Structure Click here
A0A0N7KSZ4 View 3D Structure Click here
A0A0P0V4W2 View 3D Structure Click here
A0A0P0VEY2 View 3D Structure Click here
A0A0P0VF15 View 3D Structure Click here
A0A0P0VF33 View 3D Structure Click here
A0A0P0VGF8 View 3D Structure Click here
A0A0P0VHL9 View 3D Structure Click here
A0A0P0VJH3 View 3D Structure Click here
A0A0P0VLJ3 View 3D Structure Click here
A0A0P0VWT6 View 3D Structure Click here
A0A0P0WFJ3 View 3D Structure Click here
A0A0P0WIF5 View 3D Structure Click here
A0A0P0WR41 View 3D Structure Click here
A0A0P0WTL7 View 3D Structure Click here
A0A0P0WYI2 View 3D Structure Click here
A0A0P0WYL7 View 3D Structure Click here
A0A0P0X077 View 3D Structure Click here
A0A0P0XI79 View 3D Structure Click here
A0A0P0XKQ2 View 3D Structure Click here
A0A0P0XM98 View 3D Structure Click here
A0A0P0XR54 View 3D Structure Click here
A0A0P0XS56 View 3D Structure Click here
A0A0P0XUB1 View 3D Structure Click here
A0A0P0XV52 View 3D Structure Click here
A0A0P0XVI7 View 3D Structure Click here
A0A0P0XVK4 View 3D Structure Click here
A0A0P0XZM1 View 3D Structure Click here
A0A0P0Y052 View 3D Structure Click here