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84  structures 1531  species 0  interactions 13497  sequences 326  architectures

Family: LRR_9 (PF14580)

Summary: Leucine-rich repeat

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

Leucine-rich repeat Edit Wikipedia article

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An example of a leucine-rich repeat protein, a porcine ribonuclease inhibitor
Pfam clanCL0022
Leucine rich repeat variant
PDB 1lrv EBI.jpg
a leucine-rich repeat variant with a novel repetitive protein structural motif
Pfam clanCL0020
LRR adjacent
PDB 1h6u EBI.jpg
internalin h: crystal structure of fused n-terminal domains.
Leucine rich repeat N-terminal domain
PDB 1xec EBI.jpg
dimeric bovine tissue-extracted decorin, crystal form 2
Leucine rich repeat N-terminal domain
PDB 1ogq EBI.jpg
the crystal structure of pgip (polygalacturonase inhibiting protein), a leucine rich repeat protein involved in plant defense
Leucine rich repeat C-terminal domain
PDB 1w8a EBI.jpg
third lrr domain of drosophila slit
LRV protein FeS4 cluster
PDB 1lrv EBI.jpg
a leucine-rich repeat variant with a novel repetitive protein structural motif
Pfam clanCL0020

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 tandem 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]


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 310-helices arranged in a right-handed superhelix, with the absence of the beta-sheets present in other leucine-rich repeats.[6]

Associated domains

Leucine-rich repeats are often flanked by N-terminal and C-terminal cysteine-rich domains, but not always as is the case with C5orf36

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.

See also


  1. ^ 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.
  2. ^ 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. S2CID 19951452.
  3. ^ 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.
  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. S2CID 84294221.
  5. ^ 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.
  6. ^ 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. S2CID 36535731.
  7. ^ 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.
  8. ^ 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. S2CID 17232767.
  9. ^ 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.

Further reading

External links

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

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Leucine-rich repeat Provide feedback

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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


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Curation and family details

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Seed source: CATH:1a9nC00
Previous IDs: none
Type: Repeat
Sequence Ontology: SO:0001068
Author: Coggill P
Number in seed: 6
Number in full: 13497
Average length of the domain: 142.70 aa
Average identity of full alignment: 25 %
Average coverage of the sequence by the domain: 29.17 %

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 30.5 30.5
Trusted cut-off 30.5 30.5
Noise cut-off 30.4 30.4
Model length: 175
Family (HMM) version: 9
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Species distribution

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Archea Archea Eukaryota Eukaryota
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Viroids Viroids Unclassified sequence Unclassified sequence


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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_9 domain has been found. There are 84 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
A0A0G2JWS1 View 3D Structure Click here
A0A0G2K8U5 View 3D Structure Click here
A0A0G2KV07 View 3D Structure Click here
A0A0R0HSC1 View 3D Structure Click here
A0A0R4I9Y7 View 3D Structure Click here
A0A0R4ICF0 View 3D Structure Click here
A0A140LGC0 View 3D Structure Click here
A0A144A431 View 3D Structure Click here
A0A1D6LBZ6 View 3D Structure Click here
A0A1L8G016 View 3D Structure Click here
A0A1Y7VMI0 View 3D Structure Click here
A0A2R8PZV1 View 3D Structure Click here
A0JM56 View 3D Structure Click here
A2AL36 View 3D Structure Click here
A4I0N9 View 3D Structure Click here
A4I0U0 View 3D Structure Click here
A4I1L7 View 3D Structure Click here
A4I4T0 View 3D Structure Click here
A4I655 View 3D Structure Click here
A4I7I1 View 3D Structure Click here
A4IBM1 View 3D Structure Click here
A4ICR3 View 3D Structure Click here
A4IDR6 View 3D Structure Click here
A6H759 View 3D Structure Click here
A6NJI9 View 3D Structure Click here
B3DH20 View 3D Structure Click here
B4GT53 View 3D Structure Click here
B6CZ40 View 3D Structure Click here
B6CZ45 View 3D Structure Click here
B6CZ54 View 3D Structure Click here
B6CZ61 View 3D Structure Click here
B7ZDB1 View 3D Structure Click here
C0H576 View 3D Structure Click here
C0H5L8 View 3D Structure Click here
C0PGS3 View 3D Structure Click here
C4ALD3 View 3D Structure Click here
C6T8S2 View 3D Structure Click here
D3ZVQ1 View 3D Structure Click here
D3ZZR5 View 3D Structure Click here
D4A619 View 3D Structure Click here