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The extracellular Leucine-Rich Repeat superfamily; a comparative survey and analysis of evolutionary relationships and expression patterns

BACKGROUND: Leucine-rich repeats (LRRs) are highly versatile and evolvable protein-ligand interaction motifs found in a large number of proteins with diverse functions, including innate immunity and nervous system development. Here we catalogue all of the extracellular LRR (eLRR) proteins in worms,...

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Autores principales: Dolan, Jackie, Walshe, Karen, Alsbury, Samantha, Hokamp, Karsten, O'Keeffe, Sean, Okafuji, Tatsuya, Miller, Suzanne FC, Tear, Guy, Mitchell, Kevin J
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2007
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2235866/
https://www.ncbi.nlm.nih.gov/pubmed/17868438
http://dx.doi.org/10.1186/1471-2164-8-320
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author Dolan, Jackie
Walshe, Karen
Alsbury, Samantha
Hokamp, Karsten
O'Keeffe, Sean
Okafuji, Tatsuya
Miller, Suzanne FC
Tear, Guy
Mitchell, Kevin J
author_facet Dolan, Jackie
Walshe, Karen
Alsbury, Samantha
Hokamp, Karsten
O'Keeffe, Sean
Okafuji, Tatsuya
Miller, Suzanne FC
Tear, Guy
Mitchell, Kevin J
author_sort Dolan, Jackie
collection PubMed
description BACKGROUND: Leucine-rich repeats (LRRs) are highly versatile and evolvable protein-ligand interaction motifs found in a large number of proteins with diverse functions, including innate immunity and nervous system development. Here we catalogue all of the extracellular LRR (eLRR) proteins in worms, flies, mice and humans. We use convergent evidence from several transmembrane-prediction and motif-detection programs, including a customised algorithm, LRRscan, to identify eLRR proteins, and a hierarchical clustering method based on TribeMCL to establish their evolutionary relationships. RESULTS: This yields a total of 369 proteins (29 in worm, 66 in fly, 135 in mouse and 139 in human), many of them of unknown function. We group eLRR proteins into several classes: those with only LRRs, those that cluster with Toll-like receptors (Tlrs), those with immunoglobulin or fibronectin-type 3 (FN3) domains and those with some other domain. These groups show differential patterns of expansion and diversification across species. Our analyses reveal several clusters of novel genes, including two Elfn genes, encoding transmembrane proteins with eLRRs and an FN3 domain, and six genes encoding transmembrane proteins with eLRRs only (the Elron cluster). Many of these are expressed in discrete patterns in the developing mouse brain, notably in the thalamus and cortex. We have also identified a number of novel fly eLRR proteins with discrete expression in the embryonic nervous system. CONCLUSION: This study provides the necessary foundation for a systematic analysis of the functions of this class of genes, which are likely to include prominently innate immunity, inflammation and neural development, especially the specification of neuronal connectivity.
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spelling pubmed-22358662008-02-09 The extracellular Leucine-Rich Repeat superfamily; a comparative survey and analysis of evolutionary relationships and expression patterns Dolan, Jackie Walshe, Karen Alsbury, Samantha Hokamp, Karsten O'Keeffe, Sean Okafuji, Tatsuya Miller, Suzanne FC Tear, Guy Mitchell, Kevin J BMC Genomics Research Article BACKGROUND: Leucine-rich repeats (LRRs) are highly versatile and evolvable protein-ligand interaction motifs found in a large number of proteins with diverse functions, including innate immunity and nervous system development. Here we catalogue all of the extracellular LRR (eLRR) proteins in worms, flies, mice and humans. We use convergent evidence from several transmembrane-prediction and motif-detection programs, including a customised algorithm, LRRscan, to identify eLRR proteins, and a hierarchical clustering method based on TribeMCL to establish their evolutionary relationships. RESULTS: This yields a total of 369 proteins (29 in worm, 66 in fly, 135 in mouse and 139 in human), many of them of unknown function. We group eLRR proteins into several classes: those with only LRRs, those that cluster with Toll-like receptors (Tlrs), those with immunoglobulin or fibronectin-type 3 (FN3) domains and those with some other domain. These groups show differential patterns of expansion and diversification across species. Our analyses reveal several clusters of novel genes, including two Elfn genes, encoding transmembrane proteins with eLRRs and an FN3 domain, and six genes encoding transmembrane proteins with eLRRs only (the Elron cluster). Many of these are expressed in discrete patterns in the developing mouse brain, notably in the thalamus and cortex. We have also identified a number of novel fly eLRR proteins with discrete expression in the embryonic nervous system. CONCLUSION: This study provides the necessary foundation for a systematic analysis of the functions of this class of genes, which are likely to include prominently innate immunity, inflammation and neural development, especially the specification of neuronal connectivity. BioMed Central 2007-09-14 /pmc/articles/PMC2235866/ /pubmed/17868438 http://dx.doi.org/10.1186/1471-2164-8-320 Text en Copyright © 2007 Dolan et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Dolan, Jackie
Walshe, Karen
Alsbury, Samantha
Hokamp, Karsten
O'Keeffe, Sean
Okafuji, Tatsuya
Miller, Suzanne FC
Tear, Guy
Mitchell, Kevin J
The extracellular Leucine-Rich Repeat superfamily; a comparative survey and analysis of evolutionary relationships and expression patterns
title The extracellular Leucine-Rich Repeat superfamily; a comparative survey and analysis of evolutionary relationships and expression patterns
title_full The extracellular Leucine-Rich Repeat superfamily; a comparative survey and analysis of evolutionary relationships and expression patterns
title_fullStr The extracellular Leucine-Rich Repeat superfamily; a comparative survey and analysis of evolutionary relationships and expression patterns
title_full_unstemmed The extracellular Leucine-Rich Repeat superfamily; a comparative survey and analysis of evolutionary relationships and expression patterns
title_short The extracellular Leucine-Rich Repeat superfamily; a comparative survey and analysis of evolutionary relationships and expression patterns
title_sort extracellular leucine-rich repeat superfamily; a comparative survey and analysis of evolutionary relationships and expression patterns
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2235866/
https://www.ncbi.nlm.nih.gov/pubmed/17868438
http://dx.doi.org/10.1186/1471-2164-8-320
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