Dolan, Jackie, Walshe, Karen, Alsbury, Samantha, Hokamp, Karsten, O'Keeffe, Sean, Okafuji, Tatsuya, Miller, Suzanne F.C., Tear, Guy and Mitchell, Kevin J. (2007) The extracellular Leucine-rich repeat superfamily; a comparative survey and analysis of evolutionary relationships and expression patterns. BMC Genomics, 8. p. 320. ISSN 1471-2164 (doi:10.1186/1471-2164-8-320)

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Abstract

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.

Item Type:	Article
Additional Information:	[1] Published: 14 September 2007. [2] A correction for this article was published in BMC Genomics 2009, 10:230 - http://www.biomedcentral.com/1471-2164/10/230 (The electronic version of this article is the complete one and can be found online at: http://www.biomedcentral.com/1471-2164/8/320). [3] ISSN 1471-2164 (Online). [4] (c) 2007 Dolan et al; licensee BioMed Central Ltd. 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.
Uncontrolled Keywords:	Leucine-rich repeat superfamily, LRR, comparative survey, expression patterns
Subjects:	Q Science > QD Chemistry Q Science > QR Microbiology
Pre-2014 Departments:	School of Science
Related URLs:	Publisher Organisation
Last Modified:	18 Nov 2016 15:47
URI:	http://gala.gre.ac.uk/id/eprint/9298

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