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Short Toxin-like Proteins Attack the Defense Line of Innate Immunity
Department of Biological Chemistry, Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem 91904, Israel
* Author to whom correspondence should be addressed.
Received: 15 May 2013; in revised form: 16 July 2013 / Accepted: 16 July 2013 / Published: 23 July 2013
Abstract: ClanTox (classifier of animal toxins) was developed for identifying toxin-like candidates from complete proteomes. Searching mammalian proteomes for short toxin-like proteins (coined TOLIPs) revealed a number of overlooked secreted short proteins with an abundance of cysteines throughout their sequences. We applied bioinformatics and data-mining methods to infer the function of several top predicted candidates. We focused on cysteine-rich peptides that adopt the fold of the three-finger proteins (TFPs). We identified a cluster of duplicated genes that share a structural similarity with elapid neurotoxins, such as α-bungarotoxin. In the murine proteome, there are about 60 such proteins that belong to the Ly6/uPAR family. These proteins are secreted or anchored to the cell membrane. Ly6/uPAR proteins are associated with a rich repertoire of functions, including binding to receptors and adhesion. Ly6/uPAR proteins modulate cell signaling in the context of brain functions and cells of the innate immune system. We postulate that TOLIPs, as modulators of cell signaling, may be associated with pathologies and cellular imbalance. We show that proteins of the Ly6/uPAR family are associated with cancer diagnosis and malfunction of the immune system.
Keywords: neurotoxin; protein families; disulfide bonds; antimicrobial peptide; ion channel inhibitor; ClanTox; complete proteome; comparative proteomics; functional annotation
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Cite This Article
MDPI and ACS Style
Tirosh, Y.; Ofer, D.; Eliyahu, T.; Linial, M. Short Toxin-like Proteins Attack the Defense Line of Innate Immunity. Toxins 2013, 5, 1314-1331.
Tirosh Y, Ofer D, Eliyahu T, Linial M. Short Toxin-like Proteins Attack the Defense Line of Innate Immunity. Toxins. 2013; 5(7):1314-1331.
Tirosh, Yitshak; Ofer, Dan; Eliyahu, Tsiona; Linial, Michal. 2013. "Short Toxin-like Proteins Attack the Defense Line of Innate Immunity." Toxins 5, no. 7: 1314-1331.