Short toxin-like proteins attack the defense line of innate immunity

Michal Linial*, Yitshak Tirosh, Dan Ofer, Tsiona Eliyahu

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


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.

Original languageAmerican English
Pages (from-to)1314-1331
Number of pages18
Issue number7
StatePublished - Jul 2013


  • Antimicrobial peptide
  • Clantox
  • Comparative proteomics
  • Complete proteome
  • Disulfide bonds
  • Functional annotation
  • Ion channel inhibitor
  • Neurotoxin
  • Protein families


Dive into the research topics of 'Short toxin-like proteins attack the defense line of innate immunity'. Together they form a unique fingerprint.

Cite this