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We report a protein sequence analysis of the cell cycle regulatory protease, separase. The sequence and structural conservation of the C-terminal protease domain has long been recognized, whereas the N-terminal regulatory domain of separase was reported to lack detectable sequence similarity. Here we reveal significant sequence conservation of the separase regulatory domain and report a discovery of a cysteine motif (CxCxxC) conserved in major lineages of Metazoa including nematodes and vertebrates. This motif is found in a solvent exposed linker region connecting two TPR-like helical motifs. Mutation of this motif in Caenorhabditis elegans separase leads to a temperature sensitive hypomorphic protein. Conservation of this motif in organisms ranging from C. elegans to humans suggests its functional importance. Reviewers: This article was reviewed by Lakshminarayan Iyer and Michael Galperin.
Melesse, M., Bembenek, J. N., & Zhulin, I. B. (2018). Conservation of the separase regulatory domain. Biology Direct, 13(1). https://doi.org/10.1186/s13062-018-0210-0