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Nat Rev Mol Cell Biol. 2012 Jul 11;13(8):489-98. doi: 10.1038/nrm3392.

New lives for old: evolution of pseudoenzyme function illustrated by iRhoms.

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Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, UK.


Large-scale sequencing of genomes has revealed that most enzyme families include inactive homologues. These pseudoenzymes are often well conserved, implying a selective pressure to retain them during evolution, and therefore that they have significant function. Mechanistic insights and evolutionary lessons are now emerging from the study of a broad range of such 'dead' enzymes. The recently discovered iRhoms - inactive homologues of rhomboid proteases - have joined derlins and other members of the rhomboid-like clan in regulating the fate of proteins as they pass through the secretory pathway. There is a strong case that dead enzymes, which have been rather overlooked, may be a rich source of biological regulators.

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