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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Carrier Proteins / genetics*
  • Carrier Proteins / metabolism
  • Catalysis
  • Drosophila melanogaster
  • Enzymes / genetics*
  • Enzymes / metabolism
  • Evolution, Molecular*
  • Genome
  • Humans
  • Mice
  • Phylogeny
  • Selection, Genetic
  • Sequence Homology, Amino Acid*


  • Carrier Proteins
  • Enzymes
  • iRhom2 protein, mouse