New lives for old: evolution of pseudoenzyme function illustrated by iRhoms.
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.
Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge                 CB2 0QH, UK.
Colin
C
Adrain
Matthew
M
Freeman
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D002384:Catalysis; D004331:Drosophila melanogaster; D004798:Enzymes / Q000235:genetics* / Q000378:metabolism; D019143:Evolution, Molecular; D016678:Genome; D006801:Humans; D051379:Mice; D010802:Phylogeny; D012641:Selection, Genetic; D017386:Sequence Homology, Amino Acid
D002352:Carrier Proteins; D004798:Enzymes; C569468:iRhom2 protein, mouse