Bioinformatics perspective on rhomboid intramembrane protease evolution and function

Lisa N. Kinch, Nick V. Grishin

Research output: Contribution to journalReview articlepeer-review

19 Scopus citations


Endopeptidase classification based on catalytic mechanism and evolutionary history has proven to be invaluable to the study of proteolytic enzymes. Such general mechanistic- and evolutionary- based groupings have launched experimental investigations, because knowledge gained for one family member tends to apply to the other closely related enzymes. The serine endopeptidases represent one of the most abundant and diverse groups, with their apparently successful proteolytic mechanism having arisen independently many times throughout evolution, giving rise to the well-studied soluble chemotrypsins and subtilisins, among many others. A large and diverse family of polytopic transmembrane proteins known as rhomboids has also evolved the serine protease mechanism. While the spatial structure, mechanism, and biochemical function of this family as intramembrane proteases has been established, the cellular roles of these enzymes as well as their natural substrates remain largely undetermined. While the evolutionary history of rhomboid proteases has been debated, sorting out the relationships among current day representatives should provide a solid basis for narrowing the knowledge gap between their biochemical and cellular functions. Indeed, some functional characteristics of rhomboid proteases can be gleaned from their evolutionary relationships. Finally, a specific case where phylogenetic profile analysis has identified proteins that contain a C-terminal processing motif (GlyGly-Cterm) as co-occurring with a set of bacterial rhomboid proteases provides an example of potential target identification through bioinformatics. This article is part of a Special Issue entitled: Intramembrane Proteases.

Original languageEnglish (US)
Pages (from-to)2937-2943
Number of pages7
JournalBiochimica et Biophysica Acta - Biomembranes
Issue number12
StatePublished - 2013


  • Bioinformatics
  • Classification
  • Evolution
  • Intramembrane proteolysis
  • Rhomboid protease
  • Structure

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Cell Biology


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