Function of site-2 Proteases in Bacteria and Bacterial Pathogens

Biochim Biophys Acta. 2013 Dec;1828(12):2808-14. doi: 10.1016/j.bbamem.2013.04.019.


Site-2 proteases (S2Ps) are a class of intramembrane metalloproteases named after the founding member of this protein family, human S2P, which control cholesterol and fatty acid biosynthesis by cleaving Sterol Regulatory Element Binding Proteins which control cholesterol and fatty acid biosynthesis. S2Ps are widely distributed in bacteria and participate in diverse pathways that control such diverse functions as membrane integrity, sporulation, lipid biosynthesis, pheromone production, virulence, and others. The most common signaling mechanism mediated by S2Ps is the coupled degradation of transmembrane anti-Sigma factors to activate ECF Sigma factor regulons. However, additional signaling mechanisms continue to emerge as more prokaryotic S2Ps are characterized, including direct proteolysis of membrane embedded transcription factors and proteolysis of non-transcriptional membrane proteins or membrane protein remnants. In this review we seek to comprehensively review the functions of S2Ps in bacteria and bacterial pathogens and attempt to organize these proteases into conceptual groups that will spur further study. This article is part of a Special Issue entitled: Intramembrane Proteases.

Keywords: Bacterial signal transduction; Site two protease.

Publication types

  • Review

MeSH terms

  • Bacterial Proteins / classification
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Gene Expression Regulation, Bacterial*
  • Gram-Negative Bacteria / enzymology*
  • Gram-Negative Bacteria / genetics
  • Gram-Negative Bacteria / pathogenicity
  • Gram-Positive Bacteria / enzymology*
  • Gram-Positive Bacteria / genetics
  • Gram-Positive Bacteria / pathogenicity
  • Lipid Metabolism
  • Membrane Proteins / classification
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Metalloendopeptidases / classification
  • Metalloendopeptidases / genetics
  • Metalloendopeptidases / metabolism*
  • Mutation
  • Pheromones / genetics
  • Pheromones / metabolism
  • Proteolysis
  • Signal Transduction
  • Substrate Specificity
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Virulence Factors / genetics
  • Virulence Factors / metabolism


  • Bacterial Proteins
  • Membrane Proteins
  • Pheromones
  • Transcription Factors
  • Virulence Factors
  • Metalloendopeptidases