Human clade B serpins (ov-serpins) belong to a cohort of evolutionarily dispersed intracellular proteinase inhibitor clades that protect cells from promiscuous proteolysis

G. A. Silverman, J. C. Whisstock, D. J. Askew, S. C. Pak, C. J. Luke, S. Cataltepe, J. A. Irving, P. I. Bird

Research output: Contribution to journalReview articlepeer-review

142 Scopus citations

Abstract

Serpins are unique among the various types of active site proteinase inhibitors because they covalently trap their targets by undergoing an irreversible conformational rearrangement. Members of the serpin superfamily are present in the three major domains of life (Bacteria, Archaea and Eukarya) as well as several eukaryotic viruses. The human genome encodes for at least 35 members that segregate evolutionarily into nine (A-I) distinct clades. Most of the human serpins are secreted and circulate in the bloodstream where they reside at critical checkpoints intersecting self-perpetuating proteolytic cascades such as those of the clotting, thrombolytic and complement systems. Unlike these circulating serpins, the clade B serpins (ov-serpins) lack signal peptides and reside primarily within cells. Most of the human clade B serpins inhibit serine and/or papain-like cysteine proteinases and protect cells from exogenous and endogenous proteinase-mediated injury. Moreover, as sequencing projects expand to the genomes of other species, it has become apparent that intracellular serpins belonging to distinct phylogenic clades are also present in the three major domains of life. As some of these serpins also guard cells against the deleterious effects of promiscuous proteolytic activity, we propose that this cytoprotective function, along with similarities in structure are common features of a cohort of intracellular serpin clades from a wide variety of species.

Original languageEnglish
Pages (from-to)301-325
Number of pages25
JournalCellular and Molecular Life Sciences
Volume61
Issue number3
DOIs
StatePublished - Feb 1 2004
Externally publishedYes

Keywords

  • Apoptosis
  • Cell death
  • Clade B serpin
  • Cysteine proteinase
  • Evolution
  • Innate immunity
  • Intracellular serpin
  • Proteinase inhibitor
  • Serine proteinase
  • Serpin
  • Tumor invasion
  • ov-serpin

Fingerprint Dive into the research topics of 'Human clade B serpins (ov-serpins) belong to a cohort of evolutionarily dispersed intracellular proteinase inhibitor clades that protect cells from promiscuous proteolysis'. Together they form a unique fingerprint.

Cite this