Seprase: an overview of an important matrix serine protease

Biochim Biophys Acta. 2008 Sep;1784(9):1130-45. doi: 10.1016/j.bbapap.2008.01.006. Epub 2008 Jan 26.

Abstract

Seprase or Fibroblast Activation Protein (FAP) is an integral membrane serine peptidase, which has been shown to have gelatinase activity. Seprase has a dual function in tumour progression. The proteolytic activity of Seprase has been shown to promote cell invasiveness towards the ECM and also to support tumour growth and proliferation. Seprase appears to act as a proteolytically active 170-kDa dimer, consisting of two 97-kDa subunits. It is a member of the group type II integral serine proteases, which includes dipeptidyl peptidase IV (DPPIV/CD26) and related type II transmembrane prolyl serine peptidases, which exert their mechanisms of action on the cell surface. DPPIV and Seprase exhibit multiple functions due to their abilities to form complexes with each other and to interact with other membrane-associated molecules. Localisation of these protease complexes at cell surface protrusions, called invadopodia, may have a prominent role in processing soluble factors and in the degradation of extracellular matrix components that are essential to the cellular migration and matrix invasion that occur during tumour invasion, metastasis and angiogenesis.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Female
  • Gelatinases / chemistry*
  • Gelatinases / genetics
  • Gelatinases / physiology*
  • Humans
  • Male
  • Membrane Proteins / chemistry*
  • Membrane Proteins / genetics
  • Membrane Proteins / physiology*
  • Models, Molecular
  • Molecular Sequence Data
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / physiopathology
  • Neoplasms / enzymology
  • Neoplasms / genetics
  • Protein Conformation
  • Sequence Homology, Amino Acid
  • Serine Endopeptidases / chemistry*
  • Serine Endopeptidases / genetics
  • Serine Endopeptidases / physiology*
  • Signal Transduction
  • Substrate Specificity
  • Tissue Distribution

Substances

  • Membrane Proteins
  • Serine Endopeptidases
  • fibroblast activation protein alpha
  • seprase, human
  • Gelatinases