Proteolytic cleavage of the EMR2 receptor requires both the extracellular stalk and the GPS motif

FEBS Lett. 2003 Jul 17;547(1-3):145-50. doi: 10.1016/s0014-5793(03)00695-1.


EMR2 is a human myeloid-restricted member of the EGF-TM7 receptor family that contains a highly conserved G protein-coupled receptor proteolysis site (GPS) in the membrane-proximal region. Here the post-translational proteolytic cleavage of EMR2 at GPS was investigated. We show the cleavage occurs at Leu517-Ser518 and is independent of the transmembrane domains. The non-covalent association of the resulting extracellular alpha-subunit and transmembrane beta-subunit requires a minimum of eight amino acids in the beta-subunit. The GPS motif is necessary, but not sufficient for receptor cleavage, which requires the entire extracellular stalk. Thus, an alternatively spliced EMR2 isoform with a truncated stalk fails to undergo proteolytic cleavage. Alternative splicing therefore provides a means to regulate GPS cleavage, producing receptors with two distinct structures.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing
  • Amino Acid Sequence
  • Base Sequence
  • Binding Sites
  • DNA Primers
  • Endopeptidases / metabolism*
  • Epidermal Growth Factor / chemistry
  • Epidermal Growth Factor / genetics
  • Epidermal Growth Factor / metabolism*
  • Genetic Vectors
  • Humans
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Peptide Fragments / chemistry
  • Receptors, G-Protein-Coupled
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism


  • ADGRE2 protein, human
  • DNA Primers
  • Peptide Fragments
  • Receptors, G-Protein-Coupled
  • Recombinant Proteins
  • Epidermal Growth Factor
  • Endopeptidases