Identification of a novel family of G protein-coupled receptor associated sorting proteins

J Neurochem. 2004 May;89(3):766-75. doi: 10.1111/j.1471-4159.2004.02411.x.


During the past few years several new interacting partners for G protein-coupled receptors (GPCRs) have been discovered, suggesting that the activity of these receptors is more complex than previously anticipated. Recently, candidate G protein-coupled receptor associated sorting protein (GASP-1) has been identified as a novel interacting partner for the delta opioid receptor and has been proposed to determine the degradative fate of this receptor. We show here that GASP-1 associates in vitro with other opioid receptors and that the interaction domain in these receptors is restricted to a small portion of the carboxyl-terminal tail, corresponding to helix 8 in the three-dimensional structure of rhodopsin. In addition, we show that GASP-1 interacts with COOH-terminus of several other GPCRs from subfamilies A and B and that two conserved residues within the putative helix 8 of these receptors are critical for the interaction with GASP-1. In situ hybridization and northern blot analysis indicate that GASP-1 mRNA is mainly distributed throughout the central nervous system, consistent with a potential interaction with numerous GPCRs in vivo. Finally, we show that GASP-1 is a member of a novel family comprising at least 10 members, whose genes are clustered on chromosome X. Another member of the family, GASP-2, also interacts with the carboxyl-terminal tail of several GPCRs. Therefore, GASP proteins may represent an important protein family regulating GPCR physiology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Central Nervous System / metabolism
  • Chromosomes, Human, Pair 10 / genetics
  • Cloning, Molecular
  • Conserved Sequence
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Mice
  • Molecular Sequence Data
  • Multigene Family / genetics*
  • Organ Specificity
  • Protein Binding
  • Protein Transport / physiology
  • RNA, Messenger / biosynthesis
  • Receptors, G-Protein-Coupled / genetics*
  • Receptors, G-Protein-Coupled / metabolism*
  • Receptors, Opioid, delta / genetics
  • Receptors, Opioid, delta / metabolism
  • Receptors, Opioid, mu / genetics
  • Receptors, Opioid, mu / metabolism
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Sequence Homology, Amino Acid
  • Two-Hybrid System Techniques
  • Vesicular Transport Proteins / genetics*
  • Vesicular Transport Proteins / metabolism*


  • GPRASP1 protein, human
  • Gprasp2 protein, mouse
  • Intracellular Signaling Peptides and Proteins
  • RNA, Messenger
  • Receptors, G-Protein-Coupled
  • Receptors, Opioid, delta
  • Receptors, Opioid, mu
  • Recombinant Fusion Proteins
  • Vesicular Transport Proteins