Fig. 1.

GPCR post-translational modifications. GPCRs are seven-transmembrane proteins subjected to multiple types of PTMs on ECLs, ICLs, and the C-terminal domain. Here we show the most common sites of GPCR PTMs. PTMs that occur on ECLs include the following: N-glycosylation at asparagine (N)-X-serine (S)/threonine (T) sites, where X is any amino acid other than proline; O-glycosylation at S or T residues; and tyrosine (Y) sulfation. Nitrosylation has been shown to occur at transmembrane cysteine (C) residues. PTMs on intracellular loops include the following: SUMOylation on K residues present in the motif ψ-K-X-(D/E), where ψ is aliphatic amino acid, X is any amino acid, aspartic acid is D, and glutamic acid is E; methylation at arginine (R) residues of R-G-G or R-X-R sites, where glycine is G and X is any amino acid; and palmitoylation at cysteine (C). GPCR C-terminal PTMs include phosphorylation on S or T, rarely on Y residues, and ubiquitination (Ub) on specific K residues.