GPCR proteolysis site, GPS, motif; The GPS motif is found in GPCRs, and is the site for auto-proteolysis, so is thus named, GPS. The GPS motif is a conserved sequence of ~40 amino acids containing canonical cysteine and tryptophan residues, and is the most highly conserved part of the domain. In most, if not all, cell-adhesion GPCRs these undergo autoproteolysis in the GPS between a conserved aliphatic residue (usually a leucine) and a threonine, serine, or cysteine residue. In higher eukaryotes this motif is found embedded in the C-terminal beta-stranded part of a GAIN domain - GPCR-Autoproteolysis INducing (GAIN). The GAIN-GPS domain adopts a fold in which the GPS motif, at the C-terminus, forms five beta-strands that are tightly integrated into the overall GAIN domain. The GPS motif, evolutionarily conserved from tetrahymena to mammals, is the only extracellular domain shared by all human cell-adhesion GPCRs and PKD proteins, and is the locus of multiple human disease mutations. The GAIN-GPS domain is both necessary and sufficient functionally for autoproteolysis, suggesting an autoproteolytic mechanism whereby the overall GAIN domain fine-tunes the chemical environment in the GPS to catalyze peptide bond hydrolysis. In the cell-adhesion GPCRs and PKD proteins, the GPS motif is always located at the end of their long N-terminal extracellular regions, immediately before the first transmembrane helix of the respective protein.

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                   ....*....|....*....|....*....|....*....|...
gi 808357856   579 NYTCVYYDEEEKAWSTKGIRRIEHSyHGYVKCETNHFGVFALL 621
Cdd:smart00303   2 NPICVFWDESSGEWSTRGCELLETN-GTHTTCSCNHLTTFAVL 43

G-protein-coupled receptor proteolytic site domain; Present in latrophilin/CL-1, sea urchin REJ and polycystin.

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                   ....*....|....*....|....*....|....*....|...
gi 808357856   579 NYTCVYYDEEEKAWSTKGIRRIEHSyHGYVKCETNHFGVFALL 621
Cdd:smart00303   2 NPICVFWDESSGEWSTRGCELLETN-GTHTTCSCNHLTTFAVL 43

G-protein-coupled receptor proteolytic site domain; Present in latrophilin/CL-1, sea urchin REJ and polycystin.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|...
gi 808357856   579 NYTCVYYDEEEKAWSTKGIRRIEHSyHGYVKCETNHFGVFALL 621
Cdd:smart00303   2 NPICVFWDESSGEWSTRGCELLETN-GTHTTCSCNHLTTFAVL 43