Conserved Protein Domain Family

pfam01825: GPS 
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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.
PSSM-Id: 426458
Aligned: 333 rows
Threshold Bit Score: 32.3218
Created: 26-Apr-2021
Updated: 29-Sep-2021
Aligned Rows:
PubMed ReferencesClick to see Conserved Features Help

Sequence Alignment
Format: Row Display: Color Bits: Type Selection:
20_pfamImport    1 ATCSFL------DsndGDWSDSGCT------------VtSQNIThVT-CSCDHNTSFALL 41  
XP_011683521   906 SLCVFWEfl-eDEesgGVWSTVGCYR-----------NqT-NGSqIT-CRCDHLTNFAIL 951  purple sea urchin
XP_011662273   846 SLCVFYDf--sADnytGAWSTEGCRA-----------SdI-NAThVT-CSCDHLTNFAIL 890  purple sea urchin
KJE88802       780 PVCAYWN-----Ft-tNLWETNGCTL-----------VrV-VGRnVT-CACTHLTNFAVL 820  Capsaspora owczarzaki ATCC 30864
KJE89316      1594 LVCAFW------NytlNNWDTNGCV------------SaNATATsID-CACTHATNFAIL 1634 Capsaspora owczarzaki ATCC 30864
EDO36967        11 ASCFFY------NtttNSYDTTGIT------------VgGLTTPeLSqCFSTHLTSFASD 52   starlet sea anemone
CBJ33736      1271 PSCVYY------NeitGLWDEDGLVTeaaitpmdesnAdGLTGLnVT-CWSFHLSDFTIS 1323 Ectocarpus siliculosus
XP_026693134   394 LSCGFWD-----Fk-aSDWSTHGCIm-------------T-SQSpVM-CQCNHMTNFAIL 432  vase tunicate
6_pfamImport     1 ETCKFYNsgakRE---SVWSTDGCNT-----------NkT-NTT-VI-CTCNHMTPFAVL 43  
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