PROSITE documentation PDOC50221
GPS domain profile


The GPS domain is a cysteine-rich domain of about 75 amino acid, which was identified in a number of G-protein-coupled receptors (GPCRs) including CIRLs/ latrophilins and in other membrane-associated proteins like the sea urchin receptor for egg jelly protein (REJ). The GPS domain is located immediately N-terminal to transmembrane region (TMRs). For the CIRL-1, CIRL-2, CIRL-3 and CD-97 proteins, it has been shown that they are each made of two non-covalently bound subunits resulting from the endogenous proteolytic cleavage of a precursor protein. Because the cysteine-rich domain of CIRL-1 and possibly other receptors is involved in the endogenous proteolytic processing of CIRL-1 and possibly other receptors, it has been named GPS for GPCR proteolytic site. As the amino acids surrounding the putative cleavage site are the most conserved residues in the GPS domain, it has been suggested that all proteins containing it may be cleaved at this position [1,2,3].

Some proteins known to contain a GPS domain are listed below:

  • Mammalian CIRL/latrophilin 1, 2 and 3 (CL1, CL2 and CL3), G-protein-coupled receptors performing a general and ubiquitous function in cellular signaling. These multidomain proteins also contain a SUEL-type lectin domain (see <PDOC50228>),
  • Mammalian GPCRs Emr1, Emr2 and Emr3, which contain EGF domains (see <PDOC00021>).
  • Mammalian polycystin-1 (PKD-1), a plasma-membrane protein. In human, defects in PKD1 are the cause of autosomal dominant polycystic kidney disease (ADPKD), a common autosomal dominant genetic disease, the cardinal manifestations of which are renal and liver cysts and intracranial aneurysm.
  • Mammalian MEGF2, a type I membrane protein of the cadherin family.
  • Human brain-specific angiogenesis inhibitor (BAI) 1, 2 and 3, GPCRs, which contain thrombospondin type I repeats (TSP1) (see <PDOC50092>).
  • Human leucocyte antigen CD97. It could be a receptor potentially involved in both adhesion and signaling processes early after leukocyte activation.
  • Purple sea urchin sperm receptor for egg jelly (REJ). This type I membrane protein induces the acrosome reaction.

The profile we have developed covers the entire GPS domain.

Last update:

December 2001 / First entry.


Technical section

PROSITE method (with tools and information) covered by this documentation:

GPS, PS50221; GPS domain profile  (MATRIX)


1AuthorsIchtchenko K. Bittner M.A. Krasnoperov V. Little A.R. Chepurny O. Holz R.W. Petrenko A.G.
TitleA novel ubiquitously expressed alpha-latrotoxin receptor is a member of the CIRL family of G-protein-coupled receptors.
SourceJ. Biol. Chem. 274:5491-5498(1999).
PubMed ID10026162

2AuthorsSugita S. Ichtchenko K. Khvotchev M. Suedhof T.C.
Titlealpha-Latrotoxin receptor CIRL/latrophilin 1 (CL1) defines an unusual family of ubiquitous G-protein-linked receptors. G-protein coupling not required for triggering exocytosis.
SourceJ. Biol. Chem. 273:32715-32724(1998).
PubMed ID9830014

3AuthorsPonting C.P. Hofmann K. Bork P.
TitleA latrophilin/CL-1-like GPS domain in polycystin-1.
SourceCurr. Biol. 9:R585-R588(1999).
PubMed ID10469603

PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND 4.0) License, see prosite_license.html.


View entry in original PROSITE document format
View entry in raw text format (no links)