Schultz et al. (1998) Proc. Natl. Acad. Sci. USA 95, 5857-5864
Letunic et al. (2012) Nucleic Acids Res , doi:10.1093/nar/gkr931

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GPS G-protein-coupled receptor proteolytic site domain

                             +-----------------+
                             |                 |
           +-----------------+---------------+ |
           |                 |               | |
        XXXCXXXXXXXXXXXXXXXXXCXXXXXXXXXXXXXXXCXCXXLTXXXXXXX
                                                   ^
                                                   cleavage site

There are 1492 GPS domains in 1485 proteins in SMART's nrdb database.

Click on the following links for more information.

• Evolution (species in which this domain is found)

• Click on to expand nodes. To display all proteins with a GPS domain in a specific node, click on it.

  This tree shows only several representative species. The complete taxonomic breakdown of all proteins with GPS domain is also avaliable.

  Useful shortcuts: Expand all nodes or Collapse tree
  Go to specific node: Anopheles gambiae, Caenorhabditis elegans, Drosophila melanogaster, Homo sapiens, Mus musculus, Rattus norvegicus, Takifugu rubripes

• Literature (relevant references for this domain)

• Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.

  • Krasnoperov V, Bittner MA, Holz RW, Chepurny O, Petrenko AG
  • Structural requirements for alpha-latrotoxin binding and alpha-latrotoxin-stimulated secretion. A study with calcium-independent receptor of alpha-latrotoxin (CIRL) deletion mutants.
  • J Biol Chem. 1999; 274: 3590-6
  • Display abstract

  • Stimulation of neurotransmitter release by alpha-latrotoxin requires its binding to the calcium-independent receptor of alpha-latrotoxin (CIRL), an orphan neuronal G protein-coupled receptor. CIRL consists of two noncovalently bound subunits, p85, a heptahelical integral membrane protein, and p120, a large extracellular polypeptide with domains homologous to lectin, olfactomedin, mucin, the secretin receptor family, and a novel structural motif common for large orphan G protein-coupled receptors. The analysis of CIRL deletion mutants indicates that the high affinity alpha-latrotoxin-binding site is located within residues 467-891, which comprise the first transmembrane segment of p85 and the C-terminal half of p120. The N-terminal lectin, olfactomedin, and mucin domains of p120 are not required for the interaction with alpha-latrotoxin. Soluble p120 and all its fragments, which include the 467-770 residues, bind alpha-latrotoxin with low affinity suggesting the importance of membrane-embedded p85 for the stabilization of the complex of the toxin with p120. Two COOH-terminal deletion mutants of CIRL, one with the truncated cytoplasmic domain and the other with only one transmembrane segment left of seven, supported both alpha-latrotoxin-induced calcium uptake in HEK293 cells and alpha-latrotoxin-stimulated secretion when expressed in chromaffin cells, although with a different dose dependence than wild-type CIRL and its N-terminal deletion mutant. Thus the signaling domains of CIRL are not critically important for the stimulation of exocytosis in intact chromaffin cells by alpha-latrotoxin.

  • Ponting CP, Hofmann K, Bork P
  • A latrophilin/CL-1-like GPS domain in polycystin-1.
  • Curr Biol. 1999; 9: 5858-5858

  • Sugita S, Ichtchenko K, Khvotchev M, Sudhof TC
  • alpha-Latrotoxin receptor CIRL/latrophilin 1 (CL1) defines an unusual family of ubiquitous G-protein-linked receptors. G-protein coupling not required for triggering exocytosis.
  • J Biol Chem. 1998; 273: 32715-24
  • Display abstract

  • alpha-Latrotoxin, a potent excitatory neurotoxin, binds to two receptors: a G-protein-coupled receptor called CIRL/latrophilin 1 (CL1) and a cell-surface protein called neurexin Ialpha. We now show that CL1 belongs to a family of closely related receptors called CL1, CL2, and CL3. CLs exhibit an unusual multidomain structure with similar alternative splicing and large extra- and intracellular sequences. CLs share domains with other G-protein-coupled receptors, lectins, and olfactomedins/myocilin. In addition, CLs contain a novel, widespread cysteine-rich domain that may direct endoproteolytic processing of CLs during transport to the cell surface. Although the mRNAs for CLs are enriched in brain, CLs are ubiquitously expressed in all tissues. To examine how binding of alpha-latrotoxin to CL1 triggers exocytosis, we used PC12 cells transfected with human growth hormone. Ca2+-dependent secretion of human growth hormone from transfected PC12 cells was triggered by KCl depolarization or alpha-latrotoxin and was inhibited by tetanus toxin and by phenylarsine oxide, a phosphoinositide kinase inhibitor. When CL1 was transfected into PC12 cells, their response to alpha-latrotoxin was sensitized dramatically. A similar sensitization to alpha-latrotoxin was observed with different splice variants of CL1, whereas CL2 and CL3 were inactive in this assay. A truncated form of CL1 that contains only a single transmembrane region and presumably is unable to mediate G-protein-signaling was as active as wild type CL1 in alpha-latrotoxin-triggered exocytosis. Our data show that CL1, CL2, and CL3 perform a general and ubiquitous function as G-protein-coupled receptors in cellular signaling. In addition, CL1 serves a specialized role as an alpha-latrotoxin receptor that does not require G-protein-signaling for triggering exocytosis. This suggests that as an alpha-latrotoxin receptor, CL1 recruits alpha-latrotoxin to target membranes without participating in exocytosis directly.

• Metabolism (metabolic pathways involving proteins which contain this domain)

• % proteins involved KEGG pathway ID Description 100.00 map04115 p53 signaling pathway This information is based on mapping of SMART genomic protein database to KEGG orthologous groups. Percentage points are related to the number of proteins with GPS domain which could be assigned to a KEGG orthologous group, and not all proteins containing GPS domain. Please note that proteins can be included in multiple pathways, ie. the numbers above will not always add up to 100%.

• Links (links to other resources describing this domain)

• INTERPRO	IPR000203