PROSITE documentation PDOC00754

G-protein coupled receptors family 3 signatures and profile

Glutamate and calcium bind to G-protein coupled receptors that, while structurally similar to the majority of G-protein coupled receptors (R7G) (see the relevant entry <PDOC00210>), do not show any similarity at the level of their sequence, thus representing a new family whose current known members are listed below:

• The metabotropic glutamate receptors which evoke a variety of function, such as long-tern potentiation, memory acquisition and learning, etc., through the modulation of intracellular effectors [1,2,3]. Currently there are eight known subtypes of metabotropic glutamate receptors; mGluR1 to mGluR8. The subtypes mGluR1 and mGluR5 are coupled to the stimulation of the phosphatidylinositol-calcium second messenger system while mGluR2, mGluR3, mGluR4, mGluR6, mGluR7 and mGluR8 are coupled to G proteins that inhibit adenylate cyclase activity.
• The extracellular calcium-sensing receptor [4] which sense changes in the extracellular concentration of calcium ions. The activity of this receptor is coupled to the stimulation of the phosphatidylinositol-calcium second messenger system.
• Caenorhabditis elegans hypothetical protein ZC506.4.

Structurally these receptors are composed of:

 a) A signal sequence;
 b) A  very  large  hydrophilic extracellular region of about 540 to 600 amino
    acid  residues. This region contains 17 conserved cysteines which could be
    involved in disulfide bonds;
 c) A region of about 250 residues that  seem  to  contain seven transmembrane
    domains;
 d) A C-terminal cytoplasmic domain of variable length (50 to 350 residues).

There are quite a number of regions of high sequence conservation both in the N-terminal domain and in the region containing the transmembrane domains. We have selected three of these conserved regions as signature patterns. The first one corresponds to a highly conserved hydrophobic segment in the central part of the N-terminal extracellular region. The second corresponds to a section that contains a cluster of six cysteines in the C-terminal part of the extracellular domain. The last one corresponds to the C-terminal part of the cytoplasmic loop between the fifth and sixth transmembrane domains.

We also developed a profile which covers the seven transmembrane regions.