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
 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.

Expert(s) to contact by email:

Kolakowski L.F. Jr.

Last update:

April 2006 / Patterns revised.


Technical section

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

G_PROTEIN_RECEP_F3_4, PS50259; G-protein coupled receptors family 3 profile  (MATRIX)

G_PROTEIN_RECEP_F3_1, PS00979; G-protein coupled receptors family 3 signature 1  (PATTERN)

G_PROTEIN_RECEP_F3_2, PS00980; G-protein coupled receptors family 3 signature 2  (PATTERN)

G_PROTEIN_RECEP_F3_3, PS00981; G-protein coupled receptors family 3 signature 3  (PATTERN)


1AuthorsTanabe Y. Masu M. Ishii T. Shigemoto R. Nakanishi S.
TitleA family of metabotropic glutamate receptors.
SourceNeuron 8:169-179(1992).
PubMed ID1309649

2AuthorsOkamoto N. Hori S. Akazawa C. Hayashi Y. Shigemoto R. Mizuno N. Nakanishi S.
TitleMolecular characterization of a new metabotropic glutamate receptor mGluR7 coupled to inhibitory cyclic AMP signal transduction.
SourceJ. Biol. Chem. 269:1231-1236(1994).
PubMed ID8288585

3AuthorsDuvoisin R.M. Zhang C. Ramonell K.
TitleA novel metabotropic glutamate receptor expressed in the retina and olfactory bulb.
SourceJ. Neurosci. 15:3075-3083(1995).
PubMed ID7722646

4AuthorsBrown E.M. Gamba G. Riccardi D. Lombardi M. Butters R. Kifor O. Sun A. Hediger M.A. Lytton J. Hebert S.C.
TitleCloning and characterization of an extracellular Ca(2+)-sensing receptor from bovine parathyroid.
SourceNature 366:575-580(1993).
PubMed ID8255296

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