{PDOC00754} {PS00979; G_PROTEIN_RECEP_F3_1} {PS00980; G_PROTEIN_RECEP_F3_2} {PS00981; G_PROTEIN_RECEP_F3_3} {PS50259; G_PROTEIN_RECEP_F3_4} {BEGIN} *************************************************************** * 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 ), 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. -Consensus pattern: [LV]-x-N-[LIVM](2)-x-L-F-x-I-[PA]-Q-[LIVM]-[STA]-x- [STA](3)-[STAN] -Sequences known to belong to this class detected by the pattern: ALL. -Other sequence(s) detected in Swiss-Prot: NONE. -Consensus pattern: C-C-[FYW]-x-C-x(2)-C-x(4)-[FYW]-x(2,5)-[DNE]-x(2)- [STAHENRI]-C-x(2)-C -Sequences known to belong to this class detected by the pattern: ALL. -Other sequence(s) detected in Swiss-Prot: NONE. -Consensus pattern: [FLY]-N-[ED]-[STA]-K-x-[IV]-[STAG]-[FM]-[ST]-[MVL] -Sequences known to belong to this class detected by the pattern: ALL. -Other sequence(s) detected in Swiss-Prot: NONE. -Sequences known to belong to this class detected by the profile: ALL. -Other sequence(s) detected in Swiss-Prot: NONE. -Expert(s) to contact by email: Kolakowski L.F. Jr.; kolakowski@uthsca.edu -Last update: April 2006 / Patterns revised. [ 1] Tanabe Y., Masu M., Ishii T., Shigemoto R., Nakanishi S. "A family of metabotropic glutamate receptors." Neuron 8:169-179(1992). PubMed=1309649 [ 2] Okamoto N., Hori S., Akazawa C., Hayashi Y., Shigemoto R., Mizuno N., Nakanishi S. "Molecular characterization of a new metabotropic glutamate receptor mGluR7 coupled to inhibitory cyclic AMP signal transduction." J. Biol. Chem. 269:1231-1236(1994). PubMed=8288585 [ 3] Duvoisin R.M., Zhang C., Ramonell K. "A novel metabotropic glutamate receptor expressed in the retina and olfactory bulb." J. Neurosci. 15:3075-3083(1995). PubMed=7722646 [ 4] Brown E.M., Gamba G., Riccardi D., Lombardi M., Butters R., Kifor O., Sun A., Hediger M.A., Lytton J., Hebert S.C. "Cloning and characterization of an extracellular Ca(2+)-sensing receptor from bovine parathyroid." Nature 366:575-580(1993). PubMed=8255296; DOI=10.1038/366575a0 -------------------------------------------------------------------------------- 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 https://prosite.expasy.org/prosite_license.html -------------------------------------------------------------------------------- {END}