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- ***************************************************
- * G-protein coupled receptors family 3 signatures *
- ***************************************************
-
- 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 section), 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]. Currently there
- are seven known subtypes of metabotropic glutamate receptors; mGluR1 to
- mGluR7. The sutbypes mGluR1 and mGluR5 are coupled to the stimulation of
- the phosphatidylinositol-calcium second messenger system while mGluR2,
- mGluR3, mGluR4, mGluR6 and mGluR7 are coupled to G proteins that inhibit
- adenylate cyclase activity.
- - The extracellular calcium-sensing receptor [3] 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.
-
- 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.
-
- -Expert(s) to contact by email: Kolakowski L.F. Jr.
- lfk@receptor.mgh.harvard.edu
-
- -Consensus pattern: V-x-N-[LIVM](2)-x-L-F-x-I-P-Q-[LIVM]-[STA]-Y-[STA](4)
- -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(2,4)-D-x(2)-[TA]-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: F-N-E-A-K-x-I-[STAG]-F-[ST]-M
- -Sequences known to belong to this class detected by the pattern: ALL.
- -Other sequence(s) detected in SWISS-PROT: NONE.
-
- -Last update: June 1994 / First entry.
-
- [ 1] Tanabe Y., Masu M., Ishii T., Shigemoto R., Nakanishi S.
- Neuron 8:169-179(1992).
- [ 2] Okamoto N., Hori S., Akazawa C., Hayashi Y., Shigemoto R., Mizuno N.,
- Nakanishi S.
- J. Biol. Chem. 269:1231-1236(1994).
- [ 3] Brown E.M., Gamba G., Riccardi D., Lombardi M., Butters R., Kifor O.,
- Sun A., Hediger M.A., Lytton J., Hebert Sc.
- Nature 366:575-580(1993).
-