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* G-protein coupled receptors family 3 signatures *
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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.

-Expert(s) to contact by email:
           Kolakowski L.F. Jr.; kolakowski@uthsca.edu

-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(2,4)-[DN]-x(2)-[STAH]-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-[STA]-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: July 1998 / Patterns and text revised.

[ 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] Duvoisin R.M., Zhang C., Ramonell K.
     J. Neurosci. 15:3075-3083(1995).
[ 4] Brown E.M., Gamba G., Riccardi D., Lombardi M., Butters R., Kifor O.,
     Sun A., Hediger M.A., Lytton J., Hebert S.C.
     Nature 366:575-580(1993).
