| Literature References | 1. ATTWOOD, T.K. AND FINDLAY, J.B.C.
Fingerprinting G protein-coupled receptors.
PROTEIN ENG. 7(2) 195-203 (1994).
2. MASU, M., TANABE, Y., TSUCHIDA, K., SHIGEMOTO, R. AND NAKANISHI, S.
Sequence and expression of a metabotropic glutamate receptor.
NATURE 349 760-765 (1991).
3. HOUAMED, K.M., KUIJPER, J.L., GILBERT, T.L., HALDEMAN, B.A., OHARA, P.J.,
MULVIHILL, E.R., ALMERS, W. AND HAGEN, F.S.
Cloning, expression and gene structure of a G protein-coupled glutamate
receptor from rat brain.
SCIENCE 252 1318-1321 (1991).
4. ABE, T., SUGIHARA, H., NAWA, H., SHIGEMOTO, R., MIZUNO, N. AND
NAKANISHI, S.
Molecular characterisation of a novel metabotropic glutamate receptor
MGLUR5 coupled to inositol phosphate/Ca2+ signal transduction.
J.BIOL.CHEM. 267(19) 13361-13368 (1992).
5. TANABE, Y., MASU, M., ISHII, T., SHIGEMOTO, R. AND NAKANISHI, S.
A family of metabotropic glutamate receptors.
NEURON 8(1) 169-179 (1992).
6. WATSON, S. AND ARKINSTALL, S.
Glutamate receptors.
IN THE G PROTEIN-LINKED RECEPTOR FACTSBOOK, ACADEMIC PRESS, 1994, PP.130-141.
7. MAKOFF, A., VOLPE, F., LELCHUK, R., HARRINGTON, K. AND EMSON, P.
Molecular characterization and localization of human metabotropic glutamate
receptor type 3.
BRAIN RES.MOL.BRAIN RES. 40 55-63 (1996).
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| Documentation | G protein-coupled receptors (GPCRs) constitute a vast protein family that
encompasses a wide range of functions (including various autocrine, para-
crine and endocrine processes). They show considerable diversity at the
sequence level, on the basis of which they can be separated into distinct
groups. We use the term clan to describe the GPCRs, as they embrace a group
of families for which there are indications of evolutionary relationship,
but between which there is no statistically significant similarity in
sequence [1]. The currently known clan members include the rhodopsin-like
GPCRs, the secretin-like GPCRs, the cAMP receptors, the fungal mating
pheromone receptors, and the metabotropic glutamate receptor family.
The metabotropic glutamate receptors are functionally and pharmacologically
distinct from the ionotropic glutamate receptors. They are coupled to G-
proteins and stimulate the inositol phophate/Ca2+ intracellular signalling
pathway [2-5]. The amino acid sequences of the receptors contain 2 domains:
a large extracellular domain, and a membrane-associated domain that contains
high proportions of hydrophobic residues grouped into 7 regions, in a manner
reminiscent of the rhodopsins and other receptors believed to interact with
G proteins. However, while a similar 3D framework has been proposed to
account for this, there is no significant sequence identity between these
and receptors of the rhodopsin-type family: the metabotropic glutamate
receptors thus bear their own distinctive `7TM' signature. This 7TM
signature is also shared by the calcium-sensing receptors.
At least eight sub-types of metabotropic receptor (MGR1-8) have been
identified in cloning studies. The sub-types differ in their agonist
pharmacology and signal transduction pathways [6]. MGR3 is brain-specific,
and is expressed in neurones in the cerebral cortex, caudate-putamen,
thalamus and cerebellum [7]. MGR3 inhibits adenylyl cyclase through a
pertussis-toxin-sensitive G protein, probably of the Gi/Go class [6].
MTABOTROPC3R is a 10-element fingerprint that provides a signature for the
metabotropic glutamate receptor 3 precursor. The fingerprint was derived
from an initial alignment of 2 sequences: the motifs were drawn from short
conserved regions spanning the full alignment length, focusing on those
sections that characterise the metabotropic glutamate type 3 receptors but
distinguish them from the rest of the metabotropic glutamate receptor family
- motifs 1-8 reside in the N-terminal extracellular domain; and motifs 9 and
10 lie in the C-terminal cytoplasmic domain. A single iteration on OWL31.1
was required to reach convergence, no further sequences being identified
beyond the starting set. Two partial matches were found, MGR2_HUMAN and
MGR2_RAT, both of which are type 2 receptors that match motifs 4 and 10.
An update on SPTR37_9f identified a true set of 2 sequences, and 2
partial matches.
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