| 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.
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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].
MTABOTROPICR is a 6-element fingerprint that provides a signature for the
metabotropic glutamate receptors. The fingerprint was derived from an
initial alignment of 8 sequences: the motifs were drawn from conserved
sections within both the extracellular and 7TM domains, focusing on those
areas of the alignment that characterise the metabotropic receptors but
distinguish them from the rest of the metabotropic receptor superfamily
- motifs 1-3 lie in the extracellular domain; motif 4 lies at the N-terminus
of TM domain 1; motif 5 lies in TM domain 3; and motif 6 spans the N-
terminus of TM domain 7. Two iterations on OWL28.1 were required to reach
convergence, at which point a true set comprising 15 sequences was
identified. A single partial match was also found, CEZC5063, a fragment
matching motifs 3-6.
An update on SPTR37_9f identified a true set of 19 sequences, and 2
partial matches.
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