| 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., O'HARA, 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. BROWN, E.M., GAMBA, G., RICCARDI, D., LOMBARDI, M., BUTTERS, R.,
KIFOR, O., SUN, A., HEDIGER, M.A., LYTTON, J. AND HEBERT, S.C.
Cloning an characterisation of an extracellular Ca(2+)-sensing receptor from
bovine parathyroid.
NATURE 366 575-580 (1993).
7. KEVERNE, E.B.
The vomeronasal organ.
SCIENCE 286 716-720 (1999).
8. PANTAGES, E. AND DULAC, C.
A novel family of candidate pheromone receptors in mammals.
NEURON 28 835-845 (2000).
9. RYBA, N.J.P. AND TIRINDELLI, R.
A new multigene family of putative pheromone receptors.
NEURON 19(2) 371-379 (1997).
10. NAITO T., SAITO, Y., YAMAMOTO, J., NOZAKI, Y., TOMURA, K., HAZAMA, M.,
NAKANISHI, S. AND BRENNER, S.
Putative pheromone receptors related to the Ca2+ sensing receptor in Fugu.
PROC.NATL.ACAD.SCI.U.S.A. 95 5178-5181 (1998).
11. SPECA, D.J., LIN, D.M., SORENSEN, P.W., ISACOFF, E.Y., NGAI, J.
AND DITTMAN, A.H.
Functional identification of a goldfish odorant receptor.
NEURON 23(3) 487-498 (1999).
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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 phosphate/Ca2+ intracellular
signalling pathway [2-5]. The amino acid sequences of the receptors contain
high proportions of hydrophobic residues grouped into 7 domains, 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.
Pheromones have evolved in all animal phyla, to signal sex and dominance
status, and are responsible for stereotypical social and sexual behaviour
among members of the same species. In mammals, these chemical signals are
believed to be detected primarily by the vomeronasal organ (VNO), a
chemosensory organ located at the base of the nasal septum [8]. The VNO is
present in most amphibia, reptiles and non-primate mammals but is absent in
birds, adult catarrhine monkeys and apes [7]. An active role for the human
VNO in the detection of pheromones is disputed; the VNO is present in the
foetus but appears to be atrophied or absent in adults [7]. Three distinct
families of putative pheromone receptors have been identified in the
vomeronasal organ (V1Rs, V2Rs and V3Rs). All are G protein-coupled receptors
but are only distantly related to the receptors of the main olfactory
system, highlighting their different role [8].
The V2 receptors are members of the metabotropic glutamate receptor-like
family of GPCRs and have close similarity to the extracellular Ca2+-sensing
receptors [9]. Rodents appear to have around 100 functional V2 receptors and
many pseudogenes [8]. These receptors are expressed in the basal regions of
the VNO, where they couple to Go proteins to mediate inositol trisphosphate
responses [7]. Homologues have also been identified in fish [10], and the
ligand specificity of one such receptor has been determined: a receptor from
goldfish olfactory epithelium has been reported to bind basic amino acids,
which are odorants for fish [11].
VOMERONASL2R is a 9-element fingerprint that provides a signature for the
vomeronasal type 2 receptor family. The fingerprint was derived from an
initial alignment of 11 sequences: the motifs were drawn from conserved
sections within N-terminal and external loop regions, focusing on those
areas of the alignment that characterise the vomeronasal type 2 receptors
but distinguish them from the rest of the metabotropic glutamate receptor
superfamily - motifs 1-6 lie within the large N-terminal domain; motif 7
spans part of TM domain 2, leading into the first external loop; and motifs
8 and 9 span the second external loop. Two iterations on SPTR39_15f were
required to reach convergence, at which point a true set comprising 14
sequences was identified. Several partial matches were also found, all of
which are vomeronasal type 2 receptors or members of the closely related
extracellular Ca2+-sensing receptor family. Many of the vomeronasal
receptors that fail to match a number of motifs are pseudogenes.
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