| Literature References | 1. ATTWOOD, T.K. AND FINDLAY, J.B.C.
Fingerprinting G protein-coupled receptors.
PROTEIN ENG. 7(2) 195-203 (1994).
2. ATTWOOD, T.K. AND FINDLAY, J.B.C.
G protein-coupled receptor fingerprints.
7TM, VOLUME 2, EDS. G.VRIEND AND B.BYWATER (1993).
3. BIRNBAUMER, L.
G proteins in signal transduction.
ANNU.REV.PHARMACOL.TOXICOL. 30 675-705 (1990).
4. CASEY, P.J. AND GILMAN, A.G.
G protein involvement in receptor-effector coupling.
J.BIOL.CHEM. 263(6) 2577-2580 (1988).
5. ATTWOOD, T.K. AND FINDLAY, J.B.C.
Design of a discriminating fingerprint for G protein-coupled receptors.
PROTEIN ENG. 6(2) 167-176 (1993).
6. WATSON, S. AND ARKINSTALL, S.
Neuropeptide Y.
IN THE G PROTEIN-LINKED RECEPTOR FACTSBOOK, ACADEMIC PRESS, 1994, PP.194-198.
7. WEINBERG, D.H., SIRINATHSINGHJI, D.J., TAN, C.P., SHIAO, L.L., MORIN, N.,
RIGBY, M.R., HEAVENS, R.H., RAPOPORT, D.R., BAYNE, M.L., CASCIERI, M.A.,
STRADER, C.D., LINEMEYER, D.L. AND MACNEIL, D.J.
Cloning and expression of a novel neuropeptide Y receptor.
J.BIOL.CHEM. 271 16435-16438 (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 rhodopsin-like GPCRs themselves represent a widespread protein family
that includes hormone, neurotransmitter and light receptors, all of
which transduce extracellular signals through interaction with guanine
nucleotide-binding (G) proteins. Although their activating ligands vary
widely in structure and character, the amino acid sequences of the
receptors are very similar and are believed to adopt a common structural
framework comprising 7 transmembrane (TM) helices [3-5].
Neuropeptide Y (NPY) is one of the most abundant peptides in mammalian
brain, inducing a variety of behavioural effects (e.g., stimulation of food
intake, anxiety, facilitation of learning and memory, and regulation of the
cardiovascular and neuroendocrine systems) [6]. In the periphery, NPY
stimulates vascular smooth muscle contraction and modulates hormone
secretion. NPY has been implicated in the pathophysiology of hypertension,
congestive heart failure, affective disorders and appetite regulation [6].
Several pharmacologically distinct neuropeptide Y receptors have been
characterised, designated NPY Y1-Y6. NPY Y6 shares 60% sequence identity
with the Y1 receptor. Its pharmacology resembles that of the Y1 receptor
and is distinct from that described for Y2, Y3 and Y4 receptors [7]. The
receptor is expressed within discrete regions of the hypothalamus, including
the suprachiasmatic nucleus, anterior hypothalamus, bed nucleus stria
terminalis, and the ventromedial nucleus, with no localisation apparent
elsewhere in the brain [7].
NRPEPTIDEY6R is a 6-element fingerprint that provides a signature for
neuropeptide Y6 receptors. The fingerprint was derived from an initial
alignment of 2 sequences: the motifs were drawn from conserved sections
within either loop or TM regions, focusing on those areas of the alignment
that characterise the Y6 receptors but distinguish them from the rest of
the neuropeptide Y family - motifs 1 and 2 span the N-terminus, leading
into TM domain 1; motifs 3 and 4 span the C-terminus of TM domain 4, leading
into the second external loop; motif 5 resides in the third cytoplasmic
loop; and motif 6 lies at the C-terminus. A single iteration on OWL30.2 was
required to reach convergence, no further sequences being identified beyond
the starting set. Four partial matches were found: D86519 and HSU59431 are
neuropeptide Y6 receptor fragments that lack the portion of sequence bearing
the final motif; and AF005779 and OAU62122 are neuropeptide Y1 receptors
that match motifs 3 and 5.
An update on SPTR37_9f identified a true set of 2 sequences, and 3
partial matches.
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