| 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.
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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].
NRPEPTIDEYR is a 5-element fingerprint that provides a signature for
neuropeptide Y receptors. The fingerprint was derived from an initial
alignment of 11 sequences: the motifs were drawn from conserved sections
within either loop or TM regions, focusing on those areas of the alignment
that characterise the neuropeptide Y receptors but distinguish them from the
rest of the rhodopsin-like GPCR superfamily - motif 1 spans the first
cytoplasmic loop; motif 2 spans the first external loop; motif 3 encodes
the N-terminal portion of TM domain 3; motif 4 spans the central portion
of TM domain 7; and motif 5 lies at the C-terminus. Two iterations on
OWL30.2 were required to reach convergence, at which point a true set
comprising 20 sequences was identified. Several partial matches were also
found, all of which are superfamily members that match two motifs.
An update on SPTR37_9f identified a true set of 22 sequences, and 9
partial matches.
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